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1. 发明专利

JPS60161999A PEPTIDE 失效
公开(公告)号：JPS60161999A
公开(公告)日：1985-08-23
申请号：JP1912684
申请日：1984-02-02
申请人： CHEMO SERO THERAPEUT RES INST , FUJISAWA PHARMACEUTICAL CO
发明人： MIAKE FUMIO , MIYANOHARA KOUJI , OOTOMO SHINYA , MATSUBARA KENICHI , HASHIMOTO SHINJI , HENMI KEIJI , HAGIWARA DAIJIROU
IPC分类号： C07K7/08 , A61K38/00 , A61K39/29 , C07K14/00
摘要： NEW MATERIAL:A compound (salt) expressed by formulas I -VII (R is H or protecting group of mercapto). USE:An antigen for analyzing hepatitis B viruses and antigen for hepatitis B vaccines. PREPARATION:For example, serine having amino group protected with tert- butoxycarbonyl group is linked to a chloromethylated styrene-divinylbenzene copolymer resin as a carrier to give N-tert-butoxycarbonyl-O-benzylserine resin. The amino group of the resultant resin is then eliminated, and amino acids having protected amino groups are condensed with the resin according to the amino acid sequence of the aimed peptide in the presence of a condensing agent. The operation to eliminate protecting groups is repeated successively to afford a peptide resin, which is then treated with hydrogen fluoride in the presence of a solvent to separate the peptide from the carrier and give the aimed peptide expressed by formulas I -VII.

2. 发明专利

JPS6013718A B-TYPE HEPATITIS VACCINE 失效
公开(公告)号：JPS6013718A
公开(公告)日：1985-01-24
申请号：JP12294583
申请日：1983-07-05
申请人： CHEMO SERO THERAPEUT RES INST
发明人： MIZUNO KIYOUSUKE , ISHIHARA YOSHIMITSU , KAWAHARA TETSUO , OOTOMO SHINYA
IPC分类号： A61K39/29 , A61K39/00 , C07K14/02
摘要： PURPOSE:To obtain an improved lyophilized pharmaceutical preparation of B- type hepatitis vaccine having no reduction in titer, stability, and solubility of rapid disssolution, obtained by adding aluminum gel and a stabilizer to a surface antigen of deactivated purified B-type hepatitis virus, lyophilizing it. CONSTITUTION:A surface antigen of deactivated purified B-type hepatitis virus (HBsAg for short) is blended with a aluminum gel (aluminum hydroxide gel, aluminum phosphate gel) and a stabilzer, and lyophilized to give a lyophilized pharmaceutical preparation of B-type hapatitis vaccine. The stabilizer consists of one of an amino acid or its salt (e.g., glycine, alanine, lysine, etc.) and a saccharide (e.g., glucose, xylose, etc.), preferably both, and, more preferably, a colloidal agent (e.g., gelatine, dextran, etc.). It has better storage stability than liquid HBsAg, no reduction in titer, and good solubility in use.

3. 发明专利

JPS60162000A NOVEL PEPTIDE 失效
公开(公告)号：JPS60162000A
公开(公告)日：1985-08-23
申请号：JP1912784
申请日：1984-02-02
申请人： CHEMO SERO THERAPEUT RES INST , FUJISAWA PHARMACEUTICAL CO
发明人： MIAKE FUMIO , MIYANOHARA KOUJI , OOTOMO SHINYA , MATSUBARA KENICHI , HASHIMOTO SHINJI , HENMI KEIJI , HAGIWARA DAIJIROU
IPC分类号： C07K7/08 , A61K38/00 , A61K39/29 , C07K14/00
摘要： NEW MATERIAL:A compound (salt) expressed by formulas I -IV (R is H or protecting group of mercapto). USE:An antigen for analyzing hepatitis B viruses and antigen for hepatitis B vaccines. PREPARATION:For example, amino acids having amino group protected with tert-butoxycarbonyl group are successively condensed with a chloromethylated styrene-divinylbenzene copolymer resin as a carrier according to the amino acid sequence of the aimed peptide, and protecting groups are removed. The above- mentioned operation is repeated successively to give a peptide resin, which is then treated with hydrogen fluoride in the presence of a solvent to separate the resultant peptide from the carrier. Mercuric acetate and acetic acid are if necessary added thereto to adjust pH to 4, and hydrogen sulfide gas is blown thereinto under agitation to reduce the peptide and form an intramolecular cystine type peptide. Thus, the aimed peptide expressed by formulas I -IV is obtained.

4. 发明专利

JPH0552190B2 失效
公开(公告)号：JPH0552190B2
公开(公告)日：1993-08-04
申请号：JP26246584
申请日：1984-12-11
申请人： CHEMO SERO THERAPEUT RES INST
发明人： NOZAKI CHIKAHIDE , MAKIKADO KEIICHI , KINO YOICHIRO , ETO TATSUO , OOTOMO SHINYA
IPC分类号： C12N15/09 , A61K39/00 , A61K39/245 , A61P31/12 , C07K14/035 , C12N1/19 , C12N15/81 , C12P21/02 , C12R1/865 , C12N15/38

5. 发明专利

JPS60193925A Lyophilized pharmaceutical preparation vaccine 失效
标题翻译： LYOPHILIZED PHARMACEUTICAL PREPARATION VACCINE
公开(公告)号：JPS60193925A
公开(公告)日：1985-10-02
申请号：JP4866984
申请日：1984-03-13
申请人： Chemo Sero Therapeut Res Inst
发明人： OOTOMO SHINYA , MIZUNO KIYOUSUKE , HAMADA FUKUSABUROU , MIZOGAMI HIROSHI
IPC分类号： C12N15/09 , A61K39/00 , A61K39/29 , C07K14/02 , C12P21/00 , C12R1/865 , C12R1/91
CPC分类号： C07K14/005 , A61K39/00 , C12N2730/10122
摘要： PURPOSE: To obtain the titled vaccine, by adding aluminum gel and a stabilizer to a purified HBs antigen prepared by a recombinant provided with BHs antigen preparation ability, transformed by recombinant DNA method, lyophilizing the blend.
CONSTITUTION: A purified HBs antigen derived from a recombinant, prepared by a recombinant provided with HBs antigen preparation ability, transformed by a recombinant DNA method, is blended with aluminum gel (e.g., aluminum hydroxide gel, aluminum phosphate gel, etc.), a stabilizer (e.g., amino acid such as glycine, saccharide such as glucose, etc.), and, preferably a colloidal agent (e.g., gelatin, etc.), and lyophilized, to obtain lyophilized pharmaceutical preparation of hepatitis B vaccine. It has no reduction in titer, good shelf stability, rapidly dissolving properties and is an extremely improved pharmaceutical preparation. A dose is 5W50μg HBs antigen protein/day, and it is inoculated hypodermically.
COPYRIGHT: (C)1985,JPO&Japio
摘要翻译：目的：为了获得标题疫苗，通过用提供BHs抗原制备能力的重组体制备的纯化HBs抗原中加入铝凝胶和稳定剂，通过重组DNA方法转化，冻干该混合物。构成：通过重组DNA方法转化的具有HBs抗原制备能力的重组体制备的纯化HBs抗原与铝凝胶（例如氢氧化铝凝胶，磷酸铝凝胶等）共混，稳定剂（例如甘氨酸等氨基酸，葡萄糖等糖类），优选胶体剂（例如明胶等），冻干，得到乙型肝炎疫苗的冻干药物制剂。滴定度降低，贮存稳定性好，易溶解性好，是药物制剂极其改良。剂量为5-50毫升HBs抗原蛋白/天，并接种于皮下。

6. 发明专利

JPH0574599B2 失效
公开(公告)号：JPH0574599B2
公开(公告)日：1993-10-18
申请号：JP27143284
申请日：1984-12-21
申请人： CHEMO SERO THERAPEUT RES INST
发明人： SUGAWARA KEISHIN , IMAMURA TAKAYUKI , HAMADA FUKUSABURO , OOTOMO SHINYA
IPC分类号： A61K39/29 , C07K1/16 , C07K14/02 , C12N15/09 , C12P21/08 , G01N33/576 , C07K3/20 , C07K15/04 , C12P21/02

7. 发明专利

JPS6110598A Peptide compound 失效
标题翻译：肽类化合物
公开(公告)号：JPS6110598A
公开(公告)日：1986-01-18
申请号：JP12963284
申请日：1984-06-23
申请人： Chemo Sero Therapeut Res Inst , Fujisawa Pharmaceut Co Ltd
发明人： MIAKE FUMIO , MIYANOHARA KOUJI , OOTOMO SHINYA , MATSUBARA KENICHI , HASHIMOTO SHINJI , HENMI KEIJI , HAGIWARA DAIJIROU
IPC分类号： G01N33/576 , A61K39/29 , C07K7/08 , C07K14/00 , G01N33/53
CPC分类号： Y02P20/55
摘要： NEW MATERIAL:A compound (salt) expressed by formula I (R
4 is H or a protecting group of the mercapto group) and formula II.
USE: An antigen composition for analyzing hepatitis B viruses and hepatitis B vaccines.
PREPARATION: The protecting group of N-tert-butoxycarbonyl-O-benzylserine resin as a starting material is eliminated therefrom, and amino acids having amino group protected with tert-butoxycarbonyl group are condensed therewith using dicyclohexylcarbodiimide, etc. as a condensing agent according to the amino acid sequence. The above-mentioned operation is repeated to extend the peptide chain. In the process, functional groups in the side chain are protected as follows; Benzyl group for Ser and Thr, Acetamidomethyl group for Cys, cyclohexyl ester for Asp and 2-chlorobenzyloxycarbonyl group for Lys to carry out the condensation reaction. After completing the peptide chain synthesis, the protecting groups are eliminated from the resin to afford the aimed compound expressed by formulas I and II.
COPYRIGHT: (C)1986,JPO&Japio
摘要翻译：新材料：由式I表示的化合物（盐）（R 4是H或巯基的保护基）和式II。用途：用于分析乙型肝炎病毒和乙型肝炎疫苗的抗原组合物。制备：将N-叔丁氧基羰基-O-苄基丝氨酸树脂作为起始原料的保护基被除去，用叔丁氧基羰基保护的氨基的氨基酸用二环己基碳二亚胺等作为缩合剂缩合，根据氨基酸序列。重复上述操作以延长肽链。在该过程中，侧链中的官能团如下保护： Ser和Thr的苄基，Cys的酰氨基甲基，Asp的环己酯和Lys的2-氯苄氧基羰基进行缩合反应。完成肽链合成后，从树脂中除去保护基，得到由式I和II表示的目标化合物。

8. 发明专利

JPS615786A RECOMBINANT DNA HAVING INTEGRATED HERPES SIMPLEX VIRUS, TRANSFORMANT ANIMAL CELL AND PRODUCTION OF HERPES SIMPLEX VIRUS PROTEIN 失效
公开(公告)号：JPS615786A
公开(公告)日：1986-01-11
申请号：JP12715284
申请日：1984-06-19
申请人： CHEMO SERO THERAPEUT RES INST
发明人： ETOU TATSUO , NOZAKI CHIKAHIDE , KINO YOUICHIROU , MAKIKADO KEIICHI , OOTOMO SHINYA
IPC分类号： C12N15/09 , A61K39/00 , A61K39/245 , C07H21/04 , C07K14/035 , C12N5/10 , C12N15/85 , C12P21/00 , C12R1/91
摘要： PURPOSE:To utilize a gB glycoprotein for producing a safe component vaccine, by integrating herpes simplex virus (HSV), particularly HSVgB gene in a specific plasmid, transforming the resultant plasmid to an animal cell, and obtaining the above-mentioned gB glycoprotein coded by the gene. CONSTITUTION:A gene of glycoprotein gB of vesicular stomatitis virus (VSV) which is an important infection protectant antigen of herpes simplex virus (HSV) is inserted into a recombinant DNA vector of thymidine kinase gene from HSVDNA and Escherichia coli plasmid pBR322, and the resultant novel recombinant DNA is reacted with preferably animal cells deficient in TK to give a transformant, which is then cultivated to obtain HSVgB. GK fragments (0.348- 0.381) obtained by treating herpes simplex virus DNA with a restriction enzyme BamHI, and treating the resultant BamHIG fragment with a restriction enzyme KpnI are used as the gB gene.

9. 发明专利

JPS6078999A PURIFICATION OF HBS ANTIGEN 失效
公开(公告)号：JPS6078999A
公开(公告)日：1985-05-04
申请号：JP18618783
申请日：1983-10-05
申请人： CHEMO SERO THERAPEUT RES INST
发明人： SUGAWARA KEISHIN , NOZAKI CHIKAHIDE , HAMADA FUKUSABUROU , MIAKE FUMIO , OOTOMO SHINYA
IPC分类号： C12N15/09 , A61K39/00 , C07K1/22 , C07K14/005 , C07K14/02 , C07K14/10 , C07K14/18 , C07K14/195 , C12P21/00 , C12P21/02 , C12R1/19 , C12R1/865
摘要： PURPOSE:To obtain the titled substance industrially, by treating a raw material for HBs antigen with an acid, subjecting it to hydroxy apatite gel affinity chromatography, so that a protease active substance is completely eliminated. CONSTITUTION:An acid (e.g., acetic acid, etc.) is added to a solution of a raw material for HBs antigen containing components derived from cell, obtained from a culture of a recombinant utilizing recombinant DNA technique, most of lipids and protein admixtures are removed as precipitate, and, if necessary, the solution is purified by salting-out, concentrated, and subjected to affinity chromatography by hydroxy apatite, to give the desired substance.

10. 发明专利

JPS6051120A HERPES SIMPLEX SUBUNIT VACCINE 失效
公开(公告)号：JPS6051120A
公开(公告)日：1985-03-22
申请号：JP15964183
申请日：1983-08-31
申请人： CHEMO SERO THERAPEUT RES INST
发明人： KINO YOUICHIROU , OOTOMO SHINYA
IPC分类号： A61K39/245 , A61K39/00 , A61K39/12 , A61K47/00 , C07K14/035 , C12N7/06 , C12N15/00 , C12P21/00
摘要： PURPOSE:To obtain the titled vaccine free from the problems of the herpes simplex virus infection caused by the vaccination, by using glucoproteins gA.gB which is a common constituent of the herpes simplex viruses 1 and 2. CONSTITUTION:Particles of herpes simplex virus (HSV) 1 or 2 or the viral envelope component of their infected cells are solubilized with a surface active agent (e.g. dodecylsulfuric acid sodium salt, deoxycholic acid sodium salt, etc.), and subjected to the affinity chromatography using a monoclonal antibody of the HSV glucoprotein gA.gB as a ligand to obtain the purified specimen of glucoprotein gA.gB. The product is adsorbed to an aluminum gel to afford the objective vaccine composed of a suspension of aluminum gel adsorbed with plucoprotein gA.gB. A highly purified vaccine free from the danger of the HSV infection in vaccination and having high safety can be produced by this process.

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