Complex, medicine, therapeutic agent for cancer, kit and conjugate

Patent metadata

Field	Value
Publication number	US-2022265836-A1
Application number	US-202017613912-A
Country	US
Kind code	A1
Filing date	May 29, 2020
Priority date	May 29, 2019
Publication date	Aug 25, 2022
Grant date	—

Abstract

A complex is provided comprising a conjugate in which a polymer having a boronic acid group and a compound having a diol structure are bonded, and a substance that is complexed with the conjugate.

First claim

1 . A complex comprising:
a conjugate in which a polymer having a boronic acid group is bonded to a compound having a diol structure; and a substance that is complexed with the conjugate.

2 . The complex according to claim 1 ,
wherein the substance that is complexed with the conjugate is at least one selected from the group consisting of a protein, a virus, an inorganic particle, a nucleic acid, and a small molecule medicine.

3 . The complex according to claim 1 ,
wherein the complex comprises the conjugate in which a polymer having a boronic acid group is bonded to a compound having a diol structure, and a protein.

4 . The complex according to claim 1 ,
wherein the compound having a diol structure is a polyphenol.

5 . The complex according to claim 1 ,
wherein the compound having a diol structure is at least one selected from the group consisting of tannic acid, gallic acid, and derivatives thereof.

6 . The complex according to claim 1 ,
wherein the polymer has two or more boronic acid groups.

7 . The complex according to claim 1 ,
wherein the boronic acid group is a phenylboronic acid group which may have a substituent or a pyridylboronic acid group which may have a substituent.

8 . The complex according to claim 1 ,
wherein the boronic acid group is a phenylboronic acid group represented by General Formula (I) or a pyridylboronic acid group represented by General Formula (II):

(in the formulae, X represents a halogen atom or a nitro group, and n a is an integer of 0 to 4).

9 . The complex according to claim 1 ,
wherein the polymer is at least one biocompatible polymer selected from the group consisting of a polyethylene glycol, an acrylic resin, a polyamino acid, a polyvinylamine, a polyallylamine, a polynucleotide, a polyacrylamide, a polyether, a polyester, a polyurethane, a polysaccharide, and copolymers thereof.

10 . The complex according to claim 1 ,
wherein the polymer having a boronic acid group contains a first biocompatible polymer chain and a second biocompatible polymer chain that is different from the first biocompatible polymer chain.

11 . The complex according to claim 10 ,
wherein the second biocompatible polymer chain is a polyamino acid, and the boronic acid group is introduced into a side chain of the polyamino acid.

12 . The complex according to claim 10 ,
wherein the first biocompatible polymer chain is a polyethylene glycol.

13 . The complex according to claim 10 ,
wherein the polymer having a boronic acid group contains a structure represented by General Formula (1) or (1-1),

(in Formulae (1) and (1-1), A represents the first biocompatible polymer chain; L represents a linker part; and B represents the second biocompatible polymer chain having a boronic acid group and includes a repeating structure represented by the following (b2), or a repeating structure represented by (b1) and the repeating structure represented by (b2)),

(in Formulae (b1) and (b2), R 1 represents an amino acid side chain, R 2 is a structure in which the boronic acid group is introduced into an amino acid side chain, and n represents the total number of (b1) and (b2), n is an integer of 1 to 1,000, m is an integer of 1 to 1,000 (here, m≤n), in a case where n−m is 2 or more, a plurality of R 1 's may be the same or different from each other, and in a case where m is 2 or more, a plurality of R 2 's may be the same or different from each other).

14 . The complex according to claim 1 ,
wherein an average particle diameter of the complex determined by dynamic light scattering (DLS) or fluorescence correlation spectroscopy (FCS) is 5 nm or more and 200 nm or less.

15 . The complex according to claim 1 ,
wherein a number average molecular weight of the polymer having a boronic acid group is 2,000 to 200,000.

16 . A medicine containing:
the complex according to claim 1 as an active ingredient.

17 . A therapeutic agent for cancer, comprising:
the complex according to claim 1 as an active ingredient.

18 . A kit comprising:
a polymer having a boronic acid group; and a compound having a diol structure.

19 . A conjugate in which a polymer having a boronic acid group is bonded to a compound having a diol structure.

Assignees

• Tokyo Inst Tech
• Kawasaki Inst Of Industrial Promotion

Inventors

• Nishiyama Nobuhiro
• Honda Yuto
• Nomoto Takahiro
• Takemoto Hiroyasu
• Matsui Makoto
• Kinoh Hiroaki
• Kataoka Kazunori
• Liu Xueying
• DIRISALA Anjaneyulu

Classifications

• A61K38/1767

  from invertebrates · CPC title

• A61K31/19

  Carboxylic acids, e.g. valproic acid (salicylic acid A61K31/60) · CPC title

• A61K47/60

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title

• A61K47/645

  Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT · CPC title

• A61P35/00 Primary

  Antineoplastic agents · CPC title