Pharmaceutical and/or food compositions of short-chain fatty acids

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutics and represents an oral pharmaceutical composition for treating intestinal disorders, containing butyric acid or its salt in a combination with water-soluble or water-dispersed dietary fibre specified in inulin, maltodextrin or a mixture thereof, at least one flavouring agent specified in vanillin, vanilla essence or a mixture thereof and one or more pharmacologically acceptable excipients differing by the fact that it contains: a) a matrix containing lipophilic compounds with a melting point of less than 90°C, and an amphiphilic matrix wherein an active ingredient is at least ball-shaped; b) an amphiphilic matrix; c) an outer hydrophilic matrix wherein the lipophilic matrix and the amphiphilic matrix are dispersed; e) a coating; and a portion of the above at least one flavouring agent is dispersed in one or more of the above matrixes, and a portion of the flavouring agent is dispersed in the coating.

EFFECT: preparing the pharmaceutical composition for treating intestinal disorders.

22 cl, 5 ex

 

2420-170514RU/019

Short-chain fatty acids (KGK) represent a linear or branched C1-C5 monocarboxylic organic acids such as acetic, propionic, butyric and isovalerianic acid.

They are produced in the colon by fermentation of undigested sugars and dietary fiber with saprophytic bacterial flora that live in the colon.

Production of short-chain fatty acids occurs throughout the colon with a gradient decreasing from the ileocecal valve to the rectum. At the moment of contact short-chain fatty acids with epithelial cells (koloritni) of the mucous membrane of the colon they are quickly captured in the cells where metabolized to acetylcoenzyme A (acetyl-CoA), which is a fundamental factor in energy metabolism. The most important source of energy for Kolotilov of the four short-chain fatty acids, mentioned above, is butyric acid, because it is responsible for about 70% of the oxygen consumption koloritni. About 70-90% of all generated in the colon butyric acid is metabolized by koloritni (O. C. Velazquez et al, Dietary Fiber in Health and Disease, Plenum Press, N. Y. , 1977,123-134; Wachtershauser A. et al., Eur. J. Nutr., 2000,39, 164-171). Short-chain fatty acids are the main energy source for cells were slit the stay membrane of the colon, and also one of the fundamental factors to control growth, differentiation and immediate protection of the mucous membrane.

In fact, the lack of or significant reduction in the number CJK often associated with many functional disorders or organic pathological conditions, such as, for example, disorders caused by disturbance of bowel function, inflammatory condition of the bowel, ulcerative colitis, Crohn's disease, tumors, colon cancer, etc. KIK and, in particular, butyric acid or its salts, also affect the regulation of proliferation of epithelial cells of the colon, not only contributing to the processes of reepithelization normal mucosa, but also by inhibiting the proliferation of tumor cells, in particular, inhibition of DNA synthesis in tumor cells and restore their natural apoptosis (Wachtershauser A. Et al, Eur. J. Nutr., 2000,39, 164-171). Given the key role that butyric acid plays in the regulation of these critical biological functions of the colon, its introduction in terms of absolute or relative deficiency appears to be the performance of fundamental importance.

For endogenous production of butyric acid requires the presence of soluble dietary fibers that are broken down by the bacterial flora thick the intestine.

The splitting of the bacterial flora of soluble dietary fibers, in particular, inulin, leads to the production of endogenous butyric acid, therefore, inulin is an important factor to stimulate the growth of saprophytic bacteria, contributing thus activation of bacterial colonization and the regulation of the balance of bacterial flora of the intestine (Gibson, R. G. et al., Gastroenterology, 1995, 108,975-982; Nyman, M. Br. J. Nutr. 2002,87, s163-168).

In this regard, can be considered a constant need for the intake of short-chain fatty acids and fiber, even for subjects who do not show signs of disorders or pathological conditions on the part of the intestine, this is due to the increasingly frequent recourse about improper manners of food, inadequate diet and consumption of increasingly refined foods, which are becoming less and less coarse and, in particular, less rich in rough fiber.

In many cases, despite the presence of normal consumption of fibers, the fermentation process may be imperfect, which can lead to insufficient development of butyric acid. This reduction or absence of the function of intestinal fermentation in most cases caused by qualitative and quantitative changes in the bacterial flora of the intestine, which in turn caused upot what blenhiem in food substances, slowing down the development and normal growth of flora, such as antibacterial agents, preservatives, antibiotics, etc.

Thus, as a result of this common food-enzyme depletion production of butyric acid may be reduced, for example, to such a level that there is a lack of energy and defense, the supply of the intestine.

In this regard, the disorder delicate balance between external factors (dietary fiber) and endogenous factors (bacterial flora) can cause the above-mentioned organic or functional changes involving the intestine and, in particular, colon cancer.

Thus, with reduced or insufficient concentrations of butyric acid in the cavity of the large intestine is the most appropriate action is exogenous sufficient butyric acid directly into the large intestine.

Currently available compositions created on the basis of butyric acid only or on the basis of its salts of Na+, Ca++ and Mg++, and because oral KIK is extensive early absorption, the only way of introduction, in which you are guaranteed to achieve revenues of suitable concentrations of the indicated acid inside the colon represents the rectal route of administration. However, rectal the first path does not allow to reach the proximal part of the colon, therefore, admission is limited to the distal part of the colon, and this is due to the obvious and significant inconvenience to the indicated route of administration.

In addition, it is known that short-chain fatty acids, and, in particular, butyric acid, have a very unpleasant smell and sharp taste, with a sweetish residual aftertaste (like ether), resulting in a mammal, in particular humans, capable of detecting CZK even at very low concentrations (e.g., 10 ppm). This adverse property causes various problems when working with these compounds, especially when using them as components or active ingredients for the manufacture of pharmaceutical and/or food compositions. In such cases, in fact, unpleasant smell CZK, in particular, butyric acid, causing slow performance and error during all stages of the production process, and also during the final stage of packaging and storage.

Given the inappropriateness of the specified last route of administration for the purposes of food additives, the need to reduce the energy deficit and restore intestinal balance, and problems arising during production and packaging, to my surprise, it was found that the combination of at least one short-chain fatty acids, for example, t is coy, directly butyric acid, or its salt, ester or amide, at least one soluble or water-dispersible dietary fiber, such as inulin, and at least one flavoring agent, such as vanilla essence, in the formulation for oral administration leads to a very pronounced synergistic effect between these components, which causes strengthening actions, which, if can have a separate matter, and to improvements in the production processes and packaging specified products for oral use, which is the subject of the present invention.

The combination of these substances according to the invention actually leads to synergies their effects, which thus compensates for the deficit of energy and protection, which creates a lack of or reduced production of endogenous butyric acid and guarantees an optimized final product.

Thus, an object of the present invention are oral pharmaceutical and/or food compositions containing at least one short-chain fatty acid, in particular, oil acid or its salt, ester or amide, in combination with at least one soluble or water-dispersible dietary fiber, in particular, inulin, and less is th least one flavoring agent.

The oral formulation of pharmaceutical and/or food composition according to the invention can be produced in the form of tablets, capsules, granules or microspheres, and the preferred form is a tablet.

Short-chain fatty acid according to the present invention can be selected from linear or branched monocarboxylic organic acid C1-C5, preferably acetic acid, propionic acid, butyric acid, isovalerianic acid, or mixtures thereof, more preferred is butyric acid.

Soluble or water-dispersible dietary fiber according to the present invention can be selected from inulin, pectin, dextrin, maltodextrin, or derivatives thereof, and mixtures is preferred inulin.

According to the present invention, useful aromatic agents can be selected from natural aromatic substances, natural essences extracted essences, essential oils or their mixtures. Preferably, at least one specified flavouring agent is chosen from vanillin, vanilla essence, geraniol, geranium essences, alkaliphilous essential oil, almond oil, fruit flavors, honey, or a mixture thereof. According to the present invention, the number of present short-chain fatty acids is in the range from 5 d is 60% by weight, preferably from 10 to 50% by weight; soluble or water-dispersible dietary fiber is present in an amount in the range from 5 to 50% by weight, preferably from 10 to 30% by weight; and the amount present flavouring agent is in the range from 0.01 to 3%, relative to the total weight of the composition.

The above active ingredients according to the invention can be used to manufacture suitable for the introduction of forms in the most appropriate physical condition; as a dietary Supplement or pharmaceutical composition according to the invention are intended for oral administration, the preferred form is a solid form.

Because short-chain fatty acids, in particular, butyric acid, are liquids, for manufacturing the above solid forms, in particular tablets, you can use the solid salt of the specified acids, such as butyrate calcium butyrate sodium or magnesium butyrate, or the acid can be applied to a solid substrate of inert material by known techniques dry spray or adsorption.

As solid substrates according to the invention it is possible to use fillers that are typically used for the manufacture of tablets, such as gum Arabic, corn starch, pre-gelatinisation the initial starch, pectin, sugars monosaccharides and polysaccharides, alginates, microcrystalline cellulose, alkyl derivatives or hydroxyalkyl derivatives of cellulose with low, medium and high viscosity, monoprotonated and polydiethylene mineral salt, cyclodextrin, alkylcyclohexane, hydroxyalkyloxy, pyrrolidone or derivatives of monocarboxylic organic salts and/or esters, polycarboxylic organic salts and/or esters, inorganic bases, such as colloidal silica, talc, and organic and inorganic ion exchange resin.

For the manufacture of powder from the liquid carry out sputtering by drying the suspension liquid short-chain fatty acids, preferably butyric acid, and a solid substrate using the technology of dry spray, or these substances adsorb on one of the above substrates.

In both cases, get the powder containing the proportional number of short-chain fatty acids, preferably butyric acid, dispersed in a solid substrate.

In a preferred embodiment, the formulation of the compositions according to the invention preferably create a solid dosage form for oral administration, which can reach a certain area of the colon Kish and virtually unchanged, or so that most active ingredients directly enters the lumen of the colon, passing through the gastro Department and upper sections of the intestinal tract.

This requirement takes into account the fact that a very rapid and complete small bowel absorption of short-chain fatty acids, preferably butyric acid or its salts, when administered orally (e.g., capsules or tablets), and the extent of absorption does not allow them to reach the large intestine.

Admission to the colon can be achieved using the technology of controlled release, sustained release, modified release, using gastric resistance and/or disguise the taste of medicines, which are characterized by target localization are divisions of the colon. These technologies are known in the field of pharmacy and are typically used to create other types of active substances that require a specific time and/or localization of the release such as intestinal anti-inflammatory drugs (N. Brunner Et al., Aliment oil displayed pure. Pharmacol. Ther., 2003, 17, 395-402), systemic anti-inflammatory agents, antiulcer agents, antibacterial agents or substances to stimulate the mucous membranes.

For example, European patent application EP1183014 included with Silkov the present invention, describes the technology multinational controlled release, which is known under the trademark MMX and differs consistent and increasing dispersion of the active component in a mixture of three different interconnected matrix.

Thus, according to an additional variant implementation, the composition of the present invention contains:

a) a matrix containing lipophilic compounds with melting point below 90°C, and optional, amphiphilic compounds, in which the active component or components at least partially are spherical;

b) optional amphiphilic matrix;

c) an outer hydrophilic matrix in which is dispersed lipophilic matrix and optional amphiphilic matrix;

d) optionally other excipients;

e) optional coverage.

Amphiphilic compounds which can be used according to the invention, contain polar lipids I or type II (lecithin, phosphatidylcholine, phosphatidylethanolamine), ceramide, alkylether glycol, such as monomethylether diethylene glycol (Transcutol (R)).

Lipophilic matrix consists of substances selected from unsaturated or hydrogenated alcohols or fatty acids, salts, esters or amides, fatty acid mono-, di - or tri-glycerides, polyethoxylated derivatives, waxes, ceramides, produced adnych cholesterol or mixtures thereof, having a melting point in the range from 40 to 90°C, preferably from 60 to 70°C.

Hydrophilic matrix consists of fillers, known as hydrogels, i.e. substances which, during the transition from dry to hydrated state are the so-called "molecular relaxation", namely, substantially increase their mass and weight with subsequent coordination of a large number of water molecules by means of polar groups present in the polymer chains themselves fillers.

Examples of hydrogels that can be used according to the invention, are compounds selected from polymers or copolymers of acrylic or methacrylic acid, alkylvinyl polymers, hydroxyethylcellulose, karboksimetsiltsellyulozy, polysaccharides, dextrins, pectins, starches and derivatives, natural resins or synthetic origin, alginic acid.

The coating, which can be used for the present invention is a coating that can slow down, modify and/or regulate the release of the active ingredient/component and/or have the property of masking the unpleasant taste of the active ingredient. Preferably, the coating according to the invention is a gastro-resistant coating. Examples of the gastro-resistant coating, which is can be used for the invention, are the polymers of acrylic and/or methacrylic acid (Eudragit (R) or cellulose derivatives, such as acatitla cellulose, hydroxypropyl-cellulose, hydroxypropylmethyl-cellulose, hydroxyethyl-cellulose, or a mixture.

Other methods that may be suitable for creating compositions of the present invention described in the patent EP572942 and WO 00/28974, which is also included in the invention as a reference.

According to one variant of the invention, at least one of the above-mentioned flavouring agent may be dispersed in one of the above matrices: lipophilic matrix, amphiphilic matrix, a hydrophilic matrix, or in all of these matrices.

According to an additional variant of the invention, at least one specified flavouring agent may be fully or partially dispersed in the coating.

According to the invention, one portion of at least one of the specified flavouring agent may be dispersed in one and/or more of the above matrices, and one portion can be dispersed in the coating.

These methods can determine the active protection component/components all the way their passage through the stomach and during the passage through the upper parts of the small intestine (in particular through dvenadtsatyi the local gut and skinny intestine), to their release occurred directly in contact with the wall of the colon, the exact localization, where necessary, the maximum concentration for optimal effect.

These methods differ growing and slow washout of the composition, preferably, tablets or other suitable solid dosage forms, within the time required for transit through the gastrointestinal tract, with guaranteed optimal and uniform distribution of the active component/components in the mucosa of all departments of the colon.

Thus, the ability to provide local local treatment using the maximum stimulating and protective potential of short-chain fatty acids, preferably, butyric acid, which can thus act directly on the mucous membrane of the specific section of the large intestine, in combination with the following agents: soluble or water-dispersible dietary fiber, preferably, inulin, flavouring agent, and which is in contact with the bacteria, capable of direct fermentation of these agents and the development of additional quantities of short-chain fatty acids.

In this regard, on the basis of the above facts, an additional object of the present is subramania are oral pharmaceutical and/or food compositions with controlled release a slow release, modified release, taste masking and/or gastro-resistant composition containing at least one short-chain fatty acid, at least one soluble fiber or water-dispersible dietary fiber and at least one flavoring agent that can pass unaltered without splitting through all departments of the stomach and upper intestine, and can release the active components directly at the level of the colon. Preferably, the dosage form of the composition according to the invention is a tablet.

An additional object of the present invention is the above-described oral pharmaceutical and/or food composition is used to treat intestinal disorders, inflammatory bowel diseases and pathological conditions of the mucous membrane of the intestine and/or used for the prevention or treatment of intestinal tumors.

Preferably, the above-described oral pharmaceutical and/or food composition is used to treat intestinal disorders, inflammatory diseases or disorders of the bowel, irritable bowel syndrome, actinic colitis, dysbacteriosis after taking the antibiotics and for recovery of dysmetabolism, for the treatment of acute and chronic Diar anyh disorders and pathological conditions of the mucous membrane of the intestine.

An additional object of the invention is a method of manufacturing the above-mentioned oral pharmaceutical and/or food compositions containing at least one short-chain fatty acid, at least one soluble or water-dispersible dietary fiber, and at least one flavoring agent, at the specified method contains the following steps:

1) mixing at least one short-chain fatty acid, at least one soluble or water-dispersible dietary fiber, amphiphilic substance (s), lipophilic substance (s) and do not necessarily part of the fillers to obtain a homogeneous mixture

2) adding to the previously made the matrix of the hydrophilic substance (s) and optionally, other excipients to produce the final form.

Received multimachine composition can then undergo one or more stages of the coating that contained active ingredient (s) acquired the properties of controlled release, sustained release, modified release, taste masking and/or gastric resistance. You don't need to add additional flavoring coating on the surface of the specified composition, preferably in the case of a tablet form of the composition.

the opening according to the invention can be applied using known methods as, for example, in the drageeing boiler, fluidized bed, is equipped with a suitable nozzle and/or pumping systems.

The following examples are included in the present invention for further explanation without limiting the scope of invention.

EXAMPLES

Example 1
Gastro-resistant tablet with controlled release
IngredientsOnce the number
(mg/tablet).
Butyrate calcium
(i.e. butyric acid 250 mg/tab).
307,50
Corn starch37,50
Maltodextrins200,00
Citric acid22,50
Microcrystalline cellulose50,00
Inulin50,00
Sorbitol105,00
Hydroxyethylcellulose40,00
Stearic acid 17,00
Lecithin5,00
Colloidal silicon dioxide10,00
Magnesium stearate7,50
Vanilla essence3,00

Composition cover:
Shellac17,50
Talc20,00
Titanium dioxide4,00
Hydroxypropylcellulose4,00
Triethylcitrate4,00
Vanilla essence4,00
Ethanolq.s.

Were made 1000 tablets are coated with a single dose of 250 mg/cpr butyric acid and a small amount of inulin and vanilla essence. Then the tablets were Packed in blister aluminium/PVC (polivinlhlorida)/PE (polyethylene). Add vanilla essence in a matrix mixture and the slurry coating allows the t to minimize the unpleasant odor of butyric acid and to avoid odour problems during the final stage of the manufacturing process and packaging. The result is a very good product stability during storage under various conditions, about 10% limit, usually used to assess stability in pharmacology and medicine.

In order to produce coated tablets, used the following techniques:

wet granulation of calcium butyrate, corn starch, maltodextrins, inulin, stearic acid, lecithin, citric acid and sorbitol using a suspension of hydroxyethyl cellulose with a low viscosity. After drying complement the composition of microcrystalline cellulose, colloidal silicon dioxide and magnesium stearate. After mixing, the composition was subjected to pelletizing. Then the mixture was covered with an alcohol suspension of shellac, which also contain hydroxypropylcellulose, titanium dioxide, talc, triethylcitrate and vanilla essence.

Manufactured tablets show profile solubility slow release, when the release of less than 40% after 2 hours, using as an assessment tool test raspadaemost and a buffer with a pH of 6.8 as the environment. After coating, the tablets were Packed in blister and subjected to test raspadaemost.

Example 2
Gastro-resistant tablet with controlled release
IngredientsOnce the number
(mg/tablet).
Butyrate calcium
(i.e. butyric acid 250 mg/cpr).
307,50
Corn starch37,50
Maltodextrins210,00
Citric acid22,50
Microcrystalline cellulose50,60
Inulin250,00
Sorbitol146,25
Hydroxyethylcellulose60,00
Stearic acid7,50
Lecithin5,00
Colloidal silicon dioxide10,00
Magnesium stearate7,50
Composition cover:
Shellac17,
Talc21,3
Titanium dioxide4,2
Hydroxypropylcellulose4,2
Triethylcitrate4,2

Vanillaa 3.9
Ethanolq.s.

Were made 1000 tablets are coated with a single dose of 250 mg/cpr butyric acid and inulin, and with a small amount of vanilla. Then the tablets were Packed in blister aluminium/PVC/PE.

Add vanilla into a slurry coating helps to minimize the unpleasant odor of butyric acid and to avoid odour problems during the final stage of the manufacturing process and packaging. The result is a very good product stability during storage under various conditions, about 10% limit, usually used to assess stability in pharmacology and medicine.

Example 3
Gastro-resistant tablet with reguliruemym release
IngredientsOnce the number
(mg/tablet).
Butyrate calcium
(i.e. butyric acid 250 mg/cpr).
615,00
Corn starch37,50
Maltodextrins160,00
Citric acid22,50
Microcrystalline cellulose50,61
Inulin50,00
Sorbitol146,25
Hydroxyethylcellulose60,00
Stearic acid7,50
Lecithin5,00
Colloidal silicon dioxide10,00
Magnesium stearate7,50
Composition cover:

Shellac17,4
Talc21,348
Titanium dioxide4,185
Hydroxypropylcellulose4,185
Triethylcitrate4,185
Vanilla essence3,900
Ethanol315

Were made 1000 tablets are coated with a single dose of 500 mg/cpr butyric acid and 50 mg/tab. inulin with a small amount of vanilla essence. Then the tablets were Packed in blister aluminium/PVC/PE.

Add vanilla essence into a slurry coating helps to minimize the unpleasant odor of butyric acid and to avoid odour problems during the final stage of the manufacturing process and packaging. The result is a very good product stability during storage under various conditions, about 10% limit, usually used to assess stability in pharmacology and medicine.

Example 4
Gastro-resistant tablet with controlled release
IngredientsOnce the number
(mg/tablet).
Butyrate calcium
(i.e. butyric acid 250 mg/cpr).
307,50
Corn starch37,50
Maltodextrins210,00
Citric acid22,50
Microcrystalline cellulose50,60
Inulin250,00
Sorbitol146,25
Hydroxyethylcellulose60,00

Stearic acid7,50
Lecithin5,00
Colloidal silicon dioxide10,00
Magnesium stearate7,50
The composition of the coating - phase a:
Shellacto 12.0
Tal is to of 17.0
Titanium dioxide4,5
Triethylcitrate3,7
Ethanolq.s.
The composition of the coating - stage:
Shellac2,0
Vanilla4,0
Hydroxypropylcellulosethe 3.8
Talc2,0
Ethanolq.s.

Were made 1000 tablets are coated with a single dose of 250 mg/cpr butyric acid and inulin and using a different way to add flavouring agent in tablets. In fact, there is described a coating involving 2 stages: the first stage included compound capable of slow and prolonged release of the active ingredient from the tablets in the environment, and the composition of the second coating, which is consistently applied on the coated tablet comprises a flavoring agent is vanilla with a small amount of hydrophilic the polymer, used for fixing the flavoring on the surface coating of the tablets.

Two stage application cover sheet, do not change indicators solubility of the tablets in both cases the coating, with stage and without phase B, showed the same profile of solubility slow release, when the release of less than 40% after 2 hours, and in the quality assessment tool used test raspadaemost and a buffer with a pH of 6.8 as the environment. Then the tablets were Packed in blister aluminium/PVC (polivinlhlorida)/PE (polyethylene).

Add vanilla into a slurry coating with separate stages allows to minimize the unpleasant odor of butyric acid with a minimum of change stages of the production process and without any minimum impact on the stability of the product. The result is increased stability of the product during storage under different conditions is very good, significantly in the 10% limit, which is usually used to assess stability in pharmacology and medicine.

Example 5
Gastro-resistant tablet with controlled release
IngredientsButyrate calcium
(i.e. butyric acid 250 mg/tab).
307,517
Inulin250,000
Corn starch50,000
Maltodextrins300,000
Citric acid30,000
Microcrystalline cellulose67,483
Sorbitol195,000
Hydroxyethylmethylcellulose80,000
Stearic acid5,000
Colloidal silicon dioxide20,000
Lecithin5,000
Magnesium stearate10,000

Vanilla essence4,000
The composition of the coating - phase a:
Shellac 14,000
Talc17,000
Titanium dioxide4,500
Hydroxypropylcellulose1,800
Triethylcitrate3,700
Ethanolq.s.
The composition of the coating - stage:
Talc17,000
Hydroxypropylcellulose1,800
Shellac2,000
Stearic acid2,000
Flavor honey4,000
Ethanolq.s.

Were made 1000 tablets with the coating according to the method described in example 4. In fact, the coating was carried out in 2 stages: the first stage involves the application of compounds able to slow and prolonged release of the active ingredient from the tablets in the environment, and the second floor, where the composition, the follower is about to be applied on coated tablets, includes flavouring agent with a small amount of hydrophilic polymers used to fasten the flavoring on the surface coating of the tablets.

Two stage application cover sheet, do not change indicators solubility of the tablets in both cases the coating, with stage and without phase B, showed the same profile of solubility slow release, when the release of less than 40% after 2 hours, and in the quality assessment tool used test raspadaemost and a buffer with a pH of 6.8 as the environment. Then the tablets were Packed in blister aluminium/PVC/PE for best profile stability.

1. Oral pharmaceutical composition for the treatment of intestinal disorders, containing butyric acid or a salt thereof, in combination with at least one soluble or dispersible in water dietary fiber selected from inulin, maltodextrin, or a mixture thereof, at least one flavoring agent selected from vanillin, vanilla essence or mixtures thereof and one or more pharmacologically acceptable excipients, characterized in that it includes:
a) a matrix containing lipophilic compounds with melting point below 90°C, and amphiphilic matrix in which the active component at least partially is spherical;
b) am filou matrix;
c) an outer hydrophilic matrix in which is dispersed lipophilic matrix and amphiphilic matrix;
e) coating;
and the part of the said at least one flavoring agent dispersed in one or more of the following matrices and part of the flavoring agent dispersed in the specified coverage.

2. Oral pharmaceutical composition for the prevention or treatment of neoplasms, containing butyric acid or a salt thereof, in combination with at least one soluble or dispersible in water dietary fiber selected from inulin, maltodextrin, or a mixture thereof, at least one flavoring agent selected from vanillin, vanilla essence or mixtures thereof and one or more pharmacologically acceptable excipients, characterized in that it includes:
a) a matrix containing lipophilic compounds with melting point below 90°C, and amphiphilic matrix in which the active component at least partially is spherical;
b) an amphiphilic matrix;
c) an outer hydrophilic matrix in which is dispersed lipophilic matrix and amphiphilic matrix;
e) coating;
and the part of the said at least one flavoring agent dispersed in one or more of the following matrices and part of the flavoring agent dispersed in the specified coverage.

3. Peror is supplemented flax pharmaceutical composition according to claim 1, where intestinal disorders include inflammatory diseases or disorders of the bowel, irritable bowel syndrome, actinic colitis, dysbacteriosis after taking antibiotics and dysmetabolism, acute and chronic diarrheal disorders and pathological conditions of the mucous membrane of the intestine.

4. The composition according to claim 1 or 2, additionally including other fillers.

5. The composition according to claim 1 or 2, in which salts of butyric acid selected from calcium butyrate, butyrate sodium or magnesium butyrate.

6. The composition according to claim 1 or 2, in which butyric acid is contained in an amount of 5 to 60 wt.%, preferably from 10 to 50% wt. of the total weight of the composition.

7. The composition according to claim 1 or 2, which is soluble or dispersible in water dietary fiber is contained in an amount of 5 to 50 wt.%, preferably from 10 to 30% wt. of the total weight of the composition.

8. The composition according to claim 1 or 2, in which the flavouring agent is contained in an amount of from 0.001% to 5% wt., preferably from 0.01 to 3 wt.%. of the total weight of the composition.

9. The composition according to claim 1 or 2 in the form of tablets, capsules, granules or microgranules.

10. The composition according to claim 1 or 2, where the said coating is selected from coatings with controlled release coatings, sustained release coatings with modified-release coating, taste masking and/or gelado the but-resistant coating.

11. The composition according to claim 1 or 2, characterized in that it is a composition with controlled release, delayed release, modified release, taste masking and/or is a gastro-resistant.

12. The use of oral pharmaceutical composition according to claims 1 and 3-11 for the treatment of intestinal disorders, inflammatory diseases or disorders of the bowel, irritable bowel syndrome, actinic colitis, dysbacteriosis after taking antibiotics and dysmetabolism, for the treatment of acute and chronic diarrheal disorders and pathological conditions of the mucous membrane of the intestine.

13. The use of oral pharmaceutical composition according to claim 2 or 4-11, to prevent or treat intestinal novoobrazovanii.

14. Food composition containing butyric acid or a salt thereof, in combination with at least one soluble or dispersible in water dietary fiber selected from inulin, maltodextrin, or a mixture thereof, at least one flavoring agent selected from vanillin, vanilla essence or mixtures thereof and one or more pharmacologically acceptable excipients, characterized in that it includes:
a) a matrix containing lipophilic compounds with melting point below 90°C, and amphiphilic matrix in which the active component is at least partially JW is aetsa spherical;
b) an amphiphilic matrix;
c) an outer hydrophilic matrix in which is dispersed lipophilic matrix and amphiphilic matrix;
e) coating;
and the part of the said at least one flavoring agent dispersed in one or more of said matrices, and a part of the flavoring agent dispersed in the specified coverage.

15. The food composition according to 14, further including other fillers.

16. The food composition according to 14, in which the salt of butyric acid selected from calcium butyrate, butyrate sodium or magnesium butyrate.

17. The food composition according to 14, in which butyric acid is contained in an amount of 5 to 60 wt.%, preferably from 10 to 50% wt. of the total weight of the composition.

18. Food composition 14, which is soluble or dispersible in water dietary fiber is contained in an amount of 5 to 50 wt.%, preferably from 10 to 30% wt. of the total weight of the composition.

19. The food composition according to 14, in which the flavouring agent is contained in an amount of from 0.001% to 5% wt., preferably from 0.01 to 3 wt.%. of the total weight of the composition.

20. The food composition according to claim 19 in the form of tablets, capsules, granules or microgranules.

21. The food composition according to 14, where the said coating is selected from coatings with controlled release coating with a slow release, cover with Modific is included in the release, coating, taste masking and/or gastro-resistant coating.

22. The food composition according to 14, characterized in that it is a composition with controlled release, delayed release, modified release, taste masking and/or is a gastro-resistant.



 

Same patents:

FIELD: medicine.

SUBSTANCE: compounds are administered intraperitoneally, intravenously or orally in a dose of 0.5-90 mg/kg, particularly in a dose of 1-3 mg/kg 10-120 minutes before simulating a stress situation, particularly 30 minutes before simulating the stress situation that enables decreasing a damage area of the gastric mucosa by 1.5-5 times as compared to a reference group exposed to stress and taking no declared compounds. For the therapeutic purposes, these compounds are administered intraperitoneally, intravenously or orally in a dose of 0.5-90 mg/kg a day, particularly in a dose of 1 mg/kg a day for three days after the stress-induced damage of the gastric mucosa that enables decreasing the damage area of the gastric mucosa by 2.5-5 times as compared to the reference group exposed to stress and taking no declared compounds. The invention can be used for preventing and treating the stress-induced gastric ulcer.

EFFECT: decreased area of the stress-induced ulceration.

5 cl, 8 dwg, 11 ex

FIELD: medicine.

SUBSTANCE: 2-hydroxyphenylthioacetamide derivatives are used. The prophylactic effect is ensured by intragastric, intravenous or oral administration of the compound 0.5-90 mg/kg 10-120 min before taking an ethanol liquid. The therapeutic effect is ensured by intragastric, intravenous or oral administration of the compound 0.5-90 mg/kg a day for three days after a gastric mucosal injury caused by taking the ethanol liquid.

EFFECT: reducing gastric ulceration area caused by oral administration of ethanol liquids.

5 cl, 6 dwg, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the pharmaceutical industry, in particular to a peroral pharmaceutical composition, which contains polysaccharides from platyclades of Opuntia Ficus Indica, an extract of Olea Europeae leaves, alginate and sodium bicarbonate in a specified ratio. Components of the composition described above act with respect to reduction of gastroesophageal reflux.

EFFECT: peroral pharmaceutical composition is intended for the prevention and treatment of gastroesophageal reflux and GERD.

4 cl, 9 tbl, 6 dwg

FIELD: medicine.

SUBSTANCE: group of inventions relates to medicine and can be used for treatment of Crohn's disease, ulcerous colitis and type 1 diabetes mellitus. For this purpose applied is APL peptide or its analogues, obtained from a human heat shock protein with a size of 60 kDa (hps60) in order to obtain a pharmaceutical composition. Also claimed are the pharmaceutical composition and the application of a medication for induction of apoptosis of pathogenic clones of T-cells in patients with inflammatory intestinal disease or type 1 diabetes.

EFFECT: group of inventions possesses an immunomodulating action and makes it possible to regulate mechanisms of the peripheral tolerance in gastrointestinal tract.

10 cl, 6 dwg, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the pharmaceutical industry, namely an agent having pro-kinetic and antidyspeptic activity. A composition possessing pro-kinetic and antidyspeptic activity containing: a lipophilic extract of Zingiber officinale prepared by extraction of roots and rhizomes in carbon dioxide under the supercritical conditions, and an extract of Cynara scolymus prepared by extraction of elevated parts of the plant in alcohol and aqueous-alcohol solution, and resin fractionation, taken in certain proportions. Using the lipophilic extract of Zingiber officinale and the extract of Cynara scolymus for preparing the composition possessing pro-kinetic and antidyspeptic activity. Using the lipophilic extract of Zingiber officinale and the extract of Cynara scolymus for preparing the composition for preventing and treating somnolence following meals.

EFFECT: compositions possess pro-kinetic and antidyspeptic activity and are used for preventing and treating somnolence following meals.

7 cl, 3 ex

FIELD: medicine.

SUBSTANCE: what is performed is an endoscopic approach; further, biopsy forceps with a rolled complex bioplastic material cut in size of an ulcerous defect are introduced into a working path of a fibrogastroduodenoscope, laid on the ulcerous defect with the use of the biopsy forceps, and controlled with the use of an endoscopic examination 5-7 days later. The bioplastic material contains hyaluronic acid, a phosphate buffer system, omeprazole and clarithromycin taken in a certain equivalence ratio.

EFFECT: non-invasive treatment of ulcer and reduced length of mucosal tissue regeneration.

1 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: 1 glass of an aqueous infusion of swallowwort herb or garden sage herb is orally administered daily on an empty stomach in the morning 1-2 hours before meals for 10 days. That is followed by administering an aqueous infusion of camomile blossom daily on an empty stomach for 10 days also. For the further 10 days, an aqueous infusion of plantain leaves is administered daily on an empty stomach; the infusions of chamomile blossom and plantain leaves are taken in a dose of 1/2 glass 3-5 times a day 30 minutes before meals. Administering the aqueous infusions is combined with orally daily administering an infusion of Saint-John's-wort for 30 days orally in a dose of 50 drops per 1/2 glass of water 3 times a day 30 minutes before meals. After that, the liquid biocomplex Normoflorin is orally administered 3 times a day daily for 4 weeks 30 minutes before meals in age doses. Normoflorin L is used for the first and second administration, and Normoflorin B - for the third one.

EFFECT: effective treatment ensured by Helicobacter pylori growth inhibition, antiseptic, anti-inflammatory herb action improving gastric mucosa trophism in a combination with the positive effect on the nervous system.

1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to granules as a laxative, containing particles of magnesium oxide of formula Mg2+1-xZn2+x)O (1) with the average diameter of secondary particles 0.1-25 mcm and apparent specific volume 3-20 ml/g. In formula (1) X represents number from 0 to 0.02, content of magnesium oxide particles constitutes from 80 to 95 wt %. Granules also include mannitol and carmellose and have the average particle diameter 0.2-0.4 mm and bulk density 0.4-0.7 g/ml. Content of particles in granules, which have particle diameter from less than 500 mcm to not less than 355 mcm, constitutes from 30 to 45 wt %, content of particles, which have particle diameter from less than 355 mcm to not less than 180 mcm constitutes from 40 to 50 wt %, content of particles, which have particle diameter from less than 180 mcm to not less than 150 mcm, constitutes from 10 to 28 wt %.

EFFECT: granules of magnesium oxide possess good solubility, attractive taste and outlook and do not leave sense of roughness in the oral cavity.

4 cl, 7 tbl, 2 dwg, 7 ex

FIELD: medicine.

SUBSTANCE: group of inventions refers to compositions and methods of treating colitis and other inflammatory intestinal diseases. There are presented: using the compound of the formula (1) or a salt thereof for preparing a drug preparation for treating an inflammatory disease of intestinal epithelial tissue (particularly, indeterminate colitis, Crohn's disease, irritable colon syndrome and ischemic colitis) and a pharmaceutical composition for the same application. What is presented is the pharmaceutical composition for treating colitis containing the compounds of the formula (1) or the salt thereof.

EFFECT: achieving the declared application: what is shown is treating colitis and colon cancer.

35 cl, 3 dwg, 9 tbl

FIELD: medicine.

SUBSTANCE: human recombinant interferon alpha-2b is orally administered into a patient's body as an ingredient of an anti-acid protective medium in a dose of 500 thousand IU twice a day for at least 7 days. The length of the therapeutic course is no more than 14 days. As human recombinant interferon alpha-2b, the preparation contains Reaferon-EC or Reaferon-EC-Lipint; as the anti-acid protective medium, the preparation contains aluminium hydroxide and magnesium hydroxide in the following quantitative ratio: aluminium hydroxide - 25-35 mg/ml; magnesium hydroxide - 15-30 mg/ml; human recombinant interferon alpha-2b - 0.35·105-5·105 IU/ml.

EFFECT: using the given method enables providing higher clinical effectiveness in gastric or duodenal ulcer in a combination with reducing the content of human recombinant interferon alpha-2b in 4 times in a single dose, and in 2 times in a daily dose that is ensured by the preparation delivery directly into the ulcer.

3 cl, 1 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: what is presented is a group of inventions involving a pharmaceutical composition, a method of preparing it, a method of treating Parkinson's disease and a method of reducing a 'wear' effect in the given patients by administering the same. The pharmaceutical composition in the form of a single oral dose for treating Parkinson's disease consists of a mixture of a) Levodopa or its salt in an amount of 50 mg to 300 mg in the form of prolonged release, b) Carbidopa or its salt in an amount of 10 mg to 100 mg in the form of prolonged release, wherein the prolonged release is ensured by coating or mixing Levodopa and Carbidopa with one or more rate control polymers, and c) Entacapone or its salt in an amount of 100 mg to 1000 mg in the form of prolonged release, optionally with other pharmaceutically acceptable excipients.

EFFECT: group of inventions promotes patient's treatment compliance; using it leads to a stable blood content of active antigens and to reducing administration rate that provides reducing the 'wear' effect in the patients with Parkinson's disease; besides, the additional technical effect ensured by the composition consists in its stability at high temperature and humidity.

9 cl, 15 tbl

FIELD: medicine.

SUBSTANCE: invention refers to using a polyurethane polymer as a drug delivery system to provide the biologically active risperidone delivery at a constant speed for a relatively long period of time, as well as to methods for using it.

EFFECT: system provides high biological compatibility and biological stability and is applicable as an implant in patients (humans and animals) for the risperidone delivery to tissues and organs.

25 cl, 13 dwg, 3 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: group concerns a prolonged delivery of a compstatin analogue, as well as an optional additional active agent when released from a microscopic gel-like inclusion formed if a liquid composition containing the compstatin analogue is introduced into an extravascular space, such as a vitreous chamber of eye in a mammalian body. The invention also refers to a method of treating an individual suffering age-related macular degeneration (ARMD).

EFFECT: improving the compstatin delivery system for the complement system inhibition required for treating ARMD.

58 cl, 4 ex, 6 tbl, 5 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical compositions containing (2-hydroxyethoxy)amide 6-(4-brom-2-chlorophenylamino)-7-fluor-3-methyl-3H-benzoimidazole-5-carboxylic acid hydrosulphate and solvates, crystalline forms and amorphous forms thereof, to using the above compositions as a drug; and to methods for preparing the above compositions.

EFFECT: preparing the new pharmaceutical compositions.

20 cl, 7 tbl, 7 ex, 5 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a pharmaceutical composition for outpatient treatment and prevention of the cardiovascular diseases, containing therapeutic amounts of a vasodilator, a renin-angiotensin system inhibitor, a thrombocyte aggregation inhibitor, a cholesterol-lowering agent, and an antihypoxic agent. As a vasodilator, the declared composition contains an agent possessing α-adrenergic receptor antagonist action, and a thrombocyte aggregation inhibitor is presented by an ADP-dependent thrombocyte activation mechanism blocking agent.

EFFECT: invention provides the integrated therapeutic effect on the cardiovascular system after acute administration that improves the compliance with treatment regimen by the patient.

20 cl, 1 tbl, 15 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: microparticle contains an agglomerate of particles containing a hydrophilic active substance, wherein the particle contains an amphiphilic polymer composed of a hydrophobic segment of polyhydroxy acid and a hydrophilic segment of polysaccharide or polyethylene glycol, and a hydrophilic active substance. What is also disclosed is a method of producing the agglomerated microparticles, which involves (a) a stage of preparing a reverse phase emulsion, (b) a stage of preparing a solid residue containing the hydrophilic active substance, and (c) a stage of introducing the solid residue into a liquid phase containing a surface modifier.

EFFECT: agglomerated microparticles provide the effective encapsulation of the hydrophilic active substance and the release of the hydrophilic active substance at an appropriate speed.

14 cl, 22 dwg, 4 tbl, 31 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and represents gel-forming mixed dextran esters containing phosphate and carbamate groups of general formula: {C6H7O2(OH)3-x-y{[(OP(O)ONa)mONa)]xl[(O2P(O)ONa)k]x2}x(OCONH2)y}n, wherein x=x1+x2 is a degree of substitution in phosphate groups (mono- and diesters), x=0.47-1.09; X1 is a degree of substitution in monoesters, X1=0.01-0.48; m is a number of phosphates in monoesters, m=1-2; x2 is a degree of substitution in diesters, x2=0.01-1.09; k is a number of phosphates in diesters, k=1-2; y is a degree of substitution in carbamate groups, y=0.39-1.23; n is a degree of polymerisation, 20≥n≤1000.

EFFECT: invention provides producing low-toxic low- and high-substituted dextran phosphates in the form of hydrogels containing additionally carbamate groups and possessing antiproliferative activity with respect to cancer cells.

2 cl, 3 dwg, 14 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of pharmacy and represents microsphere with controlled release, which has covering layer and contains core, which contains exendin as active ingredient and biodegradable polymer, and covering layer, which covers core with covering material, exendin being exendin-4 (SEQ ID NO:2), biodegradable polymer represents polymer, selected from group, consisting of polylactide (PLA), polyglycolide (PGA), lactide and glycolide copolymer (PLGA), polyorthoester, polyanhydride, polyhydroxybutyric acid, polycaprolactone and polyalkylcarbonate; copolymer or simple mixture of two or more polymers, selected from said group of polymers; copolymer of said polymer and polyethylene glycol (PEG); or polymer-sugar complex, in which sugar is bound with said polymer or said copolymer, covering material is selected from group, consisting of essential amino acids, polypeptides and organic nitrogenous compounds, essential amino acid being one or more, selected from group, consisting of arginine, lysine and histidine; polypeptide represents L-Lys-L-Thr-L-Thr-L-Lys-L-Ser; and organic nitrogenous compound is selected from group, consisting of creatine, creatinine and urea, content of covering layer constitutes from 0.01 to 5 wt fractions in terms per 100 wt fractions of microsphere.

EFFECT: invention ensures increase of bioaccessability and reduction of initial peak of exendin for prevention of such side effects as vomiting, nausea, headache.

10 cl, 7 ex, 5 tbl, 7 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: dosage form contains oxycodone hydrochloride as a physiologically active substance (A), optionally one or more physiologically combined excipients (B), a synthetic or natural polymer (C) and optionally natural, semisynthetic or synthetic wax (D).

EFFECT: dosage form of oxycodone hydrochloride possess degradation resistance of at least 400 N to less than 500 N, and releases max 99% of oxycodone hydrochloride in the physiological conditions after 5 h.

14 cl, 7 dwg, 17 ex

FIELD: medicine.

SUBSTANCE: declared invention refers to medicine. What is declared is a delayed release complex pharmaceutical composition containing a delayed release part and an immediate release part. The delayed release part contains AII-receptor blocker as an 'active ingredient'. The immediate release part contains HMG-CoA reductase inhibitor as an active ingredient.

EFFECT: declared composition is effective for treating hypertension and preventing complications in the patients suffering metabolic syndromes, such as diabetes, obesity, hyperlipidemia, coronary vessel disease, etc.

10 dwg, 13 bl, 8 ex

FIELD: medicine.

SUBSTANCE: group of inventions refers to a metadoxin composition and to a drug delivery device with the above composition. The composition for oral administration and release of metadoxin for at least 8 hours contains a portion of metadoxin in the formulation for prolonged release and a portion of metadoxin in the formulation for immediate release; the total amount of metadoxin makes 10-3,000 mg, and a proportion of metadoxin for prolonged release is related to metadoxin for immediate release as 60:40 to 80:20. The composition provides an optimum pharmacokinetic profile with a short period of time to reach the maximum concentration and a stable half-elimination period.

EFFECT: method provides improving cognitive functions in individuals suffering from attention deficit/hyperactivity disorder in as little as 90 min after intake of the composition.

8 cl, 4 dwg

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