公开(公告)号：US07138489B2

公开(公告)日：2006-11-21

申请号：US10500018

申请日：2003-04-10

申请人： Yoshiharu Minamitake ,  Masaru Matsumoto ,  Tomohiro Makino

发明人： Yoshiharu Minamitake ,  Masaru Matsumoto ,  Tomohiro Makino

IPC分类号： C07K1/00 ,  C07K1/06 ,  C07K1/08 ,  C07K1/107 ,  A61K38/02

CPC分类号： C07K14/60 ,  C07K14/465

摘要： The present invention is a method for producing a peptide or a protein in which a side chain contains a modified amino acid residue, which comprises chemically producing a peptide fragment containing an amino acid residue having a modified side chain using an weak acid-cleavable resin, producing a peptide fragment containing no amino acid residue having a modified side chain using a genetic recombination method or/and an enzymatic method, and condensing the resulting two kinds of peptide fragments and, according to the present invention, a peptide or a protein containing modification such as acylation, glycosylation and phosphorylation can be obtained effectively and at high quality.

摘要翻译： 本发明是一种生产肽或蛋白质的方法，其中侧链含有修饰的氨基酸残基，其包括使用弱酸可裂解树脂化学制备含有具有改性侧链的氨基酸残基的肽片段， 使用遗传重组法或/或酶法产生不含具有修饰侧链的氨基酸残基的肽片段，并将得到的两种肽片段缩合，根据本发明，将肽或含有蛋白质的修饰 可以有效和高质量地获得酰化，糖基化和磷酸化等功能。

公开(公告)号：US20060128707A1

公开(公告)日：2006-06-15

申请号：US10560503

申请日：2004-06-11

申请人： Hidekazu Inoue ,  Hidenobu Murafuji ,  Yasuhiro Hayashi

发明人： Hidekazu Inoue ,  Hidenobu Murafuji ,  Yasuhiro Hayashi

IPC分类号： A61K31/53 ,  C07D487/04

CPC分类号： C07D487/04

摘要： The present invention provides the compounds inhibiting PDE 7 selectively, and therefore, enhances cellular cAMP level. Consequently, the compound is useful for treating various kinds of disease such as allergic disease, inflammatory disease or immunologic disease. The compound is imidazotirazinone compound represented by the following formula (IA) or (IB): especially, R1 is cyclohexyl group, R2 is methyl group; R3 is a hydrogen atom; nitro group; cyano group; a halogen atom; heteroaryl group; substituted or unsubstituted C1-C6 alkyl group; substituted or unsubstituted C2-C6 alkenyl group; saturated or unsaturated heterocycloalkyl group which is substituted or unsubstituted; a group: —NR5R6, —C(O)R7, —SO2R7, —OR8, —NR8COR7, —NR8S02R7; A is CR4; and B is CH.

摘要翻译： 本发明提供了选择性抑制PDE7的化合物，因此增强细胞cAMP水平。 因此，该化合物可用于治疗各种疾病如过敏性疾病，炎性疾病或免疫疾病。 该化合物是由下式（IA）或（IB）表示的咪唑并嗪酮化合物：特别是R 1是环己基，R 2是甲基; R3是氢原子; 硝基; 氰基; 卤素原子; 杂芳基; 取代或未取代的C 1 -C 6烷基; 取代或未取代的C 2 -C 6烯基; 取代或未取代的饱和或不饱和杂环烷基; 基团：-NR5R6，-C（O）R7，-SO2R7，-OR8，-NR8COR7，-NR8S02R7; A是CR4; 而B是CH。

公开(公告)号：US20110077195A1

公开(公告)日：2011-03-31

申请号：US12848638

申请日：2010-08-02

申请人： Masaru Matsumoto ,  Masako Matsumoto ,  Takeshi Hanada ,  Naomi Wakabayashi

发明人： Masaru Matsumoto ,  Masako Matsumoto ,  Takeshi Hanada ,  Naomi Wakabayashi

IPC分类号： A61K38/02 ,  A61K38/28 ,  A61K38/18 ,  A61K38/27 ,  A61K38/26 ,  A61K38/29 ,  A61K38/22

CPC分类号： A61K9/0019 ,  A61K38/25 ,  A61K47/10 ,  A61K47/12 ,  A61K47/22 ,  A61K47/26 ,  A61K47/40

摘要： An effective liquid preparation achieves high bioavailability (BA) of physiologically active peptides or proteins, including ghrelins, that are administered as drugs. Also provided is a method for improving the BA of physiologically active peptides or proteins, including ghrelins, that are subcutaneously injected in aqueous solutions. The liquid preparation contains: a physiologically active peptide or protein, such as ghrelins, as an active ingredient; an acid solution including one or a combination of two or more selected form the group consisting of acetic acid, lactic acid, phosphoric acid, glycine, citric acid, hydrochloric acid, propionic acid, butyric acid, benzoic acid and salts thereof; an alcohol; and a polar organic liquid including one or a combination of two or more selected from the group consisting of N-methyl-2-pyrrolidone, dimethylformamide, dimethylsulfoxide and methylparaben.

摘要翻译： 有效的液体制剂实现了作为药物施用的生理活性肽或蛋白质（包括生长素释放肽）的高生物利用度（BA）。 还提供了一种用于改善皮下注射在水溶液中的生理活性肽或蛋白质（包括生长素释放肽）的BA的方法。 液体制剂含有：生理活性肽或蛋白质，如生长素释放肽，作为活性成分; 包括选自乙酸，乳酸，磷酸，甘氨酸，柠檬酸，盐酸，丙酸，丁酸，苯甲酸及其盐中的一种或两种以上组合的酸溶液; 酒精; 以及包含选自N-甲基-2-吡咯烷酮，二甲基甲酰胺，二甲基亚砜和对羟基苯甲酸甲酯中的一种或两种以上的组合的极性有机液体。

公开(公告)号：US07642262B2

公开(公告)日：2010-01-05

申请号：US11002793

申请日：2004-12-03

申请人： Hirokazu Annoura ,  Kyoko Nakanishi ,  Shigeki Tamura

发明人： Hirokazu Annoura ,  Kyoko Nakanishi ,  Shigeki Tamura

IPC分类号： A61K31/495 ,  C07D295/135

CPC分类号： C07D295/088 ,  C07C217/84 ,  C07C271/28 ,  C07D211/22 ,  C07D211/52 ,  C07D295/13 ,  Y02P20/55

摘要： A compound having the formula (I) or its salt, hydrate, hydrate salt or solvate: wherein R1 to R4 independently represent H, halogen, OH, alkoxy, optionally substituted alkyl, aryl, or aralkyl group, R5 represents H, optionally substituted alkyl, aryl, or aralkyl group, E1 represents O, S, or —NR6, where R6 represents H, an optionally substituted alkyl, aryl, or aralkyl group, E2 represents O, S, or —NR7, where R7 represents H, an optionally substituted alkyl, aryl, or aralkyl group, A represents CH, C(OH), or N, X represents H, halogen, alkoxy, or an optionally substituted alkyl group, and Q represents an optionally substituted phenyl group, phenoxy, phenylmethyl, or cycloalkyloxy group, where when E1 represents O or S, E2 does not represent O or S, which has an action of suppressing the cytotoxic Ca2+ overload and lipid peroxidation and effective for pharmaceutical preparation for the alleviation and treatment of symptoms due to ischemic diseases, etc.

摘要翻译： 具有式（I）的化合物或其盐，水合物，水合物盐或溶剂合物：其中R 1至R 4独立地表示H，卤素，OH，烷氧基，任选取代的烷基，芳基或芳烷基，R 5表示H，任选取代的烷基 ，芳基或芳烷基，E1表示O，S或-NR6，其中R6表示H，任选取代的烷基，芳基或芳烷基，E2表示O，S或-NR7，其中R7表示H， 取代的烷基，芳基或芳烷基，A表示CH，C（OH）或N，X表示H，卤素，烷氧基或任选取代的烷基，Q表示任选取代的苯基，苯氧基，苯甲基或 环状烷氧基，当E1表示O或S时，E2不表示O或S，其具有抑制细胞毒性Ca 2+过载和脂质过氧化的作用，并且有效用于缓解和治疗由于缺血性疾病引起的症状的药物制剂等 。

公开(公告)号：US20090325288A1

公开(公告)日：2009-12-31

申请号：US12298565

申请日：2007-04-27

申请人： Uichi Koshimizu ,  Tomofumi Tanaka ,  Kayoko Kawashima ,  Michinori Kadokura

发明人： Uichi Koshimizu ,  Tomofumi Tanaka ,  Kayoko Kawashima ,  Michinori Kadokura

IPC分类号： C12N5/08 ,  C12N5/02

CPC分类号： C12N5/0657 ,  C12N2501/415 ,  C12N2506/02

摘要： The present invention provides a method for inducing differentiation of cardiomyocytes efficiently and selectively from stem cells.A method for inducing differentiation of cardiomyocytes from pluripotent stem cells, which comprises: (i) culturing the pluripotent stem cells in a culture medium containing no substance that promotes activation of the canonical Wnt signaling pathway during the time period between initiation of differentiation induction and 24 hours before the period of elevated canonical Wnt gene expression; and then (ii) culturing the pluripotent stem cells in a culture medium containing a substance that promotes activation of the canonical Wnt signaling pathway during a time period of 24 to 96 hours, starting from 24 to 0 hours before the period of elevated canonical Wnt gene expression.

摘要翻译： 本发明提供了从干细胞中有效且选择性地诱导心肌细胞分化的方法。 一种从多能干细胞诱导心肌细胞分化的方法，其特征在于：（i）在分化诱导开始和诱导分化诱导期间的时间段内培养不含有促进典型Wnt信号通路活化的物质的培养基中的多能干细胞 在正常Wnt基因表达升高之前的几个小时; 然后（ii）在培养基中培养多能干细胞，培养基含有促进典型Wnt信号通路活化的物质的培养基，时间为24至96小时，从高达标准Wnt基因的时间之前的24至0小时开始 表达。

公开(公告)号：US07598228B2

公开(公告)日：2009-10-06

申请号：US10642272

申请日：2003-08-18

申请人： Fumiyuki Hattori ,  Keijiro Sugimura ,  Mayumi Furuya

发明人： Fumiyuki Hattori ,  Keijiro Sugimura ,  Mayumi Furuya

IPC分类号： A61K48/00 ,  A01N63/00

CPC分类号： A61K48/005 ,  A61K31/711 ,  A61K38/00 ,  A61K48/00 ,  C12N9/0089 ,  C12N2799/022 ,  C12N2799/04 ,  G01N33/576 ,  G01N33/6893 ,  G01N2500/00 ,  G01N2800/085 ,  G01N2800/102 ,  G01N2800/2842 ,  G01N2800/325 ,  G01N2800/347

摘要： A prophylactic or therapeutic method for a disease associated with decreased expression of AOP-1 gene or AOP-1, comprising (1) transfecting a nucleic acid encoding AOP-1 or a nucleic acid encoding a polypeptide having an addition, deletion or substitution of one or more amino acids as compared with the amino acid sequence of AOP-1 while retaining the function of AOP-1, or (2) administering a material enhancing the expression of AOP-1 gene, a material enhancing the production of AOP-1 or a material enhancing the function of AOP-1.

摘要翻译： 一种与AOP-1基因或AOP-1表达降低相关的疾病的预防或治疗方法，包括（1）转染编码AOP-1的核酸或编码具有添加，缺失或取代的多肽的核酸 或更多的氨基酸与AOP-1的氨基酸序列相比较，同时保留AOP-1的功能，或（2）施用增强AOP-1基因表达的材料， 一种增强AOP-1功能的材料。

公开(公告)号：US20090074788A1

公开(公告)日：2009-03-19

申请号：US12147331

申请日：2008-06-26

申请人： Yoshiaki Taniyama ,  Ryuichi Morishita ,  Naruto Katsuragi

发明人： Yoshiaki Taniyama ,  Ryuichi Morishita ,  Naruto Katsuragi

IPC分类号： A61K39/395 ,  C07K16/00 ,  G01N33/68 ,  A61P25/00 ,  A61P1/18 ,  A61P31/12 ,  A61P35/00 ,  A61P11/00 ,  A61P9/00 ,  C12N5/00

CPC分类号： C07K16/18 ,  A61K2039/505 ,  C07K2317/73

摘要： The present invention provides an antibody against a periostin isoform having anti-cell adhesive activity, especially an anti-periostin antibody having the ability to neutralize anti-cell adhesive properties, as well as a prophylactic or therapeutic agent for periostin-related diseases comprising the antibody. The present invention also provides methods for detecting and quantifying the periostin isoform in a sample by using the antibody, as well as a method for diagnosing periostin-related diseases comprising measuring the amount of the periostin isoform by the detection or quantification method.

摘要翻译： 本发明提供具有抗细胞粘附活性的抗骨膜素同种型抗体，特别是具有中和抗细胞粘附性能的抗骨膜素抗体，以及包含抗体的骨膜素相关疾病的预防或治疗剂 。 本发明还提供了通过使用抗体检测和定量样品中骨膜素异构体的方法，以及用于诊断骨膜素相关疾病的方法，包括通过检测或定量方法测量骨膜素同种型的量。

公开(公告)号：US07459551B2

公开(公告)日：2008-12-02

申请号：US10508659

申请日：2003-03-26

申请人： Akira Kaneko

发明人： Akira Kaneko

IPC分类号： C07D499/00 ,  C07D487/00 ,  C07D487/08 ,  C07D501/00 ,  C07D221/00 ,  C07D237/00 ,  C07D239/00 ,  C07D241/00 ,  C07D251/00 ,  C07D253/00 ,  C07D255/00 ,  C07D257/00 ,  C07D259/00 ,  C07D205/00

CPC分类号： C07D403/12 ,  C07D499/00 ,  C07D501/00

摘要： The present invention provides a method for preparing a β-lactam compound of the following Formula (3), which comprises the step of reacting a compound of the following Formula (1) with a trialkyl phosphite represented by the formula (R5O)3P (wherein R5 represents an ethyl group, etc.) in an amount of 2 to 5 moles per mole of the compound and the step of heating the resulting reaction mixture in a diluent, wherein said method is characterized by having the step of completely removing unreacted trialkyl phosphite from the reaction mixture prior to the step of heating. (wherein X represents S, etc., Y represents N, etc., n represents 0 or 1, R1 represents an optionally substituted alkyl group containing 1 to 10 carbon atoms, etc., R2 and R3 each represent an optionally substituted alkyl or heterocyclic group, etc., and R4 represents an alkenyloxy group containing 1 to 6 carbon atoms, etc., provided that R1 and R2 may together form a β-lactam ring, etc.)

摘要翻译： 本发明提供了制备下式（3）的β-内酰胺化合物的方法，该方法包括使下式（1）的化合物与式（R5O）3P表示的亚磷酸三烷基酯反应的步骤（其中 R5代表乙基等），每摩尔化合物的量为2至5摩尔，和将所得反应混合物加热到稀释剂中的步骤，其特征在于具有完全除去未反应的亚磷酸三烷基酯的步骤 在加热步骤之前的反应混合物中。 （其中X表示S等，Y表示N等，n表示0或1，R1表示可以具有取代基的碳原子数为1〜10的烷基等，R2和R3各自表示任意取代的烷基或杂环 基团等，R 4表示含有1至6个碳原子的烯氧基等，条件是R 1和R 2可以一起形成β-内酰胺环等）

公开(公告)号：US20080193997A1

公开(公告)日：2008-08-14

申请号：US11660406

申请日：2005-08-24

申请人： Masaru Matsumoto ,  Masako Matsumoto ,  Takeshi Hanada ,  Naomi Wakabayashi

发明人： Masaru Matsumoto ,  Masako Matsumoto ,  Takeshi Hanada ,  Naomi Wakabayashi

IPC分类号： C12N9/94

CPC分类号： A61K9/0019 ,  A61K38/25 ,  A61K47/10 ,  A61K47/12 ,  A61K47/22 ,  A61K47/26 ,  A61K47/40

摘要： An effective liquid preparation achieves high bioavailability (BA) of physiologically active peptides or proteins, including ghrelins, that are administered as drugs. Also provided is a method for improving the BA of physiologically active peptides or proteins, including ghrelins, that are subcutaneously injected in aqueous solutions. The liquid preparation contains: a physiologically active peptide or protein, such as ghrelins, as an active ingredient; an acid solution including one or a combination of two or more selected form the group consisting of acetic acid, lactic acid, phosphoric acid, glycine, citric acid, hydrochloric acid, propionic acid, butyric acid, benzoic acid and salts thereof; an alcohol; and a polar organic liquid including one or a combination of two or more selected from the group consisting of N-methyl-2-pyrrolidone, dimethylformamide, dimethylsulfoxide and methylparaben.

摘要翻译： 有效的液体制剂实现了作为药物施用的生理活性肽或蛋白质（包括生长素释放肽）的高生物利用度（BA）。 还提供了一种用于改善皮下注射在水溶液中的生理活性肽或蛋白质（包括生长素释放肽）的BA的方法。 液体制剂含有：生理活性肽或蛋白质，如生长素释放肽，作为活性成分; 包括选自乙酸，乳酸，磷酸，甘氨酸，柠檬酸，盐酸，丙酸，丁酸，苯甲酸及其盐中的一种或两种以上组合的酸溶液; 酒精; 以及包含选自N-甲基-2-吡咯烷酮，二甲基甲酰胺，二甲基亚砜和对羟基苯甲酸甲酯中的一种或两种以上的组合的极性有机液体。

公开(公告)号：US07361759B2

公开(公告)日：2008-04-22

申请号：US11066255

申请日：2005-02-28

申请人： Shinnosuke Tazawa

发明人： Shinnosuke Tazawa

IPC分类号： C07D475/04 ,  C07H19/19

CPC分类号： C07D475/04

摘要： To provide a method for producing L-biopterin on a large industrial scale by using a reagent which is inexpensive and easy to handle, without requiring a use of any particular equipment or plants.A method for porducing a biopterin derivative represented by the formula (6): wherein R1 and R2, which are the same or different from each other, each represents a hydrogen atom, an alkyl group, or an aryl group, comprising: reacting a compound belonging to triacetoxy-5-deoxy-L-arabinose phenylhydrazones represented by the formula (4): wherein R1 and R2 are the same as defined above, with 6-hydroxy-2,4,5-triaminopyrimidine (5) under catalytic influence of a Lewis acid in an aqueous solvent.

摘要翻译： 通过使用廉价且易于处理的试剂，而不需要使用任何特定的设备或植物，提供了在大型工业规模生产L-生物蝶呤的方法。 一种由式（6）表示的生物蝶呤衍生物的制备方法：其中R 1和R 2彼此相同或不同，各自表示氢 原子，烷基或芳基，其包括：使由式（4）表示的属于三乙酰氧基-5-脱氧-L-阿拉伯糖苯基腙的化合物：其中R 1和R 2彼此反应 > 2 与上述定义相同，其中6-羟基-2,4,5-三氨基嘧啶（5）在路易斯酸在水性溶剂中的催化作用下。