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1. 发明授权

US5047247A Dispersible tablets of dihydroergotoxine methanesulfonate and of acid addition salts thereof 失效
标题翻译：二氢麦角毒素甲磺酸盐的分散片及其酸加成盐
公开(公告)号：US5047247A
公开(公告)日：1991-09-10
申请号：US412740
申请日：1989-09-26
申请人： Jenny Milovac , Mateja Kovacic , Zdravko Kopitar , Janja Urbancic-Smerkolj , Andrej Lenardic , Mirjan Zorz , Bojan Kofler , Angela Vene-Mozina , Vida Nikolic , Marija Lampret , Breda Meden
发明人： Jenny Milovac , Mateja Kovacic , Zdravko Kopitar , Janja Urbancic-Smerkolj , Andrej Lenardic , Mirjan Zorz , Bojan Kofler , Angela Vene-Mozina , Vida Nikolic , Marija Lampret , Breda Meden
IPC分类号： C07D519/02 , A61K9/20 , A61K31/48 , A61P9/00 , A61P25/28
CPC分类号： A61K9/2059 , A61K31/48 , A61K9/2013 , A61K9/2027 , A61K9/2054
摘要： There are described novel dispersible tablets of dihydroergotoxine or of acid addition salts thereof, containing 0.1 to 4% by weight of dihydroergotoxine or its acid addition salts, 4 to 60% by weight of one or more disintegrating agents, 0.8 to 10% by weight of an organic acid and, optionally, 0.2 to 2% by weight of an antioxidizing agent together with other common adjuvants. The process for the manufacture of dispersible tablets of dihydroergotoxine and of acid addition salts thereof is carried out on the basis of known methods by granulating the ingredients and by compressing the granulate to tablets. Dispersible tablets disintegrate within less than 1 minute when brought in contact with water at room temperature to yield a fine dispersion, which facilitates the oral application. Therefore such tablets are particularly suitable for the aged. Dispersible tablets containing dihydroergotoxine or acid addition salts thereof excell by their improved rate of dissolution and good bioavailability.

2. 发明授权

US5079237A Inclusion complex of nicardipine or its hydrochloride with beta-cyclodextrin and a sustained release pharmaceutical preparation containing the same 失效
标题翻译：包括尼卡地平或其盐酸盐与β-环糊精的复合物和含有其的持续释放药物制剂
公开(公告)号：US5079237A
公开(公告)日：1992-01-07
申请号：US298151
申请日：1989-01-18
申请人： Breda Husu , Jenny Milovac , Zdravko Kopitar , Branko Huc , Janko Zmitek , Peter Bukovec , Mirjan Zorz , Boris Rusjakovski , Polona Cvelbar , Zdenka Jerala-Strukelj , Bojan Kofler
发明人： Breda Husu , Jenny Milovac , Zdravko Kopitar , Branko Huc , Janko Zmitek , Peter Bukovec , Mirjan Zorz , Boris Rusjakovski , Polona Cvelbar , Zdenka Jerala-Strukelj , Bojan Kofler
IPC分类号： C07D211/90 , A61K31/44 , A61K31/455 , A61K47/40 , A61K47/48 , A61P9/08 , A61P9/10 , A61P9/12 , C08B37/00
CPC分类号： B82Y5/00 , A61K31/44 , A61K47/48969 , C08B37/0015 , Y10S514/929 , Y10S514/964
摘要： There is described a new inclusion complex of nicardipine or its hydrochloride with beta-cyclohdextrin, which is prepared by admixing nicardipine or its hydrochloride with beta-cyclodextrin in a molar ratio of the compounds 1:0.9-1.1 under stirring at a temperature from about room temperature to the boiling temperature of the reaction mixture in an aqueous or ethanolic medium, cooling the reaction mixture to 0.degree. to 5.degree. C. and isolating the desired complex.The inclusion complex of nicardipine or its hydrochloride posesses cerebrovascular-vasodilatory and coronary-vasodilatory properties, which are equally well expressed as those of nicardipine or its hydrochloride themselves, yet owing to the better solubility of the complex at a higher pH range, such as it exists e.g. in the intestinal tract, the manufacture of sustained release pharmaceutical forms is made possible, whereby a greater extent of dissolution of the active substance is provided also in the intestinal juice.

3. 发明授权

US6042847A Three-phase pharmaceutical form with constant and controlled release of amorphous active ingredient for single daily application 失效
公开(公告)号：US6042847A
公开(公告)日：2000-03-28
申请号：US945984
申请日：1997-11-12
申请人： Janez Kerc , Ljubomira Barbara Rebic , Bojan Kofler
发明人： Janez Kerc , Ljubomira Barbara Rebic , Bojan Kofler
IPC分类号： A61K9/20 , A61K9/22 , A61K9/28 , A61K9/30 , A61K31/455 , A61K45/08 , A61K47/30 , A61P9/00 , A61K9/24
CPC分类号： A61K9/2077 , A61K9/2886 , A61K9/2846 , A61K9/2866
摘要： Described is a novel three-phase pharmaceutical form with constant and controlled release of an amorphous active ingredient stabilized with polymers for a single daily peroral application, which is especially suitable for active ingredients existing in amorphous form or in one or more polymorphous forms, which exhibit poor solubility in crystal form depending on the polymorphous form, particle size and the specific surface area of the active ingredient. The active ingredient can be used in its amorphous or any polymorphous form, which in the process of the preparation of the three-phase pharmaceutical form according to the invention is converted into the amorphous form. The three-phase pharmaceutical form with constant and controlled release of an amorphous active ingredient for a single daily peroral application contains a core consisting of a first and a second phase and a coating representing the third phase. In the first phase the three-phase pharmaceutical form contains an amorphous active ingredient, the water-soluble polymer polyvinylpyrrolidone and a cellulose ether as carriers of the amorphous active ingredient and simultaneously as inhibitors of its crystallization, a surfactant that improves the solubility of the active ingredient and promotes the absorption of the amorphous active ingredient from gastrointestinal tract, in the second phase it contains a cellulose ether and a mixture of mono-, di- and triglycerides as sustained release agents and the third phase is represented by a poorly soluble or gastro-resistant film coating, which in the first few hours after the application controls the release of the active ingredient and can consist of an ester of hydroxypropylmethylcellulose with phthalic anhydride or of a copolymerizate based on methacrylic acid and ethyl acrylate. Described is also a process for the preparation of this pharmaceutical form.

4. 发明授权

US06511972B1 Pharmaceutical suspension formulation comprising amoxycillin clavulanic acid and cellulose 有权
标题翻译：药物悬浮液制剂，其包含阿莫西林克拉维酸和纤维素
公开(公告)号：US06511972B1
公开(公告)日：2003-01-28
申请号：US09743998
申请日：2001-03-01
申请人： Bojan Kofler , Mateja Kovacic
发明人： Bojan Kofler , Mateja Kovacic
IPC分类号： A61K3143
CPC分类号： A61K47/38 , A61K9/146 , A61K31/43 , A61K31/42 , A61K2300/00
摘要： A liquid aqueous pharmaceutical suspension formulation containing as amoxycillin trihydrate, potassium clavulanate and microcrystalline cellulose filler is provided.
摘要翻译：提供含有阿莫西林三水合物，克拉维酸钾和微晶纤维素填料的液体水性药物悬浮液制剂。

5. 发明授权

US5069910A Dispersible cimetidine tablets 失效
标题翻译：不同的CIMETIDINE TABLETS
公开(公告)号：US5069910A
公开(公告)日：1991-12-03
申请号：US366437
申请日：1989-06-15
申请人： Mateja Kovacic , Jenny Milovac , Polona Cvelbar , Anton Stalc , Zvezdana Trost , Zdravko Kopitar , Bojan Kofler , Vida Nikolic , Marija Lampret , Marija Lippai
发明人： Mateja Kovacic , Jenny Milovac , Polona Cvelbar , Anton Stalc , Zvezdana Trost , Zdravko Kopitar , Bojan Kofler , Vida Nikolic , Marija Lampret , Marija Lippai
IPC分类号： A61K9/20 , A61K31/415 , A61P1/04
CPC分类号： A61K31/415 , A61K9/2004 , A61K9/2013 , A61K9/2031
摘要： There are described novel dispersible cimetidine tablets containing 30 to 90% by weight of one of the polymorphous modifications of cimetidine A, B or C, 5 to 55% by weight of one or more disintegrationg agents, 0.05 to 5.0% by weight of a surfactant, such as sodium lauryl sulphate together with other common adjuvants. The process for the manufacture of dispersible cimetidine tablets is effected on the basis of known methods by granulating the ingredients and by compressing the granulate to tablets. Dispersible tablets disintegrate when brought in contact with water at room temperature within less than 1 minute to yield a fine dispersion, which facilitates the oral application. Therefore such tablets are particularly suitable for certain groups of patients, especially for the aged and children. Dispersible tablets containing cimetidine excell by their improved rate of dissolution and good bioavailability.

6. 发明授权

US06576258B1 Pharmaceutical formulation with controlled release of active substances 失效
标题翻译：具有活性物质控制释放的药物制剂
公开(公告)号：US06576258B1
公开(公告)日：2003-06-10
申请号：US09462698
申请日：2000-01-12
申请人： Bojan Kofler , Ljubomira Barbara Rebi{haeck over (c)} , Judita {haeck over (S)}irca , Peter Venturini
发明人： Bojan Kofler , Ljubomira Barbara Rebi{haeck over (c)} , Judita {haeck over (S)}irca , Peter Venturini
IPC分类号： A61K916
CPC分类号： A61K9/1652 , A61K9/2095 , A61K9/5073
摘要： There is disclosed a method for stabilizing active substances that are unstable in acidic medium, unstable when stored for longer periods of time in the presence of water and at the same time sensitive to heating, by means of anhydrous granulation of active substances and dried pharmaceutically acceptable auxiliary substances for the preparation of pellet cores or granules. All pharmaceutically acceptable auxiliary substances employed are dried before use so that their weight loss at drying is less than 1.0% of the total weight of the pharmaceutically acceptable auxiliary substance, preferably less than 0.5%. Organic solvents used in process of anhydrous granulation should contain less than 0.2% of water. A novel pharmaceutical formulation with controlled release of active substances that are unstable in acidic medium, unstable when stored for longer periods of time in the presence of water and at the same time sensitive to heating, is disclosed as well.
摘要翻译：公开了一种稳定在酸性介质中不稳定的活性物质的方法，在水存在下储存更长时间并且对加热敏感的同时，通过活性物质的无水造粒和干燥的药学上可接受的方法不稳定用于制备颗粒芯或颗粒的辅助物质。使用的所有药学上可接受的辅助物质在使用前被干燥，使得它们在干燥时的重量损失小于药学上可接受的辅助物质总重量的1.0％，优选小于0.5％。在无水造粒过程中使用的有机溶剂应含有少于0.2％的水。还公开了一种在酸性介质中不稳定的活性物质的控制释放的新型药物制剂，在水存在下储存更长时间并且对加热敏感的同时存在时不稳定。

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