Medicinal agent "gastropek" for improving digestion process and method for its using

FIELD: medicine, pharmacology, pharmacy.

SUBSTANCE: invention relates to the development of a new medicinal agent representing the complex enzyme preparation with the digestive effect. Agent comprises enzyme pectate lyase providing effective cleavage of vegetable food intercellular substances, in particular, pectin and protopectin that results to formation of the homogenous and easily digestible mass, and promotes to assimilation vegetable food that is not assimilated by human organism that results to the more complete digestion of food, its cleavage and assimilation of nutrient substances. The optimal content of enzyme pectate lyase and pancreatin in a tablet covered by the enterosoluble envelope promotes to the more rapid and complete digestion of food in intestine and shows significant advantages as compared with the known digestive preparations.

EFFECT: improved and valuable properties of agent.

5 cl, 11 tbl

The invention relates to medicine, in particular to medicines used for the treatment and prevention of diseases associated with disorders of the digestive processes (3). The main indications for use of drugs digestive enzymes are: chronic pancreatitis with exocrine insufficiency; pancreatectomy, pancreatic cancer, liver disease and biliary tract, stomach resection, small bowel, chronic enteritis, gastritis with secretory insufficiency, advanced age, errors in diet when taking bold, unusual or hard-to-digest food and other

It is known that the treatment of these diseases is used Pancreatin (9), which compensates for the deficiency of pancreatic enzymes, contains excretory pancreatic enzymes lipase, amylase, protease, trypsin, chymotrypsin, contributes to the breakdown of proteins to amino acids), fats (up to glycerol and fatty acids) and starch to dextrins and sugars) and normalizes digestion. Pancreatin is present in domestic formulations and foreign, and its content varies widely. So, Anchorman (Germany) - contains 35 mg of Pancreatin; Pancreatin (Germany) - 170 mg; Festal N (Germany) and Enzistal (India) - 192 mg; Digital (USA) 200 mg; Pancreas 10000 (G is Romania) - 250 mg; CREON (France) - 300 mg. Domestic product Pancreatin contains 250 mg. it is Known that the addition of Pancreatin in the composition of certain drugs, such as Digital, Pental, Pansinin, Dagestan, Festal, Holenzim and Enzistal included components of bile, providing emulsification of fats. The composition of the tablets of Vegeration includes Pancreatin and liver extract dried; Pansinin - cholic acid, hydrochloride amino acids; in Anchorman - extract of turmeric; Simplex - Dimethicone. It is known that drugs Abomin, Digital, Pental, Dagestan, Festal and Enzistal additionally contain cellulase and hemicellulase, which assist in the breakdown of plant tissue (6, 7). However, the presence of cellulases in medicines cannot ensure complete digestion of plant foods and for cleavage is also necessary pectolytic enzymes, such as pectinase and spectacles.

Analysis of drugs used in disorders of digestion, showed that no medicinal product manufactured, which would contain enzymes pectolytic actions that can break down the pectin and > protopectin plant tissue of fruits and vegetables (6, 8).

One of the analogues of the claimed invention is patent No. 1375857, UK, 27 November 1974, the priority of the Federal Republic of Germany 7 but the December 1970 No. 2053948, "an Enzyme that destroys the plant material, the process of its production and use in compositions for digestion" (4), a significant drawback is that the enzyme acts only on the vegetable part of the food consumed. The result will require additional medication, such as Pancreatin, Festal, etc. for the digestion of proteins, fats and starchy carbs. Another disadvantage of this invention is the large mass of the enzyme per unit doses up to 200 mg, whereas in the invention the dose of the enzyme spectacles is 25 mg. in Addition, the industrial enzyme is not produced, so to compare it materialsa properties of the claimed product is not possible.

The closest prototype to the technical essence and the achieved result to the claimed medicinal product Gastropub is the drug Pancreatin and its synonyms, CREON, Mezim-Forte, Pancreas 10000, Panzytrat. A significant drawback of these drugs is that they do not adequately contribute to the digestion of food of plant origin, as the enzymes of Pancreatin are unable to break down the pectin and > protopectin which form the basis of intercellular substances and "cementing" the plant tissue. This function shall pentolaacciaio, for example, pectolyase.

The aim of the invention is the creation of new medicines with a wide range of activities that contribute to the digestion and assimilation of food, both animal and vegetable origin, and method of its use for the treatment and prevention of diseases associated with disorders of the digestion, which in contrast to all currently available digestive drugs high activity of the enzyme pectolyase providing efficient cleavage of pectin and > protopectin vegetable food; and a complete set of enzymes of Pancreatin for the breakdown of proteins, fats and starchy carbohydrates.

The purpose of the invention is achieved by developing medicines Gastropub, consisting of the original substance of Gastropathy containing the enzyme spectacles, and substance of Pancreatin containing enzymes - protease, amylase and lipase.

The substance of Gastrolith is a purified enzyme pectolyase (4.2.2.2.) and has the ability to materiality, i.e. to break down the intercellular substances of plant tissue, in a weak alkaline zone pH for a short period of time (2-4 hours). Enzyme pectolyase obtained from the culture fluid of a producer Bacillus macerans BS-04, grown by submerged culture with aeration on a specially developed with the food. The molecular mass of the enzyme pectolyase determined by the method of gel filtration is 41000-42000 D. Isoelectric point set method isoelectrofocusing and is in the range of pH of 9.4, pectolyase stable in the zone of pH 6.5 to 8.5, shows the optimal specific activity in the area of 7,5-8,2 at a temperature of 35-40°With and is activated by calcium ions.

In the compounds of Pancreatin and Gastropathy in one tablet at their optimum content created drug Gastropub with a wide range of activities that contribute to the digestion and assimilation of proteins, fats, starch, and non-starchy polysaccharides in plant foods.

Enzyme pectolyase by maceration of plant tissue provides high availability components of food consumed for the action of pancreatic enzymes, which is confirmed by the data obtained in the study of the specific activity of the drug Gastropub in vitro.

People and many other omnivores not able to digest the cell wall of plants because they do not have the anatomical and physiological features that are herbivores. Most plant food is grooveliker mass, which has no nutritional value, so as not digested in the digestive process. Therefore, the application aspect is tliese in the composition of the proposed medications appropriate and leads to the breakdown of pectin and > protopectin plant food to unsaturated di - and tregulatory acids.

To determine drug doses of the substance of Gastropathy investigated the specificity of its action on plant substrates. When determining the specificity was guided by the Methodological Guidelines for experimental research of new enzyme products offered for clinical trials (1). Used various types of vegetable substrates, most commonly used in the diet. Assessment of the validity of the substance of Gastropathy was performed according to the degree of maceration (in %) of these plant substrates, which was reflected in the reduction in the content of dry substances in the substrate due to the exit of cells from plant tissues easily digestible soluble compounds. In addition, were used to define the accumulation of degradation products of pectic substances, converted to soluble form and represents an unsaturated galacturonase acid, by spectrophotometrically their optical density in quartz cuvettes with a thickness of the light absorbing layer 1 cm at a wavelength of 235 nm (2).

As plant substrates used fresh and boiled vegetables and fruits in powdered form. To determine the specific steps used standard drug Gastropathy with activity spectacles 3000000 units/year For determining the minimum number of Gastropathy required on the I cleavage of the substrate, researched various amounts of enzyme from 1000 to 12000 units per 20 g of substrate.

The examples in table 1 show that the maximum percentage of maceration installed when exposed to 9000 units pectolyase activity (3 mg Gastropathy activity 3000000 units/g) 20 g of a clear substrate. Further increase in the number of Gastropathy increases the percentage of maceration slightly and is impractical.

The examples in table 2 show that during the processing of boiled vegetables, such as cabbage, carrots, beets, degree of maceration on 9-13 % lower than fresh, as the heat treatment of the substrates is their partial hydrolysis and transfer of certain substances in soluble form. The greatest degree of maceration among boiled substrates mounted on the potatoes, as the heat treatment of the potatoes partially gidrolizute starch, the content of which reaches 17-20%. This is evidenced by the low accumulation of products of hydrolysis of pectic substances (unsaturated galacturonic acid)content in the supernatant of potatoes is much lower than in the case of other substrates. This explains the fact that the total solids content in the substrates in the process of preliminary heat treatment is reduced. It is established that the maximum maceration boiled substrates as well as with the action of the enzyme on fresh substrates is observed at a ratio of 3 mg (9000 units) Gastropathy 20 g of substrate.

The examples of table 3 show that when exposed to Gastropathy PA fresh fruit there is an increase in the degree of maceration in comparison with fresh vegetables on average by 10%, since the content of pectin and insoluble > protopectin in fruit is higher (5). It is established that the maximum maceration of fruits and vegetables in boiled and fresh observed in step 3 mg (9000 ed) Gastropathy 20 g of substrate. The concentration of the products of the hydrolysis of pectic substances increases with increasing concentration of the enzyme and reaches its maximum at a concentration of Gastropathy 3 mg (9000 ed) 20 g of the substrate, which is consistent with the degree of maceration substrates.

According to the Institute of supply, the quantity consumed by the individual plant foods per day is not less than 500 g, so it will take 75 mg (activity 3000000 units/g) - at 225,000 units of Gastropathy, ie, 25 mg three times a day.

It was found that optimal conditions actions Gastropathy is slightly alkaline zone pH and temperature 37°that meets the conditions of the small intestine where the main processes of digestion and assimilation of food. Food entering the stomach, is subjected to acid hydrolysis under the influence of gastric juice, therefore, studied the effect of Gastropathy on substrates pre-treated with gastric juice. The substrates, after a two-hour exposure to gastric juice "EQUINE" at a temperature of 37°and With stirring, was podslushivaet to pH 8.0 and subjected to the influence of Gastropathy within 6 hours Studies were performed on fresh and from the ary vegetables. Examples are given in table. 4 and 5.

From the use of the s in table 4 and 5 shows, due to the acid hydrolysis of the soluble phase goes from 9% to 15% of dry matter. The highest percentage of acid hydrolysis (up 23%) was observed PA potatoes as the starch content in the composition of the potato is 15-20%, more actively undergoes hydrolysis by acid gastric juice unlike other polysaccharides of plant substrates such as cellulose, hemicellulose, glucans and pectins. Subsequent processing of boiled vegetables with Gastrolith increases the degree of maceration from 38% to 42%, and potatoes to 59.4%. Partial acid hydrolysis of substrates gastric juice intensifies the process of decomposition of plant food Gastrolith.

Due to the fact that the claimed medicinal product contains two substances: Gastrolith and Pancreatin, conducted studies but their compatibility.

Since the content of Pancreatin and known drugs varies from 0,192 g (Festal) to 0.2 g (Digital, Pansinin) in one pill, so average its contents were of 0.2, the Content of Gastropathy in one tablet installed as of 0.025,

To study the compatibility of complex enzymes of Pancreatin and Gastropathy was mixed with 0.2 g of Pancreatin and 0.025 g of Gastropathy. The mixture was dissolved in 100 ml of phosphate buffer solution with pH 8.0 and kept at a temperature of 37±0,5°t is the increase in the 6 o'clock Then determined the residual activity of the enzymes. Activity spectacles determined by spectrophotometrically unsaturated reaction products of pectolite having the maximum optical density at a wavelength of 235 nm (2), the activity of amylase, protease and lipase of Pancreatin was determined in accordance with FS 42-3647-98 (9). Examples are given in table 6.

Example of table 6 shows that the enzymes of Pancreatin and Gastropathy not have inhibitory effect on the activity of each other.

The specificity of action of the composition of Gastropathy with Pancreatin studied in mixtures of plant substrates. The number of Pancreatin was calculated in accordance with the Instruction manual 1-2 tablets 3 times a day (the content of Pancreatin in 1 tablet 0.1 g), per day (from 0.3 g to 0.6 g). Therefore, 20 grams of vegetable food used from 12 mg to 24 mg of Pancreatin and 3 mg Gastropathy.

The progress of experiment: six chemical glasses made substrate, gastric juice and kept at a temperature of 37°and shaking with SC is the rate of 60 rpm for 2 hours Then the pH of the substrates conveyed to the values of 8.0; was made a certain number of Gastropathy and Pancreatin dissolved in 0.001 M phosphate buffer (table 7), incubated at 37 ° °and With shaking at 60 rpm for 6 h

For comparison of the effect of enzyme substrates similarly processed Tour is zoé and Pancreatin separately. Used a mixture of vegetables both cooked and fresh, in the song, eat in salads. Examples are given in table 8.

Example of table 8 found that the effect of Pancreatin on fresh vegetables degree of maceration of plant substrates is insignificant and is 4-7%. In a mixture of boiled vegetables containing potatoes (experiment 2, 3, table 8) the degree of hydrolysis of the substrate reaches 29-54%, which is the result of the action of Pancreatin amylase, effective on substrates containing starch. The greater the percentage of potatoes in a mixture of vegetables, the higher the rate of hydrolysis of substrates.

Study of the specificity of action of the composition of Gastropathy with Pancreatin on plant substrates pre-treated gastric juice showed the effectiveness of the composition. The combined effect of Gastropathy with Pancreatin provides a more efficient hydrolysis of vegetable substrate is due to the maceration of plant tissues by Gastrolith, resulting substrates become more accessible to the action of enzymes of Pancreatin. Thus, the effect of the composition of substances of Gastropathy with Pancreatin more effectively than their effect individually.

When developing medicines Gastropub were considered the property of substances of Gastropathy and Pancreatin to inaktivirovanie in an acidic environment, so to protect the core tablet of the proposed drug from the action of gastric juice used is known excipients and enteric-soluble film coating that protects the tablet in the zone of pH 1.2 to 6.0 and retains its activity in the area of pH 7.0 to 8.5, corresponding to the pH of the intestine.

The composition of the tablets Gastropub: Gastrolith - 0.025 g, containing not less than 70000 units pectolyase activity: Pancreatin - 0,200, containing not less than 36 units of proteolytic activity: excipients (microcrystalline cellulose, lactose, corn starch, sodium chloride, oksipropilmetiltselljuloza, magnesium stearate). The mass of the nucleus-tablets - 0.35 g, the mass of tablets, coated enteric-soluble shell - 0.36 g ±5%.

Appearance: tablets white or white with a grayish uhsnkem color, coated enteric-soluble shell biconvex shape, the cross section is visible grey homogeneous mass.

To implement the inventive image the plants investigated specific and General pharmacological activity of the drug Gastropub in vitro.

When examining the specific action of drug Gastropub on plant substrates as Comparators were used - Pancreatin; Mezim-Forte (containing only Pancreatin) and Festal; Enzistal (containing Pancreatin and enzyme hemicellulase).

Used chopped vegetable substrates and their mixtures both fresh and boiled.

The experiment

In chemical beakers were placed 150 g of substrate was added 150 ml natural gastric juice "EQUINE" and kept at a temperature of 37±0,5°and shaking about 60/h for 2 h, simulating the stomach. Then the contents of the cups were podslushivaet to pH 8.0, made Gastropub and Comparators and kept at a temperature of 37±0,5°C and shaken at a speed of 60 Rev/h for 6 h after 6 h the contents of the glasses was centrifuged at 10,000 rpm for 15 minutes and Then the supernatant liquid was decanted, and the precipitate was twice washed with distilled water 50 ml and centrifuged. The washed precipitate was transferred into buxy previously brought to constant weight, and dried to constant weight at 105°C.

The action of the medicinal product has been evaluated but the reduced mass of the substrate (the degree of maceration) in the feedback Gastropacha and Comparators and expressed in percent p is the ratio of the experimental sample to a control.

The degree of maceration was calculated by the formula:

where:

M₀is the mass of absolutely dry residue of the substrate of the experimental samples;

M_tois the mass of absolutely dry residue of the substrate of the control sample.

The supernatant obtained after the first separation of the biomass substrate, was determined by the accumulation of the products of hydrolysis of pectin and > protopectin - unsaturated galacturonic acids by spectrophotometrically their optical density (1). The number of products of hydrolysis of pectin was determined by the difference of optical densities (Δ (D) supernatant experimental and control samples. In the supernatant was determined quantitative content of soluble carbohydrates (2).

Action Gastropacha and Comparators investigated for mixtures of cooked and fresh substrates in various compositions. As the comparison drug used drug Festal, which contains the enzymes of Pancreatin and hemicellulase and, therefore, should carry out the hydrolysis of the hemicellulose of plant substrate. The examples presented in tabl and 10.

The given examples show that the degree of maceration of boiled vegetables less than 7-8% compared with the degree of maceration of fresh vegetables. Study of different doses Gastropacha showed that significant difference of action of the drug on the degree of maceration using different concentrations of the drug (1 or 2 tablets) is not observed. When making 2 tablets Gastropacha degree of maceration increases only slightly by 4-10% depending on the type of substrate. The examples presented in tabl; 10, show that the degree of maceration of plant substrate treated with Fes is scarlet on 17-20% lower compared with the degree of maceration of plant substrate under the action of Gastropacha. A higher level of maceration substrates medicine Gastropub due to the fact that due to the destruction of intercellular compounds in plant tissue facilitates access to the substrate for the enzymes of Pancreatin, resulting in increased formation of soluble carbohydrates in vegetables and fruit in the form of polysaccharides. As a result, the amount of carbohydrates that have fallen into the solution under the action of Gastropacha 15-20% more than under the action of Festal in the rooting medium.

A comparative study of the action of drugs the nearest analogues and Gastropacha were carried out on mixtures of vegetable substrates. The examples presented in table show that the greatest effect on the degree of maceration of the substrate is observed when using Gastropacha that achieves 52-54%. In the case of the use of Pancreatin and Mezim-Forte degree of maceration is only 6-9%. Under the action of Festal and Enzistal vegetable substrates are oxidized at 23-30% due hemicellulase. among these is the courthouse square, which hydrolyzes the hemicellulose of plant substrates. Under the action of a boiled substrates of these drugs (mix 3, table) patterns of variation in the degree of maceration remain the same, in absolute figures 2-4% lower than the effect on fresh substrates.

At action of preparations on a mixture of boiled substrates containing potatoes (SMEs, 5; table no. 11) the degree of maceration is higher than a mixture of boiled substrates without potatoes. When using Gastropacha it is 69-75% depending on the content of the potato mixture. Pancreatin and Mezim-Forte carry out the hydrolysis of the substrate on 45-58%, which is explained by the presence of amylase, which is part of a complex of enzymes of Pancreatin, hydrolysing the starch. Drugs Enzistal and Festal due to the presence hemicellulase under the action of a mixture of substrates with potatoes provide their hydrolysis on 51-61%.

Comparative analysis Gastropacha with digestive enzyme preparations (Pancreatin, Festal, Enzistal, Mezim-Forte) showed that the efficiency of plant substrates Gastropacha for 17-25% higher.

Action Gastropacha on pectic substances of plant substrates is confirmed by the formation of the products of their hydrolysis - unsaturated galacturonic acid content in the supernatant is 22-24% of control. In the case of Comparators the accumulation of products of hydrolysis of pectic substances contained in the plant substrate, practically does not occur and is only 0.1-1%, which is explainable by the presence of minor amounts of free galacturonic acids.

Making 2 tablets medicines Gastropacha on 150 g of vegetable substrate increases the degree of maceration only 3-5%, in comparison with the effect of 1 pill for the same amount of substrate. Therefore, when a normal diet is recommended Gastropacha 1 tablet 3 times a day immediately before or during a meal without chewing or 2 tablets 3 times in the Yan with overeating.

A comparative study of specificity of action Gastropacha and drugs Pancreatin, Mezim-Forte, Festal, Enzistal showed that Gastropub provides a more complete breakdown of plant substrates 18 - 20% higher compared to drugs Festal, Enzistal, contain the enzyme hemicellulase, and 22-25% higher in comparison with preparations containing only Pancreatin (Pancreatin, Mezim-Forte).

The specific activity of the drug Gastropacha in vivo was determined by the degree of assimilation of nutrients and the balance on the core elements of the metabolism of animals, namely nitrogen, calcium and phosphorus. As a comparison, used a known enzyme preparations - Pancreatin and Enzistal. Found that when taking Gastropacha the absolute value of the weight gain is higher than the reception Enzistal and Pancreatin.

The study of nutrient absorption (10) the group of experimental animals when feeding a normal diet with the introduction of Gastropacha showed that the use of Gastropacha, Pancreatin and Enzistal increases the percentage of food digestion by indicators such as: dry matter, organic compounds, protein, fat, fiber and biological energy substances. With the introduction of animal Gastropacha coefficient of absorption for all higher in comparison with controlgroups animals and for 6-10% more than when using Pancreatin and Enzistal. The greatest differences were observed in the digestion of fiber animals in the experimental group, where the absorption coefficients when applying Gastropacha 17.6% higher than in animals of the control group and 11.5 and 7.5% higher than when using Pancreatin and Enzistal respectively.

The group of experimental animals treated with Gastropub at the optimal dose, the percentage of nitrogen absorption by 5% and 3.5% exceeded these figures are compared with the groups of animals treated with Pancreatin and Enzistal respectively. Studies done on the balance sheet (11) of macronutrients such as calcium and phosphorus showed that all three drugs contribute to a more efficient breakdown of food and absorption of calcium and phosphorus. However, when using Gastropacha phosphorus absorbed by 11.4% compared with the groups of animals treated with Pancreatin and 6.1% compared with Enzistal, and calcium is absorbed by 5.3% and 4.9% compared with Pancreatin and Enzistal respectively.

Stable and reliable for a long time, the increase of body weight in experimental animals treated with Gastropub, and a significant excess of this indicator compared to the values obtained when applying Pancreatin and Enzistal, allowed to conclude that a higher specificity composition and digestive enzymes drug Gastropub.

Thus, the drug Gastronic contributes to a more efficient and complete digestion of the food, her cleavage and, as a consequence, absorption and assimilation of nutrients than the known medicinal enzymes. used for disorders of digestion.

Preclinical Toxicological research Gastropacha held in LLC OXFARM" on an experimental basis of the laboratory of pharmacology and chemotherapy GU NIINA them. Grause RAMP in accordance with the "Manual on experimental (doklinicheskogo) study of new pharmacological substances", 2000 (12).

Studies of acute toxicity Gastropacha conducted on mice SHK according to the method of Litchfield and Wilcoxon signed in the modification of Western Roth (13). For monitoring the status and behavior of the experimental animals did not differ from the norm. To determine the dose that characterize the toxicity of the drug, was not possible because of low toxicity introduction the maximum possible doses did not lead to the death of mice. Also acute toxicity of the drug Gastropub investigated (13) in Wistar rats after a single application in the stomach. At autopsy, the animals on the 30 day of macroscopic changes in organs not found. Study of acute toxicity Gastropacha showed that acute drug use to the maximum possible the x quantities of lethal doses cannot be reached therefore, the drug belongs to a group of drugs with low toxicity. In chronic experiments on rats it was shown that the drug is well tolerated by animals. In all studied doses, the drug does not cause dysfunction of organs and systems and does not affect the structure of internal organs.

Studies on chronic toxicity Gastropacha conducted on Wistar rats (13). Throughout the experiment, the variance in the behavioural responses of animals were observed. In any case, no marked effects of mydriasis and actically. Animals in the experimental groups received the drug. normally put on body weight.

In the study of peripheral blood of rats in the experimental and control groups of animals not observed significant differences (14, 15). Changes in morphology of cells was not detected in any of the groups. Changes in the coagulation system is not detected in either group nor for one term. Analysis of biochemical parameters of blood indicates the absence of the animal signs of intoxication after drug Gastropub. Indicators such as total protein, glucose, enzymes, electrolytes remained almost unchanged during all periods of observation. In the study of renal function in experimental groups of rats diuretic violations have been found.

When studying the cardiovascular system of animals (16), receiving Gastropub within 30 days abnormalities not detected.

The Central nervous system of rats was not affected. It is established that 30-times daily drug Gastropub not had any action on the Central nervous system of experimental animals.

When determining the mass coefficients of internal organs no significant differences in the experimental and control groups was not detected. At autopsy, the animals macroscopic changes of internal organs was not found.

Pathological examination of the internal organs of rats was performed after oral administration Gastropacha. Damage to the structure of organs and tissues was not found.

The study of chronic toxicity Gastropub applied orally daily for 30 days in single doses of 250 and 500 mg/kg (equivalent to 100 and 200 of therapeutic doses to humans) have shown that the drug is well tolerated by animals. The drug, used even at a high dose, amounting to a total of 15000 mg/kg does not change and the status and behavior of animals, did not cause death.

Physiological tests showed that the drug Gastropub does not affect the peripheral blood, does not impair the function of the liver, kidneys, cardiovascular system and Central nervous system.

It is established that the drug Gastropub has no, anafilaktichesky and immunotoxic properties, does not affect the basic parts of humoral and cellular immunity.

Study of reproductive toxicity Gastropacha and its impact on the generative function conducted on Wistar rats (12). It is established that the drug Gastropub no effect on the generative function of Wistar rats.

The study of the embryotoxic properties Gastropacha conducted in accordance with the recommendations (12) on rats female Wistar. It is established that the introduction Gastropacha does not lead to a breach of weight gain in females compared with control. Gastropub when introduced into the stomach at doses of 250 and 500 mg/kg did not result in increased embryonic mortality, changes in the weight and size of fruits. The study of the internal organs of fetuses (17) also showed no differences from control in the experimental groups of animals. Found that the offspring of Wistar rats to measure emotional and motor development does not differ from the control. The drug did not produce the embryo and fetotoksicheskogo action, registered in the antenatal and postnatal period of development and the damaging effect on the generative function of animals when introduced into the stomach at all tested doses.

Thus, the drug Gastropub has no, anaphylactogenic and immunotoxic properties, does not affect the basic parts of humoral and cellular immunity. Teratogenic and embryotoxic effects have been detected.

References

1. Methodical Recommendations for a pilot study of new enzyme products offered for clinical trials. Moscow, 1981

2. Starr M.P., Moran F. "Eliminative split of pectin substances by phyto-pathogonic soft - rot bacterio", Sci, 1962, v.135, p.920-921.

3. Medicine and man. The world of drugs. Moscow, radar - 2001

4. Y.Graham and J.W.Sockman, Gastroenterology; 83(3), c.638-644, 1982. Patent No. 1375857 from 27.11.1974, UK "an Enzyme that breaks down the plant material, the process of its production and use in the composition of medicines to improve digestion".

5. Lveel. Technology of pectin and machineproduced. Moscow, 2000

6. Register of medicines of Russia, 97/98, Remake, Moscow, 1997.

7. Dvico, Ohalei, Drugs for substitution therapy of digestive insufficiency (review), UNISANTA, Moscow, 1988.

8. Vasyukov, Nbegin, Yea, Whakamana, Velyaminov. Enzyme preparations used in case of insufficiency of digestive processes (overview), Chemical and Pharm. Zhur., Moscow, t, No. 3, p.3-7, 2000.

9. FS 42-3647-98.

10. Methods for determining the digestibility of feeds and rations. Moscow, agricultural Sciences, 1969

11. Appmetrics, Pdicy. Feeding farm animals. Leningrad, 1961

12. Manual on experimental (preclinical) study of new pharmacological substances. Mosk is and. 2000

13. Belenky, M. - elements of a quantitative evaluation of the pharmacological effect. L., 1963

14. Coast E. - Handbook of clinical and laboratory research methods. M. 1966.

15. Kudryavtsev A.A., Kudryavtseva L.A. - Clinically. Hematology animals. M., 1974

16. Oivin I.A. J. Pathological physiology and experimental therapy", 1960. No. 4, p.76.

17. "Methods of developmental biology" Ed. by Blastwave, M., "Nauka", 1974, 217.

1. Medicine for improving digestion, containing Pancreatin, which includes amylase, lipase, trypsin, chymotrypsin, and an excipient, which is a tablet, coated enteric-soluble shell, characterized in that it further comprises the enzyme spectacles isolated from the culture fluid of bacterial producer Bacillus macerans BS-04, the following ratio of components in the tablet core:

Pancreatin 0,200 g and proteolytic activity of at least 36 units,

pectolyase 0.025 g and spectaclecase activity of at least 70000 units,

excipients to 0.35,

2. The drug according to claim 1, characterized in that the enzyme pectolyase able to materiality pectin and > protopectin plant foods, promoting its digestion and assimilation.

3. Medicinal product according to claims 1 and 2, characterized in that the farm is NT pectolyase stable in the zone of pH 6.5 to 8.5, shows the optimal specific activity in the area of pH 7.5 to 8.2 at a temperature of 35-40°has a molecular weight D-D, isoelectric point P19,8 and is activated by calcium ions.

4. Medicinal product according to claims 1 to 3, characterized in that it further comprises excipients: microcrystalline cellulose, lactose, corn starch, sodium chloride, oksipropilmetiltselljuloza, magnesium stearate.

5. The way to improve digestive processes, including the introduction of enzyme preparation, wherein administering the agent according to claims 1-4.