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1. 发明授权

US4968616A Superoxide dismutase derivatives, method of producing same and medicinal use of same 失效
标题翻译：超氧化物歧化酶衍生物，其生产方法及其用途
公开(公告)号：US4968616A
公开(公告)日：1990-11-06
申请号：US049349
申请日：1987-05-13
申请人： Masayasu Inoue , Tetsuya Ogino , Yoshimasa Morino , Masahiko Hirota
发明人： Masayasu Inoue , Tetsuya Ogino , Yoshimasa Morino , Masahiko Hirota
IPC分类号： C12N9/08 , A61K38/44 , A61K47/48 , C12N11/08
CPC分类号： A61K47/48176 , A61K38/446 , C12N11/08
摘要： Novel superoxide dismutase derivatives are provided in which the enzymatic activity of superoxide dismutase capable of decomposing superoxide, a substance harmful to living organisms, is for the most part maintained with the plasma half-life being significantly prolonged as compared with superoxide dismutase itself. They have pharmacological activities such as anti-inflammatory, anti-ischemic and cerebral edema-preventing activities. Also provided are a method of producing such superoxide dismutase derivatives and medicinal uses of them.
摘要翻译：提供了新型超氧化物歧化酶衍生物，其中与超氧化物歧化酶本身相比，能够分解超氧化物的超氧化物歧化酶的酶活性，其对活生物体有害的物质大部分维持在血浆半衰期显着延长。它们具有抗炎，抗缺血和脑水肿预防活性等药理活性。还提供了生产这种超氧化物歧化酶衍生物的方法和它们的药用。

2. 发明授权

US5360914A Long chain carboxylic acid maleimides 失效
标题翻译：长链羧酸马来酰亚胺
公开(公告)号：US5360914A
公开(公告)日：1994-11-01
申请号：US59759
申请日：1993-05-11
申请人： Masayasu Inoue , Iwao Ebashi , Tetsuo Takigawa
发明人： Masayasu Inoue , Iwao Ebashi , Tetsuo Takigawa
IPC分类号： A61K38/44 , C12N9/02 , A61K37/50 , C07D207/452 , C07K15/12
CPC分类号： C12N9/0089
摘要： Provided are novel superoxide dismutase derivatives represented by the following general formula (I) ##STR1## wherein [SOD] is a superoxide dismutase residue derived by removal of two mercapto groups, and W is a divalent long chain hydrocarbon residue which may optionally be interrupted by one or more groups each independently selected from the group consisting of an oxygen atom, a sulfur atom and a group of -N(R)- (R being a lower alkyl group). The SOD derivatives retain most of the enzymatic activities of unmodified SOD and have much longer plasma half-life than unmodified SOD. They are effective for treating various diseases caused by active oxygen species.Also provided are chemical modifiers to prepare the above SOD derivatives.
摘要翻译：提供了由以下通式（I）表示的新型超氧化物歧化酶衍生物，其通过除去两个巯基衍生得到的酪蛋白酶残基，W是二价长链烃残基，其可以任选地被一个或多个各自独立地选自由氧原子，硫原子和-N（R） - （R为低级烷基）的基团组成。 SOD衍生物保留大部分未修饰的SOD的酶活性，并且具有比未修饰的SOD更长的血浆半衰期。它们对于治疗由活性氧引起的各种疾病是有效的。还提供了制备上述SOD衍生物的化学改性剂。

3. 发明授权

US5336782A Long chain carboxylic acid imide ester 失效
标题翻译：长链羧酸酰亚胺酯
公开(公告)号：US5336782A
公开(公告)日：1994-08-09
申请号：US872534
申请日：1992-04-23
申请人： Iwao Ebashi , Tetsuo Takigawa , Masayasu Inoue
发明人： Iwao Ebashi , Tetsuo Takigawa , Masayasu Inoue
IPC分类号： C07D207/46 , C07D209/48 , C07D209/76 , C07D211/94 , C07K1/00 , C07K14/00 , C07K16/00 , C07K17/00
CPC分类号： C07D209/48 , C07D207/46 , C07D209/76 , C07D211/94
摘要： Provided is a long chain carboxylic acid imide ester (I) represented by the following general formula (I) ##STR1## wherein W is a divalent long chain hydrocarbon group which may optionally be interrupted by one or more groups each independently selected from the group consisting of an oxygen atom, a sulfur atom and a group of --N(R.sup.1)-- (R.sup.1 being a lower alkyl group) and X represents a divalent hydrocarbon group which may optionally be substituted, or salts thereof. The above long chain carboxylic acid imide ester or its salts is useful for modifying enzymes or proteins having biological activities to give their derivatives which have, while retaining most of the original biological activities, an extremely prolonged plasma half-life as compared with the proteins and have no antigenecities and can be administered to animals.
摘要翻译：提供由以下通式（I）表示的长链羧酸酰亚胺酯（I）：其中W是二价长链烃基，其可任选地被一个或多个各自独立地选自由氧原子，硫原子和-N（R1） - （R1为低级烷基）组成的基团，X表示任选被取代的二价烃基或其盐。上述长链羧酸酰亚胺酯或其盐可用于修饰具有生物活性的酶或蛋白质以产生其衍生物，其与原始蛋白质相比具有极大延长的血浆半衰期，同时保留大部分原始生物活性，没有抗原性，可以给予动物。

4. 发明授权

US4968495A Chemically modified bilirubin oxidase 失效
标题翻译：化学修饰胆红素氧化酶
公开(公告)号：US4968495A
公开(公告)日：1990-11-06
申请号：US226088
申请日：1988-07-29
申请人： Masayasu Inoue , Hiroshi Maeda
发明人： Masayasu Inoue , Hiroshi Maeda
IPC分类号： A61K38/44 , A61K47/48 , A61P1/16 , A61P7/00 , C12N9/06
CPC分类号： A61K47/48215 , A61K38/44 , A61K47/48176 , A61K47/4823 , C12Y103/03005
摘要： A bilirubin oxidase derivative resulting from chemical modification of a water-soluble polymeric substance. The chemically modified bilirubin oxidase is useful as a drug for treating jaundice.
摘要翻译：由水溶性高分子物质的化学改性而产生的胆红素氧化酶衍生物。化学修饰的胆红素氧化酶可用作治疗黄疸的药物。

5. 发明授权

US5238837A Superoxide dismutase derivatives 失效
标题翻译：超氧化物歧化酶衍生物
公开(公告)号：US5238837A
公开(公告)日：1993-08-24
申请号：US803414
申请日：1991-12-06
申请人： Masayasu Inoue , Iwao Ebashi , Tetsuo Takigawa
发明人： Masayasu Inoue , Iwao Ebashi , Tetsuo Takigawa
IPC分类号： A61K38/44 , C12N9/02
CPC分类号： C12N9/0089
摘要： Provided are novel superoxide dismutase derivatives represented by the following general formula (I) ##STR1## wherein [SOD] is a superoxide dismutase residue derived by removal of two mercapto groups, and W is a divalent long chain hydrocarbon residue which may optionally be interrupted by one or more groups each independently selected from the group consisting of an oxygen atom, a sulfur atom and a group of --N(R)-- (R being a lower alkyl group). The SOD derivatives retain most of the enzymatic activities of unmodified SOD and have much longer plasma half-life than unmodified SOD. They are effective for treating various diseases caused by active oxygen species.Also provided are chemical modifiers to prepare the above SOD derivatives.
摘要翻译：提供了由以下通式（I）表示的新型超氧化物歧化酶衍生物：其中[SOD]是通过除去两个巯基衍生的超氧化物歧化酶残基，W是可任意选择的二价长链烃残基被一个或多个各自独立地选自氧原子，硫原子和-N（R） - （R是低级烷基）的基团的基团中断）。 SOD衍生物保留大部分未修饰的SOD的酶活性，并且具有比未修饰的SOD更长的血浆半衰期。它们对于治疗由活性氧引起的各种疾病是有效的。还提供了制备上述SOD衍生物的化学改性剂。

6. 再颁专利

USRE36359E Long chain carboxylic acid imide ester 失效
标题翻译：长链羧酸酰亚胺酯
公开(公告)号：USRE36359E
公开(公告)日：1999-10-26
申请号：US850021
申请日：1997-05-01
申请人： Iwao Ebashi , Tetsuo Takigawa , Masayasu Inoue
发明人： Iwao Ebashi , Tetsuo Takigawa , Masayasu Inoue
IPC分类号： C07D207/46 , C07D209/48 , C07D209/76 , C07D211/94 , C07K1/00 , C07K14/00 , C07K16/00 , C07K17/00
CPC分类号： C07D209/48 , C07D207/46 , C07D209/76 , C07D211/94
摘要： Provided is a long chain carboxylic acid imide ester (I) represented by the following general formula (I) ##STR1## wherein W is a divalent long chain hydrocarbon group which may optionally be interrupted by one or more groups each independently selected from the group consisting of an oxygen, atom, a sulfur atom, and a group of --N(R.sup.1)-- (R.sup.1 being a lower alkyl group) and X represents a divalent hydrocarbon group which may optionally be substituted, or salt thereof. The above long chain carboxylic acid imide ester or its salts is useful for modifying enzymes or proteins having biological activities to give their derivatives which have, while retaining most of the original biological activities, an extremely prolonged plasma half-life as compared with the proteins and have no antigenecities and can be administered to animals.
摘要翻译：提供由以下通式（I）表示的长链羧酸酰亚胺酯（I），其中W是二价长链烃基，其可以任选地被一个或多个各自独立地选自氧，原子，硫原子和-N（R 1） - （R 1为低级烷基）的基团，X表示可任意取代的二价烃基或其盐。上述长链羧酸酰亚胺酯或其盐可用于修饰具有生物活性的酶或蛋白质以产生其衍生物，其与原始蛋白质相比具有极大延长的血浆半衰期，同时保留大部分原始生物活性，没有抗原性，可以给予动物。

7. 发明授权

US5414089A Long chain carboxylic acid imide ester 失效
标题翻译：长链羧酸酰亚胺酯
公开(公告)号：US5414089A
公开(公告)日：1995-05-09
申请号：US106644
申请日：1993-08-16
申请人： Iwao Ebashi , Tetsuo Takigawa , Masayasu Inoue
发明人： Iwao Ebashi , Tetsuo Takigawa , Masayasu Inoue
IPC分类号： C07D207/46 , C07D209/48 , C07D209/76 , C07D211/94 , C07K1/00 , C07K14/00 , C07K16/00 , C07K17/00
CPC分类号： C07D209/48 , C07D207/46 , C07D209/76 , C07D211/94
摘要： Provided is a long chain carboxylic acid imide ester (I) represented by the following general formula (I) ##STR1## wherein W is a divalent long chain hydrocarbon group which may optionally be interrupted by one or more groups each independently selected from the group consisting of an oxygen atom, a sulfur atom, and a group of --N(R.sup.1)-- (R.sup.1 being a lower alkyl group) and X represents a divalent hydrocarbon group which may optionally be substituted, or salts thereof. The above long chain carboxylic acid imide ester or its salts is useful for modifying enzymes or proteins having biological activities to give their derivatives which have, while retaining most of the original biological activities, an extremely prolonged plasma half-life as compared with the proteins and have no antigenecities and can be administered to animals.
摘要翻译：提供由以下通式（I）表示的长链羧酸酰亚胺酯（I）：其中W是二价长链烃基，其可任选地被一个或多个各自独立地选自由氧原子，硫原子和-N（R 1） - （R 1为低级烷基）的基团组成的基团，X表示可以被取代的二价烃基或其盐。上述长链羧酸酰亚胺酯或其盐可用于修饰具有生物活性的酶或蛋白质以产生其衍生物，其与原始蛋白质相比具有极大延长的血浆半衰期，同时保留大部分原始生物活性，没有抗原性，可以给予动物。

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