# US 2013/0253136 A1 · Biodegradable particles, vascular occlusion material, and method for producing biodegradable particles

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- Number: US 2013/0253136 A1
- Document ID: US20130253136A1
- Status: Published application
- Kind: A1
- Application number: 13/991,495
- Filed: 2011-12-09
- Published: 2013-09-26
- Earliest claimed: 2010-12-09
- Assignees: Toray Industries, Inc.
- Inventors: Kazuhiro Tanahashi; Megumi Nakanishi; Yasufumi Yamamura; Masaki Fujita
- Web page: https://patentgrep.com/patent/US20130253136A1

## CPC

- C08G 65/00: Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- A61L 24/0031: {Hydrogels or hydrocolloids}
- A61L 24/0042: {Materials resorbable by the body}
- A61L 24/046: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds (A61L24/043 takes precedence)}
- A61L 31/14: Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials}
- A61L 31/148: {Materials at least partially resorbable by the body}
- C08G 65/332: containing carboxyl groups, or halides, or esters thereof
- C08G 65/3322: {acyclic}
- C08J 3/12: Powdering or granulating
- C08J 3/24: Crosslinking, e.g. vulcanising, of macromolecules (mechanical aspects B29C35/00; crosslinking agents C08K)
- A61L 2300/60: characterised by a special physical form
- A61L 2430/36: for embolization or occlusion, e.g. vaso-occlusive compositions or devices
- C08G 2650/30: branched
- C08J 2300/16: Biodegradable polymers
- C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- C08J: WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H (working, e.g. shaping, of plastics B29)

## Abstract

Spherical biodegradable particles have improved flexibility, cause less aggregation among particles, and have improved particle shape-recovering ability after passing through a catheter or the like. The biodegradable particles include a synthetic polymer chemically cross-linked to a polyvalent carboxylic acid, the biodegradable particles having a water content of 20 to 90% in a water-saturated state.

## Claims

### Claim 1

Biodegradable particles comprising a synthetic polymer chemically cross-linked to a polyvalent carboxylic acid, and having a water content of 20 to 90% in a water-saturated state.

### Claim 2 (depends on 1)

The biodegradable particles according to claim 1, whose compression ratio is 15 to 60% and whose recovery ratio is not less than 15% in the water-saturated state.

### Claim 3 (depends on 1)

The biodegradable particles according to claim 1, wherein said synthetic polymer is: a homopolymer or block copolymer of a water-soluble polymer(s) selected from the group consisting of polyethylene glycol, polypropylene glycol, poly-vinyl alcohol, polyacrylic acid, polyhydroxyethylacrylate, polyhydroxyethylmethacrylate, poly-vinylpyrrolidone, carboxymethylcellulose, hydroxymethylcellulose and hydroxyethylcellulose; or a block copolymer of said water-soluble polymer(s) and a monomer(s) selected from the group consisting of α-hydroxy acids, cyclic dimers of α-hydroxy acids, hydroxydicarboxylic acids and cyclic esters.

### Claim 4 (depends on 3)

The biodegradable particles according to claim 3, wherein said water-soluble polymer is a branched polymer in which polyethylene glycol and/or polypropylene glycol is/are bound to all hydroxyl groups in a polyalcohol.

### Claim 5 (depends on 4)

The biodegradable particles according to claim 4, wherein said polyalcohol is selected from the group consisting of glycerin, polyglycerin and pentaerythritol.

### Claim 6 (depends on 1)

The biodegradable particles according to claim 1, wherein said polyvalent carboxylic acid is a dicarboxylic acid selected from the group consisting of oxalic acid, malonic acid, succinic acid, fumaric acid, glutaric acid, adipic acid, pimelic acid, suberic acid and sebacic acid.

### Claim 7 (depends on 4)

The biodegradable particles according to claim 4, wherein said polyvalent carboxylic acid is a polyvalent carboxylic acid in which carboxylic groups are introduced to terminal hydroxyl groups of said branched polymer, or a polyvalent carboxylic acid in which carboxyl groups are introduced to terminal hydroxyl groups of a block copolymer of said branched polymer and a monomer(s) selected from the group consisting of α-hydroxy acids, cyclic dimers of α-hydroxy acids, hydroxydicarboxylic acids and cyclic esters.

### Claim 8 (depends on 1)

A vascular embolization material composed of the biodegradable particles according to claim 1.

### Claim 9

A method of producing biodegradable particles comprising:
a dissolving step wherein a synthetic polymer, polyvalent carboxylic acid and condensing agent are dissolved in an aprotic polar organic solvent having a dielectric constant of 35 to 50, to obtain Solution A;
a droplet-forming step wherein said Solution A is added dropwise to a poor solvent for said aprotic polar organic solvent, to obtain droplets of Solution A; and
a chemical cross-linking step wherein a chemical cross-linking reaction of said synthetic polymer is allowed to proceed in said droplets, to obtain biodegradable particles.

### Claim 10 (depends on 9)

The method according to claim 9, wherein said synthetic polymer is:
a homopolymer or block copolymer of a water-soluble polymer(s) selected from the group consisting of polyethylene glycol, polypropylene glycol, polyvinyl alcohol, polyacrylic acid, polyhydroxyethylacrylate, polyhydroxyethylmethacrylate, polyvinylpyrrolidone, carboxymethylcellulose, hydroxymethylcellulose and hydroxyethylcellulose; or
a block copolymer of said water-soluble polymer(s) and a monomer(s) selected from the group consisting of α-hydroxy acids, cyclic dimers of α-hydroxy acids, hydroxydicarboxylic acids and cyclic esters.

### Claim 11 (depends on 9)

The method according to claim 9, wherein said condensing agent is a water-soluble carbodiimide.

### Claim 12 (depends on 9)

The method according to claim 9, wherein said aprotic polar organic solvent is selected from the group consisting of N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile and dimethylsulfoxide.

### Claim 13 (depends on 9)

The method according to claim 9, wherein said poor solvent comprises a natural oil selected from the group consisting of cottonseed oil, corn oil, coconut oil, olive oil, palm oil, rapeseed oil, safflower oil, sesame oil, soybean oil, sunflower oil, turpentine oil, almond oil, avocado oil, bergamot oil, castor oil, cedar wood oil, chlorophyll oil, clove oil, croton oil, eucalyptus oil, fennel oil, fusel oil, grape seed oil, jojoba oil, candlenut oil, lavender oil, lemon oil, linseed oil, macadamia nut oil, meadowfoam oil, orange oil, origanum oil, persic oil and rose hip oil.

### Claim 14

Biodegradable particles produced by:
dissolving a synthetic polymer, polyvalent carboxylic acid and condensing agent in an aprotic organic solvent having a dielectric constant of 35 to 50;
adding the obtained solution dropwise to a poor solvent for said aprotic polar organic solvent; and
causing a chemical cross-linking reaction to proceed in the obtained droplets.

### Claim 15 (depends on 2)

The biodegradable particles according to claim 2, wherein said synthetic polymer is: a homopolymer or block copolymer of a water-soluble polymer(s) selected from the group consisting of polyethylene glycol, polypropylene glycol, polyvinyl alcohol, polyacrylic acid, polyhydroxyethylacrylate, polyhydroxyethylmethacrylate, polyvinylpyrrolidone, carboxy-methylcellulose, hydroxymethylcellulose and hydroxyethylcellulose; or a block copolymer of said water-soluble polymer(s) and a monomer(s) selected from the group consisting of α-hydroxy acids, cyclic dimers of α-hydroxy acids, hydroxydicarboxylic acids and cyclic esters.

### Claim 16 (depends on 5)

The biodegradable particles according to claim 5, wherein said polyvalent carboxylic acid is a polyvalent carboxylic acid in which carboxylic groups are introduced to terminal hydroxyl groups of said branched polymer, or a polyvalent carboxylic acid in which carboxyl groups are introduced to terminal hydroxyl groups of a block copolymer of said branched polymer and a monomer(s) selected from the group consisting of α-hydroxy acids, cyclic dimers of α-hydroxy acids, hydroxydicarboxylic acids and cyclic esters.

### Claim 17 (depends on 6)

The biodegradable particles according to claim 6, wherein said polyvalent carboxylic acid is a polyvalent carboxylic acid in which carboxylic groups are introduced to terminal hydroxyl groups of said branched polymer, or a polyvalent carboxylic acid in which carboxyl groups are introduced to terminal hydroxyl groups of a block copolymer of said branched polymer and a monomer(s) selected from the group consisting of α-hydroxy acids, cyclic dimers of α-hydroxy acids, hydroxydicarboxylic acids and cyclic esters.

### Claim 18 (depends on 10)

The method according to claim 10, wherein said condensing agent is a water-soluble carbodiimide.

### Claim 19 (depends on 10)

The method according to claim 10, wherein said aprotic polar organic solvent is selected from the group consisting of N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile and dimethylsulfoxide.

### Claim 20 (depends on 11)

The method according to claim 11, wherein said aprotic polar organic solvent is selected from the group consisting of N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile and dimethylsulfoxide.