POLYMER PARTICLES

• US 20170283536A1
• Filed: 06/22/2017
• Published: 10/05/2017
• Est. Priority Date: 09/19/2013
• Status: Active Grant

• Current Assignee: Terumo Corporation
• Original Assignee: Terumo Corporation
• Inventors: Cruise, Gregory M., Hincapie, Gloria, Harris, Clayton
• Granted Patent: US 9,938,367 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 9/0029 Parenteral nutrition; Parenteral nutrition compositions as drug carriers
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61L 24/001 Use of materials characterised by their function or physical properties
• CPC Class Codes: A61L 24/06 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043, A61L24/046 take precedence
• CPC Class Codes: A61L 2430/36 for embolization or occlusion, e.g. vaso-occlusive compositions or devices artificial blood vessels A61L27/507
• CPC Class Codes: A61L 31/048 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: C08F 220/38 Esters containing sulfur
• CPC Class Codes: C08F 220/382 and containing oxygen, e.g. 2-sulfoethyl (meth)acrylate
• CPC Class Codes: C08F 220/56 Acrylamide; Methacrylamide
• CPC Class Codes: C08F 222/1006 of polyhydric alcohols or polyhydric phenols
• CPC Class Codes: C08F 222/102 of dialcohols, e.g. ethylene glycol di(meth)acrylate or 1,4-butanediol dimethacrylate
• CPC Class Codes: C08F 222/385 Monomers containing two or more (meth)acrylamide groups, e.g. N,N'-methylenebisacrylamide
• CPC Class Codes: C08F 222/408 substituted imides comprising other heteroatoms
• CPC Class Codes: C08L 2203/02 for biomedical use
• CPC Class Codes: C08L 2312/00 Crosslinking
• CPC Class Codes: C08L 33/02 Homopolymers or copolymers of acids; Metal or ammonium salts thereof
• CPC Class Codes: C08L 33/08 Homopolymers or copolymers of acrylic acid esters
• CPC Class Codes: C08L 33/14 of esters containing halogen, nitrogen, sulfur, or oxygen atoms in addition to the carboxy oxygen
• CPC Class Codes: C08L 33/26 Homopolymers or copolymers of acrylamide or methacrylamide
• CPC Class Codes: Y10T 428/2982 : Particulate matter [e.g., sphere, flake, etc.]

Abstract

Biodegradable, cross-linked polymer particle embolics and methods of making the same are described. The particle embolics can be used as embolization agents.

Claims

1. An embolic system including:

a delivery device; and

an embolic solution including polymer particles, wherein the polymer particles include;

an acrylate, acrylamide, methacrylamide, methyl methacrylate, or a combination thereof, and

a crosslinker,

wherein the polymer particles have a spherical diameter between about 40 μ

m and about 1,200 μ

m.

2. The embolic system of claim 1, wherein the polymer particles are susceptible to degradation through hydrolysis or enzymatic action, and wherein the degradation provides less than about 10% of the polymer particles intact after about 5 days.

3. The embolic system of claim 1, wherein the spherical diameter is between about 75 μ

m and about 1,200 μ

m.

4. The embolic system of claim 1, wherein the crosslinker includes at least two functional groups.

5. The embolic system of claim 1, wherein the crosslinker includes at least one linkage susceptible to degradation through hydrolysis or enzymatic action.

6. The embolic system of claim 1, wherein the crosslinker is bis-glycidyl amino alcohol,

7. The embolic system of claim 5, wherein the at least one linkage is an ester, a thioester, a carbonate, a peptide cleavable by matrix metalloproteinases, a peptide cleavable by matrix collagenases, a peptide cleavable by matrix elastases, a peptide cleavable by matrix cathepsins, or a combination thereof.

8. The embolic system of claim 1, including a second crosslinker including a second linkage selected from an ester, a thioester, a carbonate, a peptide cleavable by matrix metalloproteinases, a peptide cleavable by matrix collagenases, a peptide cleavable by matrix elastases, and a peptide cleavable by matrix cathepsins.

9. The embolic system of claim 1, wherein the crosslinker is bis-glycidyl amino alcohol or bi-functionalized methacryloyl-Ala-Pro-Gly-Leu-AEE-methacrylate.

10. The embolic system of claim 1, wherein the delivery device is a catheter.

11. The embolic system of claim 1, wherein the delivery device is a microcatheter.

12. The embolic system of claim 1, wherein the delivery device is a needle.

13. The embolic system of claim 1, wherein the delivery device and the embolic solution are sterilized.

14. The embolic system of claim 1, wherein the embolic solution includes a monomer including an ionizable functional group.

15. The embolic system of claim 14, wherein the ionizable functional group is basic or acidic.

16. The embolic system of claim 1, wherein the embolic solution includes a radiopaque contrast agent.

17. The embolic system of claim 1, wherein the embolic solution includes a dye.

18. The embolic system of claim 1, wherein the embolic solution is provided in a vial.

19. The embolic system of claim 1, wherein the embolic solution is provided in a syringe.

20. The embolic system of claim 1, wherein the polymer particles have a circularity greater than about 0.9.