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“A PHAMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF SHODHANA W.S.R. TO KUPEELU SHODHANA” BY Dr.SANGAMESH.I.P Dissertation submitted to the RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA, BENGALURU In partial fulfillment of the requirements for the degree of AYURVEDA VACHASPATI (Doctor of Medicine) In RASASHASTRA UNDER THE GUIDANCE OF Dr. T. R. DATTATRI, B.S.A.M, B.A.M.S, M.D.(Ayu),D.N.Y Professor Dept. Of PG studies in Rasashastra G.A.M.C, BENGALURU DEPARTMENT OF RASASHASTRA GOVT. AYURVEDIC MEDICAL COLLEGE, BENGALURU 583101 (Karnataka) 2011-2012

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Page 1: “A PHAMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF …

“A PHAMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF

SHODHANA W.S.R. TO KUPEELU SHODHANA”

BY

Dr.SANGAMESH.I.P

Dissertation submitted to the

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA,

BENGALURU

In partial fulfillment of the requirements for the degree of

AYURVEDA VACHASPATI

(Doctor of Medicine)

In

RASASHASTRA

UNDER THE GUIDANCE OF

Dr. T. R. DATTATRI,

B.S.A.M, B.A.M.S, M.D.(Ayu),D.N.Y

Professor Dept. Of PG studies in Rasashastra

G.A.M.C, BENGALURU

DEPARTMENT OF RASASHASTRA

GOVT. AYURVEDIC MEDICAL COLLEGE,

BENGALURU 583101

(Karnataka)

2011-2012

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RAJIV GANDHI UNIVERSITY OF HEALTH

SCIENCES BANGALORE.

DECLARATION BY THE CANDIDATE

I hereby declare that this dissertation entitled “A

PHAMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF SHODHANA

W.S.R. TO KUPEELU SHODHANA” is a bonafide and genuine research

work carried out by me under the guidance of

Dr. T. R. Dattatri, B.S.A.M, B.A.M.S, M.D.(Ayu),D.N.Y,

Professor, Dept. of P.G. Studies, in Rasashastra, G.A.M.C, Bengaluru.

Date: Signature of the candidate

Place: (Dr.SANGAMESH.I.P)

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RAJIV GANDHI UNIVERSITY OF HEALTH

SCIENCES, KARNATAKA, BANGALORE.

CERTIFICATE BY THE GUIDE

This is to certify that the dissertation entitled “A PHAMACEUTICO-

ANALYTICAL STUDY ON CONCEPT OF SHODHANA W.S.R. TO

KUPEELU SHODHANA” is a bonafide research work done by

Dr. Sangamesh.I.P, in partial fulfillment of the requirement for the degree of

AYURVEDA VACHASPATI, (DOCTOR OF MEDICINE) IN

RASASHASTRA.

Signature of the Guide,

Dr.T.R.Dattatri, B.S.A.M, B.A.M.S,M.D .(Ayu),D.N.Y

Professor,

P.G. Dept. of Rasashastra Date: G.A.M.C, Bengaluru

Place:

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RAJIV GANDHI UNIVERSITY OF HEALTH

SCIENCES, BANGALORE.

ENDORSEMENT BY THE HOD, PRINCIPAL

/ HEAD OF THE INSTITUTION

This is to certify that the dissertation entitled “A PHAMACEUTICO-

ANALYTICAL STUDY ON CONCEPT OF SHODHANA W.S.R. TO KUPEELU

SHODHANA” is a bonafide research work done by Dr.SANGAMESH.I.P under

the guidance of

Dr. T. R. Dattatri, B.S.A.M, B.A.M.S, M.D.(Ayu),D.N.Y, Asst. Professor, Dept. of P.G.

Studies, in Rasashastra, G.A.M.C, Bengaluru.

Dr. Shobha. G. Hiremath M.D. (AYU) . Phd(R.S) Dr. H. T. Shreenivas MD. (Ayu)

H. O. D Principal

P. G Dept. of Rasashastra G.A.M.C Bengaluru.

G.A.M.C Bengaluru.

Date: Date:

Place: Place:

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RAJIV GANDHI UNIVERSITY OF HEALTH

SCIENCES, BANGALORE.

DECLARATION BY THE CANDIDATE

I hereby declare that the Rajiv Gandhi University of Health Science, Karnataka

shall have the rights to preserve use and disseminate this dissertation in print or

electronic format for academic / research purpose.

Signature of the candidate

Dr.Sangamesh.I.P

Date:

Place:

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ACKNOWLEDGMENT

Every big work seems difficult, but once started keeps going and going. This very

dissertation work too seemed difficult but with the blessings of GOD & my parents, this

Herculean task became an interesting journey and today on the verge of completion of

this dissertation, I pay my gratitude to all those who helped me through the tough paths,

ups & downs of this journey.

With sense of respect and full devotion I bow my head in sacred feet of Lord

“Shiva” who bestowed upon me his blessings & inculcated in me enough strength and

courage for carrying out this work.

It is next to impossible to express the sense of honor and gratitude to my

illustrious, veracious, affectionate, prudent & endeavoring guru and my guide Dr.

Dattatri B.S.A.M, B.A.M.S., M.D.DNY professor .Dept. of P.G. studies in Rasashastra

,GAMC,Bangalore for his scholarly guidance, constant encouragement throughout my

study.

It is very difficult to vocabularise my whole hearted gratitude and deep sense of

indebtedness to my H.O.D.&Prof of Dept of P.G.studies in Rasashastra . Dr .Shobha .G.

Hiremath B.A.M.S.,M.D ,PhD, for scholarly guidance & constant encouragement

throughout my study& for providing all the facilities to make the study success.

I am extremely thankful to my juniors Dr.Ravi Mathapati, Dr.Sripal,

Dr.Sanmati.P.Rao ,Dr.Kavitha, Dr.Divya.K. and Dr.Shailashree.G.Koppal, Dr.Pratibha,

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Dr.Jyotsna, Dr.Nagraj., Dr.Manjula, Dr.Malavi, Dr.Varsha. for joining their ever

helping hands with me to complete this present work.

I could not forget to thank my ever enthusiastic seniors Dr.Sudarshan.Achar,

Dr.Ambujakshi V.M, Dr.Sadaguna.D.N, Dr.Jyoti.varatti, Dr.Indrani and

Dr.Naveenkumar.H.M for their help, cooperation and support in dissertation work.

I thank Dr.B.G.Deshpande, Lecturer, ayurveda college Bidar for his continuous

help and encouragement.

I thank my friends Dr.Pratibha, Dr.Ali ,Dr.Sacchidanand, Dr.Amol,

Dr.Bhagyalaxmi, Miss.Spandana.P.M, Dr.Anand.Managutti and Mr

Prakash.S.Kademani for their cooperation, valuable support and help.

I express my profound sense of gratitude to Dr. Chandrashekar B.A.M.S ,M.D.

Former H.O.D,& present Deputy Registrar R.G.U.H.S. Bengaluru for his valuable

suggestions and earnest support.

I Wish to express my thanks Mr.Ashwin and Mr.Muralidhar.Nayak .S.I.D

Department Indian institute of Science, Bengaluru, and for their kind co-operation.

I am immensely grateful to Dr. Revathi B.A.M.S. Bangalore test house (BTH) for

their kind co-operation.

At this juncture it is my duty to pay my gratitude to my parents & sister for

their whole hearted encouragement and continuous help.

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Lastly I would like to express my sincere thank to each and every person who have

contributed directly or indirectly throughout my career & in accomplishing this task

without any faults.

Mistakes are stepping stone to Success. Apologizing for faults and memorizing one and

all.

Dr Sangamesh.I.P

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AABBBBRREEVVIIAATTIIOONNSS

AAsshhttaannggaa HHrriiddaayyaa AA..HH

Ashtanga Samgraha A.S

Amara kosha A.K

Ayurveda prakasha A.P.

Bhaishajya Ratnavali B.R

Bhavaprakasha Nighantu B.P.N

Charaka Samhita C. S

Dhanvantari Nighantu D.N

Fourier transform infra red F.T.I.R

Kaiyadeva Niganthu K.N

Madanapala Nighantu M.Ni.

Nighantu Adarsha N.A

Priya Nighantu P.N

Raja Nighantu R.N.

Rasatarangini R.T

Rasaratnasamucchaya R.R.S.

Shodhala nighantu Sh.d.ni

Sharangadhara samhitha S.D

Sharanghadhara Samhita S.S

Shabda Kalpadruma S.K.D

Sushruta Samhita S.S

Thin layer chromatography T.L.C

Yoga Ratnakara Y.R

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i

ABSTRACT

OBJECTIVE

The study was designed to evaluate pharmaceutico-analytically, the effect of shodana on

the seeds of kupeelu purified by 2 different methods viz. swedana in godugdha and

bharjana in goghruta.

INTRODUCTION

Kupeelu is one among the poisonous plants used in therapeutics of Rasashastra which is

classified under upavisha varga.It has been widely used in the treatment of various

disorders mainly vatavyadhis.Strychnine and brucine are the 2 main alkaloids among all

the alkaloids present in the seeds of kupeelu,responsible for its toxicity.The drug is

intended to be used only after the process of shodhana in a specified dose or else it may

prove fatal.

METHODOLOGY

In the present study, the seeds of kupeelu were subjected to shodhana by 2 different

methods as mentioned in Rasa Tarangini.The cleand and dried seeds were tied in a pottali

and subjected to swedana in dolayantra for 3 hours using godugdha as media.The Seeds

were then washed with hot water,the seed coat and embryonic axis was removed ,the

cotyledons were powdered in a khalwa yantra.

In another method bharjana was carried out using goghrita till the seeds turned to

yellowish red.The seeds were washed with hot water, the seed coat was removed and

powdering of seeds was done in khalwa yantra.

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ii

Thus obtained samples along with raw sample were subjected to analysis of organoleptic

characters,physico-chemical constants,quantative assay for strychnine,thin layer

chromatography of their methanolic extracts and Fourier transform infra red

spectroscopy.

RESULTS

Organoleptic analysis revealed that the seeds were devoid of trichomes ,seeds became

soft in case of godugdha swedana and brittle,crispy in case of goghrita bharjana which

could be easily powdered.Alteration of ash and extractive values was noted in analysis of

physico-chemical constants.In quantative assay of strychnine there was a reduction of

strychnine by 11.11% in godugdha swedita seeds & 50.70 % in gogritha bharjita

seeds.TLC analysis showed a qualitative and quantative change in phytochemistry of

seeds after shodhana.There was also a change in the spectras as revealed by FTIR

analysis.

CONCLUSION

It may be concluded from the present study that shodhana is effective in reducing the

toxic principles strychnine and brucine.Method of goghrira bharjana is better than the

method of swedana .Shodhana brings about qualitative and quantitative changes in the

phytochemistry of drug.It is evident from the study that techniques like quantative

assay,thin layer chromatography and FTIR are very much useful in the assessment of

qualitative and quantitative changes before and after shodhana.

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iii

FURTHER SCOPE FOR STUDY

Since the present study is limited to only two methods of shodhana, there is a room for

study to extend it to other various shodhana procedures mentioned in the texts. Other

ultramodern chromatographic and spectroscopic techniques can be used to assess the

influence of shodhana.

KEYWORDS

Shodhana, kupeelu, bharjana, swedana, strychnine, upavisha, TLC, FTIR.

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TABLE OF CONTENTS

SL NO. CONTENTS PAGE NO.

I INTRODUCTION 1-8

II AIMS AND OBJECTIVES 9

III REVIEW OF LITERATURE

Drug Review

Pharmaceutical Review

Analytical Review

10-79

17-54

55-68

69-79

IV MATERIALS AND METHODS

Pharmacognostic study

Pharmaceutical study

Analytical study

80-103

80-85

86-94

95-103

V RESULTS 104-112

VI DISCUSSION 113-131

VII CONCLUSION 132-133

VIII SUMMARY 134-136

IX LIMITATION OF THE STUDY 137

X SCOPE FOR FURTHER STUDY 138

XI BIBILOGRAPHY 139-157

XII PHOTOS 158-162

XIII ANNEXURES

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LIST OF TABLES

SI NO TABLES PAGE

NO.

1 TABLE NO.1 :SHOWING THE SYNONYMS OF

KUPEELU

22-23

2 TABLE NO. 2 : DENOTING RASA PANCHAKA OF

KUPEELU

25

3 TABLE NO. 3 SHOWING DOSHA KARMA OF

KUPEELU

26

4 TABLE NO. 4 : SHOWING SAMANYA KARMA

OF KUPEELU

26

5 TABLE NO. 5 : SHOWING ROGAGHNATA OF

KUPEELU

27

6 TABLE NO. 6 : SHOWING VISISTA YOGAS OF

KUPEELU AND THEIR THERAPEUTIC USES AS

MENTIONED IN BHAISHAJYA RATNAVALI

32

7 TABLE NO. 7 : SHOWING VISISTA YOGAS OF

KUPEELU AND THEIR THERAPEUTIC USES AS

MENTIONED IN YOGARATNAKARA

33

8 TABLE NO. 8 SHOWING VISISTA YOGAS OF

KUPEELU AND THEIR THERAPEUTIC USES AS

MENTIONED IN RASA TARANGINI.

33

9 TABLE NO. 9 : SHOWING VISISTA YOGAS OF

KUPEELU AND THEIR THERAPEUTIC USES AS

MENTIONED IN RASENDRA SAARA SANGRAH

34

10 TABLE NO. 10 : SHOWING SCIENTIFIC

CLASSIFICATION OF KUPEELU.

35

11 TABLE NO. 11 : SHOWING CLASSIFICATION

OF GOKSHEERA IN SAMHITAS

48

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SI NO TABLES PAGE

NO.

12 TABLE NO. 12 : SHOWING GUNAKARMAS

OF GOKSHEERA

48

13 TABLE NO. 13 : SHOWING COMPARISON OF

VISHA AND KSHEERA GUNAS

49

14 TABLE NO. 14 : SHOWING ANALYSIS OF MILK

COMPOSITION

50

15 TABLE NO. 15 : SHOWING CLASSIFICATION

OF GOGHRITA IN SAMHITAS

53

16 TABLE NO. 16 : SHOWING GUNAKARMAS

OF GOGHRITA IN CHARAKA SAMHITA

53

17 TABLE NO. 17 : SHOWING THE SHODHANA OF

KUPEELU WITH DIFFERENT MEDIA AS

MENTIONED IN VARIOUS TEXTS

63-64

18 TABLE NO. 18 : SHOWING EXAMPLES FOR

SWEDANA PROCESS MENTIONED FOR RASA

DRAVYA SHODHANA IN RASA TEXTS

65

19 TABLE NO. 19 : SHOWING EXAMPLE FOR

BHARJANA PROCESS MENTIONED FOR RASA

DRAVYA SHODHANA IN RASA TEXTS

66

20 TABLE NO. 20 : SHOWING THE

ABBREVATIONS OF DIFFERENT SAMPLES

86

21 TABLE NO. 21: SHOWING OBSERVATIONS OF

THE SEEDS BEFORE AND AFTER SWEDANA.

90

22 TABLE NO. 22: SHOWING OBSERVATIONS IN

THE MILK BEFORE AND AFTER SWEDANA.

91

23 TABLE NO. 23 : SHOWING OBSERVATIONS OF

THE SEEDS BEFORE AND AFTER BHARJANA

93

24 TABLE NO. 24 : SHOWING COMPARATIVE

ORGANOLEPTIC CHARACTERISTICS

104

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GRAPH

SL. NO. GRAPH PAGE

NO.

1. % OF STRYCHNINE CONTENT BEFORE AFTER

SHODHANA

106

SI NO TABLES PAGE

NO.

25 TABLE NO. 25 : SHOWING RESULTS OF

COMPARATIVE PHYSICO-CHEMICAL

CONSTANTS

104

26 TABLE NO. 26 : SHOWING COMPARATIVE

QUALITATIVE TESTS FOR PRESENCE OF

ALKALOIDS

105

27 TABLE NO. 27 : SHOWING COMPARATIVE

VALUES OF ASSAY FOR STRYCHNINE

105

28 TABLE NO. 28 : SHOWING THE FTIR PEAK

POSITIONS AND THEIR ASSIGNMENTS OF

AHSUDDHA KUPEELU SEEDS

110

29 TABLE NO. 29 : SHOWING THE FTIR PEAK

POSITIONS AND THEIR ASSIGNMENTS OF

GODUGDHA SWEDITA KUPEELU SEEDS

111

30 TABLE NO 30 : SHOWING THE FTIR PEAK

POSITIONS AND THEIR ASSIGNMENTS OF

GOGHRITA BHARJITA KUPEELU SEEDS

112

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LIST OF PHOTOS

SI.NO. FIGURES PAGE

NO.

1 KUPEELU TREE 158

2 TREE WITH FRUITS 158

3 KUPEELU PHALA 158

4 KUPEELU BEEJA 158

5 GOKSHEERA 158

6 GO-GHRUTA 158

7 ASHUDDHA KUPEELU BEEJA 159

8 POTTALI 159

9 DOLA YANTRA 159

10 BEEJA AFTER SWEDANA 159

11 AFTER REMOVAL OF SEED COAT 159

12 SEPARATED COTYLEDON 159

13 KUPEELU BEEJA 160

14 PROCESS OF BHARJANA 160

15 BEEJA AFTER BHARJANA 160

16 BEEJA WITH SEED COAT 160

17 REMOVAL OF SEED COAT 160

18 END PRODUCT OF BHARJANA 160

19 TRICHOMES BEFORE SHODHANA 161

20 ALEURONE GRAINS WITH FAT GLOBULES

BEFORE SHODHANA

161

21 TRICHOMES AFTER SWEDANA

161

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SI.NO. FIGURES PAGE

NO.

22 ALEURONE GRAINS WITH FAT GLOBULES

AFTER SWEDANA

161

23 SCANTY TRICHOMES AFTER BHARJANA 161

24 ALEURONE GRAINS WITH FAT GLOBULES

AFTER BHARJANA

161

25 TOTAL ASH ANALYSIS 162

26 ACID INSOLUBLE ASH ANALYSIS 162

27 PREPARATION OF TLC 162

28 CHROMATOGRAM OF ALL 3 SAMPLES 162

29 FOURIER TRANSFORM INFRA-RED

SPECTROPHOTOMETER

162

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KUPEELU SHODHANA Page 1

INTRODUCTION

Ayurveda, the science of life has mainly two objectives, maintenance of health in

the healthy individuals and cure of the diseases in the diseased.1

To achieve this, Ayurveda describes Swasthahita (one which improves

the quality of health) , Doshaprashamana(which is used for pacifying the vitiated

disease causing factors i.e., doshas), and Dhatupradushana which vitiates the factors

that support life system i.e., Dhatus.2

Ayurveda emphasizes on the fact that there is no substance in this world

which cannot be used as medicine.3 i.e., homologous or non-homologous, man with

his intellectual power, has the ability to convert these substances for usage of health

and medicine. Then there can arise a doubt, can poison be used as medicine?

Definitely, with usage of Ayurvedic and Rasashastra principles, even poison can be

converted to ambrosia, for example, when food is prepared or consumed in an

improper manner, even the life source called ‘food’ can become venomous, contrary

to this, the life taking poison can serve as medicine when it is modified according to

one’s logical intelligence.4

There are 8 branches in Ayurveda, Agada Tantra being one, where in

this branch deals with Toxicology5. It describes signs and symptoms caused by

poisons, management of the same resulting from the bites of snakes, insects, worms

,spiders, rodents etc.6. The poisonous dravyas have been documented by our Samhitha

seers; where in their maximum usage is for external application.

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The practice of medicine went smoothly until the diseases subsided due

to the therapeutic action of the drugs. But as time evolved, some diseases became

unresponsive to the medicines then formulated, and so, sought for quicker, efficient,

effective and palatable form of medicine. And as an answer, the newer research and

development brought in the much awaited Rasashastra, an unique science relating to

philosophy, tantricism , alchemy and Ayurveda. The usage of organic poisons and

parthiva dravya as medicine was being developed. Metals, minerals and poisons were

modified and launched as new drugs. Numerous reasons can be attributed for the need

of this science-

1. The unresponsiveness of the herbal medicines to diseases.

2. Insight of flora being extinct in future.

3. The powerful action of the new therapeutics.

4. Usage of advanced pharmaceutical procedures which were based on siddhantas etc.

The Rasa Ratna Samucchaya, a pioneer Rasa Shastra text, has a reference of

poison intensifying the Amritha and converting into a substance better than ambrosia

itself. ‘The nectar which is mixed with halahala visha has more excellent qualities

than mere amritha, and is more potent’.6

Rasashastra developed after a numerous trials before concluding to its

final siddantas. How were these Siddhantas formulated? Observations were made that

when metals, minerals and the poisonous plants in natural form directly ingested

without following the drug preparatory rules and regulations, they proved to be fatal.

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This gave rise to new modified principles to gain supreme drugs. This advanced

Ayurvedic branch formulated these principles schematically, some of them including

Shodhana, Marana, Satvapatana, Amritrikarana etc. Not all drugs needed all

procedures, some proved excellent just after shodhana and some required the more

tedious Amritikarana to prove its medicinal value. The organic poisons, herbal in

specific were converted to medicine with the Shodhana procedure.

Shodhana included conversion of poisonous metals, minerals and plants

to non- poisonous drugs. This is related to ‘Samskara”, a fine technicality which

brings in the required change in the physical and chemical constituents. These

Shodhana Samskaras were documented in texts and the procedures were recorded.

The shodhana samkara was designed to remove the impurities which may be in the

form of physical, chemical or biological and make the substance fit for medicinal

usage.

How can a poison become ambrosia? It can be done so by a procedure which can

cause the following.

i. Eradication- Might have lost its toxic principle completely.

ii. Reduction-a considerable reduction in the concentration of the toxic principle

iii. Conversion- the principle form into another principle (toxic into non-toxic)

iv. Potentiation- Medias which are anti-poisonous and antidote to that drug can

check its toxicity or toxic effect completely and bring in its medicinal value.

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The Rasavaidyas explain Shodhana Samskara as the process which is used to

cleanse a substance by using techniques such as trituration, frying, drying, melting,

quenching, boiling, soaking etc. When shodhana process is scanned, we find

i. Different medias of shodana have been mentioned for a single drug.

ii. Single method is said for shodhana of a single drug.

iii. Usage of different shodhana procedures in the shodhana of a single drug

iv. Only one shodhana process is mentioned collectively for a group of drugs.

This permutation and combination gives the physician a lot of options

regarding the method of adoption of purification for poisonous drugs, as to which

method will give him a better, easier, quicker result. Keeping this in mind, the present

study was hypothesized that the shodhana must have a qualitative and quantitative

influence on the phytochemical profile of the toxic herbs, Kupeelu (Strychnos nux-

vomica Linn.) is one among such herb described under the 'Upavisa Vargas' (semi

poisonous group) 8 and its seeds have been used successfully in cure of many diseases

after proper Shodhana 9.Hypothesis is planned to validate scientifically the shodhana

process as mentioned by Rasatarangini for the seeds of Kupeelu (Strychnos

nuxvomica Linn.) wherein 2 processes for Shodhana samskara have been

comparatively evaluated .viz.,

1. Shodhana of Kupeelu seeds by Swedana in Cow’s milk 10

2. Shodhana of Kupeelu seeds by Bharjana with cow’s ghee.11

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AIMS AND OBJECTIVES:

Aim of the study is to carry out Shodhana of Kupeelu by two selected methods

Objectives

1) Procurement of standard raw material i.e seeds of Kupeelu.

2) To carry out shodhana of Kupeelu by the method of Swedana using godugdha as

the media.10

3) To carry out shodhana of Kupeelu by the method of Bharjana using goghrita 11

.

REVIEW OF LITERATURE

It is presented as drug review; reviews of pharmaceutical procedures adopted

and review of analytical methods adopted.

In literature review detailed explanation of vishas and upavisha is given. In

drug review critical and thorough review of Ayurvedic and modern literatures and

published articles regarding Kupeelu and detail description of identification,

pharmacological activity, chemical constituents, regional names etc, of Kupeelu are

compiled in scientific manner, also drugs used for Shodhana have been elaborated.

In pharmaceutical review the concept of shodhana and Shodhana w.s.r to

Kupeelu is reviewed.

In review of analytical methods, physico-chemical constants, assay for

strychnine, thin layer chromatography and Fourier transform infra red

spectrophotometric analysis are reviewed.

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MATERIALS AND METHODS

It is presented as Pharmacognosy study, Pharmaceutical study and

Analytical study

Pharmacognosy study

The crude drugs form the basis for the manufacture of medicinal preparations.

The Pharmacognostic study of these drugs is the key for getting therapeutically potent

medicines which are prepared from genuine drug material. Accurate determination of

drug identity, its sources and evaluating standards are an important and essential part

of the research work. The plant materials are studied according to sensory,

macroscopic and microscopic characteristics. These parameters are helpful for the

identification and authentification of the plant.

In this phase of study, the procured samples of Kupeelu (Strychnos nux-vomica Linn.)

has been identified and studied by Macroscopic and Microscopic examination.

Pharmaceutical study

Rasashastra, the unique Ayurvedic pharmaceutics, deals with the preparation

of drugs from metals, minerals, animal products and poisonous herbal drugs. These

are rarely administered in their crude form, often combined with a number of

substances through various pharmaceutical processes, which in turn transform them to

a convenient dosage form that can be administered. The prime objective of

pharmaceutical research is to produce a safe, effective and quality drug.

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INRODUCTION

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In this phase of study, shodana of Kupeelu has been done by two methods viz.

Swedana in Dolayantra using godugdha as media and Bharjana using Goghruta.

Analytical study

In this phase of study, the Organoleptic analysis, the Physico-chemical

analysis which includes Loss on drying, Total ash, determination of pH, Acid

insoluble ash, Moisture content, Extractive values and Assay for strychnine.

Qualitative and semi-quantitative analysis is done by thin layer chromatography,

Fourier transform infra red analysis, of Raw Kupeelu and Shodhita Kupeelu have

been carried out.

RESULTS:

The results and observations of Pharmacognostical, Pharmaceutical and

Analytical, studies were recorded.

DISCUSSION

This includes possible explanations about observations, findings and results

CONCLUSION

The facts, results and observations of whole study have been summarized and

possible conclusion regarding Pharmacognostical, Pharmaceutical and Analytical

profiles of raw Kupeelu, Shuddha Kupeelu by using different media, based on

obtained results and discussion conclusion is drawn.

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SUMMARY

The gist of the whole study is given in a concise form.

REFERENCES AND BIBLIOGRAPHY:

All the relevant references are mentioned wherever necessary with

bibliography in a serial manner.

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AIMS AND OBJECTIVES

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AIMS AND OBJECTIVES

Aim of the study is to carry out Shodhana of Kupeelu by two selected

methods acc to Rasatarangini.

Objectives:

1) Procurement of standard raw material i.e. seeds of kupeelu.

2) To carry out the shodhana of kupeelu by method of swedana using

godugdha as the media.

3) To carry out the shodhana of kupeelu by method of bharjana using

goghrita.

4) To carry out comparative physico-chemical analysis of the shodhita

samples.

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REVIEW OF LITERATURE:

Review of literature is divided into 3 parts

1) Drug review

2) Pharmacuetuical review and

3) Analytical review.

Drug review consists of historical review, vernacular names, synonyms, rasa

panchakas, dosha karma,dose,strychnine and its toxicity, treatment, previous works ,

review of drugs used in shodhana i.e godugdha and goghruta their gunas etc.In

pharmacuetical review, Shodhana procedure in detail including Swedana and Bharjana is

reviewed. In case of analytical review the quantitative and qualitative analysis of kupeelu

seeds is reviewed.

INTRODUCTION TO VISHA-UPAVISHA1:

The word Visha is derived from “vish” dhatu by having ka pratyaya which

means to encompass or to get fully pervaded or to get occupied, thus the one which

pervades the whole body immediately after ingestion is called as Visha. 12

From this

dhatu a naamapada Vishada, is formed which indicates stage of lethargy. It also means

dejection, sadness, grief, sorrow, disappointments, despondency, dispair, etc. Hence a

substance which creates “Vishadatwa” in body is termed as “Visha”.13, 14

The verse

further states that it can lead even to death. Any substance which produces very harmful

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effects on mind and body is called as Visha or poison.The less virulent form of visha is

named as upavisha.

The usage of poisonous plants in Ayurvedic System of Medicine is prevalent

since the time of Charaka and Sushruta Samhita .Both the texts describe the types of

poisons. The toxic effects of the poisonous plants are also described.

As per Charaka, poisonous plants when used in its proper dosage and in proper

manner and in proper stage of the disease can prove as a medicine.15

On the contrary if

any medicinal or food substance when not taken in proper manner vitiates the dhatus (i.e

tissues) and doshas of the body which in turn can prove as a poison. Thus, poison is that

substance which vitiates the doshas and dhatus and is life threatening.

Texts have broadly classified poisons into three types depending on their source

and origin: (1) Sthavara Visha (2) Jangama Visha (3) krutrima visha16

(1) Sthavara Visha: The poison,of plant and mineral origin. Adhistana bheda of

sthavara visha (classification based on site) includes Kanda (a kind of root), Sara, Niryasa

(Oleoresin), Pushpa (flower), Mula (root), Phala (fruit), Patra (leaf), Twak (skin of the

bark), Dugdha (milky exudates from the plants) and Khanija (minerals).17

Adhistana is the

site of poison means to say that part and parcel of the origin where it resides or media

through which the visha gets manifested.

It is also classified as Visha and Upavisha, Visha includes plants like

vatsanabha(aconitum ferox) and Upavisha includes plants like vishamusti (strychnos

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nuxvomica).18

These type of poisons when ingested by any person are said to cause

symptoms like fever, dysphasia, respiratory distress, vomiting , and might be fatal too.19

(2) Jangama Visha: A Type of poison which originates from animals. Poisons like snake

venom, scorpion sting, rodents, dogs, leeches, and insect bite come under this type.20

Symptoms like dizziness, burning, oedema and diarrhoea are generally developed due to

this type of poison. 21

(3) Krutrima Visha : This type of poison is other than the above two types which is

neither of plant nor of animal origin.

There is a mention of 2 other types of vishas in texts, garavisha and dushivisha.

Garavisha: It is a toxic combination of substances, non poisonous or which exerts toxic

effect after interval of sometimes and as such does not kill the patient instantly.22

Dushivisha: A constant exposure to a particular time, place, diet as well as constant and

regular day sleep tends to vitiate the dhatus of the body and this poison is consequently

known as dushivisha.23

In medicine, among the above of the three types of poisons, plant poison is most

frequently used. When poisonous plants are used in therapeutics the action is very fast

and the dosage is too less.

Before using these plants for medicinal use, they are subjected to different purificactory

procedures, which helps to reduce its toxicity and improve its efficacy. This procedure is

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called as „Shodhana Samskar‟. In this type of procedure, the part of the plant to be used

in the medicine has to undergo processes like boiling, frying etc. It is said that if these

procedures are not performed properly then the poisonous plant used in the medicine

may prove fatal.24

Upvisha Varga as mentioned in Rasaratnasamuchchaya include Langali, Vishatinduka,

Bhallataka, Karavira, Bhanga, Dhatura and Arka25

,in contrary Rasatarangini has

mentioned eleven plants in Upavisha Gana . They are: Vishatinduka, Ahiphena, Jayapala,

Dhatura, Bhanga, Gunja, Bhallataka, Arka, Langali Snuhi, and Karavira. 26

Shodhana of Visha27

Before therapeutic utilization, the Visha dravyas should be subjected to the

process of “Shodhana”. This process reduces the toxicity of the poisonous plant product

considerably and keeps it to required optimum level.

When such purification is carried out the poisonous substances are attributed with

certain properties. These are28

1. Rasayana

2. Yogavahi

3. Tridoshaghna

4. Brimhana

5. Veeryavardhaka

6. Pranadayi

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GENERAL DOSE OF VISHA DRAVYAS29

1tila matra to 8yava matra( 8mg-500mg)

(1tila=1/8 yava, 1yava=1/2 ratti ie;62.5mg,=1/8x62.5=8mg, 8yava=8x62.5=500mg)

GENERAL METHODS OF PURIFICATION OF VISHA DRAVYAS30

1. Cut the drug in to small pieces.

2. Soak in cow‟s urine for 3 days.

3. Change the cow‟s urine every day.

4. 4th day wash with warm water.

5. Dry under sun & store.

PRESERVATION OF PURIFIED VISHA DRAVYAS31

Storage- Tie in a cloth smeared with oil of red mustard seeds.

MARANA OF THE VISHA32

Before the visha is used therapeutically it is subjected to yet another process

called as Marana. Marana usually consists of giving intense heat to incinerate the

substance, here, in this case it consists of just intimately mixing Tankana(Borax) and

Visha in equal proportion.This reduces the toxicity of the Visha. Further if black pepper

is added in twice the quantity of the poison by weight, and then the mixture triturated

both Shodhana and Marana can be achieved together.

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Further it has been said that , if the severity of the disesas is not brought under control by

rasa and dhatu bhasmas, then usage of visha dravyas gives a fruitful result especially in

the disorders of vata and kapha vikaras.

TOXICOLOGY33

A poison is described as any substance, which has a harmful effect on a living system.

Paracelsus (1493 – 1541) was one of the first to distinguish between the therapeutic and

toxic properties of substances in modern era. He thought that the only difference between

a medicine and a poison was the dose. The same quotation is also laid down in Charak

Samhita 2000 years back.

Very few substances are actually classed as a “poison”. Harmful chemicals are

not necessarily poisons. We are exposed to potentially toxic substances every day without

immediate harm. Our body can safely metabolise toxins, if we are exposed to them in

small amounts. It is only when we overwhelm our body and reach the toxic dose of a

substance, they may be life threatening.

This means all substances have a potential toxicity. All herbs can therefore be

harmful, but most of them have to be ingested in amounts which are not toxic. Herbs,

which have a high toxicity, such as Strychnos nuxvomica and Aconitum ferox, can be

used safely and effectively if taken in a small, therapeutic dose. Thus, the primary

determinate of the safety of a substance is the dose. It is the dose, not the herb, which

turns to be poisonous. For example -Salt is not toxic in small doses. However, a single

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large dose can be lethal. Just two tablespoons can kill a one-year-old child. Caffeine, one

of the many alkaloids found in coffee can kill at a dose of 100 strong cups of coffee.

CLASSIFICATION OF POISON 34

I.CORROSIVES: (1) STRONG ACIDS:

a. inorganic or mineral acids

b. organic acids

(2) STRONG ALKALIS

(3) METALLIC SALTS

II. IRRITANTS:

(1)INORGANIC – metallic, non metallic, mechanical

(2)ORGANIC - plant & animal origin

III. SYSTEMIC: (1) CEREBRAL:

a. CNS depressants: alcohol, opioid, analgesics, hypnotics

b. CNS stimulants : caffeine

c. delirients : datura, cannabis

(2) SPINAL: nux vomica

(3) PERIHERAL: curare

(4) CARDIOVASCULAR: aconite, oleander

(5) ASPHYXIANTS: carbon monoxide

IV. MISCELLANEOUS: food poisoning, botulism etc

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Every substance has potential toxicity, from the most benign to the most obvious.

Even so, the same dose will not affect every person in the same way. It is this fact, which

makes toxicology such a complex science. There are a myriad of factors, which may

make the substance more or less toxic to a particular individual.

Toxicity depends not only on the dose of the substance but also on the toxic properties

of the substances. The relationships between these two factors are important in the

assessment of therapeutic dose.

DRUG REVIEW

In drug review the detail discription kupeelu , drugs used in shodhana that is

ksheera and ghritha is given.

HISTORICAL REVIEW

Drug history gives us thorough knowledge with respect to its identification,

controversy, pharmacological properties and therapeutic uses, so before giving a drug as

a whole it is equally important in knowing the drug as a whole.

VEDA KALA

There is no reference of kupeelu in veda kaala. Dr P.V.Sharma,in his book

“Ayurveda ka Vaignanika Itihasa and Dravyaguna Vignana part-4”has mentioned that

there is no reference of kupeelu neither in veda kaala nor in the samhita .35

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SAMHITA KALA

Kupeelu is not mentioned, instead the term vishamustika is mentioned under

Surasadi gana of Susruta36

and Vagbhata37

.It is considered as mahanimba or alambusha

or karkotika by Dalhana and Hemadri.

NIGHANTU KALA

Amarakosha (10th AD)

Kupeelu is mentioned under Vanaushadhi varga with 4 synonyms i.e. kakendu,

kulak, kakapeelu, kakatinduka38

Dhanwantari Nighantu (10th -11th century)

Kupeelu is mentioned under Amradi varga,considered as a variety of tinduka and

its synonym is mentioned by the name markatatinduka.39

Siddha mantra (12th A.D)

Kupeelu is mentioned under kapha pittagna varga,kutindu mentioned as

kakatindu.40

Shodala Nighantu (11th -13th century)

Kupeelu is mentioned under Karaveeradi varga as visha tinduka,with properties

like mahatiktaka and kapha vatahara,vishahara and visha tinduka beeja is said to be best

in all types of bhagna.41

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Madhava Dravya guna (13th A.D)

Kupeelu is mentioned under Phala varga as visha tinduka.42

Madanapala Nighantu (1347 A.D)

Kupeelu is mentioned under Phala varga with synonyms like kakapeelu, visha

tinduka and properties like sheeta and grahi are attributed to it.43

Kaiyadeva Nighantu (1425-1450 A.D)

Kupeelu is mentioned under Oushadi varga and described along with the

tinduka,but explained with 4 synonyms with separate qualities. Sthoola binduka is

considered as its synonym.44

Bhavaprakasha Nighantu (16th century)

Kupeelu is mentioned under Amradi phala varga with 7 synonyms.45

Saligrama Nighantu (1896 A.D)

Kupeelu is mentioned under Phala varga .The term karaskara is used in place of

kupeelu with 8 synonyms-

karaskara,kimpaka,vishatindu,vishadruma,graduma,ramyaphala,kupaka,kaalakutaka and

explained it in detail with its guna and karma46

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Raja Nighantu (17th -18th century)

Kupeelu is mentioned under Prabhadraadi varga with 8 synonyms and specially

indicated in kushta, kaarshya, vrana, prameha, kandu.47

Priya Nighantu (20th century)

Karaskara is mentioned under Shatapushpadi varga with properties like katu tikta

rasa,ushna veerya, sara guna, balya , and vaajikara. 48

Rasaratna Samucchaya49

and Rasa Tarangini 50

have mentioned vishamusti in

Upavisha varga.

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VERNACULAR NAMES51

Hindi : Kuchla, Kajra, Chibbinge, Makartendu, Kuchila etc.

Marathi : Kajarakar, Karaskara etc.

Gujarati : Jherakochala, Kochala, Jheri etc.

Bengal : Kuchila, Kutichla, Thalkesar

Orissa : Kachila

Kannada : Nanjina koradu, Kasarka, Hemmushti

Tamil : Yettikottai, Kanjirai, Silti.

Telugu : Musthtivittulu

Malayalam : Kajjola, Kanniram

English : Nuxvomica, Crowfig, Kachita

Nepal : Nirmali

Bombay : Jharkotchura

Punjab : Kagphala, Kuchila, Harbal Jarab

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TABLE NO.1 SYNONYMS OF KUPEELU

Synonyms M.

Ni.

Shal.

Ni.

Sh.

D.

Ni.

Kai.

Ni.

Dh.

Ni.

Raj.

Ni.

Sa.

Van.

Ni.

Abhi.

Ni.

Bh.

Pr.

Ni.

Bhar.

Van.

San.

Ni.

Rat.

A.P R.T.

Tinduka + + + + + + + + +

Syandana + +

Sphurja + +

Kalsara + +

Ravana + + + +

Kalpilu + + + + + + +

Vishatinduka + + + + + + + +

Karaskara + + + + +

Kimpapa + + +

Vishdruma + + + +

Gardroom + + +

Ramyaphala + + + +

Kupaka + + + +

Kalkutaka + + + +

Nagvalidala + +

Padapa + +

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Synonyms M.

Ni.

Shal.

Ni.

Sh.

D.

Ni.

Kai.

Ni.

Dh.

Ni.

Raj.

Ni.

Sa.

Van.

Ni.

Abhi.

Ni.

Bh.

Pr.

Ni.

Bhar.

Van.

San.

Ni.

Rat.

A.P R.T.

Kalskanda + + + + +

Tanuka + + +

Dirghapatra + +

Sphurjan + + + +

Skandita + +

Syandana + + + + +

Visfurjani +

Tinduki +

Virla + +

Kakenduka + + +

Kupeelu + + + + + + +

Stholtinduka + +

Neelsara + +

Mustaka + + + +

Sfurjaka + + + + + +

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Synonyms and their meanings

Karaskara: poisonous medicinal plant

Kupeelu: a poisonous plant pertaining to a lower variety

Ramyaphala: pleasing and beautiful fruit according to morphology.

Dirghapatra: the leaves are long and wide (morphology)

Visha druma &gara druma: druma is a synonym of plant,whereas visha is poison.

Vishamushti: mushti is 1 pala according to maana paribhasha. This indicates dose decides

the effect of poisonous plant.

Vishatinduka: poisonous variety of tinduka

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TABLE NO. 2 RASA PANCHAKA OF KUPEELU

SL

NO

REFERENCE RASA GUNA VEERYA VIPAKA

1 D.N Madhura Madhura

Guru

2 M.N Laghu (unripe)

Guru (ripe)

3 K.N Tikta

kashaya

Laghu Sheeta Katu

4 R.N Katu

Tikta

Ushna

5 N.R Katu

Sheeta

6 BPN Tikta

Laghu Sheeta

7 SA.N Mahatikta

Vishada ,guru Ushna Madhura

8 N.A Katu Ushna

Katu

9 P.N Katu , tikta

Sara Ushna

10 SH.N Mahatikta

11 M.D.G

Vishada ,guru Sheeta

12 Y.R Katu , tikta

Ushna,Teekshna Ushna

13 R.T Katu

Teekshna Ushna

14 D.G.V Katu , tikta

Ushna

15 D.G.H Katu , tikta

Teekshna,laghu,ruksha Ushna Katu

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TABLE NO. 3 SHOWING DOSHA KARMA OF KUPEELU

SL.

NO

DOSHA KARMA

P.

N

SH.

N

R.N M.D.

G

M.

N

K.

N

B.

P

SA.

N

1 VAATAMAYAHARA

+ + +

2 KAPHAVAATAHARA

+

3 KAPHAPITTASRANASHA

NAM

+ + + + + +

4 VAATALAM

+ +

TABLE NO. 4 SHOWING SAMANYA KARMA OF KUPEELU

SL.NO SAMANYA KARMA P.N M.D.G M.N K.N B.P Sh.N

1 DEEPANA +

2 PACHANA +

3 GRAHI + + + + +

4 MADAKARA +

5 BALYA +

6 VAJIKARA +

7 KANDUGHNA + +

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TABLE NO. 5 SHOWING ROGAGHNATA OF KUPEELU

SL.NO ROGAGHNATA P.N R.N M.D.G M.N SH.N

1 JWARA + +

2 BHAGNA +

3 KUSTA + +

4 ARSHA + +

5 VRANA + + +

6 PRAMEHA + + +

7 KARSHYA +

VISHISHTA GUNA KARMA OF VISHATINDUKA52

Vishishta Guna: It is Agneya in nature with Katu rasa, Parama deepana, Ugra veerya,

Teekshna, Uttama kamoddeepaka , Mootrala, Deepana, Pachaka, Shleshma hara,

Balasanjanaka, Medohara, Ruchikara,

Vishishta Karma: Grahanihara, Unmada vinashaka, Adhmanahara, Ajeerna vinashaka,

Amashayasta shoolahara, best Hrudaya dourbalyahara, Shwasaprashamaka, Alleviates

puppusa shotha, Ardhanga ardita vata nashaka, Nadibala vardhaka, Dusta naga

sevanajanya dosha, Madatyaya, Ardhangavatahara, Angashoshahara, Used in the

treatment of rabid animal bite, Pakshaghata associated with karshya, Rigidity and

Numbness, Nadishoola, Anidrahara, Arshoghna, Alleviates excessive perspiration at

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night due to Rajayakshma and Manasika shrama sambhoota avasada.

Also useful in Ajeerna due to Anidra, Dugdha pachakaamla and tikta udgaara,

Chitta dourbalya due to shrama, Malabhaddata, Adhmana, Amlapitta sambhoota

antrashoola, Painful defecation, Difficulty to defecate and with decreased quantity of

feaces, Patient presenting with an urge of micturition with less quantity associated with

daha, Chronic bleeding disorders, Decrease in length of menstrual cycle less than 28

days, Metromenorrhagia, Shweta pradara with durgandha and srava with yellowish

colour, Prista shoola which begins at night, Kativedana, Shwasa due to Pitta dosha which

increases after consumption of food, Nava pratishyaya, Vartmaspandanakam,

Atisara caused by Ratri jagarana and Atibhojana ,characterised by Bowel sounds,

Bleeding and watery stools, and where in Urge of defecation associated with increased

frequency which is painful and decreased quantity of stools. If a person is alone and

agitated, angry then the quantity administered must be less.

EXTERNAL USES53

Vatashamak, it alleviates pain, oedema and is an analgesic (Vedanasthapana). It is

used for external application in rheumatoid arthritis, osteoarthritis. An application of

seeds with turmeric cures oozing and foul smelling ulcers. This paste is also effective in

ulcers with toxic symptoms. The leaves in the form of poultice are very useful in oozing

ulcers.

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INTERNAL USES54

Central nervous system:

It alleviates vata and pain. It stimulates and strengthens nerves because of its

sharpness. Useful in vata disorders like Neuralgia, Facial palsy, Hemiplegia, Insomnia.

Excess dose leads to intoxication and convulsions.

Digestive system :

Being bitter and pungent, it is a good appetizer, digestive and (pachana),

astringent (grahi), useful in abdominal pain by its ushna and vata alleviating property. It

is used in loss of appetite, gastric inflammation, amadosha, colitis, piles, and parasitic

infections. It is the best medicine for gastric laxity and spasm.

Circulatory system :

Being Ushna and Tikshna, it is a cardiac stimulant (Hrdayottejaka) and

hypertensive. It alleviates oedema caused by Kapha. Useful in disorders of cardiac laxity.

Respiratory system :

Being pungent and bitter, it is Kaphaghna and alleviates cough. It is also useful in

inflammation of lungs.

Urinary system :

Dribbling of the urine due to Atonicity of bladder is corrected by it. It is an

effective medicine for nocturia in children and adults.

Reproductive system :

It is an aphrodisiac (Vajikarna). It cures premature ejaculation and impotency.

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Satmikarana :

It is an excellent rasayana. It cures the laxity of body tissue. It is a good medicine

for the loss of appetite, insomnia and laxity of body in elderly..

Skin :

Nux-vomica is useful in dermatosis, pruritis and excess perspiration.

Temperature :

It is effective in fever with shivering and periodical fever. It reduces shivering and

rigors.

PRACTICAL USE IN FOLKLORE MEDICINE55,56

1. Seed paste is applied on swelling and inflammation due to Filariasis.

2. Seed paste is applied externally on dog bite.

3. One seed is rubbed with water and 1-2 cloves are mixed into it. This is applied

over the gum twice daily for 6 months, with gentle massage to treat pyorrhoea.

4. Ripe fruits boiled in water. Foot or palm is kept over the water so as to reach vapours

on skin eruptions.

5. Seed oil is applied on scabies.

6. Roasted seeds made into powder are given orally to treat joint pain.

7. Powder of roasted seed mixed with ginger, sugar and water is given to drink in case

of Diarrhoea.

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DOSAGE57

The therapeutic dose of Nuxvomica is 30-125 mg. The smallest dose which is

known to produce death in humans is 30 grains i.e. equal to one seed of Nuxvomica. The

minimal oral dose of strychnine in adults is 30-120 mg. The lethal dose in children is 15

mg. If strychnine is given parenterally, the lethal dose is again lowered.

Adverse effects of vishatinduka58

Consumption of vishatinduka without purification or excessive consumption

causes Dhanusthambha, Aaskhepaka, Angamarda, Kampa, Dantaharasha, Drishti

mandala Vyakocha(Pupil dilatation), Nadi mandata (Dull Pulse)

Management of visha tinduka poisoning59

Nagavallidala Swarasa with goghrita. By drinking this receipe, the poisonous

effect of vishatinduka can be cured.

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VISHISHTA YOGAS:

TABLE NO. 6: SHOWING VISISHTA YOGAS OF KUPEELU AND THEIR

THERAPEUTIC USES AS MENTIONED IN BHAISHAJYA RATNAVALI60

Sl.no Visista yogas Therapeutic uses

1 Vishatindukaadi thaila Vataraktha

2 Vishatindukaadi lepa Upadamsha

3 Kupeelubeejadi kwatha Lasika meha

4 Kupeelu choorna Shayya shoola

5 Khanjanikaari rasa Pakshaghata, khanjanika

6 Arshogna dhooma Arsha roga

7 Arkapushpaadi vatika Agnimandya, udarashoola

8 Saptaparnasatvaadi vati Vishama jwara

9 Virechani gutika Naadi vrana, bhagandara

10 Vicharchikaadi taila Krimi, virechana, jwara

11 Vishweshwara rasa Vataraktha, jwara, agnimandya, kushta

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TABLE NO. 7: SHOWING VISHISHTA YOGAS OF KUPEELU AND THEIR

THERAPEUTIC USES AS MENTIONED IN YOGARATNAKARA 61

Sl.no Visista yogas Therapeutic uses

1 Vardhamaana karaskara

prayoga

Alarka visha

2 Trailokya tapahara rasa Nava jwara

3 Vishagarbha taila Sandhivata, gridhrasi, sarvanga vata,

karna nada.

TABLE NO. 8 : SHOWING VISHISHTA YOGAS OF KUPEELU AND THEIR

THERAPEUTIC USES AS MENTIONED IN RASA TARANGINI. 62

Sl.no Vishishta yogas Therapeutic uses

1 Vishatindukaadi taila Pakshaghata

2 Supta vatari rasa Supta vata

3 Navajeevana rasa Agnimandya, antra shoola.

4 Agnitundi vati Atisara, nadibala vardhaka.

5 Lakshmivilasa rasa Veeryavardhaka

6 Shoolanirmoolana rasa Gulma, grahani, shoola.

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TABLE NO. 9: SHOWING VISHISHTA YOGAS OF KUPEELU AND THEIR

THERAPEUTIC USES AS MENTIONED IN RASENDRA SAARA SANGRAHA63

Sl.no Vishishta yogas Therapeutic uses

1 Sarvanga sundara rasa Shoola, vatavikara

2 Shoolaharana yoga Gulma, atisara ,grahani.

3 Agnimukha rasa Agnimandya

4 Galatkustari rasa Kusta

Rasaprakashsudakar64

- Krimi Virechani Vati used in kostagata krimi.

Bharatabhaisajya Ratnakara65

- Sameera Gajakesari rasa used in vatavyadhi.

Precautions:

Drug is used only after purification and within limitation of doses for avoiding

complications and toxic effects. Prolonged use of drug also needs due care. Proper care

for using purified seeds needs to be followed in oral uses of the drug.

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TABLE NO. 10: SHOWING SCIENTIFIC CLASSIFICATION66

Kingdom: Plantae

(unranked): Angiosperms

(unranked): Eudicots

(unranked): Asterids

Order Gentianales

Family Loganiaceae

Genus Strychnos

Species nux-vomica

Binomial name Strychnos nux-vomica.linn

BOTANICAL SOURCE67

Nux vomica consists of the dried ripe seeds of Strychnos nux-vomica Linn.Containing not

less than 1.2% Strychnine.

DISTRIBUTION68

It occurs in India, Sri Lanka and Burma. It is found in tropical forests specially in

Manbhund, Tamilnadu, Tranvancore - Cochin, Konkan Malabar, Orissa and other regions

of country. It is also occasionally planted in gardens. Plant occurs in warm regions of

India up to an altitude of 1204 meters (4000 ft.) in wild state. Frequently growing in

Orissa, Madras, Cochin, Bengal and Bihar.

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COLLECTION / DESCRIPTION69

The plant is small to medium sized tree, up to 10-18 meters in height, branches spreading,

often with axillary thorns, bark smooth, whitish in colour.

Leaves - shining, opposite, broadly ovate to elliptic, rounded or slightly cordate and 5-

nerved at base, up to 15 cm long, petiole up to 1.5 cm long. Tree changes leaves during

hot season, occasionally leafless for a short time.

Flowers – greenish white, interminal, pedunculate, compound cymes. Calyx -lobes cute,

pubescent outside. Corolla - hypocrateriform, lobes minutely tomentose on margins.

Stamens -subsessile inserted inside the mouth of corolla tube. Style - sparsely woolly

hairy.

Berry -as large as an orange or subspherical yellowish brown orange like berries. Berry

on strongly thickened branches, globular, orange red, upto 7 cm across. Seeds 4,

sariceous, flat, nearly circular, grey, shining clothed on both sides with fine silky hairs

radiating from the centre. At one point on the margin the micropyle forms a prominence

from which a raised line passes to the centre of the seed. The drug is odourless, but

possesses an intensely bitter taste. Epicarp -is leathery and the pulp is bitter whitish and

mucilagenous in which seeds are embedded.

The tree is found growing in regions where the absolute maximum shade temperature

varies from 350Cto 45

0C and minimum from 4

0C to 18

0C, and where rainfall ranges from

75 to 375 cm or more. The tree is a shade - bearer, growing under a moderate canopy

even in semi evergreen forests. It produces root-suckers and is free from damage by

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browsing, as animals avoid it. In most forests, the tree is evergreen, but in dry areas it

sheds the leaves for a short time.

MORPHOLOGY OF STRYCHNOS NUX-VOMICA .LINN(SEEDS) 70

Size: 10 to 30 mm in diameter, 3 to 5 mm thick.

Shape: Disc shaped, flat, some concavo-convex, few seeds irregularly bent, margin

rounded or acute.

Outer surface: Grey to greenish-grey covered with numerous, closely appressed silky

hairs, radiating from the centre, hairs impart a characteristic hilum is present in the centre

of the flat surface of the seed. From the hilum a ridge which is not raphe connects the

position of the micropyle at the circumference. They are very hard when dried.

Endosperm: It is present below the testa and is grey and horny. Below the endosperm in

the centre is a narrow slit like cavity.

Embryo: It is seen at the micropylar end with a cylindrical radicle and two cordate

cotyledons.

Odour: None

Taste: possesses an intensely and persistently bitter taste.

Flowering and Fruiting time:

Plant flowers in May-July and fruits in November - January.

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CHEMICAL COMPOSITION71

It contains two important alkaloids namely Strychnine and Brucine. They also

contain vomicine, colubrine, loganine, glucoside and fatty substance up to 3% alkaloids.

Total content of the alkaloids ranges from 2.6% to 5.3% of which approximately half

proportion is of strychnine, but bark yields only brucine. Strychnine (C21H22O2 N2) and

brucine (C23H26O4N2) are the most important and strongly toxic alkaloids present in this

plant, besides other minor alkaloidal constituents. These alkaloids occur not only in the

seed but also in the roots, wood bark, leaves, fruit pulp and the hard fruit shells. No

quaternary bases are found in the seeds. Minor alkaloids present are vomicine

(C22H21N2O4), colubrine (C22H24O3N2), pseudostrychnine (C21H22O3N2), pseudobrucine

(C24H28O5N2). The glucoside loganine is also present. Pseudostrychnine is nontoxic. The

leaves have earlier been reported to contain strychnine and brucine (together 1.6%) and

strychnicine (0.025%). Recent investigations have revealed that in addition to strychnine

the leaves contain vomicine as the major constituent alkaloid along with an unidentified

alkaloid. Another alkaloid, (N-methyl pseudostrychnine), has been reported from the

leaves of very young plants.

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THE CHEMICAL STRUCTURES OF MAJOR ALKALOIDS.

Strychnine Brucine

Molecular Weight: 334.412g/mol Molecular Weight: 394.464g/mol

Molecular Formula: C21H22N2O2 Molecular Formula: C23H26N2O4

Vomicine Pseudostrychnine

Molecular Weight: 380.437g/mol Molecular Weight: 350.411g/mol

Molecular Formula: C22H24N2O4 Molecular Formula: C21H22N2O3

α-Colubrine β-Colubrine

Molecular Weight: 364.438g/mol Molecular Weight: 364.438g/mol

Molecular Formula: C22H24N2O3 Molecular Formula: C22H24N2O3

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Icajine Novacine

Molecular Weight: 364.438g/mol Molecular Weight: 424.49g/mol

Molecular Formula: C22H24N2O3 Molecular Formula: C24H28N2O5

Strychnine N-oxide Brucine N-oxide

Molecular Weight: 350.411g/mol Molecular Weight: 410.463g/mol

Molecular Formula: C21H22N2O3 Molecular Formula: C23H26N2O5

Isostrychnine Isostrychnine N-oxide II

Molecular Weight: 334.412g/mol Molecular Weight: 350.411g/mol

Molecular Formula: C21H22N2O2 Molecular Formula: C21H22N2O3

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STRYCHNINE73

Occurs as colourless, transparent crystals, or as a white crystalline powder. It is

odourless and has an extremely bitter taste, perceptible even in such aqueous dilutions as

1 in 7,00,000. It has a reputation as a cardiovascular and respiratory stimulant and a bitter

tonic, stimulating all parts of the central nervous system.

Strychnine has relatively more powerful stimulant action on the motor cells of

the central nervous system, especially on the spinal cord. On account of its action on the

cerebrum, the mental faculties are stimulated, the tactile and pain sensations are

augmented and the sense of hearing, smell and taste becomes more acute. It appears to be

clinically useful in some forms of chronic heart diseases, especially myocarditis, but the

efficacy of strychnine as a circulatory stimulant in such conditions as surgical shock,

collapse from haemorrhage, poisoning by depressant (ether, chloroform, barbiturates, or

alcohol) and a dynamic stages of infectious fevers, is open to serious question. It lessens

irritability of the heart and is useful in extra systoles, but may be harmful in other forms

of cardiac irregularities. As a respiratory stimulant, it is valued in narcotic or hypnotic

poisoning, as by opium or chloral. It has also been claimed to be useful in the treatment

of toxic amblyopias, especially that due to nicotine poisoning.

Strychnine has been widely used as stomachic. It was frequently incorporated in

laxative mixtures and tablets, but this use is without therapeutic justification and may be

responsible for fatal poisoning. Small doses of strychnine delay the onset of fatigue, but

this delay is followed by a phase of depression in muscular activity.

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Strychnine is said to be useful in the treatment of various spasmodic diseases, such as

Cholera, Asthma and Epilepsy. It is also employed as an aphrodisiac.

The ripe and dried Nux-vomica seeds, as well as Strychnine hydrochloride, are

official in I.P. The ripe and dried seeds should contain: Strychnine, < 1.2%; foreign

organic matter, > 1.0; and ash, > 3.0% Strychnine hydrochloride (dose: 2-8 mg) should

contain not less than 97.5% and not more than the equivalent of 100.5% of C21H22O2N2.

HCl, calculated with reference to the substance dried to constant weight at 130o C.The

loss on drying shall be 7-9%, and sulphated ash not more than 0.1%. Official preparations

include strychnine hydrochloride solution, nuxvomica powder, liquid extract, and

tincture, and prepared nux-vomica.

Strychnine is rapidly absorbed from the gastrointestinal tract, carried in the blood

by both the plasma and erythrocytes, and rapidly leaves the circulation for the tissues. It

is readily destroyed in the body, mainly by the enzymes of the liver microsomes. Nearly

20% of the alkaloid escapes into the urine.

TOXICOLOGY OF STRYCHNINE:

Ordinarily, the fatal dose for a human being lies between 30 and 60 mg of

Strychnine, however, under proper treatment recovery may occur from much larger

doses. Toxic doses of strychnine and powdered seeds for the different animals have been

reported as follows respectively: horse, 0.192 - 0.288, 19.2 - 28.8; 0.192 - 0.384, 19.2 -

33.6; Pig. 0.0096 - 0.048, 3.8 - 5.8; and dog, 0.0048 - 0.0192, 0.5 - 1.0 g. Guinea pigs and

some monkeys appear to be remarkably insusceptible to strychnine administered poisons.

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SYMPTOMS

The symptoms of poisoning of strychnine usually develop with great violence. The

first noticeable effect is stiffness of the face and neck muscles. Sudden movements, such

as shrugging of shoulder or abrupt jerking of an arm or leg are some of characteristic

manifestations. Heightened reflex-excitability soon becomes evident. All voluntary

muscles, including, those of the face, are in full contraction. Respiration ceases due to the

contraction of the diaphragm and the thoracic and abdominal muscles.74

TREATMENT

The treatment of strychnine poisoning should aim at two operations: (1) To

prevent convulsions, and (2) To support respiration. Many agents have been suggested

for the control of convulsions, these include the use of Chloroform by inhalation, Sodium

bromide by rectum, and Chloral hydrate by mouth, but the best is probably one of the

barbiturates (like Phenobarbital sodium or amytal sodium) administered intravenously.

Endo-tracheal intubation to provide proper control of respiration is an important

safeguard; following this, small amounts of curariform drugs may be employed to lessen

the intensity of the muscular contractions. 74

Gastric lavage may be performed if some of the poison is still suspected to be

present in the stomach. Potassium permanganate in a 1:1,000 concentration is an effective

antidote. Iodine tincture, diluted with water (1: 250) or tannic acid solution (2% or in the

form of strong tea), may be employed. It is important to minimize tactile and auditory

stimulation of the patient during the course of treatment.

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Other alkaloids - Brucine closely resembles strychnine in its physiological action, but is

much feebler, 30-80 times of the alkaloid being required to produce the same effect. In 5-

10% solutions, it possesses a distinct local anaesthetic action. One of the main uses of

brucine has been as a denaturant for alcohol, used in cosmetics and perfumery.

In Britain, the use of brucine in this manner is confined to surgical spirit which may

contain not more than 0.015% of it. On account of bitter taste, it is an adequate deterrent

to the use of denatured alcohol for portable purposes without imparting any adverse

effect on odour or other properties of compounded perfumes. In 1959, new uses of

brucine in petroleum technology in USA were reported, and its demand from petroleum

companies suddenly increased.

Vomicine produces clonic convulsions differing from those produced by strychnine,

apparently due to some action on the cerebrum.74

ANTIDOTE:

As soon as toxic symptoms appear, give stomach wash and give cow's ghee along

with cow's milk. Use antidotes like opium, belladona, camphor, ganja and tobacco.

PHARMACOKINETICS:

Nuxvomica is rapidly absorbed from gastro-intestinal tract while strychnine is

absorbed from G.I. tract, nasal passage or parenterally injection site. Strychnine is found

in plasma RBC, bile, liver and tissue of G.I. tract. The half-life of strychnine is 10 hrs.

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METABOLISM:

Strychnine is mainly metabolized in liver. It is metabolized by enzyme of hepatic

microsomes. Strychnine is excreted from urine without any change. 10-20% of strychnine

is eliminated through urine in first 24 hrs. The excretion is inversely proportional to the

dose ingested. Strychnine is totally excreted within 48 to 72 hrs.

TOXICITY

In toxic dose, strychnine produces restlessness and suffocation. There after

tremors are developed all over the body. Convulsions are developed and all the muscles

are affected at the same time. Poisthotonus, i.e. the body resting on head and healing

takes place. The patient is very much excited and very small stimulus can aggravate the

symptoms. In the period of convulsions patient is completely conscious and depressed.

Convulsions occur intermittently. The frequency and intensity of the convulsions depends

upon the sensory stimulus. If the patient is not treated properly patient may die due to

respiratory arrest within 2-4 hrs. If the patients survive for more than 12 hours even after

the fatal doses, then prognosis is said to be good.

CONTRAINDICATIONS:

Nuxvomica is contraindicated in pregnancy and breast-feeding. It is also

contraindicated in contact dermatitis.

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REVIEW OF PREVIOUS WORK DONE: 75

(1) Varanasi (1983) – Department of R.S.

Katiyar C.K. – Study on Kupeelu Sattva. Pharmaceutical Chemical and

Pharmacological Study. (M.D. thesis)

Katiyar Chandrakant (1988) – Neuro clinical and neuro pharmacological studies on

Shuddha Kupeelu. (Ph.D. thesis)

Tewari O.P. (1979) – Sarvanga Gata Vata (peripheral neuritis) and its management

by an indigenous drug Karaskara (S. nuxvomica).

Tripathi S.K. (1983) – Evaluation of Shuddha Kupeelu in the management of

Amavata (Rheumatoid Arthritis).

(2) Lucknow (1984)

Yadav R.S. – Kupeelu Bheshajika evam Dravya Gunatmaka Adhyayana.

(3) Bangalore (Koppa) (2000)

Pradeep H.R. – Effect of Shodhana on toxicity (Purification) of Kupeelu.

(4) Shimla (H.P.) (2003)

Saharan Dipti - A comparative clinical study on the role of Simhanada Guggulu

and Shuddha Kupeelu in management of Amavata w.s.r. Rheumatoid arthritis.

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(5) Nagpur (2000)

Thakare P.G. – Vanaspatika Visha – Kupeelu Beeja Ka Sanskara Poorva Evam

Sanskara Paschat Prayogashaleeya Adhyana.

(6) Ujjain (2005-2006)

A pharmacotherapeutic study of Kupeelu as a Vatahar w.s.r. katisoola (low back

pain).

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REVIEW OF DRUGS USED IN KUPEELU SHODHANA

GOKSHEERA

Goksheera is one among a jangama dravya which is obtained from the cow. It was

used as a media for kupeelu swedana, the description is as follows.

TABLE NO. 11 CLASSIFICATION OF GOKSHEERA IN SAMHITAS

76,77,78

Sl. No. Text Varga

1 Charaka. Gorasavarga

2 Shushrutha Ksheeravarga

3 Vaghbhata Ksheeravarga

TABLE NO. 12: GUNAKARMAS OF GOKSHEERA

79

Rasa Madhura

Guna Mrudu, sheetha

Virya Sheetha

Vipaka Madhura

Karma Karma -brumhana, balya, jeevaneeya, vrushya, rasayana ojo

gunasama, aajanma satmya dravya.

Doshagnata Vatapittaprashanam

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TABLE NO. 13: COMPARISON OF VISHA AND KSHEERA GUNAS80,81

Sl.no Visha guna Ojo guna & ksheera

guna

1 Laghu Guru

2 Ushna Sheeta

3 Teekshna Mrudu

4 Sukshma Sthula

5 Ashukari Prasada

6 Vyavayi Sthira

7 Vikasi Slakshna

8 Vishada Picchila

9 Ruksha Snigdha

10 Anirdeshya rasa (charaka)

Apaki (sushruta)

Vishamapaki (vagbhata)

Madhura

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Physical properties of Cow’s milk 82

1. pH : 6.5 to 6.7

2. R.I. of Milk : 1.3440-1.3485 at 200C

3. Viscosity : 2.0 Cp at 250C

4. Surface Tension : 50 dyn/cm at 200C

5. Specific gravity : 1.029 to 1.035

6. Freezing point : -0.58 to 0.54°C

TABLE NO.14: ANALYSIS OF MILK COMPOSITION.83

Sl.No Constituents Percentage Sl.No Constituents Percentage

1. Solids 12.63 8. Solids (not fat) 08.94

2. Proteins 03.14 9. Fat 03.69

3. Lactose 04.82 10. Ash 0.71

4. Potassium 23.54 11. Sodium 11.44

5. Calcium 22.57 12. Magnesium 2.84

6. Iron 00.31 13. Phosphorus 27.68

7. Chlorine 15.01

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GHRITA

Ghrita is one among the four snehas mentioned in Ayurveda and considered to be

the best among them.84

It increases smriti, buddhi, agni ,shukra, oja, kapha, medas. Cures

vata, pitta and visha. 85

For all these actions to be possible it should be easily digestible.

Ghrita contains approximately 8% lower saturated fatty acids which makes it easily

digestible.These lower saturated fatty acids are the most edible fat and which are not

found in any other edible oil or fat. The melting point of Ghrita is 35 0C which is less

than the normal temperature of the human body. Its digestibility co-efficient or rate of

absorption is 96% which is highest of all oils and fats.

Concept of free radical and ghrita in degenerative diseases will explain its kaanti,

smruti, dhee bala, medhokara action. Ghrita contains beta carotene and Vit. E which are

known antioxidants. It is estimated that 80% to 90% of degenerative diseases are related

to excessive production of free radicals of reactive oxygen species (ROS).

When free radicals are in excess they try to catch on to whatever is available in

their surrounding area and this is how the lipids in the blood and cell membrane are

oxidized. The oxidized lipids or the lipid peroxides are injurious to the system. The

reactive oxygen species cause damage to the DNA in the cells.

The effectiveness of compounds is due to potent anti-oxidant properties of

removing of scavenging free radicals. Antioxidants are helpful in preventing oxidative

injury to the body.

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Ghrita also contains 4-5% linoleic acid an essential fatty acid which promotes proper

growth of human body.

EFFECTS OF HEAT ON GHRITA.

Ghee is said to be the primary most important sneha because of its samskarasya

anuvartana guna 86

Ghee is an ideal fat for deep frying because its smoke point (where its

molecules begin to break down) is 250 0C (482 degrees F), which is well above typical

cooking temperatures of around 200 0C (392 degrees F) and above that of most vegetable

oils. Samskarasya anuvartana means it brings in its qualities and reduces the tikshnata of

the dravya.

Ghrita has very high smoke point and does not burn or smoke easily on heating

because it has more stable saturated bonds. Ghrita lacks the double bonds which can be

easily damaged by heat.So it is not likely to form the dangerous free radicals on heating.

Short chain fatty acids are also readily metabolised by body. This quality allows ghrita to

imbibe the potency of drugs and not even to leave its own property on heating.

It is used as media for absorption of lipid soluble vitamins or other active

principles in the food or medicine. Goghrita is used for kupeelu bharjana.

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TABLE NO. 15 CLASSIFICATION OF GOGHRITA IN SAMHITAS

87,88,89

8Sl. No. Text Varga

1 Charaka Gorasavarga

2 Shushrutha Gruthavarga

3 Vaghbhata Ksheeravarga

TABLE NO.16 :GUNAKARMAS OF GOGHRITA IN CHARAKA SAMHITA

90

Rasa Madhura

Guna Mrudu, sheetha

Virya Sheetha

Vipaka Madhura

Karma It increases smriti, buddhi, agni, shukra, oja, kapha, medas. Cures

vata, pitta, visha, unmada, shosha and jwara , snehana, vrushya,

rasayana.

Doshagnata Vatapittaprashanam

`

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CHEMICAL COMPOSITION OF GHEE91

(Per 100g. edible portion)

Moisture (g) - 0.5

Fat (g.) - 99.5

Vitamin A (I.U.) - 2,000

Energy - 900 K. cal

The composition of fat content of Ghee is as follows:

Triglycerides, diglycerides, monoglycerides, ketoacid glycerides, glyceryle esters Free

fatty acids, Phospholipids, Sterol, Ghee contains beta carotene (600 mcg) and Vit E, both

known antioxidants.

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PHARMACEUTICAL REVIEW

CONCEPT OF SHODHANA:

Shodhana

Shodhana is pharmaceutical procedure in which all the rasa dravyas are

subjected to a process, before subjecting them to marana or before internal

administration.

The literary meaning of shodhana is purification, But in Rasashastra, shodhana is

not merely purification, but it is a samskara, which essentially brings out modification or

alteration in properties along with purification.

Historical Background:

It is only in Rasashastra and Nigantu period when the shodhana of minerals and

metals as well as herbal drugs specifically, was evolved.

Most of the raw materials in Rasashastra are extracted from earth, so there is every

chance of impurities, toxicity, mixing of other substances and unwanted qualities to a

large extent. So Shodhana is indicated to eliminate all such toxic qualities such that the

substance becomes easily assimilable in the body.

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NIRUKTI

According to vachaspati word shodhana is a pullinga shabdha derived from

“shudh” dhatu “nich” pratyaya and “plut” upasarga

Definition

The process which eliminates the untoward quality is called Shodhana.

When a substance is subjected to trituration etc with appropriate drugs for

removal of unwanted materials or impurities is known as shodhana.

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Subjecting the Loha, Dhatu, Rasa-uparasas and Visa-upavisas etc to the procedures like

Swedana, Marana etc with appropriate materials to remove the doshas is termed as

shodhana

Shodhana is a process of separation by which physical and chemical

impurities get separated from the substances by treatment with various drugs. It is a

process by which blemishes are separated from the substance by means of pharmaceutical

processing such as Swedana, Mardana etc. with particular drugs.

Some kind of changes may also take place apart from these, which may

be beneficial for therapeutic purposes.

In Rasashastra, most of the raw materials used to prepare medicines are

metals, minerals and poisonous plants etc. which are said to be toxic and are not intended

to be used for therapeutic purposes. They may be fatal when used in the natural form

because they may contain either of the following impurities.

(1) Natural impurities.

(2) Physical impurities.

(3) Chemical impurities.

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(1) Natural impurities:

By the virtue of the nature some drugs are toxic e.g. drugs of Visha and

Upavisha groups. So to eliminate or minimize their toxicity the Shodhana process is most

important.

(2) Physical impurities:

Normally minerals are obtained from the earth. So there is possibility of

mixing of unwanted substance with these minerals i.e. stone, clay etc. Sometimes,

businessmen adulterate some low quality substances. These are physical impurities which

are to be eliminated by Shodhana.

(3) Chemical impurities:

Metals like copper, mercury, arsenic are having such type of impurities.

These metals are under the earth for so many years. So there is a chance of chemical

reaction with other metals and thus chemical impurities are formed.

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In order to make such drugs safe, effective and fit for human usage they

have to be subjected to many pharmaceutical procedures and shodhana is one among

them.

SIGNIFICANCE OF SHODHANA

Elimination of physical and chemical impurities, which are not desired.

Eradication or minimization of toxicity of the material.

Transformation of the hard and non-homogeneous material to soft,

brittle, and homogeneous material.

Induction of desired qualities.

Potentiation of therapeutic efficacy of the drug material.

Conversion of the material in suitable form for further processing.

Leads to unique and suitable physico-chemical changes.

For the therapeutic uses in some cases, Shodhana process is described in

classics of Rasashastra which is not merely a process of separation, purification or

detoxification, rather it increases the therapeutic potency of the drug also.

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Principles used in shodhana Procedure: 95

Swedana (Boiling under liquid bath): The material is boiled in prescribed liquid

media through Dola Yantra method e.g. Kupeelu Shodhana.

Bharjana (Frying): The material is fried with specific liquid media on Mandagni

e.g. Kupeelu Shodhana, Gairika Shodhana etc.

Nimajjana (Dipping): The material is kept immersed in the prescribed liquid for

specific period e.g. Kupeelu Shodhana, Vatsanabha Shodhana.

Prakshalana (Washing): The material is washed with prescribed liquid to remove

its physical impurities e.g. Godanti Shodhana.

Prithakikarana (Separation:Physical impurities are removed manually e.g.

Guggulu Shodhana.

Atapa Soshana (Drying): The material is kept on fire or exposed to sun rays till it

dries e.g. Shilajatu Shodhana.

Mardana (Trituration): The material is ground properly with prescribed drug for

specific period. e.g. Parada Shodhana.96

Bhavana (Levigation): The material is triturated with prescribed liquid media for

specific time period e.g. Kasisa Shodhana.

Abhisheka (Sprinkling): The material is heated strongly and liquid media is

sprinkled on it .e.g. Mandura Shodhana.

Nirvapa (Heating and Quenching): The red hot material is dipped into the

prescribed liquid e.g. Rajata Shodhana.

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Dhalana (Melting and Quenching): At first the material is melted by intense heat

and then poured into a liquid media e.g. Naga Shodhana.

Galana (Melting and Straining): The solid material is melted first by heating and

then filtered through a cloth e.g. Gandhaka Shodhana.

Achushana (Absorption): Oily content of certain toxic material is minimized

through different absorption means e.g. Bhallataka Shodhana.

Nirjalikarana (Evaporation of water): Whole water content of the material is

evaporated by heating e.g. Sphatika Shodhana.

Patana (Sublimation): Through patana yantra the material is heated to convert into

vapour from which the material is regained again by condensing e.g. Parad Shodhana.

Parishravana (Straining): The solid material is dissolved in suitable liquid media

and separated from insoluble impurities through straining e.g. Navasadara Shodhana.

Vilayana (Elutriation) : The material is firstly dissolved in prescribed liquid media

and left as such for some time, then the upper part of the liquid containing the soluble

drug material is decanted into another pot leaving behind the impurities in the bottom of

first pot e.g. Shilajatu Shodhana.

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Shodhana process is grossly subdivided into two major categories as follows:

i.e. Samanya Shodhana and Vishesha Shodhana.97

Samanya Shodhana (General Purification):

In Rasashastra, drugs are grouped into Rasa, Maharasa, Uparasa,

Sadharana Rasa, Dhatu, Upadhatu etc. The Shodhana Samskara prescribed commonly for

a group of drugs is called as Samanya Shodhana. This process eliminates the general

impurities of metals and minerals and convert them into powder form which is essential

for the further processing i.e marana e.g. Samanya Shodhana of Dhatu.

Vishesha Shodhana (Specific Purification):

After Samanya Shodhana, Vishesha Shodhana is suggested for each drug. The

drugs of one group differs from others in origin, structure, form, impurities etc. Therefore

a specific procedure for each drug is suggested separately. Moreover for including

desired therapeutic values in a particular drug, "Vishesha Shodhana" is mentioned.

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TABLE-17 : SHODHANA OF KUPEELU WITH DIFFERENT MEDIAS

SL.

N

TEXT METHOD MEDIA DURATION

1 RASASANKETA

KALIKA98

BHARJANA GOGHRITA TILL IT

BECOMES

REDDISH

BROWN

2 RASAKAMADENU99

DO DO DO

3 AYURVEDA

PRAKASHA100

DO DO DO

4 RASAJALANIDHI101

1.SWEDANA

2.SWEDANA AND

BHARJANA

1.KANJI

2.GOMAYAJALA,

PAYASA AND

GOGHRITA

1. 2 PRAHARA

5 RASENDRA

PURANA102

SWEDANA

& BHARJANA

KANJI AND

GOGHRITA

SWEDANA FOR

2 PRAHARAS

6 RASARAJMAHAUDA

DHI103

1. BHARJANA

2. STAPANA AND

SWEDANA

1.GOGHRITA

2.GOMUTRA AND

GODUGDHA

2. 10 DAYS, 1

PRAHARA

7 RASAMRUTA104

STHAPANA

FOLLOWED

BY PACHANA

GOMUTRA

(STHAPANA)

GODUGDHA

(PACHANA)

7 DAYS

3 HOURS

8 RASACHIKITSA105

STHAPANA

FOLLOWED BY

BHARJANA

GORASA OR

KANJI

(SWEDANA)

GOGHRITA

(BHARJANA)

2 PRAHARAS

9 RASADARPANA106

SWEDANA

FOLLOWED

BY BHARJANA

GODUGDHA,

GOMAYARASA,

GOMUTRA,

KANJI

(SWEDANA)

(GOGHRITA

BHARJANA)

10 SIDDHAYOGA

SANGRAHA107

NIMAJJANA

FOLLOWED

BY SWEDANA

GOMUTRA

(NIMAJJANA)

GODUGDHA

(SWEDANA)

7 DAYS

(NIMAJJANA)

1 PRAHARA

(SWEDANA)

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SL.

N

TEXT METHOD MEDIA DURATION

11 BHARATIYA

RASA

PADDHATI108

1. SWEDANA

2. BHARJANA

1. GOMUTRA

2. GOGHRITA

12 RASASHASTRA

AT A

GLANCE109

1. NIMAJJANA

2. SWEDANA

3. BHARJANA

1. KANJI

2. GODUGDHA

3. GOGHRITA

1. 3 DAYS

2. 3HOURS

13 AGADA

TANTRA110

STHAPANA PANCHAGAVYA 1 PRAHARA

14 RASADHATU

PRAKASHA111

SWEDANA KANJI 3 DAYS

15 BRIHAT RASA

RAJA

SUNDARA112

SWEDANA

FOLLOWED BY

BHARJANA

KANJI (SWEDANA)

GOGHRITA

(BHARJANA)

2 PRAHARAS

16 RASENDRA

BHASKARA113

SWEDANA

FOLLOWED BY

BHARJANA

KANJI (SWEDANA)

GOGHRITA

(BHARJANA)

2 PRAHARAS

17 RASENDRA

SAMPRADAYA1

14

NIMAJJANA KANJI OR DADHI

JALA OR NIMBU

RASA OR SALT

WATER

3 DAYS

18 VAIDYA YOGA

RATNAVALI115

SWEDANA AND

BHARJANA

DECOTION OF

TANDULIYAKA

GOGHRITA

(BHARJANA)

1 PRAHARA

19 BHARATIYA

RASA

SHATRA116

1. SWEDANA

2. NIMAJJANA

3. BHARJANA

1. GOKSHIRA

2. GOMUTRA AND

GOMAYA

3. GOGHRITA

1. 3 HOURS

2. 3 DAYS

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SHODHANA PROCEDURES ADOPTED AND YANTRAS USED IN THE

PRESENT STUDY

Swedana and Bharjana methods are adopted in the present study.

SWEDANA: Boiling the material that has to be purified in the prescribed liquid using

Dola Yantra for specified duration is termed as swedana .

TABLE NO. 18 : EXAMPLES FOR SWEDANA PROCEDURE MENTIONED

FOR RASA DRAVYA SHODHANA IN RASA TEXTS:

Sl.No Varga Examples References

1. Rasa Parada Ra.Ra.Sa.8/59, 9/30

2. Maharasa Makshika Ra.Ra.Sa.2/83-84

3. Uparasa Gandhaka Ra.Ra.Sa.3/94

4. Sadharana Rasa Gowripashana Ra.Ra.Sa.3/125

5. Dhatu Tamra Ra.Ra.Sa.5/52

6. Ratna Vajra Ra.Ra.Sa.4/34

7. Sudhavarga Shankha Ra.Ta12/69

8. Visha Vatsanabha Ra.Ta.24/24

9. Upavisha Gunja Ra.Ra.Sa.8/59

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BHARJANA: The process by which the material is fried with the prescribed media till

the required change in the material is observed is termed as bharjana.

TABLE NO. 19: EXAMPLES FOR BHARJANA PROCESS MENTIONED FOR

RASA DRAVYA SHODHANA IN RASA TEXTS:

Sl.No Varga Examples References

1. Maharasa Makshika Ra.Ta.21/8-9

2. Uparasa Gairika Ayu.pra.2/272

3. Visha Kupeelu Ra.Ta.24/174

Shodhana procedures explained in Rasatarangini117, 118,119

Procedure I:

Vishatinduka beejas are kept in kanji for three days. After three days, take the seed from

kanji, Separate the pericarp and dry it in sunshine. Then make into powder in a Khalva

yantra. By this process purity sustains for longer time.

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Procedure II:

Vishatinduka beejas are taken in an iron pan added with small amount of Ghee to it,

roasted with mild heat. When it is turned to brown colour, taken out from the pan and

separate the pericarp. By this procedure, it will be purified immediately. But it should be

powdered when it is hot. This process can be adopted at the time of immediate

requirement of purified vishatinduka.

Procedure III:

Seeds of Vishatinduka are in a cloth, made into a pottali, placed in dola yantra which is

filled with cow‟s milk. By doing svedana for three hours vishatindika gets purified. And

this purified vishatinduka is used in any medicinal purpose without any doubt. While

using the purified vishatinduka, the pericarp should be separated from the seeds,

powdered and then used.

In the present study II and III procedures have been followed.

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REVIEW OF YANTRA USED IN THE PHARMACEUTICAL PROCEDURE

DOLA YANTRA: Dolayantra is commonly mentioned in most of the Rasashastra

books like Rasarnavam, Rasaratnasamuchchaya, Rasendra Chudamani, Ananda Kanda,

Parada Samhitam, etc. In all the texts this has been described in the context of yantras

such as in Rasarnavam120

it is described in the fourth chapter while explaining Yantras,

Mushas, etc.

In Rasaratnasamuchchaya121

it is described in the ninth chapter while explaining Yantras.

In Parada Samhitam122

it is described in the sixth chapter while explaining Yantras,

mushas, etc.

Description121

: The process of purification through hot liquid media is done in this

apparatus. Since the material for purification is kept amidst thr… liquid in a pot, this is

named as dola yantra. A pot is taken and two holes are made diametrically opposite to

each other at the neck level. A stick is entered in these holes. The liquid prescribed in the

text is poured into the pot filling to its two third levels. The material to be subjected to the

purification is tied in cloth into a poultice which is tied to the stick in the centre at the

neck level of the pot and kept hanging in the liquid. The pot is kept on a stove or hearth.

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ANALYTICAL REVIEW

Analytical review

Analysis123

It is defined as the resolution of chemical compound into its proximate or ultimate

parts, the determination of its elements or of the foreign substances it may contain.

This definition outlines in very broad terms the scope of analytical chemistry.

When a completely unknown sample is presented to an analyst, the first requirement is

usually to ascertain what substances are present in it. This fundamental problem may

sometimes be converted in the modified form of deciding what impurities are present in a

given sample or perhaps of confirming that certain specified impurities absent. The

solution of such problem lies within the province of “Qualitative analysis”. This gives

information regarding presence or absence of one or more components of the sample.

Having ascertained the nature of the constituents of a given sample, the analyst is

then frequently called up on to determine how much of each component or of specified

components is present. Such determination lies within the realm of “Quantitative

analysis”. This gives information regarding the quantity of components present in the

samples.

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Type of analysis;

Proximate analysis: In which the amount of each element in the sample is determined

with no concern as to the actual compounds present.

Partial analysis: This deals with the determination of selected constituents in the sample

Trace element analysis: A specialized instance of partial analysis in which we are

concerned with the determination of specified components present in very minute

quantity.

Complete analysis: When the propotion of each component of the sample is determined.

THIN LAYER CHROMATOGRAPHY124

It is a type of planar chromatography. TLC is routinely used by researcher in the field of

phyto-chemicals, biochemistry etc. to identify the components in a compound mixture

like alkaloids, phospholipids, amino acids etc.

It is a semi quantitative method of analysis.

Thin layer chromatography principle:

Similar to other chromatographic methods TLC is also based on the principle of

separation. The separation depends on the relative affinity of compounds towards

stationary and mobile phase. The compounds under the influence of mobile phase (driven

by capillary action) travel over the surface of stationary phase. During this movement the

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compounds with higher affinity to stationary phase travel slowly while the others travel

faster. Thus separation of components in the mixture is achieved.

Once separation occurs individual components are visualized as spots at respective level

of travel on the plate. Their nature or characters are identified by means of suitable

detection techniques.

TLC chromatography System components:

TLC System consists of

a) TLC plates preferably ready made with stationary phase: These are stable and

chemically inert plates on to whose surface a thin layer of stationary phase is applied. The

stationary phase on the plates is of uniform thickness and consists of fine particle size.

b) TLC chamber: This is used for the development of TLC plate. The chamber maintains

uniform environment inside for proper development of spots. It also prevents the

evaporation of solvents and keep the process dust free.

c) Mobile phase: This comprises of a solvent or solvent mixture recommended for the

purpose. The mobile phase used should be particulate free and of highest purity for

proper development of TLC spots. The solvents recommended are chemically inert with

the sample, stationary phase.

d) A filter paper moistened in the mobile phase, to be placed inside the chamber. This

helps uniform rise in mobile phase over the length of stationary phase.

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TLC chromatography

Thin layer chromatography procedure:

The stationary phase is applied onto the plate uniformly and then allowed to dry and

stabilize. But now a days ready made plates are preferred.

A thin mark is made at the bottom of the plate with a pencil to apply the sample spots.

Then samples solutions are applied on the spots marked on the line at equal distances.

The mobile phase is poured into the TLC chamber to a level few centimeters above the

chamber bottom. A filter paper moistened in mobile phase is placed on the inner wall of

the chamber to maintain equal humidity in the entire chamber and there by edge effect

can be avoided.

Then the plate prepared with sample spotting is placed in TLC chamber such that the side

of the plate with sample line is towards the mobile phase. Then the chamber is closed

with a lid.

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The plate is immersed such that sample spots are well above the level of mobile phase but

not immersed in the solvent as shown in the picture for development.

Allow sufficient time for development of spots. Then the plates are removed and allowed

to dry. The sample spots are visualized in suitable UV light chamber or any other

methods as recommended for the said sample.

Advantages of TLC

The Thin layer chromatography advantages include:

1. It is simple process with short development time.

2. It helps in visualization of separated compound spots easily.

3. The method helps to identify the individual compounds.

4. It helps in isolation of most of the compounds.

5. The separation process is faster and the selectivity for compounds is higher (even

small differences in chemistry is enough for clear separation).

6. The purity standards of the given sample can be assessed easily.

7. It is a cheaper chromatographic technique.

Applications of Thin layer chromatography

1. To check purity of given samples.

2. Identification of compounds like acids, alcohols, proteins, alkaloids, amines,

antibiotics etc.

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3. To evaluate reaction process by assessment of intermediates, reaction course etc.

4. To purify samples i.e for purification process.

5. To keep a check on the performance of other separation processes.

Being a semi quantitative technique, thin layer chromatography is used for rapid

qualitative measurements than for quantitative purposes. But due its rapidity of results,

easy handling and inexpensive procedure, it finds its application as one of the most

widely used chromatography techniques

Liquid chromatography was carried on total alkaloid content of Ashuddha Kupeelu seeds

and the total alkaloid content of Godugdha Swedita seeds ,the results of which are as

follows125 ,126

.

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LC-MS chromatogram of the TAC obtained from raw kupeelu seeds.

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LC-MS chromatogram of the TAC obtained from Sample B. The chromatogram shows

the peak at tR of 21.20 min (MW 341) and 28 min (MW 382) which was not found in the

Sample E (unprocessed sample).

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FOURIER TRANSFORM INFRARED SPECTROSCOPY (FTIR) 126

Introduction:

FTIR is most useful for identifying chemicals that are either organic or

inorganic. It can be utilized to quantitate some components of an unknown mixture. It can

be applied to the analysis of solids, liquids, and gasses. The term Fourier Transform

Infrared Spectroscopy (FTIR) refers to a fairly recent development in the manner in

which the data is collected and converted from an interference pattern to a spectrum.

Today's FTIR instruments are computerized which makes them faster and more sensitive

than the older dispersive instruments.

Principle:

Molecular bonds vibrate at various frequencies depending on the elements and the

type of bonds. For any given bond, there are several specific frequencies at which it can

vibrate. According to quantum mechanics, these frequencies correspond to the ground

state (lowest frequency) and several excited states (higher frequencies). One way to cause

the frequency of a molecular vibration to increase is to excite the bond by having it

absorb light energy. For any given transition between two states the light energy

(determined by the wavelength) must exactly equal the difference in the energy between

the two states [usually ground state (E0) and the first excited state (E1)].

The energy corresponding to these transitions between molecular vibrational states is

generally 1-10 kilocalories/mole which corresponds to the infrared portion of the

electromagnetic spectrum.

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Difference in

Energy States

=

Energy of

Light Absorbed

E1 - E0 = h c / l

Where h = Planks constant

c = Speed of light, and

l = The wavelength of light.

Typical Applications of FTIR

1. Identification of simple mixtures of organic and inorganic compounds both as

solids or liquids.

2. Identification of polymers and polymer blends.

3. Indirect verification of trace organic contaminants on surfaces.

4. Routine qualitative & quantitative FTIR Analysis.

5. Thin film analysis.

6. Analysis of adhesives, coatings and adhesion promoters or coupling agents.

7. Small visible particle chemical analysis.

8. Analysis of stains and surface blemishes remnant from cleaning and degreasing

processes combined with optical microscopy, SEM/EDX, XPS and SIMS techniques.

9. Analysis of resins, composite materials and release films.

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10. Solvent extractions of leachables or contaminants, plasticisers, mould release

agents and weak boundary layers coupled with XPS surface chemical analysis

techniques.

11. Identification of rubbers and filled rubbers.

12. Determination of degrees of crystallinity in polymers (eg LDPE and HDPE).

13. Comparative chain lengths in organics.

14. Extent of thermal, UV or other degradation or depolymerisation of polymers and

paint coatings.

15. Analysis of a gaseous samples using a gas cell for headspace analysis or

environmental monitoring.

16. Analysis of unknown solvents, cleaning agents and detergents.

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MATERIALS AND METHODS

INTRODUCTION

Although it is described in Ayurveda that there is no substance in the world

which cannot be used as medicine, most of the drugs as such cannot be easily

administered into the biological system. Hence, to prepare a palatable, convenient

dosage form, which can be administered easily into the body, some modifications are

required through specialized techniques called “pharmaceutical processes”, or

samskaras in Ayurveda.

The Rasoushadhis prepared properly are boon to physicians, as well as for the

patients. They are not only known for their swift and effective nature but also for the

magnitude effectiveness achieved in minimum dosage when prepared rightly. So,

when is the harmful effects observed? When the Rasaushadhis are not prepared

according to the framed procedures or when the Rasaushadhis are administered

without using the power of intellect. To establish the efficacy along with safety of

Rasaushadhis, care must be taken throughout the process of preparing the medicine.

Rasashastra says that there is therapeutic usage of poisonous plant drugs in

various formulations after a particular pharmaceutical procedure, called as shodhana.

Various liquid medias and multiple processings which are organic purificants are

used for shodhana of these poisonous plant drugs like gomutra, gomaya, swarasas of

plants, goghrita, godugdha, kanji, etc., with specialized procedure like bharjana,

swedana, nimajjana etc., procedures which help in the removal of toxins present in

the drugs.

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In this era of globalization, it is the need to explore the scientific basis for the

medicaments of Ayurveda. In this exploration, it is the prime duty of the scholars

related to Rasashastra to provide the scientific data about the preparation of

medicaments.

PROCUREMENT OF RAW MATERIAL

Kupeelu seeds were purchased from an authentic source , FRLHT research centre.

Bangalore, Voucher number- Sb000676. The sample specimen was kept in the

department museum for future reference.

PHARMACOGNOSTICAL STUDY

Pharmacognocy, prior known as materia medica, may be defined as

The scientific study of those substances which are used or have been used in

Medicine and pharmacy. C.A. Seydler, a medical student at Halle, Germany,

in his doctoral thesis, coined the word “pharmacognocy” in 1815. The

science of pharmacognocy, always closely allied to medicine, developed

during early nineteenth century as a branch of materia medica and applied

biology. It was, of course, necessary to make distinct the materia medica as

taught to medical students and a distinguished physician named Jonathan

Pareira, recognized as the first British pharmacognosist, achieved this from

beginning. Pharmacognocy can be considered as a valuable part of the

cultural heritage of pharmacy.

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The word Pharmacognosy is derived from two Greek words pharmakon

Meaning drug, and gnosis meaning knowledge. Thus pharmacognocy has

been defined as “simultaneous application of various scientific disciplines

with the object of acquiring knowledge of drugs from every point of view”.

Furthermore, the subject of pharmacognocy can also be expressed as an

Applied science that deals with biological, biochemical, therapeutic and

Economic features of natural drugs and their constituents. It is the study of

drugs having their origin in plant and animal kingdom.

Modern aspects of pharmacognocy include not only the crude drugs

but also their natural derivatives.

For product standardization, the raw material should be of standard quality.

The quality of finished product entirely depends on the quality of the raw materials.

Therefore first step of standardization is the quality control aspects of raw material. It

can be achieved by macroscopic and microscopic examination of the crude drugs.

In the present study an attempt was done to standardize the raw material used for the

pharmaceutical process. Here, the drug Kupeelu was authenticated morphologically,

microscopically.

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PLACE OF WORK:

1. Post graduate department of Rasashastra government Ayurvedic medical college

Bangalore.

2. Bangalore test house. Bangalore.

MACROSCOPICAL CHARACTERS

Strychnos nux-vomica seeds were extremely hard, greenish-gray, disc-shaped, 10-30

mm diameter and 4-6 mm thick. The edge was round or acute. The testa was covered

with silky, closely apprised radiating hairs. In the center of the seed was a distinct

hilum and a small prominence marks the position of the micropyle which is joined to

the hilum by a radial ridge. The small embryo with two cordate cotyledons and a

cylindrical radicle, gray, horny endosperm. In the center of the seed a silt-like cavity

was present. The seeds are odourless when dry, but if soaked in water and left for a

day or two, they develop a very unpleasant odour.

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MICROSCOPIC STUDY

Trichomes:

Entire or fragments of Trichomes, lignified. Base was pitted and broad. Apex

was rounded. Ridges were present on the surface.

Endosperm:

Polygonal cellulosic cells, with oil globules and aleurone grains.

Lignified Trichomes:

Thick walled, bent and twisted lignified trichomes, immerged from epidermis,

parallel in one direction.

Epidermal Cell:

Single layer, forms lignified trichomes large thick walled with oblique linear

pits (Base of trichomes).

Collapsed Parenchyma:

2 layers, flattened parenchyma.

Endosperm:

Thick walled cellulosic parenchymatous cells.

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Plasmodesma:

Fine protoplasmic strands between the walls of endospermic cells.

Aleurone Grains:

About 30µ in diameter.

Oil Globules:

Fixed oil was seen small oil droplets in the cells.

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PHARMACEUTICAL STUDY

AIM AND OBJECTIVES

Aim of the study is to carry out Shodhana of Kupeelu by two selected methods

Objectives

1) To use standard raw material , kupeelu seeds as studied previously by

pharmacognostic study.

2) To carry out the shodhana of kupeelu by method of swedana using godugdha as the

media.

3) To carry out the shodhana of kupeelu by method of bharjana using goghrita

TABLE NO. 20 ABBREVIATIONS OF DIFFERENT SAMPLES

Sr. No.

Abbreviations Description

1 ASK ASHUDDHA KUPEELU

2

GSK GODUGDHA SWEDITA

KUPEELU

3 GBK GOGHRITA BHARJITA KUPEELU

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PHARMACEUTICAL PROCEEDINGS

PRACTICAL NO. 1

Name of Practical : Cleaning and selection of seeds

Procedure used: washing with water

Date of starting: 1/7/2011

Date of completion: 1/07/2011

Weight of the ingredients:

1. Kupeelu seeds:1 kg

2. Water: Q.S.

Final weight of seeds: 920 grams

Weight loss: 80 grams.

EQUIPMENTS: Stainless steel vessel, analytical balance, source of tap water.

PROCEDURE:

After studying the seeds pharmacognostically 1 kg of raw kupeelu seeds

were taken in a steel vessel containing water. The seeds were rubbed and washed

with hands until all the seeds were devoid of mud sticking to seeds. The black

colored seeds which floated on the surface of the water were taken out and discarded

as these were not conducive for further procedure. The settled seeds at the bottom of

the vessel were taken out and sun-dried to get rid of the moisture content. Thus

obtained seeds were selected for further Shodhana procedures.

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OBSERVATIONS

Before cleaning

1. The seeds contained mud which was sticking to them

2. Presence of extraneous matter like fibers etc. was found.

3. Water was transparent.

After cleaning

1. The seeds were devoid of mud particles and other foreign matter.

2. Colour of water turned reddish due to presence of mud.

Precautions

1. The vessel should be large enough to hold the seeds and water.

2. Water should be sufficient.

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PRACTICAL NO.2

Name of Practical : Kupeelu Shodhana

Reference: Rasatarangini (24/176-177)

Procedure used: Swedana

Date of starting:12/07/2011 9:00 am

Date of completion: 12/07/2011 12:00 pm

Weight of the ingredients:

1. kupeelu seeds:250 grams.

2. Godugdha : 2660 ml.

Final weight of seeds: 390 grams.

Weight of the powder:370 grams.

Weight gain: 120 grams.

EQUIPMENTS:

Induction heater, earthen pot , steel ladle(30 cm),iron-rod(20 cm), cotton thread(30 cm),

kora cloth(30x30 cm), pyrometer, measuring jar, Knife, analytical balance.

PROCEDURE:

250 Grams of selected seeds were procured from procedure 1. They were placed

in middle of a khora cloth. A pottali was made and tied to the middle of an iron rod with

a cotton thread. Cow’s milk measuring 2 lts is poured in a clean earthern pot

(approximately 3/4th

of the volume). The iron rod with the pottali at its centre is placed

horizontally over the mouth of the pot such that the pottali which contained seeds of

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kupeelu is immersed completely in the milk.The earthen pot is kept on an induction

heater. Temperature is controlled and maintained for 3 hours using a pyrometer such that

milk does not spill over. The milk is added on and often such that pottali remains

immersed in milk.

After completing the Swedana process, seeds were collected from Pottali and

washed with warm water.

The kernel of the seed was peeled off by a knife and discarded. The tongue

shaped embryonic axis in the shaved cotyledons was removed. These cotyledons were

sun-dried and powdered in a khalwa yantra. Thus obtained powder is kept in an air tight

container and utilized for analysis.

TABLE NO. 21 : OBSERVATIONS OF THE SEEDS BEFORE AND AFTER

SWEDANA .

PARAMETERS BEFORE SHODHANA AFTER SHODHANA

COLOUR LIGHT BROWN DARK BROWN

HARDNESS HARD SOFT

ODOUR NON SPECIFIC CHARACTERSTIC

TASTE NOT ELICITED BITTER

SIZE STANDARD INCREASED

OUTER COAT NON SEPARABLE EASILY SEPARABLE

WEIGHT(grams) 250 390

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TABLE NO. 22 : OBSERVATIONS OF THE MILK BEFORE AND AFTER

SWEDANA .

PARAMETERS BEFORE SHODHANA AFTER SHODHANA

Colour White Creamish

Consistency Liquid Thick liquid

OBSERVATIONS AFTER POWDERING:

1. Powdering was easier when compared to raw seeds.

2. The colour of the powder was whitish orange.

3. The odour of the powder was characterstic.

4. The weight of the powder was 370 grams.

PRECAUTIONS:

1. Care must be taken that the pottali is immersed in milk throughout the procedure.

2. Pottali should not touch the bottom of the pot.

3. Quantity of milk should be maintained by adding milk such that the pottali is

completely immersed.

4. Milk must be stirred and cream should be removed to avoid spilling and over-

heating of milk

5. Seed coat should be removed without delay otherwise removal of seed coat will

be difficult.

6. Seeds must be washed with hot water in order to prevent fungus formation.

7. Drying of seeds in sunlight is a must after shodhana.

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PRACTICAL NO. 3:

Name of Practical : Kupeelu Shodhana

Reference : Rasatarangini (24/174-175)

Procedure used : Bharjana

Date of starting: 15/07/2011

Date of completion: 15/07/2011

Weight of the ingredients:

1.kupeelu seeds:250 grams.

2.Goghrita: 80 ml.

Final weight of seeds: 270 grams

Weight of the powder:245 grams.

Weight loss: 5 grams

Time taken for Bharjana 16 minutes.

EQUIPMENTS: Iron Pan (Tawa), Goghrita, Knife, Induction heater, Steel ladelle(30

cm), pyrometer, measuring jar, analytical balance.

PROCEDURE:

250 gms of seeds which were selected by procedure 1 were taken in an iron pan.

The iron pan was kept on an induction heater and low temperature was maintained,

measured by digital pyrometer. Bharjana was done with Goghrita till the kernel became

slightly reddish brown (kinchit kapeesha varna). Kernel was peeled off with a sharp knife

to get rid of the trichomes . The procured matter was pounded well in a khalwa yantra

and stored in an air tight container for further analytical study.

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TABLE NO. 23 OBSERVATIONS OF THE SEEDS BEFORE AND AFTER

BHARJANA.

PARAMETERS BEFORE SHODHANA AFTER SHODHANA

COLOUR LIGHT BROWN REDDISH BROWN

HARDNESS HARD CRISPY BRITTLE

ODOUR NON SPECIFIC AROMATIC LIKE

COFFEE

TASTE NOT ELICITED BITTER

SIZE STANDARD INCREASED

OUTER COAT NON SEPARABLE EASILY SEPARABLE

WEIGHT(gms) 250 270

Observations during bharjana

1. The smoke came during bharjana which was comparable to burning of ghee

initially,then after 5 to 6 minutes roasted coffee smell started till the end of the

procedure.

2. The seeds jumped out of the pan .

3. The seeds were getting swollen.

4. The colour started to change from light brown to reddish brown.

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OBSERVATIONS AFTER POWDERING

1. Powdering was easier when compared to raw seeds.

2. The colour of the powder was coffee brown.

3. The odour of the powder was aromatic,comparable to roasted coffee seeds .

4. The weight of the powder was 245 grams.

PRECAUTIONS:

1. Wear mask and maintain distance from pan as seeds likely to jump when fried

with ghee.

2. Continuous stirring required to prevent excess burning.

3. Removal of seed coat and powdering should be immediately done when the

Seeds are warm or it will become difficult.

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These were observed and

documented during various steps

of the procedures including before

and after the main procedure -

Kupeelu Shodhana.

EVALUATION OF ANALYTICAL PARAMETERS:

Time tested remedies and Ayurvedic concepts demand a base of evidence in

the modern era of globalization. Hence, to fulfill the needs an approach has been

made to test by the relevant parameters.

PLACE OF WORK:

1. Post Graduate Department of Rasashastra, Government Ayurvedic Medical College

Bangalore.

2. Bangalore Test House, Bangalore.

3. Indian Institute of Science, Bangalore.

4.Government Central Pharmacy.Bangalore

.

ANALYSIS

(1) ORGANOLEPTIC ANALYSIS

COLOUR

ODOUR

TASTE

TOUCH

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2) PHYSICO CHEMICAL CONSTANTS:

These procedures of analysis were adopted and results were recorded

according to the standardized parameters.

Description of the adopted procedures are as follows-

1. Loss on drying:

Excess of moisture content promotes microbial, fungi and insect activity in

plant material and deterioration hydrolysis. Limits for water content are already

standardized by the API for herbo-mineral materials that absorb or deteriorate quickly

in the presence of water. Using them as the parameter, the following analysis was

conducted-

Loss on drying was determined by weighing about 2 gm of the powdered

material in a dried petridish (tarred evaporating dish) and dried in an oven at 100 -

105 C, till two consecutive weights which do not differ by more than 5 mg. The

weight after drying was noted and loss on drying was calculated. The percentage was

calculated with reference to air dried sample.

2. Determination of Total Ash:

The total ash method is designed to measure the total amount of material

remaining after ignition. This includes “physiological ash”, which is derived from the

plant tissue itself and “non-physiological ash", which includes the residue of the

extraneous matters (e.g. Sand and Soil) adhering to the plant surface.

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The ash value was determined by incinerating about 2 gm of the powdered air dried

seed material in a previously weighed silica crucible at gradually increasing heat up to

500-600 C until it is carbon free. This is cooled and weighed. The percentage of ash

was calculated with reference to the air dried sample.

3.Determination of Acid insoluble ash:

Acid insoluble ash is the residue obtained after boiling the total ash with dilute

hydrochloric acid, and igniting the remaining insoluble matter. This measures the

amount of silica present, especially as sand and siliceous earth.

The ash obtained in (c) was boiled for five minutes with 25 ml of dilute (6N)

hydrochloric acid; the insoluble matter was collected on an ashless filter paper and

washed with hot water until the filtrate is neutral or chloride free. Then the filter paper

was dried in an oven and transferred to the crucible, and ignited to constant weights.

The percentage of acid insoluble ash was calculated with reference to air dried

sample.

4.Determination of Water soluble ash:

Water soluble ash is the difference in weight between the total ash and the

residue after treatment of the total ash with water.

To the total ash 25 ml of water was added and boiled for 5 minutes in a

beaker. The insoluble matter was collected on ashless filter paper. The residue (ash)

was washed and then dried in an oven. The ashless filter paper was ignited in a

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crucible for 15 minutes at a temperature not exceeding 450 C. The percentage was

calculated with reference to the air dried sample.

5. pH:

The pH value of an aqueous liquid may be defined as negative log of hydrogen

ion concentration. The pH of the filtrate of a particular concentration of aqueous

solution of the sample is often used as one of the parameters.

10gm of seed powder was weighed and transferred into a clean conical flask;

100 ml of distilled water was added to it. After shaking continuously with the help of

clean and dry glass rods for about 45 minutes it was filtered through cotton so as to

remove the insoluble portion. The pH of the filtrate was noted in Elico's digital pH

meter using combined glass electrode.

6.Extractive value:

This method determines the amount of active constituents extracted with

solvents from a given amount medicinal plant materials. It is employed for materials

to which ,yet no suitable chemical or biological assay exists.

Determination of Water soluble extractive:

5 gm of accurately weighed seed powder was macerated in a glass plugged

conical flask. 100 ml chloroform water was added and stirred for 6 hrs, shaking

frequently, and then allowed to stand for 18 hrs. Then after 24 hrs, it was filtered

rapidly and 25 ml of the filtrate was transferred in a tarred flat bottomed evaporating

dish with a pipette and evaporated to dryness on a boiling waterbath. Then

evaporating dish was dried at 105 C for 6 hrs, and then cooled and weighed. From the

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weight of the residue the percentage of water soluble extractive was calculated with

reference to air dried sample.

Determination of Alcohol soluble extractive:

5 gm of accurately weighed, sample was stirred with 100 ml of alcohol

(methanol) in a closed conical flask for 24 hrs, shaking frequently during 6 hrs and

allowed to stand for 18 hours. It was filtered rapidly to prevent loss of solvent and 25

ml of the filtrate was evaporated to dryness in a tared flat bottomed evaporating dish

and dried at 105 C to constant weight. From the weight of the residue the percentage

of alcohol soluble extractive value was calculated with reference to air dried sample.

7. QUALITATIVE TESTS :

The methods employed to isolate active substance are termed as extractive

method. Crude extracts obtained from such extraction can be qualitatively tested to

ascertain the presence of different types of components. Qualitative tests are used to

detect the presence of functional groups, which play very important role in the

expression of biological activity. Using the methanol, water and chloroform soluble

extracts of samples carried out qualitative tests. These tests indicate the types of

phyto-constituents present in the sample.

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Tests for alkaloids:

Powdered seed material was moistened with ammonium hydroxide and kept in

a stoppered flask for about 1 hour. This was then extracted with chloroform 2-3 times.

About 5 ml chloroform extract was taken in a dish and chloroform evaporated. The

dried substance was tested for the presence of alkaloid.

Dragendorff's reagent :

The substance was treated with few drops of dilute 2N HCl and 0.5 ml

Dragandorff's reagents (Potassium iodide added to a solution of bismuth nitrate) gave

an orange- red precipitrate.

Mayer's reagent :

The substance was treated with few drops of 2N HCl and 0.5 ml Mayer's

reagents (Potassium mercuric iodide solution) when added with gave a pale yellow

precipitate.

Hager's reagent ;

The substance was treated with few drops of 2N HCl and 0.5 ml Hager's

reagent (saturated solution of Picric acid) gave a reddish brown precipitate.

Wagner's reagent :

The substance was treated with few drops of 2N HCl and 0.5 ml Wagner's

reagent (Potassium iodide) gave brown flocculent precipitate.

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8.QUANTATIVE ASSAY FOR STRYCHNINE

Weigh accurately about 109 in fine powder, add 100 ml of a 33 per cent v/v

mixture of chloroform in solvent ether and set aside for ten minutes. Add 5 ml of

dilute ammonia solution and shake continuously for six hours. Transfer to a

continuous extraction apparatus with more of the same solvent mixture and extract for

two hours. Filter the solvent extract, washing the filter with solvent ether and extract

with successive quantities of 20 ml, 20 ml , 10 ml and 10 ml of 1N sulphuric acid,

until complete extraction of the alkaloids is effected. Combine the acid extracts and

make alkaline with dilute ammonia solution. Extract with successive quantities of 20

ml, 20 ml, 10 ml and 10 ml of chloroform until complete extraction of the alkaloids is

effected. Evaporate the chloroform, add 5 ml of alcohol and evaporate to dryness.

Dissolve the residue in a mixture of 15 ml of a 3 per cent w/v solution of sulphuric

acid and 2 ml of nitric acid, add a few crystals of sodium nitrite and set aside at 18°C

for thirty minutes. Transfer to a separator containing 20 ml of solution of sodium

hydroxide, shake for two minutes and then shake with 20 ml of chloroform, separate

the chloroform solution, wash it with 5 ml of solution of sodium hydroxide and then

with two quantities each of 10 ml of water. Continue the extraction with successive

quantities of 10 ml of chloroform, until complete extraction of the alkaloids is

effected, washing each chloroform solution separately with the 5 ml of solution of

sodium hydroxide and with the two quantities of water, which were used for washing

the first chloroform solution. Titrate the second wash with 0.1 N sulphuric acid using

solution of methyl orange as indicator if more than 0.1 ml is required, wash the

combined chloroform solutions with further quantities, each of 10 ml of water until on

titration not more than 0.1 ml of 0.1 N sulphuric acid is required. Remove the

chloroform, add 5 ml of alcohol, evaporate, and dry for thirty minutes, at 100°C.

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Dissolve the residue in 10 ml of 0.1 N sulphuric acid and titrate the excess of acid

with 0.1 N sodium hydroxide, using solution of methlyl orange as indicator. Each ml

of 0.1 N sulphuric acid is equivalent to 0.03344 g of strychinine, multiply the result

by 1.02 to correct for loss of strychinine.

9. THIN LAYER CHROMATOGRAPHY

TLC of alcoholic extracts All 3 samples viz.ashuddha kupeelu, godugdha

swedita and goghrita bharjita one were marked on the on silica gel „G‟, which was

used as a stationary phase. Using mobile phase as Toluene: Ethylacetate

Diethylamine (70:20:10) T.L.C was carried out. Dragendorff reagent was sprayed

followed by 5% Methanolic- Sulphuric acid .

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10) FOURIER TRANSFORM INFRARED SPECTROSCOPY (FTIR)

This analysis was choosen as it is a powerful tool for identifying types of

chemical bonds in a molecule by producing an infrared absorption spectrum that is

like a molecular "fingerprint".

FTIR is used particularly for identification of organic molecular groups and

compounds due to the range of functional groups, side chains and cross-

links involved, all of which will have characteristic vibrational frequencies in the

infra-red range present in the samples of kupeelu seeds. FTIR analysis was chosen for

the spectral analysis to evaluate the possible changes in any functional groups that

might take place after shodhana.

Procedure:

All 3 samples viz.ashuddha, godugdha swedita and goghrita bharjita were

milled with potassium bromide (KBr) to form a very fine powder. This powder was

then compressed into a thin pellet which was analyzed by FTIR.

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RESULTS

TABLE NO. 24 : COMPARATIVE ORGANOLEPTIC CHARACTERISTICS

TABLE NO. 25 RESULTS OF COMPARATIVE PHYSICO-CHEMICAL

CONSTANTS

SL.NO PARAMETERS

ASK GSK GBK

1 Loss on drying at 110 c.

4.4 11.2 2.8

2 Total ash (% w/w)

1.125 1.035 1.445

3 Acid insoluble ash. (%

w/w)

0.185 0.16 0.18

4 Water soluble ash. (%

w/w)

0.52 0.45 0.72

5 Determination of pH.

5.5 6.3 5.8

6 Determination of Water

soluble extractive

9.5 7.2 8.6

7 Determination Of Alcohol

Soluble Extractive

3.2 2.8 3.0

Sl. no. Organoleptic characteristics After Shodhana

GSK GBK

1 Colour Greyish Dark Brown

2 Odour Characteristic Coffee like

3 Taste Bitter Bitter

4 Touch Soft rubbery Crispy

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TABLE NO. 26 COMPARATIVE QUALITATIVE TESTS FOR

PRESENCE OF ALKALOIDS

Sr. No. Parameters

Tests for

alkaloids

Observations

ASK GSK GBK MILK(A.S)

1 Dragendorff's

Reagent

+ve +ve +ve +ve

2 Mayer’s

Reagent

+ve +ve +ve +ve

3 Wagner’s

Reagent

+ve +ve +ve +ve

TABLE NO. 27 QUANTITATIVE ASSAY FOR STRYCHNINE

Sl.no ASK GSK GBK

1 1.26% 1.16% 0.62%

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THIN LAYER CHROMATOGRAPHY

Extract used: Alcoholic extract

Mobile phase: Toluene:Ethyl acetate:Diethylamine(70:20:10)

On spraying with Dragendroff’s reagent followed by 5% methanolic sulphuric

acid: Two orange spots at Rf 0.44 and 0.65 were seen.

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4000

.036

0032

0028

0024

0020

0018

0016

0014

0012

0010

0080

060

040

0.0

-20.

0

-100102030405060708090

100.

0

cm-1

%T

3356

.12,

3.16

2924

.79,

3.48

2854

.58,

9.21

2361

.20,

87.1

4

2140

.15,

83.3

1

1744

.30,

14.9

2

1655

.78,

9.88

1543

.11,

39.1

9

1510

.76,

34.8

0

1460

.24,

20.2

5

1378

.22,

22.9

4

1259

.61,

26.1

3

1160

.47,

12.8

9

1052

.75,

4.88

893.

85,7

8.82

813.

94,7

6.53

763.

89,7

0.43

704.

21,5

6.45

668.

02,5

2.61

609.

80,4

9.95

529.

77,6

2.79

469.

79,8

2.44

432.

68,9

0.94

405.

81,7

5.70

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4000

.036

0032

0028

0024

0020

0018

0016

0014

0012

0010

0080

060

040

0.0

-20.

0

-100102030405060708090

100.

0

cm-1

%T

3420

.52,

6.96

2925

.29,

3.16

2855

.46,

7.08

2358

.98,

89.4

6

2146

.65,

82.1

4

1743

.45,

17.5

9

1661

.03,

10.3

8

1545

.98,

36.9

7

1460

.98,

19.6

0

1381

.35,

26.1

8

1234

.16,

39.3

2

1166

.75,

20.4

7

1033

.59,

16.3

6880.

89,6

1.27

813.

27,5

6.80

780.

79,6

6.88

705.

52,7

3.86

669.

45,8

6.38

608.

01,8

6.49

524.

82,8

4.07

464.

04,9

3.89

442.

97,9

5.82

421.

17,8

8.18

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4000

.036

0032

0028

0024

0020

0018

0016

0014

0012

0010

0080

060

040

0.0

-20.

0

-100102030405060708090

100.

0

cm-1

%T

3947

.14,

91.4

3

3515

.88,

42.6

5

2924

.76,

3.16

2854

.55,

12.3

7

2676

.91,

94.1

1

2503

.66,

94.3

0

2335

.37,

92.7

4

2058

.93,

84.3

4

1745

.36,

5.19

1460

.84,

37.8

3

1375

.72,

51.5

9

1238

.18,

50.2

0

1163

.81,

20.5

8

1095

.29,

34.5

5

870.

77,7

7.22

810.

84,7

6.23

763.

39,7

5.74

719.

47,7

2.25

606.

35,8

9.70

522.

61,8

9.42

462.

76,9

3.33

417.

54,8

7.48

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INTERPRETATION OF FTIR RESULTS

TABLE NO 28 PEAK POSITIONS AND THEIR ASSIGNMENTS OF

AHSUDDHA KUPEELU SEEDS

Sl.

No.

Peak Position cm-1

Assignment

1 3356 O-H monomeric alcohols, phenols stretch, hydrogen bounded

alcohols, amines N-H(stretch)

2 2924.79 C-H (Alkanes), also O-H carboxylic acid stretch

3 2854.58 C-H (Alkanes), also O-H carboxylic acid stretch

4 2361.20 Not identified

5 2140.15 C0_C (stretch Alkyne)

6 1744.30 Phenyl ring substitution C=O Aldehydes, ketones, carboxylic

acids, esters(stretch)

7 1655.75 Phenyl ring substitution, C=C alkene(stretch), nitro compounds

NO2 asymmetric stretch.

8 1543.11 C=O Aromatic ring stretch, nitro compounds NO2 asymmetric

stretch.

9 1510.76 C=O Aromatic ring stretch, nitro compounds NO2 asymmetric

stretch.

10 1460.24 CH3

11 1378.22 CH3, , nitro compounds NO2 symmetric stretch.

12 1259.61 nitro compounds NO2 symmetric stretch, C-O Alcohol, Ethers,

Carboxylic acid esters(stretch), also C-N Amine Stretch.

13 1160.47 nitro compounds NO2 symmetric stretch, C-O Alcohol, Ethers,

Carboxylic acid esters(stretch), also C-N Amine Stretch.

14 1052.75 nitro compounds NO2 symmetric stretch, C-O Alcohol, Ethers,

Carboxylic acid esters(stretch), also C-N Amine Stretch.

15 893.85 Phenyl ring substitution band.

16 813.94 Phenyl ring substitution band, C=C Alkene(bend)

17 763.89 Phenyl ring substitution band. C=C Alkene(bend)

18 704.21 Phenyl ring substitution band. C=C Alkene(bend)

19 668.02 C-H (Alkyne bend)

20 609.80 C-H (Alkyne bend)

21 529.77 Not identified

22 405.80 Not identified

23 469.79 Not identified

24 432.68 Not identified

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TABLE NO 29: PEAK POSITIONS AND THEIR ASSIGNMENTS OF

GODUGDHA SWEDITA KUPEELU SEEDS

Sl. No. Peak Position cm-1

Assignment

1 3420.52 Monomeric alcohols phenols stretch, O-H hydrogen bonded alcohols,

phenols stretch, N-H amine stretch.

2 2925.29 C-H(Alkanes) and O-H carboxylic acids (stretch).

3 2855.46 C-H(Alkanes) and O-H carboxylic acids (stretch).

4 2358.98 Not identified

5 2146.65 Alkyne C0_C stretch

6 1743.45 Phenyl ring substitution, C=O aldehydes, ketones, carboxylic acids,

esters (stretch)

7 1661.03 Phenyl ring substitution, C=C alkene(stretch)

8 1545.98 C=O Aromatic ring stretch, NO2 Nitric compounds asymmetrical

stretch.

9 1460.98 CH3

10 1381.35 CH3, NO2 Nitric compounds symmetrical stretch.

11 1234.16 C-O Alcohol, Ethers, Carboxylic acid, Esters (stretch), C-N Amine

stretch

12 1166.75 C-O Alcohol, Ethers, Carboxylic acid, Esters (stretch), C-N Amine

stretch

13 1033.59 C-O Alcohol, Ethers, Carboxylic acid, Esters (stretch), C-N Amine

stretch

14 880.89 C=C Alkene (bend).

15 813.27 C=C Alkene (bend), Phenyl ring substitution band.

16 780.79 C=C Alkene (bend), Phenyl ring substitution band.

17 705.52 C=C Alkene (bend), Phenyl ring substitution band.

18 669.45 C-H Alkyne bend

19 608.01 C-H Alkyne bend

20 524.82 Not identified

21 464.04 Not identified

22 442.97 Not identified

23 421.17 Not identified

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TABLE NO 30: PEAK POSITIONS AND THEIR ASSIGNMENTS OF

GOGHRITA BHARJITA KUPEELU SEEDS

Sl.

No.

Peak Position cm-1

Assignment

1 3947.14 Not identified

2 3515.88 O-H monomeric alcohols, Phenols, stretch (hydrogen bundle

alcohols phenols stretch)

3 2924.76 O-H Carboxylic Acids (stretch), C-H (Alkanes)

4 2854.55 O-H Carboxylic Acids (stretch)

5 2676.91 O-H Carboxylic Acids (stretch)

6 2503.66 O-H Carboxylic Acids (stretch)

7 2335.37 Not identified

8 2058.93 Not identified

9 1745.36 Phenyl ring substitution overtone, C=O Aldehydes Ketones,

Carboxylic acids, ester (stretch)

10 1460.84 CH3

11 1375.72 CH3, NO2 Nitric compounds symmetrical stretch

12 1238.18 C-O Alcohol, Ethers, Carboxylic acid esters (stretch), also Amine

C-N (stretch)

13 1163.81 C-O Alcohol, Ethers, Carboxylic acid esters (stretch), also Amine

C-N (stretch)

14 1095.29 C-O Alcohol, Ethers, Carboxylic acid esters (stretch), also Amine

C-N (stretch)

15 870.77 C=C and Alkene (bend), Phenyl ring substitution band.

16 810.84 C=C and Alkene (bend), Phenyl ring substitution band.

17 763.39 C=C and Alkene (bend), Phenyl ring substitution band.

18 719.47 C=C and Alkene (bend), Phenyl ring substitution band.

19 606.35 Alkyne bend (C-H)

20 522.61 Not identified

21 462.76 Not identified

22 417.54 Not identified

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DISCUSSION

The present work entitled “A Pharmaceutco-Analytical Study on Concept of Shodana

with Special Reference to “Kupeelu Shodhana” has been discussed based on Review of

literature, Pharmaceutical study and Analytical study and the comparative results.

DISCUSSION BASED ON REVIEW OF LITERATURE

DRUG REVIEW

The reference of kupeelu is not found in veda kala. Acharya Sushruta and

Vagbhata mentioned Vishamusti,a synonym of Kupeelu in Surasadi Gana which is

commented as Mahanimba or Alambusha or Karkotika by the respective commentators.

When the drugs of Surasadi gana are seen, they are indicated in Krimi ,Shwasa,

Pratishyaya and Vrana.No poisonous drugs have been included in this Gana.By this we

can infer that Vishamusti mentioned here cannot be considered as Kupeelu.Going

through the cross reference from the world history of herbs ,there is a mention regarding

nux vomica as being used in Europe in 16th century for poisoning dogs, cats, crows

etc.127

Different nighantus have mentioned many synonyms of kupeelu .Some of

them indicate morphology of the fruit (Ramyaplala), leaf(Dirghapatraka,Nagavallidala),

some indicate its poisonous effect (Garadruma, Ravana, Vishadruma) etc . During

Nighantu kala vishamusti and kupeelu became synonymous as mentioned in different

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Samucchaya(13th century AD) where it is placed under Upavisha varga. Later on the

other texts added the information to it like synonyms, habit, habitat, shodhana

procedures, dose, and formulations etc.

The genus strychnos comprises of about 200 species. 128

The tree is native of

tropical regions and monsoonal forests. Rasa Tarangini also mentioned its habitat as

konkana Bengal and South India.129

(24/160)

When the rasa of kupeelu mentioned in the Nighantus was tabulated, majority of

Acharyas mentioned it as having katu and tikta rasa.When an attempt was made to

understand with respect to modern literature it says that kupeelu seeds are bitter in taste.

This taste is because of the presence of alkaloids majorly strychnine which is bitter in

taste.130

Thus we may say it is a tikta rasa pradhana dravya. According to samhitas, tikta

rasa is said to have vishagna karma. This may seem contrary to the study because one

might think if that the inherent rasa in kupeelu which is tikta acts as a vishagna, then how

is it that it is included in upavisha varga? Charaka in the context of tikta rasa karma

explains that excessive intake of tikta rasa will cause vatavikaras( ch.su-26/5) suh as

Aakshepaka, which is compared to convulsions that occurs as a result of kupeelu seed

toxicity.

In contrast to this, Rasa Tarangini a renowned Rasashastra text mentions the

indications of kupeelu in the contexts of many vatavikaras. This includes the nadibala

vivardhana ,which can be compared as neurotonic.

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The above doubt is clarified by the fact that Strychnine, which is the toxic and

principle alkaloid present in the seeds of strychnus nuxvomica is also bitter. After

shodhana, we find a considerable decrease in the quantity of strychnine by which it can

be inferred that tiktata is reduced in the drug. This decrease may be due to the

samskaarana by goksheera and ghrita used in shodhana. And can be considered as

therapeutically safe in prescribed dose. When we see the mythological origin of visha and

Amrita, we come to know that both of them arise from the same yoni during

Samudramanthana, so by this we can infer the opposite action of drug before and after

shodana.

Commenting on the guna we can attribute it as having the dashagunas of Visha, but the

virulence is less as compared to the mahavisha like vatsanabha. By the virtue of its ushna

and tikshna guna it will act on vata kapha vikaras which is in accordance to its dosha

karma mentioned in texts like Ayurveda Prakasha.

Even though Nighantus mention the veerya of kupeelu as sheeta, majority of the

Acharyas say it as ushna .When we look into the karma like deepana ,pachana,grahi,the

veerya may be attributed as ushna.

When the karma and rogaghnata of kupeelu is seen, then we find many of them can be

correlated to research works as under.

Parama kamoddepaka where in it has been evaluated in modern medicine as

„small doses of strychnine can give subjective feeling of stimulation‟131

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Grahi action has been evaluated as antidiarrhoeal activity ,by animal

experimentation.132

Prameha and rasayana property has been evaluated as study of antidiabetic and

free radical scavenging activity of the seed Extract of strychnos nuxvomica 133

Vatagna,shoolahara karma by, Analgesic and anti-inflammatory properties of

brucine and brucine N-oxide extracted from seeds of Strychnosnux-vomica 134

Toxicity Studies135Anti Tumour Activity136

and Antisnake venom activity137

have also been evaluated.

By the above studies the multifaceted actions of kupeelu is clearly evident.

Drugs may act owing to the properties inherent within them with respect to their

rasa, veerya, vipaka, guna or prabhava also called the Rasapanchakas.(ch.su-26/61) .By

this pharmacodynamics and pharmacokinetics may be inferred .Considering this cross

reference in context of visha dravyas, Visha is said to be vishagna because of

prabhava.(ch.su-26/69).

The rasa panchaka of a drug may be similar but it differs in action which is called

prabhava. (ch.su-26/68).. This may be the reason why jangama visha acts as prativisha to

sthavara vishas and vice versa. The study “Antisnake venom activity of ethanolic seed

extract of Strychnosnux vomica Linn”.may be influenced by the above reference

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PHARMACEUTICAL REVIEW

When the chronological development of shodhana is viewed, we can infer that

the siddhantas laid down in samhitas have influenced its development. Shodhana process

is a kind of Samskara which brings about gunantaradana as mentioned in charaka

(ch.vi.1/21). Some opine both are different from each other and debate that shodhana is

said to have doshaharana property only and samskara is bala tejo abhivardhana.

Rasaratna samucchaya a rasa text of 13th

century mentioned vishatinduka as one

among the upavishas. He has mentioned shodhana process for vatsanabha and used it as

rasayana in vishakalpas. An inference can be drawn from this point that Rasa Vagbhata

was aware of the poisonous drugs ,their shodhana and therapeutic utility.

Rasasanketa kalika a text by Rasaacharya Chamunda and Rasakamadhenu by

Rasaacharya Chudamani of 16th century introduced the Shodhana of kupeelu by the

method of goghrita bharjana. Ayurveda Prakasha followed the same, he added the

general dose and method of storing vishadravyas. He also added the samanya shodhana

and marana process for vishas as described below.

Samanya shodhana is done by nimajjana in gomutra for 3 days, changing

gomutra daily. On 4th

day the seeds are washed in hot water and dried in sunlight .

Marana usually consists of giving intense heat to incinerate the substance, in this case it

consists of mixing tankana(borax) and visha in equal proportion, this reduces the

toxicity of the visha.

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Further if black pepper is added in twice the quantity of the poison by weight,

then by the process of trituration, both shodhana and marana can be achieved together.

Later on, other texts added many procedures like swedana combined with

nimajjana,bharjana etc.many medias for shodhana like gorasa ,kanji, gomutra,

panchagavya,goghrita,godugdha,swarasa of tanduliyaka etc.

Ayurveda formulary has adopted a single method of shodhana which is done in 3

steps.138

Step 1: The clean and dried seeds kept in cow‟s urine for 7 nights. The urine is changed

every day.

Step 2: The seeds after 1st step are collected and subjected to swedana in dolayantra for 3

hours.

Step 3: The above seeds are collected and washed with water. The seed coat and the

embryo are removed. Then they are roasted with cow‟s ghee in low flame on iron pan.

When the seeds become dark brown and crispy, they are immediately powdered.

Another method is followed by the local native practitioner by name Sri

Raghavendra of Shimoga, Karnataka, India. In this process step 1 & 3 are same as

described above, but in step 2 instead of swedana, the seeds after 1st step are immersed in

cow‟s milk for 3 days, the milk is changed is everyday.

Some of the research works were carried out in modern medicine using the above similar

references. They are as follows

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-Ayurvedic processings of nux vomica: Qualitative and quantitative determination of

total alkaloidal contents and relative toxicity.139

- Effect of purification (shodhana) on the acute Toxicity of seeds of strychnos nux-

vomica 140

In Alternative systems of medicine,shodhana exists in different names, for

example in Unani it is called Mudabbar

141, in Siddha as suthi

142 and in Chinese native

system of medicine 144

(kampoo system of medicine) it is called as detoxification.

In unani system, we find 4 different methods of detoxification143

1. Seeds are immersed in excess of water for 5 days and then taken out ,immersed in milk

for 2 days.everyday the medias will be changed.the seeds are boiled in milk and seed

coat embryonic axis removed and powdered.

2. Seeds are soaked in milk for 7 days with changing of milk everyday,as we do

in nimajjana.

3. Roasting the seeds in cow‟s ghee till the colour changes to reddish as we do in

bharjana.

4. Seeds are buried in yellow clay for 10 days the clay is kept moist throughout.then

taken out tied in cloth and boiled in 2 liters of milk as we do swedana in dolayantra.

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In addition to the procedures told in Ayurveda, two additional method are followed by

them.One is the method of burial in yellow clay paste and the other being nimajjana in

water.

In Chinese kampoo system of medicine detoxification of the seeds of Strychnos

nux-vomica L. is done by the method of roasting in sea sand until the seeds become dark

yellow. Then the seeds are boiled in water for ten minutes and dried .Later these dried

seeds are parched with sesame oil turning the seeds to pale yellow colour.144

By all the above said references we can say that the concept is existing not only in

ayurveda but also in unani, siddha , chinese systems and folklore practice.

The liquid medias used in Shodhana processes play an important role. Sometimes

medias acts like solvents, dissolve the material for easy separation from the insoluble

impurities like in Guggulu and Navasadara Shodhana. In some other cases, medias

eradicate toxic chemical substances from the drug. For example Churnodaka (lime

water) is generally used for Manahshila Shodhana. Here Churnodaka reacts to eradicate

highly toxic As2O3 from Manahshila. Some materials are used directly in therapeutics

after Shodhana, here media may provide some organic and inorganic principles, which

have important role to increase the bioavailability of the drugs. Media helps in physical

transformation of some metals and minerals. In Nirvapa process repeated heating and

quenching in liquid media causes brittleness, breaking and size reduction of the metals

and minerals. During Shodhana process, some physical changes might take place, like.,

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Elimination of physical impurities: Like in Shodhana of Kampillaka, Guggulu etc

where there is removal of physical impurities.

Reduction in hardness, brittleness and particle size : By Nirvapa process, repeated

heating and quenching in liquid media.

Elimination of chemical impurities: During Shodhana of Makshika (CuFeS2)

impurities like arsenic get eliminated by heating.

Formation of chemical compounds: Lauha when heated up to red hot reacts with

atmospheric oxygen to form ferroso-ferric oxide, which is favourable to the body.

Change into desired compound: During Shodhana of Tankana and Kankshi, water

portion is evaporated and desired chemical compound is formed.

Biological changes: Vatsanabha (Aconitum ferox purified in cow‟s urine) is converted

into cardiac stimulant, where as crude Vatsanabha is claimed to be cardiac depressant145

.

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DISCUSSION BASED ON ANALYTICAL REVIEW

Different techniques have been used for analysis and quantification of strychnine and

brucine in raw and processed seeds. Some of the studies have used chemical methods

some others the optical methods, chromatographic techniques such as thin layer

chromatography (tlc) 146,147

,hplc with uv detection148,149

, liquid chromatography coupled

with mass spectrometry (lc-ms) 150

,tandem mass spectrometry (lc-ms/ms)151,152

,gas

chromatography coupled with mass spectrometry 153,154

,nuclear magnetic resonance

spectroscopy (1h-nmr)155

,liquid chromatography electrospray mass spectroscopy156

hplc 157

,gas chromatography158

,ultraviolet spectrophotometry159

,sweeping micellar

,electrokinetic chromatography160

,rapid commun mass spectrum161

,capillary zone

electrophoresis162,163

,non aqueous capillary electrophoresis 164,165

etc.

TLC and FTIR analytical tests have been used in the present study to assess the changes

in the seeds that might have taken place by shodhana.

DISCUSSION BASED ON MATERIALS AND METHODS

MICROSCOPIC ANALYSIS

The microscopical characteristics of ashodhita kupeelu were in accordance with

the standards given in API volume I, part IV.

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On microscopic analysis of ashuddha kupeelu, the aleurone grains, trichomes and

the yellow parenchyma, fat globules were clearly seen. After swedana in goksheera the

quantity of trichomes were scarce and almost nil after goghrita bharjana. This is because

of the peeling of outer covering that was done after shodhana. The amount of yellow

parenchyma and the aleurone grains were also decreased after shodhana.

DISCUSSION BASED ON PHARMACEUTICAL STUDY

In order to get a good quality of end procuct the selection of raw material and the

process of manufacturing should be of optimum quality keeping this in mind, the

procured seeds were first cleaned by washing with water and the seeds which were black

colored , floated on the surface of the water, were taken out. The settled seeds at the

bottom of the vessel were taken out and dried to get rid of the moisture content. Thus

obtained seeds were selected for further Shodhana procedures and shodhana was done by

2 specified methods viz.swedana in godugdha and bharjana in goghrita.

Godugdha which has madhura rasa,sheeta veerya,madhura vipaka is jeevaniya and

best among the ksheera varga according to samhitas. Daily consumption of goksheera

and goghrita acts as rasayana.It has dasha gunas which are exactly opposite to visha

gunas by virtue of which it reduces the toxic effect of visha. After shodhana samskara

gunantaradana takes place which converts visha to amrita i.e by imbibing therapeutic

qualities from godugdha.

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During swedana which involves indirect heat treatment through the media i.e milk

may affect the heat sensitive alkaloids present in kupeelu seeds. Milk contains both water

and fatty acids. The water soluble and lipid soluble alkaloids from seeds will get

dissolved in milk there by reducing the concentration of the toxic alkaloids.

Ghrita which has madhura rasa,sheeta veerya,madhura vipaka, vatapittaprashamana

karma is considered to be the best among the chatuh snehas. It increases smriti, buddhi,

agni ,skukra, oja, kapha, medas. Cures visha vikaras.It is said to be the most important

sneha because of it‟s samskarasya anuvartana guna .During bharjana, due to its guna of

samskarasya anuvartana, it gains the property of visha without leaving its own gunas.Its

vishagna karma will combat against the illefects caused due to visha.Thus we can infer

that it brings therapeutic value to kupeelu after shodhana.

Analyzing through the modern aspect, cow‟s ghee is an ideal fat for deep frying

because it‟s smoke point (where it‟s molecules begin to break down) is 250 degrees C ,

which is well above typical cooking temperatures of around 200 degrees C and above that

of most vegetable oils. It does not burn or smoke easily on heating because it has more

stable saturated bonds. It lacks the double bonds which can be easily damaged by heat.

So it is not likely to form the dangerous free radicals on heating. It contains

approximately 8% lower saturated fatty acids which makes it easily digestible. These

lower saturated fatty acids are the most edible fats and are not found in any other edible

oil or fat.

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Ghrita contains Short chain fatty acids are also readily metabolised by body. The

melting point of Ghrita is 35 0C which is less than the normal temperature of the human

body. Its digestibility co-efficient or rate of absorption is 96% which is highest of all oils

and fats thus reducing formation of free radicals. It contains beta carotene and Vit. E and

both are known antioxidants.It also contains essential fatty acid like linoleic acid,

Triglycerides, diglycerides, monoglycerides, ketoacid glycerides ,glyceryle esters, free

fatty acids, Phospholipids, Sterol.

Bharjana is done in open air which may facilitate formation of strychnine and

brucine N oxides which are said to be pharmacologically safe.

In classics, we find scattered and multiple references of kupeelu shodhana . The

question arises which type of shodhana has to be followed. In this regard, we have to

consider in which context of the disease which media suits well.

For example, in a patient presenting with kshaya janya vatavyadhi which may be

compared to wasting disease induced neurological deficit, shodhana done with the

procedure of swedana with milk may be given in order to enhance the brimhana, rasayana

and ojovardhana effect. In contrast to it if we doubt about the safety and efficacy of the

drug with special reference to toxicological manifestation, ghrita bharjita kupeelu may

be given. This may also check the ill-effects of the drug by the virtue of its vishagna

karma.

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DISCUSSION BASED ON RESULTS OF ANALYTICAL STUDY

Various physico-chemical constants were analysed in order to assess the changes

in the seeds of kupeelu before and after shodhana procedure. Viz. loss on drying, ash

values (water and alcohol soluble), pH, microscopic analysis, qualitative and

semiquantative analysis was done by thin layer chromatography. Fourier transform

infrared spectroscopy was used to analyse the effect of shodhana with respect to the

changes in functional groups.

a) Loss on drying before shodhana and after the shodhana i.e., by method of

godugdha swedana, goghrita bharjana is 4.4, 11.2 and 2.8 respectively.

This is understandable because the water content from cow‟s milk had been absorbed

during swedana process. The loss on drying after goghrita bharjana is less as

compared to swedita kupeelu, because the process of bharjana includes heat treatment

where the water content is evaporated.

b) Total ash value and the acid insoluble ash were also altered by the shodhana

treatment. The exact reason for the altered ash values cannot be identified. This may

be attributed to the altered qualitative and quantitative phytoconstituents of the seeds

after shodhana.

c) Comparing Water soluble and alcohol soluble extractive values after godugdha

swedana and goghrita bharjana .It is more in bharjita and in contrary less in the seeds

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after godugdha swedana .This change may be due to the presence of extractable

phytoconstituents . Concentration of phytoconstituents in goghrita bharjita seeds is

more as compared to phytoconstituents in godugdha swedita seeds. Due to the

leaching action, the phytoconstituents present in the seeds might have transferred to

the milk during the swedana process Thus we may find a considerable decreased

extractive values after shodhana.

d) pH of kupeelu seeds after godugdha swedana and goghrita bharjana has been

increased. This may be due to the alkalinity of milk and ghee influencing the seeds

after shodhana.

The qualitative tests for the presence of alkaloids showed its presence in all

the 3 samples as well as in milk after swedana. This test confirms the presence of

alkaloids in milk after shodana indicating the seeping of alkaloids from the seeds to the

milk thereby reducing its toxicity.

The assay of strychnine was done according to the standards laid in API.

Interestingly the strychnine content in ashuddha kupeelu was 1.26% when

compared to the API standards where it is said that the strychnine content should not be

less than 1.2%.The result is in accordance to the standard value.

The strychnine content in ashuddha kupeelu was 1.26 %. After swedana in milk

,when analysed by chemical assay method it was 1.11% and after goghrita bharjana it

was found to be 0.62%. Thus there is reduction of strychnine by 11.11% in godugdha

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swedita seeds & 50.70 % in gogritha bharjita seed which is less when compared to the

ashuddha kupeelu seeds.

Thus the principle alkaloid strychnine is reduced in both the samples after

shodhana. When compared to the strychnine content in godugdha swedita and goghrita

bharjita sample, the latter contained less strychnine. This may be explained because the

cell wall of kupeelu seeds is non lignified but contains appreciable amount of complex

carbohydrates. Therefore on coming in contact with milk during swedana, it swells and

facilitates leaching strychnine out of the seed cotyledons. Boiling the seeds in milk

reduces strychnine content by converting it to its derivatives like isostrychnine (cai.et.all).

During bharjana the heat is applied which may alter the phytochemical profile of

heat sensitive alkaloids present in kupeelu seeds. The process of bharjana is carried out in

open air which may facilitate the formation of new derivative compounds of strychnine

and brucine such as strychnine –N- oxide and brucine-N-oxide which are said to be

pharmacologically safe.

Ghrita which has vishahara guna , implied in the process of bharjana has an effect

on the phytochemical profile of the drug which is seen as a decrease in the toxic principle

alkaloid strychnine as shown by assay. Ghrita might have been advised for shodhana in

order to combat the toxic effects of visha. To use kupeelu as a medicament, authors of

Rasashastra texts might have thought double surity in the aspect of safety that is imbibing

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the anti-poisonous quality in the drug as well as reduction in toxicological manifestations

of the drug when ingested internally.

These findings are in concurrent with the report that, Chinese system of

detoxification of nuxvomica seeds also has reduced the concentration of major alkaloid

strychinine and brucine and increased the N-oxides of the same (Han Q.B et.al)

The qualitative and semi quantitive analysis of the major alkaloids strychnine and

brucine was done by thin layer chromatography and all the chromatograms were

compared.

The chromatogram of ashuddha kupeelu was in accordance with the standard mentioned

in API.

The chromatogram of both the samples after shodhana showed presence of two distinct

orange colour bands of strychnine and brucine with Rf value of 0.44 and 0.65

respectively. Intensity and band width of both the alkaloids were decreased after

shodhana. The band width , intensity of gogrutha bharjitha kupilu was decreased when

compared to godugdha sweditha kupilu. Thus the decrease in the quantity of the principle

alkaloids is more in goghrita bharjitha kupilu when compared to godugdha sweditha

kupilu. The change can be attributed to the effect of shodhana which proves the

hypothesis.

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Cross referring LCMS study of shuddha kupilu and godugda sweditha kupilu which was

of the same view that there was significant decrease in the principle alkaloid content

after shodhana.

LCMS spectra of godugda sweditha kupilu showed distinct peaks at masses (ES

+450 for ;341 and 382) which were not evident in the LCMS spectra of ashuddha kupilu

seeds. The analysis confirmed the presence of some new adducts. This shows that

transformations might have occurred after the process of swedana. 139

Optical methods for the evaluation of chemical constituents in drug strychnos

nuxvomica are prevalent since early 20th century. Bhanu and Vasudevan (1989) used UV

spectrophotometer to demonstrate strychnine and brucine contents in the processed nux

vomica166.

Cross referring a study in unani system of medicine ,Strychnine contents in raw

Strychnos nux-vomica seeds and processed seeds in different medias as determined

using UV-Visible spectrophotometer167

have shown following results.

1. Crude seeds 1.21 %

2. Detoxification using identical method like swedana in milk 0.47 %

3. Detoxification using bharjana method using cow‟s ghee 1.06%

The results show a decrease in the concentration of strychnine content after detoxification

which is in concurrence with the present study.

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Fourier transform infrared spectroscopy is also an optical method which was used in the

present study.

FTIR spectral fingerprints of all the 3 samples revealed peaks which arise due the

presence of multiple functional groups . Presence of such multiple functional groups

indicates towards the multifaceted action of the single drug.

When comparison is done to evaluate the effect of shodhana, for example we

found changes in the stretch of –OH functional group. Ashuddha kupeelu ,godugdha

swedita, goghruta bharjita kupeelu showed –oh stretches , with frequencies

3356,3420.52, 3515.88 and with transmittance values 3.16,6.96 and 42.65 respectively.

Based on these results an inference is made that,there is a considerable increase in

the transmittance after shodhana indicating the decrease in absorption .Absorption is

directly proportional to the concentration according to beer-lambert‟s law. From this it is

derived that concentration of phytoconstituents is reduced after shodhana and on

comparing 2 samples after shodhana , concentration in bharjita seeds is less. Similarly

the other functional groups also show variations which may be attributed to effect of

shodhana.

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CONCLUSION

1) References of Kupeelu is neither available in Veda Kala nor in Samhita Kala. The drug

Vishamusti in samithas can not considered as kupeelu.

2) The drug Kupeelu is a non controversial drug as far its identification is concerned.

3) Kupeelu is Tikta Rasa Pradhana Dravya

4) Strychnine and Brucine are two important toxic alkaloids present in the seeds of

Strychnos nux-vomica.

5) The raw kupeelu seeds contained appreciable amount of strychnine, when compared to

the standards laid down by the Ayurvedic pharmacopoeia of India.

6) The Trichomes were easily separable after Shodhana by Gogrutha Bharjana method

when compared to Shodhana by Godugdha Swedana method.

7) Seeds were easily pounded after Shodhana by Gogritha Bharjana method when

compared to the Godugda swedana method proving that they had become brittle.

8) The decrease of strychnine contents by 11.11% was observed when Swedana by

Godugda was done where as the Gogritha Bharjana showed 50.70% decrease in

strychnine contents, indicating that the Gogritha Bharjana method is better in

reducing the percentage of toxic alkaloids.

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9) Shodhana has altered the functional groups present in kupeelu as shown

by FTIR analysis and this spectra can be used as a fingerprint standard..

10) Shodhana has also reduced the concentration of toxic principles Strychnine and

Brucine as shown by the qualitative and semi-quantative analysis done by using thin

layer chromatography.

11) Amongst the two methods of Shodhana, Gogritha Bharjana is considered to be better,

because it consumes lesser time, and there is marked reduction of Strychnine and

Brucine.

12) The reduction of toxic principles- Strychnine and Brucine, brought in by the

shodhana methods, caused the required change in the phytochemical profile of the

seeds of Kupeelu. This proves and concludes the Hypothesis successfully.

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SUMMARY

The visha-upavisha varga dravyas are the group of poisonous drugs which have

potential lethal effect when consumed internally in their native form.Acharya Charaka

mentions that ,even poisonous plants when used in a proper manner according to the

intellect will turn as ambrosia. Acharyas of Rasashastra have mentioned various

methods of shodhana in order to detoxify and bring about therapeutic effect in such

plants.Kupeelu is one among the upavisha dravya possessing multifaceted action is taken

for the study entitled “A Pharmaceutico Analytical Study On Concept Of Shodhana

With Special Reference To Kupeelu Shodhana” was presented as introduction, aims

and objectives, review of literature, materials and methods,results, discussion and

conclusion.

The review of literature was handled in different sections namely drug review,

review of pharmaceutical procedures and analytical review.

Seeds of kupeelu were purchased from an Authentic source, FRLHT research centre.

Bangalore. Pharmacognostic study was done in the post graduate department of

Rasashastra, Government ayurveda medical college, Bangalore and Bangalore test

house(BTH) ,Bangalore .

The seeds of kupeelu were then subjected to shodhana by 2 different methods as

mentioned in rasa tarangini.The cleand and dried seeds were tied in a pottali and

subjected to swedana in dolayantra for 3 hours using godugdha as media.The seeds were

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then washed with hot water,the seed coat and embryonic axis was removed ,the

cotyledons were powdered in a khalwa yantra.

In another method bharjana was carried out using goghrita till the seeds turned to

yellowish red.The seeds were washed with hot water,the seed coat was removed and

powdering of seeds was done in khalwa yantra.

Thus obtained samples along with raw sample were subjected to analysis of

organoleptic characters,physico-chemical constants,quantative assay for strychnine,thin

layer chromatography of their methanolic extracts and fourier transform infra red

spectroscopy in different centres namely, post graduate Department of Rasashastra,

Government Ayurveda medical college, Bangalore,Government central

pharmacy.Bangalore Bangalore test house(BTH) ,Bangalore. Indian institute of science

(iisc, tata institute) Bangalore.

Appropriate discussion was done on every aspect of the study. Organoleptic

analysis revealed that the seeds were devoid of trichomes after shodhana ,seeds became

soft in case of godugdha swedana and brittle,crispy in case of goghrita bharjana which

could be easily powdered.alteration of ash and extractive values was noted in analysis of

physico-chemical constants.in quantative assay of strychnine there was a reduction of

strychnine by 11.11% in godugdha swedita seeds & 50.70 % in gogritha bharjita

seeds.tlc analysis showed a qualitative and quantative change in phytochemistry of seeds

after shodhana.there was also a change in the spectras as revealed by ftir analysis.

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It was then concluded from the present study that shodhana was effective in

reducing the toxic principles strychnine and brucine.Method of goghrira bharjana was

better than the method of swedana as far as reduction in quantity of toxic alkaloids and

the ease for powdering was concerned .Shodhana brings about qualitative and

quantitative changes in the phytochemistry of drug.It was evident from the study that

techniques like quantative assay,thin layer chromatography and FTIR were very much

useful in the assessment of qualitative and quantitative changes before and after

shodhana.Thus proving the hypothesis.

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LIMITATIONS OF THE STUDY

A PHARMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF SHODHANA W.S.R TO

KUPEELU SHODHANA Page 137

LIMITATIONS

1. The research work is particularly based only on pharmaceutical and

analytical parameters since it is a time bound research.

2. The study was restricted to only 2 Shodhana procedures.

3. Even though Modern parameters have helped to know the changes in the

drug after shodhana to some extent, there is a limitation by them in the

total assessment of alteration in the drug profile after classical

processing.

4. There was lack of advanced and sophisticated instruments for analytical

study so the study was carried out using possible technology.

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SCOPE FOR FURTHER STUDIES

A PHARMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF SHODHANA W.S.R TO

KUPEELU SHODHANA Page 138

SCOPE FOR FURTHER STUDIES

Research is a process which is continuous one, thus following

suggestions may be carried out in the following regards.

1. A wide number of procedures which are described for Kupeelu

shodhana are also to be studied and standardized.

2. Combined usage of sophisticated and ultramodern analytical

instruments to identify, isolate, characterise and evaluate the active

principles responsible for the usefulness in treating various

diseases may be done.

3. Toxicity studies must be carried out in order to evaluate the safety

and efficacy in animals.

4. Pharmacological studies should be carried out for proper

evaluation of the Kinetics and Dynamics.

5. Clinical evaluation of shodhita kupeelu choorna may give an exact

picture of rationality behind the effect of shodhana which is used

in a wide number of disorders.

6. Formulations of kupeelu may also be studied clinically with

respect to their specific indications.

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BIBILOGRAPHY

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KUPEELU SHODHANA Page 139

BIBILOGRAPHY

INTRODUCTION

1) Agnivesa, Charaka, Dridhabala, CharakaSamhita, Sutra Sthana, 1/126, edited by

Sharma R. K, Das Bhagwan. CharakaSamhita, Text with English translation and critical

exposition based on CakrapaniDutta's Ayurveda Dipika, Chowkhamba Sanskrit Series

Office; Varanasi, 2008. p.59.

2) Agnivesa, Charaka, Dridhabala, CharakaSamhita, Sutra Sthana,1/67, edited by Sharma

R. K, Das Bhagwan. CharakaSamhita, Text with English translation and critical

exposition based on CakrapaniDutta's Ayurveda Dipika, Chowkhamba Sanskrit Series

Office; Varanasi, 2008.p.47

3) Agnivesa, Charaka, Dridhabala, CharakaSamhita, Sutra Sthana,26/12, edited by

Sharma R. K, Das Bhagwan. CharakaSamhita, Text with English translation and critical

exposition based on CakrapaniDutta's Ayurveda Dipika, Chowkhamba Sanskrit Series

Office; Varanasi, 2008. P.138

4) Agnivesa, Charaka, Dridhabala, CharakaSamhita, chikitsa Sthana, 24/60, edited by

Sharma R. K, Das Bhagwan. CharakaSamhita, Text with English translation and critical

exposition based on CakrapaniDutta's Ayurveda Dipika, Chowkhamba Sanskrit Series

Office; Varanasi, 2008.p.397

5) Agnivesa, Charaka, Dridhabala, CharakaSamhita, Sutra Sthana, 30/28, edited by

Sharma R. K, Das Bhagwan. CharakaSamhita, Text with English translation and critical

exposition based on CakrapaniDutta's Ayurveda Dipika, Chowkhamba Sanskrit Series

Office; Varanasi, 2008.p.203

6) Sushruta,Sushruta samhita,P.V.Sharma,Chaukamba oriental 2003 Varanasi, sutra

sthana chapter-1, shloka-6 pp824,p.no.10

Page 158: “A PHAMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF …

BIBILOGRAPHY

A PHARMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF SHODHANA W.S.R TO

KUPEELU SHODHANA Page 140

7) Shri. Vagbhattachary Rasa Rata Sammucchaya “Vigyan Bodhini”, Hindi

Commentary, by Prof. Dattatreya Anant Kulkarni Mehracanda Laccamandasa

Publication. Chapter- 10 shloka-74 pg.199

8) Sharma SN, Shastri KN. Rasa Tarangini. 11 th ed. New Delhi: MotilalBanarasidas

Publication; 2000. Chapter 24 shloka-163 P. 676.

9) Gogte VM. Ayurvedic pharmacology and therapeutic uses of medicinal plants. 1 st ed.

Mumbai: BharatiyaVidyaBhavan; 2000. P. 345-7

10) Sharma SN, Shastri KN. Rasa Tarangini. 11 th ed. New Delhi: MotilalBanarasidas

Publication; 2000. Chapter 24 shloka-176-177 P. 679.

11) Sharma SN, Shastri KN. Rasa Tarangini. 11 th ed. New Delhi: MotilalBanarasidas

Publication; 2000. Chapter 24 shloka-174-175 P. 678.

REVIEW OF LITERATURE.

12) U.R.S. Namburi, A text book of Agada tantra, choukambha sanskrita bhavana,

chapter-2 pg:6

13) Agnivesa, Charaka, Dridhabala, CharakaSamhita, chikitsa Sthana, 23/5, edited by

Sharma R. K, Das Bhagwan. CharakaSamhita, Text with English translation and critical

exposition based on CakrapaniDutta's Ayurveda Dipika, Chowkhamba Sanskrit Series

Office; Varanasi, 2008.p.323

14) Sushruta,Sushruta samhita, P.V.Sharma,Chaukamba oriental 2003 Varanasi, sutra

sthana chapter-3, shloka-21 p.no.57.

Page 159: “A PHAMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF …

BIBILOGRAPHY

A PHARMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF SHODHANA W.S.R TO

KUPEELU SHODHANA Page 141

15) Agnivesa, Charaka, Dridhabala, CharakaSamhita, sutra Sthana, 1/126, edited by

Sharma R. K, Das Bhagwan. CharakaSamhita, Text with English translation and critical

exposition based on CakrapaniDutta's Ayurveda Dipika, Chowkhamba Sanskrit Series

Office; Varanasi, 2008. P.60

16) Vagbhatacharya,Astanga hridaya,Pt Bhishagacharya harishastri paradkar vaidya,

Nirmay sagar press,2002,Varanasi,uttar tantra chapter-35 shloka-5 pp 956.

17) Sushruta,Sushruta samhita,Ambikadatta shastrii,Chaukamba oriental 2003 Varanasi,

kalpa sthana chapter-3, shloka-3 ,p.no.26

18) Sharma SN, Shastri KN. Rasa Tarangini. 11 th ed. New Delhi: MotilalBanarasidas

Publication; 2000. Chapter 24 shloka-6 p-648

19) Agnivesa, Charaka, Dridhabala, CharakaSamhita, chikitsa Sthana, 23/16, edited by

Sharma R. K, Das Bhagwan. CharakaSamhita, Text with English translation and critical

exposition based on CakrapaniDutta's Ayurveda Dipika, Chowkhamba Sanskrit Series

Office; Varanasi, 2008.p.327

20) Sushruta,Sushruta samhita, Ambikadatta shastrii ,Chaukamba oriental 2003 Varanasi,

kalpa sthana chapter-3, shloka-4-5.p.no.27

21) Agnivesa, Charaka, Dridhabala, CharakaSamhita, chikitsa Sthana, 23/15, edited by

Sharma R. K, Das Bhagwan. CharakaSamhita, Text with English translation and critical

exposition based on CakrapaniDutta's Ayurveda Dipika, Chowkhamba Sanskrit Series

Office; Varanasi, 2008.p.327

22) Agnivesa, Charaka, Dridhabala, CharakaSamhita, chikitsa Sthana, 23/14, edited by

Sharma R. K, Das Bhagwan. CharakaSamhita, Text with English translation and critical

Page 160: “A PHAMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF …

BIBILOGRAPHY

A PHARMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF SHODHANA W.S.R TO

KUPEELU SHODHANA Page 142

exposition based on CakrapaniDutta's Ayurveda Dipika, Chowkhamba Sanskrit Series

Office; Varanasi, 2008.p.326

23) Sushruta,Sushruta samhita, Ambikadatta shastri ,Chaukamba oriental 2003 Varanasi,

kalpa sthana chapter-2 shloka-33.p.no.34

24) ) Agnivesa, Charaka, Dridhabala, CharakaSamhita, chikitsa Sthana, 24/60, edited by

Sharma R. K, Das Bhagwan. CharakaSamhita, Text with English translation and critical

exposition based on CakrapaniDutta's Ayurveda Dipika, Chowkhamba Sanskrit Series

Office; Varanasi, 2008.p.397

25) Shri. Vagbhattachary Rasa Rata Sammucchaya “Vigyan Bodhini”, Hindi

Commentary, by Prof. Dattatreya Anant Kulkarni Mehracanda Laccamandasa

Publication. Chapter 10 shloka-74 pg.199

26) Sharma SN, Shastri KN. Rasa Tarangini. 11 th ed. New Delhi: MotilalBanarasidas

Publication; 2000. Chapter 24 shloka-163-164, p-675-676.

27) Acharya Srimadhava Ayurveda praksha edited by GulrajMishra,Choukambha

bharathi academy,Varanasi, edition 2nd

, 1962,6th chapter,shloka 47-48, page no.461

28) Acharya Srimadhava Ayurveda praksha edited by GulrajMishra,Choukambha

bharathi academy,Varanasi, edition 2nd

, 1962,6th chapter,shloka45-46,page no.461

29) Acharya Srimadhava Ayurveda praksha edited by GulrajMishra,Choukambha

bharathi academy,Varanasi, edition 2nd

, 1962,6th chapter,shloka-71,page no.465

30) ) Acharya Srimadhava Ayurveda praksha edited by GulrajMishra,Choukambha

bharathi academy,Varanasi, edition 2nd

, 1962,6th chapter,shloka-49-52,page no.461,462

31) ) Acharya Srimadhava Ayurveda praksha edited by GulrajMishra,Choukambha

bharathi academy,Varanasi, edition 2nd

, 1962,6th chapter,shloka-51,page no.462

Page 161: “A PHAMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF …

BIBILOGRAPHY

A PHARMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF SHODHANA W.S.R TO

KUPEELU SHODHANA Page 143

32) Acharya Srimadhava Ayurveda praksha edited by GulrajMishra,Choukambha

bharathi academy,Varanasi, edition 2nd

, 1962,5th chapter,shloka 60-62, page no.463

33) Mukund Sabnis, Chemistry & Pharmacology of Ayurvedic Medicinal Plants, First

edition:,pg. 409-411,(2006)

34) K.R.Narayan Reddy,The essentials of forensic medicine and toxicology 28th

edition

(2009) ,pp604,page number 442.

DRUG REVIEW

35) P.V.sharma, Dravya Guna Vignana part 4,Chaukamba Bharati

Academy,Varanasi,1999 pp.392-p.no.239

36) Sushruta,Sushruta samhita,Acharya yadavji trikamji,Chaukamba oriental 2003

Varanasi,pp824,p.no:160

37) Vagbhatacharya,Astanga hridaya,Pt Bhishagacharya harishastri paradkar vaidya,

Nirmay sagar press,2002,Varanasi,pp 956,p.no.164

38) Harigvinda shastri,Amarakkosha-Choukamba samskrita sansthana Varanasi,3rd

edition,1997 ,pp 668, p.no.181

39) Proff.P.V.Sharma,Dhanwantari Nighantu,Chaukamba orientalia,Varanasi,pp

360,p.no.155

40) Vaidyacharya Keshava,Siddha mantra prakasha, Proff.P.V. Sharma, Chaukamba,

Amarabharati prakashana, 1997, Varanasi, pp,188, pg-107.

41) Vaidyacharya shodhala,Shodala nighantu,Proff.P.V.Sharma,Orientala

literature,1978,Baroda pp 267,p.no.53

Page 162: “A PHAMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF …

BIBILOGRAPHY

A PHARMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF SHODHANA W.S.R TO

KUPEELU SHODHANA Page 144

42) Dr.P.V.Sharma,Madhava Dravya Guna,Chaukamba vaidya bharana

,1973,Varanasi,pp 124,p.no.46

43) Nrupa,Madanapala,Madanapala nighantu,Chaukamaba publications

,1998,Varanasi,pp 171,p.no.127

44) Kaiyadeva Nighantu,Proff.P.V.Sharma,Chaukamba orientalia,Varanasi

pp696,p.no.74

45) Bhavamishra,Bhavaprakasha nighantu,Dr.G.S.Pandey,Chaukamba Bharati

Academy2004 ,Varanasi,pp 984,p.no.569

46) Saaligrama vaidya, Saaligrama nighantu ,Khemraja,shri krishna das,2002,Mumbai

,pp995,p.no.452

47) Pandit Narahari,Raja nighantu,Dr,Indradev Tripati,Chau Chaukamba Bharati

Academy2003 ,Varanasi,pp 704,p.no.293

48) P.V.Sharma ,1999,Priya nigantu Chau Chaukamba Bharati Academy1999

,Varanasi,pp 114,p.no.112

49) Shri. Vagbhattachary Rasa Rata Sammucchaya “Vigyan Bodhini”, Hindi

Commentary, by Prof. Dattatreya Anant Kulkarni Mehracanda Laccamandasa

Publication. Chapter-10 shloka-74 pg.199

50) Sharma SN, Shastri KN. Rasa Tarangini. 11 th ed. New Delhi: MotilalBanarasidas

Publication; 2000. Chapter 24 shloka-163-164, p-675-676.

51) Kirtikar KR, Basu BD, Indian medicinal plants, 2nd ed., Periodical experts book

agency, New Delhi, Vol. 2, M/s Bishen singh Mahendrapal singh, Dehradun,

1975;2:1645-1647.

Page 163: “A PHAMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF …

BIBILOGRAPHY

A PHARMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF SHODHANA W.S.R TO

KUPEELU SHODHANA Page 145

52) Rasatarangani, Commentary by Acharya Haridutta Shastri, Stanza, Sunder Lal Jain

Motilal Banarasidas, Varanasi, 1954;chapter : 24, shloka-178-202.

53) Gogte VM. Ayurvedic pharmacology and therapeutic uses of medicinal plants. 1 st ed.

Mumbai: BharatiyaVidyaBhavan; 2000. Pg-346

54) Gogte VM. Ayurvedic pharmacology and therapeutic uses of medicinal plants. 1 st ed.

Mumbai: BharatiyaVidyaBhavan; 2000. Pg-348

55) Medicinal plants in Floklores of Northen India CCRUM publication: 1st edition june

2001 pg: 463.

56) Medicinal plants in Bihar and Orrisa, CCRUM publication: 1st edition june 2001 pg:

954.

57) www.wikipidia/nuxvomica.

58) Dr. Dole Vilas & Dr. Paranjpe Prakash, Text book of Rasashastra pg. 408-409.

59) Dr. Siddhinandana Mishra, Ayurvediya Rasashastra, First Edition, Chaukhambha

Orientalia Varanasi, (1999).

60) Govinda dasa sena, bhaisajaya ratnavali ,edited by siddhinandan Mishra, Chaukamba

Bharati Academy2008,1st edition,p.no.569

61) Yogaratnakara, edited and translated by madham shetty suresh babu, Chaukambha

sanskrita seriers.

62) Rasatarangani, Commentary by Acharya Haridutta Shastri, Stanza, Sunder Lal Jain

Motilal Banarasidas, Varanasi, 1954;chapter : 24,

Page 164: “A PHAMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF …

BIBILOGRAPHY

A PHARMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF SHODHANA W.S.R TO

KUPEELU SHODHANA Page 146

63) AshokSathpute Rasendra Sara Samgraha of Sri Gopala Krishna,Choukambha

Krishnadasa academy,edition 1st ,2003.

64) Siddinandan Mishra Rasa Prakasha sudhakara of Yashodhara,Choukambha

orientalaya Varanasi,year of publication 2009.

65) Bharata bhaisajya ratnakara, Choukambha orientalaya Varanasi,year of publication

2009.

66) ) www.wikipidia.org/wiki/strychnine_po

67) Nadakarni AK, The Indian Materia Medica, Popular prakashan, Mumbai, Vol.2,

1976; 1175-1180.

68) Nadakarni AK, The Indian Materia Medica, Popular prakashan, Mumbai, Vol.2,

1976; 1175-1180.

69) Nadakarni AK, The Indian Materia Medica, Popular prakashan, Mumbai, Vol.2,

1976; 1175-1180.

70) www.ncbi.nlm.nih.gov/pubmed/10617902

71) Genevie`ve Philippe, Luc Angenot, Monique Tits, Michel Fre´de´rich. About the

toxicity of some Strychnos species and their alkaloids. Toxicon 2004; 44 : 405–416.

72) Yan-Yan Xu1,2, Duan-Yun Si2, Chang-Xiao Liu1* Research on bioresponse of

active compounds of Strychnos nux-vomica L.

73) www.wikipidia.org/wiki/strychnine_po

Page 165: “A PHAMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF …

BIBILOGRAPHY

A PHARMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF SHODHANA W.S.R TO

KUPEELU SHODHANA Page 147

74) Goodman & Gilman,Pharmacological basis of Therapeutics,5th

Edition,pg.345-348

75) Baghel M.S., Researches in Ayurveda, Mridu Ayurvedic Publications and Sales,

Jamnagar, 2005.

76) Agnivesa, Charaka, Dridhabala, CharakaSamhita, sutra Sthana – 26/5-7, edited by

Sharma R. K, Das Bha`gwan. CharakaSamhita, Text with English translation and critical

exposition based on CakrapaniDutta's Ayurveda Dipika, Chowkhamba Sanskrit Series

Office; Varanasi, 2008.p.no.493

77) Sushruta,Sushruta samhita,P.V.Sharma,Chaukamba oriental 2003 Varanasi, sthana

chapter-45/47.p.no.425

78) Vagbhata, Astanga hrudaya with Hindi commentary by P.V.Sharma, 7th edition

1999, sutra sthana 5/21.p.no.68.

79) Bhavamishra, Bhava Prakasha Nighantu,Hindi commentary by Shrikrishna Chandra

Chunekar, Chaukambha Vidya bhavan Varanasi, 1st edn, 1960, Version 1-2, Page no

605

80) Agnivesa, Charaka, Dridhabala, CharakaSamhita, chikitsa Sthana – 23/24, edited by

Sharma R. K, Das Bhagwan. CharakaSamhita, Text with English translation and critical

exposition based on CakrapaniDutta's Ayurveda Dipika, Chowkhamba Sanskrit Series

Office; Varanasi, 2008.p.no.331

81) Agnivesa, Charaka, Dridhabala, CharakaSamhita, sutra Sthana – 1/127, edited by

Sharma R. K, Das Bhagwan. CharakaSamhita, Text with English translation and critical

exposition based on CakrapaniDutta's Ayurveda Dipika, Chowkhamba Sanskrit Series

Office; Varanasi, 2008.page no.60

82) USDA national nutrient database for standard reference. Ars.usda.gov. Retrieved on

2011-11-24. )

Page 166: “A PHAMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF …

BIBILOGRAPHY

A PHARMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF SHODHANA W.S.R TO

KUPEELU SHODHANA Page 148

83) "Milk analysis". North wales buffalo. Archived from the original on 2007-09-29.

Retrieved 3 august 2009. (citing mccane, widdowson, scherz, kloos, international

laboratory services.)

84) Agnivesa, Charaka, Dridhabala, CharakaSamhita, sutra Sthana – 13/13, edited by

Sharma R. K, Das Bhagwan. CharakaSamhita, Text with English translation and critical

exposition based on CakrapaniDutta's Ayurveda Dipika, Chowkhamba Sanskrit Series

Office; Varanasi, 2008.p.no.247

85) Agnivesa, Charaka, Dridhabala, CharakaSamhita, sutra Sthana – 13/14, edited by

Sharma R. K, Das Bhagwan. CharakaSamhita, Text with English translation and critical

exposition based on CakrapaniDutta's Ayurveda Dipika, Chowkhamba Sanskrit Series

Office; Varanasi, 2008.p.no.248

86) Agnivesa, Charaka, Dridhabala, CharakaSamhita, sutra Sthana – 13/40, edited by

Sharma R. K, Das Bhagwan. CharakaSamhita, Text with English translation and critical

exposition based on CakrapaniDutta's Ayurveda Dipika, Chowkhamba Sanskrit Series

Office; Varanasi, 2008.p.no.253

87) Agnivesa, Charaka, Dridhabala, CharakaSamhita, sutra Sthana – 26/5-7, edited by

Sharma R. K, Das Bhagwan. CharakaSamhita, Text with English translation and critical

exposition based on CakrapaniDutta's Ayurveda Dipika, Chowkhamba Sanskrit Series

Office; Varanasi, 2008.p.no.493

88) Sushruta,Sushruta samhita,P.V.Sharma,Chaukamba oriental 2003 Varanasi, sthana

chapter-45/96.p.no.435

89)Vagbhata, Astanga Sangraha with Hindi commentary by vaidya Lakshmi Shastri,

Edited by Brahmananda Shastri, 7th edition 1999

90)Agnivesa, Charaka, Dridhabala, CharakaSamhita, sutra Sthana – 13/14, edited by

Sharma R. K, Das Bhagwan. CharakaSamhita, Text with English translation and critical

Page 167: “A PHAMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF …

BIBILOGRAPHY

A PHARMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF SHODHANA W.S.R TO

KUPEELU SHODHANA Page 149

exposition based on CakrapaniDutta's Ayurveda Dipika, Chowkhamba Sanskrit Series

Office; Varanasi, 2008.p.no.248

91) www.mendeley.com/research

92) J.L.N. shastry,Dravyaguna vignana,VolI,Choukambha publications,Varanasi,Ed 1st

,2002,pno320.

93) Sri sadananda sharma, rasatarangini,edited by kashinatha shastry,motilala banarasi

das,v aranasi,ed 11th ,1979,reprint 2000,2nd chapter,shloka no 52,pno22.

94) Bhajandas swami dadupanth Rasadarpana,1st part,nath pustak bhandar,

rohtak,paristhista, page no 369.

95)Prashant Sarkar, Evaluation of Shodhana Process and Antidotal Study on

Vatsanabha,2008

96) Dr. Dole Vilas & Dr. Paranjpe Prakash, Text book of Rasashastra pg. 408-409.

97) Mukund Sabnis, Chemistry & Pharmacology of Ayurvedic Medicinal Plants, First

edition:,pg. 409-411,(2006)

98) Rasa Sanketa Kalika by kayastha chamunda English translation by Pammi

Satyanarayana shastry, published by Krishnadas chowkhambha Ayurveda academy 3rd

Ullasa.

99) Rasakamadhenu compiled by chudamani, revised by Vaidya Yadavji Trikamji

Acharya published by Chowkhambha publisher edition 2 prathama upakarana pada, 4th

adhikarana page 51.

100) Ayurveda Prakasha edited by Gulrajsharma Mishra, published by Chowkhambha

Vidyabhavan Varanasi, 6th chap, pp.501

Page 168: “A PHAMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF …

BIBILOGRAPHY

A PHARMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF SHODHANA W.S.R TO

KUPEELU SHODHANA Page 150

101) BhudebMukerjee, Rasa Jala Nidhi or Ocean of Indian Chemistry, Medicine and

Alchemy, compiled in Sanskrit text with English translation, 4th edition, Varanasi,

Chaukhambha Publishers, 2004, Volume II, 2nd chapter, page no. 130.

102) Rasendra Purana ,Ramprasad Vaidya Padyoga, 30th chapter , pp.170.

103) Rasa Raja Mahodadhi ,Vinodkumar Vaidya shastri, published by Ganga book depot

Ghila Mandi Mathura, 1st edition 1961 ,p.p. 54.

104) Yadavji trikamji Acharya, Rasamrita, edited by Motilal Banarasidas , Banaras-2008

105) Rasachikitsa by Kaviraj Prabhakar Chatterjee, 1956, by Chowkhambha

Vidyabhavan Varanasi, pp. 103

106) RasaDarpana by Bhajandas Swamy Dadu Panthya published by Nath Pustak

Bhandar, rohtak 1st part 10th adhyayapp.353-355.)

107) Siddha Yoga Sangraha by Yadavji trikamji Acharya 1st edition published by Shree

Baidyanath Ayurved bhavan private limited, parishishta.

108) Bharateeya Rasa Paddhati by Atridev Gupta 2nd edition Chowkhambha Sanskrit

series. Pg-87

109) Dr.Sudhaldev Mohapatra, Rasa shatra at a glance, Chowkhambha krishnadas

academy,Varanasi.p.no.85

110) Agadatantram, by jagannath Prasad shukla, published by sudha Nidhi Karyalayam 3

sammelan marg prayog. Pg-56

111) Rasa Dhatu Prakasha by Pandit D.Mule 1st edition 1957, published by author .

chapter 58, page 777.

112) Dattaram Chowbe, Brihat Rasa Raja Sundara, published by Chowkhamba orientala,

3rd edition 2000, page 223-224.

Page 169: “A PHAMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF …

BIBILOGRAPHY

A PHARMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF SHODHANA W.S.R TO

KUPEELU SHODHANA Page 151

113) Pant Shree Lakshmi Narayan Sharma, rasendra Bhaskara translated by Siddinandan

Mishra and Dr. k.k. zala 1st edition 2009.

114) Hazarilal sukula, Rasendra sampradaya ,kadamkuram pataliputra publications. 1st

edition

115) Vaidya yoga ratnavali, published by IMPCOPS, 1968 glossary 1.

116) Achrya Vishwanath Dwivedi, Bharateeya Rasashastra , sharma Ayurveda Mandir

2nd edition pp120-122

117) Sharma SN, Shastri KN. Rasa Tarangini. 11 th ed. New Delhi: MotilalBanarasidas

Publication; 2000. 24th chapter, 170-173 shloka.p.no.675-6

118) Sharma SN, Shastri KN. Rasa Tarangini. 11 th ed. New Delhi: MotilalBanarasidas

Publication; 2000. P. 24th

chapter, 174,175 shlokas.p.no.675-6

119) Sharma SN, Shastri KN. Rasa Tarangini. 11 th ed. New Delhi: MotilalBanarasidas

Publication; 2000. P. 24th chapter, 76,77 shlokas.p.no.670

120) Bhairavananda, Rasarnavam, commentator, Dr. Tripati Indradev, Fourth edition

2001; Chowkamba Samskrita Series Office; pp 442.

121) Vagbhattacharya, Rasaratnasamuchchaya, translated by Dr. Satpute D. Ashok, First

edition 2003; Chowkamba Sanskrit Pratishthan, Delhi;9TH

chapter, 3 and 4th shlokas. Pg-

204

122) Gupta Niranjanaprasada, Parada Samhitam, First edition 1997; Sri Venkateshwara

Press, Mumbai; pp549.

123) G.H.Jeffery,J.Basset,Vogel’s Text book of quantitative chemical analysis, 5th

edition ,1978-1989,1st chapter,pno 3,5,7.

Page 170: “A PHAMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF …

BIBILOGRAPHY

A PHARMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF SHODHANA W.S.R TO

KUPEELU SHODHANA Page 152

124) Hagi G, Hatami A, Safaei A. Hydrophilic-interaction chromatography with UV

detection for analysis of strychnine and brucine in the crude seeds of strychnosnux

vomica and their processed products. Chromatographia 2010;71:327-30.

125) Abhishek kumar, and B. N. Sinha, India Malaysian Journal of Pharmaceutical

Sciences, Ayurvedic Processings Of Nux Vomica: Qualitative And Quantitative

Determination Of Total Alkaloidal Contents And Relative Toxicity. Vol. 7, No. 2, 83–98

126) www.google/introduction-FTIR/126784.469

DISCUSSION

127) WilliamsEvans C. Pharmacognosy. 16 th ed. United Kingdom: Elsevier Limited;

2009. p. 39

128) BISSET, N. G. & PHILLIPSON, J. D. (1976) 3 The Asian species of Strychnos.

Part IV. The alkaloids, Lloydia, 39: 263–323.

129) Sharma SN, Shastri KN. Rasa Tarangini. 11 th ed. New Delhi: MotilalBanarasidas

Publication; 2000. 24th chapter shloka-160, pg-674

130).Genevie`ve Philippe, Luc Angenot, Monique Tits, Michel Fre´de´rich. About the

toxicity of some Strychnos species and their alkaloids. Toxicon 2004; 44 : 405–416

131) Samulesson , G. (1992). Drugs of Natural origin, Swedish Pharmaceutical Press,

Stockholm, P.282..

132) Shoba FG, Thomas M. Study of antidiarrhoeal activity of four medicinal plants in

castor-oil induced diarrhea.JEthnopharmacol 2001;76:73-6. Available from:

http://www.ncbi.nlm.nih.nov/pubmed/11378284

Page 171: “A PHAMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF …

BIBILOGRAPHY

A PHARMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF SHODHANA W.S.R TO

KUPEELU SHODHANA Page 153

133) V.CHITRA et.al .antidiabetic and free radical scavenging activity of the seed

Extract of strychnos nuxvomica .Department of Pharmacology, SRM College of

Pharmacy SRM University, Kattankulathur, Kanchipuram District Tamilnadu,,

134) Yin W, Wang TS, Yin FZ, Cai BC.. J Ethnopharmacol 2003;88:205-14.

135) Tripathi YB, Chaurasia S. Effect of Strychnosnux vomica alcohol extract on lipid

peroxidation in rat liver. Pharm Biol 1996;34:295-9.

136) Deng XK, Yin W, Li WD, Yin FZ, Lu XY, Zhang XC, et al.The anti-tumor effects

of alkaloids from the seeds of Strychnosnux-vomica on HepG2 cells and its possible

mechanism.J Ethnopharmacol2006;106:179-86. Available from:

http://www.ncbi.nlm.nih.gov/pubmed/16442763

137) Chatterjee I, Chakravarty AK, Gomes A. Antisnake venom activity of ethanolic

seed extract of Strychnosnux vomica Linn.Indian J ExpBiol 2004;42:468-75

138) AYURVEDIC PHARMACOPOEIA COMMITTEE. (2000) The ayurvedic

formulary of India, Part 1, pp. 367 (New Delhi: Ministry of Health and Family Planning).

139) Abhishek kumar and b. N. Sinha , ayurvedic processings of nux vomica: qualitative

and quantitative determination of total alkaloidal contents and relative toxicity.

Malaysian Journal of Pharmaceutical Sciences, Vol. 7, No. 2, 83–98(2009)

140) Gopalkrishna et al. Pharmacologyonline 3: 1015-1024 (2009)

141) H. K. (1924). Rafequl Atebba; In Mistahul Khazayin pp 32-38.

142) M.S.Shree Devi et.al .Effect of purification (Suthi) on the acute toxicity of seeds of

Page 172: “A PHAMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF …

BIBILOGRAPHY

A PHARMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF SHODHANA W.S.R TO

KUPEELU SHODHANA Page 154

Nux-vomica . IJPI’S Journal of Pharmacology and Toxicology. Vol 1:3 (2011)

143) Anonymous (1981). National Formularly of Unani Medicine, Ministry of Health &

family Welfare, Govt of India, vol-I pp 319.( Reprinted in2006)

144) Chung, B., Shin, M.K., 1989. Dictionary of Folk Medicine. Young Lim Press,

Seoul, p. 972.

145) Prashant Sarkar, Evaluation of Shodhana Process and Antidotal Study on

Vatsanabha,2008

146) Luo JP, Zhang ZS, Lian YL, Du ZM, Tian C.Determination of strychnine in Jinlong

Qubi Wan by TLC scanning. Chin J Pharm Anal 1999; 19: 179-181.

147) Cai, B.C., Hattori, M., Namba, T., 1990. Processing of nux vomica. II. Changes in

the alkaloid composition of the seeds of Strychno nux-vomica on traditional drug-

processing. Chemical and Pharmaceutical Bulletin 38, 1295–1298.

148), Xu XY, Cai BC, Pan Y, Wang TS. Pharmacokinetics of the alkaloids from the

processed seeds of Strychnos nuxvomica in rats. Acta Pharm Sin 2003; 38:458-461.

149) Sun J, Zhao X Y, Ren Z J. RP-HPLC determination of strychnine and brucine in

Fengshi Antai tablets. Chin J Pharm Anal 2007; 27:757-759.

150) Choi YH, Sohn Y M, Kim CY, Oh K.Y, Kim J. Analysis of strychnine from

detoxified Strychnos nux- vomica seeds using liquid chromatography- electrospray mass

spectrometry. J Ethnopharmacol 2004; 93:109-112.

Page 173: “A PHAMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF …

BIBILOGRAPHY

A PHARMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF SHODHANA W.S.R TO

KUPEELU SHODHANA Page 155

151) Stahl RS, Arjo WM, Wagner KK, Furcolow C, Nolte DL, Johnston JJ. Development

of a high performance liquid chromatography/mass spectrometry method for the

determination of strychnine concentrations in insects used to assess potential risks to

insectivores. J Chromatogr B 2004; 811:257-262.

152) Van Eenoo P, Deventer K, Roels K, Delbeke F T. Quantitative LC-MS

determination of strychnine in urine after ingestion of a Strychnos nux- vomica

preparationandits consequences in doping control. Forensic Sci Int 2006; 164 :159-163.

153) Marques EP, Gil F, Proenca P, Monsanto P, Oliveira MF, Castanheira A, Vieira

DN. Analytical method for the determination of strychnine in tissues by gas

chromatography/mass spectrometry: two case reports. Forensic Sci Int 2000; 110:145

154) Barroso M, Gallardo E, Margalho C,Ávila S, Marques EP, Vieira DN, López-

Rivadulla M. Application of solid phase microextraction to the determination of

Strychnine in blood. J Chromatogr B 2005; 816: 29-34

155) Frédérich M, Choi YH, Verpoorte R. Quantitative analysis of strychnine and

brucine in Strychnos nux- vomica using 1H-NMR. Planta Med 2003; 69 :1169-1171. and

capillary electrophoresis (CE) [58

156) Choi YH, Sohn YM, Kim CY, Oh KY, Kim J. Analysis of strychnine from

detoxified Strychnosnux-vomica [corrected] seeds using liquid chromatography-

electrospray mass spectrometry. J Ethnopharmacol 2003;93:109-12. Available from:

http://www.ncbi.nlm.nih.gov/ pubmed/15182914

157) JIANG, Y. H., YANG, W. L. & GONG, Q. F. (2002) HPLC determination of

strychnine and brucine in semen strychni and its processed products, Zhongguo Zhong

Yao Za Zhi, 27: 899–901.

Page 174: “A PHAMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF …

BIBILOGRAPHY

A PHARMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF SHODHANA W.S.R TO

KUPEELU SHODHANA Page 156

158) GAO, H., SUN, W. & SHA, Z. (1990) Quantitative determination of strychnine and

brucine in semen strychni and its preparations by gas chromatography, Zhongguo Zhong

Yao Za Zhi, 15: 670–671.

159) Kaye S, Hoff Ebbe C. Identification and determination of strychnine by Ultraviolet

Spectrophotometry.JCrimLawCriminolPolice Sci1952;43:246-9. Available from:

http://www.jstor.org/stable/1139284

160) Wang C, Han D, Wang Z, Zang X, Wu Q. Analysis of Strychnos alkaloids in

traditional Chinese medicines with improved sensitivity by sweeping micellar

electrokinetic chromatography. Anal Chim Acta 2006; 572(2):190-6.

161) Yan J, Liu Z, Yan C, Xing J, Liu S. Analysis of strychnos alkaloids using

electrospray ionization Fourier transform ion cyclotron resonance multi-stage tandem

mass spectrometry. Rapid Commun Mass Spectrom 2006; (8):1335-44.

162) .Chen W, Liu L, Li X, Li J, Ji S, Zhang G, Chai Y. Separation and determination of

strychnine and brucine in Strychnos nux-vomica L. and its preparation by capillary zone

electrophoresis. Biomed Chromatogr 2000; 14(8): 541-3.

163) Fu S, Zhang F, Zhang X, Xu Q, Xiao H, Liang X. Physicochemical characterization

of the Strychnos alkaloids by capillary zone electrophoresis. Anal Sci 2005; (11): 1303-8.

164) Li Y, He X, Qi S, Gao W, Chen X, Hu Z. Separation and determination of

strychnine and brucine in Strychnos nux-vomica L. and its preparation by nonaqueous

capillary electrophoresis. J Pharm Biomed Anal 2006 3;41(2):400-7.

Page 175: “A PHAMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF …

BIBILOGRAPHY

A PHARMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF SHODHANA W.S.R TO

KUPEELU SHODHANA Page 157

165) Gu XX, Li HX, Zhu R H, Zou H. Determination of strychnine and brucine in

Strychnos nux- vomica L. by nonaqueous capillary electrophoresis. Chromatographia

2006; 63:289-292.

166) BHANU, M. N. & VASUDEVAN, T. N. (1989) Studies on sodhna of nux-vomica,

Indian Drugs, 26: 150–152.

167)Akbar S, Khan SA, Masood A, Iqbal M. Use of strychnosnux vomica (Azraqi) seeds

in unani system of medicine: Role of detoxification. African Journal of Traditional

Complementary and Alternative Medicine 2010; volume7 page 286-90.

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158

LIST OF PHOTOS

KUPEELU TREE TREE WITH FRUITS

KUPEELU PHALA KUPEELU BEEJA

GOKSHEERA GOGHRUTA

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159

PHOTOS OF SWEDANA

ASHUDDHA KUPEELU BEEJA POTTALI

DOLA YANTRA BEEJA AFTER SWEDANA

AFTER REMOVAL OF SEED COAT SEPARATED COTYLEDON

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160

PHOTOS OF BHARJANA

ASHUDDHA KUPEELU BEEJA PROCESS OF BHARJANA

BEEJA AFTER BHARJANA BEEJA WITH SEED COAT

REMOVAL OF SEED COAT END PRODUCT

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161

PHOTOS OF MICROSCOPIC STUDY

BEFORE SHODHANA

TRICHOMES ALEURONE GRAINS WITH

FAT GLOBULES

AFTER SHODHANA(SWEDANA)

SCANTY TRICHOMES ALEURONE GRAINS WITH

FAT GLOBULES

AFTER SHODHANA(BHARJANA)

SCANTY TRICHOMES ALEURONE GRAINS WITH

FAT GLOBULES

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162

PHOTOS OF ANALYTICAL STUDY

TOTAL ASH ANALYSIS ACID INSOLUBLE ASH

ANALYSIS

PREPARATION OF TLC CHROMATOGRAM OF ALL 3

SAMPLES

FOURIER TRANSFORM INFRA-RED

SPECTROPHOTOMETER

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Page 183: “A PHAMACEUTICO-ANALYTICAL STUDY ON CONCEPT OF …

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