公开(公告)号：US20200024391A1

公开(公告)日：2020-01-23

申请号：US16493909

申请日：2018-03-23

申请人： NOF CORPORATION

发明人： Kota TANGE ,  Hiroki YOSHIOKA ,  Takuma TSUBUSAKI ,  Masaki KAMIYA

IPC分类号： C08G65/334

摘要： To provide a degradable polyethylene glycol derivative in which polyethylene glycol chains are linked by a disulfide linker capable of accurately controlling the degradation rate under different reductive environments in the living body, and whose division rate into a polyethylene glycol chain of low molecular weight in the living body is able to be accurately controlled. A degradable polyethylene glycol derivative represented by formula (1). R1, R2, R3 and R4 represent each independently a hydrogen atom or a hydrocarbon group having from 1 to 6 carbon atoms, and at least one of R1, R2, R3 and R4 is the hydrocarbon group; P1 is a straight-chain or branched polyethylene glycol chain having a number of ethylene glycol units of 3 or more; P2 is a straight-chain polyethylene glycol chain having a number of ethylene glycol units of 3 or more; w is an integer of 1 to 8; u is an integer of 1 to 10; X1 is a chemically reactive functional group; and Z1, Z2 and Z3 are each independently a selected divalent spacer.

公开(公告)号：US20180096831A1

公开(公告)日：2018-04-05

申请号：US15559540

申请日：2016-03-30

申请人： NOF CORPORATION

发明人： Masaki KAMIYA ,  Ryota MATSUKI

IPC分类号： H01J49/16 ,  G01N27/64

CPC分类号： H01J49/164 ,  G01N27/64 ,  G01N33/6851 ,  H01J49/0418

摘要： A matrix-assisted laser desorption (MALDI) mass spectrometry in which a mixture comprising a polyethylene glycol derivative having a molecular weight of 40,000 or more and a matrix is irradiated with laser beam to vaporize the polyethylene glycol derivative together with the matrix, thereby measuring a molecular weight of the polyethylene glycol derivative, wherein as the matrix, a low polar matrix having a 1-octanol/water partition coefficient (log Pow) of 4.1 to 4.8 is used. Also disclosed is a matrix for use in the matrix-assisted laser desorption (MALDI) mass spectrometry.

公开(公告)号：US20210024692A1

公开(公告)日：2021-01-28

申请号：US17041102

申请日：2019-03-27

申请人： NOF CORPORATION

发明人： Akihide ONOZAWA ,  Hiroki YOSHIOKA ,  Masaki KAMIYA

IPC分类号： C08G65/324 ,  C08G65/325 ,  C08G65/326 ,  C08G65/331 ,  C08G65/333 ,  C08G65/334 ,  A61K47/60

摘要： A method for producing a multi-arm type polyethylene glycol derivative, which includes carrying out the following in order: Step (A): protecting an even number of hydroxyl groups, while leaving only the hydroxyl group at the 1-position of a polyhydric alcohol having an odd number of hydroxyl groups, other than the hydroxyl group at the 1-position by cyclic benzylidene acetalization, Step (B): linking two molecules of the compound obtained in step (A) to a compound for introducing a specific linker by etherification reaction, Step (C): deprotecting the cyclic benzylidene acetal structure at the terminal of the compound obtained in step (B), Step (D): polymerizing 3 to 600 mol of ethylene oxide to each hydroxyl group of the compound obtained in step (C) to obtain a multi-arm type polyethylene glycol derivative, and Step (E): functionalizing the hydroxyl group at the terminal of the multi-arm type polyethylene glycol derivative obtained in step (D).

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：US20130172576A1

公开(公告)日：2013-07-04

申请号：US13632353

申请日：2012-10-01

申请人： NOF Corporation

发明人： Masaki KAMIYA ,  Ken-ichiro NAKAMOTO

IPC分类号： C07C217/08 ,  C07D207/36 ,  C07C43/205

CPC分类号： C07C217/08 ,  C07C43/205 ,  C07D207/36 ,  C07D207/46 ,  C08G65/08 ,  C08G65/33313 ,  C08G65/33317 ,  C08L2203/02

摘要： A branched hetero polyfunctional polyoxyalkylene compound represented by the following formula (1): wherein Z represents a hydroxyl group-removed residue of pentaerythritol or dipentaerythritol, OA1 and OA2 represent an oxyalkylene group having 2 to 4 carbon atoms, L1, L2 and L3 represent an alkylene group or an alkylene group that contains an ester bond, a urethane bond, an amide bond, an ether bond, a carbonate bond, a secondary amino group or a urea bond, X and Y are different from each other and represent a functional group capable of a chemical reaction; m and n are an average number of moles of the oxyalkylene group added, m represents 5 to 1,000, n represents 0 to 1,000, and p, q and r represent 0 or 1; and s1 is an integer of 2 or more and s1+s2=4 or 6.

摘要翻译： 由下式（1）表示的支链异多官能聚氧化烯化合物：其中Z表示季戊四醇或二季戊四醇的羟基去除残基，OA1和OA2表示碳原子数2〜4的氧化烯基，L1，L2和L3表示 亚烷基或含有酯键，氨基甲酸酯键，酰胺键，醚键，碳酸键，仲氨基或脲键的亚烷基，X和Y彼此不同，表示官能团 能够发生化学反应; m和n是加入的氧化烯基的平均摩尔数，m表示5至1,000，n表示0至1,000，p，q和r表示0或1; s1为2以上的整数，s1 + s2 = 4或6。

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：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.