Intracellular delivery vehicle

Patent metadata

Field	Value
Publication number	US-11452697-B2
Application number	US-202016899943-A
Country	US
Kind code	B2
Filing date	Jun 12, 2020
Priority date	Sep 7, 2015
Publication date	Sep 27, 2022
Grant date	Sep 27, 2022

Abstract

An intracellular delivery vehicle of which surface is covered by a positive charge, an intracellular delivery complex in which a component or compound desired is loaded in the intracellular delivery vehicle, a temperature-sensitive probe comprising the intracellular delivery complex, and a method for measuring the intracellular temperature by the temperature-sensitive probe are disclosed. The intracellular delivery vehicle is useful on account of its capability of easily delivering the component or compound desired inside the cell without inhibiting cell proliferation.

First claim

The invention claimed is:

1. A method for producing a gel particle, comprising performing radical polymerization reaction involving a cationic polymerization initiator having a chemical structure represented by general formula (I):

wherein
Y represents a single bond or CHR 85 ,
Z represents a single bond or CHR 86 ,
R 72 , R 73 , R 75 , R 76 , R 77 , R 78 , R 85 and R 86 are each independently selected from the group consisting of hydrogen atom, C 1-6 alkyl group, C 1-6 alkoxy group, C 1-6 alkylcarbonyl group, phenyl group and hydroxyl group, wherein said C 1-6 alkyl group, C 1-6 alkoxy group, C 1-6 alkylcarbonyl group and phenyl group are optionally substituted with 1 or 2 substituents selected from the group consisting of C 1-6 alkyl group, C 1-6 alkoxy group, C 1-6 alkylcarbonyl group, phenyl group and hydroxyl group,
R 72 and R 73 optionally each independently represent adamantyl group or C 1-6 alkyl group substituted with Si(OCH 3 ) 2 (CH 3 ), or
R 75 and R 76 or R 77 and R 78 together optionally form —(CH 2 ) 3-5 —,
R 81 , R 82 , R 83 and R 84 are each independently a substituent selected from the group consisting of C 1-4 alkyl group, C 1-4 alkylcarbonyl group and C 1-3 alkoxy group, wherein the C 1-4 alkyl is optionally substituted with one C 1-3 alkoxy group; and
R 71 and R 74 each independently are C 1-3 alkyl group, and
X f − is counter anion,

and a monomer comprising a carbon-carbon double bond, and a crosslinker.

2. The method according to claim 1 , wherein said Y and Z represent single bond.

3. The method according to claim 1 , wherein said R 81 , R 82 , R 83 , and R 84 are each independently selected from the group consisting of methyl group, ethyl group, methylcarbonyl group, isobutyl group, and 2-methyl-2-methoxypropyl group.

4. The method according to claim 1 , wherein said R 71 and R 74 are a methyl group.

5. The method according to claim 1 , wherein said R 72 and R 73 , said R 75 and R 77 , said R 76 and R 78 , said R 81 and R 84 , said R 82 and R 83 , and said R 71 and R 74 , each represent an identical substituent, and said Y and Z represent an identical substituent or a single bond.

6. The method according to claim 1 , wherein said R 71 , R 72 , R 73 , R 74 , R 81 , R 82 , R 83 , and R 84 are a methyl group, and said R 75 , R 76 , R 77 and R 78 are a hydrogen atom, and said Y and Z are a single bond.

7. A gel particle, obtained by the method according to claim 1 .

8. A method for producing a linear polymer having at least one positively charged end, comprising conducting a radical polymerization reaction using a cationic polymerization initiator having a chemical structure represented by general formula (I):

wherein
Y represents a single bond or CHR 85 ,
Z represents a single bond or CHR 86 ,
R 72 , R 73 , R 75 , R 76 , R 77 , R 78 , R 85 and R 86 are each independently selected from the group consisting of hydrogen atom, C 1-6 alkyl group, C 1-6 alkoxy group, C 1-6 alkylcarbonyl group, phenyl group and hydroxyl group, wherein said C 1-6 alkyl group, C 1-6 alkoxy group, C 1-6 alkylcarbonyl group and phenyl group are optionally substituted with 1 or 2 substituents selected from the group consisting of C 1-6 alkyl group, C 1-6 alkoxy group, C 1-6 alkylcarbonyl group, phenyl group and hydroxyl group,
R 72 and R 73 optionally each independently represent adamantyl group or C 1-6 alkyl group substituted with Si(OCH 3 ) 2 (CH 3 ), or
R 75 and R 76 or R 77 and R 78 together optionally form —(CH 2 ) 3-5 —,
R 81 , R 82 , R 83 and R 84 are each independently a substituent selected from the group consisting of C 1-4 alkyl group, C 1-4 alkylcarbonyl group and C 1-3 alkoxy group, wherein the C 1-4 alkyl is optionally substituted with one C 1-3 alkoxy group; and
R 71 and R 74 each independently are C 1-3 alkyl group, and
X f − is counter anion,

and a monomer comprising a carbon-carbon double bond.

9. A linear polymer having at least one positively charged end, obtained by the method according to claim 8 .

10. A linear polymer having at least one positively charged end, comprising a structure derived from a cationic polymerization initiator represented by formula (I′):

wherein
Y represents a single bond or CHR 85 ,
R 72 , R 75 , R 76 and R 85 are each independently selected from the group consisting of hydrogen atom, C 1-6 alkyl group, C 1-6 alkoxy group, C 1-6 alkylcarbonyl group, phenyl group and hydroxyl group, wherein said C 1-6 alkyl group, C 1-6 alkoxy group, C 1-6 alkylcarbonyl group and phenyl group are optionally substituted with 1 or 2 substituents selected from the group consisting of C 1-6 alkyl group, C 1-6 alkoxy group, C 1-6 alkylcarbonyl group, phenyl group and hydroxyl group,
R 72 optionally represents adamantyl group or C 1-6 alkyl group substituted with Si(OCH 3 ) 2 (CH 3 ), or
R 75 and R 76 together optionally form —(CH 2 ) 3-5 —,
R 81 and R 82 are each independently a substituent selected from the group consisting of C 1-4 alkyl group, C 1-4 alkylcarbonyl group and C 1-3 alkoxy group, wherein the C 1-4 alkyl is optionally substituted with one C 1-3 alkoxy group; and
R 71 is C 1-3 alkyl group, and
the asterisk * is a position at which the structure represented by formula (I′) bind to a main chain,

on at least one end of a main chain, and subsequent repeat structures derived from a monomer comprising a carbon-carbon double bond.

11. A copolymer, comprising a structure derived from a cationic polymerization initiator represented by formula (I′):

wherein
Y represents a single bond or CHR 85 ,
R 72 , R 75 , R 76 and R 85 are each independently selected from the group consisting of hydrogen atom, C 1-6 alkyl group, C 1-6 alkoxy group, C 1-6 alkylcarbonyl group, phenyl group and hydroxyl group, wherein said C 1-6 alkyl group, C 1-6 alkoxy group, C 1-6 alkylcarbonyl group and phenyl group are optionally substituted with 1 or 2 substituents selected from the group consisting of C 1-6 alkyl group, C 1-6 alkoxy group, C 1-6 alkylcarbonyl group, phenyl group and hydroxyl group,
R 72 optionally represents adamantyl group or C 1-6 alkyl group substituted with Si(OCH 3 ) 2 (CH 3 ), or
R 75 and R 76 together optionally form —(CH 2 ) 3-5 —,
R 81 and R 82 are each independently a substituent selected from the group consisting of C 1-4 alkyl group, C 1-4 alkylcarbonyl group and C 1-3 alkoxy group, wherein the C 1-4 alkyl is optionally substituted with one C 1-3 alkoxy group; and
R 71 is C 1-3 alkyl group, and
the asterisk * is a position at which the structure represented by formula (I′) bind to a main chain,

on at least one end of a main chain,
subsequent repeat structures each derived from the corresponding monomers represented by formula (a) and formula (b):

wherein
R 1 is selected from the group consisting of hydrogen atom and C 1-3 alkyl group;
R 4 and R 5 are independently selected from the group consisting of hydrogen atom and C 1-20 alkyl group, wherein the alkyl group is optionally substituted with one or more subs

Assignees

• Kirin Holdings Kk
• Univ Tokyo
• Univ Tohoku

Inventors

• Tsuji Toshikazu
• Ikado Kumiko
• Yamada Sayuri
• Uchiyama Seiichi
• Kawamoto Kyoko
• Tokuyama Hidetoshi
• Okano Kentaro

Classifications

• C08F4/04

  Azo-compounds · CPC title

• G01N33/582

  with fluorescent label · CPC title

• A61K9/5138 Primary

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates · CPC title

• C12Q1/02

  involving viable microorganisms · CPC title

• C07D233/24 Primary

  Radicals substituted by nitrogen atoms not forming part of a nitro radical · CPC title