Agent for promoting undifferentiation and cryoprotective agent using aprotic zwitterion

Patent metadata

Field	Value
Publication number	US-12484574-B2
Application number	US-202017609927-A
Country	US
Kind code	B2
Filing date	May 8, 2020
Priority date	May 13, 2019
Publication date	Dec 2, 2025
Grant date	Dec 2, 2025

Abstract

An object of the present invention is to provide an agent for promoting undifferentiation that dissolves a drug, as DMSO or the like does, but is capable of promoting undifferentiation without inducing cell differentiation when added to a medium. The agent for promoting undifferentiation of the present invention has an aprotic zwitterion represented by the following formula (1)wherein A is an anion selected from the group consisting of SO3−, —COO−, —OP═O(H)O−, —OP═O(CH3)O− and —OP═O(OR3)O−, R1 is an alkyl group having 1 to 8 carbon atoms and optionally containing one or two oxygen atoms in the molecular chain, R2 is an alkylene group having 3 to 5 carbon atoms, and R3 is hydrogen or an alkyl group optionally having a heteroatom in the molecular chain.

First claim

The invention claimed is:

1 . A medium for cryopreservation, comprising an aqueous solution of an aprotic zwitterion represented by formula (4):
R 4 -X—R 2 -A  (4)

wherein R 4 is an alkyl group having 1 to 7 carbon atoms, an alkenyl group having 1 to 7 carbon atoms, or an alkyl group having 1 to 7 carbon atoms and containing an ether bond, X is a cation moiety of the zwitterion and represents a cation selected from the group consisting of an imidazolium cation, a phosphonium cation, a sulfonium cation, a pyrazolium cation, a pyridinium cation, a pyrrolidinium cation, a morpholinium cation, a cyclopropenylium cation and a piperidinium cation, A represents an anion moiety and represents an anion selected from the group consisting of SO 3 − , —COO − , —OP═O(H)O − , —OP═O(CH 3 )O − and —OP═O(OR 3 )O − , R 2 is an alkylene group having 1 to 5 carbon atoms and optionally having a substituent, and R 3 is hydrogen or an alkyl group optionally having a heteroatom in the molecular chain, and a cell-permeable substance, wherein the amount of the cell-permeable substance is from 1 to 30 parts by weight per 100 parts by weight of the aqueous solution of the aprotic zwitterion.

2 . The medium for cryopreservation according to claim 1 , wherein the aprotic zwitterion is represented by the following formula (1):

wherein A is an anion selected from the group consisting of SO 3 − , —COO − , —OP═O(H)O − , —OP═O(CH 3 )O − and —OP═O(OR 3 )O − , R 1 is an alkyl group having 1 to 7 carbon atoms, an alkenyl group having 1 to 7 carbon atoms, or an alkyl group having 1 to 7 carbon atoms and containing an ether bond, R 2 is an alkylene group having 3 to 5 carbon atoms, and R 3 is hydrogen or an alkyl group optionally having a heteroatom in the molecular chain.

3 . The medium for cryopreservation according to claim 2 , wherein the aprotic zwitterion is represented by the following formula (2) or (3):

wherein R 1 and R 2 are as defined in claim 2 .

4 . The medium for cryopreservation according to claim 1 , wherein the R 4 is an alkenyl group having 1 to 7 carbon atoms.

5 . A medium for cryopreservation, comprising an aqueous solution of an aprotic zwitterion represented by the formula (4′):
R 4′ —X′—R 2′ -A′  (4′)

wherein R 4′ is an alkyl group having 1 to 7 carbon atoms, an alkenyl group having 1 to 7 carbon atoms, or an alkyl group having 1 to 7 carbon atoms and containing an ether bond, X′ is a cation moiety of the zwitterion and represents a cation that has a cyclic structure having 1 to 6 carbon atoms, contains one or two or more nitrogen atoms, and has one or two or more substituents on the nitrogen atom(s), A′ is —COO − or SO 3 − , the cation is present on nitrogen of the X′ or non-localized in the whole X′, and the anion is present on —COO − or —SO 3 − , R 2′ is an alkylene group having 1 to 5 carbon atoms and optionally having a substituent, and a cell-permeable substance, wherein the amount of the cell-permeable substance is from 1 to 30 parts by weight per 100 parts by weight of the aqueous solution of the aprotic zwitterion.

Assignees

• Japan Science & Tech Agency
• Univ Nat Corp Kanazawa

Inventors

• Kuroda Kosuke
• HIRATA Eishu

Classifications

• C12N5/525

  Freeze protecting agents, e.g. cryoprotectants or osmolarity regulators · CPC title

• C09K3/18 Primary

  for application to surfaces to minimize adherence of ice, mist or water thereto (rendering particulate materials free flowing, in general, e.g. making them hydrophobic B01J2/30); Thawing or antifreeze materials for application to surfaces (used in liquids for heat-transfer, heat-exchange or heat-storage or for the production of heat or cold other than by combustion, e.g. radiator liquids, C09K5/00) · CPC title

• A01N1/125 Primary

  Freeze protecting agents, e.g. cryoprotectants or osmolarity regulators · CPC title

• C12N2501/727

  Kinases (EC 2.7.) · CPC title

• C12N2501/999

  Small molecules not provided for elsewhere · CPC title