Research Institutefor Physical Chemical Problems of the

Belarusian State University

New Activated Carbon Drugs

Contact Person:

Dr. D. Grinshpan Head of the laboratory of Cellulose Solutions and Products of their Treatment

Research Institute for Physical Chemical Problems of the Belarusian State University

14, Leningradskaya, Minsk, RB, 220030Belarusian State UniversityResearch Institute for Physical Chemical Problems

TelTel../fax(+375-17) 226-47-00/fax(+375-17) 226-47-00E-mail: E-mail: grinshpan@bsu.by

grinshpan@mail.rugrinshpan@mail.ru

New Activated Carbon Drugs

«Soluble» activated carbon – new quickly

disintegrating medicinal form of activated carbon

Combined drugs containing both aspirin, antacid, antibiotics etc.

and carbon

Medicinal forms: • tablets, granules, capsules• hydrophilic ointments, gels, liniments

New quickly disintegrating tablets

New water-soluble cellulose derivative of polyelectrolyte nature is a binder of activated carbon drugs

The advantages of medicinal preparations containing new polymeric binding agent:

Prompt resolving capacity of granules and tablets

High (colloid) degree of dispersiveness Coagulating aggressiveness towards colloid-

state toxins Simultaneous combination of performance

and prolongation Absence of ballast fillers

Carbon Tablets

«Ultrasorb»

RI PCP BSU, Minsk

The advantages of carbon tablets «Ultrasorb»

spontaneously disperse in the aqueous media in 15-60 seconds (that is 10-100 times quicker than by the well-known tablets) forming homogeneous stable suspension. Up to 10% of its particles have a colloidal degree of dispersiveness

Adsorption capacity of tablets determined by conventional calibrants: methylene blue, antipyrin and iodine turned out to be higher compared with the well-known analogues, whereas vitamin B12 sorption was lower

Such tablets’ properties permit to lower the therapeutic dose and reduce the treatment period of different allergies, food poisoning, radioactive infectiousness etc.

Dispersion is in progress

«Ultrasob» RI PCP BSU, Minsk

«Carbon tablets» ICN, Russia

Particle size distribution of activated carbon tablets suspensions in stomach

medium

New activated carbon drug Ordinary activated carbon drug

in 0.1 M HCl in 0.1 M HCl

Adsorption capacity of various activated carbon tablets

PreparationAdsorption of methylene blue,

mg/gAdsorption of B12 vitamin,

mg/g

Carbon tablets(Natur Product, France) 15±5 10±3

Carbon tablets “Carbo medicinalis 0,3 g”(Poland) 140±10 30±3

Carbon tablets “Norit”(Netherlands)

170±10 34±3

Carbon tablets(JSC “Medisorb”, Perm, Russia) 190±10 35±3

Carbon tablets(Borschagovskii CPP, Ukraine) 195±10 35±3

Carbon tablets(PO “Kurskii KLS”, Russia) 230±10 35±3

Carbon tablets “Kohle-Сompretten”(Merck, Germany) 320±10 30±3

Carbon tablets “Ultrasorb” 540±10 11±3

Radio nuclides accumulation changes when using radioprotectors

0

20

40

60

80

100

120

140

160

180

Jablopeck Belsorb Ultrasorb Control

03.сен

01.окт

Averageaccumulation,Bc/kg

Name of a radio protector

The radio protectors favor to excretion of radio nuclides from the organism in the value of 31 % per 24 days when using 2 tablets a day at local ration. The merit of Ultrasorb is that is more administration friendly.

Recommendations on useof carbon enterosorbents

Tablets «Carbo medicinalis 0.3 g» - Poland

Tablet weight - 0,6 g; activated carbon weight – 0,3 g.auxiliaries: saccharose, polyvinylpyrolidon, magnesium stearate. 2-5 tablets 3-4 times a day or in case of diarrhea 10-20 pills 3-4 times a day. Grind or crack before use.

12 – 48 g/daily

Tablets«Ultracarbon» – Germany

Tablet weight – 0,4 g; activated carbon weight – 0,25 g. auxiliary - bentonite2-4 milled tablets in liquid 3-4 times a day. In case of food poisoning the dose can be

increased up to 50 tablets, stirred up in liquid.

6,4 – 20 g/daily

Powder «BELSORB – P» - Belarus

Daily dose 2,0 g of carbon per 20 kg of patient’s weight is distributed into threeintakes prescribed in the form of aqueous suspension 50-100 ml.

6 – 18 g/daily

Tablets «Ultrasorb» – RI PCP BSU

Tablet weight– 0,17 g; activated carbon weight – 0,16 g.No ballast fillers.1 tablet per 20 kg of patient’s weight. Tablets can be previously “solved” in waterand taken in the form of colloid suspension .

1,5 – 3 g/daily

New combined activated carbon drugs

New quickly disintegrating tablets (granules)

"Carbon–Potassium Permanganate"

"Carbon–Levomycetin" "Carbon–Valerian" "Carbon–Aspirin–Vitamin C" "Carbon–Aspirin–Vitamin C–

Valerian" "Carbon–Nicotinic Acid" "Carbon–Sodium Nucleinat" "Carbon–Calcium Carbonate" "Carbon–Calcium Carbonate– Magnesium Carbonate" "Carbon–Pectin–Vitamin C–

Sweet" "Calcium Carbonate"

New hydrophilic ointments, gels and liniments

hydrocortisone ointment 1 %lincomycine ointment 2 %prednisolone ointment 0,5 %prednisolone gel 0,5 %dexamethasone gel 0,1 %tetracycline gel 3 %liniment "Mumije" 10 %

Aspirin a day: advice that makes sense

«Black» aspirin

(а) – «white» aspirin (б) – «black» aspirin

Kinetics of acetylsalicylic acid isolation from ordinary aspirin «Bayer» (a) and «Black» aspirin (b)

а b((in vitroin vitro))

Content of aspirin in blood

(in vivo)

0 500 1000 15000

5

10

15

20

White aspirin

Black aspirin

Asp

irin

co

nce

ntr

atio

n, m

g/l

time, min

American Heart Association recommends the

administration of aspirin from 75 till 325 mg daily

The main problem of using aspirin - it is its dissolution in gastrointestinal tract (GIT)

Ways of problem solving:Buffered effervescent "BAYER" aspirin tablets

The basis for these quickly dissolving tablets is the increase of pH medium by buffer, ionization of ACA and owning to this process the speedup of its dissolution in GIT. However the sodium form of ACA diffuses through lipidic walls of GIT not nearly so rapid as the acid one.

Quickly dissolving "Black aspirin" tabletsThe basis for this drug form is a principle of a radically different kind. The presence of a new polymer binder and carbon in these tablets leads to the quick formation of colloid system in the liquid phase. The high degree of ACA particles dispersiveness provides for a high dissolution rate. The function of the polymer binder and carbon is to disperse and disaggregate ACA particles, not to change the degree of its ionization.

Advantages drug form of Black aspirin

acts faster than other drug forms (takes effect in 20-30 minutes); does not cause ionization of ACA and therefore provides for its

quicker passing through lipidic membranes; does not produce gassing that irritates mucosa and creates

discomfort in GIT; does not change pH medium, reduces irritation of stomach

mucosa and duodenum, does not lower the activity of digestive ferments;

does not contain ballast fillers: sodium bicarbonate, citric acid which constitute more than 80% of the "BAYER" tablet's mass;

have the same anti-fever effect as the insoluble aspirin, but the dosage is greatly smaller;

is characterized by a long-lasting effect (up to 180-240 minutes), due to the fact that 10-15% of ACA (carbon adsorbed ) are released only in alkaline medium of intestines.

Additional positive effect

While using "Black Aspirin" side-effects are not likely to appear due to the fact that its dissolution does not induce the irritation of stomach mucosa, caused by the pH medium change and there is no gassing. It can be administrated by patients with stomach or duodenum ulcer, patients, whom high content of sodium salts is contra-indicted (patients with high blood-pressure). In case the tablet is taken by the bed-patients, it will not linger on gullet and cause its ulceration, owning to its ability to disintegrate quickly. The tablets containing valerian, that reduces GIT spasms, will be particularly beneficial for these kinds of patients.

it can be taken as febrifuge, analgesic, resolvent and cardio remedy (to prevent cardiovascular diseases);

at the expense of carbon it helps to deduce toxins from GIT, which are always present in the patient's organism;

as the dosage of aspirin in the tablet is significantly small it can be administrated by children under 4.

Tablets of buffered effervescent “Bayer” aspirin and “Black aspirin”

Black Antacid

Calcium and magnesium carbonates are the main representatives of the antacid agents employed to decrease high acidity of gastric juice ( under gastritis, stomach and duodenum ulcer). Thanks to the new cohesive used in the tablets , insoluble calcium and magnesium carbonates transfer into fine-dyspersated suspension. They quickly neutralize hydrochloric acid of the stomach contents.

By comparison with well-known drugs ("Vicair", "Vicalin", "RENNIE") the application of calcium and magnesium carbonates in the combination with carbon allows to sorb carbonic acid, evolved during the neutralization of the stomach acid. This does not evoke a stimulating effect on the receptors of the stomach mucosa. This also does not intensify the secretion of the gastrin and does not cause the intensification of the secretion for the second time. Do not contain aluminates.

Kinetics Black antiacid (1) and Renni (2) interaction with 0,1 M HCI

0 10 20 300

1

2

3

4

5

6

7

8

2

1

pH

Time, min.

Degree of readiness for production

Belarusian pharmaceutical articles for the polymer binder, activated carbon and their combination are available;

there is a laboratory-scale plant for tablets' formation with capacity of 500 tablets per day;

there is an experimental-industrial order to produce polymer binder and carbon tablets, containing activated carbon and polymer binder;

in order to accelerate the process of application it is possible to draw up a joint-patent for new drug forms.

Possible ways of cooperation:

Scientific cooperation Arrangement of the joint production of a) polymeric binder b) active carbon drugs Application of the joint patent License purchase a) exclusive b) non-exclusive