Embolization

• US 7,736,671 B2
• Filed: 03/02/2004
• Issued: 06/15/2010
• Est. Priority Date: 03/02/2004
• Status: Active Grant

• Current Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Original Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Inventors: Casey, Thomas V. II, DiCarlo, Paul, Mangin, Stephan P.
• Primary Examiner(s): PRYOR, ALTON NATHANIEL
• Application Number:
  US10/791,552
• Publication Number:
  US 20050196449A1
• Time in Patent Office: 2,296 Days
• Field of Search: 424/489
• US Class Current: 424/489
• CPC Class Codes: A61B 17/12022 Occluding by internal devices, e.g. balloons or releasable wires plugging an opening in the wall of an organ A61B17/0057; occluders for the cervical canal A61F6/146; vas deferens occluders A61F6/20
• CPC Class Codes: A61B 17/12031 complete occlusion
• CPC Class Codes: A61B 17/12036 partial occlusion
• CPC Class Codes: A61B 17/12186 liquid materials adapted to be injected
• CPC Class Codes: A61B 17/42 Gynaecological or obstetrical instruments or methods ligaturing clamps or clips for the umbilical cord A61B17/122; curettage A61B17/320708; dilators A61M29/00
• CPC Class Codes: A61B 2017/1205 Introduction devices
• CPC Class Codes: A61K 9/0019 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 Class Codes: A61K 9/167 with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface with further drug-free outer coating A61K9/5073
• CPC Class Codes: A61L 2300/62 Encapsulated active agents, e.g. emulsified droplets
• CPC Class Codes: A61L 24/0015 Medicaments; Biocides
• CPC Class Codes: A61L 24/0036 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 24/046 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043 takes 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 31/04 Macromolecular materials
• CPC Class Codes: A61L 31/14 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: Y10T 428/2982 Particulate matter [e.g., sphere, flake, etc.]
• CPC Class Codes: Y10T 428/2998 including synthetic resin or polymer

Abstract

Embolization, as well as related particles, compositions, and methods, are disclosed.

Claims

1. A composition, comprising:

a plurality of particles, at least some of the plurality of particles having a diameter of from about 100 microns to about 3,000 microns, wherein the at least some of the particles having a diameter of from about 100 microns to about 3,000 microns comprise a polymer and have an interior region and a surface region, a weight percent of the polymer in the interior region being less than a weight percent of the polymer at the surface region;

wherein the polymer has the formula D-B-[O-(A-O)_n-B]_m-D, in which O is a first oligomeric segment, B is a first coupling segment, A is a second coupling segment, D is a polyfluoro oligomeric group, m is from one to 20, and n is from zero to 20; and

a carrier fluid, the plurality of particles being in the carrier fluid, wherein the carrier fluid comprises a component selected from the group consisting of a saline solution, a contrast agent, and a surfactant.

2. The composition of claim 1, wherein the carrier fluid comprises the saline solution.

3. The composition of claim 1, wherein the carrier fluid comprises the contrast agent.

4. The composition of claim 1, wherein the carrier fluid comprises the surfactant.

5. The composition of claim 1, wherein the interior region is devoid of the polymer.

6. The composition of claim 1, wherein the interior region comprises at most 50 weight percent of the polymer.

7. The composition of claim 6, wherein the plurality of particles comprise from about 0.1 weight percent to about 90 weight percent of the polymer.

8. The composition of claim 1, wherein the interior region comprises at least 0.1 weight percent of the polymer.

9. The composition of claim 1, wherein the surface region comprises at least 0.1 weight percent of the polymer.

10. The composition of claim 1, wherein the plurality of particles comprise from about 0.1 weight percent to about 90 weight percent of the polymer.

11. The composition of claim 1, wherein the surface region comprises at most 100 weight percent of the polymer.

12. The composition of claim 1, wherein the difference between the weight percent of the polymer in the interior region and the weight percent of the polymer at the surface region is at least 30 weight percent.

13. The composition of claim 1, wherein the plurality of particles have a diameter of at most 2,500 microns.

14. The composition of claim 1, wherein the polymer comprises a backbone and side groups that are more polar than the backbone.

15. The composition of claim 1, wherein the polymer has a molecular weight of from about 500 to about 15,000.

16. The composition of claim 1, wherein the polymer is linear.

17. The composition of claim 1, wherein O comprises a member selected from the group consisting of polyurethanes, polyureas, polyamides, polyalkylene oxides, polycarbonates, polyesters, polylactones, polysilicones, polyethersulfones, polyolefins, polyvinyls, polypeptide polysaccharides, and ether and amine linked segments thereof.

18. The composition of claim 17, wherein A comprises a member selected from the group consisting of diamines, diisocyanates, disulfonic acids, dicarboxylic acids, diacid chlorides, and dialdehydes.

19. The composition of claim 1, wherein B comprises a member selected from the group consisting of diamines, diisocyanates, disulfonic acids, dicarboxylic acids, diacid chlorides, and dialdehydes.

20. The composition of claim 19, wherein B further comprises a functional group selected from the group consisting of esters, carboxylic acid salts, sulfonic acid salts, phosphonic acid salts, thiols, vinyls, and secondary amines.

21. The composition of claim 1, wherein D comprises CF₃(CF₂)_pCH₂CH₂—

, wherein p is from two to 20.

22. The composition of claim 1, wherein D comprises CF₃(CF₂)_m(CH₂CH₂O)_q—

, wherein m is from one to 20 and q is from one to ten.

23. The composition of claim 22, wherein the plurality of particles further comprise a therapeutic agent.

24. The composition of claim 1, wherein the plurality of particles further comprise a therapeutic agent.

25. The composition of claim 1, wherein the plurality of particles further comprise an additional polymer.

26. The composition of claim 25, wherein the additional polymer comprises a member selected from the group consisting of polyvinyl alcohols, polyacrylic acids, polymethacrylic acids, poly vinyl sulfonates, carboxymethyl celluloses, hydroxyethyl celluloses, celluloses, polyacrylamides, polyethylene glycols, polyamides, polyureas, polyurethanes, polyesters, polyethers, polystyrenes, polysaccharides, polylactic acids, polyethylenes, polymethylmethacrylates, polycaprolactones, polyglycolic acids, poly(lactic-co-glycolic) acids, and combinations thereof.

27. The composition of claim 25,

wherein the additional polymer comprises a member selected from the group consisting of polyvinyl alcohols, polyacrylic acids, polymethacrylic acids, poly vinyl sulfonates, carboxymethyl celluloses, hydroxyethyl celluloses, celluloses, polyacrylamides, polyethylene glycols, polyamides, polyureas, polyurethanes, polyesters, polyethers, polystyrenes, polysaccharides, polylactic acids, polyethylenes, polymethylmethacrylates, polycaprolactones, polyglycolic acids, poly(lactic-co-glycolic) acids, and combinations thereof;

wherein O comprises a member selected from the group consisting of polyurethanes, polyureas, polyamides, polyalkylene oxides, polycarbonates, polyesters, polylactones, polysilicones, polyethersulfones, polyolefins, polyvinyls, polypeptide polysaccharides, and ether and amine linked segments thereof;

wherein A comprises a member selected from the group consisting of diamines, diisocyanates, disulfonic acids, dicarboxylic acids, diacid chlorides, and dialdehydes;

wherein B comprises a member selected from the group consisting of diamines, diisocyanates, disulfonic acids, dicarboxylic acids, diacid chlorides, and dialdehydes; and

wherein D is selected from the group consisting of CF₃(CF₂)_pCH₂CH₂— and

CF₃(CF₂)_m(CH₂CH₂O)_q—

, wherein p is from 2 to 20, m is from 1 to 20 and q is from 1 to 10.

28. The composition of claim 25, wherein the plurality of particles further comprise a therapeutic agent.

29. The composition of claim 28, wherein the therapeutic agent is bound to the polymer.

30. The composition of claim 1, wherein the plurality of particles further comprise a polysaccharide.

31. The composition of claim 1, wherein the plurality of particles are spherical.

32. The composition of claim 1, wherein the plurality of particles further comprise a coating disposed over the surface region.

33. The composition of claim 32, wherein the coating is bioabsorbable.

34. The composition of claim 1, wherein the plurality of particles comprise from about 0.25 weight percent to about 50 weight percent of the polymer.

35. The composition of claim 1, wherein the plurality of particles comprise from about 15 weight percent to about 35 weight percent of the polymer.

36. The composition of claim 1, wherein the interior region has a density of large pores and the surface region has a density of large pores, and the density of large pores of the interior region is greater than the density of large pores at the surface region.

37. A composition, comprising:

a plurality of particles, at least some of the plurality of particles having a diameter of from about ten microns to about 3,000 microns, wherein, the at least some of the particles comprise a polymer, the at least some of the particles have a center and a radius r, the at least some of the particles have an interior region extending from the center of the particles to 2r/3, the at least some of the particles have a surface region extending from 2r/3 to r, a weight percent of the polymer in the interior region being less than a weight percent of the polymer at the surface region; and

the interior region comprising an additional polymer in a greater amount than in the surface region, the additional polymer being different from the polymer;

wherein the polymer has the formula D-B-[O-(A-O)_n-B]_m-D, in which O is a first oligomeric segment, B is a first coupling segment, A is a second coupling segment, D is a polyfluoro oligomeric group, m is from one to 20, and n is from zero to 20; and

a carrier fluid, the plurality of particles being in the carrier fluid, wherein the carrier fluid comprises a component selected from the group consisting of a saline solution, a contrast agent, and a surfactant,

wherein the interior region comprises at most 50 weight percent of the polymer.

38. The composition of claim 37, wherein the plurality of particles comprise from 0.1 weight percent to 90 weight percent of the polymer.

39. A composition, comprising:

a plurality of particles, at least some of the plurality of particles having a diameter of from about ten microns to about 3,000 microns, wherein, the at least some of the particles comprise a polymer, the at least some of the particles have a center and a radius r, the at least some of the particles have an interior region extending from the center of the particles to 2r/3, the at least some of the particles have a surface region extending from 2r/3 to r, a weight percent of the polymer in the interior region being less than a weight percent of the polymer at the surface region; and

the interior region comprising an additional polymer in a greater amount than in the surface region, the additional polymer being different from the polymer;

wherein the polymer has the formula D-B-[O-(A-O)_n-B]_m-D, in which O is a first oligomeric segment, B is a first coupling segment, A is a second coupling segment, D is a polyfluoro oligomeric group, m is from one to 20, and n is from zero to 20; and

a carrier fluid, the plurality of particles being in the carrier fluid, wherein the carrier fluid comprises a component selected from the group consisting of a saline solution, a contrast agent, and a surfactant,

wherein the interior region comprises at least 0.1 weight percent of the polymer.

40. A composition, comprising:

a plurality of particles, at least some of the plurality of particles having a diameter of from about ten microns to about 3,000 microns, wherein, the at least some of the particles comprise a polymer, the at least some of the particles have a center and a radius r, the at least some of the particles have an interior region extending from the center of the particles to 2r/3, the at least some of the particles have a surface region extending from 2r/3 to r, a weight percent of the polymer in the interior region being less than a weight percent of the polymer at the surface region; and

the interior region comprising an additional polymer in a greater amount than in the surface region, the additional polymer being different from the polymer;

wherein the polymer has the formula D-B-[O-(A-O)_n-B]_m-D, in which O is a first oligomeric segment, B is a first coupling segment, A is a second coupling segment, D is a polyfluoro oligomeric group, m is from one to 20, and n is from zero to 20; and

a carrier fluid, the plurality of particles being in the carrier fluid, wherein the carrier fluid comprises a component selected from the group consisting of a saline solution, a contrast agent, and a surfactant,

wherein the surface region comprises at least 0.1 weight percent of the polymer.

41. A composition, comprising:

a plurality of particles, at least some of the plurality of particles having a diameter of from about ten microns to about 3,000 microns, wherein, the at least some of the particles comprise a polymer, the at least some of the particles have a center and a radius r, the at least some of the particles have an interior region extending from the center of the particles to 2r/3, the at least some of the particles have a surface region extending from 2r/3 to r, a weight percent of the polymer in the interior region being less than a weight percent of the polymer at the surface region; and

the interior region comprising an additional polymer in a greater amount than in the surface region, the additional polymer being different from the polymer;

wherein the polymer has the formula D-B-[O-(A-O)_n-B]_m-D, in which O is a first oligomeric segment, B is a first coupling segment, A is a second coupling segment, D is a polyfluoro oligomeric group, m is from one to 20, and n is from zero to 20; and

a carrier fluid, the plurality of particles being in the carrier fluid, wherein the carrier fluid comprises a component selected from the group consisting of a saline solution, a contrast agent, and a surfactant.

42. A composition, comprising:

a plurality of particles, at least some of the plurality of particles having a diameter of from about ten microns to about 3,000 microns, wherein, the at least some of the particles comprise a polymer, the at least some of the particles have a center and a radius r, the at least some of the particles have an interior region extending from the center of the particles to 2r/3, the at least some of the particles have a surface region extending from 2r/3 to r, a weight percent of the polymer in the interior region being less than a weight percent of the polymer at the surface region; and

the interior region comprising an additional polymer in a greater amount than in the surface region, the additional polymer being different from the polymer;

wherein the polymer has the formula D-B-[O-(A-O)_nB]_m-D, in which O is a first oligomeric segment, B is a first coupling segment, A is a second coupling segment, D is a polyfluoro oligomeric group, m is from one to 20, and n is from zero to 20; and

a carrier fluid, the plurality of particles being in the carrier fluid, wherein the carrier fluid comprises a component selected from the group consisting of a saline solution, a contrast agent, and a surfactant,

wherein the polymer comprises a backbone and side groups that are more polar than the backbone.

43. A composition, comprising:

a plurality of particles, at least some of the plurality of particles having a diameter of from about ten microns to about 3,000 microns, wherein, the at least some of the particles comprise a polymer, the at least some of the particles have a center and a radius r, the at least some of the particles have an interior region extending from the center of the particles to 2r/3, the at least some of the particles have a surface region extending from 2r/3 to r, a weight percent of the polymer in the interior region being less than a weight percent of the polymer at the surface region; and

the interior region comprising an additional polymer in a greater amount than in the surface region, the additional polymer being different from the polymer;

wherein the polymer has the formula D-B-[O-(A-O)_nB]_m-D, in which O is a first oligomeric segment, B is a first coupling segment, A is a second coupling segment, D is a polyfluoro oligomeric group, m is from one to 20, and n is from zero to 20; and

a carrier fluid, the plurality of particles being in the carrier fluid, wherein the carrier fluid comprises a component selected from the group consisting of a saline solution, a contrast agent, and a surfactant,

wherein the polymer has a molecular weight of from 500 to 15,000.

44. A composition, comprising:

a plurality of particles, at least some of the plurality of particles having a diameter of from about ten microns to about 3,000 microns, wherein, the at least some of the particles comprise a polymer, the at least some of the particles have a center and a radius r, the at least some of the particles have an interior region extending from the center of the particles to 2r/3, the at least some of the particles have a surface region extending from 2r/3 to r, a weight percent of the polymer in the interior region being less than a weight percent of the polymer at the surface region; and

the interior region comprising an additional polymer in a greater amount than in the surface region, the additional polymer being different from the polymer; and

a carrier fluid, the plurality of particles being in the carrier fluid, wherein the carrier fluid comprises a component selected from the group consisting of a saline solution, a contrast agent, and a surfactant,

wherein the polymer has the formula D-B-[O-(A-O)_nB]_m-D, in which O is a first oligomeric segment, B is a first coupling segment, A is a second coupling segment, D is a polyfluoro oligomeric group, m is from one to 20, and n is from zero to 20.

45. The composition of claim 44, wherein O comprises a member selected from the group consisting of polyurethanes, polyureas, polyamides, polyalkylene oxides, polycarbonates, polyesters, polylactones, polysilicones, polyethersulfones, polyolefins, polyvinyls, polypeptide polysaccharides, and ether and amine linked segments thereof.

46. The composition of claim 45, wherein A comprises a member selected from the group consisting of diamines, diisocyanates, disulfonic acids, dicarboxylic acids, diacid chlorides, and dialdehydes.

47. The composition of claim 44, wherein B comprises a member selected from the group consisting of diamines, diisocyanates, disulfonic acids, dicarboxylic acids, diacid chlorides, and dialdehydes.

48. The composition of claim 47, wherein B further comprises a functional group selected from the group consisting of esters, carboxylic acid salts, sulfonic acid salts, phosphonic acid salts, thiols, vinyls, and secondary amines.

49. The composition of claim 44, wherein D comprises CF₃(CF₂)_pCH₂CH₂—

, wherein p is from two to 20.

50. The composition of claim 44, wherein D comprises CF₃(CF₂)_m(CH₂CH₂O)_q—

, wherein m is from one to 20 and q is from one to ten.

51. The composition of claim 50, wherein the plurality of particles further comprise a therapeutic agent.

52. A composition, comprising:

a plurality of particles, at least some of the plurality of particles having a diameter of from about ten microns to about 3,000 microns, wherein, the at least some of the particles comprise a polymer, the at least some of the particles have a center and a radius r, the at least some of the particles have an interior region extending from the center of the particles to 2r/3, the at least some of the particles have a surface region extending from 2r/3 to r, a weight percent of the polymer in the interior region being less than a weight percent of the polymer at the surface region; and

the interior region comprising an additional polymer in a greater amount than in the surface region, the additional polymer being different from the polymer;

wherein the polymer has the formula D-B-[O-(A-O)_nB]_m-D, in which O is a first oligomeric segment, B is a first coupling segment, A is a second coupling segment, D is a polyfluoro oligomeric group, m is from one to 20, and n is from zero to 20; and

a carrier fluid, the plurality of particles being in the carrier fluid, wherein the carrier fluid comprises a component selected from the group consisting of a saline solution, a contrast agent, and a surfactant,

wherein the plurality of particles further comprise a therapeutic agent.

53. The composition of claim 52, wherein the therapeutic agent is bound to the polymer.

54. A composition, comprising:

a plurality of particles, at least some of the plurality of particles having a diameter of from about ten microns to about 3,000 microns, wherein, the at least some of the particles comprise a polymer, the at least some of the particles have a center and a radius r, the at least some of the particles have an interior region extending from the center of the particles to 2r/3, the at least some of the particles have a surface region extending from 2r/3 to r, a weight percent of the polymer in the interior region being less than a weight percent of the polymer at the surface region; and

the interior region comprising an additional polymer in a greater amount than in the surface region, the additional polymer being different from the polymer;

wherein the polymer has the formula D-B-[O-(A-O)_n-B]_m-D, in which O is a first oligomeric segment, B is a first coupling segment, A is a second coupling segment, D is a polyfluoro oligomeric group, m is from one to 20, and n is from zero to 20; and

a carrier fluid, the plurality of particles being in the carrier fluid, wherein the carrier fluid comprises a component selected from the group consisting of a saline solution, a contrast agent, and a surfactant,

wherein the plurality of particles further comprise a polysaccharide.

55. A composition, comprising:

a plurality of particles, at least some of the plurality of particles having a diameter of from about ten microns to about 3,000 microns, wherein, the at least some of the particles comprise a polymer, the at least some of the particles have a center and a radius r, the at least some of the particles have an interior region extending from the center of the particles to 2r/3, the at least some of the particles have a surface region extending from 2r/3 to r, a weight percent of the polymer in the interior region being less than a weight percent of the polymer at the surface region; and

the interior region comprising an additional polymer in a greater amount than in the surface region, the additional polymer being different from the polymer;

wherein the polymer has the formula D-B-[O-(A-O)_n-B]_m-D, in which O is a first oligomeric segment, B is a first coupling segment, A is a second coupling segment, D is a polyfluoro oligomeric group, m is from one to 20, and n is from zero to 20; and

a carrier fluid, the plurality of particles being in the carrier fluid, wherein the carrier fluid comprises a component selected from the group consisting of a saline solution, a contrast agent, and a surfactant,

wherein the plurality of particles are spherical.

56. A composition, comprising:

a plurality of particles, at least some of the plurality of particles having a diameter of from about ten microns to about 3,000 microns, wherein, the at least some of the particles comprise a polymer, the at least some of the particles have a center and a radius r, the at least some of the particles have an interior region extending from the center of the particles to 2r/3, the at least some of the particles have a surface region extending from 2r/3 to r, a weight percent of the polymer in the interior region being less than a weight percent of the polymer at the surface region; and

the interior region comprising an additional polymer in a greater amount than in the surface region, the additional polymer being different from the polymer;

wherein the polymer has the formula D-B-[O-(A-O)_n-B]_m-D, in which O is a first oligomeric segment, B is a first coupling segment, A is a second coupling segment, D is a polyfluoro oligomeric group, m is from one to 20, and n is from zero to 20; and

a carrier fluid, the plurality of particles being in the carrier fluid, wherein the carrier fluid comprises a component selected from the group consisting of a saline solution, a contrast agent, and a surfactant,

wherein the plurality of particles comprise a coating over the surface region.

57. The composition of claim 56, wherein the coating is bioabsorbable.

58. A composition, comprising:

a plurality of particles, at least some of the plurality of particles having a diameter of from about ten microns to about 3,000 microns, wherein, the at least some of the particles comprise a polymer, the at least some of the particles have a center and a radius r, the at least some of the particles have an interior region extending from the center of the particles to 2r/3, the at least some of the particles have a surface region extending from 2r/3 to r, a weight percent of the polymer in the interior region being less than a weight percent of the polymer at the surface region; and

the interior region comprising an additional polymer in a greater amount than in the surface region, the additional polymer being different from the polymer;

wherein the polymer has the formula D-B-[O-(A-O)_n-B]_m-D, in which O is a first oligomeric segment, B is a first coupling segment, A is a second coupling segment, D is a polyfluoro oligomeric group, m is from one to 20, and n is from zero to 20; and

a carrier fluid, the plurality of particles being in the carrier fluid, wherein the carrier fluid comprises a component selected from the group consisting of a saline solution, a contrast agent, and a surfactant,

wherein the interior region has a density of large pores and the surface region has a density of large pores, and the density of large pores of the interior region is greater than the density of large pores at the surface region.