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1. 发明授权

US08501998B2 Method for producing polyoxyalkylene derivative and polyoxyalkylene derivative 有权
标题翻译：聚氧化烯衍生物和聚氧化烯衍生物的制备方法
公开(公告)号：US08501998B2
公开(公告)日：2013-08-06
申请号：US12751150
申请日：2010-03-31
申请人： Satoshi Matsuo , Kazuhiro Hashimoto , Ken-ichiro Nakamoto , Chika Itoh
发明人： Satoshi Matsuo , Kazuhiro Hashimoto , Ken-ichiro Nakamoto , Chika Itoh
IPC分类号： C07C41/09 , C07C43/11
CPC分类号： C08G65/2609 , C08G65/2696
摘要： A method for producing a polyoxyalkylene derivative represented by the following general formula (1): Z(OA)n-OH]m (1) wherein Z is a residue of glycerin or diglycerin, OA is an oxyalkylene group having 2 to 4 carbon atoms, n is an average number of moles of the oxyalkylene group added and is 80 to 800, and m is 3 to 4, the method comprising steps (A), (B), (C), (D), (E), and (F) defined in the present description.
摘要翻译：制备由以下通式（1）表示的聚氧化烯衍生物的方法：Z（OA）n-OH] m（1）其中Z是甘油或双甘油的残基，OA是具有2至4个碳原子的氧化烯基（A），（B），（C），（D），（E），（E），（C），（C），和（F）。

2. 发明授权

US08828373B2 Polyalkylene glycol derivative and modified bio-related substance 有权
标题翻译：聚亚烷基二醇衍生物和改性生物相关物质
公开(公告)号：US08828373B2
公开(公告)日：2014-09-09
申请号：US11142683
申请日：2005-06-02
申请人： Ken-ichiro Nakamoto , Syunsuke Ohashi , Yuji Yamamoto , Kenji Sakanoue , Chika Itoh , Tohru Yasukohchi
发明人： Ken-ichiro Nakamoto , Syunsuke Ohashi , Yuji Yamamoto , Kenji Sakanoue , Chika Itoh , Tohru Yasukohchi
IPC分类号： A61K31/765 , C08F283/00 , C08G65/329 , C08G65/333 , C08G65/26 , A61K47/48
CPC分类号： C08G65/2609 , A61K47/48215 , A61K47/60 , C08G65/329 , C08G65/333
摘要： A polyalkylene glycol derivative containing a compound of the formula (1): wherein R is a hydrocarbon group having 1 to 24 carbon atoms, OA1 and OA2 are each an oxyalkylene group having 2 to 4 carbon atoms, the groups represented by R are the same or different from each other in one molecule, the groups represented by OA2 are the same or different from each other in one molecule, m is an average number of moles of the above oxyalkylene group added, m represents 10 to 1000, X represents a functional group capable of chemically reacting with a bio-related substance, and Y is a linker and represents an ether bond, an amide bond, a urethane bond, an ester bond, a secondary amino group, a carbonate bond, or an alkylene group containing these bonds, polydispersity Mw/Mn of the above polyalkylene glycol derivative in gel permeation chromatography satisfying the following relationship: Mw/Mn≦1.08 wherein Mw represents a weight average molecular weight and Mn represents a number average molecular weight.
摘要翻译：含有式（1）化合物的聚亚烷基二醇衍生物：其中R为碳原子数为1〜24的烃基，OA1和OA2分别为碳原子数2〜4的氧化烯基，由R表示的基团相同或在一个分子中彼此不同，在一个分子中由OA2表示的基团相同或不同，m为上述加成的氧化烯基的平均摩尔数，m表示10〜1000，X表示官能团能够与生物相关物质进行化学反应的基团，Y为连接基，表示醚键，酰胺键，氨基甲酸酯键，酯键，仲氨基，碳酸酯键或含有这些基团的亚烷基键，多分散性上述聚亚烷基二醇衍生物的Mw / Mn满足以下关系式：Mw / Mn＆nlE 1.08其中Mw表示重均分子量，Mn表示数均mol 精神重量

3. 发明授权

US08569444B2 Polyalkylene glycol derivative and process for producing same 有权
标题翻译：聚亚烷基二醇衍生物及其制备方法
公开(公告)号：US08569444B2
公开(公告)日：2013-10-29
申请号：US13128470
申请日：2009-11-11
申请人： Ken-ichiro Nakamoto , Chika Itoh , Shuichi Yoshimura , Tsuyoshi Takehana
发明人： Ken-ichiro Nakamoto , Chika Itoh , Shuichi Yoshimura , Tsuyoshi Takehana
IPC分类号： C08G59/68 , C08G65/34 , C08G59/00 , C08G65/00
CPC分类号： C08G65/2648 , C08G65/2696
摘要： A process for producing a polyalkylene glycol derivative having such high molecular weight and purity that the derivative can be used in pharmaceutical applications, which produces a polyalkylene glycol derivative of the formula (X) by steps (A), (B), (C) and (D), wherein R is as defined: R—(OA)nOH (X) (step (A)) 5 to 50% by mol of an alkali catalyst is added to a compound represented by the formula (Y), wherein R is as defined: R—OH (Y) (step (B)) an alkylene oxide having 2 to 4 carbon atoms is reacted under a condition of 50 to 130° C. until the average number of moles of an oxyalkylene group OA added reaches the range of 5 to 500 to obtain a polyalkylene glycol derivative; (step (C)) 10 to 5000% by mass of a hydrocarbon solvent is added to the derivative of the step (B) to dilute it, and remaining water is removed by azeotropy; and (step (D)) the derivative of the step (B) is reacted with an alkylene oxide having 2 to 4 carbon atoms under a condition of 50 to 130° C. until the average number of moles of the oxyalkylene group (OA) reaches the range of 600 to 2000.
摘要翻译：一种制备具有如此高分子量和纯度的聚亚烷基二醇衍生物的方法，该衍生物可用于药物应用，其通过步骤（A），（B），（C）产生式（X）的聚亚烷基二醇衍生物，和（D），其中R定义如下：R-（OA）nOH（X）（步骤（A））将5〜50摩尔碱性催化剂加入到式（Y）表示的化合物中，其中 R定义如下：R-OH（Y）（步骤（B））将具有2至4个碳原子的烯化氧在50至130℃的条件下反应，直到加入的氧化烯基OA的平均摩尔数达到5〜500的范围，得到聚亚烷基二醇衍生物; （步骤（C））将10〜5000质量％的烃类溶剂加入步骤（B）的衍生物中以稀释，并通过共沸除去剩余的水; 和（步骤（D）），使步骤（B）的衍生物在50至130℃的条件下与具有2至4个碳原子的烯化氧反应，直到氧化烯基（OA）的平均摩尔数达到600〜2000的范围。

4. 发明申请

US20090192320A1 MODIFIED BIO-RELATED SUBSTANCE, PROCESS FOR PRODUCING THE SAME, AND INTERMEDIATE 有权
标题翻译：改良的生物相关物质，其生产方法和中间体
公开(公告)号：US20090192320A1
公开(公告)日：2009-07-30
申请号：US12399249
申请日：2009-03-06
申请人： Ken-ichiro NAKAMOTO , Syunsuke Ohashi , Yuji Yamamoto , Kenji Sakanoue , Chika Itoh , Tohru Yasukohchi
发明人： Ken-ichiro NAKAMOTO , Syunsuke Ohashi , Yuji Yamamoto , Kenji Sakanoue , Chika Itoh , Tohru Yasukohchi
IPC分类号： C07D207/404 , C07C43/13 , C07C309/68
CPC分类号： C08G65/329 , A61K47/60 , C08G65/2609
摘要： A modified bio-related substance, wherein at least one poly(alkylene glycol)oxy group represented by the following formula (1) is combined in a molecule: wherein R is a hydrocarbon group having 1 to 24 carbon atoms, OA1 and OA2 are each an oxyalkylene group having 2 to 4 carbon atoms, the groups represented by R are the same or different from each other in one molecule, and the groups represented by OA2 are the same or different from each other in one molecule, n and m are each average number of moles of the oxyalkylene group added, n represents 0 to 1000, and m represents 10 to 1000.
摘要翻译：一种改性的生物相关物质，其中至少一种由下式（1）表示的聚（亚烷基二醇）氧基在分子中组合：其中R是具有1至24个碳原子的烃基，OA1和OA2各自具有2至4个碳原子的氧化烯基，由一个分子中由R表示的基团彼此相同或不同，并且由OA2表示的基团在一个分子中彼此相同或不同，n和m各自为氧化烯基的平均加成摩尔数，n表示0〜1000，m表示10〜1000。

5. 发明申请

US20110082277A1 MODIFIED BIO-RELATED SUBSTANCE, PROCESS FOR PRODUCING THE SAME, AND INTERMEDIATE 有权
标题翻译：改良的生物相关物质，其生产方法和中间体
公开(公告)号：US20110082277A1
公开(公告)日：2011-04-07
申请号：US12942554
申请日：2010-11-09
申请人： Ken-ichiro Nakamoto , Syunsuke Ohashi , Yuji Yammamoto , Kenji Sakanoue , Chika Itoh , Tohru Yasukohchi
发明人： Ken-ichiro Nakamoto , Syunsuke Ohashi , Yuji Yammamoto , Kenji Sakanoue , Chika Itoh , Tohru Yasukohchi
IPC分类号： C08G65/28 , C08G63/06
CPC分类号： C08G65/329 , A61K47/60 , C08G65/2609
摘要： A modified bio-related substance, wherein at least one poly(alkylene glycol)oxy group represented by the following formula (1) is combined in a molecule: wherein R is a hydrocarbon group having 1 to 24 carbon atoms, OA1 and OA2 are each an oxyalkylene group having 2 to 4 carbon atoms, the groups represented by R are the same or different from each other in one molecule, and the groups represented by OA2 are the same or different from each other in one molecule, n and m are each average number of moles of the oxyalkylene group added, n represents 0 to 1000, and m represents 10 to 1000.
摘要翻译：一种改性的生物相关物质，其中至少一种由下式（1）表示的聚（亚烷基二醇）氧基在分子中组合：其中R是具有1至24个碳原子的烃基，OA1和OA2各自具有2至4个碳原子的氧化烯基，由一个分子中由R表示的基团彼此相同或不同，并且由OA2表示的基团在一个分子中彼此相同或不同，n和m各自为氧化烯基的平均加成摩尔数，n表示0〜1000，m表示10〜1000。

6. 发明授权

US08034981B2 Modified bio-related substance, process for producing the same, and intermediate 有权
标题翻译：改性生物相关物质，其生产方法和中间体
公开(公告)号：US08034981B2
公开(公告)日：2011-10-11
申请号：US12942554
申请日：2010-11-09
申请人： Ken-ichiro Nakamoto , Syunsuke Ohashi , Yuji Yamamoto , Kenji Sakanoue , Chika Itoh , Tohru Yasukohchi
发明人： Ken-ichiro Nakamoto , Syunsuke Ohashi , Yuji Yamamoto , Kenji Sakanoue , Chika Itoh , Tohru Yasukohchi
IPC分类号： C07D249/18
CPC分类号： C08G65/329 , A61K47/60 , C08G65/2609
摘要： A modified bio-related substance, wherein at least one poly(alkylene glycol)oxy group represented by the following formula (1) is combined in a molecule: wherein R is a hydrocarbon group having 1 to 24 carbon atoms, OA1 and OA2 are each an oxyalkylene group having 2 to 4 carbon atoms, the groups represented by R are the same or different from each other in one molecule, and the groups represented by OA2 are the same or different from each other in one molecule, n and m are each average number of moles of the oxyalkylene group added, n represents 0 to 1000, and m represents 10 to 1000.
摘要翻译：一种改性的生物相关物质，其中至少一种由下式（1）表示的聚（亚烷基二醇）氧基在分子中组合：其中R是具有1至24个碳原子的烃基，OA1和OA2各自具有2至4个碳原子的氧化烯基，由一个分子中由R表示的基团彼此相同或不同，并且由OA2表示的基团在一个分子中彼此相同或不同，n和m各自为氧化烯基的平均加成摩尔数，n表示0〜1000，m表示10〜1000。

7. 发明申请

US20110218322A1 POLYALKYLENE GLYCOL DERIVATIVE AND PROCESS FOR PRODUCING SAME 有权
标题翻译：聚乙烯醇衍生物及其生产方法
公开(公告)号：US20110218322A1
公开(公告)日：2011-09-08
申请号：US13128470
申请日：2009-11-11
申请人： Ken-ichiro Nakamoto , Chika Itoh , Shuichi Yoshimura , Tsuyoshi Takehana
发明人： Ken-ichiro Nakamoto , Chika Itoh , Shuichi Yoshimura , Tsuyoshi Takehana
IPC分类号： C08G65/08
CPC分类号： C08G65/2648 , C08G65/2696
摘要： An object of the present invention is to provide a process for producing a polyalkylene glycol derivative having such high molecular weight and purity that the derivative can be used in pharmaceutical applications.The production process of the invention produces a polyalkylene glycol derivative of the formula (X) by steps (A), (B), (C), (D), and (E). R—(OA)nOH (X) (Step (A)) 5 to 50% by mol of an alkali catalyst is added to a compound represented by the formula (Y). R—OH (Y) (Step (B)) An alkylene oxide having 2 to 4 carbon atoms is reacted under a condition of 50 to 130° C. until the average number of moles of an oxyalkylene group OA added reaches the range of 5 to 500 to obtain a polyalkylene glycol derivative. (Step (C)) 10 to 5000% by mass of a hydrocarbon solvent is added to the derivative of the step (B) to dilute it, and remaining water is removed by azeotropy. (Step (D)) The derivative of the step (B) is reacted with an alkylene oxide having 2 to 4 carbon atoms under a condition of 50 to 130° C. until the average number of moles of the oxyalkylene group (OA) reaches the range of 600 to 2000.
摘要翻译：本发明的目的是提供一种具有如此高分子量和纯度的聚亚烷基二醇衍生物的方法，以使该衍生物可用于药物应用。本发明的制备方法通过步骤（A），（B），（C），（D）和（E）制备式（X）的聚亚烷基二醇衍生物。 R-（OA）nOH（X）（工序（A））将5〜50摩尔碱性催化剂加入到由式（Y）表示的化合物中。 R-OH（Y）（工序（B））将碳原子数为2〜4的烯化氧在50〜130℃的条件下进行反应，直到添加的氧化烯基OA的平均摩尔数达到5 至500以获得聚亚烷基二醇衍生物。（工序（C））将10〜5000质量％的烃类溶剂加入步骤（B）的衍生物中以使其稀释，并通过共沸除去剩余的水。（步骤（D））步骤（B）的衍生物在50〜130℃的条件下与碳原子数为2〜4的烯化氧反应，直到氧化烯基（OA）的平均摩尔数达到范围从600到2000。

8. 发明授权

US07524875B2 Modified bio-related substance, process for producing the same, and intermediate 有权
标题翻译：改性生物相关物质，其生产方法和中间体
公开(公告)号：US07524875B2
公开(公告)日：2009-04-28
申请号：US11142255
申请日：2005-06-02
申请人： Ken-ichiro Nakamoto , Syunsuke Ohashi , Yuji Yamamoto , Kenji Sakanoue , Chika Itoh , Tohru Yasukohchi
发明人： Ken-ichiro Nakamoto , Syunsuke Ohashi , Yuji Yamamoto , Kenji Sakanoue , Chika Itoh , Tohru Yasukohchi
IPC分类号： A61K31/075 , A61K31/4015 , A61K31/4164 , A61K31/4192 , C07C43/11 , C07D207/444 , C07D233/64 , C07D249/04 , C07D487/06
CPC分类号： C08G65/329 , A61K47/60 , C08G65/2609
摘要： A modified bio-related substance, wherein at least one poly(alkylene glycol)oxy group represented by the following formula (1) is combined in a molecule: wherein R is a hydrocarbon group having 1 to 24 carbon atoms, OA1 and OA2 are each an oxyalkylene group having 2 to 4 carbon atoms, the groups represented by R are the same or different from each other in one molecule, and the groups represented by OA2 are the same or different from each other in one molecule, n and m are each average number of moles of the oxyalkylene group added, n represents 0 to 1000, and m represents 10 to 1000.
摘要翻译：一种改性的生物相关物质，其中至少一种由下式（1）表示的聚（亚烷基二醇）氧基在分子中组合：其中R是具有1至24个碳原子的烃基，OA1和OA2各自具有2至4个碳原子的氧化烯基，由一个分子中由R表示的基团彼此相同或不同，并且由OA2表示的基团在一个分子中彼此相同或不同，n和m各自为氧化烯基的平均加成摩尔数，n表示0〜1000，m表示10〜1000。

9. 发明申请

US20060115450A1 Polyalkylene glycol derivative and modified bio-related substance 有权
标题翻译：聚亚烷基二醇衍生物和改性生物相关物质
公开(公告)号：US20060115450A1
公开(公告)日：2006-06-01
申请号：US11142683
申请日：2005-06-02
申请人： Ken-ichiro Nakamoto , Syunsuke Ohashi , Yuji Yamamoto , Kenji Sakanoue , Chika Itoh , Tohru Yasukohchi
发明人： Ken-ichiro Nakamoto , Syunsuke Ohashi , Yuji Yamamoto , Kenji Sakanoue , Chika Itoh , Tohru Yasukohchi
IPC分类号： A61K31/765 , C08F283/00
CPC分类号： C08G65/2609 , A61K47/48215 , A61K47/60 , C08G65/329 , C08G65/333
摘要： A polyalkylene glycol derivative containing a compound of the formula (1): wherein R is a hydrocarbon group having 1 to 24 carbon atoms, OA1 and OA2 are each an oxyalkylene group having 2 to 4 carbon atoms, the groups represented by R are the same or different from each other in one molecule, the groups represented by OA2 are the same or different from each other in one molecule, m is an average number of moles of the above oxyalkylene group added, m represents 10 to 1000, X represents a functional group capable of chemically reacting with a bio-related substance, and Y is a linker and represents an ether bond, an amide bond, a urethane bond, an ester bond, a secondary amino group, a carbonate bond, or an alkylene group containing these bonds, polydispersity Mw/Mn of the above polyalkylene glycol derivative in gel permeation chromatography satisfying the following relationship: Mw/Mn≦1.08 wherein Mw represents a weight average molecular weight and Mn represents a number average molecular weight.
摘要翻译：含有式（1）化合物的聚亚烷基二醇衍生物：其中R为碳原子数为1〜24的烃基，OA 1和O 2各自为氧化烯具有2至4个碳原子的基团，由R表示的基团在一个分子中彼此相同或不同，在一个分子中由OA 2表示的基团彼此相同或不同， m是上述氧化烯基的平均加成摩尔数，m表示10〜1000，X表示与生物相关物质发生化学反应的官能团，Y为连接基，表示醚键，酰胺键氨基甲酸酯键，酯键，仲氨基，碳酸酯键或含有这些键的亚烷基，上述聚亚烷基二醇衍生物在凝胶渗透色谱中的多分散性Mw / Mn满足以下关系： -formulae description =“In-line Formulas”end =“lead”？> Mw / Mn <= 1.08 < in-line-formula description =“In-line Formulas”end =“tail”？>其中Mw表示重均分子量，Mn表示数均分子量。

10. 发明授权

US08716435B2 Multibranched polyoxyalkylene compound and producing method thereof 有权
标题翻译：多分支聚氧化烯化合物及其制备方法
公开(公告)号：US08716435B2
公开(公告)日：2014-05-06
申请号：US12750844
申请日：2010-03-31
申请人： Tsuyoshi Takehana , Ken-ichiro Nakamoto , Chika Itoh
发明人： Tsuyoshi Takehana , Ken-ichiro Nakamoto , Chika Itoh
IPC分类号： C08G65/34
CPC分类号： C08G65/33337 , A61K47/34 , C08G65/2609 , C08G65/2648 , C08G65/3322 , C08G65/3326 , C08G65/33303 , C08G65/33372 , C08G65/33389 , C08G65/3346 , C08G2650/26 , C08G2650/60
摘要： A multibranched polyoxyalkylene compound represented by the following formula (1): wherein R1 is the same or different and is a hydrocarbon group having 1 to 24 carbon atoms, OA1 and OA2 are the same or different and are an oxyalkylene group having 2 to 4 carbon atoms, n and m are the same or different and are an average number of moles of the oxyalkylene group added, n represents 0 to 1000, m is the same or different and represents 10 to 1000, X represents a functional group capable of reacting with an amino group, a mercapto group, an aldehyde group, a carboxyl group, a triple bond, or an azide group to form a chemical bond, and L1 and L2 are the same or different and are a single bond, an alkylene group, or an alkylene group in which at least one bond selected from an ester bond, a urethane bond, an amide bond, an ether bond, and an amino is interposed.
摘要翻译：由下式（1）表示的多支链聚氧化烯化合物：其中R1相同或不同，为碳原子数1〜24的烃基，OA1和OA2相同或不同，为碳数2〜4的氧化烯基原子，n和m相同或不同，是加成的氧化烯基的平均摩尔数，n表示0〜1000，m相同或不同，表示10〜1000，X表示可与氨基，巯基，醛基，羧基，三键或叠氮基，形成化学键，L1和L2相同或不同，为单键，亚烷基或其中插入了选自酯键，氨基甲酸酯键，酰胺键，醚键和氨基中的至少一个的亚烷基。

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