公开(公告)号：US20210147624A1

公开(公告)日：2021-05-20

申请号：US17042711

申请日：2019-03-29

申请人： NOF CORPORATION ,  TOKYO INSTITUTE OF TECHNOLOGY

发明人： Hiroki YOSHIOKA ,  Masaki KAMIYA ,  Yuji YAMAMOTO ,  Midori HIRAI ,  Akiko SASAKI ,  Nobuhiro NISHIYAMA ,  Makoto MATSUI ,  Hiroyasu TAKEMOTO ,  Kazuki MIYAUCHI ,  Takahiro NOMOTO ,  Keishiro TOMODA

IPC分类号： C08G65/333 ,  C08G65/325 ,  A61K47/65

摘要： The invention provides a high-molecular-weight polyethylene glycol derivative that does not cause vacuolation of cells. The degradable polyethylene glycol derivative is represented by the following formula (1): wherein m is 1-7, n1 and n2 are each independently 45-682, p is 1-4, R is an alkyl group having 1-4 carbon atoms, Z is an oligopeptide with 2-8 residues composed of neutral amino acids excluding cysteine, Q is a residue of a compound having 2-5 active hydrogens, X is a functional group capable of reacting with a bio-related substance, and L1, L2, L3, L4 and L5 are each independently a single bond or a divalent spacer.

公开(公告)号：US20210023231A1

公开(公告)日：2021-01-28

申请号：US17042039

申请日：2019-03-29

申请人： NOF CORPORATION ,  TOKYO INSTITUTE OF TECHNOLOGY

发明人： Hiroki YOSHIOKA ,  Masaki KAMIYA ,  Yuji YAMAMOTO ,  Midori HIRAI ,  Akiko SASAKI ,  Nobuhiro NISHIYAMA ,  Makoto MATSUI ,  Hiroyasu TAKEMOTO ,  Kazuki MIYAUCHI ,  Takahiro NOMOTO ,  Keishiro TOMODA

IPC分类号： A61K47/60 ,  C08G65/333 ,  C07K19/00 ,  C07K5/103 ,  C07K7/06 ,  A61K38/23 ,  A61K38/19 ,  A61K38/27

摘要： The invention provides a bio-related substance bonded to a high-molecular-weight polyethylene glycol derivative that does not cause vacuolation of cells. The bio-related substance bonded to a degradable polyethylene glycol derivative is represented by the formula (A):
wherein m is 1-7, n1 and n2 are each independently 45-682, p is 1-4, R is an alkyl group having 1-4 carbon atoms, Z is an oligopeptide with 2-8 residues composed of neutral amino acids excluding cysteine, Q is a residue of a compound having 2-5 active hydrogens, D is the bio-related substance, L1, L2, L3, L4 and L5 are each independently a single bond or a divalent spacer, and y is 1-40.

公开(公告)号：US20220363824A1

公开(公告)日：2022-11-17

申请号：US17788841

申请日：2020-12-21

申请人： NOF CORPORATION

发明人： Midori HIRAI ,  Kyu TAKEUCHI

IPC分类号： C08G65/30

摘要： A method for purifying a branched polyethylene glycol, which includes adding, to a branched polyethylene glycol compound represented by the following formula [1] and having a weight average molecular weight of 40000 or more: where Z, Y1, Y2, A, Polymer, l, m and b are as defined herein, at least one solid acid selected from magnesium silicate, aluminum silicate, and aluminum magnesium silicate and having a specific surface area of 50 to 250 m2/g in the presence of an aprotic organic solvent to obtain a mixture; stirring the mixture; and subsequently separating the solid acid.

公开(公告)号：US20200079905A1

公开(公告)日：2020-03-12

申请号：US16498248

申请日：2018-03-22

申请人： NOF CORPORATION

发明人： Midori HIRAI ,  Hiroki Yoshioka

IPC分类号： C08G65/46

摘要： A purification method of a polyethylene glycol compound having one carboxyl group. In the method, an aqueous solution of the compound having a pH of 8 to 11 is prepared, the aqueous solution and a mixed organic solvent are mixed at a temperature of 15° C. or more and 50° C. or less and the mixture is separated into an organic layer and an aqueous layer. In the mixed organic solvent, a ratio of solvent I is from 25 to 60% by mass, and a ratio of solvent II is from 75 to 40% by mass. Solvent I is a hydrocarbon, solvent II is a halogenated hydrocarbon, a mixing ratio Y (organic solvent I/organic solvent II), a temperature T (° C.) at mixing and a weight average molecular weight M of the compound satisfy a relationship of 3.11×10−6M+0.084≤Y−0.0135T≤−1.77×10−6M+0.404.

公开(公告)号：US20230050758A1

公开(公告)日：2023-02-16

申请号：US17788618

申请日：2020-12-21

申请人： NOF CORPORATION

发明人： Ryo KAWAHARA ,  Atsushi SATO ,  Midori HIRAI ,  Kyu TAKEUCHI

IPC分类号： C08G65/30 ,  C08G65/325

摘要： A method for purifying a polyethylene glycol compound represented by formula [1], including a Step (A) of dissolving the compound represented by formula [1] in an organic solvent having a Hildebrand solubility parameter of 8 to 10 (cal/cm3)1/2 to obtain a solution, and a Step (B) of mixing the solution with 0.1 to 1 part by mass of an adsorbent made from a hydrotalcite having a specific surface area of 50 to 200 m2/g with respect to 1 part by mass of the compound of the formula [1] to prepare a slurry, where Z, Y1, Y2, A, Polymer, X, a, b, l and m are as defined herein.

公开(公告)号：US20160046762A1

公开(公告)日：2016-02-18

申请号：US14780310

申请日：2014-03-24

申请人： NOF CORPORATION

发明人： Hiroki YOSHIOKA ,  Shingo KIMURA ,  Midori HIRAI

IPC分类号： C08G65/34

CPC分类号： C08G65/34 ,  C08G65/30 ,  C08G65/333

摘要： A method for purifying a polyethylene glycol compound having one amino group, which includes (A) preparing an aqueous solution of the compound having a pH of 1 to 5, (B) an extracting step of mixing the aqueous solution with a mixed organic solvent to cause layer separation into organic and aqueous layers, wherein a ratio of an organic solvent I is 25 to 65% by mass and a ratio of an organic solvent II is 75 to 35% by mass, the organic solvent I is selected from an aromatic hydrocarbon and an ester, the organic solvent II is a halogenated hydrocarbon, and a mixing ratio Y of I to II, temperature T (° C.) at mixing, and molecular weight M of the compound satisfy the following relationship: 1.9×10−6M+0.09≦Y−0.015T≦−1.4×10−6M+0.44 and (C) recovering the compound from the aqueous layer.

摘要翻译： 一种纯化具有一个氨基的聚乙二醇化合物的方法，其包括（A）制备pH为1〜5的化合物的水溶液，（B）将水溶液与混合有机溶剂混合的萃取步骤 使层分离成有机层和水层，其中有机溶剂I的比例为25〜65质量％，有机溶剂II的比例为75〜35质量％，有机溶剂I选自芳香族烃 和酯，有机溶剂II为卤代烃，混合比为I，混合温度T（℃）和化合物的分子量M满足下式：1.9×10-6M + 0.09＆nlE; Y-0.015T＆nlE; -1.4×10-6M + 0.44和（C）从水层中回收化合物。

公开(公告)号：US20220185969A1

公开(公告)日：2022-06-16

申请号：US17603275

申请日：2019-04-15

申请人： NOF CORPORATION ,  UNIVERSITA' DEGLI STUDI DI PADOVA

发明人： Hiroki YOSHIOKA ,  Midori HIRAI ,  Masaki KAMIYA ,  Gianfranco PASUT

IPC分类号： C08G81/02 ,  A61K47/59 ,  A61K47/54 ,  A61K38/27

摘要： The invention provides a modified bio-related substance that shows further prolonged half-life in blood and further improved stability in the blood of living organisms. In particular, the invention provides a conjugate of a block polymer and a bio-related substance, which conjugate is represented by the following formula (I), wherein each symbol is as described herein.

公开(公告)号：US20160326317A1

公开(公告)日：2016-11-10

申请号：US15216573

申请日：2016-07-21

申请人： NOF CORPORATION

发明人： Hiroki YOSHIOKA ,  Midori HIRAI ,  Hitoshi NAKATSUHARA ,  Yuji YAMAMOTO

IPC分类号： C08G65/26

CPC分类号： C08G65/2609 ,  C08G65/2696 ,  C08G65/329 ,  C08G65/3322 ,  C08G65/33306 ,  C08G65/33337 ,  C08G65/33368 ,  C08G65/33389 ,  C08G2650/30

摘要： A multi-arm polyethylene glycol derivative having a narrow molecular weight distribution represented by the formula (1): wherein, L represents a group selected from a linear or branched alkylene, arylene, or cycloalkylene group having two or more carbon atoms and combinations thereof, which may have an ether bond in a chain; X represents a dehydroxylation residue of a linear sugar alcohol having 5 or 7 carbon atoms; m is the number of polyethylene glycol chains bonded to X and represents 4 or 6; n is the average addition molar number of oxyethylene groups and represents an integer of 3 to 600; Y represents a single bond or an alkylene group as further defined herein; and Z represents a chemically reactive functional group.

摘要翻译： 其中，L表示选自具有两个或更多个碳原子的直链或支链亚烷基，亚芳基或亚环烷基及其组合，其可以在链中具有醚键; X表示具有5或7个碳原子的直链糖醇的脱羟基残基; m是与X键合的聚乙二醇链的数目，代表4或6; n是氧乙烯基的平均加成摩尔数，为3〜600的整数。 Y代表本文进一步定义的单键或亚烷基; Z表示化学反应性官能团。