公开(公告)号：WO2005068435A1

公开(公告)日：2005-07-28

申请号：PCT/CZ2004/000088

申请日：2004-12-17

Applicant: ZENTIVA, a. s. ,  SEBEK, Pavel ,  RADL, Stanislav ,  STACH, Jan

Inventor： SEBEK, Pavel ,  RADL, Stanislav ,  STACH, Jan

IPC: C07D239/42

CPC classification number: C07D239/42

Abstract: A method of preparation of the hemi-calcium salt of rosuvastatin of formula (I) consists in extracting an aqueous solution of the sodium or potassium salt of (E)-7-[4-(4-fluorophenyl)-6­isopropyl-2- [methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxy-6-heptenoic acid, with optional admixture of sodium or potassium hydroxide or other sodium or potassium salts having inorganic anions, with an organic solvent, incompletely miscible with water, selected from the series of R 1 COOR 2 , R 1 COR 2 and R 1 OH, wherein R 1 and R 2 independently represent hydrogen or a residue of a C 1 -C 10 aliphatic hydrocarbon, C 6 aromatic hydrocarbon, C 5 or C 6 cyclic hydrocarbon, or a combination of an aliphatic and aromatic or cyclic hydrocarbon, the extract being subsequently shaken with an aqueous solution of an inorganic or C 1 -C 5 organic calcium salt, and the product of formula I is further isolated by cooling and/or adding an anti-solvent and filtration, and optionally, is converted into its amorphous form.

Abstract translation: 制备式（I）的瑞舒伐他汀的半钙盐的方法在于提取（E）-7- [4-（4-氟苯基） - 异丙基-2- [（甲基磺酰基）氨基]嘧啶-5-基]（3R，5S）-3,5-二羟基-6-庚烯酸，具有任选的氢氧化钠或氢氧化钾或其它具有无机阴离子的钠盐或钾盐的混合物， 选自R 1 COOR 2，R 1 COR 2和R 1 OH的不完全与水混溶的有机溶剂，其中R 1和R 2独立地表示氢 或C 1 -C 10脂族烃，C 6芳族烃，C 5或C 6环烃或脂族和芳族或环烃的组合的残基，随后与无机或C 1 -C 5有机物的水溶液一起摇动该提取物 钙盐，并且式I的产物通过冷却和/或加入抗溶剂进一步分离并过滤，并且任选地被转化为 其无定形形式。

公开(公告)号：WO2005011638A3

公开(公告)日：2005-02-10

申请号：PCT/CZ2004/000045

申请日：2004-08-05

Applicant: ZENTIVA, A. S. ,  SEBEK, Pavel ,  PROKOPOVA, Alena ,  SVOBODA, Eduard ,  RADL, Stanislav ,  STACH, Jan ,  SVOBODA, Martin ,  KOVACIK, Andrej ,  DANKO, Adrian ,  PETRO, Roman ,  STRIZINEC, Miroslav

Inventor： SEBEK, Pavel ,  PROKOPOVA, Alena ,  SVOBODA, Eduard ,  RADL, Stanislav ,  STACH, Jan ,  SVOBODA, Martin ,  KOVACIK, Andrej ,  DANKO, Adrian ,  PETRO, Roman ,  STRIZINEC, Miroslav

IPC: A61K9/20

Abstract: Stabilization of the pharmaceutical active solid substance atorvastatin alone or in a mixture with other solid substances embedded in a gaseous mixture is carried out in such a manner that in the surrounding gaseous mixture a partial pressure of oxygen of at most 2 kPa, preferably less than 1 kPa, more preferably less than 0.4 kPa is maintained. The corresponding partial pressure is achieved either by use of oxygen absorbers, by packaging under a pressure of 0.3 - 10 kPa, or by packaging under a slight overpressure of an inert gas, preferably nitrogen, the gas being introduced, by means of nozzles, into the cavities, optionally also into the space of the press roller and of the wiper station.

公开(公告)号：WO2005084682A1

公开(公告)日：2005-09-15

申请号：PCT/CZ2004/000012

申请日：2004-03-08

Applicant: PHARMACEUTICAL SERVICES INC. (PSI NV.) ,  ZENTIVA, a. s. ,  van ENGELGEM, Tim ,  MARECHAL, Julie

Inventor： van ENGELGEM, Tim ,  MARECHAL, Julie

IPC: A61K31/57

CPC classification number: B82Y5/00 ,  A61K31/57 ,  A61K47/6951

Abstract: A pharmaceutical composition comprising a cyclodextrin complex of (7α, 17α)-17-hydroxy­7-methyl-l9-nor-l7-pregn-5(10)-en-20-yn-3-one (Tibolone) and methods for the manufacture thereof.

Abstract translation: 一种药物组合物，其包含（7α，17α）-17-羟基-7-甲基-19-去甲孕酮-5（10）-en-20-炔-3-酮（Tibolone）的环糊精复合物及其制造方法 它们。

公开(公告)号：WO2004101534A1

公开(公告)日：2004-11-25

申请号：PCT/CZ2004/000029

申请日：2004-05-14

Applicant: ZENTIVA, a. s. ,  RADL, Stanislav ,  STACH, Jan ,  DEDINOVA, Eva

Inventor： RADL, Stanislav ,  STACH, Jan ,  DEDINOVA, Eva

IPC: C07D257/04

CPC classification number: C07D257/04 ,  Y02P20/55

Abstract: From the starting 4-bromomethyl-2'-(1-triphenylmethyltetrazol-5-yl)biphenyl, N-[(2'­(1-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl)methyl]-(L)-valine benzyl ester of formula 7 is obtained via a reaction with L-valine benzyl ester, and is converted to valsartan of formula I via a reaction with valeryl chloride and removing of protective groups. The method consists in converting, with hydrochloric acid, N-[(2'-(l-triphenylmethyl-tetrazol-5-yl)biphenyl-4­yl)methyl]-(L)-valine benzyl ester of formula 7, obtained in the first stage, to N -[(2'-(1-­triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl)methyl]-(L)-valine benzyl ester hydrochloride of formula III, which is optionally re-crystallized.

Abstract translation: 从起始的4-溴甲基-2' - （1-三苯基甲基四唑-5-基）联苯，N - [（2'（1-三苯基甲基 - 四唑-5-基）联苯-4-基）甲基] - （L） 通过与L-缬氨酸苄酯的反应获得式7的缬氨酸苄酯，并通过与戊酰氯反应和除去保护基团而转化成式I的缬沙坦。 该方法包括用盐酸转化得自式7的N - [（2' - （1-三苯甲基 - 四唑-5-基）联苯-4-基）甲基] - （L） - 缬氨酸苄基酯 转化为式III的N - [（2' - （1-三苯基甲基 - 四唑-5-基）联苯-4-基）甲基] - （L） - 缬氨酸苄酯盐酸盐，其任选地重结晶。

公开(公告)号：WO2007143959A3

公开(公告)日：2007-12-21

申请号：PCT/CZ2007/000056

申请日：2007-06-18

Applicant: ZENTIVA, A. S. ,  ZELEZNIK, Juraj ,  VLADOVICOVA, Beata ,  KORMANOVA, Viera ,  HUBINOVA, Viera ,  LEHOCKY, Mikulas

Inventor： ZELEZNIK, Juraj ,  VLADOVICOVA, Beata ,  KORMANOVA, Viera ,  HUBINOVA, Viera ,  LEHOCKY, Mikulas

IPC: A61K9/20

Abstract: Tablet containing metformin or pharmacologically acceptable salts thereof, where the active substance release is controlled by a hydrophobic polymer; the tablet contains 60 to 80 percent by weight of the active substance and 9 to 25 percent by weight of the hydrophobic polymer.

公开(公告)号：WO2005121084A1

公开(公告)日：2005-12-22

申请号：PCT/CZ2005/000048

申请日：2005-06-08

Applicant: ZENTIVA, a. s. ,  STEPANKOVA, Hana ,  PIHERA, Pavel ,  HAJICEK, Josef

Inventor： STEPANKOVA, Hana ,  PIHERA, Pavel ,  HAJICEK, Josef

IPC: C07D209/52

CPC classification number: C07D209/52

Abstract: A method of preparation of ramipril of formula (I), during which the benzyl ester hydrochloride of formula (III) is converted to the benzyl ester of formula (II), which in turn affords, by reaction with the carboxyanhydride of formula (V), the benzyl ester of ramipril of formula (IV), which is subsequently converted to ramipril of formula (I).

Abstract translation: 制备式（I）的雷米普利的方法，其中式（III）的苄酯盐酸盐转化成式（II）的苄基酯，其又通过与式（V）的羧酸酐反应， ，式（IV）的雷米普里的苄基酯，其随后转化成式（I）的雷米普利。

公开(公告)号：WO2004073585A2

公开(公告)日：2004-09-02

申请号：PCT/CZ2004/000009

申请日：2004-02-20

Applicant: ZENTIVA, a. s. ,  RADL, Stanislav ,  JARRAH, Kamal

Inventor： RADL, Stanislav ,  JARRAH, Kamal

IPC: A61K

CPC classification number: C07C211/35 ,  C07B2200/07 ,  C07D207/38

Abstract: A method of manufacturing glimepiride of formula I wherein trans-4-methylcyclohexylamine pivalate of formula VII is reacted, either directly or after conversion to trans-4-methylcyclohexylamine or to its another salt, with an alkyl [4-(2-{[(3-ethyl-4-methyl-2-oxo-2,5-dihydro-lH-pyrrol-l yl)carbonyl]amino)ethyl)phenyl]-sulfonyl carbamate of general formula IV wherein R is a C1-C5 alkyl, giving glimepiride of formula I. trans-4-Methylcyclohexylamine pivalate of formula VII.

Abstract translation: 式I的格列美脲的制备方法，其中式VII的反式-4-甲基环己胺新戊酸直接或在转化成反式-4-甲基环己胺或其另一种盐之后与[4-（2 - {[（ 3-乙基-4-甲基-2-氧代-2,5-二氢-1H-吡咯-1-基）羰基]氨基）乙基）苯基] - 磺酰基氨基甲酸酯，其中R是C1-C5烷基，得到 式I的格列美脲。式VII的反式-4-甲基环己胺新戊酸酯。