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21. 发明授权

US07378394B2 Sustained-release microparticle preparation of human growth hormone and process for producing thereof 失效
标题翻译：人生长激素的缓释微粒制剂及其制备方法
公开(公告)号：US07378394B2
公开(公告)日：2008-05-27
申请号：US10554574
申请日：2004-06-15
申请人： Yasuaki Ogawa , Takao Fujii , Yoko Miyamoto , Jun Niimi , Toshiyuki Ikoma , Junzo Tanaka
发明人： Yasuaki Ogawa , Takao Fujii , Yoko Miyamoto , Jun Niimi , Toshiyuki Ikoma , Junzo Tanaka
IPC分类号： A61K38/27 , A61K9/22
CPC分类号： A61K9/0019 , A61K9/1611 , A61K9/1694 , A61K9/19 , A61K38/27
摘要： Provided is a sustained-release microparticle preparation of a human growth hormone which combines biodegradability with sustained-release performance while avoiding the use of an organic solvent as much as possible, allows the sustained-release of a human growth hormone over 3 days or more and reduction in the initial burst release, can contain a human growth hormone at 10% or more, can quantitatively adsorb and encapsulate a human growth hormone at up to 20%, and has excellent dispersion and needle penetration properties. A process for producing the sustained-release microparticle preparation of a human growth hormone is also provided. The sustained-release microparticle preparation comprises a porous apatite derivative, a human growth hormone, and a water-soluble divalent metal compound.
摘要翻译：本发明提供了尽可能地避免使用有机溶剂的生物降解性与持续释放性能结合的人生长激素的持续释放微粒制剂，能够持续释放3天以上的人生长激素，初始爆发释放的减少可以含有10％以上的人生长激素，可以定量吸附和包封人生长激素达20％，具有优异的分散性和针刺性。还提供了生产人生长激素的缓释微粒制剂的方法。缓释微粒制剂包括多孔磷灰石衍生物，人生长激素和水溶性二价金属化合物。

22. 发明授权

US5668111A Sustained-release preparation 失效
标题翻译：缓释制剂
公开(公告)号：US5668111A
公开(公告)日：1997-09-16
申请号：US471382
申请日：1995-06-06
申请人： Shigeru Kamei , Yasutaka Igari , Yasuaki Ogawa
发明人： Shigeru Kamei , Yasutaka Igari , Yasuaki Ogawa
IPC分类号： A61K9/52 , A61K20060101 , A61K9/16 , A61K9/22 , A61K9/50 , A61K38/04 , A61K38/09 , A61K38/12 , A61K47/34 , A61K47/42 , C07K7/23 , A61K38/00 , C08G63/08
CPC分类号： C07K7/23 , A61K38/09 , A61K9/1647 , A61K38/00
摘要： A sustained-release preparation which comprises a physiologically active peptide of general formula ##STR1## wherein X represents an acyl group; R.sub.1, R.sub.2 and R.sub.4 each represents an aromatic cyclic group; R.sub.3 represents a D-amino acid residue or a group of the formula ##STR2## wherein R.sub.3 ' is a heterocyclic group; R.sub.5 represents a group of the formula --(CH.sub.2).sub.n --R.sub.5 ' wherein n is 2 or 3, and R.sub.5 ' is an amino group which may optionally be substituted, an aromatic cyclic group or an O-glycosyl group;R.sub.6 represents a group of the formula --(CH.sub.2).sub.n --R.sub.6 ' wherein n is 2 or 3, and R.sub.6 ' is an amino group which may optionally be substituted;R.sub.7 represents a D-amino acid residue or an azaglycyl residue; andQ represents hydrogen or a lower alkyl group, or a salt thereof and a biodegradable polymer having a terminal carboxyl group.The sustained-release preparation shows a constant release of the peptide over a long time and is substantially free from an initial burst.
摘要翻译：包含通式的生理活性肽的缓释制剂含有酰基; R1，R2和R4各自表示芳族环状基团; R 3表示D-氨基酸残基或式（D）的基团，其中R 3'为杂环基; R5表示式 - （CH2）n-R5'的基团，其中n为2或3，R5'为任选取代的氨基，芳族环基或O-糖基; R6表示式 - （CH2）n-R6'的基团，其中n为2或3，R6'为可任意取代的氨基; R7表示D-氨基酸残基或氮杂十八烷基残基; Q表示氢或低级烷基，或其盐和具有末端羧基的生物降解性聚合物。持续释放制剂显示长时间的肽的恒定释放并且基本上没有初始爆发。

23. 发明授权

US5651990A Prolonged release microparticle preparation and production of the same 失效
标题翻译：延长释放微粒的制备和生产相同
公开(公告)号：US5651990A
公开(公告)日：1997-07-29
申请号：US387392
申请日：1995-02-13
申请人： Shigeyuki Takada , Yoshiaki Uda , Yasuaki Ogawa
发明人： Shigeyuki Takada , Yoshiaki Uda , Yasuaki Ogawa
IPC分类号： A61K9/16 , A61K9/50 , A61K9/58 , A61K9/62 , B01J13/04
CPC分类号： A61K9/1694 , A61K9/1647 , A61K9/5015 , A61K9/5057 , A61K9/5073 , A61K9/5089 , Y10S514/963 , Y10T428/2984 , Y10T428/2985
摘要： A novel microparticle preparation comprising microparticles of a polymer which contain a drug and are coated with a film of an agent for preventing aggregation of the microparticles is disclosed. The preparation is produced by spraying a solution of a polymer containing a drug and an aqueous solution of an agent for preventing aggregation of the microparticles separately from different nozzles and contacting them with each other in a spray dryer.
摘要翻译：公开了一种新颖的微粒制剂，其包含含有药物的聚合物的微粒并涂覆有用于防止微粒聚集的试剂的膜。该制剂是通过喷雾含有药物的聚合物的溶液和用于防止微粒聚集的试剂的水溶液与不同的喷嘴分开并在喷雾干燥器中彼此接触来制备的。

24. 发明授权

US5631021A Method for producing microcapsule 失效
公开(公告)号：US5631021A
公开(公告)日：1997-05-20
申请号：US604022
申请日：1996-02-20
申请人： Hiroaki Okada , Yasuaki Ogawa , Takatsuka Yashiki
发明人： Hiroaki Okada , Yasuaki Ogawa , Takatsuka Yashiki
IPC分类号： A61K9/66 , A61K9/16 , A61K9/50 , A61K9/52 , A61K38/05 , A61K38/08 , A61K38/09 , A61K38/22 , A61K38/33 , A61K38/37 , B01J13/02 , B01J13/12 , A61K9/14
CPC分类号： A61K9/5031 , A61K38/05 , A61K38/08 , A61K38/09 , A61K38/33 , A61K38/37 , A61K9/1647 , A61K9/1694 , A61K9/5089 , B01J13/02 , B01J13/125 , Y10S424/15 , Y10S514/80 , Y10S514/822 , Y10S514/843 , Y10S514/952 , Y10S514/963 , Y10S514/965 , Y10T428/2984 , Y10T428/2985 , Y10T428/2989
摘要： A microcapsule produced by preparing a water-in-oil emulsion comprising an inner aqueous layer containing said water-soluble drug and a drug retaining substance therefor and an oil layer containing a polymer substance, then thickening or solidifying said inner aqueous layer to a viscosity of not lower than about 5000 centiposes and finally subjecting the resulting emulsion to in water drying gives prolonged release of water-soluble drug.

25. 发明授权

US5575987A Method of producing sustained-release microcapsules 失效
标题翻译：缓释微胶囊的制备方法
公开(公告)号：US5575987A
公开(公告)日：1996-11-19
申请号：US562634
申请日：1995-11-27
申请人： Shigeru Kamei , Minoru Yamada , Yasuaki Ogawa
发明人： Shigeru Kamei , Minoru Yamada , Yasuaki Ogawa
IPC分类号： A61K9/50 , A61K9/16 , A61K9/52 , A61K38/06 , A61K38/09 , A61K38/21 , A61K47/34 , B01J13/02 , B01J13/04 , A61K9/48 , A61K9/14 , B32B5/16
CPC分类号： A61K38/212 , A61K38/066 , A61K38/09 , A61K9/1647 , A61K9/1694 , B01J13/02 , Y10S514/963 , Y10T428/2982 , Y10T428/2984 , Y10T428/2985
摘要： A method of producing sustained-release microcapsules containing a biologically active substance from an W/O emulsion comprising an inner aqueous phase containing said biologically active substance and an external oil phase containing a biodegradable polymer, characterized in that microcapsules formed on microencapsulation of said biologically active substance with said biodegradable polymer are heated at a temperature not lower than the glass transition temperature of said biodegradable polymer but not so high as to cause aggregation of the microcapsules. This method enables the production of very useful sustained release microcapsules adapted to release a bologically active substance at a calculated rate over a protracted time period starting immediately following administration without an initial burst within one day following administration.
摘要翻译：一种从W / O乳液制备含有生物活性物质的缓释微胶囊的方法，包括含有所述生物活性物质的内部水相和含有可生物降解的聚合物的外部油相，其特征在于，在所述生物活性物质的微胶囊化与所述可生物降解聚合物的物质在不低于所述可生物降解聚合物的玻璃化转变温度的温度下加热，但不会高到使微胶囊聚集。该方法使得能够生产非常有用的持续释放微胶囊，其适用于在给药后立即开始的持续时间段内以计算的速率释放勃起活性物质，而在给药后一天内没有初始爆发。

26. 发明授权

US5416071A Water-soluble composition for sustained-release containing epo and hyaluronic acid 失效
标题翻译：含有epo和透明质酸的持续释放水溶性组合物
公开(公告)号：US5416071A
公开(公告)日：1995-05-16
申请号：US909160
申请日：1992-07-06
申请人： Yasutaka Igari , Minoru Yamada , Yasuaki Ogawa
发明人： Yasutaka Igari , Minoru Yamada , Yasuaki Ogawa
IPC分类号： A61K38/18 , A61K47/36 , A61K47/42 , A61K38/14
CPC分类号： A61K38/1816 , A61K47/36 , A61K47/42 , Y10S514/964
摘要： (1) A composition which comprises erythropoietin and hyaluronic acid shows a sustained-release of the medicine in a living body, and(2) A water-soluble composition which comprises (a) a pharmacologically active polypeptide secreted by an animal body or its derivative or a chemically synthesized pharmacologically active substance, (b) a water-soluble species of hyaluronic acid or its nontoxic salt and (c) a water-soluble protein injectable into body fluids without showing any substantial pharmacological activity brings about a prolonged action in vivo of a pharmacologically active substance. In addition, the composition can be administered using a small-gauge needle and thereby contributes ot relieving pain in patients.
摘要翻译：（1）包含促红细胞生成素和透明质酸的组合物，在活体中显示药物的持续释放，（2）水溶性组合物，其包含（a）动物体或其衍生物分泌的药理活性多肽或化学合成的药理活性物质，（b）透明质酸或其无毒盐的水溶性物质，和（c）不显示任何实质性药理学活性的体内液体注射的水溶性蛋白质，会导致体内延长的作用药理活性物质。此外，组合物可以使用小规格的针头施用，从而有助于减轻患者的疼痛。

27. 发明授权

US5330767A Sustained release microcapsule 失效
标题翻译：持续释放微胶囊
公开(公告)号：US5330767A
公开(公告)日：1994-07-19
申请号：US936726
申请日：1992-08-31
申请人： Masaki Yamamoto , Shigeyuki Takada , Yasuaki Ogawa
发明人： Masaki Yamamoto , Shigeyuki Takada , Yasuaki Ogawa
IPC分类号： A61K9/56 , A61K9/16 , A61K9/50 , A61K9/52 , A61K9/58 , A61K9/62 , B01J13/02 , B01J13/12 , B01J13/04
CPC分类号： A61K9/5031 , A61K9/1647 , A61K9/1652 , A61K9/1658 , A61K9/1694 , B01J13/02 , Y10S514/80 , Y10S514/885 , Y10S514/963 , Y10T428/2984 , Y10T428/2985 , Y10T428/2987
摘要： Microcapsules are advantageously produced with high take-up of a water-soluble drug by preparing a W/O emulsion composed of a water-soluble drug-containing solution as the inner aqueous phase and a polymer-containing solution as the oil phase, dispersing said emulsion in an aqueous phase and subjecting the resulting W/O/W emulsion to an in-water drying, wherein the viscosity of the W/O emulsion used in preparing the W/O/W emulsion is adjusted to about 150 to about 10,000 centipoises.
摘要翻译：通过制备由作为内部水相的水溶性药物溶液和作为油相的含有聚合物的溶液组成的W / O乳液，有利地生产水溶性药物的高吸收性的微胶囊，将所述在水相中的乳液，并将所得W / O / W乳液进行水中干燥，其中用于制备W / O / W乳液的W / O乳液的粘度调节至约150至约10,000厘泊。

28. 发明授权

US5252336A Liposome composition whose liposome membrane contains a polyoxyethylene derivative 失效
标题翻译：脂质体组成的脂质体膜含有聚氧乙烯衍生物
公开(公告)号：US5252336A
公开(公告)日：1993-10-12
申请号：US687918
申请日：1991-06-05
申请人： Katsumi Iga , Kazuhiro Ohkouchi , Yasuaki Ogawa
发明人： Katsumi Iga , Kazuhiro Ohkouchi , Yasuaki Ogawa
IPC分类号： A61K9/127 , B01J13/02
CPC分类号： A61K9/1272 , Y10S436/829 , Y10T428/2984
摘要： A liposome composition is obtained by using as constituent components of the liposome membrane a polyoxyethylene derivative represented by the general formula:X--O--(CH.sub.2 CH.sub.2 O).sub.n --Y (I)wherein X represents an alkanoyl group or an alkyl group, Y represents a residue of a compound having a negative charge, and n is an integer of 2 to 50, and a phospholipid. The liposome composition has good dispersibility, high drug-encapsulation property and high stability.
摘要翻译： PCT No.PCT / JP91 / 00481 Sec。 371日期1991年6月5日 102（e）1991年6月5日PCT 1991年4月12日提交PCT公布。出版物WO91 / 16040 1991年10月31日。脂质体组合物通过以脂质体膜的构成成分作为通式XO-（CH 2 CH 2 O）n Y（I）表示的聚氧乙烯衍生物，其中X表示烷酰基或烷基， Y表示具有负电荷，n为2〜50的整数的化合物的残基和磷脂。脂质体组成具有良好的分散性，高的药物包封性和高稳定性。

29. 发明授权

US4917893A Prolonged release microcapsules 失效
标题翻译：延长释放微胶囊
公开(公告)号：US4917893A
公开(公告)日：1990-04-17
申请号：US103117
申请日：1987-09-30
申请人： Hiroaki Okada , Yasuaki Ogawa , Takatsuka Yashiki
发明人： Hiroaki Okada , Yasuaki Ogawa , Takatsuka Yashiki
IPC分类号： A61K9/66 , A61K9/16 , A61K9/50 , A61K9/52 , A61K38/05 , A61K38/08 , A61K38/09 , A61K38/22 , A61K38/33 , A61K38/37 , B01J13/02 , B01J13/12
CPC分类号： A61K9/5031 , A61K38/05 , A61K38/08 , A61K38/09 , A61K38/33 , A61K38/37 , A61K9/1647 , A61K9/1694 , A61K9/5089 , B01J13/02 , B01J13/125 , Y10S424/15 , Y10S514/80 , Y10S514/822 , Y10S514/843 , Y10S514/952 , Y10S514/963 , Y10S514/965 , Y10T428/2984 , Y10T428/2985 , Y10T428/2989
摘要： A microcapsule produced by preparing a water-in-oil emulsion comprising an inner aqueous layer containing said water-soluble drug and a drug retaining substance therefor and an oil layer containing a polymer substance, then thickening or solidifying said inner aqueous layer to a viscosity of not lower than about 5000 centiposes and finally subjecting the resulting emulsion to in water drying gives prolonged release of water-soluble drug.

30. 发明授权

US4683288A Polymer and its production 失效
标题翻译：聚合物及其生产
公开(公告)号：US4683288A
公开(公告)日：1987-07-28
申请号：US751671
申请日：1985-07-03
申请人： Motoaki Tanaka , Yasuaki Ogawa , Tsutomu Miyagawa , Toshio Watanabe
发明人： Motoaki Tanaka , Yasuaki Ogawa , Tsutomu Miyagawa , Toshio Watanabe
IPC分类号： A61K9/16 , C08G63/06 , C08G63/04
CPC分类号： C08G63/06 , A61K9/1647
摘要： A polymer or copolymer of lactic acid and/or glycolic acid which has a weight-average molecular weight of not less than about 5,000 and a dispersity of about 1.5 to 2 is advantageously used as a biodegradable polymer or copolymer for medical preparation.

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