PROBLEMS & PROSPECT OF DISCOVERING NEW DRUGS FROM HIGHER PLANTS.

Advanced Pharmacognosy,Cource#804

Presented by,

Syed Asif Raza

OverviewOverview

• Introduction.• Important Drugs From Higher Plants.• Drug Development From Plants.• Challenges in Drug Discovery From Medicinal Plants.• Problem in discovering new drugs From higher plants.• WHO Guidelines For Herbal Medicines.• Pakistan & Herbal Medicines. • Prospect & Conclusion

جائزہ عمومی

INTRODUCTIONINTRODUCTION

• Drug discovery from plants involves a multidisciplinary approach combining botanical, ethnobotanical, phytochemical & biological techniques . plants continue to provide us new chemical entities for the development of drugs against various pharmacological targets, including HIV/AIDS,malaria,Alzheimer disease,cancer & pain.

• Many higher plants produce economically important compounds such as, resins, tannins, gums, flavors, fragrance, oils, natural rubber etc.

• Apart from the core disciplines related to pharmaceutical research classical sciences like taxonomy and the newer discipline ethnobotany have now become an integral part of drug discovery from plants.

IMPORTANT DRUGS FROM HIGHER PLANTS.

1. Morphine2. Quinine.3. Cocaine.4. Reserpine.5. Atropine.6. Vincristine.7. Digitoxine.8. Digoxine.9. Sennosides.10.Diosgenine.11.Stigmasterol.

1. Papaver somniferum.2. Cinchona species.3. Erythoxylon coca.4. Rauwolfia serpentina.5. Atropa belladonna.6. Catharantus roseus.7. Digitalis purpurea.8. Digitalis lanata.9. Cassia angustifolia.10.Dioscorea species.11.Glycine soja.

DRUG DEVLOPMENT FROM PLANTS.

• Selection of Approaches;

Folklore Use High Ratio of Activity.

Lower screening Cost.

Role of Psychology in folk medicine. Secrecy of primitive cultures.

Botanical Relationship

Discovery of useful Analogs.

Re-isolation of known compounds.

Random Collection

Best chance to find novel active compounds.

Plants are more readily available.

Low % of active Leads.

High cost per lead.

Large bioassay capacity needed.

Advantages Disadvantages

DRUG DEVLOPMENT FROM PLANTS . [cont]

• Steps Required;1. Decision on selection method.

2. Preparation of extracts for bioassay.

3. Recollection of active plants for activity conformation.

4. Isolation & structural elucidation.

5. Pharmacological profile.

6. Toxicity studies.

7. Large scale preparation of active compounds.

8. Formulation studies.

9. New drug application & clinical trials.

10. Market the new drug.

DRUG DEVLOPMENT FROM PLANTS . [cont]

• Ethno-medical / Scientific & technical Data bases;

CA SEARCH®

IMEPLAM

NAPRALERT AGRICOLA

1974

1975

1969

1978

1974

1970

1969

1973

*Note; yr indicating

literature coverage

from.

CHALLENGES IN DRUG DISCOVERY PROCESS FROM PLANTS.

Clinical trial

Drug candidates

Pharmacology, toxicology, pharmacokinetics, ADME, Drug delivery

Medicinal chemistry, combinatorial chemistry

Target based qualitative bioassays

Plant sample acquisition

Lead optimization

Lead identification

Lead development

PROBLEMS IN DISCOVERING NEW DRUGS FROM PLANTS.

1. Herbal drugs are usually mixtures of many constituents.2. The active principle are in most cases unknown.3. Selective analytical methods or reference compounds may

not be available commercially.4. Plant materials are chemically and naturally variable.5. The source and quality of the raw material are variable.6. The methods of harvesting, drying, storage,

transportation, and processing (for example, mode of extraction and polarity of the extracting solvent, instability of constituents, etc.) have an effect.

7. Many of the plant species are rare &difficult to cultivate.8. Plants contain only small amounts of the required

compounds.9. The harvest can be destroyed by insects and plant

diseases.10.The plant are growing in countries with political unrest.

WHO Guidelines For Herbal Medicines.

According to a World Health Organization (WHO) survey, the traditional healers prescribe herbal drugs to treat 65% patients in Sri Lanka , 85% in Burma , 80% in India , 60% in Indonesia , 75% in Nepal , 90% in Bangladesh and 60% in Pakistan . According to WHO Guidelines;

1. The manufacturing procedure and the formula including the amount of excipients should be described in details.

2. A method of identification & where possible quantification of the plant material in the finished product should be defined.

3. According to WHO herbal medicines should be regarded as finished labeled medicinal products that contain as active ingredients or combinations thereof whether in crude state or as plant preparations. plant material combined with chemically defined active substances which are not of plant/natural origin not considered as herbal medicines.

PAKISTAN&HERBAL MEDICINES

There is no registration system. Herbal medicines are not included on an essential drug list. A post marketing surveillance system is being developed. In Pakistan, herbal medicines are sold in pharmacies as over the counter drugs, by licensed practitioners, and in special outlets without any restrictions.

The Drugs Act of 1962 controls the regulation of herbal medicines as regards advertising and prevention of misuse. Herbal medicines are regulated as over the counter medicines and dietary supplements. No claims may legally be made about herbal medicines. The national pharmacopoeia is the Tibbi pharmacopoeia (1967); the information is not legally binding. The Monographs of unani medicines (Vol. 1) has been prepared and published.

In the Islamic Republic of Pakistan, a national policy on Traditional medicines is being developed. Laws and regulations were developed in 1965 and amended in 1970 and 2002.

PROSPECT & CONCLUSION

• It is clear that the herbal industry can make great strides in the world with the co-operation between drug regulatory authorities, scientists and industries. However, standardisation of methods and quality control data on safety and efficacy are required for proper understanding of the use of herbal medicines.

Plant based discovery programme continues to provide new drug leads.the drug from biological origin are the back bone of medicinal therapy, abouth 50% of drugs arrived from natural origin, such as vitamins, hormones, glycosides, antibiotics, alkaloids and many more.

© 2009 Department of Pharmacognosy, Uok, Pakistan.

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