公开(公告)号：WO2008017278A2

公开(公告)日：2008-02-14

申请号：PCT/CZ2007/000078

申请日：2007-08-09

Applicant: ZENTIVA, A.S. ,  SVOBODA, Martin ,  JAMPILEK, Josef ,  KACIRKOVA, Martina ,  TOMASEK, Vaclav ,  LEHOCKY, Mikulas ,  HEJTMANKOVA, Ludmila ,  VOSATKA, Vaclav

Inventor： SVOBODA, Martin ,  JAMPILEK, Josef ,  KACIRKOVA, Martina ,  TOMASEK, Vaclav ,  LEHOCKY, Mikulas ,  HEJTMANKOVA, Ludmila ,  VOSATKA, Vaclav

IPC: C07C213/10 ,  C07C215/54 ,  A61K31/137

CPC classification number: C07C215/54 ,  C07C213/10

Abstract: A crystalline salt of 2-[(1R)-3-[bis(l-methylethyl)amino]-1-ρhenylρropyl]-4-methyl-phenol with (2R,3R)-2,3-dihydroxybutanedioic acid, known under the name R-tolterodine tartarate, wherein: a) at least 90 % of all crystals are present in a size smaller than 30 μm, b) at least 40 % of crystalline matter are smaller than 250 μm, c) the maximum size of crystals does not exceed 800 μm, d) the salt contains less than 0.1 weight % of the undesirable enantiomer S-tolterodine tartarate, e) analytical test for sulfate ashes (Pharm. Eur.) provides a value lower than 0.1%. The method of its preparation involves at least one crystallization from water. A pharmaceutical composition containing tolterodine or its pharmaceutically acceptable salts further contains a filler, a disintegrant and a lubricant, said composition being free of ions of alkaline earth metals.

Abstract translation: （2R，3R）-2,2-二甲基苯胺的2 - [（1R）-3- [双（1-甲基乙基）氨基] -1-苯基丙基] -4-甲基 - 苯酚的晶体盐， 其中：a）全部晶体的至少90％以小于30μm的尺寸存在，b）至少40％的晶体物质小于250μm， c）晶体的最大尺寸不超过800μm，d）盐含有小于0.1重量％的不希望的对映体S-托特罗定酒石酸盐，e）硫酸盐灰分（欧洲药典）的分析测试提供的值低于 0.1％。 其制备方法涉及至少一次从水中结晶。 包含托特罗定或其药学上可接受的盐的药物组合物还含有填充剂，崩解剂和润滑剂，所述组合物不含碱土金属离子。

公开(公告)号：WO2008106901A8

公开(公告)日：2008-09-12

申请号：PCT/CZ2008/000024

申请日：2008-03-03

Applicant: ZENTIVA, A.S. ,  PROKOPOVA, Alena ,  SEBEK, Pavel ,  HANOVSKA, Anna ,  DUBOVSKA, Michaela ,  TOMASEK, Vaclav

Inventor： PROKOPOVA, Alena ,  SEBEK, Pavel ,  HANOVSKA, Anna ,  DUBOVSKA, Michaela ,  TOMASEK, Vaclav

IPC: A61K31/40 ,  A61K9/16 ,  A61K9/28

Abstract: A pharmaceutical composition containing the active substance atorvastatin in the form of oblong-shaped tablets with the length of 5 to 22 mm and the width of 2 to 11 mm or round tablets with the diameter of 3 to 16 mm, the core of which is constituted of compressed granulate and contains: i. Atorvastatin and/or at least one physiologically acceptable salt thereof in the quantity of 5 to 10% by weight, related to pure atorvastatin; ii. An organic or inorganic base selected from meglumine or an alkali metal hydroxide or their combination in the quantity of 0.01 to 7% by weight; iii. A pharmaceutically acceptable filler in the quantity of 20 to 90% by weight; iv. A disintegrant in the quantity of 0.5 to 50% by weight; provided with a coat that makes up 1 to 15% of the weight of the core, the selected base being uniformly distributed in the tablet core by means of spraying the same on the solid mixture in the granule production process. The composition can be obtained by a procedure consisting of the following steps: i. Mixing a mixture of atorvastatin, a filler and a disintegrant; ii. Dissolving a base in a mixture of water and a C 1 to C 3 alcohol in the quantity of 10 : 90 to 90 : 10 (water/alcohol, by weight); iii. Spraying the dry mixture with the base solution either in a masticating or fluidizing device; iv. Adapting the size of particles of the resulting granulate, preferably by re-sieving to the granule size of 0.1 to 1.5 mm; v. Adding other extragranular components to the granulate that will further improve its ability to be compressed into tablets; vi. Compressing the mixture; and vii. Applying a coat on the compressed tablets.

公开(公告)号：WO2009012733A2

公开(公告)日：2009-01-29

申请号：PCT/CZ2008000087

申请日：2008-07-23

Applicant: ZENTIVA AS ,  RIHA JAROSLAV ,  REZAC JAROSLAV ,  MUZIKAR JAN ,  GOMOLA RUDOLF ,  TOMASEK VACLAV ,  TRCKA MIROSLAV

Inventor： RIHA JAROSLAV ,  REZAC JAROSLAV ,  MUZIKAR JAN ,  GOMOLA RUDOLF ,  TOMASEK VACLAV ,  TRCKA MIROSLAV

CPC classification number: A61K31/565 ,  A61K9/2018 ,  A61K9/2095

Abstract: Method of manufacture of compressed pharmaceutical formulation with the active substance tibolone by direct compression into tablets, whereas during the manufacturing process the formulation is subjected to the action of a protic solvent, either by addition of 0.1 to 3% by weight of said solvent in the liquid state and/or in the vapor form by ensuring the ambient atmosphere with the contents of solvent vapors above 50% relative.

Abstract translation: 通过将活性物质替勃龙直接压制成片剂制造压制药物制剂的方法，而在制造过程中，制剂经受质子溶剂的作用，或者通过加入0.1-3％重量的所述溶剂 液态和/或蒸汽形式，通过确保环境大气中溶剂蒸汽的含量高于50％。

公开(公告)号：WO2008017278B1

公开(公告)日：2008-08-28

申请号：PCT/CZ2007000078

申请日：2007-08-09

Applicant: ZENTIVA AS ,  SVOBODA MARTIN ,  JAMPILEK JOSEF ,  KACIRKOVA MARTINA ,  TOMASEK VACLAV ,  LEHOCKY MIKULAS ,  HEJTMANKOVA LUDMILA ,  VOSATKA VACLAV

Inventor： SVOBODA MARTIN ,  JAMPILEK JOSEF ,  KACIRKOVA MARTINA ,  TOMASEK VACLAV ,  LEHOCKY MIKULAS ,  HEJTMANKOVA LUDMILA ,  VOSATKA VACLAV

IPC: C07C213/10 ,  A61K31/137 ,  C07C215/54

CPC classification number: C07C215/54 ,  C07C213/10

Abstract: A crystalline salt of 2-[(1R)-3-[bis(l-methylethyl)amino]-1-?henyl?ropyl]-4-methyl-phenol with (2R,3R)-2,3-dihydroxybutanedioic acid, known under the name R-tolterodine tartarate, wherein: a) at least 90 % of all crystals are present in a size smaller than 30 µm, b) at least 40 % of crystalline matter are smaller than 250 µm, c) the maximum size of crystals does not exceed 800 µm, d) the salt contains less than 0.1 weight % of the undesirable enantiomer S-tolterodine tartarate, e) analytical test for sulfate ashes (Pharm. Eur.) provides a value lower than 0.1%. The method of its preparation involves at least one crystallization from water. A pharmaceutical composition containing tolterodine or its pharmaceutically acceptable salts further contains a filler, a disintegrant and a lubricant, said composition being free of ions of alkaline earth metals.

Abstract translation: 2 - [（1R）-3- [双（1-甲基乙基）氨基] -1-苯基乙酰基] -4-甲基 - 苯酚与（2R，3R）-2,3-二羟基丁二酸的结晶盐， 以名称R-tolterodine酒石酸盐，其中：a）至少90％的晶体以小于30μm的尺寸存在，b）至少40％的结晶物质小于250μm，c）最大尺寸 的晶体不超过800μm，d）盐含有小于0.1重量％的不需要的对映体S-托特罗定酒石酸酯，e）硫酸盐灰分析（Pharm.Eur。）的分析测试提供的值低于0.1％。 其制备方法涉及至少一种从水中的结晶。 含有托特罗定或其药学上可接受的盐的药物组合物还含有填料，崩解剂和润滑剂，所述组合物不含碱土金属的离子。

公开(公告)号：WO2003068203A1

公开(公告)日：2003-08-21

申请号：PCT/CZ2003/000008

申请日：2003-01-30

Applicant: LECIVA, a.s. ,  DOLEZAL, Tomàs ,  KRSIAK, Miloslav ,  TOMASEK, Vaclav

Inventor： DOLEZAL, Tomàs ,  KRSIAK, Miloslav ,  TOMASEK, Vaclav

IPC: A61K31/09

CPC classification number: A61K31/09 ,  A61K31/522 ,  A61K2300/00

Abstract: The use of the combination of a non-steroidal anti-inflammatory agent and 3-(2-methoxyphenoxy)-1, 2-propanediol (guaifenesin) and optionally caffeine, for the manufacture of a pharmaceutical intended for the treatment of acute pains.

Abstract translation: 使用非甾体抗炎剂和3-（2-甲氧基苯氧基）-1,2-丙二醇（愈创甘油醚）和任选的咖啡因的组合来制造用于治疗急性疼痛的药物。

公开(公告)号：WO2010012248A1

公开(公告)日：2010-02-04

申请号：PCT/CZ2009/000096

申请日：2009-07-28

Applicant: ZENTIVA, K.S. ,  PROKOPOVA, Alena ,  GRYCZOVA, Eva ,  TOMASEK, Vaclav

Inventor： PROKOPOVA, Alena ,  GRYCZOVA, Eva ,  TOMASEK, Vaclav

IPC: A61K9/20 ,  A61K31/4184

CPC classification number: A61K9/2009 ,  A61K9/2013 ,  A61K9/2018 ,  A61K9/2027 ,  A61K31/4184

Abstract: A composition containing the active substance telmisartan, which consists of granules of a telmisartan mixture, in which there is the active substance in the form of alkali salts, further contained is an organic or inorganic base selected from meglumine, sodium or potassium hydroxide, or a mixture of said bases, a binder, most preferably polyvinylpyrrolidone, sorbitol, and optionally other auxiliary substances; the composition further containing, outside the granules, particles of sorbitol, and optionally of other auxiliary substance, the size of 99 % by\ weight of all particles of the telmisartan mixture being smaller than 1.0 mm and the size of 95 % by weight of all particles of sorbitol contained in the composition inside as well as outside the granules of the telmisartan mixture being within the range of 0 to 0.250 mm.

Abstract translation: 含有活性物质替米沙坦的组合物，其中还含有选自葡甲胺，氢氧化钠或氢氧化钾的有机或无机碱，其中存在碱金属盐形式的活性物质的替米沙坦混合物的颗粒， 所述碱的混合物，粘合剂，最优选聚乙烯吡咯烷酮，山梨糖醇和任选的其它辅助物质; 所述组合物还含有颗粒外的山梨醇颗粒和任选的其它辅助物质，所述替米沙坦混合物的所有颗粒的重量为99％，所述颗粒的重量小于1.0mm，并且所有尺寸为95重量％ 包含在组合物内部以及替米沙坦混合物的颗粒外的山梨糖醇颗粒在0至0.250mm的范围内。

公开(公告)号：WO2009012733A3

公开(公告)日：2009-01-29

申请号：PCT/CZ2008/000087

申请日：2008-07-23

Applicant: ZENTIVA A.S. ,  RIHA, Jaroslav ,  REZAC, Jaroslav ,  MUZIKAR, Jan ,  GOMOLA, Rudolf ,  TOMASEK, Vaclav ,  TRCKA, Miroslav

Inventor： RIHA, Jaroslav ,  REZAC, Jaroslav ,  MUZIKAR, Jan ,  GOMOLA, Rudolf ,  TOMASEK, Vaclav ,  TRCKA, Miroslav

IPC: A61K31/565

Abstract: Method of manufacture of compressed pharmaceutical formulation with the active substance tibolone by direct compression into tablets, whereas during the manufacturing process the formulation is subjected to the action of a protic solvent, either by addition of 0.1 to 3% by weight of said solvent in the liquid state and/or in the vapor form by ensuring the ambient atmosphere with the contents of solvent vapors above 50% relative.

公开(公告)号：WO2008106901A1

公开(公告)日：2008-09-12

申请号：PCT/CZ2008000024

申请日：2008-03-03

Applicant: ZENTIVA AS ,  PROKOPOVA ALENA ,  SEBEK PAVEL ,  DUBOVSKA MICHAELA ,  TOMASEK VACLAV

Inventor： PROKOPOVA ALENA ,  SEBEK PAVEL ,  DUBOVSKA MICHAELA ,  TOMASEK VACLAV

IPC: A61K31/40 ,  A61K9/16 ,  A61K9/28

CPC classification number: A61K9/2077 ,  A61K9/2018 ,  A61K9/2054 ,  A61K31/40

Abstract: A pharmaceutical composition containing the active substance atorvastatin in the form of oblong-shaped tablets with the length of 5 to 22 mm and the width of 2 to 11 mm or round tablets with the diameter of 3 to 16 mm, the core of which is constituted of compressed granulate and contains: i. Atorvastatin and/or at least one physiologically acceptable salt thereof in the quantity of 5 to 10% by weight, related to pure atorvastatin; ii. An organic or inorganic base selected from meglumine or an alkali metal hydroxide or their combination in the quantity of 0.01 to 7% by weight; iii. A pharmaceutically acceptable filler in the quantity of 20 to 90% by weight; iv. A disintegrant in the quantity of 0.5 to 50% by weight; provided with a coat that makes up 1 to 15% of the weight of the core, the selected base being uniformly distributed in the tablet core by means of spraying the same on the solid mixture in the granule production process. The composition can be obtained by a procedure consisting of the following steps: i. Mixing a mixture of atorvastatin, a filler and a disintegrant; ii. Dissolving a base in a mixture of water and a C 1 to C 3 alcohol in the quantity of 10 : 90 to 90 : 10 (water/alcohol, by weight); iii. Spraying the dry mixture with the base solution either in a masticating or fluidizing device; iv. Adapting the size of particles of the resulting granulate, preferably by re-sieving to the granule size of 0.1 to 1.5 mm; v. Adding other extragranular components to the granulate that will further improve its ability to be compressed into tablets; vi. Compressing the mixture; and vii. Applying a coat on the compressed tablets.

Abstract translation: 一种药物组合物，其含有长度为5〜22mm，宽度为2〜11mm的椭圆形片状的活性物质阿托伐他汀或其核心构成的直径为3〜16mm的圆形片剂 压缩颗粒，包含：i。 阿托伐他汀和/或其至少一种生理上可接受的盐，其量为5至10重量％，与纯阿托伐他汀有关; II。 选自葡甲胺或碱金属氢氧化物或其组合的有机或无机碱的量为0.01至7重量％; III。 一种药学上可接受的填料，其量为20至90重量％; IV。 崩解剂的量为0.5〜50重量％; 其具有构成芯的重量的1〜15％的涂层，通过在颗粒制造工序中将固体混合物喷雾而将选定的基体均匀地分布在片芯中。 组合物可以通过以下步骤组成的方法获得：i。 混合阿托伐他汀，填充剂和崩解剂的混合物; II。 以10：90至90：10（水/醇，重量比）的量将水与C 1〜3的混合物中的碱溶解于C 3醇中; III。 在干燥的混合物中用基础溶液喷洒在咀嚼或流化装置中; IV。 适应所得颗粒的颗粒大小，优选通过重新筛分至0.1至1.5mm的颗粒尺寸; v。向颗粒中加入其他颗粒外成分，进一步提高其压制成片剂的能力; 六。 压缩混合物; 和vii。 在压片上涂上外套。

公开(公告)号：WO2008017278A3

公开(公告)日：2008-07-10

申请号：PCT/CZ2007000078

申请日：2007-08-09

Applicant: ZENTIVA AS ,  SVOBODA MARTIN ,  JAMPILEK JOSEF ,  KACIRKOVA MARTINA ,  TOMASEK VACLAV ,  LEHOCKY MIKULAS ,  HEJTMANKOVA LUDMILA ,  VOSATKA VACLAV

Inventor： SVOBODA MARTIN ,  JAMPILEK JOSEF ,  KACIRKOVA MARTINA ,  TOMASEK VACLAV ,  LEHOCKY MIKULAS ,  HEJTMANKOVA LUDMILA ,  VOSATKA VACLAV

IPC: C07C213/10 ,  A61K31/137 ,  C07C215/54

CPC classification number: C07C215/54 ,  C07C213/10

Abstract: A crystalline salt of 2-[(1R)-3-[bis(l-methylethyl)amino]-1-?henyl?ropyl]-4-methyl-phenol with (2R,3R)-2,3-dihydroxybutanedioic acid, known under the name R-tolterodine tartarate, wherein: a) at least 90 % of all crystals are present in a size smaller than 30 µm, b) at least 40 % of crystalline matter are smaller than 250 µm, c) the maximum size of crystals does not exceed 800 µm, d) the salt contains less than 0.1 weight % of the undesirable enantiomer S-tolterodine tartarate, e) analytical test for sulfate ashes (Pharm. Eur.) provides a value lower than 0.1%. The method of its preparation involves at least one crystallization from water. A pharmaceutical composition containing tolterodine or its pharmaceutically acceptable salts further contains a filler, a disintegrant and a lubricant, said composition being free of ions of alkaline earth metals.

Abstract translation: 2 - [（1R）-3- [双（1-甲基乙基）氨基] -1-苯基丙基] -4-甲基 - 苯酚与（2R，3R）-2,3-二羟基丁二酸的结晶盐， 以名称R-托特罗定酒石酸盐公知，其中：a）全部晶体的至少90％以小于30μm的尺寸存在，b）至少40％的晶体物质小于250μm，c）最大尺寸 的晶体不超过800μm，d）盐含有小于0.1重量％的不良对映体S-托特罗定酒石酸盐，e）硫酸盐灰分（欧洲药典）的分析测试提供的值低于0.1％。 其制备方法涉及至少一次从水中结晶。 含有托特罗定或其药学上可接受的盐的药物组合物还含有填充剂，崩解剂和润滑剂，所述组合物不含碱土金属离子。