RU2302255C2 - Anti-ulcerous plant composition, method for its obtaining and application - Google Patents

Abstract

FIELD: pharmaceutics.

SUBSTANCE: the suggested anti-ulcerous plant composition contains ingredients at the quantity of a) 2-5 weight% the extract of Utlaria solicifolia, b) 1-3 weight% - the extract of Asparagus racemosus, c) 2-4 weight% - the extract of Foeniculum vulgare, d) 3-5 weight% - the extract Ficus glomerata, e) 83-92 weight% - pharmaceutically applied additives. It is necessary to a) obtain necessary parts of medicinal plants, b) dry in shadow plant material of stage (a), c) reduce dried plant material of stage (b) to obtain finely reduced powder, d) extract the reduced plant material of stage (c) with aqueous-alcoholic solution at about 25-35°C for 4-7 d to obtain aqueous-alcoholic extract, e) concentrate the extracts of stage (d) at decreased pressure at about 40-60°C to obtain concentrated extract, f) lyophilize concentrated extract of stage (e) to remove residues of the solvent and obtain plant extract and g) supplement plant extract of stage (f) with pharmacologically applied additives to obtain the composition suggested. This composition should be applied at the dosage ranged 100-200 mg/kg body weight in case of ulcers induced with cold stress or at ulcers induced due to applying a ligature onto gastric pylorus. The innovation enables to widen the quantity of anti-ulcerous preparations.

EFFECT: higher efficiency.

24 cl, 4 ex, 1 tbl

Description

Technical field

The present invention relates to the development of antiulcer plant composition (s) and a method for producing extracts that are used in the preparation of a plant composition used in the treatment of ulcers.

State of the art

A stomach and duodenal ulcer is a huge health problem, while both morbidity and mortality are taken into account. Scientific studies of the last ten years have led to a deep penetration of the essence of therapy and the prevention of ulceration of the stomach and duodenum, aimed more at strengthening the mucosal defense system than at weakening the aggressive acid-pepsin factors responsible for the induction of ulcers. Increased gastric acidity and digestive activity are usually a manifestation of a physiological disorder that affects one or more of the mechanisms that normally regulate gastric secretion. Neurotransmitters or hormones that directly stimulate the secretion of hydrochloric acid and pepsin by the gastric glands include acetylcholine, gastrin, and histamine. In addition, there are other factors that play an important role in the manifestation of stomach ulcers and duodenal ulcers. It has been shown that the activity of secreting gastric cells is stimulated by caffeine, alcohol, hydrochloric acid, sodium chloride, non-steroidal anti-inflammatory drugs (NSAIDS) and stress [3, 4, 5].

Modern daily life is stressful aging, and the chances of getting stressed are constantly increasing due to rapid changes in the environment and the complexity of personal relationships. In addition, there is an increased chance of being influenced by virtual factors that do not exist in nature.

As a result, the number of people suffering from these factors, gastric ulcer, duodenal ulcer, etc., has increased, and various anti-ulcer drugs have been developed and are currently used. Antiulcer drugs that have been used to date, can be classified into large groups: agents that suppress the release of digestive enzymes and their activity; agents that suppress the secretion of gastric juice; agents that stimulate the repair and protection of tissues of the mucous membrane, etc. These drugs are prescribed for oral or subcutaneous administration. However, these drugs either have a one-sided effect, or are synthesized drugs, each of these drugs has its own side effects, so the limitations associated with their intake and the quantities used have become especially noticeable, while at the same time, an effective and safe anti-ulcer drug is still not was developed and not applied [1].

Thus, for safety reasons, these traditional antiulcer drugs cannot be used regularly for the prevention and prevention of relapse.

On the other hand, drugs used to treat intestinal disorders and drugs that inhibit only the secretion of gastric juice are used to prevent ulcers. As a result, they cannot be attributed to the aforementioned preventive antiulcer drugs in the true meaning of this word. Currently, the side effects of drugs are becoming a problem for humans, and therefore it was necessary to create drugs with antiulcer activity, which are natural products, do not have side effects and are safe enough even when used regularly as a preventative measure or to prevent relapse of the disease [1 , 2].

Until now, based on the oral traditions of Malasar and Kadar, the Kerala tribes use the plant Utlaria solciifolia to treat intestinal diseases like colic or stomach bleeding. Conventional synthetic drugs either inhibit acid secretion or heal an ulcer. Long-term use of modern synthetic drugs completely inhibits the secretion of acid and pepsin, which are normally responsible for the digestion of food and the functioning of the stomach, and causes the development of cancer. Aggressive acid, pepsin and the protective mucous membrane of the stomach play a critical role in its functioning. The bacteria Helicobacter pylori, aggressive acid, pepsin, the use of hot food break the contacts between the cells, which leads to ulceration and cancer of the stomach. Complete cure still does not exist. Therefore, a new herbal composition is necessary for the treatment of acute forms of stomach ulcers and duodenal ulcers and the fight against H. pylori. In accordance with this, studies have been undertaken aimed at creating an oral form of a herbal composition, including medicinal plants and supplements for oral administration [6, 7], which can be used in the treatment of acute forms of stomach ulcers and duodenal ulcers, as well as for the treatment of internal bleeding.

SUMMARY OF THE INVENTION

The main objective of the present invention is the creation of a new antiulcer plant composition, which may be useful in the treatment of acute and chronic forms of gastric ulcers and duodenal ulcers.

Another objective of the present invention is to obtain a plant composition (s), which causes an immediate decrease in the acidity of the stomach by neutralizing excess acid.

In addition, the purpose of the present invention is to obtain a plant composition (s) from a mixture of plants that are used in the treatment of diarrhea, intestinal discomfort and which have antimicrobial properties.

Accordingly, the present invention provides a herbal composition useful in the treatment of acute and chronic forms of gastric and duodenal ulcers. As an active ingredient, the herbal composition includes the plant Utlaria solicifolia, which was used by the tribes of Malasar and Kadar, Kerala, for the purposes mentioned in the "Prior art" section. Along with this plant and suitable additives, other traditional plants, such as Asparagus racemosus, Foeniculum vulgare and Ficus glomerata, which are used in the treatment of intestinal discomfort and as a milk product, are also included in the composition.

DETAILED DESCRIPTION OF THE INVENTION

Thus, the present invention provides a new antiulcer synergistic herbal composition, which can be used in the treatment of acute and chronic forms of gastric ulcer and duodenal ulcer; the above composition includes:

a) 50% aqueous-alcoholic extracts of plants, including Utlaria solicifolia 2-5 mass%, Asparagus racemosus 1-3 mass%, Foeniculum vulgare 2-4 mass% and Ficus glomerata 3-5 mass%, in an oral dosage form in in the form of tablets, capsules, powders and liquids.

The novelty of the present invention is as follows: (1) it is a herbal composition for treating stomach and duodenal ulcers, (2) the herbal composition neutralizes excess acid in the stomach, (3) the herbal composition is suitable for healing and healing ulcers, (4) in contrast from the marketed anti-ulcer drugs, this herbal composition also prevents the appearance of internal bleeding.

In the present invention, extracts from Utlaria solicifolia, Asparagus racemosus, Foeniculum vulgare and Ficus glomerata are used as plant extracts.

One aspect of the present invention relates to the creation of a composition, which can be made in the form of tablets, capsules or powder, ready for use in suspension.

Another aspect of the present invention is that the binder used can be either starch, or Arabian gum, or carboxymethyl cellulose.

Another aspect of the present invention is that the diluent used to obtain the dosage form may be lactose.

Another aspect of the present invention is that the plant extracts used are 50% aqueous-alcoholic extracts.

In addition, another aspect of the invention relates to the fact that the alcohol used is ethanol.

Another aspect of the present invention relates to the fact that the composition (s) treats stomach discomfort, stomach cancer, stomach pain, intestinal discomfort, stomach ulcers and duodenal ulcers.

In addition, another aspect of the present invention relates to the fact that plant extracts are mixed in a ratio of Utlaria solicifolia 2-5% by weight, Asparagus racemosus 1-3% by weight, Foeniculum vulgar e 2-4% by weight and Ficus glomerata 3-5% by weight, together with suitable additives used to create oral solid dosage forms.

Another aspect of the present invention relates to the fact that the composition (s) comprises about 8-17 weight% of the total weight of the composition.

Another aspect of the present invention relates to the fact that Utlaria solicifolia extract is an extract from rhizomes.

Another aspect of the present invention relates to the fact that plant extracts are obtained from specially selected parts of the plant: leaves, rhizomes and aerial parts.

In addition, another aspect of the present invention relates to the use of starch and lactose as lubricants.

Another aspect of the present invention relates to the fact that the composition is used in the treatment of diarrhea, intestinal discomfort and as an antimicrobial agent.

Another aspect of the present invention relates to the fact that the composition immediately reduces the acidity of the stomach, neutralizing the excess amount of acid.

Another aspect of the present invention relates to the fact that the composition in a dosage of from 100 to 200 mg / kg of weight for ulcers caused by cold stress, reduces the ulcer index to values from 11.2 ± 3.1 to 4.2 ± 1.0.

Another aspect of the present invention relates to the fact that the composition in a dosage of from 100 to 200 mg / kg of body weight for ulcers caused by cold stress, provides a cure rate of from 83.59 to 56.25.

Another aspect of the present invention relates to the fact that the composition in a dosage of from 100 to 200 mg / kg of weight for ulcers caused by ligature on the pylorus reduces the ulcer index to values from 6.1 ± 0.8 to 4.8 ± 1, 2.

Another aspect of the present invention relates to the fact that the composition in a dosage of from 100 to 200 mg / kg of body weight for ulcers caused by ligature on the pylorus gives a cure rate of 57.93 to 66.90.

Another aspect of the present invention relates to the fact that when applying the composition in a dosage of from 100 to 200 mg / kg weight, the level of lipid peroxidation in the rat gastric mucosa is from 0.1 ± 0.01 to 0.21 ± 0.01.

Another aspect of the present invention relates to the fact that the composition in a dosage of from 100 to 200 mg / kg of weight in case of ethanol-induced gastric ulcers has a protective effect of 64.94 to 86.75% and significantly increases the gastric mucosa in rats.

Another aspect of the present invention relates to the fact that the composition in a dosage of from 100 to 200 mg / kg of body weight for ulcers caused by aspirin in rats reduces the ulcer index to values from 7.1 ± 2.2 to 6.2 ± 1.3 and gives a cure rate of 61.41 to 66.30.

Another aspect of the present invention relates to the fact that when using the composition in a dosage of from 100 to 200 mg / kg of weight in chronic stomach ulcers induced in rats with acetic acid (ulcer healing),% of perforation cases is from 2.1 to 0.0% by compared with 31.2% for control.

As a result of an intensive study conducted by the inventors for the aforementioned purposes, new compositions for oral administration using medicinal herbs of natural origin were created, and compositions were incorporated into binders and diluents to create oral dosage forms.

Thus, the present invention relates to oral dosage forms of a composition (s). Each composition is described in detail with an indication of the composition of the ingredients, as well as the method for its preparation.

Information confirming the possibility of carrying out the invention

The examples described below are for illustrative purposes only and should not be construed as limitations of the invention.

The first step in the preparation of these compositions includes a method for producing a plant material suitable for converting the composition into tablets or capsules. Collect the specified number of plants, dry them in the shade at room temperature (25-35 ° C) for 72 hours or until the material dries. The material is then ground to a fine powder. The indicated amounts of ground material are then completely extracted with a 50% aqueous-alcoholic solution at room temperature (25-35 ° C.). The extraction is carried out in a closed container, where the indicated amounts of plant material are placed in the specified solvent (in a ratio of 1: 8-1: 15) for 4-7 days. At the end of this step, the solvent is decanted and, if necessary, filtered to get rid of the plant waste. The solvent is then concentrated by evaporation under vacuum at a temperature below 40-60 ° C. The concentrate is then lyophilized to obtain the final product in powder form. The final product is then converted into a dosage form, using it as an ingredient in the preparation of tablets and capsules. Suitable binders, such as starch, and diluents, such as lactose, are added to formulate the composition.

Example 1

Utlaria solicifolia 3 mass% Asparagus racemosus 2 mass% Foeniculum vulgare 3 mass% Ficus glomerata 3 mass% Starch paste 15 mass% Talc 1 mass% Lactose q.s. up to 100%

Utlaria solicifolia, Asparagus racemosus, Foeniculum vulgare and Ficus glomerata were collected and dried in the shade. The dried material (1 kg) was then crushed and extracted with a 50% aqueous solution of alcohol (3 L) for 5 days. Then the solvent was decanted and, if necessary, filtered to remove plant waste. The extract was then concentrated in vacuo at a temperature below 50 ° C. After that, the extract was lyophilized to obtain a powder form.

15 g of starch are mixed with water and heated to obtain a paste. Then, weighed amounts of plant extracts are mixed with starch paste and lactose is added to bring the composition to 100 g. Then the ingredients are thoroughly mixed with starch paste to obtain a thick mixture. The mixture is then granulated in a granulator, dried at 104 ° F, and sieved through a 16 mesh sieve. To dry the granules, talc is added and then uniform tablets are punched with a special machine.

The composition is applicable in the treatment of acute and chronic forms of stomach ulcers and duodenal ulcers and with internal bleeding.

Example 2

Utlaria solicifolia 2 mass% Asparagus racemosus 1 mass% Foeniculum vulgare 4 mass% Ficus glomerata 4 mass% Lactose q.s. up to 100%

Utlaria solicifolia, Asparagus racemosus, Foeniculum vulgare and Ficus glomerata were collected and dried in the shade. The dried material (1 kg) was then crushed and extracted with a 50% aqueous solution of alcohol (3 L) for 5 days. Then the solvent was decanted and, if necessary, filtered to remove plant waste. The extract was then concentrated in vacuo at a temperature below 50 ° C. After that, the extract was lyophilized to obtain a powder form. The weighed amounts of the plant extracts indicated above are mixed with lactose diluent, then the gelatin capsules are filled with this mixture and the dosage is made.

The composition is applicable in the treatment of acute and chronic forms of stomach ulcers and duodenal ulcers and with internal bleeding.

Anti-ulcer activity screening procedure:

1. Ethanol-induced ulcers. The appearance of stomach ulcers in rats was induced by ethanol (1 ml per 200 g of weight, 1 hour), the animals were sacrificed by displacement of the cervical vertebra, the stomach was incised along a large bend and examined for ulcers.

2. Ulcers induced by aspirin. Animals were given aspirin at a dosage of 200 mg per kg of body weight and after 4 hours the number of ulcers was counted. The stomach was removed and opened along a large bend, the number of ulcers in the glandular part of the stomach was counted with the help of personnel not familiar with the experimental protocol.

3. Ulcers induced by cold stress. Rats were tied with a strap to a wooden plank and kept at 4-6 ° C for 2 hours. Then the animals were killed by displacement of the cervical vertebra, the stomach was incised along a large bend, and the number of ulcers was counted on the dissected stomach.

4. Ulcers induced by ligature on the pylorus. Animals were anesthetized using pentobarbital (35 mg per kg of body weight, intraperitoneally), the abdominal cavity was opened, a ligature was placed on the pylorus without damaging the blood supply to the stomach. The stomach was returned to its place and the abdominal wall was sutured in 2 layers with a stitch seam. In the postoperative period, the animals were not given water. After 4 hours, the stomach was dissected, the contents were collected and the ulcer index was calculated.

5. Ulcers induced by acetic acid. Rats were anesthetized using pentobarbital (35 mg per kg of body weight). The abdominal cavity was opened and the stomach examined. A cylindrical glass tube 6 mm in diameter was tightly pressed against the anterior serous surface of the glandular stomach at a distance of 1 cm from the end of the pyloric stomach. 50% acetic acid (0.06 ml per animal) was poured into the tube and left on the wall of the stomach for 60 sec. After removal of the acid solution, the abdominal cavity was sutured in 2 layers, the animals were put in a cage and fed, as usual. Then after taking the last dose on either the 6th or 11th day of the experiment, the animals were killed to determine the degree of cure for the ulcer. The ulcer index was calculated as the product of the length and width of the ulcers (mm ² per rat).

6. Duodenal ulcers induced by cysteamine. To cause the appearance of a duodenal ulcer, cysteamine 400 mg / kg was administered in 2 divided doses over 4 time periods. After exposure to the drug, animals were killed and examined for the presence or absence of an ulcer.

Table 1. The effect of antiulcer plant composition (HC ₁ ) and a composition not containing Utlaria solicifolia (HC ₂ ) on gastric ulcers induced by cold stress (CRS) and ligation of the pyloric stomach (PL). CRS-induced ulcers PL-induced ulcers Impact Dose Ulcerative index % cure Ulcerative index % cure The control - 25.6 ± 4.2 - 14.5 ± 2.5 - HC ₁ one hundred 11.2 ± 3.1 ^a 56.25 6.1 ± 0.8 ^b 57.93 HC ₁ 200 4.2 ± 1.0 ⁱⁿ 83.59 4.8 ± 1.2 ^b 66.90 HC ₂ one hundred 17.2 ± 3.1 32.81 10.5 ± 2.8 27.59 HC ₂ 200 13.3 ± 4.5 48.05 7.8 ± 1.6 ^a 46.21 Ranitidine fifty 5.2 ± 1.1 ⁱⁿ 79.68 5.1 ± 1.3 ^b 64.82

The ± SEM mean values for six rats are presented.

P: ^a <0.05, ^b <0.01 and ^c <0.001 compared with the corresponding control group.

NOTE:

- None of the studied groups had lethal cases.

- In animals treated with the herbal composition HC ₁ , there were no significant deviations in behavior.

The composition of HC ₁ showed the dependence of the effect on the applied dose and a significant (from P: ^a <0.05 to P: ^a <0.001) protective effect in the range of 56.25-83.59%. Ranitidine blocking the H ₂ receptor showed a protective effect,% of protection was 64.82 and 79.68% in cases of ulcers induced by CRS and ligature on the pylorus.

Example 3

Utlaria solicifolia 4 mass% Asparagus racemosus 2 mass% Foeniculum vulgare 3 mass% Ficus glomerata 3 mass% Bicarbonate of soda 0.5 mass% Lemon acid 0.5 mass% Lactose q.s. up to 100%

Utlaria solicifolia, Asparagus racemosus, Foeniculum vulgare and Ficus glomerata were collected and dried in the shade. The dried material (1 kg) was then crushed and extracted with a 50% aqueous solution of alcohol (3 L) for 5 days. Then the solvent was decanted and, if necessary, filtered to remove plant waste. The extract was then concentrated in vacuo at a temperature below 50 ° C. After that, the extract was lyophilized to obtain a powder form. Plant extracts were mixed with sodium bicarbonate and citric acid. Then the mixture was subjected to dry granulation, sieved and pressed to obtain effervescent tablets.

The composition is applicable in the treatment of acute and chronic forms of stomach ulcers and duodenal ulcers and with internal bleeding.

Example 4

Asparagus racemosus 1 mass% Foeniculum vulgare 4 mass% Ficus glomerata 4 mass% Starch paste 15 mass% Talc 1.5 mass% Lactose q.s. up to 100%

Asparagus racemosus, Foeniculum vulgare and Ficus glomerata were collected and dried in the shade. The dried material (1 kg) was then crushed and extracted with a 50% aqueous solution of alcohol (3 L) for 5 days. Then the solvent was decanted and, if necessary, filtered to remove plant waste. The extract was then concentrated in vacuo at a temperature below 50 ° C. After that, the extract was lyophilized to obtain a powder form.

15 g of starch are mixed with water and heated to obtain a paste. Then, weighed amounts of plant extracts are mixed with starch paste and lactose is added to bring the composition to 100 g. Then the ingredients are thoroughly mixed with starch paste to obtain a thick mixture. The mixture is then granulated in a granulator, dried at 104 ° F, and sieved through a 16 mesh sieve. To dry the granules, talc is added and then uniform tablets are punched with a special machine.

The composition is applicable in the treatment of acute forms of ulcers.

In the case of HC ₂ composition (without the addition of Utlaria solicifolia), a significant (P <0.05) protective effect was observed at a dosage of 200 mg / kg of weight only for ulcers induced by ligature on the pylorus.

Advantages of the Invention

1. Neutralizes excess acid in the stomach.

2. Applicable for acute and chronic forms of gastric and duodenal ulcers.

3. Applicable in the healing and treatment of ulcers.

4. Applicable in the treatment of internal bleeding.

Information sources

1. US patent 6187313 February, 2001, Segelman

2. US patent 5728384 March, 1998, Tokuyama

3. Sairam et al. J. Ethnopharmacology. 82 pp. 1-9, 2002.

4. Sairam et al. Phytomedicine, 86 (6), pp. 423-430, 2001.

5. Raw et al. J. Physiol. Pharmacol, 44 (4), pp. 435-441, 2000.

6. Remington, The science and practice of pharmacy, 19 ^th edition, Vol II. pp. 1635, 1995.

7. Anonymous. Indian Pharmacopoeia. Govt of India, 1996.

Claims (24)

1. Antiulcer plant composition, comprising the following ingredients in an amount, wt.%: a) Utlaria solicifolia extract from 2 to 5 b) extract of Asparagus racemosus from 1 to 3 c) extract of Foeniculum vulgare 2 to 4 d) extract of Ficus glomerata from 3 to 5 e) used in pharmaceuticals additives from 83 to 92 2. The composition according to claim 1, made in an oral dosage form in the form of tablets, capsules, powder or liquid. 3. The composition according to claim 1, in which the extract of the plants used is obtained by extraction with a 50% aqueous-alcoholic solution. 4. The composition according to claim 3, in which the alcohol used is ethanol. 5. The composition according to claim 1, in which% (wt./wt.) Used plant extracts is from 8 to 17 of the total weight of the composition. 6. The composition according to claim 1, in which the extract of Utlaria solicifolia used is an extract of rhizomes. 7. The composition according to claim 1, in which the used plant extracts are obtained from individual parts of the plant: leaves, rhizomes and aerial parts. 8. The composition according to claim 1, which uses pharmaceutical additives for binders, diluents, lubricants, glidants, disintegrants, or combinations thereof. 9. The composition of claim 8, in which lactose, starches, sugars such as mannitol, sorbitol, xylitol, dextrose, sucrose, microcrystalline cellulose, basic calcium phosphate, calcium sulfate, or a mixture thereof are used as diluents. 10. The composition of claim 8, in which starch paste, sorbitol, alginates, polyvinylpyrrolidone, gum arabic, cellulose derivatives: hydroxypropyl methylcellulose, hydroxypropyl cellulose, methyl cellulose, carboxymethyl cellulose, methyl cellulose, peptized them, are used as binders. 11. The composition of claim 8, in which derivatives of silica, talc, starch and a mixture thereof are used as glidants. 12. The composition of claim 8, in which metal stearates, stearic acid, talc, polyethylene glycols, soluble salts such as sodium chloride, sodium benzoate, sodium lauryl sulfate, dried by spray drying, magnesium lauryl sulfate, boric acid, starch are used as a lubricant lactose or a mixture thereof. 13. The method of obtaining the composition according to claim 1, comprising the following stages: a) obtaining the necessary parts of medicinal plants, b) drying in the shade of the plant material of stage (a), C) grinding the dried plant material of stage (b) to obtain a fine powder, g) extraction of the crushed plant material of stage (c) with an aqueous-alcoholic solution at a temperature of 25-35 ° C for 4-7 days to obtain an aqueous-alcoholic extract, d) concentration of the extract of stage (g) under reduced pressure at a temperature of 40-60 ° C to obtain a concentrated extract, e) lyophilization of the concentrated extract of stage (e) to remove residual solvent and obtain a plant extract and g) introducing into the plant extract stage (e) the additives used in pharmacology to obtain a composition. 14. The method according to item 13, in which at stage (a) the medicinal plants are obtained from Utlaria solicifolia, Asparagus racemosus, Foeniculum vulgare and Ficus glomerata. 15. The method according to 14, in which parts of the medicinal plants are selected in the form of leaves, rhizomes and aerial parts. 16. The method according to item 13, in which the aqueous solution of ethanol used in stage (d) contains water: ethanol in proportions from 6.4 to 1: 1. 17. The method according to item 13, in which the ratio of plants and aqueous ethanol used in stage (d) is from 1: 8 to 1:15. 18. The method according to item 13, in which the total percentage of plant extracts is from 8 to 17 wt.% From the total weight of the composition. 19. The method according to item 13, in which the pharmaceutically acceptable excipients are selected from the group consisting of diluents, lubricants, glidants, disintegrating compounds, or mixtures thereof. 20. The method according to claim 19, in which lactose, starches, sugars such as mannitol, sorbitol, xylitol, dextrose, sucrose, microcrystalline cellulose, basic calcium phosphate, calcium sulfate and a mixture thereof are used as diluents. 21. The method according to claim 19, in which the binders used are starch paste, sorbitol, alginates, polyvinylpyrrolidone, gum arabic, such cellulose derivatives as hydroxypropyl methylcellulose, hydroxypropyl cellulose, methyl cellulose, carboxymethyl cellulose, methyl cellulose, ethyl cellulose, 22. The method according to claim 19, in which the used glidants are derivatives of silica, talc, starch, or a mixture thereof. 23. The method according to claim 19, in which the lubricants used are metal stearates, stearic acid, talc, polyethylene glycols, soluble salts such as sodium chloride, sodium benzoate, sodium lauryl sulfate, spray of dried magnesium lauryl sulfate, boric acid, starch, lactose or their mixture. 24. The use of the composition according to claim 1 in a dosage of from 100 to 200 mg / kg of body weight for ulcers induced by cold stress or for ulcers induced by ligature on the pylorus.