Triblock copolymer and use therefor

Patent metadata

Field	Value
Publication number	US-9849186-B2
Application number	US-201314374015-A
Country	US
Kind code	B2
Filing date	Jan 24, 2013
Priority date	Jan 24, 2012
Publication date	Dec 26, 2017
Grant date	Dec 26, 2017

Abstract

Provided is a triblock copolymer represented by General Formula (I):

CNR-PEG-CNR  (1)

or a polycation thereof, wherein
each CNR is independently a polymer segment having a repeating unit containing as part of a pendant group a cyclic nitroxide radical that binds to the polymer main chain via a linking group having at least one imino group or ether bond, and PEG is a segment containing poly(ethylene glycol).

First claim

The invention claimed is:

1. A composition comprising:
a polyion complex comprising a polyanion selected from the group consisting of poly(acrylic acid), poly(methacrylic acid), poly(sulfonic acid), DNA, RNA and anionic proteins, and a triblock copolymer or salt thereof of following formula:

wherein each L 1 is independently selected from the group consisting of a single bond, —S—(CH 2 ) c —, —S—(CH 2 ) c CO—, —(CH 2 ) c S— and —CO(CH 2 ) c S—, in which c is an integer from 1 to 5; each L 2 is independently —C 1-6 alkylene-NH—(C 1-6 alkylene) q -, in which q is the integer 0 or 1; and at least 50% of the total number n of R in the formula independently represent residues of cyclic nitroxide radical compounds selected from the group consisting of 2,2,6,6-tetramethylpiperidine-1-oxyl-4-yl, 2,2,5,5-tetramethylpyrrolidine-1-oxyl-3-yl, 2,2,5,5-tetramethylpyrroline-1-oxyl-3-yl, 2,4,4-trimethyl-1,3-oxyazolidine-3-oxyl-2-yl, 2,4,4-trimethyl-1,3-thiazolidine-3-oxyl-2-yl and 2,4,4-trimethyl-imidozolidine-3-oxyl-2-yl, with other R if any representing hydrogen atoms, halogen atoms or hydroxy groups, and m is an integer from 20 to 5,000 while each n is independently an integer from 3 to 1,000,
wherein the polyion complex is in the form of a polyion complex micelle in Na 2 HPO 4 buffer (0.1M) at pH 6.28,
wherein said composition forms a gel when injected into a living body and said gel is retained in a specific area of the body selected from the group consisting of a periodontal pocket, a cancer lesion and a site affected by arthritis; and wherein the composition further provides at least one property selected from the group consisting of suppressing inflammation, scavenging active oxygen, and regulating fluidity.

2. A method for suppressing inflammation, comprising administering the composition according to claim 1 to a patient requiring elimination of active oxygen.

3. The composition according to claim 1 , further comprising a physiologically acceptable diluent or excipient.

4. The composition according to claim 1 , wherein the polyanion is selected from the group consisting of poly(acrylic acid), poly(methacrylic acid), and poly(sulfonic acid).

5. The composition according to claim 1 , wherein in the triblock copolymer m is an integer from 20 to 1,000.

6. The composition according to claim 1 , wherein in the triblock copolymer m is an integer from 50 to 200.

7. The composition according to claim 1 , wherein in the triblock copolymer each n is independently an integer from 3 to 100.

8. The composition according to claim 1 , wherein in the triblock copolymer each n is independently an integer from 3 to 50.

9. The composition according to claim 1 , wherein in the triblock copolymer R is selected from the groups represented by the following formulae:

in which R′ is a methyl group, and groups represented by these formulae constitute at least 80% of the total number n of R.

Assignees

• Univ Tsukuba

Inventors

• Nagasaki Yukio
• Pua Min Ley
• Chonpathompikunlert Pennapa
• Yoshitomi Toru

Classifications

• A61P39/06

  Free radical scavengers or antioxidants · CPC title

• C08F2810/40

  taking place solely at one end or both ends of the polymer backbone, i.e. not in the side or lateral chains · CPC title

• A61P1/02

  Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis · CPC title

• A61K47/58 Primary

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title