Embolization

• US 7,588,780 B2
• Filed: 08/09/2002
• Issued: 09/15/2009
• Est. Priority Date: 03/29/2002
• Status: Active Grant

• Current Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Original Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Inventors: Knapp, David, Bellisario, Marc, Lanphere, Janel, Buiser, Marcia, Mangin, Stephan
• Primary Examiner(s): Azpuru; Carlos A.
• Application Number:
  US10/215,594
• Publication Number:
  US 20030185896A1
• Time in Patent Office: 2,594 Days
• Field of Search: 424/489, 424/501, 264/4.1, 264/4.33, 264/4.7, 427/213.34, 428/402.21
• US Class Current: 424/501
• CPC Class Codes: A61F 2/0036 implantable A61F2/0018 takes precedence
• CPC Class Codes: A61K 49/0452 Solutions, e.g. for injection
• 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: A61L 24/001 Use of materials characterised by their function or physical properties
• CPC Class Codes: A61L 24/0036 Porous materials, e.g. foams or sponges
• 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 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 31/048 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: B29B 2009/125 Micropellets, microgranules, microparticles
• CPC Class Codes: B29B 2009/166 Deforming granules to give a special form, e.g. spheroidizing, rounding
• CPC Class Codes: B29B 9/16 Auxiliary treatment of granules
• CPC Class Codes: C08J 2329/04 Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
• CPC Class Codes: C08J 3/12 Powdering or granulating
• CPC Class Codes: C08J 3/24 Crosslinking, e.g. vulcanising, of macromolecules mechanical aspects B29C35/00; crosslinking agents C08K
• CPC Class Codes: C08L 29/04 Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
• CPC Class Codes: Y10T 428/2985 Solid-walled microcapsule from synthetic polymer

Abstract

Embolic polymer particles are described. For example, the particles include pores such that the predominant size of pores near the center of the particles is greater than the predominant size of pores adjacent to periphery of the particle

Claims

1. An embolic composition, comprising:

substantially spherical embolic particles having a diameter of about 1500 micron or less, the particles comprising polyvinyl alcohol, and including a first region including pores having a first predominant pore size and a second region surrounding the first region and including pores having a second predominant pore size,

wherein the first predominant pore size is larger than the second predominant pore size.

2. The composition of claim 1 wherein the first predominant pore size is about 20 micron or more.

3. The composition of claim 1 wherein the first predominant pore size is about 30 micron or more.

4. The composition of claim 1 wherein the second region is about r to 0.8r, and r is a radius of the particles.

5. The composition of claim 1 wherein the second region is about r to 2r/3, and r is a radius of the particles.

6. The composition of claim 5 including a third region from about 2r/3 to r/3 and including pores having a third predominant pore size,

wherein the third predominant pore size is larger than the second predominant pore size and smaller than the first predominant pore size.

7. The composition of claim 6, wherein the first region is from about r/3 to C, and C is a center of the particles.

8. The composition of claim 7 wherein the first predominant pore size is about 20 micron or more.

9. The composition of claim 8 wherein the third predominant pore size is from about 2 to about 18 microns.

10. The composition of claim 1 wherein the second region is substantially free of pores greater than about 5 micron.

11. The composition of claim 1 wherein the predominant pore size generally, progressively increases from surface to the center of the particle.

12. The composition of claim 1 wherein the predominant pore size on the particle surface is about 1 micron or less.

13. The composition of claim 5, wherein the second predominant pore size is about 1 micron or less.

14. The composition of claim 13 wherein the second predominant pore size is about 0.1 micron or less.

15. The composition of claim 13 wherein the particles, interior of said second region, have a predominant pore size in the range of about 2 to 35 microns.

16. The composition of claim 14 wherein the first region is from about C to r/3 and the first predominant pore size is about 20 to 35 micron, and r is a radius of the particles.

17. The composition of claim 15 wherein the particles have a third region from r/3 to (2r)/3 and including pores having a third predominant pore size, in which the third predominant pore size is about 2 to 18 micron.

18. The composition of claim 1 wherein the second region is from about (2r)/3 to the surface and the second predominant pore size is about 10% or less than the first predominant pore size, and r is a radius of the particles.

19. The composition of claim 1 wherein the particles have a density of about 1.1 to about 1.4 g/cm³.

20. The composition of claim 1 wherein the particles have a density of about 1.2 to 1.3 g/cm³.

21. The composition of claim 1 wherein the embolic particles have a sphericity of about 90% or more.

22. The composition of claim 21 wherein the particles have an initial sphericity of about 97% or more.

23. The composition of claim 22 wherein the particles have a sphericity of about 0.90 after compression to about 50%.

24. The composition of claim 1 wherein the collection has a size uniformity of about ±

15% or more.

25. The composition of claim 1 wherein the particles include about 1% or less polysaccharide.

26. The composition of claim 25 wherein the polysaccharide is alginate.

27. The composition of claim 26 wherein the alginate has a guluronic acid content of about 60% or greater.

28. The composition of claim 1 wherein the embolic particles are substantially insoluble in DMSO.

29. The composition of claim 1 wherein the embolic particles are substantially free of collagen.

30. The composition of claim 1 wherein the polyvinyl alcohol is composed of substantially unmodified polyvinyl alcohol prepolymer.

31. The composition of claim 1 wherein the polyvinyl alcohol is predominantly intrachain 1,3-diols acetalized.

32. The composition of claim 1 wherein the particles are suspended in a pharmaceutically acceptable medium.

33. The composition of claim 32 wherein the pharmaceutically acceptable medium comprises saline.

48. The composition of claim 6, wherein the third predominant pore size is between 50% and 70% of the first predominant pore size.

34. A method comprising administering to a patient in need of embolization a therapeutically effective amount of substantially spherical embolic polymer particles having a diameter of 1500 microns or less, the particles comprising polyvinyl alcohol, and including a first region including pores having a first predominant pore size and a second region surrounding the first region and including pores having a second predominant pore size,

wherein the first predominant pore size is larger than the second predominant pore size.

35. The method of claim 34 wherein the method of administration is by percutaneous injection.

36. The method of claim 34 wherein the method of administration is by a catheter.

37. The method of claim 34 wherein the particles are compressible, and are introduced to the body through a lumen, of a medical device, the lumen having a smaller diameter than the diameter of the uncompressed particles.

38. The method of claim 34 for treatment of uterine fibroids.

39. The method of claim 34 for treatment of a tumor.

40. The method of claim 34 for treatment of arteriovenous tumors.

41. An embolic composition, comprising:

embolic polymer particles having a diameter of about 1500 micron or less, and including a surface including pores with a predominant pore size of about 2 micron or less and pores interior to said surface with a predominant pore size of about 10 micron or more.

42. The composition of claim 41 wherein the particles include a surface region from about 0.8r to r wherein the predominate pore size is about 1 micron or less, and r is a radius of the particles.

43. The composition of claim 42 wherein particles include a region from about C to 0.8r which includes pores having a diameter of 10 microns or more.

44. The composition of claim 42 wherein the region C to 0.8r has a predominant pore size of about 3.5 to 2 micron.

45. An embolic composition comprising:

embolic polymer particles having a diameter of about 1500 microns or less, and including a surface region from about 0.8r to r, the predominant pore size in the surface region being smaller than the predominant pore size in a region C to 0.3r, and r is a radius of the particles.

47. The composition of claim 45 or 46 wherein the embolic particles are substantially spherical.

46. An embolic composition, comprising:

embolic particles having a diameter of about 1500 microns or less, and including a surface region defined primarily by surface region pores and an interior region defined primarily by interior region pores, wherein the surface region pores are smaller than the interior region pores.