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1. 发明授权

US5360615A Solvent system enhancing the solubility of pharmaceuticals for encapsulation 失效
标题翻译：溶剂体系提高药物的包封溶解度
公开(公告)号：US5360615A
公开(公告)日：1994-11-01
申请号：US890285
申请日：1992-05-26
申请人： Man S. Yu , Foo S. Hom , Sibaprasanna Chakrabarti , Chong-Heng Huang , Mahendra Patel
发明人： Man S. Yu , Foo S. Hom , Sibaprasanna Chakrabarti , Chong-Heng Huang , Mahendra Patel
IPC分类号： A61K9/08 , A61K9/00 , A61K9/20 , A61K9/48 , A61K9/66 , A61K45/00 , A61K47/00 , A61K47/04 , A61K47/32 , A61K47/34
CPC分类号： A61K9/2009 , A61K9/2031 , A61K9/485 , A61K9/4858 , A61K9/4866
摘要： This invention relates to a solvent system for enhancing the solubility of an acidic, basic, or amphoteric pharmaceutical agent to produce a highly concentrated solution suitable for softgel filling or two piece encapsulation. The solvent system comprises polyethylene glycol containing 0.2-1.0 mole equivalents of an ionizing agent per mole equivalent pharmaceutical agent and 1-20% water. Glycerin or polyvinylpyrrolidone may be added to further enhance the solubility of certain drugs. The disclosed solvent system is capable of enhancing solubilities of pharmaceutical agents 40-400%.The ionizing agent functions by causing partial ionization (neutralization) of the free pharmaceutical agent. When the pharmaceutical agent is acidic, the ionizing agent is preferably a hydroxide ion species, whereas when the pharmaceutical agent is basic, the ionizing agent is preferably a hydrogen ion species. For amphoteric pharmaceutical agents, either hydroxide ion or hydrogen ion sources may be utilized to effect partial ionization.The disclosed solvent system is useful because it not only provides for the enhancement or improvement of bioavailability of acidic, basic and amphoteric pharmaceutical agents by delivering them already in solution, but it also provides for a highly concentrated solution capable of encapsulation in a small enough vessel to permit easy swallowing.The highly concentrated solid solutions of the present invention are also useful for conversion into tablets and as veterinary spot and pour on preparations.
摘要翻译：本发明涉及一种用于增强酸性，碱性或两性药剂在产生适于软胶囊填充或两片封装的高度浓缩溶液中的溶解度的溶剂体系。溶剂系统包含每摩尔当量药剂和1-20％水含有0.2-1.0摩尔当量离子化剂的聚乙二醇。可以加入甘油或聚乙烯吡咯烷酮以进一步提高某些药物的溶解度。所公开的溶剂系统能够提高40-400％的药剂的溶解度。电离剂通过引起游离药剂的部分电离（中和）起作用。当药剂为酸性时，电离剂优选为氢氧根离子，而当药剂为碱性时，电离剂优选为氢离子。对于两性药剂，可以使用氢氧根离子或氢离子源来实现部分电离。所公开的溶剂系统是有用的，因为它不仅通过将其输送到溶液中来提供酸性，碱性和两性药物的生物利用度的增强或改善，而且还提供能够在足够小的容器中包封的高度浓缩的溶液容易吞咽。本发明的高度浓缩的固体溶液也可用于转化成片剂和兽药斑点并倒入制剂上。

2. 发明授权

US5071643A Solvent system enhancing the solubility of pharmaceuticals for encapsulation 失效
标题翻译：溶剂系统提高药物的溶解度
公开(公告)号：US5071643A
公开(公告)日：1991-12-10
申请号：US104911
申请日：1987-10-09
申请人： Man S. Yu , Foo S. Hom , Sibaprasanna Chakrabarti , Chong-Heng Huang , Mahendra Patel
发明人： Man S. Yu , Foo S. Hom , Sibaprasanna Chakrabarti , Chong-Heng Huang , Mahendra Patel
IPC分类号： A61K9/08 , A61K9/00 , A61K9/20 , A61K9/48 , A61K9/66 , A61K45/00 , A61K47/00 , A61K47/04 , A61K47/32 , A61K47/34
CPC分类号： A61K9/2009 , A61K9/2031 , A61K9/485 , A61K9/4858 , A61K9/4866
摘要： This invention relates to a solvent system for enhancing the solubility of an acidic, basic, or amphoteric pharmaceutical agent to produce a highly concentrated solution suitable for softgel filling or two piece encapsulation. The solvent system comprises polyethylene glycol containing 0.2-1.0 mole equivalents of an ionizing agent per mole equivalent pharmaceutical agent and 1-20% water. Glycerin or polyvinylpyrrolidone may be added to further enhance the solubility of certain drugs. The disclosed solvent system is capable of enhancing solubilities of pharmaceutical agents 40-400%.The ionizing agent functions by causing partial ionization (neutralization) of the free pharmaceutical agent. When the pharmaceutical agent is acidic, the ionizing agent is preferably a hydroxide ion species, whereas when the pharmaceutical agent is basic, the ionizing agent is preferably a hydrogen ion species. For amphoteric pharmaceutical agents, either hydroxide ion or hydrogen ion sources may be utilized to effect partial ionization.The disclosed solvent system is useful because it not only provides for the enhancement or improvement of bioavailability of acidic, basic and amphoteric pharmaceutical agents by delivering them already in solution, but it also provides for a highly concentrated solution capable of encapsulation in a small enough vessel to permit easy swallowing.The highly concentrated solid solutions of the present invention are also useful for conversion into tablets and as veterinary spot and pour on preparations.
摘要翻译：本发明涉及一种用于增强酸性，碱性或两性药剂在产生适于软胶囊填充或两片封装的高度浓缩溶液中的溶解度的溶剂体系。溶剂系统包含每摩尔当量药剂和1-20％水含有0.2-1.0摩尔当量离子化剂的聚乙二醇。可以加入甘油或聚乙烯吡咯烷酮以进一步提高某些药物的溶解度。所公开的溶剂系统能够提高40-400％的药剂的溶解度。电离剂通过引起游离药剂的部分电离（中和）起作用。当药剂为酸性时，电离剂优选为氢氧根离子，而当药剂为碱性时，电离剂优选为氢离子。对于两性药剂，可以使用氢氧根离子或氢离子源来实现部分电离。所公开的溶剂系统是有用的，因为它不仅通过将其输送到溶液中来提供酸性，碱性和两性药物的生物利用度的增强或改善，而且还提供能够在足够小的容器中包封的高度浓缩的溶液容易吞咽。本发明的高度浓缩的固体溶液也可用于转化成片剂和兽药斑点并倒入制剂上。

3. 发明授权

US4532126A Masticatory soft elastic gelatin capsules and method for the manufacture thereof 失效
标题翻译：咀嚼软弹性明胶胶囊及其制造方法
公开(公告)号：US4532126A
公开(公告)日：1985-07-30
申请号：US549998
申请日：1983-11-08
申请人： William R. Ebert , Foo S. Hom , Warren W. Kindt
发明人： William R. Ebert , Foo S. Hom , Warren W. Kindt
IPC分类号： A23G3/00 , A23G3/36 , A23G3/44 , A23G4/00 , A23G4/10 , A23G4/12 , A23G4/14 , A61K9/00 , A61K9/48 , A23G3/30 , A61K9/68
CPC分类号： A23G3/44 , A23G3/368 , A23G3/54 , A23G4/10 , A23G4/126 , A23G4/14 , A61K9/0056 , A61K9/4816 , A61K9/4858 , Y10S514/962
摘要： A chewable, filled, one-piece soft elastic gelatin (SEG) capsule. The capsule includes a shell which is formed from a formulation of gelatin, water, a plasticizer, and a masticatory substance. The masticatory substance is present in the shell in an amount of about 1-75 percent by weight and the gelatin is present in the shell in an amount of about 10-90 percent by weight. A fill material is contained within the shell. The fill may be selected from a variety of materials, including candy, various confectionaries, antacids, cough and cold preparations, sore throat remedies, antiseptics, dental preparations, such as fluorides, breath fresheners, and the like. In manufacturing the SEG capsules, a molten gel mass is prepared with a dispersion of a molten masticatory substance therein. A suitable fill material is also prepared. The gelatin formulation containing the masticatory substance dispersed therein is formed as a shell around the fill material. The capsules are dried until the desired chewing characteristics are attained.
摘要翻译：一种咀嚼，填充，单件软弹性明胶（SEG）胶囊。胶囊包括由明胶，水，增塑剂和咀嚼物质的制剂形成的壳。咀嚼物质以约1-75重量％的量存在于壳中，明胶以约10-90重量％的量存在于壳中。填充材料包含在外壳内。填充物可以选自各种材料，包括糖果，各种糖果，抗酸剂，咳嗽和冷制剂，喉咙痛补救剂，防腐剂，牙科制剂如氟化物，呼吸清新剂等。在制造SEG胶囊时，用熔融咀嚼物质的分散体制备熔融凝胶块。还制备合适的填充材料。包含分散在其中的咀嚼物质的明胶制剂形成为填充材料周围的壳。将胶囊干燥直到达到所需的咀嚼特性。

4. 发明授权

US4800083A Sustained release method and product 失效
标题翻译：持续释放方法和产品
公开(公告)号：US4800083A
公开(公告)日：1989-01-24
申请号：US921069
申请日：1986-10-20
申请人： Foo S. Hom , William R. Ebert
发明人： Foo S. Hom , William R. Ebert
IPC分类号： A61K9/48 , A61K9/52 , A61K9/68
CPC分类号： A61K9/4858 , A61K9/4866
摘要： A capsule product and method for gradually releasing a medicament for absorption to a body of a warm blooded animal through the gastrointestinal system. The capsule has a fill material which includes a masticatory substance and a medicament that is dispersed throughout the gum. The medicament is of a type that is effectively and desirably released for absorption by the body through the gastrointestinal tract over an extended period of time. The masticatory substance forms a supporting cohesive matrix for the medicament. The gelatin shell, usually formed from gelatin, water, and a plasticizer, formed around the fill material into a capsule of a size and shape to be readily swallowable. Upon swallowing, the gelatin shell is rapidly dissolved in the gastrointestinal juices, while the fill material is substantially insoluble in the gastrointestinal juices. The matrix having the medicament dispersed throughout is subjected to substantially continuous random motion while contained within the gastrointestinal juices, while at body temperatures, and while under the influence of peristaltic movement for substantially varying the exposed surface area of the fill. As the surface area of the fill material is being changed, the medicament is gradually released from the exposed surface area for an extended period of time for ultimate absorption of the drug by the body.
摘要翻译：一种胶囊产品和方法，用于通过胃肠系统逐渐释放用于吸收温血动物身体的药物。胶囊具有填充材料，其包括咀嚼物质和分散在整个牙龈中的药物。药物是一种有效和期望地释放的类型，其被身体通过胃肠道在延长的时间段内吸收。咀嚼物形成用于药物的支持性内聚基质。通常由明胶，水和增塑剂形成的明胶壳体，其形成在填充材料周围，成为容易吞咽的尺寸和形状的胶囊。吞咽后，明胶壳迅速溶解在胃肠液中，而填充物质基本上不溶于胃肠液。具有分散在其中的药物的基质在包含在胃肠液中的同时在体温下并且在蠕动运动的影响下受到基本上连续的随机运动，用于基本上改变填充物的暴露的表面积。随着填充材料的表面积改变，药物从暴露的表面区域逐渐释放一段较长的时间，以最终吸收身体的药物。

5. 发明授权

US4428927A Masticatory soft elastic gelatin capsules and method for the manufacture thereof 失效
标题翻译：咀嚼软弹性明胶胶囊及其制造方法
公开(公告)号：US4428927A
公开(公告)日：1984-01-31
申请号：US376115
申请日：1982-05-07
申请人： William R. Ebert , Foo S. Hom , Warren W. Kindt
发明人： William R. Ebert , Foo S. Hom , Warren W. Kindt
IPC分类号： A23G3/00 , A23G3/36 , A23G3/44 , A23G4/00 , A23G4/10 , A23G4/12 , A23G4/14 , A23G4/20 , A61K9/00 , A61K9/48 , A23G3/30 , A61K9/68
CPC分类号： A23G3/44 , A23G3/368 , A23G3/54 , A23G4/10 , A23G4/126 , A23G4/14 , A23G4/20 , A61K9/0056 , A61K9/4816 , A61K9/4858
摘要： A chewable, filled, one-piece soft elastic gelatin (SEG) capsule. The capsule includes a shell which is formed from a formulation of gelatin, water, a plasticizer, and a masticatory substance. The masticatory substance is present in the shell in an amount of about 1-75 percent by weight and the gelatin is present in the shell in an amount of about 10-90 percent by weight. A fill material is contained within the shell. The fill may be selected from a variety of materials, including candy, various confectionaries, antacids, cough and cold preparations, sore throat remedies, antiseptics, dental preparations, such as fluorides, breath fresheners, and the like. In manufacturing the SEG capsules, a molten gel mass is prepared with a dispersion of a molten masticatory substance therein. A suitable fill material is also prepared. The gelatin formulation containing the masticatory substance dispersed therein is formed as a shell around the fill material. The capsules are dried until the desired chewing characteristics are attained.
摘要翻译：一种咀嚼，填充，单件软弹性明胶（SEG）胶囊。胶囊包括由明胶，水，增塑剂和咀嚼物质的制剂形成的壳。咀嚼物质以约1-75重量％的量存在于壳中，明胶以约10-90重量％的量存在于壳中。填充材料包含在外壳内。填充物可以选自各种材料，包括糖果，各种糖果，抗酸剂，咳嗽和冷制剂，喉咙痛补救剂，防腐剂，牙科制剂如氟化物，呼吸清新剂等。在制造SEG胶囊时，用熔融咀嚼物质的分散体制备熔融凝胶块。还制备合适的填充材料。包含分散在其中的咀嚼物质的明胶制剂形成为填充材料周围的壳。将胶囊干燥直到达到所需的咀嚼特性。

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