Pharmaceutical composition containing aleglitezar

FIELD: medicine, pharmaceutics.

SUBSTANCE: pharmaceutical composition contains aleglitezar or its sodium salt in a dose of 0.01 to 0.9 mg.

EFFECT: pharmaceutical composition of aleglitezar is used for treating or preventing type II diabetes mellitus or cardiovascular diseases.

32 cl, 3 ex

 

The present invention relates to pharmaceutical compositions and especially to pharmaceutical compositions containing aleglitazar or its salt. More specifically, the invention relates to pharmaceutical compositions containing aleglitazar or its salt in an amount of from 0.01 to 0.9 mg, which can be obtained by

(a) spraying a solution containing aleglitazar or its salt, a solvent, and baking powder;

(b) mixing the composition obtained in stage (a), with sizing; and

(C) optionally compacting the composition obtained in stage (b).

The invention relates also to a method for preparing the pharmaceutical compositions, namely, that:

(a) spraying a solution containing aleglitazar or its salt,

thinner and baking powder;

(b) mixing the composition obtained in stage (a), with sizing;

and

(C) optionally pressed composition obtained in stage (b).

Aleglitazar is a (8)-2-methoxy-3-{4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]benzo[b]thiophene-7-yl}propionic acid. He belongs to the class of agonists activating peroxisome proliferation receptor (PPAR). Aleglitazar described in WO 02/092084. The sodium salt of aleglitazar is a (5)-2-methoxy-3-{4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]benzo[b]thiophene-7-yl}propanoate sodium.

Activating PR is literaly peroxisome receptors are members of the superfamily of nuclear hormone receptors, which are activated by ligands, transcription factors that regulate gene expression. Identified and cloned their various subtypes. These include PPARα, PPARβ (also known as PPARδ and PPARγ. There are at least two major isoforms of PPARγ. While PPARγ1 is expressed ubiquitously in most types of fabrics, longer PPARγ2 isoform is present almost exclusively in adipocytes. In contrast, the expression of PPARα is predominantly in the liver, kidneys and heart. Different PPAR isoforms modulate a variety of responses of the body, including glucose and lipid homeostasis, cell differentiation, inflammatory responses and cardiovascular status.

The results showed that if the joints have magonista against PPARα and PPARγ, it enhances their therapeutic potential, namely, they allow to improve the lipid profile on the background normalization of glucose levels and insulin (Keller and Wahli: Trends Endocrin. Metab., 4, 1993,. 291-296, Macdonald and Lane: Current Biology, volume 5, 199, 5 cc. 618-621).

Aleglitazar has the ability to simultaneously and with high efficiency to contact and activate both PPARα and PPARγ. So aleglitazar allows you to combine antiglycemic action, caused by the activation of PPARγ, with antidyslipidemic action, also decided the slow activation of PPARα. This leads to reduced levels of glucose and insulin in plasma (= sensitization to insulin), lower levels of triglycerides and higher levels of HDL-cholesterol (= improvement of lipid profile). In addition, it lowers LDL cholesterol, lowers blood pressure and prevents the development of inflammatory atherosclerosis. Since many aspects of the syndrome of diabetes type II is associated with coagonist PPARα and PPARγ, aleglitazar has a higher therapeutic potential in comparison with the already known in this field connections.

When creating the present invention unexpectedly found that for the treatment or prevention of type II diabetes is the most effective pharmaceutical composition comprising aleglitazar in a dose of from 0.01 to 0.9 mg due to the extremely low solubility and high activity aleglitazar never been able to successfully incorporate homogeneous low dose preparative solid forms suitable for industrial production and sales.

In the context of the present description the term "diluent" refers to excipient, which complement the amount of tablets or capsules to the appropriate value, which is practical from the point of view of manufacture and convenient to use by the consumer. Suitable diluents include, for example, in pharmaceutical preparations is automatic acceptable inert fillers, such as microcrystalline cellulose, lactose, secondary acidic calcium phosphate, sugar, sugar alcohols, corn starch, sucrose, silicon dioxide, polysaccharides, N-organic (Pharmasolve (ISP company) and mixtures thereof. The concept of "sugar" and "sugar alcohols include mannitol, lactose, fructose, sorbitol, xylitol, maltodextrin, dextrans, dextrins, lactic and mixtures thereof.

To improve the cohesive ability of powders to preparative forms as tablets add the binder, thereby providing a grip that is required for the formation of granules, after which seals form a compact mass in the form of tablets. Suitable examples of binders include methylcellulose, carboxymethylcellulose, hydroxypropylcellulose, hydroxymethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, starch and pre-generowanie starch. For the preparation of the preparative form you can apply a mixture of two, three or more binders.

Containing aleglitazar solution can be an aqueous or organic solution. The preferred organic solvent is ethanol.

Buffer solutions are used as a means of maintaining the pH value approximately at a constant level. The buffer solution is typically an aqueous solution, Ostoji of a mixture of weak acid and conjugate acid-base or weak base and acid, paired with the base. It has the property that the pH value of the solution undergoes very little change, if added in a small amount of acid or base. Examples of buffers include: a buffer containing acetic acid/sodium acetate buffer containing monopotassium phosphate potassium or sodium/secondary acid phosphate potassium or sodium, the buffer containing boric acid/sodium hydroxide, Tris(Tris(hydroxymethyl)aminomethan)-buffer buffer containing the carbonate/bicarbonate and etc.

Containing aleglitazar solution is preferably a buffered aqueous solution, preferably buffered phosphate buffer. Phosphate buffer is preferably a buffer that contains the secondary acid sodium phosphate and monopotassium phosphate.

The term "surfactant" refers to excipient, which reduces the surface tension of the liquid. Examples of surfactants are tween 80, a copolymer of polyoxyethylene-polyoxypropylene and sodium lauryl sulfate.

The term "powder" refers to excipient, which has the ability to grow and dissolve when wet, which leads to the destruction of the tablets in the digestive tract, resulting in the release day is adequate substance and its absorption. To fit the leavening agents include, for example, weakly crosslinked polyvinylpyrrolidone, corn starch, potato starch, corn starch and modified starches, croscarmellose sodium, calcium carboxymethyl cellulose, sodium carboxymethyl cellulose, crosspovidone, nitroglycol starch and mixtures thereof.

Suitable sizing, which include agents that affect the fluidity of the powder by reducing friction and adhesion between particles, designed for crushing, are colloidal silicon dioxide, such as Aerosil, talc, stearic acid, magnesium stearate, calcium stearate, beginat of glyceryl, fumarate, sodium and silica gel.

The concept of "material for coating" refers to excipient, which is applied to the surface of the tablet and which protects the ingredients in the tablet from damage under the influence of moisture contained in the air, or facilitates the swallowing of tablets, which has an unpleasant taste. Examples of substances used for coating are PVA (polyvinyl alcohol), HPMC (hypromellose) and PEG (polyethylene glycol).

The concept of "aleglitazar or its salt" refers to aleglitazar or the product of the interaction of aleglitazar to the base, which results in the substitution of a hydrogen atom of the carboxylic group keys is the notes in aleglitazar on the metal atom. The preferred salt of aleglitazar is the sodium salt of aleglitazar.

Unless otherwise stated, all percentages are wt.% in terms of the total weight of the composition.

When you specify the mass range of aleglitazar or its salt is assumed that the mass represents the mass of aleglitazar in the form. the free acid, or, if it is used in salt form, the mass is the mass of a mass corresponding to the same number of moles of aleglitazar in the form of the free acid.

The number of aleglitazar or its salts is present in the pharmaceutical composition, or used in the method is preferably from 0.01 to 0.9 mg, preferably from 0.01 to 0.6 mg, more preferably from 0.15 to 0.6 mg Other preferred amounts of aleglitazar are 0.15 or 0.3 mg

Preferred/preferred is a pharmaceutical composition or method where the solution containing aleglitazar or its salt used in stage (a) is an aqueous solution.

In addition, preferred/preferred is a pharmaceutical composition or method where the solution containing aleglitazar or its salt used in stage (a) is an organic solution, preferably ethanol rest the R.

Preferred/preferred is a pharmaceutical composition or method offered/proposed invention where the fluid used in stage (a) is an aqueous solution, preferably buffered phosphate buffer. The buffer is preferably selected from the above buffers, more preferably it contains secondary acidic sodium phosphate and monopotassium phosphate.

When the buffer is Na2HPO4and NaH2PO4then both molarity of the buffer system is preferably from 0.05 to 0.4 mm, preferably from 0.1 to 0.2 mm. PH buffered solution is preferably from 6.0 to 12.

In addition, preferred/preferred is a pharmaceutical composition or method offered/proposed invention where the diluent is chosen from sugars, microcrystalline cellulose, lactose, starch and mixtures thereof, and preferably it is a mixture of lactose and microcrystalline cellulose.

Preferred/preferred is a pharmaceutical composition or method offered/proposed invention where an aqueous solution used in stage (a) contains a binder selected from povidone, HPMC and previously as the new starch.

The amount of binder is preferably from 1 to 15%, more preferably from 2 to 10%, even more preferably from 4 to 6% based on the total weight of the composition.

The binder preferably is a povidone. In addition, it is preferable to pre-generowanie starch.

Preferred/preferred is a pharmaceutical composition or method offered/proposed invention where an aqueous solution used in stage (a) contains a surfactant selected from tween 80, copolymer of polyoxyethylene and polyoxypropylene and lauryl sodium.

The amount of surfactants is preferably from 0.1 to 2%, more preferably from 0.25 to 1%, even more preferably from 0.4 to 0.6% based on the total weight of the composition.

Surfactant preferably is a sodium lauryl sulfate.

Baking powder is preferably selected from cross-linked polyvinylpyrrolidone, starch, croscarmellose sodium, sodium salt of carboxymethyl cellulose and matriptase starch.

The amount of baking powder is preferably from 0.5 to 15%, more preferably from 1 to 10%, even more preferably from 2 to 3% based on the total weight of the composition.

predpochtitelno baking powder represents croscarmellose sodium.

Preferred/preferred is a pharmaceutical composition or method offered/proposed invention where the lubricant is chosen from stearic acid, magnesium stearate, behenate of glyceryl and sodium fumarate.

The amount of the lubricant is preferably from 0.2 to 3%, more preferably from 0.5 to 1.0% based on the total weight of the composition.

Preferably the lubricant is a stearate.

Preferably the composition contains the sodium salt of aleglitazar.

Preferably the invention relates also to a pharmaceutical composition, which includes:

Aleglitazar or its sodium salt0.01 to 2%
Secondary acidic sodium phosphate0,5-1,5%
Monopotassium phosphate sodiumof 0.005 to 0.25%
Sodium lauryl sulfate0,1-2%
Povidone or GPMC1-15%
Lactose15-85%
Microcrystalline cellulose3-85%
Croscarmellose sodium0.5 to 15%
Magnesium stearate0.2 to 3%.

The invention preferably relates also to a pharmaceutical composition, which includes:

Aleglitazar or its sodium salt0.01 to 0.9 mg
Secondary acidic sodium phosphate1-1 .5 mg
Monopotassium phosphate sodium0.01 to 0.3 mg
Sodium lauryl sulfate0.1 to 2 mg
Povidone or GPMC0.1 to 20 mg
Lactose20-110 mg
Microcrystalline cellulose5-100 mg
Croscarmellose sodium0.5 to 20 mg
Magnesium stearate0.5 to 3 mg

Optionally, the pharmaceutical composition proposed in the present invention may contain one or more antioxidants to prevent, for example, or what about the oxidation of compounds representing a medicinal substance. Suitable for use according to the present invention antioxidants include, but are not limited to) bottled hydroxyanisole, sodium ascorbate, bottled hydroxytoluene, metabisulfite sodium, malic acid, citric acid, ascorbic acid and mixtures thereof. The preferred antioxidant is a mixture of bottled hydroxyanisole and bottled hydroxytoluene (in the ratio 1:1).

In addition, the invention relates also to a pharmaceutical composition, which includes:

Aleglitazar0.01 to 2%
Bottled hydroxyanisol0,01-0,5%
Bottled hydroxytrol0,01-0,5%
Sodium lauryl sulfate0,1-2%
Povidone1-15%
Lactose15-85%
Microcrystalline cellulose3-85%
Croscarmellose sodium0.5 to 15%
Magnesium stearate0.2 to 3%

The invention relates also to a pharmaceutical composition, which includes:

Aleglitazar0.01 to 0.9 mg
Bottled hydroxyanisol0.01 to 0.5 mg
Bottled hydroxytrol0.01 to 0.5 mg
Sodium lauryl sulfate0.1 to 2 mg
Povidone0.1 to 20 mg
Lactose20-110 mg
Microcrystalline cellulose5-100 mg
Croscarmellose sodium0.5 to 20 mg
Magnesium stearate0.5 to 3 mg

The above composition containing the antioxidant is preferred, if at the stage of (a) used ethanol solution.

The pharmaceutical composition proposed in the invention may be in the form of tablets or capsules, preferably in tablet form.

Preferably the weight of the tablet is between 50 to 250 mg, preference is sustained fashion from 60 to 200 mg, more preferably from 70 to 150 mg Most preferably the weight is 130 mg

In the pharmaceutical composition proposed in the invention can be coated using any material for coating, known in the field, preferably, for example, Opadry II White.

The invention relates also to the above-described pharmaceutical compositions intended for use as a medicine, preferably for use as a drug for treatment or prevention of type II diabetes or cardiovascular diseases.

In addition, the invention relates also to the application of the above pharmaceutical compositions for the treatment or prevention of type II diabetes or cardiovascular diseases.

In addition, the invention relates to a method for the treatment or prevention of type II diabetes or cardiovascular disease, namely, what does the introduction of the above pharmaceutical compositions to a patient in need of it.

Aleglitazar shown primarily to reduce mortality from cardiovascular causes non-fatal outcome of myocardial infarction or stroke, especially in patients with stable coronary syndrome cardiac arteries and diabetes type II.

The composition can be prepared according to the following procedure. Get a buffered solution containing water, aleglitazar, sautereau salt, binder and surfactant. Aleglitazar preferably present in an amount of from 0.2 to 0.8% (wt/about). The active substance is preferably completely dissolved in the liquid for granulation. In the granulator, fluidized bed type thinners and baking powder. The solution is evenly dispersed in the excipients, receiving granules with a very high degree of homogeneity of content, due to these low dose levels, and with the corresponding distribution of particle sizes (d 63,2 is preferably from 0.15 to 0.8 mm (the size of the openings through which 63.2% of granules)) in order to avoid possible significant dust formation and to achieve good flow characteristics. The pellets are preferably dried in a fluidized bed dryer. After this operation is preferably carried out screening of the resulting granules through a sieve of a certain number (with a certain size of the holes) to obtain granules, dried in the fluidized bed (FBG). The dried granules are preferably mixed with the lubricant and then pressed into tablets using conventional equipment for the por is Slovenia tablets. Tablets offered in the invention can have any desired shape, such as discoid, round, oval, elongated, cylindrical, triangular, hexagonal, etc., Drug load contained in the cores ranges from 0.01 to 0.3%, preferably from 0.05 to 0.15%. The hardness of the tablets should preferably be more than 60 N in order to ensure a good coating quality and good packing characteristics. The tablets should preferably have an oval shape to them it would be easy to swallow and can be easily accessed. It is established that all the tablets had a quick raspadaemost (less than 300, the water environment, standard method and equipment using baskets). On the compressed tablets may be coated film coating, which leads to the increase of mass by 4%.

The invention is illustrated in the following examples, without limiting its scope.

Examples

Example 1: the Pill

Aleglitazar or its sodium salt0.3 mg
Secondary acidic sodium phosphate1,106 mg
Monopotassium phosphate sodium0.037 mg
Sodium lauryl sulfate0.625 mg
GPMC6.25 mg
Lactose100,43 mg
Microcrystalline cellulose12.5 mg
Croscarmellose sodium2.5 mg
Magnesium stearate1.25 mg

Opadry II White 5,00 mg were Prepared buffered aqueous solution containing aleglitazar (0,3% (wt/V)), the secondary acid sodium phosphate, monopotassium phosphate, HPMC and sodium lauryl sulfate. The active substance is completely dissolved in the liquid for granulation. For complete dissolution of the necessary mixing. In the granulator, fluidized bed added lactose, microcrystalline cellulose and croscarmellose sodium. The solution is uniformly sprayed (spray rate of 180-220 g/min; the temperature of the inlet air from 60 to 80°C, air pressure from 2 bar to 4 bar, the product temperature from 22°C to 35°C) solid excipients to obtain granules. The obtained granules were characterized by a very high degree of uniformity of content, due to these low dose levels, and the appropriate distribution of the size of the s particles (d 63,2 was 250 mm), to avoid possible significant dust formation. In addition, the granules had a good flow characteristics. The pellets were dried in the fluidized bed dryer. Thereafter, the resulting granules were sieved through a sieve with a specific size holes (the size of the sieve mesh of 2 mm, a rotation speed of 1000 rpm) to obtain granules, dried in the fluidized bed (FBG). The dried granules were mixed with the lubricant and then compressed into tablets using conventional equipment for pressing tablets.

Example 2: Pill

Aleglitazar or its sodium salt0.3 mg
Secondary acidic sodium phosphate1,106 mg
Monopotassium phosphate sodium0.037 mg
Sodium lauryl sulfate0.625 mg
Povidone6.25 mg
Lactose100,43 mg
Microcrystalline cellulose12.5 mg
Croscarmellose sodium 2.5 mg
Magnesium stearate1.25 mg

Opadry II White 5,00 mg Repeated the procedure described in example 1, using povidone instead GPMC. The granules had a uniformity of content, size distribution and flow characteristics similar to the corresponding parameters of the granules obtained according to example 1. The dried granules were mixed with the lubricant and then compressed into tablets using conventional equipment for pressing tablets.

Example 3: Pill

Aleglitazar0.15 mg
Bottled hydroxyanisolof 0.0125 mg
Bottled hydroxytrolof 0.0125 mg
Sodium lauryl sulfate0.625 mg
Povidone6.25 mg
Lactoseof 101.7 mg
Microcrystalline cellulose12.5 mg
Croscarmellose sodium2.5 mg
Magnesium stearate/td> 1.25 mg
Opadry II White5,00 mg

Prepared ethanol solution containing aleglitazar, bottled hydroxyanisol, bottled hydroxytoluene, povidone and sodium lauryl sulfate. The active substance is completely dissolved in the liquid for granulation. In the granulator, fluidized bed added lactose, microcrystalline cellulose and croscarmellose sodium. The solution is uniformly sprayed (with a speed of from 200 to 400 g/min), solid excipients to obtain granules. The granules had a uniformity of content, size distribution and flow characteristics similar to the corresponding parameters of the granules obtained according to examples 1 and 2. The dried granules were mixed with the lubricant and then compressed into tablets using conventional equipment for pressing tablets.

1. The pharmaceutical composition containing aleglitazar or its salt in an amount of from 0.01 to 0.9 mg, which can be obtained by
(a) spraying a solution containing aleglitazar or its salt, a solvent, and baking powder;
(b) mixing the composition obtained in stage (a), with sizing; and
(C) optionally compacting the composition obtained in stage (b).

2. The pharmaceutical composition according to p. 1 in which the solution used in stage (a) is an aqueous solution.

3. The pharmaceutical composition under item 1, in which the solution used in stage (a) is a solution, buffered phosphate buffer.

4. The pharmaceutical composition under item 1, in which the diluent is chosen from sugars, microcrystalline cellulose, lactose, starch and mixtures thereof.

5. The pharmaceutical composition under item 1, in which the solution used in stage (a) contains a binder selected from povidone, HPMC and pre generowania starch.

6. The pharmaceutical composition under item 5, in which the binder is a povidone.

7. The pharmaceutical composition under item 1, in which the solution used in stage (a) contains a surfactant selected from tween 80, copolymer of polyoxyethylene and polyoxypropylene and lauryl sodium.

8. The pharmaceutical composition according to p. 7, in which the surfactant is a sodium lauryl sulfate.

9. The pharmaceutical composition under item 1, in which the baking powder selected from cross-linked polyvinylpyrrolidone, starch, croscarmellose sodium, sodium salt of carboxymethyl cellulose and matriptase starch.

10. The pharmaceutical composition according to p. 9, in which the baking powder is croscarmellose sodium.

1. The pharmaceutical composition under item 1, in which the lubricant is chosen from stearic acid, magnesium stearate, behenate of glyceryl and sodium fumarate.

12. The pharmaceutical composition under item 1, in which the lubricant is a stearate.

13. The pharmaceutical composition under item 1, which used the sodium salt of aleglitazar.

14. Pharmaceutical composition, which comprises:

Aleglitazar or its sodium salt0.01 to 0.9 mg
Secondary acidic sodium phosphate1-1 .5 mg
Monopotassium phosphate sodium0.01 to 0.3 mg
Sodium lauryl sulfate0.1 to 2 mg
Povidone0.1 to 20 mg
Lactose20-110 mg
Microcrystalline cellulose5-100 mg
Croscarmellose sodium0.5 to 20 mg
Magnesium stearate0.5 to 3 mg

15. The pharmaceutical composition under item 1 in the form of tablets.

p> 16. The pharmaceutical composition according to one of paragraphs.1-15 intended for use as a drug for treatment or prevention of type II diabetes or cardiovascular diseases.

17. Method of preparation of a pharmaceutical composition, which contains aleglitazar or its salt, which consists in the fact that:
(a) spraying a solution containing aleglitazar or its salt, a solvent, and baking powder;
(b) mixing the composition obtained in stage (a), with sizing; and
(C) optionally pressed composition obtained in stage (b).

18. The method according to p. 17, in which the solution used in stage (a) is an aqueous solution.

19. The method according to p. 17, in which the solution used in stage (a) is a solution, buffered phosphate buffer.

20. The method according to p. 17, in which the diluent is chosen from sugars, microcrystalline cellulose, lactose, starch and mixtures thereof.

21. The method according to p. 17, in which the solution used in stage (a) contains a binder selected from povidone, HPMC and pre generowania starch.

22. The method according to p. 17, in which the binder is a povidone.

23. The method according to p. 17, in which the solution used in stage (a) contains a surfactant selected from tween 80, copolymer of polyoxyethylene and is of oxypropylene and lauryl sodium.

24. The method according to p. 17, in which the surfactant is a sodium lauryl sulfate.

25. The method according to p. 17, in which the baking powder selected from cross-linked polyvinylpyrrolidone, starch, croscarmellose sodium, sodium salt of carboxymethyl cellulose and matriptase starch.

26. The method according to p. 17, in which the baking powder is croscarmellose sodium.

27. The method according to p. 17, in which the lubricant is chosen from stearic acid, magnesium stearate, behenate of glyceryl and sodium fumarate.

28. The method according to p. 17, in which the lubricant is a stearate.

29. The method according to p. 17, in which the composition is pressed into tablets.

30. The method according to p. 17 for use as a drug for treatment or prevention of type II diabetes or cardiovascular diseases.

31. The use of the pharmaceutical composition according to one of PP 1-16 for the treatment or prevention of type II diabetes or cardiovascular diseases.

32. Method for the treatment or prevention of type II diabetes or cardiovascular disease, which is administered pharmaceutical composition according to one of paragraphs.1-16 patient who needs it.



 

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14 cl, 21 dwg, 14 tbl, 24 ex

FIELD: medicine.

SUBSTANCE: on the first experimental day, cardiopathy is simulated by a single subcutaneous administration of equally portioned mixture of native egg albumin and Freund's complete adjuvant in rats. The mixture is administered at 0.2 ml of the mixture into 5 injection points: abdominally, into inguinal and axillary regions on the left and right. The cardiopathy is prevented by daily gastric administration of succinic acid 1.5 mmole/kg for 60 days through a probe.

EFFECT: higher clinical effectiveness.

2 dwg, 1 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the pharmaceutical industry and medicine. What is presented is using treo-3-phenylglutamic acid hydrochloride of the following structural formula: as an agent possessing the cardioprotective, antiplatelet, anticoagulant and membrane-protective properties under stress stimulation.

EFFECT: compound possesses the high cardioprotective, antiplatelet, anticoagulant and membrane-protective activity.

9 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutics and medicine, and concerns a pharmaceutical composition for intrajejunal administration for reducing an undesirable high serum glucose or reducing undesirable high peak serum insulin, which contains an active compound which is a representative of the calcitonin family, however is not amylin, and which is a modified representative of the calcitonin family, which has an amino acid homology of at least 75% with calcitonin, however not with amylin, and which is modified by adding, substituting or deleting amino acids and preserving an ability to bind and activate a calcitonin receptor, or a non-peptide low-molecular molecule of a calcitonin receptor agonist.

EFFECT: invention enables reducing the undesirable high serum glucose concentration.

9 cl, 12 dwg, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to phenol derivatives of formula (1), wherein R1 represents C1-C6 alkyl group, C1-C6 alkynyl group, C1-C6 halogen alkyl group, C1-C6 alkyl sulphanyl group or a halogen atom, R2 represents a cyano group or a halogen atom, R3 represents a hydrogen atom, and X represents -S(=O)2. Besides, the invention refers to a drug preparation containing a compound of formula (I) as an active ingredient.

EFFECT: phenol derivatives of formula (1) characterised by the high urine concentration of the permanent compound, and possess the uricosuric action.

11 cl, 1 dwg, 2 tbl, 42 ex

Amide derivative // 2536409

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) , where R1 is a hydrogen atom or a C1-C6-alkyl group, substituted with one or two substitutes selected from C1-C6-alkoxy group, hydroxyl group, which can be substituted with a C1-C6-alkylcarbonyl group (substituted with one or two substitutes γ), and a 4-6-member saturated monocyclic heterocyclic carbonyl group containing a N atom; γ is a hydroxyl group, amino group, di(C1-C6-alkyl)amino group and carbamoyl group; R2 is a H atom or a C1-C6alkyl group, which can be substituted with a hydroxyl group; or R1 and R2, together with the nitrogen atom with which they are bonded, can be combined to form an azetidine group, a pyrrolidine group or morpholine group, which can be substituted with one hydroxyl group or a hydroxy-C1-C6-alkyl group; R3 and R4 is a C1-C6-alkyl group; R5 is a halogen atom or a C1-C6-alkyl group; R6 is a halogen atom; m and n denote an integer from 0 to 1; V and W are CH; X, Y and Z each independently can be CH or N. The invention also relates to a pharmaceutical composition containing a compound of formula (I), use of the compound of formula (I) and a method of treating sugar diabetes a disease associated with diabetes.

EFFECT: compounds of formula (I), having hypoglycemic activity.

21 cl, 6 tbl, 72 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds of formula

,

where values A, R1-R6 are given in i.1 of the invention formula. Methods of obtaining the formula (I) compound are described.

EFFECT: compounds demonstrate an inhibiting activity of the cathepsin enzyme, which makes it possible to use them for the preparation of a pharmaceutical composition and for the preparation of a medication.

38 cl, 12 dwg, 495 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compositions of an antioxidant composition aimed at the suppression of oxidative stress in type 2 diabetes. The said compositions contain, counted per 1 dose: 50-120 mg of coenzyme Q10, 30-160 mg of dihydroquercetin, and 30-60 mg of A-lipoic acid or 50-100 mg of coenzyme Q10, 50-100 mg of dihydroquercetin, 30-60 mg of A-lipoic acid and 50-100 mg of nicotineamide.

EFFECT: compositions possess an antioxidant activity and prevent the development of the fatty tissue dysfunction.

2 cl, 1 dwg, 2 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: method involves administering insulin-producing cells in a dose of 500 thousand cells in a solution of isotropic gel 0.5 ml, 15% ascorbic acid 10 mcl and 0.1% hydrogen peroxide 10 mcl. The preparation is administered subcutaneously into theanterior abdominal wall in a projection of the pancreas.

EFFECT: method reduces the number of complications related to developing tissue incompatibility.

3 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to treating diabetes. That is ensured by the method for transdermal administration of insulin. The method involves placing a flat applicator pre-soaked in an insulin solution in the form of a porous titanium nickelide plate of the thickness of 0.2 to 1 mm on skin. The plate and skin are heated by an infrared light source, while a procedure length is specified within 30 to 120 minutes. A device used for implementing the method comprises a body with a power supply, a heating element and the flat applicator pre-saturated with insulin. The applicator represents the removable porous titanium nickelide plate of the thickness of 0.2 to 1 mm forming one of the body walls. The heating element is represented by the infrared light source in the form of a light-emitting diode set integrated into the body above the plate.

EFFECT: invention provides the more comfortable procedure by eliminating injuring factors, simplifying the power supply configuration, as well as making the applicator process more ordinary, including a possibility to implement the process in everyday life.

2 cl, 1 ex, 3 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new phenylamide or pyridylamide derivatives of formula

or their acceptable salts, wherein A1 is CR12 or N; A2 is CR13 or N; R1 and R2 are independently specified in hydrogen, C1-7-alkyl, halogen and C1-7-alkoxygroup; R12 and R13 are independently specified in hydrogen, C1-7-alkyl, halogen, C1-7-alkoxygroup, amino group and C1-7-alkylsulphanyl; R3 is specified in hydrogen, C1-7-alkyl, halogen, C1-7-alkoxygroup, cyano group, C3-7-cycloalkyl, five-merous heteroaryl and phenyl; R4 is specified in methyl and ethyl; or R3 and R4 together represent -X-(CR14R15)n- and form a part of the ring, wherein X is specified in -CR16R17-, O, S, C=O; R14 and R15 are independently specified in hydrogen or C1-7-alkyl; R16 and R17 are independently specified in hydrogen, C1-7-alkoxycarbonyl, heterocyclyl substituted by two groups specified in a halogen, or R16 and R17 together with an atom C, which they are attached to, form =CH2 group; or X is specified in a group NR18; R14 and R15 are hydrogen; R18 is specified in hydrogen, C1-7-alkyl, halogen-C1-7-alkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-7-alkyl, heterocyclyl, heteroaryl-C1-7-alkyl, carboxyl-C1-7-alkyl, C1-7-alkoxycarbonyl-C1-7-alkyl, C1-7-alkylcarbonyloxy-C1-7-alkyl, phenyl, wherein phenyl is unsubstituted, phenylcarbonyl, wherein phenyl is substituted by C1-7-alkoxycarbonyl, and phenylsulphonyl, wherein phenyl is substituted by carboxyl-C1-7-alkyl, or R18 and R14 together represent -(CH2)3- and form a part of the ring, or R18 together with R14 and R15 represent -CH=CH-CH= and form a part of the ring; and n has the value of 1, 2 or 3; B1 represents N or CR19 and B2 represents N or CR20, provided no more than one of B1 and B2 represents N; and R19 and R20 are independently specified in a group consisting of hydrogen and halogen-C1-7-alkyl; R5 and R6 are independently specified in a group consisting of hydrogen, halogen and cyano group; and one-three, provided R4 represents methyl or ethyl, two of the residues R7, R8, R9, R10 and R11 are specified in C1-7-alkyl, halogen, halogen-C1-7-alkyl, halogen-C1-7-alkoxygroup, cyano group, C1-7-alkoxycarbonyl, hydroxy-C3-7-alkynyl, carboxyl-C1-7-alkyl, carboxyl-C2-7-alkenyl, C1-7-alkoxycarbonyl-C2-7-alkenyl, C1-7-alkoxycarbonyl-C2-7-alkynyl, C1-7-alkoxycarbonyl-C1-7-alkylaminocarbonyl, carboxyl-C1-7-alkylaminocarbonyl-C1-7-alkyl, carboxyl-C1-7-alkyl-(C1-7-alkylamino)-carbonyl-C1-7-alkyl, phenyl-carbonyl, wherein phenyl is unsubstituted, phenyl-C1-7-alkyl, wherein phenyl is substituted by 1-2 groups specified in a halogen, C1-7-alkoxygroup, carboxyl, phenyl-C2-7-alkynyl, wherein phenyl is substituted by 2 groups specified in halogen, carboxyl or C1-7-alkoxycarbonyl, and pyrrolidine carbonyl-C1-7-alkyl, wherein pyrrolidinyl is substituted by carboxyl, and the other R7, R8, R9, R10 and R11 represent hydrogen; the term 'heteroaryl' means an aromatic 5-merous ring containing one or two atoms specified in nitrogen or oxygen; the term 'heterocyclyl' means a saturated 4-merous ring, which can contain one atom specified in nitrogen or oxygen. Besides, the invention refers to a pharmaceutical composition based on the compound of formula I.

EFFECT: there are prepared new compounds possessing the GPBAR1 agonist activity.

21 cl, 1 tbl, 190 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to immunology and biotechnology. There are presented variants of antagonist antibodies binding to the interleukin-7 receptor (IL-7R). There are described: variants of nucleic acids coding the antibodies; a host cell recombinant producing the antibody; a pharmaceutical composition inhibiting the human IL-7R function, and methods of treating and/or preventing: an autoimmune disease specified in the group of type 1 diabetes, lupus, multiple sclerosis, rheumatoid arthritis; type 2 diabetes or graft-versus-host disease based on using the antibody.

EFFECT: invention provides the antagonist anti-IL-7R antibodies that can find application in medicine.

17 cl, 15 dwg, 8 tbl, 13 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a pharmaceutical composition for treating type 2 diabetes, which contains (R)-7-[3-amino-4-(2,4,5-trifluorophenyl)-butyryl]-3-trifluoromethyl-,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carboxylic acid methyl ester or its pharmaceutically acceptable salt, metformin or its salt, and additive agents. Also, the invention refers to a method of treating type 2 diabetes involving administering the above pharmaceutical composition.

EFFECT: invention possesses the high efficacy of treating type 2 diabetes and lower toxicity than the known analogues.

21 cl, 8 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention represents pharmaceutical composition for correction and therapy of manifestations of amyloid intoxication in patients with brain pathologies, which are characterised by the fact that it contains melatonin 3-10 mg and memantine 5-300 mg.

EFFECT: effective treatment of patients, including cases of moderate cognitive disorders.

4 cl, 2 ex, 6 tbl, 7 dwg

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