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1. 发明申请

US20050239998A1 Method for producing polyhydroxyalkanoate 审中-公开
标题翻译：聚羟基链烷酸酯的制备方法
公开(公告)号：US20050239998A1
公开(公告)日：2005-10-27
申请号：US11070188
申请日：2005-03-03
申请人： Koichi Kinoshita , Yoshifumi Yanagida , Fumio Osakada , Yasuyoshi Ueda , Karunakaran Narasimhan , Angella Cearley , Kenneth Yee , Isao Noda
发明人： Koichi Kinoshita , Yoshifumi Yanagida , Fumio Osakada , Yasuyoshi Ueda , Karunakaran Narasimhan , Angella Cearley , Kenneth Yee , Isao Noda
IPC分类号： C08G63/02 , C08G63/06 , C08G63/89 , C12P7/62
CPC分类号： C08G63/89 , C08G63/06 , C12P7/625
摘要： The present invention provides a method for obtaining a biodegradable polyhydroxyalkanoate by a solvent extraction method without causing a significant molecular weight decrease. The present invention relates to a method for producing a polyhydroxyalkanoate which comprises extracting a polyhydroxyalkanoate from a polyhydroxyalkanoate-containing biomass having the water content of 5% by weight or less using an extraction solvent, crystallizing, and recovering the resultant.
摘要翻译：本发明提供了一种通过溶剂萃取法获得可生物降解的聚羟基链烷酸酯的方法，而不会导致明显的分子量降低。本发明涉及一种生产聚羟基链烷酸酯的方法，该方法包括使用萃取溶剂从具有5重量％以下含水量的聚羟基链烷酸酯的生物质提取聚羟基链烷酸酯，结晶并回收所得聚合物。

2. 发明申请

US20060105440A1 Method of producing polyhydroxyalkanoate 审中-公开
标题翻译：聚羟基链烷酸酯的制备方法
公开(公告)号：US20060105440A1
公开(公告)日：2006-05-18
申请号：US11237686
申请日：2005-09-29
申请人： Koichi Kinoshita , Yoshifumi Yanagida , Fumio Osakada , Yasuyoshi Ueda
发明人： Koichi Kinoshita , Yoshifumi Yanagida , Fumio Osakada , Yasuyoshi Ueda
IPC分类号： C12P7/62
CPC分类号： C12P7/62 , C08G63/89
摘要： The present invention has its object to provide a method of producing PHA by extracting, separating, and purifying PHA from biomass containing PHA having an weight average molecular weight of more than 2,000,000, by which smooth stirring can be carried out during extraction and filterability of a residue becomes good to thereby efficiently produce PHA with good operability. In the present invention, PHA is extracted, separated, and purified from biomass by a method of producing polyhydroxyalkanoate by extracting and isolating polyhydroxyalkanoate by using an aprotic organic solvent from biomass containing polyhydroxyalkanoate having a weight average molecular weight of more than 2,000,000, which comprises decreasing the weight average molecular weight of the polyhydroxyalkanoate through any one of the following treatments: (a) the biomass is heated at 40 to 500° C. before addition of the aprotic organic solvent; (b) the biomass is heated at 40 to 500° C. before addition of the aprotic organic solvent, and is further heated at 40 to 200° C. in the aprotic organic solvent; (c) the biomass is heated at 40 to 500° C. before addition of the aprotic organic solvent, and is further heated at 40 to 200° C. in the aprotic organic solvent in the presence of water and/or an alcohol; (d) the biomass is not heated before addition of the aprotic organic solvent, but is heated at 40 to 200° C. in the aprotic organic solvent; and (e) the biomass is not heated before addition of the aprotic organic solvent, but is heated at 40 to 200° C. in the aprotic organic solvent in the presence of water and/or an alcohol.
摘要翻译：本发明的目的是提供一种通过从重均分子量大于2,000,000的PHA的生物质中提取，分离和纯化PHA来生产PHA的方法，通过该方法可以在提取过程中进行平稳的搅拌和过滤性残留物变得良好，从而有效地产生具有良好可操作性的PHA。在本发明中，通过使用含有重均分子量大于2,000,000的聚羟基链烷酸酯的生物质的非质子有机溶剂提取和分离聚羟基链烷酸酯的方法，从生物质中提取，分离和纯化PHA，其包括降低通过以下任何一种处理，聚羟基链烷酸酯的重均分子量：（a）在加入非质子有机溶剂之前，将生物质在40-500℃下加热; （b）在加入非质子有机溶剂之前将生物质在40-500℃加热，并在非质子有机溶剂中在40〜200℃下进一步加热; （c）在加入非质子有机溶剂之前将生物质加热至40-500℃，并在水和/或醇存在下，在非质子有机溶剂中在40〜200℃下进一步加热; （d）在加入非质子有机溶剂之前，不加热生物质，但在非质子有机溶剂中在40〜200℃下加热生物质; 和（e）生物质在加入非质子有机溶剂之前不被加热，但在水和/或醇的存在下，在非质子传递的有机溶剂中在40-200℃下加热。

3. 发明申请

US20050196827A1 Method for degradation of nucleic acids and use thereof 有权
标题翻译：核酸降解方法及其用途
公开(公告)号：US20050196827A1
公开(公告)日：2005-09-08
申请号：US11070083
申请日：2005-03-03
申请人： Fumio Osakada , Yoshifumi Yanagida , Yasuyoshi Ueda
发明人： Fumio Osakada , Yoshifumi Yanagida , Yasuyoshi Ueda
IPC分类号： C12P7/62
CPC分类号： C12M47/06 , C12P7/62
摘要： The present invention provides a method to efficiently degrade nucleic acids, which result in a viscosity increase of the solution thereof on the occasion of decomposition or solubilization of microbial cells, in an easy and simple manner in the step of recovering various useful substance produced by a microorganism, and a use thereof. The product recovery method of the present invention make the product recovery from within microbial cells with ease under relatively mild conditions, because, by bringing living microbial cells into contact with a little amount of hypochlorous acid or a salt thereof, autodigestion of nucleic acids is induced and following decomposition of microbial cells or viscosity increase of the solution thereof after dissolution is inhibited. The method of the present invention is particularly preferred in recovering polyhydroxyalkanoates, which are biodegradable polymers, from microbial cells.
摘要翻译：本发明提供了一种在回收各种有用物质的步骤中以容易且简单的方式有效降解核酸的方法，其在微生物细胞的分解或溶解的情况下导致其溶液的粘度增加，微生物及其用途。本发明的产品回收方法使得在相对温和的条件下容易从微生物细胞中回收产物，因为通过使活的微生物细胞与少量的次氯酸或其盐接触，诱导了核酸的自身消化并且随着微生物细胞的分解或溶解后其溶液的粘度增加被抑制。本发明的方法特别优选从微生物细胞回收可生物降解的聚合物的聚羟基链烷酸酯。

4. 发明授权

US07435567B2 Method for degradation of nucleic acids and use thereof 有权
标题翻译：核酸降解方法及其用途
公开(公告)号：US07435567B2
公开(公告)日：2008-10-14
申请号：US11070083
申请日：2005-03-03
申请人： Fumio Osakada , Yoshifumi Yanagida , Yasuyoshi Ueda
发明人： Fumio Osakada , Yoshifumi Yanagida , Yasuyoshi Ueda
IPC分类号： C12P7/62
CPC分类号： C12M47/06 , C12P7/62
摘要： The present invention provides a method to efficiently degrade nucleic acids, which result in a viscosity increase of the solution thereof on the occasion of decomposition or solubilization of microbial cells, in an easy and simple manner in the step of recovering various useful substance produced by a microorganism, and a use thereof. The product recovery method of the present invention make the product recovery from within microbial cells with ease under relatively mild conditions, because, by bringing living microbial cells into contact with a little amount of hypochlorous acid or a salt thereof, autodigestion of nucleic acids is induced and following decomposition of microbial cells or viscosity increase of the solution thereof after dissolution is inhibited. The method of the present invention is particularly preferred in recovering polyhydroxyalkanoates, which are biodegradable polymers, from microbial cells.
摘要翻译：本发明提供了一种在回收各种有用物质的步骤中以容易且简单的方式有效降解核酸的方法，其在微生物细胞的分解或溶解的情况下导致其溶液的粘度增加，微生物及其用途。本发明的产品回收方法使得在相对温和的条件下容易从微生物细胞中回收产物，因为通过使活的微生物细胞与少量的次氯酸或其盐接触，诱导了核酸的自身消化并且随着微生物细胞的分解或溶解后其溶液的粘度增加被抑制。本发明的方法特别优选从微生物细胞回收可生物降解的聚合物的聚羟基链烷酸酯。

5. 发明授权

US06335453B1 Process for preparing pharmacologically acceptable salt of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl amino acids 有权
标题翻译：制备N-（1（S） - 乙氧基羰基-3-苯基丙基）-L-丙氨酰氨基酸的药理学可接受盐的方法
公开(公告)号：US06335453B1
公开(公告)日：2002-01-01
申请号：US09269107
申请日：1999-03-19
申请人： Yasuyoshi Ueda , Koichi Kinoshita , Tadashi Moroshima , Yoshifumi Yanagida , Yoshihide Fuse
发明人： Yasuyoshi Ueda , Koichi Kinoshita , Tadashi Moroshima , Yoshifumi Yanagida , Yoshihide Fuse
IPC分类号： C07K5062
CPC分类号： C07K5/0222 , C07K5/06026
摘要： There is provided a process for preparing a pharmacologically acceptable salt of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid which comprises condensing an amino acid and N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanine.N-carboxyanhydride under basic condition, carrying out decarboxylation under between neutral and acidic condition to obtain N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid, and forming a pharmacologically acceptable salt thereof, wherein the production of a by-product (3): is suppressed by carrying out in an aqueous liquid a series of operations till formation of the pharmacologically acceptable salt or till isolation of the pharmacologically acceptable salt. The present invention enables to prepare the pharmacologically acceptable salt of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid having high quality, in a commercial scale with high yield and economical efficiency.
摘要翻译：提供了制备N-（1（S） - 乙氧基羰基-3-苯基丙基）-L-丙氨酰 - 氨基酸的药学上可接受的盐的方法，其包括将氨基酸和N-（1（S） - 乙氧基羰基 - 3-苯基丙基）-L-丙氨酸N-羧酸酐，在中性和酸性条件下进行脱羧，得到N-（1（S） - 乙氧基羰基-3-苯基丙基）-L-丙氨酰 - 氨基酸，和形成其药理学上可接受的盐，其中通过在含水液体中进行一系列操作直到形成药理学上可接受的盐或直到药理学上可接受的盐的分离来抑制副产物（3）的产生。本发明能够以高产率和经济效益以商业规模制备质量高的N-（1（S） - 乙氧基羰基-3-苯基丙基）-L-丙氨酰 - 氨基酸的药理学上可接受的盐。

6. 发明授权

US06713628B2 Process for preparing pharmacologically acceptable salt of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid 失效
标题翻译：制备N-（1（S） - 乙氧基羰基-3-苯基丙基）-L-丙氨酰 - 氨基酸的药理学上可接受的盐的方法
公开(公告)号：US06713628B2
公开(公告)日：2004-03-30
申请号：US10295897
申请日：2002-11-18
申请人： Yasuyoshi Ueda , Koichi Kinoshita , Tadashi Moroshima , Yoshifumi Yanagida , Yoshihide Fuse
发明人： Yasuyoshi Ueda , Koichi Kinoshita , Tadashi Moroshima , Yoshifumi Yanagida , Yoshihide Fuse
IPC分类号： C07D20704
CPC分类号： C07K5/0222 , C07K5/06026
摘要： There is provided a process for preparing a pharmacologically acceptable salt of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid which comprises condensing an amino acid and N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanine.N-carboxyanhydride under basic condition, carrying out decarboxylation under between neutral and acidic condition to obtain N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid, and forming a pharmacologically acceptable salt thereof, wherein the production of a by-product (3): is suppressed by carrying out in an aqueous liquid a series of operations till formation of the pharmacologically acceptable salt or till isolation of the pharmacologically acceptable salt. The present invention enables to prepare the pharmacologically acceptable salt of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid having high quality, in a commercial scale with high yield and economical efficiency.
摘要翻译：提供了制备N-（1（S） - 乙氧基羰基-3-苯基丙基）-L-丙氨酰 - 氨基酸的药学上可接受的盐的方法，其包括将氨基酸和N-（1（S） - 乙氧基羰基 - 3-苯基丙基）-L-丙氨酸N-羧酸酐，在中性和酸性条件下进行脱羧，得到N-（1（S） - 乙氧基羰基-3-苯基丙基）-L-丙氨酰 - 氨基酸，和形成其药理学上可接受的盐，其中通过在含水液体中进行一系列操作直到形成药理学上可接受的盐或直到药理学上可接受的盐的分离来抑制副产物（3）的产生。本发明能够以高产率和经济效益以商业规模制备质量高的N-（1（S） - 乙氧基羰基-3-苯基丙基）-L-丙氨酰 - 氨基酸的药理学上可接受的盐。

7. 发明授权

US06359155B1 Process for the preparation of 3-hydroxytetrahydrofuran 失效
标题翻译： 3-羟基四氢呋喃的制备方法
公开(公告)号：US06359155B1
公开(公告)日：2002-03-19
申请号：US09719686
申请日：2001-02-15
申请人： Koichi Kinoshita , Tadashi Moroshima , Yoshifumi Yanagida , Nobuo Nagashima , Yasuhiro Saka , Tatsuya Honda , Yoshihide Fuse , Yasuyoshi Ueda
发明人： Koichi Kinoshita , Tadashi Moroshima , Yoshifumi Yanagida , Nobuo Nagashima , Yasuhiro Saka , Tatsuya Honda , Yoshihide Fuse , Yasuyoshi Ueda
IPC分类号： C07D30720
CPC分类号： C07C29/147 , C07B2200/07 , C07D307/20 , Y02P20/55 , C07C31/42
摘要： An industrial advantage process for producing high-purity 3-hydroxytetrahydrofuran easily and simply, which comprises reducing a 4-halo-3-hydroxybutyric acid ester (1) with a boron hydride compound and/or an aluminum hydride compound as a reducing agent in an organic solvent immiscible with water; treating the reaction mixture with an acid and water to thereby effect conversion to the corresponding 4-halo-1,3-butanediol and at the same time giving an aqueous solution containing said compound; carrying out the cyclization reaction of the 4-halo-1,3-butanediol in said aqueous solution; extracting the resulting 3-hydroxytetrahydrofuran from the 3-hydroxytetrahydrofuran-containing aqueous solution using an organic solvent immiscible with water; and isolating the 3-hydroxytetrahydrofuran by concentration and/or distillation of the solution obtained.
摘要翻译：用于容易且简单地生产高纯度3-羟基四氢呋喃的工业优势方法，其包括用硼氢化合物和/或氢化铝化合物作为还原剂还原4-卤代-3-羟基丁酸酯（1）与水不混溶的有机溶剂;用酸和水处理反应混合物，从而转化为相应的4-卤代-1,3-丁二醇，同时得到含有所述化合物的水溶液;进行环化反应所述水溶液中的4-卤代-1,3-丁二醇;使用与水不混溶的有机溶剂从含3-羟基四氢呋喃的水溶液中萃取所得3-羟基四氢呋喃; 通过所得溶液的浓缩和/或蒸馏来使3-羟基四氢呋喃分离。

8. 发明授权

US06518436B2 Process for preparing pharmacologically acceptable salt of n-(1(s)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid 失效
标题翻译：制备正（（S） - 乙氧基羰基-3-苯基丙基）-L-丙氨酰 - 氨基酸的药学上可接受的盐的方法
公开(公告)号：US06518436B2
公开(公告)日：2003-02-11
申请号：US09989186
申请日：2001-11-21
申请人： Yasuyoshi Ueda , Koichi Kinoshita , Tadashi Moroshima , Yoshifumi Yanagida , Yoshihide Fuse
发明人： Yasuyoshi Ueda , Koichi Kinoshita , Tadashi Moroshima , Yoshifumi Yanagida , Yoshihide Fuse
IPC分类号： C07D20704
CPC分类号： C07K5/0222 , C07K5/06026
摘要： There is provided a process for preparing a pharmacologically acceptable salt of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid which comprises condensing an amino acid and N-(1(S) -ethoxycarbonyl-3-phenylpropyl)-L-alanine N-carboxy-anhydride under basic condition, carrying out decarboxylation under between neutral and acidic condition to obtain N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid, and forming a pharmacologically acceptable salt thereof, wherein the production of a by-product (3): is suppressed by carrying out in an aqueous liquid a series of operations till formation of the pharmacologically acceptable salt or till isolation of the pharmacologically acceptable salt. The present invention enables to prepare the pharmacologically acceptable salt of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid having high quality, in a commercial scale with high yield and economical efficiency.
摘要翻译：提供了制备N-（1（S） - 乙氧基羰基-3-苯基丙基）-L-丙氨酰 - 氨基酸的药学上可接受的盐的方法，其包括将氨基酸和N-（1（S） - 乙氧基羰基 - 3-苯基丙基）-L-丙氨酸N-羧酸酐，在中性和酸性条件下进行脱羧，得到N-（1（S） - 乙氧基羰基-3-苯基丙基）-L-丙氨酰 - 氨基酸，并形成其药学上可接受的盐，其中通过在含水液体中进行一系列操作直至形成药理学上可接受的盐或直到药理学上可接受的盐的分离来抑制副产物（3）的产生。本发明能够以高产率和经济效益以商业规模制备质量高的N-（1（S） - 乙氧基羰基-3-苯基丙基）-L-丙氨酰 - 氨基酸的药理学上可接受的盐。

9. 发明授权

US06204393B1 Method for crystallizing maleic acid salt of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-L-proline 失效
标题翻译： N-（1（S） - 乙氧基羰基-3-苯基丙基）-L-丙氨酰-L-脯氨酸的马来酸盐结晶方法
公开(公告)号：US06204393B1
公开(公告)日：2001-03-20
申请号：US09508801
申请日：2000-03-17
申请人： Koichi Kinoshita , Tadashi Moroshima , Yoshifumi Yanagida , Yoshihide Fuse , Yasuyoshi Ueda
发明人： Koichi Kinoshita , Tadashi Moroshima , Yoshifumi Yanagida , Yoshihide Fuse , Yasuyoshi Ueda
IPC分类号： C07K5062
CPC分类号： C07K5/06026
摘要： A process for simply and easily crystallizing a maleate salt of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-L-proline (enalapril) having a high quality out of an aqueous liquid, which comprises mixing an aqueous liquid having a pH of not less than 4 and containing N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-L-proline, maleic acid and a base with an amount of an acid sufficient to convert substantially all the base into a neutral salt.
摘要翻译：一种从水性液体中简单且容易地结晶出具有高质量的N-（1（S） - 乙氧基羰基-3-苯基丙基）-L-丙氨酰-L-脯氨酸（依那普利）的马来酸盐的方法，其包括将含有不少于4的pH并含有N-（1（S） - 乙氧基羰基-3-苯基丙基）-L-丙氨酰-L-脯氨酸，马来酸和碱的量的水溶液，其含量足以基本上转化所有的碱都成为中性盐。

10. 发明授权

US06271393B1 Process for producing N2-(1(S)-carboxy-3-phenylpropyl)-L-lysyl-L-proline 有权
标题翻译：制备N2-（1（S） - 羧基-3-苯基丙基）-L-赖氨酰-L-脯氨酸的方法
公开(公告)号：US06271393B1
公开(公告)日：2001-08-07
申请号：US09554827
申请日：2000-07-17
申请人： Tadashi Moroshima , Yoshifumi Yanagida , Yoshihide Fuse , Yasuyoshi Ueda
发明人： Tadashi Moroshima , Yoshifumi Yanagida , Yoshihide Fuse , Yasuyoshi Ueda
IPC分类号： C07D20706
CPC分类号： C07K5/0222
摘要： The process for producing N2-(1(S)-carboxy-3-phenylpropyl)-L-lysyl-L-proline in a simple, efficient and industrially advantageous manner, including the following steps: 1) subjecting N2-(1(S)-alkoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysyl-L-proline (1) to alkali hydrolysis in a mixed solution composed of water and a hydrophilic organic solvent using an inorganic base in an amount of n molar equivalents (n ≧ 3) per mole of the above compound (1), 2) neutralizing the hydrolysis product using an inorganic acid in an amount of (n − 1) to n molar equivalents (n ≧ 3) to form a compound (2) and removing the inorganic salt formed by causing the same to precipitate out from a solvent system suited for decreasing the solubility of the inorganic salt, and 3) causing the compound (2) existing in the mixture after removal of the inorganic salt to crystallize out at the isoelectric point thereof and thereby recovering the compound (2) in the form of crystals while retaining the salts including the trifluoroacetic acid-derived organic acid salt in a state dissolved in the mother liquor.
摘要翻译：包括以下步骤制备N2-（1（S） - 羧基-3-苯基丙基）-L-赖氨酰-L-脯氨酸的方法，包括以下步骤：1）使N2-（1（S ） - 烷氧基羰基-3-苯基丙基）-N6-三氟乙酰基-L-赖氨酰-L-脯氨酸（1）在由水和亲水性有机溶剂组成的混合溶液中使用n摩尔当量的无机碱进行碱水解（ n）= 3），2）使用（n-1）〜n摩尔当量（n> = 3）的无机酸中和水解产物，形成化合物（2）），并且通过使其从适合于降低无机盐的溶解度的溶剂体系中析出而形成的无机盐，以及3）除去无机盐以使其结晶出来，使存在于混合物中的化合物（2）结晶出来其等电点，从而以晶体的形式回收化合物（2），同时保留盐将三氟乙酸衍生的有机酸盐以溶解在母液中的状态。

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