EP2164469A2 - Stabile formulierung von amorphen perindopril-salzen, verfahren zu ihrer herstellung im industriellen massstab und ihre verwendung bei der behandlung von hypertonie - Google Patents
Stabile formulierung von amorphen perindopril-salzen, verfahren zu ihrer herstellung im industriellen massstab und ihre verwendung bei der behandlung von hypertonieInfo
- Publication number
- EP2164469A2 EP2164469A2 EP08754036A EP08754036A EP2164469A2 EP 2164469 A2 EP2164469 A2 EP 2164469A2 EP 08754036 A EP08754036 A EP 08754036A EP 08754036 A EP08754036 A EP 08754036A EP 2164469 A2 EP2164469 A2 EP 2164469A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- perindopril
- process according
- preparation
- alkali
- alkaline earth
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical class C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 title claims abstract description 31
- 239000000203 mixture Substances 0.000 title claims abstract description 20
- 238000009472 formulation Methods 0.000 title claims abstract description 11
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 238000000034 method Methods 0.000 title claims description 16
- 206010020772 Hypertension Diseases 0.000 title description 4
- 229960002582 perindopril Drugs 0.000 claims abstract description 25
- 239000000243 solution Substances 0.000 claims abstract description 21
- 239000008187 granular material Substances 0.000 claims abstract description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000002253 acid Substances 0.000 claims abstract description 9
- 239000003513 alkali Substances 0.000 claims abstract description 7
- 229960004569 indapamide Drugs 0.000 claims abstract description 7
- NDDAHWYSQHTHNT-UHFFFAOYSA-N indapamide Chemical compound CC1CC2=CC=CC=C2N1NC(=O)C1=CC=C(Cl)C(S(N)(=O)=O)=C1 NDDAHWYSQHTHNT-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000000126 substance Substances 0.000 claims abstract description 7
- 239000002585 base Substances 0.000 claims abstract description 5
- 150000003839 salts Chemical class 0.000 claims abstract description 5
- 239000013543 active substance Substances 0.000 claims abstract description 4
- 239000007864 aqueous solution Substances 0.000 claims abstract description 4
- 239000002934 diuretic Substances 0.000 claims abstract description 4
- 229940030606 diuretics Drugs 0.000 claims abstract description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 6
- 229910052708 sodium Inorganic materials 0.000 claims description 6
- 239000011734 sodium Substances 0.000 claims description 6
- -1 alkaline earth metal cation Chemical class 0.000 claims description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 2
- 239000013078 crystal Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 229940060367 inert ingredients Drugs 0.000 claims description 2
- 239000003921 oil Substances 0.000 claims description 2
- 239000012261 resinous substance Substances 0.000 claims description 2
- 239000011877 solvent mixture Substances 0.000 claims description 2
- 150000001342 alkaline earth metals Chemical class 0.000 claims 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 1
- 229910052783 alkali metal Inorganic materials 0.000 claims 1
- 150000001340 alkali metals Chemical class 0.000 claims 1
- 230000003276 anti-hypertensive effect Effects 0.000 claims 1
- 229910052791 calcium Inorganic materials 0.000 claims 1
- 239000011575 calcium Substances 0.000 claims 1
- 230000001882 diuretic effect Effects 0.000 claims 1
- 239000008240 homogeneous mixture Substances 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims 1
- 229910052749 magnesium Inorganic materials 0.000 claims 1
- 239000011777 magnesium Substances 0.000 claims 1
- 238000002156 mixing Methods 0.000 claims 1
- 230000007935 neutral effect Effects 0.000 claims 1
- 229910052700 potassium Inorganic materials 0.000 claims 1
- 239000011591 potassium Substances 0.000 claims 1
- 230000000304 vasodilatating effect Effects 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- IYNMDWMQHSMDDE-MHXJNQAMSA-N perindopril erbumine Chemical compound CC(C)(C)N.C1CCC[C@@H]2N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H](C(O)=O)C[C@@H]21 IYNMDWMQHSMDDE-MHXJNQAMSA-N 0.000 description 8
- 229920002261 Corn starch Polymers 0.000 description 7
- 239000008120 corn starch Substances 0.000 description 7
- 229960003929 perindopril erbumine Drugs 0.000 description 7
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical group CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 7
- 239000004615 ingredient Substances 0.000 description 5
- 159000000000 sodium salts Chemical class 0.000 description 5
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 4
- 229950005127 erbumine Drugs 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 4
- 239000008108 microcrystalline cellulose Substances 0.000 description 4
- 229940016286 microcrystalline cellulose Drugs 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000005469 granulation Methods 0.000 description 3
- 230000003179 granulation Effects 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 229960001375 lactose Drugs 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 229960001021 lactose monohydrate Drugs 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000001665 trituration Methods 0.000 description 2
- 229910002012 Aerosil® Inorganic materials 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960005168 croscarmellose Drugs 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Definitions
- B + represents an alkali or alkaline earth metal cation, a process for the preparation thereof on an industrial scale and the use thereof in treating hypertension.
- formulations comprise the active component perindopril erbumine in different polymorphic forms of formula II:
- Patent application US 6,696,481 discloses the salt of perindopril with arginine, which is more stable than erbumine. At the same time the disadvantages of erbumine are stated and it is also mentioned that sodium salt of perindopril in its pure form is unstable for the formulation, because it turns to oil and decomposes when exposed to air.
- Our previous patent application WO 2007/058634 Al discloses the preparation of a stable formulation of perindopril in the form of an amorphous sodium salt on an inert carrier, starting from perindopril erbumine or perindopril erbumine hydrate.
- the stable formulations of amorphous perindopril salts are prepared directly from perindopril (acid) without the intermediate step of erbumine salt.
- Perindopril in the form of a free acid is (2S,3aS,7aS)-l-[(2S)-2-[[(l 1 S)-l- ethoxycarbonyl)butyl] amino- 1 -oxopropyl] octahydro- lH-indole-2-carboxylic acid of formula III:
- Free acid of formula III can be used in the form of an oil, resinous substance, crystals, aqueous solution, or a solution in a water-solvent mixture.
- perindopril salts with alkali and earth alkaline bases can be formed directly when perindopril is dissolved in alcohol and to which a solution of a suitable base in water in a molar ratio 1 : 1 is added during intense stirring. This solution is then sprayed onto a calculated amount of inert ingredients for tabletting (lactose, starch, cellulose) and dried in a stream of warm air at 30-50 0 C or in vacuum.
- dry substance (first granulate) other additives are admixed, optionally also other active substances (diuretics), by trituration in order to obtain a final mixture - second granulate, which is then tabletted.
- common disintegrating agents such as croscarmellose, crospovidone, aerosil etc.
- This process can also be used to prepare said composition by triturating the first granulate, obtained after the granulation phase, in an air stream with other necessary ingredients, wherein simultaneously micronized indapamide is added.
- the ratio of perindopril and indapamide is 4 : 1.25.
- Perindopril (free acid) (7.9 g, 21.4 mmole) was dissolved separately in ethanol (96 %; 35 mL). The solution of sodium hydrogen carbonate (2.0 g, 23.8 mmole) in water (35 mL) was prepared separately. Both solutions were combined and stirred for 10 min, pH must be in the range from 7.0 to 7.5.
- This mixture was then sprayed in a stream of warm air having a temperature of 30-50 0 C onto the previously prepared mixture consisting of lactose (142 g), corn starch (6 g) and microcrystalline cellulose (42.6 g). It was dried with warm air to reach the water content 0.5-1.5 % (K. Fischer method). About 200 g of the first granulate, containing 4.17 % of sodium salt of perindopril was obtained.
- Perindopril (7.9 g, 21.4 mmole) was dissolved in ethanol (96 %; 35 mL).
- Perindopril (7.9 g, 21.4 mmole) was dissolved in ethanol (96 %; 35 mL) and the obtained solution was slowly added to the suspension of calcium hydroxide (0.95 g, 12.8 mmole) during intense stirring, and stirred for 30 min.
- the pH-value must be in the range from 7.0 to 7.5.
- the obtained slightly turbid solution was filtered to clarify.
- Example 1 The solution was further processed to granulate and tablets as described in Example 1.
- Perindopril (7.9 g, 21.4 mmole) was dissolved in ethanol (96 %; 35 mL).
- This mixture was then sprayed in a stream of warm air having a temperature of 30-50 0 C to the previously prepared mixture consisting of lactose (140.0 g), corn starch (5.9 g) and microcrystalline cellulose (41.75 g). It was dried in a stream of warm air to reach the water content of 0.5-1.5 %.
- composition for 22000 tablets of perindopril sodium salt contains 3.53 mg of perindopril sodium (which corresponds to 4 mg of perindopril erbumine).
- Perindopril (acid) (0.079 kg) was dissolved in ethanol (96 %; 400 mL). Separately a solution of sodium hydrogen carbonate (0.018 kg) in water (200 mL) was prepared. Both solutions were mixed whilst stirring.
- WSG type Glatt GPCG-I a dry blend of the following ingredients was prepared:
- the final granulate was used for tabletting. It was tabletted on the tabletting machine KILIAN RLA with the rate of 30000 tablets/hour.
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SI200700131A SI22542A (sl) | 2007-06-04 | 2007-06-04 | Stabilna formulacija amorfnih soli perindoprila, postopek za njeno pripravo v industrijskem merilu in njena uporaba za zdravljenje hipertenzije |
| PCT/SI2008/000031 WO2008150245A2 (en) | 2007-06-04 | 2008-05-30 | Stable formulation of amorphous perindopril salts, a process for the preparation thereof on industrial scale and use thereof in the treatment of hypertension |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP2164469A2 true EP2164469A2 (de) | 2010-03-24 |
Family
ID=39930588
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP08754036A Withdrawn EP2164469A2 (de) | 2007-06-04 | 2008-05-30 | Stabile formulierung von amorphen perindopril-salzen, verfahren zu ihrer herstellung im industriellen massstab und ihre verwendung bei der behandlung von hypertonie |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP2164469A2 (de) |
| CN (1) | CN101742986B (de) |
| RU (1) | RU2464022C2 (de) |
| SI (1) | SI22542A (de) |
| WO (1) | WO2008150245A2 (de) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SI22543A (sl) * | 2007-06-27 | 2008-12-31 | Krka, Tovarna Zdravil, D.D., Novo Mesto | Nove soli perindoprila |
| AU2013201812B2 (en) * | 2007-06-27 | 2015-04-02 | Les Laboratoires Servier | Salts of perindopril |
| SI23149A (sl) | 2009-09-21 | 2011-03-31 | Silverstone Pharma | Nove benzatinske soli ACE inhibitorjev, postopek za njihovo pripravo in njihova uporaba za zdravljenje kardiovaskularnih bolezni |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2838648B1 (fr) * | 2002-04-18 | 2004-05-21 | Servier Lab | Nouveau sel de perindopril et les compositions pharmaceutiques qui le contiennent |
| SI21704A (en) * | 2004-01-14 | 2005-08-31 | Lek Farmacevtska Druzba Dd | New crystal form of perindopril, procedure of its preparation, pharmaceutical preparations containing this form and their application in treatment of hypertensia |
| SI21703A (en) * | 2004-01-14 | 2005-08-31 | Lek Farmacevtska Druzba Dd | Inclusion complexes of perindopril, procedure of their preparation, pharmaceutical compositions containing these complexes and their application in treatment of hypertensia |
| HRP20140476T1 (hr) * | 2005-11-17 | 2014-07-18 | Silverstone Pharma Est. | Stabilni oblik amorfnih soli perindoprila, postupak njihove pripreme, posebno industrijske pripreme i njihova uporaba u lijeäśenju hipertenzije |
-
2007
- 2007-06-04 SI SI200700131A patent/SI22542A/sl not_active IP Right Cessation
-
2008
- 2008-05-30 RU RU2009149675/15A patent/RU2464022C2/ru not_active IP Right Cessation
- 2008-05-30 EP EP08754036A patent/EP2164469A2/de not_active Withdrawn
- 2008-05-30 CN CN2008800187504A patent/CN101742986B/zh not_active Expired - Fee Related
- 2008-05-30 WO PCT/SI2008/000031 patent/WO2008150245A2/en not_active Ceased
Non-Patent Citations (1)
| Title |
|---|
| See references of WO2008150245A2 * |
Also Published As
| Publication number | Publication date |
|---|---|
| RU2464022C2 (ru) | 2012-10-20 |
| WO2008150245A2 (en) | 2008-12-11 |
| CN101742986B (zh) | 2013-07-17 |
| RU2009149675A (ru) | 2011-07-20 |
| CN101742986A (zh) | 2010-06-16 |
| SI22542A (sl) | 2008-12-31 |
| WO2008150245A3 (en) | 2009-02-05 |
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