# US 10,946,028 B2 · Polymer conjugate of sulfoxide derivative-coordinated platinum(II) complex

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- Number: US 10,946,028 B2
- Document ID: US10946028B2
- Status: Granted
- Kind: B2
- Application number: 16/062,212
- Filed: 2016-12-16
- Published: 2018-12-27
- Granted: 2021-03-16
- Earliest claimed: 2015-12-22
- Assignees: Nippon Kayaku Kabushiki Kaisha
- Applicants: Nippon Kayaku Kabushiki Kaisha
- Inventors: Masaharu Nakamura; Tsuyoshi Fukuda; Ken Yamakawa; Takuya Kato
- Web page: https://patentgrep.com/patent/US10946028B2

## CPC

- A61K 31/555: containing heavy metals, e.g. hemin, hematin, melarsoprol
- A61K 31/282: Platinum compounds
- A61K 47/541: {Organic ions forming an ion pair complex with the pharmacologically or therapeutically active agent}
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- A61K 47/62: the modifying agent being a protein, peptide or polyamino acid
- A61K 47/645: {Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT}
- A61P 35/00: Antineoplastic agents
- C08G 65/3344: {containing oxygen in addition to sulfur}
- C08G 69/08: derived from amino-carboxylic acids
- C08G 69/48: Polymers modified by chemical after-treatment
- C08G 81/00: Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers (involving only carbon-to-carbon unsaturated bond reactions C08F299/00 {; polyester-amides C08G69/44; polyester-imides C08G73/16; polyamides-imides C08G73/14; block- or graft polymers containing polysiloxane sequences C08G77/42})
- C08L 71/02: Polyalkylene oxides
- C08G 2261/126: block
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06)

## Abstract

A DDS preparation of a platinum complex, which exhibits a superior antitumor effect required as a medicine and reduced side effects, that is, a clinically usable DDS preparation of a platinum complex, which is conjugated to a polymer carrier that is different from conventional carriers, is desired. Provided is a polymer conjugate of a platinum(II) complex, the polymer conjugate including: a block copolymer having a polyethylene glycol structural moiety and a polyaspartic acid moiety or a polyglutamic acid moiety; a sulfoxide derivative introduced into a side-chain carboxyl group of the block copolymer; and a platinum(II) complex coordinate-bonded to a sulfoxide group of the sulfoxide derivative.

## Claims

### Claim 1

A polymer conjugate of a platinum(II) complex, the polymer conjugate comprising:
a block copolymer having a polyethylene glycol structural moiety and a polyaspartic acid moiety;
a sulfoxide derivative introduced into a side-chain carboxyl group of the block copolymer; and
a platinum(II) complex coordinate-bonded to a sulfoxide group of the sulfoxide derivative;
wherein the polymer conjugate is represented by the following General Formula (I):
wherein R1 represents a methyl group; R2 represents a trimethylene group; R3 represents an acetyl group; R4 represents a substituent selected from the group consisting of substituents represented by the following Formula (V):
or a substituent selected from the group of substituents represented by the following Formula (VI):
wherein A1, A2, A3 each represent a ligand of the platinum complex and Z− represents a counter anion;
at least one of R4 represents a substituent coordinate-bonded to the platinum complex represented by Formula (VI);
R5 represents a substituent represented by the following General Formula (IV) obtained by eliminating H from an α-amino group of an α-amino acid derivative:
with a benzyl group as Q, or —NR9CONHR10; and R9 and R10 both represent a cyclohexyl group or an isopropyl group;
a represents an integer from 10 to 2,000; d, e, f, g, h, i, and j each represent an integer from 0 to 100; d+e represents an integer from 1 to 100; d+e+f+g+h+i+j represents an integer from 4 to 100; and the order of bonding of the various constituent units of polyaspartic acid is random.

### Claim 2 (depends on 1)

The polymer conjugate of a platinum(II) complex according to claim 1, wherein the ligands A1 and A2 of the platinum complex both represent ammonia or a primary, secondary or tertiary amine, or are bonded together to form a non-cyclic or cyclic diamine optionally having a substituent; and A3 represents a halogen atom, a water molecule, an amine optionally having a substituent, a heteroaryl compound, or a sulfoxide compound.

### Claim 3 (depends on 2)

The polymer conjugate of a platinum(II) complex according to claim 2, wherein the ligands A1 and A2 of the platinum complex both represent ammonia or a ligand selected from the group of ligands represented by the following Formula (XIII):
and A3 represents a chlorine atom.

### Claim 4 (depends on 1)

A medicine comprising the polymer conjugate of a platinum(II) complex according to claim 1 as an active ingredient.

### Claim 5 (depends on 1)

An antitumor agent comprising the polymer conjugate of a platinum(II) complex according to claim 1 as an active ingredient.