Composition with modified release, containing1-[(3-hydroxyadamant-1-ylamino)acetyl]pyrrolidin-2(s)-carbonitryl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to pharmaceutical composition for obtaining tablets, which includes in one standard form, for instance, in one tablet, the following ingredients: (a) active ingredient, such as (S)-1-[(3-hydroxy-1-adamantyl)amino]acetyl-2-cyano-pyrrolidin (vildagliptin), or its pharmaceutically acceptable salt, (b) hydroxypropylmethylcellulose, whose apparent viscosity in 1% solution constitutes from 80000 cP to 120000 cP (nominal value 100000 cP), (c) microcrystalline cellulose and (d) magnesium stearate.

EFFECT: composition possesses high stability and efficiency.

35 cl, 42 tbl, 26 dwg

 

The text descriptions are given in facsimile form.

1. Pharmaceutical composition to obtain tablets, including one standard dosage form such as tablet the following ingredients:
(a) the compound as an active ingredient, where the compound is an (S)-1-[(3-hydroxy-1-substituted)amino]acetyl-2-cyano-pyrrolidin (vildagliptin) or any of its salts in an appropriate amount,
(b) hypromellose, apparent viscosity which ranges from about 80,000 to 120,000 CP (nominal value of 100,000 CP) in 1%solution,
and optionally a filler and/or samliv the tel.

2. Pharmaceutical composition to obtain a tablet according to claim 1, in which the standard form of drug mass ratio vildagliptin or any of its respective salts to the hypromellose is from 0.16 to 2.5, preferably from 0.3 to 1.16 or from 0.4 to 1.

3. Pharmaceutical composition to obtain a tablet according to claim 1 or 2, including
(c) 15-55 wt.%, preferably 25-45 wt.% calculated on the dry weight of the pharmaceutically acceptable filler and optional
(d) 0.1 to 10 wt.%, preferably 0.1 to 3 wt.% calculated on the dry weight of the pharmaceutically acceptable lubricant.

4. Pharmaceutical composition to obtain a tablet according to one of claims 1 to 3, in which the filler is a lactose and/or microcrystalline cellulose, and a lubricant is a stearate.

5. Pharmaceutical composition to obtain a tablet according to claim 4, in which the lactose is contained in an amount of from 1 to 8 wt.%.

6. Pharmaceutical composition to obtain a tablet according to one of claims 1 to 5, in which the compound is a crystalline form vildagliptin, preferably crystalline form "A" or any of its salts.

7. Pharmaceutical composition to obtain a tablet according to one of claims 1 to 6, which contains the calculation for the weight of the composition:
(a) vildagliptin or the appropriate amount of any Sol is in the range from 15 to 35 wt.%,
(b) hypromellose in the amount of from 30 to 50 wt.%,
(c) microcrystalline cellulose in an amount of from 25 to 35 wt.% and
(d) magnesium stearate in an amount of from 0.1 to 3 wt.%.

8. Pharmaceutical composition to obtain tablets, including one tablet weight of 600 mg of the following ingredients:
(a) vildagliptin in the amount of 150 mg or the appropriate number of any of its salts,
(b) hypromellose in the amount of approximately 240 mg, apparent viscosity which a 1%solution is from about 80,000 to 120,000 CP (nominal value of 100,000 CP),
(c) microcrystalline cellulose in the amount of 180 mg
(d) lactose in the amount of approximately 24 mg and
(e) magnesium stearate in the amount of 6 mg

9. Pharmaceutical composition to obtain tablets, including one tablet weight of 400 mg of the following ingredients:
(a) vildagliptin in the amount of 100 mg or an appropriate number of any of its salts,
(b) hypromellose in the amount of about 160 mg, the apparent viscosity of which a 1%solution is from about 80,000 to 120,000 CP (nominal value of 100,000 CP),
(c) microcrystalline cellulose in an amount of 120 mg
(d) lactose in the amount of about 16 mg and
(e) magnesium stearate 4 mg

10. A method of obtaining a pharmaceutical composition to obtain the tablets according to any one of claims 1-9, include the s combine ingredients in quantities presented in any of the mentioned items.

11. Pharmaceutical multi-layer tablet in which the pharmaceutical composition according to any one of claims 1 to 9 represents one of the layers of the tablet.

12. Pharmaceutical multilayer tablet according to claim 11, in which the additional layer contains glitazone (for example pioglitazone or rosiglitazone or Metformin.

13. Pharmaceutical multilayer tablet according to item 12, in which an additional layer is a composition of immediate-release.

14. Pharmaceutical tablet obtained by compressing the pharmaceutical composition to obtain the tablets according to any one of claims 1 to 13.

15. Pharmaceutical tablet obtained by compressing the pharmaceutical composition according to any one of claims 1 to 13, which before pressing the tablet is subjected to a rotational pressing.

16. Pharmaceutical tablet according to § 15 containing 100 mg vildagliptin or its pharmaceutically acceptable salts, with the range of hardness of the tablet is between 10 to 13 CR.

17. Pharmaceutical tablet according to § 15 containing 150 mg vildagliptin or its pharmaceutically acceptable salts, with the range of hardness of the tablets ranges from 11 to 25 Kr.

18. Pharmaceutical composition to obtain the tablets according to any one of claims 1 to 9 or a pharmaceutical tablet according to any one of § § 11-17, containing at least one will complement the local therapeutic agent.

19. Pharmaceutical composition to obtain tablets or pharmaceutical tablet p, in which at least one additional therapeutic agent presents antidiabetic agent.

20. Pharmaceutical composition to obtain tablets or pharmaceutical tablet according to claim 19, in which the anti-diabetic agent is selected from pioglitazone, rosiglitazone or Metformin.

21. Pharmaceutical composition to obtain tablets or pharmaceutical tablet p, in which at least one additional therapeutic agent is represented by the antagonist of angiotensin II, or a statin.

22. The method of producing tablets in a standard dosage forms, which is that:
(a) mixing the pharmaceutical composition to obtain the tablets according to any one of the preceding paragraphs,
(b) extrude the composition obtained in stage (a) and receive compressed tablet in a standard dosage forms.

23. The method of producing tablets in a standard dosage forms, which is that:
(a) mixing the pharmaceutical composition to obtain the tablets according to any one of the preceding paragraphs,
(b) conduct rotary compressing the composition obtained in stage (a),
(c) pressing the composition obtained in stage (b), and receive compressed tablets as standard l the drug form.

24. The method of producing tablets in a standard dosage forms, which is that:
(a) mixing the pharmaceutical composition to obtain the tablets according to any one of claims 1 to 21,
(b) conduct rotary compressing the composition obtained in stage (a), the compression pressure of from 10 to 16 kN
(c) pressing the composition obtained in stage (b), and receive the compressed tablet in a standard dosage forms.

25. Solid oral pharmaceutical dosage form with a slow release, including the characteristics of any one of claims 1 to 21, such as:
i-1) a solid oral pharmaceutical dosage form comprising about 100 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the dosage form provides a mean maximum concentration vildagliptin in plasma in the range of from about to 15.8 ng/ml ± 6,85 ng/ml to approximately 173 ng/ml ± 52 ng/ml after approximately 0.5 to 16 h after oral administration of the indicated dosage form to a patient who has not previously entered vildagliptin, and specified dosage form is administered to the patient on an empty stomach, and/or
i-2) a solid oral pharmaceutical dosage form comprising about 100 mg vildagliptin in free base form or sootvetstvuyshee the number of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean maximum concentration vildagliptin in plasma in the range of from about 26,3 ng/ml ± 13,1 ng/ml to about 175 ng/ml ± 62.5 ng/ml after approximately 0.5 to 16 h after injection of the indicated dosage form to a patient in day 9, which was introduced specified dosage form once a day since day 1 and the specified patient received Breakfast, as recommended by the American Council on diabetes (ADA) for 30 min before morning the introduction of a specified dosage form, and/or
i-3) a solid oral pharmaceutical dosage form comprising about 100 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean maximum concentration vildagliptin in plasma in the range of from about to 26.9 ng/ml ± 14,1 ng/ml to approximately 186 ng/ml ± 80,6 ng/ml after approximately 0.5 to 16 h after oral administration of the indicated dosage form to a patient in day 10, which was introduced specified dosage form once a day since day 1, and specified drug the form is administered to the patient on an empty stomach, and/or
ii-1) a solid oral pharmaceutical dosage form comprising about 100 mg meldahl is ptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean value of area under the pharmacokinetic curve AUC(0-inf)vildagliptin in the range of from about 1073 to approximately 1825 ng·h/ml, i.e. 1449 ng·h/ml ± 376 ng·h/ml after oral administration of the indicated dosage form to a patient who has not previously entered vildagliptin, and specified dosage form is administered to the patient on an empty stomach, and/or
ii-2) a solid oral pharmaceutical dosage form comprising about 100 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean value of area under the pharmacokinetic curve vildagliptin AUC(0-24)in the range of from about 1001 to about 1977 (ng·h/ml, i.e. 1489 ng·h/ml ± 488 ng·h/ml after oral administration of the indicated dosage form to a patient in day 9, which was introduced specified dosage form once a day since day 1, and indicated the patient received the ADA Breakfast within 30 min before morning the introduction of a specified dosage form, and/or
ii-3) a solid oral pharmaceutical dosage form comprising about 100 mg vildagliptin in the form of free bases or the corresponding number of formats whitesky acceptable salt, and the media, and the said dosage form provides a mean value of area under the pharmacokinetic curve vildagliptin AUC(0-24)in the interval from approximately 1103 to approximately 2173 ng·h/ml, i.e. 1638 ng·h/ml ± 535 ng·h/ml after oral administration of the indicated dosage form to a patient in day 10, which was introduced specified dosage form once a day since day 1, and the specified dosage form is administered to the patient on an empty stomach, and/or
iii-1) a solid oral pharmaceutical dosage form comprising about 100 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean value of tmaxvildagliptin 3,61 h ± 1,44 h after oral administration of the indicated dosage form to a patient who has not previously entered vildagliptin, and specified dosage form is administered to the patient on an empty stomach, and/or
iii-2) a solid oral pharmaceutical dosage form comprising about 100 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and this dose provides a mean value of tmaxvildagliptin 2,59 h ± 1,4 h after oral administration of a specified drug is form patient in day 9, which was injected specified dosage form once a day since day 1, and indicated the patient received the ADA Breakfast within 30 min before morning the introduction of a specified dosage form, and/or
iii-3) a solid oral pharmaceutical dosage form comprising about 100 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean value of tmaxvildagliptin 3,74 h ± 1,44 h after oral administration of the indicated dosage form to a patient in day 10, which was introduced specified dosage form once a day since day 1, and the specified dosage form is administered to the patient on an empty stomach, and/or
iv-1) a solid oral pharmaceutical dosage form comprising about 100 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean value Withmaxvildagliptin 205 ng/ml ± 47 ng/ml after oral administration of the indicated dosage form to a patient who has not previously entered vildagliptin, and specified dosage form is administered to the patient on an empty stomach, and/or
iv-2) a solid oral pharmaceutical dosage Fort is a, comprising about 100 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean value Withmaxvildagliptin 200 ng/ml ± 64 ng/ml after oral administration of the indicated dosage form to a patient in day 9, which was introduced specified dosage form once a day since day 1, and indicated the patient received the ADA Breakfast within 30 min before morning the introduction of a specified dosage form, and/or
iv-3) a solid oral pharmaceutical dosage form comprising about 100 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean value Withmaxvildagliptin 245 ng/ml ± 68 ng/ml after oral administration of the indicated dosage form to a patient in day 10, which was introduced specified dosage form once a day since day 1, and the specified dosage form is administered to the patient on an empty stomach, and/or
v-1) a solid oral pharmaceutical dosage form comprising about 100 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, Inositol, and the said dosage form provides a mean value of inhibition (in %) activity of DPP-IV for 24 h 85,64% ± 12,76% after oral administration specified dosage form to a patient who has not previously entered vildagliptin, and specified dosage form is administered to the patient on an empty stomach, and/or
v-2) a solid oral pharmaceutical dosage form comprising about 100 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean value of inhibition (in %) activity of DPP-IV for 24 h 87,78% ± 16,37% after oral administration specified dosage form to a patient in day 9, which was introduced specified dosage form once a day since day 1, and indicated the patient received the ADA Breakfast within 30 min before morning the introduction of a specified dosage form, and/or
v-3) a solid oral pharmaceutical dosage form comprising about 100 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean value of inhibition (in %) activity of DPP-IV for 24 h 90,20% ± 7,35% after oral administration of a specified drug f RMI patient in day 10, which was injected specified dosage form once a day since day 1, and the specified dosage form is administered to the patient on an empty stomach, and/or
vi-1) a solid oral pharmaceutical dosage form comprising about 100 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a pharmacokinetic profile shown in Fig, after oral administration of the indicated dosage form to a patient who has not previously entered vildagliptin, and specified dosage form is administered to the patient on an empty stomach, and/or
vi-2) a solid oral pharmaceutical dosage form comprising about 100 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a pharmacokinetic profile shown in Fig, after oral administration of the indicated dosage form to a patient in day 9, which was introduced specified dosage form once a day since day 1, and indicated the patient received the ADA Breakfast within 30 min before morning the introduction of a specified dosage form, and/or
vi-3) a solid oral pharmaceutical dosage form, vkluchaya is approximately 100 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a pharmacokinetic profile shown in Fig, after oral administration of the indicated dosage form to a patient in day 10, which was introduced specified dosage form once a day since day 1, and the specified dosage form is administered to the patient on an empty stomach.

26. Solid oral pharmaceutical dosage form with a slow release, including the characteristics of any one of claims 1 to 21, such as:
i-a) a solid oral pharmaceutical dosage form comprising about 150 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean maximum concentration vildagliptin in plasma in the range from approximately a 30.7 ng/ml ± 21,9 ng/ml to approximately 223 ng/ml ± 77,3 ng/ml after approximately 0.5 to 16 h after oral administration of the indicated dosage form to a patient who has not previously entered vildagliptin, and specified dosage form is administered to the patient on an empty stomach, and/or
i-b) a solid oral pharmaceutical dosage form comprising about 150 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the criminal code of the related dosage form provides a mean maximum concentration vildagliptin in plasma in the range of from about to 48.7 ng/ml ± to 25.8 ng/ml to approximately 223 ng/ml ± 99,7 ng/ml after approximately 0.5 to 16 h after oral the introduction of the specified dosage form to a patient in day 9, which was introduced specified dosage form once a day since day 1, and indicated the patient received the ADA Breakfast within 30 min before morning the introduction of a specified dosage form, and/or
i-c) a solid oral pharmaceutical dosage form comprising about 150 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean maximum concentration vildagliptin in plasma in the range of from about 44,6 ng/ml ± 28.5 ng/ml to approximately 263 ng/ml ± 84.4 ng/ml after approximately 0.5 to 16 h after oral administration of the indicated dosage form to a patient in day 10, which was introduced specified dosage form once a day since day 1, and specified drug the form is administered to the patient on an empty stomach, and/or
ii-a) a solid oral pharmaceutical dosage form comprising about 150 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean value of AUC(0-inf)vildagliptin in the range of from about 1346 to approximately 3196 ng·h/ml, i.e. 2271 ng·h/ml± 925 ng·h/ml after oral administration of the indicated dosage form to a patient, which have not previously entered vildagliptin, and specified dosage form is administered to the patient on an empty stomach, and/or
ii-b) a solid oral pharmaceutical dosage form comprising about 150 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean value of AUC(0-24)vildagliptin in the range of from approximately to approximately 1277 3207 ng·h/ml, i.e. 2242 ng·h/ml ± 965 ng·h/ml after oral administration of the indicated dosage form to a patient in day 9, which was introduced specified dosage form once a day since day 1, and indicated the patient received the ADA Breakfast within 30 min before morning the introduction of a specified dosage form, and/or
ii-c) a solid oral pharmaceutical dosage form comprising about 150 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean value of AUC(0-24)vildagliptin in the range of from about 1643 to approximately 3273 ng·h/ml, i.e. 2458 ng·h/ml ± 815 ng·h/ml after oral administration of the indicated dosage form to a patient in day 10, which was introduced specified drug Fort is at once a day, since day 1, and the specified dosage form is administered to the patient on an empty stomach, and/or
iii-a) a solid oral pharmaceutical dosage form comprising about 150 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean value of tmaxvildagliptin 3,57 h ± 1,17 h after oral administration of the indicated dosage form to a patient who has not previously entered vildagliptin, and specified dosage form is administered to the patient on an empty stomach, and/or
iii-b) a solid oral pharmaceutical dosage form comprising about 150 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean value of tmaxvildagliptin 2,87 h ± 1,59 h after oral administration of the indicated dosage form to a patient in day 9, which was introduced specified dosage form once a day since day 1, and indicated the patient received the ADA Breakfast within 30 min before morning the introduction of a specified dosage form, and/or
iii-c) a solid oral pharmaceutical dosage form comprising about 150 mg vildagliptin in the form of a free base the cation or an appropriate number of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean value of tmaxvildagliptin 4,13 h ± 1,24 h after oral administration of the indicated dosage form to a patient in day 10, which was introduced specified dosage form once a day since day 1, and the specified dosage form is administered to the patient on an empty stomach, and/or
iv-a) a solid oral pharmaceutical dosage form comprising about 150 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean value Withmaxvildagliptin 257 ng/ml ± 59 ng/ml after oral administration of the indicated dosage form to a patient who has not previously entered vildagliptin, and specified dosage form is administered to the patient on an empty stomach, and/or
iv-b) a solid oral pharmaceutical dosage form comprising about 150 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean value Withmaxvildagliptin 272 ng/ml ± 111 ng/ml after oral administration of the indicated dosage form to a patient in day 9, which was introduced specified dosage form once a day, the ince from day 1, and specified the patient received the ADA Breakfast within 30 min before morning the introduction of a specified dosage form, and/or
iv-c) a solid oral pharmaceutical dosage form comprising about 150 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean value Withmaxvildagliptin 308 ng/ml ± 91 ng/ml after oral administration of the indicated dosage form to a patient in day 10, which was introduced specified dosage form once a day since day 1, and the specified dosage form is administered to the patient on an empty stomach, and/or
v-a) solid oral pharmaceutical dosage form comprising about 150 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean value of inhibition (in %) activity of DPP-IV for 24 h 90,04% ± 11,91% after oral administration specified dosage form to a patient who has not previously entered vildagliptin, and specified dosage form is administered to the patient on an empty stomach, and/or
v-b) a solid oral pharmaceutical dosage form comprising about 150 mg vildagliptin in the form of NWO is one of the bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean value of inhibition (in %) activity of DPP-IV for 24 h 90,4% ± 17,50% after oral administration specified dosage form to a patient in day 9, which was introduced specified dosage form once a day since day 1, and indicated the patient received the ADA Breakfast within 30 min before morning the introduction of a specified dosage form, and/or
v-c) a solid oral pharmaceutical dosage form comprising about 150 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a mean value of inhibition (in %) activity of DPP-IV for 24 h 91,64% ± of 8.47% after the introduction of the specified dosage form to a patient in day 10, which was introduced specified dosage form once a day since day 1, and the specified dosage form is administered to the patient on an empty stomach, and/or
vi-a) a solid oral pharmaceutical dosage form comprising about 150 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a pharmacokinetic profile shown in Fig, after oral administration indicated the Anna dosage form to a patient, which have not previously entered vildagliptin, and specified dosage form is administered to the patient on an empty stomach, and/or
vi-b) a solid oral pharmaceutical dosage form comprising about 150 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the said dosage form provides a pharmacokinetic profile shown in Fig, after oral administration of the indicated dosage form to a patient in day 9, which was introduced specified dosage form once a day since day 1, and indicated the patient received the ADA Breakfast within 30 min before morning the introduction of a specified dosage form, and/or
vi-c) a solid oral pharmaceutical dosage form comprising about 150 mg vildagliptin in the form of free bases or the corresponding amount of its pharmaceutically acceptable salts, and the media, and the specified dosage form provides a pharmacokinetic profile shown in Fig, after oral administration of the indicated dosage form to a patient in day 10, which was introduced specified dosage form once a day since day 1, and the specified dosage form is administered to the patient on an empty stomach.

27. Solid oral pharmaceutical dosage form with medlennym release on p. 25 or 26, including pharmaceutical composition to obtain the tablets according to any one of the preceding paragraphs.

28. Solid oral pharmaceutical dosage form with a slow release on p. 25 or 26, containing hypromellose preferably in quantities of from 20 to 60% or from 30 to 50% per weight of dry hydroxypropylmethylcellulose.

29. Solid oral pharmaceutical dosage form with a slow release on p. 25 or 26, containing hydroxypropylmethylcellulose, the apparent viscosity of which a 1%solution is from about 80,000 to 120,000 CP (nominal value of 100,000 CP), preferably in quantities of from 20 to 60 wt.% or from 30 to 50 wt.% calculated on the dry weight of hydroxypropylmethylcellulose, the apparent viscosity of which a 1%solution is from about 80,000 to 120,000 CP (nominal value of 100,000 CP).

30. Solid oral pharmaceutical dosage form with a slow release on p. 25 or 26, which is a
i) the composition, meaning the matrix composition containing a pharmaceutically acceptable hydrophilic polymer, slowing down the diffusion vildagliptin,
ii) a solid oral pharmaceutical dosage form in the form of compressed tablets, and is optional
iii) the degree of liberation vildagliptin 30 minutes after the start of the test is less than 0% according to the paddle method.

31. The use of ingredients in the quantities specified in one of claims 1 to 30, in the manufacture of a pharmaceutical composition to obtain tablets used for inhibiting the activity of dipeptidylpeptidase IV the subject.

32. The use of ingredients in the quantities specified in one of claims 1 to 30, in the manufacture of a pharmaceutical composition to obtain tablets used to treat conditions, the intensity of the symptoms which decreases with inhibition dipeptidylpeptidase IV for a subject suffering from such a condition.

33. Use p, in which the status indicates non-insulin-dependent diabetes mellitus.

34. Use p, in which the status indicates obesity, arthritis or osteoporosis.

35. The use according to any one of p-34, where the pharmaceutical composition to obtain tablets are used in combination with a therapeutically effective amount of anti-diabetic or antiarthritic medicines or drugs against obesity.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to system for programmed in space and time delivery of pharmaceutically active agent. In case of per oral introduction system is held in gastric part during prolonged time period. System contains core, one or more core-covering polymer layers, and preliminarily prepared empty space. Pharmaceutically active agent is in core or any of system layers, or both in core and in any of system layers. Invention also related to method of system obtaining. System of delivery in accordance with the invention is universal in type of pharmaceutically active agent, which is included into it.

EFFECT: system can be obtained on wide scale, does not require complex equipment and uses ordinary raw materials, which are biodegradable, non-toxic and biologically compatible.

32 cl, 10 dwg, 14 tbl, 24 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: as an active ingredient, a pharmaceutical composition contains 6β,7β; 15β; 16β-dimethylene-3-oxo-17α-preg-4-ene-21,17-carbolactone (drospirenone, DRSP) together with a pharmaceutically acceptable excipient or carrier. Said composition does not contain estrogen. Drospirenon is prepared in fast soluble dosage form. At least 70% of drospirenone are dissolved within 30 minutes. For ensuring said immediate release, drospirenone is either micronised, or in dosage form of surface area more than 10000 cm2/g, or is applied on the surface of particles of an inert carrier. The composition can be applied for endometriosis treatment and introduced in the form of a multiphase pharmaceutical preparation.

EFFECT: immediate-release drospirenone compositions under the invention exhibits high biological availability when administered orally.

23 cl, 7 ex

FIELD: medicine.

SUBSTANCE: there are offered a pharmaceutical composition for prevention or treatment of cardiovascular disturbances, containing Amlodipine or its pharmaceutically acceptable salt and Losartan or its pharmaceutically acceptable salt wherein Amlodipine or its pharmaceutically acceptable salt and Losartan or its pharmaceutically acceptable salt are physically separated from each other, and a method for preparing thereof. The method includes the following stages: a) wet granulation and drying of mixed Amlodipine or its salts and pharmaceutically acceptable excipients to prepare a portion containing Amlodipine granules; and b) mixing of the portion containing Amlodipine granules prepared at the stage a) and pre-mixed Losartan or its salt and pharmaceutically acceptable excipients.

EFFECT: improved preventive and therapeutic effects in cardiovascular disturbances, better stability, solubility, absence of hygroscopicity in making the tablets.

12 cl, 5 dwg, 1 tbl, 15 ex

FIELD: medicine.

SUBSTANCE: multiphase pharmaceutical preparation for ovulation inhibition in mammal contains a number of individually packed and individually removed daily units placed in a single package, and used for oral administration for at least 21 days running; specified daily units contain a combination of oestradiol and drospirenone. A daily unit contains 0.5 to 4 mg of oestradiol and 2 to 4 mg of drospirenone. At least 70% of specified drospirenone are released from specified unit within 30 minutes.

EFFECT: invention provides higher oral bioavailability of drospirenone.

6 cl, 5 dwg, 5 ex

FIELD: medicine.

SUBSTANCE: present invention concerns coated tableted form containing a tablet centre coated with a medical agent as inhibitor DPP4 sacsaglipitin, and the method for preparing such coated tableted form. The layers that coat the tablet centre are applied as a coating polymer suspension.

EFFECT: according to the invention, coated tablets are characterised with improved chemical stability as compared to the conventional tablets.

17 cl, 2 tbl, 1 ex

FIELD: food products.

SUBSTANCE: substance composition includes: (a) approximately 25 - 99% wt of emulsion, containing polymeric compound; (b) approximately 0.1 - 20% wt of zinc oxide solution; (c) approximately 0.001 - 5% wt of defoamant; (d) approximately 1 - 40% wt of emulsion on the basis of polyethylene wax or emulsion on the basis of polypropylene wax and (e) approximately 1 - 100000 wt of juvenile hormone for 1 million of coating composition wt. The proposed coating composition is applied to packing materials for food products and animal feed stuff.

EFFECT: reliable and effective protection of packed products from insect infestation.

9 cl, 7 dwg, 5 tbl, 4 ex

FIELD: pharmacology.

SUBSTANCE: invention relates to method of preliminary physical processing of clarithromycin, whose application results in such modification of technologically important physical properties of active substance which allows to obtain medicinal form with more stable profile of active substance release during all term of medication storage life in comparison with profile of release from similar composition but without preliminary processing. Claimed method includes moistening of clarithromicin or mixture of clarithromycin with other excipients with light solvent or mixture of solvents, in which clarithromycin solubility constitutes approximately less than 0.1 g/l, with further drying. Claimed invention also relates to pharmaceutical composition containing clarithromycin, processed in accordance with claimed method, and application of film covering which contains combination of low-molecular polymer representing cellulose ester, having viscosity approximately 6 mPa*s, and highly-molecular polymer, representing cellulose ester, which has viscosity approximately 15 mPa*s, for covering tablet cores, containing clarithromycin, processed in accordance with claimed method.

EFFECT: medicinal form with more stable profile of active substance release.

18 cl, 5 ex

FIELD: medicine.

SUBSTANCE: invention relates to medications and concerns composition of dissolving in mouth cavity film, which ensures easing nicotine addiction and contains: a) enterosoluble polimer; b) at least one alkali buffer agent and c) nicotine active agent. Also described are multi-component dissolving in mouth cavity film, which ensures easing nicotine addiction, and method of obtaining film composition, dissolving in mouth cavity.

EFFECT: invention compositions ensure good transbuccal absorption and ease nicotine addiction in people.

21 cl, 5 ex

FIELD: medicine; pharmacology.

SUBSTANCE: peroral pharmaceutical dosed out form for treatment of the conditions bound to secretion of acid in a stomach, includes an acid-sensible inhibitor of the proton pump and antagonist of H2-molecular switchers, with the delayed and-or prolonged liberation of the proton pump acid-sensible inhibitor, and fast liberation of antagonist of H2-molecular switchers.

EFFECT: maximum suppression of acid in a stomach after the first dose and throughout all course of treatment.

69 cl, 4 dwg, 7 ex

FIELD: medicine; pharmacology.

SUBSTANCE: system of delivery of medicinal substance includes one department consisting from (i) of a kernel from thermoplastic polymer, filled with medicinal substance, (ii) an intermediate layer from the thermoplastic polymer filled with medicinal substance, and (iii) covers from the thermoplastic polymer, covering an intermediate layer and not containing medicinal substance, where the specified intermediate layer is filled (a) with crystals of the first pharmacologically active substance, and (b) the second pharmacologically active substance in the dissolved form and where the kernel is filled specified to the second pharmacologically active substance in the dissolved form. The delivery system is intended for vaginal introduction of the medicinal substance.

EFFECT: possibility of adjustment of rate of liberation of two or more active ingredients irrespective of others, at maintenance of long physical stability of system at room temperature.

51 cl, 21 dwg, 10 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of pharmaceutical and food industry, in particular to production of vitamin-mineral complexes (VMC) and food additives, used for prevention and treatment of vitamin-mineral deficiency. Simultaneously, taken into account are all antagonistic and synergic interactions between active VMC components, arising in production, storage and application of medication. Delivery of micronutrients by time and place of their digestion is realised within one preparative form, which is made in form of tablet or capsule, containing several independent elements - pellets. Pellets have their time of dissolution, depending on acidity of surrounding medium. During movement of ready form along GIT time of beginning of substances release from one pellet follows time of end of substances release from other pellet in such a way that simultaneously in solution there were no active substances that have antagonistic interaction.

EFFECT: invention is aimed at increase of VMC efficiency and improvement of user's comfort during its application.

23 cl, 10 ex, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to chemical-pharmaceutical industry and deals with pharmaceutical composition of tablet, based on matrix, which contains alfozosin hydrochloride, polyvinylpyrrolidone, lactose and mixture HPMC K100, HPMC K100M and HPMC K15M, with controlled release.

EFFECT: form of tablet implementation ensures simplicity of tablet manufacturing and acceptable profile of alfuzosin release.

10 cl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention claims per oral drug form of neramexam with modified release, which is applied for long therapy of patients with such diseases and states as dimentia in Alzheimer's disease and neuropathic pain. Neramexane is dispersed inside hard matrix, which contains release-regulating filler. Filler is selected from copolymer of polyvinylpyrrolidone and vinyl acetate, hydroxypropylmethylcellulose. Hydroxypropylmethylcellulose is present in mixture with microsrystalline cellulose. Content of said filler is selected in such a way as to obtain profile of neramexan release in vitro, characterised by dissolution time of, at least, 1 hour for amount of neramexane, constituting 50 wt %.

EFFECT: profile of release ensures concentrations of neramexane in plasma with fluctuation index 0,4 or lower with introduction of matrix tablet of neramexane one time per day at steady state.

23 cl, 4 tbl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are offered a prolonged release composition for regional depot fat reduction containing a therapeutically effective amount of at least one glucocorticosteroid in the form of a crystalline microparticle suspension, and a therapeutically effective amount of at least one selective beta-2-adrenergic receptor agonist and a respective combined preparation of the same purpose.

EFFECT: glucocorticosteroid reduced beta-adrenergic receptor desensitisation to provide a synergetic action with the beta-2-adrenergic receptor agonist (eg, with formoterol) to enable fat amount reduction.

18 cl, 11 dwg, 5 tbl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to chemical-pharmaceutical industry and deals with composition, which contains salt of "п"-tolyolsulfonic acid of methylamide 4 {4-[3 -(4-chlor-3-tri-fluoromethylphenyl)-ureido]-phenoxypyridin-2-carbonic acid as active substance in amount not less than 55% of composition weight, and at least one pharmaceutically acceptable carrier. Invention also relates to application of said composition for treatment of hyperproliferative diseases such as cancer.

EFFECT: composition possesses high stability in storing, and possesses high bioaccessability.

16 cl, 2 ex, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to bioadhesive carrier for mucous membranes with delayed release of active component. Carrier contains primary granules, which include active component, 1-75 wt % of diluting agent 1-10 wt % of alkyl sulfate of alkaline metal and 0.5-5 wt % of binding substance, as well as 5-80 wt % of bioadhesive polymer, selected from group including natural polymers, said natural polymers represent polysaccharides, natural proteins of animal or vegetable origin, or synthetic polymers and 5-80 wt % of polymer, ensuring delayed release of active component, carrier does not contain lactose and corn starch. Said carrier ensures delivery of active component during long period, constituting more than 20 hours.

EFFECT: invention relates to method of obtaining bioadhesive carrier and to its application for treatment of mucous membrane diseases.

33 cl, 7 dwg, 2 tbl, 13 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of medicine and pharmacy, namely to tablet of prolonged release, which consists of, at least, two layers, and is different due to the fact that, at least, one layer quickly releases medication 1S,9S(RS,3S)N-(2-ethoxy-5-oxo-tetrafuran-3-yl)-6,10-dioxo-9-(isoquinolen-1-oyl-amino)-1,2,3,4,7,8,9,10-octahydro-6-H-pyridazino[1,2-a][1,2]diazepine-1-carboxamide and, at least one layer releases in delayed manner medication 1S,9S(RS,3S)N-(2- ethoxy -5-oxo-tetrafuran-3-yl)-6,10-dioxo-9-( isoquinolen-1-oyl-amino)-1,2,3,4,7,8,9,10-octahydro -6-H- pyridazino [ 1,2-a] [1,2] diazepine-1 - carboxamide for treatment of autoimmune diseases, type I and type II diabetes, rheumatoid arthritis, osteoarthritis and/or psoriasis.

EFFECT: obtaining tablet with prolonged release.

8 cl, 2 dwg, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medicine and pharmaceutical industry. Pharmaceutical composition has as active substance clozapine and auxiliary substances: hydroxypropylmethylcellulose (HPMC), micro crystalline cellulose modified by silicon dioxide (MCC MSD) and magnesium stearate. Pharmaceutical composition is made in from of coated pills. Coating contains "Opadry II" of Colorcon company or composition, which consists of polyvinyl alcohol, titanium dioxide, polyethylene glucole and acceptable dyes. Pharmaceutical composition of prolonged action based on clozapine has 2 year storage term.

EFFECT: obtaining pharmaceutical composition based on clozapine, relating to group of atypical neuroleptics for treatment of various forms of schizophrenia.

6 cl, 1 dwg, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention aims at a controlled release composition for an oral solid dosage form. The composition contains mixed hypromellose and polyvinylacetatephthalate. An amount of hypromellose makes 8 to 60 wt %, an amount of polyvinylacetatephthalate is effective for maintaining controlled release of a pharmaceutically active ingredient in vitro and makes 4 to 60 wt % of the mixture. Said mixture of hypromellose and polyvinylacetatephthalate is pressed in a swelling hydrophilic matrix.

EFFECT: invention enables controlled release of the combined pharmaceutically active ingredient.

25 cl, 6 ex

FIELD: medicine.

SUBSTANCE: pH-controlled pulse delivery system according to the invention, contains a nucleus enclosed by an external coating. Said nucleus contains an active substance which is preferentially a pharmaceutically active substance. Said external coating contains a pH-sensitive coating material embedding a swelling ingredient of water swell equal to at least 1.1 in relation to own weight. Said swelling ingredient is present in aforesaid coating in an amount which depending on particle size and structure of the coating forms a coating with a leakless system. The pH-controlled pulse delivery system aims at pH-related place-specific delivery of an active substance preferentially to a large intestine or a duodenum.

EFFECT: invention allows fast release of the active substance owing to the presence of the swelling ingredient in the external coating.

15 cl, 6 dwg, 8 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely, to hematology, cardiology and endocrinology and can be used for correction of disturbance of lipid composition of platelet membranes in patients with arterial hypertension with impaired glucose tolerance (AH and IGT). Method includes application of dosed physical exercise, consisting of morning gymnastics, therapeutic and preventive gymnastics and divided physical exercises during the day, daily swimming in swimming pool for not less than 20 minutes a day, metformin 500 mg 2 times per day and lisinopril 10 mg 1 time in the morning during 5 weeks.

EFFECT: combined application of all components of complex makes it possible to normalise lipid composition of platelet membranes in patients with AH and IGT and reduce risk of thrombotic complications.

1 ex

Up!