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1. 发明授权

US6010871A Modification of peptide and protein 失效
标题翻译：肽和蛋白质的修饰
公开(公告)号：US6010871A
公开(公告)日：2000-01-04
申请号：US809593
申请日：1997-09-08
申请人： Yoshiyuki Takahara , Naoyuki Yamada , Masao Motoki
发明人： Yoshiyuki Takahara , Naoyuki Yamada , Masao Motoki
IPC分类号： C07K14/54 , C07K14/555 , C12P21/02 , C12P21/00
CPC分类号： C07K14/54 , C07K14/555 , C12P21/02
摘要： A process for modifying a physiologically active peptide or a physiologically active protein which comprises reacting a physiologically active peptide or a physiologically active protein having at least a glutamine residue with a substance having an amino donor in the presence of a transglutaminase originating in a microorganism to thereby form an acid amide bond at the .gamma.-position acid amide group of the glutamine residue with the amino group of the amino donor; and the product of modification obtained thereby.
摘要翻译： PCT No.PCT / JP95 / 01994 Sec。 371日期：1997年9月8日 102（e）1997年9月8日PCT PCT 1995年9月29日PCT公布。 WO96 / 10089 PCT出版物日期1996年4月4日一种改变生理活性肽或生理活性蛋白质的方法，其包括使生理活性肽或具有至少谷氨酰胺残基的生理活性蛋白质与具有氨基供体的物质在转谷氨酰胺酶的存在下反应从而在氨基供体的氨基的谷氨酰胺残基的γ位酸酰胺基上形成酰胺键; 和由此获得的改性产物。

2. 发明授权

US5863908A Carboxymethylmannoglucans and derivatives thereof 失效
标题翻译：羧甲基甘露糖葡聚糖及其衍生物
公开(公告)号：US5863908A
公开(公告)日：1999-01-26
申请号：US689095
申请日：1996-07-30
申请人： Kazuhiro Inoue , Teruomi Ito , Takayuki Kawaguchi , Katsutoshi Aono , Satoshi Okuno , Toshiro Yano
发明人： Kazuhiro Inoue , Teruomi Ito , Takayuki Kawaguchi , Katsutoshi Aono , Satoshi Okuno , Toshiro Yano
IPC分类号： A61K47/36 , A61K47/48 , C08B15/00 , C08B37/00 , A61K31/725 , A61K31/715 , A61K31/72
CPC分类号： C08B37/0087 , A61K47/4823
摘要： A carboxymethylmannoglucan comprising tetrasaccharide units represented by the following general formula (I) and salt thereof. Further, the invention discloses a carboxymethylmannoglucan derivative and salt thereof produced by subjecting part or the whole of mannose of the tetrasaccharide units to ring opening and subjecting part or the whole of glucose which constitute the main chain but have no mannose as a branch ##STR1## wherein R.sup.1 to R.sup.12 each represent a hydrogen atom or a carboxymethyl group.The compounds are useful as carrier for delaying the disappearance of a drug in the blood and for enhancing the organotropism of the drug for a carcinoma.
摘要翻译：包含由以下通式（I）表示的四糖单元及其盐的羧甲基甘露糖葡聚糖。此外，本发明公开了通过使四糖单元的一部分或全部甘露糖开环并使构成主链但不具有甘露糖的部分或全部葡萄糖作为分支而制备的羧甲基葡萄糖聚糖衍生物及其盐。（I）其中R 1至R 12各自表示氢原子或羧甲基。这些化合物可用作延迟药物在血液中消失并用于增强癌症药物的有机性的载体。

3. 发明授权

US5688931A Polysaccharide derivatives and drug carriers 失效
标题翻译：多糖衍生物和药物载体
公开(公告)号：US5688931A
公开(公告)日：1997-11-18
申请号：US325296
申请日：1994-12-28
申请人： Hideo Nogusa , Hiroshi Hamana , Toshiro Yano , Masahiro Kajiki , Keiji Yamamoto , Satoshi Okuno , Shuichi Sugawara , Nobukazu Kashima , Kazuhiro Inoue
发明人： Hideo Nogusa , Hiroshi Hamana , Toshiro Yano , Masahiro Kajiki , Keiji Yamamoto , Satoshi Okuno , Shuichi Sugawara , Nobukazu Kashima , Kazuhiro Inoue
IPC分类号： A61K47/48 , C08B37/00 , C08B37/02 , C07H13/02 , C07K5/00 , C08B37/08
CPC分类号： C08B37/0063 , A61K47/48338 , C08B37/00 , C08B37/0006
摘要： A novel polysaccharide derivative, a drug carrier comprising a novel polysaccharide derivative, and a drug complex are disclosed. The polysaccharide derivative according to the present invention comprises a polysaccharide having a carboxyl group in which a peptide chain is introduced at a part or all of the carboxyl groups of the polysaccharide. The peptide chain comprises 1-8 amino acids which may be the same or different. A part or all of the amino groups in the peptide chain which are not involved in the linkages with the carboxyl groups of the polysaccharide or the carboxyl groups in the peptide chain may form an acid amide linkage or an ester linkage with a carboxyl group, an amino group or a hydroxyl group of a third compound such as drugs. The polysaccharide derivative has a property of accumulating in a high amount at a tumor, and thus can deliver efficiently a drug which has a side-effect or a limited sustainment of the drug efficacy to the tumor.
摘要翻译： PCT No.PCT / JP94 / 00322 Sec。 371日期1994年12月28日第 102（e）日期1994年12月28日PCT 1994年2月28日PCT PCT。第WO94 / 19376号公报日期1994年9月1日公开了一种新型多糖衍生物，包含新型多糖衍生物的药物载体和药物复合物。本发明的多糖衍生物含有在多糖的一部分或全部羧基上引入肽链的具有羧基的多糖。肽链包含1-8个氨基酸，其可以相同或不同。不参与与肽链中的多糖或羧基的羧基的连接的肽链中的一部分或全部氨基可以与羧基形成酸酰胺键或酯键，氨基或第三化合物如药物的羟基。多糖衍生物具有在肿瘤中高度积累的性质，因此能够有效地递送对肿瘤具有药效的副作用或有限维持性的药物。

4. 发明授权

US5580904A Formamido and carboxyamido compounds which can be retained in brain 失效
标题翻译：可以保留在脑中的甲酰氨基和羧酰氨基化合物
公开(公告)号：US5580904A
公开(公告)日：1996-12-03
申请号：US211304
申请日：1994-06-24
申请人： Toyoaki Ishikura , Teruomi Ito , Takashi Kato , Kazutoshi Horie , Hiroshi Ishihara , Takashi Senou
发明人： Toyoaki Ishikura , Teruomi Ito , Takashi Kato , Kazutoshi Horie , Hiroshi Ishihara , Takashi Senou
IPC分类号： A61K47/20 , A61K47/22 , A61K47/48 , C07C323/41 , C07C327/30 , C07D207/16 , C07D239/42 , C07D295/12 , C07D295/13 , C07D405/12 , A61K31/16 , C07C233/01
CPC分类号： C07D239/42 , A61K47/48023 , A61K47/48061 , A61K47/48215 , C07C323/41 , C07C327/30 , C07D207/16 , C07D295/13 , C07D405/12 , C07C2101/14
摘要： According to the present invention, a novel compound group which can pass through blood-brain barrier (BBB) with carrying a drug thereon and stay within brain to release the drug and a well-known compound group having the properties described above are provided.The compound represented by the general formula ##STR1## wherein, R.sup.1 represents C.sub.1-6 alkyl which may be substituted by a group selected from hydroxyl, carboxyl, amino group which may be substituted by C.sub.1-6 alkyl, and a five- to seven-membered saturated heterocyclic ring,R.sup.2 represents hydrogen or C.sub.1-6 alkyl,R.sup.3 represents hydrogen or C.sub.1-6 alkyl which may be substituted by hydroxyl,R.sup.4 represents hydrogen or C.sub.1-6 alkyl,R.sup.5 represents an amino acid residue, or --S--R.sup.6 or --CO--R.sup.6 wherein R.sup.6 represents C.sub.1-14 alkyl which may be substituted by a five- to seven-membered saturated ring; C.sub.2-6 alkenyl; aryl; or a five- to seven-membered saturated ring; or the group represented by the general formula (IVa): ##STR2## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 have the same meanings as defined above, and.multidot..multidot..multidot..multidot..multidot..multidot..multidot..multidot..multidot. represents a single bond or a double bondprovided that at least one of R.sup.1, R.sup.3 and R.sup.5 contains hydroxyl, carboxyl or amino, and a salt thereof.
摘要翻译： PCT No.PCT / JP93 / 01075 Sec。 371日期：1994年6月24日 102（e）1994年6月24日PCT 1993年7月30日PCT公布。公开号WO94 / 03424 日本1994年2月17日根据本发明，可以通过血脑屏障（BBB）携带药物并保持在脑内以释放药物的新型化合物组和具有所述性质的公知化合物组提供以上。由通式（Ia）表示的化合物，其中，R 1表示可被选自羟基，羧基，可被C 1-6烷基取代的氨基的基团取代的C 1-6烷基，至7元饱和杂环，R 2表示氢或C 1-6烷基，R 3表示氢或可被羟基取代的C 1-6烷基，R 4表示氢或C 1-6烷基，R 5表示氨基酸残基，或 - S-R6或-CO-R6，其中R6表示可被5至7元饱和环取代的C 1-14烷基; C 2-6烯基; 芳基; 或五至七元饱和环; 或由通式（IVa）表示的基团：其中R 1，R 2，R 3和R 4具有与上述相同的含义，并且+ E，uns xxxxxxxxx + EE表示单键或双键条件是R 1，R 3和R 5中的至少一个含有羟基，羧基或氨基，及其盐。

5. 发明授权

US5567690A Carboxymethylmannoglucans and derivatives thereof 失效
公开(公告)号：US5567690A
公开(公告)日：1996-10-22
申请号：US397560
申请日：1995-03-02
申请人： Kazuhiro Inoue , Teruomi Ito , Takayuki Kawaguchi , Katsutoshi Aono , Satoshi Okuno , Toshiro Yano
发明人： Kazuhiro Inoue , Teruomi Ito , Takayuki Kawaguchi , Katsutoshi Aono , Satoshi Okuno , Toshiro Yano
IPC分类号： A61K47/36 , A61K47/48 , C08B15/00 , C08B37/00 , A61K31/725 , A61K31/715 , A61K31/72
CPC分类号： C08B37/0087 , A61K47/4823
摘要： A carboxymethylmannoglucan comprising tetrasaccharide units represented by the following general formula (I) and salt thereof. Further, the invention discloses a carboxymethylmannoglucan derivative and salt thereof produced by subjecting part or the whole of mannose of the tetrasaccharide units to ring opening and subjecting part or the whole of glucose which constitute the main chain but have no mannose as a branch ##STR1## wherein R.sup.1 to R.sup.12 each represent a hydrogen atom or a carboxymethyl group.The compounds are useful as carrier for delaying the disappearance of a drug in the blood and for enhancing the organotropism of the drug for a carcinoma.

6. 发明授权

US6013526A Modified protein for gene transfer and process for producing the same 失效
标题翻译：用于基因转移的修饰蛋白及其生产方法
公开(公告)号：US6013526A
公开(公告)日：2000-01-11
申请号：US927087
申请日：1997-09-10
申请人： Yoshiyuki Takahara , Naoyuki Yamada , Masao Motoki
发明人： Yoshiyuki Takahara , Naoyuki Yamada , Masao Motoki
IPC分类号： C12N15/09 , A61K38/00 , A61K47/48 , A61K48/00 , C07K1/113 , C07K14/195 , C07K14/41 , C07K14/52 , C07K14/54 , C07K14/55 , C07K19/00 , C12N9/10 , C12N15/87 , C12P21/02 , C12N15/00
CPC分类号： C12N15/87 , A61K47/48315 , C07K14/5412
摘要： The present invention relates to a process for producing a conjugate of a biologically active peptide or protein having at least one glutamine residue with a high-molecular weight substance containing an amino group. The present invention also relates to a composite of this conjugate with a nucleic acid adsorbed thereto for transferring nucleic acids to mammalian cells.
摘要翻译：本发明涉及生产具有至少一个谷氨酰胺残基的生物活性肽或蛋白质与含有氨基的高分子量物质的缀合物的方法。本发明还涉及该结合物与吸附于其上的核酸的复合物，用于将核酸转移至哺乳动物细胞。

7. 发明授权

US6057431A Amidite derivatives and oligonucleotide derivatives 失效
标题翻译：脒衍生物和寡核苷酸衍生物
公开(公告)号：US6057431A
公开(公告)日：2000-05-02
申请号：US930677
申请日：1997-12-22
申请人： Hiroshi Ishihara , Takayuki Kawaguchi , Masahiro Ikeda , Kazutaka Nakamoto , Atsushi Sasaki
发明人： Hiroshi Ishihara , Takayuki Kawaguchi , Masahiro Ikeda , Kazutaka Nakamoto , Atsushi Sasaki
IPC分类号： C07H21/00 , C07H21/02 , C07H1/00 , C07H19/00
CPC分类号： C07H21/00
摘要： The present invention provides a compound of general formula (I): ##STR1## wherein X represents group (II) or (III): ##STR2## wherein Y represents a leaving group and Z represents an oligonucleotide. The compound can specifically transfer oligonucleotides to cells which specifically recognize a specified saccharide construction. Accordingly, the compound can be used as an antiviral agent or an antitumor agent.
摘要翻译： PCT No.PCT / JP96 / 00868 Sec。 371 1997年12月22日第 102（e）日期1997年12月22日PCT 1996年3月29日PCT公布。 WO96 / 30386 PCT公开号日期：1996年10月3日本发明提供通式（I）的化合物：其中X表示基团（II）或（III）：其中Y表示离去基团，Z表示寡核苷酸。该化合物可以将寡核苷酸特异性转移到特异性识别特定糖结构的细胞中。因此，该化合物可以用作抗病毒剂或抗肿瘤剂。

8. 发明授权

US5463022A N-acetylcarboxymethylchitosan derivatives and process for preparation thereof 失效
公开(公告)号：US5463022A
公开(公告)日：1995-10-31
申请号：US969307
申请日：1993-02-16
申请人： Kazuhiro Inoue , Teruomi Ito , Satoshi Okuno , Katsutoshi Aono
发明人： Kazuhiro Inoue , Teruomi Ito , Satoshi Okuno , Katsutoshi Aono
IPC分类号： A61K47/48 , C08B37/08 , A61K38/00 , C07G17/00 , C07K9/00 , C08B37/00
CPC分类号： C08B37/003
摘要： N-acetylcarboxymethylchitosan derivatives are provided by the present invention. They are represented by the following formula (I): ##STR1## wherein R.sub.1 and R.sub.2 individually mean H or carboxymethyl group; P denotes a group R.sub.3 CO--, a group R.sub.4 NH-- or a group R.sub.5 O-- with assuming that R.sub.3 COOH denotes a compound having carboxyl group, R.sub.4 NH.sub.2 denotes a compound having amino group and R.sub.5 OH denotes an alcohol compound; Q stands for H or a group --OH; X represents a peptide chain containing same or different, one to ten amino acids; a.sub.1 and a.sub.2 individually represent zero or a positive integer, provided that both of a.sub.1 and a.sub.2 are not zero at the same time, and b stands for a positive integer; and having the following characteristic values (1)-(4):______________________________________ (1) carboxymethylation degree: 0.5-1.2 (2) molecular weight (as measured 3,000-300,000 by gel filtration method): (3) a/(a + b): 0.01-1 [provided that a = a.sub.1 + a.sub.2 ] (4) P/X ratio (molar ratio): 0.1-1 ______________________________________ P in the formula (I) can be the residue of a pharmaceutical compound. In this case, the substances of the formula (I) are derivatives of the pharmaceutical compound, which derivatives have been improved in the properties such as organotropism in vivo.P in the formula (I) can also be protective groups. In this case, removal of the protective groups from the substances of the formula (I) by deprotection makes it possible to provide such N-acetylcarboxymethylchitosan derivative which is useful as carrier for pharmaceutical compounds and which has the terminals of the so deprotected peptide chains capable of being linked with a pharmaceutical compound.There are further obtained such derivatives of the substances of the formula (I), in which derivatives some of the N-acetylcarboxymethylglucosamine units have been replaced by units having a high solubility in water.

9. 发明授权

US5243035A Sialic acid-containing glycolipid derivatives 失效
标题翻译：含有酸性的甘氨酸衍生物
公开(公告)号：US5243035A
公开(公告)日：1993-09-07
申请号：US752604
申请日：1991-08-15
申请人： Satoru Nakabayashi , Kunio Higashi , Shiro Miyoshi , Hitoshi Yamauchi
发明人： Satoru Nakabayashi , Kunio Higashi , Shiro Miyoshi , Hitoshi Yamauchi
IPC分类号： A61K9/127 , C07H15/04 , C07H15/14
CPC分类号： C07H15/14 , A61K9/1272 , C07H15/04
摘要： Sialic acid- containing glycolipid derivatives represented by the following general formula, their production method, and the particulate carriers that contain as a constituent the sialic acid-containing glycolipid derivative(s). ##STR1## wherein represents the .alpha.- or the .beta.- linkage, R.sup.1, a hydrogen atom or an acetyl group,R.sup.2, a hydrogen atom, a lower alkyl group with 1-4 carbon atoms, an alkaline metal ion, or such,X, an oxygen or sulfur atom or a residue represented by the following formula (II) or (III),--O(CH.sub.2).sub.m NHCO-- (II) where m represents an integer from 1 to 10.--O(CH.sub.2).sub.m CONH-- (III)Y, the formula (IV). ##STR2## where A represents a linear or branched chain acylamino group with 10-40 carbon atoms, or such B, a hydrogen atom, a carboxyl group or such, or the formula (V), and ##STR3## n, an integer of 0 to 3.

10. 发明授权

US06838450B2 Drug complex 失效
标题翻译：药物复合体
公开(公告)号：US06838450B2
公开(公告)日：2005-01-04
申请号：US10155170
申请日：2002-05-28
申请人： Kazuhiro Inoue , Hiroshi Susaki , Masahiro Ikeda , Hiroshi Kuga , Eiji Kumazawa , Akiko Togo
发明人： Kazuhiro Inoue , Hiroshi Susaki , Masahiro Ikeda , Hiroshi Kuga , Eiji Kumazawa , Akiko Togo
IPC分类号： A61K47/48 , A01N43/04 , A61K31/715 , A61K38/00
CPC分类号： A61K47/61
摘要： A drug complex characterized in that a residue of a drug compound such as antineoplastic agents and a carboxy(C1-4)alkyldextran polyalcohol obtained by treating a dextran under conditions that enable substantially complete polyalcoholization are bound to each other by means of a spacer comprising an amino acid or a spacer comprising peptide-bonded 2 to 8 amino acids. Said complex is characterized in that it has excellent selectivity to tumorous sites so as to exhibit high antineoplastic activity and also achieves reduced appearance of toxicity.
摘要翻译：一种药物复合物，其特征在于药物化合物如抗肿瘤剂和通过在能够基本上完全多元醇化的条件下处理葡聚糖而获得的羧基（C 1-4）烷基葡聚糖多元醇的残基通过包含氨基酸或包含肽键合的2至8个氨基酸的间隔子。所述复合物的特征在于其对肿瘤部位具有优异的选择性，从而表现出高的抗肿瘤活性，并且还实现了毒性的降低。

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