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1. 发明授权

US4229573A 7.alpha.-Methoxycephalosporin derivatives 失效
标题翻译： 7α-甲氧基头孢菌素衍生物
公开(公告)号：US4229573A
公开(公告)日：1980-10-21
申请号：US808631
申请日：1977-06-21
申请人： Chisei Shibuya , Hirataka Itoh , Kunihiko Ishii , Torao Ishida , Mitsuru Shibukawa
发明人： Chisei Shibuya , Hirataka Itoh , Kunihiko Ishii , Torao Ishida , Mitsuru Shibukawa
IPC分类号： C07D501/20 , C07D501/57
CPC分类号： C07D501/57
摘要： Novel 7.alpha.-methoxycephalosporin derivatives having a high antimicrobial activity. They are useful for the medical treatment of diseases infected by gram-positive bacteria and gram-negative bacteria. More particularly, they show an antimicrobial activity against bacteria such as Eschericha coli Proteus, Citrobacter and Enterobacter which bacteria have resistance to the conventionally employed cephalosporins, and they are effective for the medical treatment of diseases infected by these bacteria. Such 7.alpha.-methoxycephalosporin derivatives are prepared by a relatively simple method.
摘要翻译：具有高抗微生物活性的新型7α-甲氧基头孢菌素衍生物。它们可用于治疗革兰氏阳性菌和革兰氏阴性菌感染的疾病。更特别地，它们对细菌具有抗菌活性，例如细菌对常规使用的头孢菌素具有抗性的大肠杆菌Proteus，柠檬酸杆菌和肠杆菌，并且它们对于治疗由这些细菌感染的疾病是有效的。这样的7α-甲氧头孢菌素衍生物通过相对简单的方法制备。

2. 发明授权

US4556651A Secalonic acid derivatives as antitumor agents 失效
标题翻译： Secalonic acid衍生物作为抗肿瘤剂
公开(公告)号：US4556651A
公开(公告)日：1985-12-03
申请号：US529635
申请日：1983-09-06
申请人： Mitsuru Shibukawa , Chisei Shibuya , Kunihiko Ishii
发明人： Mitsuru Shibukawa , Chisei Shibuya , Kunihiko Ishii
IPC分类号： C07D311/86 , C07D407/04 , A61K31/35
CPC分类号： C07D311/86
摘要： A secalonic acid derivative of the formula (I); ##STR1## wherein R is ##STR2## wherein R.sub.1 and R.sub.2 each independently is a hydrogen atom or a C.sub.1-4 alkyl group; R.sub.3 is a hydrogen atom, a C.sub.1-4 alkyl group, and aryl group, a C.sub.1-5 alkoxy group, a halogen atom, a cyano group, a carboxyl group, a sulfonic acid group, a carboxylic acid amide group or a sulfonic acid amide group; and R.sub.4 is a saturated or unsaturated C.sub.1-22 alkyl group, an aryl group or an aryl alkyl group, and may have a substituent; and the pharmaceutically acceptable salts thereof.

3. 发明授权

US4418061A Secalonic acid derivatives and method for preparing thereof 失效
标题翻译： Secalonic acid衍生物及其制备方法
公开(公告)号：US4418061A
公开(公告)日：1983-11-29
申请号：US366333
申请日：1982-04-07
申请人： Mitsuru Shibukawa , Chisei Shibuya , Kunihiko Ishii
发明人： Mitsuru Shibukawa , Chisei Shibuya , Kunihiko Ishii
IPC分类号： C07D311/86 , C07D405/14 , A61K31/40
CPC分类号： C07D311/86
摘要： A secalonic acid derivative of the formula (I); ##STR1## wherein R is ##STR2## wherein R.sub.1 and R.sub.2 each independently is a hydrogen atom or a C.sub.1-4 alkyl group; R.sub.3 is a hydrogen atom, a C.sub.1-4 alkyl group, an aryl group, a C.sub.1-5 alkoxy group, a halogen atom, a cyano group, a carboxyl group, a sulfonic acid group, a carboxylic acid amide group or a sulfonic acid amide group; and R.sub.4 is a saturated or unsaturated C.sub.1-22 alkyl group, an aryl group or an aryl alkyl group, and may have a substituent;and the pharmaceutically acceptable salts thereof.
摘要翻译：式（I）的secalonic acid衍生物; （I）其中R为，其中R1和R2各自独立地为氢原子或C1-4烷基; R3是氢原子，C1-4烷基，芳基，C1-5烷氧基，卤素原子，氰基，羧基，磺酸基，羧酸酰胺基或磺酸酰胺基; 并且R 4是饱和或不饱和的C 1-22烷基，芳基或芳基烷基，并且可以具有取代基; 及其药学上可接受的盐。

4. 发明授权

US4393225A AI-77 Compounds and pharmaceutically acceptable salts thereof 失效
标题翻译： AI-77其化合物及其药学上可接受的盐
公开(公告)号：US4393225A
公开(公告)日：1983-07-12
申请号：US167581
申请日：1980-07-11
申请人： Hiroshi Hayashi , Yukiji Shimojima , Takashi Shirai , Torao Ishida , Mitsuru Shibukawa
发明人： Hiroshi Hayashi , Yukiji Shimojima , Takashi Shirai , Torao Ishida , Mitsuru Shibukawa
IPC分类号： C07D311/76 , C12P13/02 , C12P17/06 , C12P17/16
CPC分类号： C12R1/07 , C07D311/76 , C12P13/02 , C12P17/06 , C12P17/162
摘要： AI-77 compounds, pharmaceutically acceptable salts thereof, and a process for the preparation thereof are described, said compounds having the formulae ##STR1## wherein: X is NR.sub.6 or O; Y is NHR.sub.5 or combine with Z to provide a link for bonding C and C; Z is H or combines with Y to provide a link for bonding C and C; R.sub.1, R.sub.3 and R.sub.5 are each H, R', --CH.sub.2 R, or --COR; R.sub.6 is H or R; R.sub.7 is H, R or CH.sub.2 R; R is a hydrocarbon group consisting of a saturated or unsaturated straight or branched aliphatic group of C.sub.1 to C.sub.17, an aromatic group of C.sub.6 to C.sub.10, a cage type group of C.sub.7 to C.sub.10, a monocyclic aliphatic group of C.sub.3 to C.sub.8, an aromatic-aliphatic group of C.sub.7 to C.sub.15, a heterocyclic hydrocarbon of C.sub.1 to C.sub.9, wherein the above hydrocarbons can be substituted with one or more groups selected from halogen, oxo, carboxyl, hydroxyl, a saturated or unsaturated straight or branched aliphatic group of C.sub.1 to C.sub.5, an aromatic group of C.sub.6 to C.sub.10, a monocyclic aliphatic group of C.sub.3 to C.sub.8, an aromatic-aliphatic group of C.sub.7 to C.sub.11, alkoxy of C.sub.1 to C.sub.5, thioalkoxyl of C.sub.1 to C.sub.5, carboalkoxyl of C.sub.1 to C.sub.6, acyl of C.sub.1 to C.sub.5, acyloxy of C.sub.2 to C.sub.6 and a heterocyclic group of C.sub.1 to C.sub.9 ; R' is the same as R exclusive of those groups wherein unsaturated carbon or tertiary carbon is directly bonded to O or N; R.sub.2 is H, or combines with T.sub.1 to provide a link for bonding C and O in a lactone ring; T.sub.1 is OH or combines with R.sub.2 to provide a link for bonding C and O in a lactone ring; R.sub.4 is H or combines with T.sub.2 to provide a link for bonding C and O in a lactone ring; and T.sub.2 is OH or combines with R.sub.4 to provide a link for bonding C and O in a lactone ring; and pharmaceutically acceptable salts thereof.
摘要翻译：描述了具有下式的化合物：其中：X为NR6或O;其中：X为NR6或O; Y是NHR5或与Z结合以提供用于键合C和C的连接; Z是H或与Y结合以提供用于键合C和C的连接; R1，R3和R5各自为H，R'，-CH2R或-COR; R6是H或R; R7是H，R或CH2R; R是由C 1〜C 17的饱和或不饱和直链或支链脂族基团，C6〜C10的芳香族基团，C7〜C10的保持基团，C3〜C8的单环式脂肪族基团，芳香族 - C 7〜C 15的脂族基团，C 1〜C 9的杂环烃，其中上述烃可以被一个或多个选自卤素，氧代，羧基，羟基，C1至C5的饱和或不饱和直链或支链脂族基团的基团取代，C 6〜C 10的芳基，C 3〜C 8的单环脂族基，C 7〜C 11的芳香族 - 脂肪族基，C 1〜C 5的烷氧基，C 1〜C 5的烷氧基，C 1〜C 6的碳烷氧基， C5，C2〜C6的酰氧基和C1〜C9的杂环基; R'与R不同，其中不饱和碳或叔碳直接与O或N键合; R2是H或与T1结合以提供用于在内酯环中键合C和O的连接; T1是OH或与R2结合以提供用于在内酯环中键合C和O的连接; R4是H或与T2结合以提供用于在内酯环中键合C和O的连接; 并且T2是OH或与R4结合以提供用于在内酯环中键合C和O的连接; 及其药学上可接受的盐。

5. 发明授权

US4409105A Dried, sterilized, gamma-globulin-fixed column and a process for preparing the same 失效
标题翻译：干燥，灭菌，γ-球蛋白固定柱及其制备方法
公开(公告)号：US4409105A
公开(公告)日：1983-10-11
申请号：US323338
申请日：1981-11-20
申请人： Hiroshi Hayashi , Takao Kiyota , Mitsuru Shibukawa
发明人： Hiroshi Hayashi , Takao Kiyota , Mitsuru Shibukawa
IPC分类号： G01N33/548 , A61K39/44 , A61L2/00 , A61L2/20 , A61M1/14 , A61M1/36 , G01N33/543 , B01J8/02
CPC分类号： A61M1/3679 , A61K39/44 , A61L2/0094 , A61L2/206 , Y10S530/868
摘要： A dried, sterilized column containing a carrier-fixed .gamma.-globulin capable of specifically combining with various harmful substances found in blood of patients suffering from certain diseases and acting as an antibody. The .gamma.-globulin fixed column according to the present invention has a prolonged storage stability, and an excellent activity and safety even after the storage for a prolonged period of time as compared with unsterilized columns. Therefore, the .gamma.-globulin fixed column according to the present invention may be advantageously used for medical instrument applications.
摘要翻译：一种干燥的无菌柱，其含有载体固定的γ-球蛋白，其能够与患有某些疾病的患者的血液中发现的各种有害物质特异性结合并作为抗体。根据本发明的γ-球蛋白固定柱具有延长的储存稳定性，即使在与未灭菌的柱相比长时间储存之后也具有优异的活性和安全性。因此，根据本发明的γ-球蛋白固定柱可有利地用于医疗仪器应用。

6. 发明授权

US4349627A Process for producing L-tryptophan or derivatives thereof using a microorganism 失效
标题翻译：使用微生物生产L-色氨酸或其衍生物的方法
公开(公告)号：US4349627A
公开(公告)日：1982-09-14
申请号：US274566
申请日：1981-06-17
申请人： Akio Mimura , Yasuyuki Takahashi , Katsumi Yuasa , Mitsuru Shibukawa
发明人： Akio Mimura , Yasuyuki Takahashi , Katsumi Yuasa , Mitsuru Shibukawa
IPC分类号： C12P13/22 , C12R1/01 , C12R1/22 , C12N1/20
CPC分类号： C12R1/22 , C12P13/227 , C12R1/01 , Y10S435/822
摘要： A process for producing L-tryptophan or a derivative thereof is disclosed, wherein an indole compound is reacted with serine, or with pyruvic acid and/or its salt and ammonium ion, in the presence of a culture or treated culture of a particular microorganism of genus Enterobacter having a special ability to produce L-tryptophan or a derivative thereof from an indole compound and serine, or from an indole compound, pyruvic acid and/or its salt, and ammonium ion.
摘要翻译：公开了一种生产L-色氨酸或其衍生物的方法，其中吲哚化合物与丝氨酸反应，或与丙酮酸和/或其盐和铵离子反应，在培养物或经处理的培养物存在下，具有从吲哚化合物和丝氨酸或从吲哚化合物，丙酮酸和/或其盐和铵离子产生L-色氨酸或其衍生物的特殊能力的肠杆菌属。

7. 发明授权

US4450233A Immobilization of microorganisms in a polymer gel 失效
标题翻译：微生物在聚合物凝胶中的固定
公开(公告)号：US4450233A
公开(公告)日：1984-05-22
申请号：US330916
申请日：1981-12-15
申请人： Akio Mimura , Katsumi Yuasa , Mitsuru Shibukawa
发明人： Akio Mimura , Katsumi Yuasa , Mitsuru Shibukawa
IPC分类号： C12N11/04 , C12N11/10 , C12N11/08
CPC分类号： C12N11/10 , C12N11/04
摘要： Microorganisms are immobilized by adding microorganism cells to an aqueous solution of a mixture of a polymerizable starch and a polymerizable monomer, and, thereafter, polymerizing the polymerizable starch and polymerizable monomer, to prepare a polymer gel with microorganism cells enclosed therein. The polymerizable starch is prepared by introducing an acrylamidomethyl group into starch. The polymer gel has high mechanical strength and can be used repeatedly over long periods of the time while maintaining at high levels the reactivity of the microorganism enclosed therein.
摘要翻译：通过将微生物细胞添加到可聚合淀粉和可聚合单体的混合物的水溶液中，然后使可聚合淀粉和可聚合单体聚合，从而制备聚合物凝胶，将微生物细胞封装在其中来固定微生物。通过将丙烯酰胺基甲基引入淀粉中制备可聚合淀粉。聚合物凝胶具有高的机械强度，并且可以在长时间内重复使用，同时保持包含在其中的微生物的反应性的高水平。

8. 发明授权

US4317882A Production of plasminogen activator 失效
标题翻译：生产纤溶酶原激活物
公开(公告)号：US4317882A
公开(公告)日：1982-03-02
申请号：US143680
申请日：1980-04-25
申请人： Sadayuki Horiguchi , Akio Hasegawa , Mitsuru Shibukawa
发明人： Sadayuki Horiguchi , Akio Hasegawa , Mitsuru Shibukawa
IPC分类号： A61K38/00 , C12N9/72 , C12N9/48
CPC分类号： C12N9/6462 , C12Y304/21073 , A61K38/00 , Y10S435/818
摘要： A plasminogen activator having a molecular weight of 45,000 to 68,000 is formed as a single fraction in the cells of human kidney or lung, and is separated and recovered with good efficiency without reducing its molecular weight. The pH of a solution to be contacted with said cells and the concentration of dissolved oxygen should be maintained within suitable ranges in order to form the plasminogen activator having a molecular weight of 45,000 to 68,000 as a single fraction. Furthermore, by properly adjusting the residence time of the solution with the cells, the activator can be formed over a long period of more than 40 days. To separate the activator, the pH of the solution in the separating step is maintained preferably at 4 to 12. By causing a metal chelating agent to be present in the solution in the separating step, the plasminogen activator can be obtained without reducing its molecular weight.
摘要翻译：在人肾或肺细胞中形成分子量为45,000至68,000的纤溶酶原激活剂作为单一部分，并且在不降低其分子量的情况下以高效率分离和回收。要与所述细胞接触的溶液的pH值和溶解氧的浓度应保持在合适的范围内，以形成分子量为45,000至68,000的纤溶酶原激活剂作为单一部分。此外，通过适当调整溶液与细胞的停留时间，可以在40天以上的长时间内形成活化剂。为了分离活化剂，分离步骤中的溶液的pH优选保持在4至12.通过在分离步骤中使溶液中存在金属螯合剂，可以在不降低其分子量的情况下获得纤溶酶原激活剂。

9. 发明授权

US4477659A Cephalosporin compound 失效
标题翻译：头孢菌素化合物
公开(公告)号：US4477659A
公开(公告)日：1984-10-16
申请号：US388937
申请日：1982-06-16
申请人： Joji Nishikido , Eiji Kodama , Mitsuru Shibukawa
发明人： Joji Nishikido , Eiji Kodama , Mitsuru Shibukawa
IPC分类号： A61K31/545 , A61K31/546 , A61P31/04 , C07D501/20 , C07D501/22 , C07D501/34 , C07D501/36 , C07D501/57 , C07D501/59
CPC分类号： C07D501/20 , Y02P20/55
摘要： A cephalosporin compound of the general formula (I): ##STR1## wherein X is a hydrogen atom, a chlorine atom, a methyl group, a methoxy group, an acetoxymethyl group or --CH.sub.2 SHet wherein Het is a 5- or 6-membered heterocyclic ring containing therein 1 to 4 nitrogen, oxygen or sulfur atoms;R.sub.1, R.sub.2 and R.sub.3 each independently is a hydrogen atom or a protective group which can be pharmaceutically hydrolyzed; andR.sub.4 is a hydrogen atom or a methoxy group;and the pharmaceutically acceptable salts thereof.
摘要翻译：通式（I）的头孢菌素化合物：其中X为氢原子，氯原子，甲基，甲氧基，乙酰氧基甲基或-CH2SHet，其中Het为5-或6 含有1至4个氮，氧或硫原子的杂环; R1，R2和R3各自独立地是氢原子或可以被药学上水解的保护基; R4为氢原子或甲氧基; 及其药学上可接受的盐。

10. 发明授权

US4465668A Method for improving intestinal absorption of cephalosporin derivatives 失效
标题翻译：改善头孢菌素衍生物肠吸收的方法
公开(公告)号：US4465668A
公开(公告)日：1984-08-14
申请号：US351613
申请日：1982-02-24
申请人： Joji Nishikido , Eiji Kodama , Mitsuru Shibukawa
发明人： Joji Nishikido , Eiji Kodama , Mitsuru Shibukawa
IPC分类号： A61K38/00 , C07D501/20 , C07K5/078 , A61K37/02
CPC分类号： C07K5/06139 , A61K38/00 , Y02P20/55 , Y10S930/19 , Y10S930/27
摘要： A method for improving the intestinal absorption of a cephalosporin derivative by bonding an oligopeptide having the general formula (I): ##STR1## wherein X is a hydrogen atom, C.sub.1-15 alkyl group, R.sub.3 CO-- group wherein R.sub.3 is a hydrogen atom or straight or branched chain C.sub.1-15 alkyl group or a protective group easily removable by acid hydrolysis, hydrogenolysis or enzyme existing in a living body;R.sub.1 and R.sub.2 each independently is a side chain of an amino acid constituting the oligopeptide; andn is integer of 1 to 3,to any side chain at the 3-, 4- or 7-position of a 7-aminocephalosporanic acid derivative having antibacterial activity.
摘要翻译：通过键合具有通式（I）的寡肽来改善头孢菌素衍生物的肠吸收的方法：其中X是氢原子，C 1-15烷基，R 3 CO-基团，其中R 3是氢原子或直链或支链C1-15烷基或通过存在于活体中的酸水解，氢解或酶容易除去的保护基; R1和R2各自独立地是构成寡肽的氨基酸的侧链; n为1〜3的整数，即具有抗菌活性的7-氨基头孢烷酸衍生物的3-，4-或7-位的任一侧链。

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