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1. 发明授权

US4771039A Botulinus toxin neutralizer 失效
标题翻译：肉毒毒素中和剂
公开(公告)号：US4771039A
公开(公告)日：1988-09-13
申请号：US844026
申请日：1986-03-25
申请人： Ryuichiro Tanaka , Koutaro Takamizawa , Hiroo Takayama , Toshizo Sakurai , Mitsuo Mada , Masahiko Mutai
发明人： Ryuichiro Tanaka , Koutaro Takamizawa , Hiroo Takayama , Toshizo Sakurai , Mitsuo Mada , Masahiko Mutai
IPC分类号： A61K35/20 , A61K31/00 , A61P39/02 , C07H15/10 , A61K31/70 , A61K31/685 , A61K35/48
CPC分类号： C07H15/10 , A61K31/00 , A61K35/20 , Y10S514/823
摘要： A botulinus toxin neutralizer comprising heat-treated fat globule membranes of animal milk or gangliosides isolated from fat globule membranes of animal milk. The neutralizer of the former nature is prepared from a material containing fat globules of animal milk by fractionating the material for separating the membranes of the fat globules from the rest of the material, and subjecting the separated fat globule membranes to heat treatment. The neutralizer of the former nature is prepared from a material containing fat globules by fractionating the material for separating the membranes of the fat globules from the rest of the material, and isolating gangliosides from the globule membranes.
摘要翻译：一种肉毒杆菌毒素中和剂，其包含动物乳的热处理脂肪球膜或从动物乳的脂肪球膜分离的神经节苷脂。前者性质的中和剂是由含有动物乳的脂肪球的材料制成的，分离用于将脂肪球的膜与其余材料分离的材料，并对分离的脂肪球膜进行热处理。前者性质的中和剂由含有脂肪球的材料制备，通过分离用于将脂肪球的膜与其余材料分离的材料，并从球状膜中分离神经节苷脂。

2. 发明授权

US4399282A Camptothecin derivatives 失效
公开(公告)号：US4399282A
公开(公告)日：1983-08-16
申请号：US166953
申请日：1980-07-08
申请人： Tadashi Miyasaka , Masahiko Mutai , Seigo Sawada , Kenichiro Nokata , Hisao Hagiwara
发明人： Tadashi Miyasaka , Masahiko Mutai , Seigo Sawada , Kenichiro Nokata , Hisao Hagiwara
IPC分类号： C07D491/22 , A61K31/47 , A61P35/00 , C07D491/147
CPC分类号： C07D491/22
摘要： New camptothecin derivatives possessing either or both of high anti-tumor activity and slight toxicity, represented by the general formula: ##STR1## wherein X is H, CH.sub.2 OH, COOH, an alkyl group, an aralkyl group or the grouping CH.sub.2 OR.sup.1 or COOR.sup.2 wherein R.sup.1 is an alkyl group or an acyl group and R.sup.2 is a lower alkyl group, Y is H, OH or the grouping OR.sup.3 wherein R.sup.3 is a lower alkyl group or an acyl group, and Z is H or an acyl group, with the proviso that when X is CH.sub.2 OH, an alkyl group or an aralkyl group, both Y and Z are H, that when X is the grouping CH.sub.2 OR.sup.1 or COOR.sup.2, Y is H, that when Y is OH, both X and Z are H, and that when Y is the grouping OR.sup.3, X is H, and water-soluble alkali metal salts thereof. These camptothecin derivatives are prepared by treating camptothecin with sulfuric acid and a persulfate or with sulfuric acid and a peroxide, if necessary, with an organic compound corresponding to the organic moiety of the substituent to be introduced directly into camptothecin, in an aqueous medium in the presence or absence of a transition metal ion, and optionally treating the resultant products, if necessary, after oxidation of the introduced substituent, with an alkylating agent or an acylating agent.

3. 发明授权

US4187321A Method for producing foods and drinks containing bifidobacteria 失效
标题翻译：生产含有双歧杆菌的食品和饮料的方法
公开(公告)号：US4187321A
公开(公告)日：1980-02-05
申请号：US861002
申请日：1977-12-15
申请人： Masahiko Mutai , Mitsuo Mada , Kiyohiro Shimada
发明人： Masahiko Mutai , Mitsuo Mada , Kiyohiro Shimada
IPC分类号： A23L1/28 , A23C9/123 , A23L1/48 , A61K35/74 , C12N1/20 , A23C9/12
CPC分类号： A23C9/1234 , A61K35/745 , C12N1/20
摘要： Foods and drinks containing bifidobacteria are prepared by growing in a milk medium under aerobic conditions a mixture of bifidobacteria containing a mutant strain of oxygen-resistant Bifidobacterium and a strain of obligatory anaerobic Bifidobacterium. Presence of the oxygen-resistant strain enables growing the obligatory anaerobic strain under aerobic conditions in a pure milk medium without added growth promoting substances.
摘要翻译：含有双歧杆菌的食品和饮料通过在需氧条件下在含有耐氧双歧杆菌突变菌株的双歧杆菌混合物和强制性厌氧双歧杆菌菌株的生殖培养基中生长。耐氧菌株的存在使得能够在需要的条件下在纯牛奶培养基中生长必需的厌氧菌，而不添加生长促进物质。

4. 发明授权

US4347240A Antitumor agent containing Lactobacillus casei YIT 9018 失效
标题翻译：含有干酪乳杆菌YIT 9018的抗肿瘤剂
公开(公告)号：US4347240A
公开(公告)日：1982-08-31
申请号：US124725
申请日：1980-02-26
申请人： Masahiko Mutai , Teruo Yokokura , Seizaburo Kobayashi , Ikuo Kato
发明人： Masahiko Mutai , Teruo Yokokura , Seizaburo Kobayashi , Ikuo Kato
IPC分类号： C12N1/20 , A61K35/74 , A61P35/00 , A61K39/02
CPC分类号： C12R1/245 , A61K35/747
摘要： Immunostimulating agent for inhibiting tumors comprising Lactobacillus casei YIT 9018 and methods for treating and/or preventing tumor growth.
摘要翻译：用于抑制肿瘤的免疫刺激剂，其包含干酪乳杆菌YIT 9018以及用于治疗和/或预防肿瘤生长的方法。

5. 发明授权

US4604463A Camptothecin derivatives and process for preparing same 失效
标题翻译：喜树碱衍生物及其制备方法
公开(公告)号：US4604463A
公开(公告)日：1986-08-05
申请号：US627980
申请日：1984-07-05
申请人： Tadashi Miyasaka , Seigo Sawada , Kenichiro Nokata , Eiichi Sugino , Masahiko Mutai
发明人： Tadashi Miyasaka , Seigo Sawada , Kenichiro Nokata , Eiichi Sugino , Masahiko Mutai
IPC分类号： A61K31/47 , A61K31/495 , A61K31/535 , A61P35/00 , C07D491/22
CPC分类号： C07D491/22
摘要： New camptothecin derivatives possessing high anti-tumor activity with slight toxicity, represented by the general formula: ##STR1## wherein R.sup.1 is a hydrogen atom, a halogen atom or an alkyl group with 1-4 carbon atoms and X is a chlorine atom or --NR.sup.2 R.sup.3 where R.sup.2 and R.sup.3 are the same or different and each represents a hydrogen atom, a substituted or unsubstituted alkyl group with 1-4 carbon atoms or a substituted or unsubstituted carbocyclic or heterocyclic group, with the proviso that when both R.sup.2 and R.sup.3 are the substituted or unsubstituted alkyl groups, they may be combined together with the nitrogen atom, to which they are bonded, to form a heterocyclic ring which may be interrupted with --O--, --S-- and/or >N--R.sup.4 in which R.sup.4 is a hydrogen atom, a substituted or unsubstituted alkyl group with 1-4 carbon atoms or a substituted or unsubstituted phenyl group and wherein the grouping --O--CO--X is bonded to a carbon atom located in any of the 9-, 10- and 11-positions in the ring A of camptothecin, as well as an ammonium salt or an alkali metal salt thereof. These new camptothecin derivatives are prepared by reacting a 7-R.sup.1 -camptothecin derivative having a hydroxyl group in any of the 9-, 10- and 11-positions on the ring A thereof with phosgen and then reacting, if necessary, the resultant 7-R.sup.1 -camptothecin derivative having a chlorocarbonyloxy group in the same position on the ring A thereof with an amine HNR.sup.2 R.sup.3 or by reacting a 7-R.sup.1 -camptothecin derivative having a hydroxyl group in any of the 9-, 10- and 11-positions on the ring A thereof with a carbamoyl chloride Cl-CONR.sup.2 R.sup.3.
摘要翻译：新的喜树碱衍生物具有高的抗肿瘤活性，具有轻微的毒性，由以下通式表示：其中R1是氢原子，卤素原子或具有1-4个碳原子的烷基，X是一个氯原子或-NR 2 R 3，其中R 2和R 3相同或不同，并且各自表示氢原子，取代或未取代的具有1-4个碳原子的烷基或取代或未取代的碳环或杂环基团，条件是当R 2和 R3是取代或未取代的烷基，它们可以与它们所键合的氮原子结合在一起形成杂环，其可被-O - ， - S-和/或> N-R 4中断其中R4是氢原子，取代或未取代的具有1-4个碳原子的烷基或取代或未取代的苯基，并且其中-O-CO-X基团键合到位于9-，十一和十一个位置在环A的以及铵盐或其碱金属盐。这些新的喜树碱衍生物通过使具有羟基的7-R1-喜树碱衍生物在其环A上的9-，10-和11-位中的光气与光气反应制备，然后如果需要，使所得的7- 在环A上具有与其相同位置上的氯羰基氧基的R1-喜树碱衍生物与胺HNR2R3反应，或通过使9-，10-和11-位任何一个具有羟基的7-R1-喜树碱衍生物在环A与氨基甲酰氯Cl-CONR2R3反应。

6. 发明授权

US4513138A Camptothecin-1-oxide derivatives 失效
标题翻译：喜树碱-1-氧化物衍生物
公开(公告)号：US4513138A
公开(公告)日：1985-04-23
申请号：US414528
申请日：1982-09-02
申请人： Tadashi Miyasaka , Seigo Sawada , Kenichiro Nokata , Masahiko Mutai
发明人： Tadashi Miyasaka , Seigo Sawada , Kenichiro Nokata , Masahiko Mutai
IPC分类号： A61K31/47 , A61P35/00 , C07D491/22
CPC分类号： C07D491/22
摘要： New 5- and/or 7-substituted camptothecin-1-oxide derivatives possessing anti-tumor activity with slight toxicity, represented by the general formula: ##STR1## wherein R is a hydrogen atom, an alkyl group, a hydroxyl group, an alkoxy group or an acyloxy group and R' is a hydrogen atom, an alkyl group, an aralkyl group, a hydroxymethyl group, an acyloxymethyl group or a carboxymethyl group, with the proviso that both of R and R' should not be hydrogen atoms. These 5- and/or 7-substituted camptothecin-1-oxide derivatives are prepared by treating the corresponding 5- and/or 7-substituted camptothecins with a peroxidant as an N-oxidizing reagent.
摘要翻译：新的5-和/或7-取代的喜树碱-1-氧化物衍生物具有轻微毒性的抗肿瘤活性，由以下通式表示：其中R是氢原子，烷基，羟基，烷氧基或酰氧基，R'为氢原子，烷基，芳烷基，羟甲基，酰氧基甲基或羧甲基，条件是R和R'都不应为氢原子这些5-和/或7-取代的喜树碱-1-氧化物衍生物通过用作为N-氧化剂的过氧化剂处理相应的5-和/或7-取代的喜树碱来制备。

7. 发明授权

US4399276A 7-Substituted camptothecin derivatives 失效
标题翻译： 7-取代的喜树碱衍生物
公开(公告)号：US4399276A
公开(公告)日：1983-08-16
申请号：US336494
申请日：1981-12-31
申请人： Tadashi Miyasaka , Masahiko Mutai , Seigo Sawada , Kenichiro Nokata
发明人： Tadashi Miyasaka , Masahiko Mutai , Seigo Sawada , Kenichiro Nokata
IPC分类号： C07D491/22
CPC分类号： C07D491/22
摘要： New 7-substituted camptothecin derivatives possessing anti-tumor activity with slight toxicity, represented by the general formula: ##STR1## wherein R stands for --CHO, --CH.sub.2 OR', --CH(OR').sub.2 or --CH.dbd.N--X where R' is a lower alkyl group with 1-6 carbon atoms or a phenylalkyl group with 1-3 carbon atoms in the alkylene moiety thereof, and X is a hydroxyl group or --NR.sup.1 R.sup.2 where R.sup.1 and R.sup.2 are the same or different and each represents a hydrogen atom or a lower alkyl group with 1-6 carbon atoms, or when R.sup.1 is hydrogen, R.sup.2 may be a lower alkyl group with 1-6 carbon atoms, a substituted or unsubstituted aryl group, a carbamoyl group, an acyl group, an aminoalkyl group or an amidino group, or when R.sup.1 is the lower alkyl group, R.sup.2 may be an aminoalkyl group, or R.sup.1 and R.sup.2 may be combined together with the nitrogen atom, to which R.sup.1 and R.sup.2 are bound, to form a heterocyclic group, and quaternary salts thereof. These 7-substituted camptothecin derivatives are prepared by treating 7-hydroxymethyl- or 7-dialkoxymethyl-camptothecin with a catinoid reagent, or treating 7-formyl- or 7-hydroxymethyl-camptothecin with an acid in the presence of a lower alkanol or phenylalkanol, or treating 7-formylcamptothecin or an acetal thereof with a nitrogen-containing carbonyl reagent and optionally treating the resulting product with a quaternating agent.
摘要翻译：新的7-取代的喜树碱衍生物具有轻微毒性的抗肿瘤活性，由以下通式表示：其中R代表-CHO，-CHOOR，-CH（OR'）2或-CH = NX 其中R'是具有1-6个碳原子的低级烷基或其亚烷基部分中具有1-3个碳原子的苯基烷基，X是羟基或-NR1R2，其中R1和R2相同或不同，表示氢原子或具有1-6个碳原子的低级烷基，或当R 1是氢时，R 2可以是具有1-6个碳原子的低级烷基，取代或未取代的芳基，氨基甲酰基，酰基，氨基烷基或脒基，或者当R 1为低级烷基时，R 2可以是氨基烷基，或者R 1和R 2可以与R 1和R 2结合的氮原子结合在一起形成杂环基团及其季盐。这些7-取代的喜树碱衍生物通过用亚麻酸试剂处理7-羟甲基 - 或7-二烷氧基甲基 - 喜树碱，或在低级烷醇或苯基链烷醇存在下用酸处理7-甲酰基或7-羟甲基 - 喜树碱来制备，或用含氮羰基试剂处理7-甲酰喜树碱或其缩醛，并任选用季铵化剂处理所得产物。

8. 发明授权

US4091117A Fermented milk product containing viable bifidobacteria 失效
标题翻译：含有活双歧杆菌的发酵乳制品
公开(公告)号：US4091117A
公开(公告)日：1978-05-23
申请号：US735413
申请日：1976-10-26
申请人： Masahiko Mutai , Mitsuo Mada , Kei Nakajima , Shusei Takahashi , Takashi Nakao , Kiyohiro Shimada , Takashi Iijima
发明人： Masahiko Mutai , Mitsuo Mada , Kei Nakajima , Shusei Takahashi , Takashi Nakao , Kiyohiro Shimada , Takashi Iijima
IPC分类号： A23C9/12 , A23C9/123 , A23C19/032 , A23G9/00 , A23G9/32 , A23G9/36 , A23L2/52 , C12N1/20
CPC分类号： A23G9/363 , A23C19/0323 , A23C9/1232 , A23C9/1234 , A23C2260/152
摘要： This invention relates to a method for producing fermented milk containing viable bifidobacteria by cultivating a variant of bifidobacteria in a milk medium, characterized in that the variant of bifidobacteria is acid-resistant and can be propagated under an aerobic condition in a pure milk medium which does not contain any growth-promoting substance.
摘要翻译：本发明涉及一种通过在乳培养基中培养双歧杆菌变体来生产含有活双歧杆菌的发酵乳的方法，其特征在于双歧杆菌的变体是耐酸的，并且可以在有氧条件下在纯牛奶培养基中繁殖不含任何生长促进物质。

9. 再颁专利

USRE32518E Camptothecin derivatives 失效
标题翻译：喜树碱衍生物
公开(公告)号：USRE32518E
公开(公告)日：1987-10-13
申请号：US676248
申请日：1984-11-29
申请人： Tadashi Miyasaka , Masahiko Mutai , Seigo Sawada , Kenichiro Nokata , Hisao Hagiwara
发明人： Tadashi Miyasaka , Masahiko Mutai , Seigo Sawada , Kenichiro Nokata , Hisao Hagiwara
IPC分类号： C07D491/22 , A61K31/47 , A61P35/00
CPC分类号： C07D491/22
摘要： New camptothecin derivatives possessing either or both of high anti-tumor activity and slight toxicity, represented by the general formula: ##STR1## wherein X is H, CH.sub.2 OH, COOH, an alkyl group, an aralkyl group or the grouping CH.sub.2 OR.sup.1 or COOR.sup.2 wherein R.sup.1 is an alkyl group or an acyl group and R.sup.2 is a lower alkyl group, Y is H, OH or the grouping OR.sup.3 wherein R.sup.3 is a lower alkyl group or an acyl group, and Z is H or an acyl group, with the proviso that when X is CH.sub.2 OH, an alkyl group or an aralkyl group, both Y and Z are H, that when X is the grouping CH.sub.2 OR.sup.1 or COOR.sup.2, Y is H, that when Y is OH, both X and Z are H, .[.and.]. that when Y is the grouping OR.sup.3, X is H, .Iadd.and that X, Y and Z are not each simultaneously hydrogen, .Iaddend.and water-soluble alkali metal salts thereof. These camptothecin derivatives are prepared by treating camptothecin with sulfuric acid and a persulfate or with sulfuric acid and a peroxide, if necessary, with an organic compound corresponding to the organic moiety of the substituent to be introduced directly into camptothecin, in an aqueous medium in the presence or absence of a transition metal ion, and optionally treating the resultant products, if necessary, after oxidation of the introduced substituent, with an alkylating agent or an acylating agent.
摘要翻译：具有以下通式表示的具有高抗肿瘤活性和轻微毒性的新喜树碱衍生物：其中X为H，CH 2 OH，COOH，烷基，芳烷基或CH 2 OR 1或COOR 2基团，其中R1 是烷基或酰基，R 2是低级烷基，Y是H，OH或OR 3，其中R 3是低级烷基或酰基，Z是H或酰基，条件是当X为CH 2 OH时，Y和Z均为H，烷基或芳烷基为H时，当X为CH 2 OR 1或COOR 2时，Y为H，当Y为OH时，X和Z均为H， Y为OR 3，X为H及其水溶性碱金属盐。这些喜树碱衍生物通过用硫酸和过硫酸盐或硫酸和过氧化物（如果需要）与对应于待直接引入喜树碱的有机部分的有机化合物在水性介质中处理来制备存在或不存在过渡金属离子，并且如果需要，可以用烷基化剂或酰化剂任选地处理所得产物，在引入的取代基氧化之后。

10. 发明授权

US4545880A Photochemical process for preparing camptothecin derivatives 失效
标题翻译：喜树碱衍生物的光化学过程
公开(公告)号：US4545880A
公开(公告)日：1985-10-08
申请号：US632039
申请日：1984-07-18
申请人： Tadashi Miyasaka , Seigo Sawada , Kenichiro Nokata , Masahiko Mutai
发明人： Tadashi Miyasaka , Seigo Sawada , Kenichiro Nokata , Masahiko Mutai
IPC分类号： C07D491/22 , B01J19/12
CPC分类号： C07D491/22
摘要： New Camptothecin derivatives possessing high anti-tumor activity with slight toxicity, represented by the general formula: ##STR1## wherein R.sup.1 stands for a hydrogen atom, an alkyl group, a hydroxyl group, an alkoxy group or an acyloxy group, R.sup.2 for a hydrogen atom, an alkyl group, an aralkyl group, a hydroxymethyl group, a carboxymethyl group or an acyloxymethyl group, and R.sup.3 for the grouping --XR' (where R' is a hydrogen atom, an alkyl group or an acyl group and X is an oxygen atom or a sulfur atom), a nitro group, an amino group, an alkylamino group, an acylamino group or a halogen atom, with the proviso that when both of R.sup.1 and R.sup.2 are hydrogen atoms, R.sup.3 should not be hydroxyl group, methoxy group or acetoxy group. These new camptothecin derivatives are prepared by treating a 5-R.sup.1 -7-R.sup.2 camptothecin derivative with a peroxidant and then reacting the resultant 5-R.sup.1 -7-R.sup.2 -camptothecin-1-oxide with an active hydrogen compound under irradiation of UV-rays or by catalytically hydrogenating the ring B of camptothecin in a solvent, treating the resultant tetrahydro product with an acylating agent, introducing nitro group into 10-position of the acylated product by the reaction with nitric acid, splitting off the acyl group in the 10-nitro product by hydrolysis and treating the hydrolyzed tetrahydro product with an oxidizing agent for dehydrogenation, and if desired, reducing the nitro group in the resultant product to amino group and modifying the amino group by N-alkylation, N-acylation or by diazotization followed by hydrolysis or Sandmeyer reaction, before or after the oxidation of the 10-nitro-tetrahydro product.

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