Novel high viscosity embolizing compositions comprising prepolymers

• US 20030228273A1
• Filed: 06/06/2002
• Published: 12/11/2003
• Est. Priority Date: 06/06/2002
• Status: Active Grant

• Current Assignee: Covidien LP (Medtronic Plc)
• Original Assignee: Micro Therapeutics, Inc. (Medtronic Plc)
• Inventors: Greff, Richard J.
• Granted Patent: US 7,459,142 B2
• Time in Patent Office: Days
• US Class Current: 424/78.35
• CPC Class Codes: A61K 31/78 of acrylic acid or derivatives thereof
• CPC Class Codes: A61K 31/785 Polymers containing nitrogen
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 49/0409 Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is not a halogenated organic compound
• 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: A61L 24/001 Use of materials characterised by their function or physical properties
• 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: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

Disclosed are novel high viscosity compositions for embolizing blood vessels which comprise a biocompatible prepolymer and a contrast agent, and optionally a thickening agent and/or a biocompatible solvent. Also disclosed are methods for embolizing a vascular site by injecting high viscosity prepolymer compositions into said site. The disclosed compositions and methods are particularly well suited for the treatment of aneurysms.

Claims

1. A composition comprising a biocompatible prepolymer and a biocompatible contrast agent, such that upon delivery of the composition to a vascular site, a solid, coherent mass forms which embolizes said vascular site and wherein the viscosity of said composition is at least about 150 centistokes at 40°

C.

2. The composition according to claim 1, which further comprises a thickening agent.

3. The composition according to claim 1, which further comprises a biocompatible solvent.

4. The composition according to claim 1, which further comprises a thickening agent and a biocompatible solvent.

5. The composition according to any one of claims 1-4, wherein the viscosity of said composition is at least about 200 centistokes at 40°

C.

6. The composition according to any one of claims 1-4, wherein the viscosity of said composition is at least about 500 centistokes at 40°

C.

7. The composition according to any one of claims 1-4, wherein the viscosity of said composition is from about 500 to about 5,000 centistokes at 40°

C.

8. The composition according to claim 1, wherein said biocompatible prepolymer is selected from the group comprising acrylates and silicone prepolymers.

9. The composition according to claim 8, wherein said biocompatible prepolymer is cyanoacrylate.

10. The composition according to claim 1, wherein said biocompatible contrast agent is a water insoluble contrast agent.

11. The composition according to claim 10, wherein said water insoluble contrast agent is selected from the group comprising tantalum, tantalum oxide, tungsten, barium sulfate, gold, and platinum.

12. The composition according to claim 11, wherein said water insoluble contrast agent is tantalum.

13. The composition according to claim 2, wherein said thickening agent is selected from the group comprising polymethyl methacrylate and silica gel.

14. The composition according to claim 13, wherein said thickening agent is polymethyl methacrylate.

15. The composition according to claim 3, wherein said biocompatible solvent is selected from the group comprising ethyl lactate, dimethylsulfoxide, ethanol, acetone, Ethiodol®

, Lipiodol®

, iodinated poppy seed oil, iodinated soy bean oil, water, and hexamethyldisiloxane.

16. The composition according to claim 15, wherein said biocompatible solvent is dimethylsulfoxide.

17. A composition comprising n-butyl cyanoacrylate monomer, tantalum, and Ethiodol®

, such that upon delivery of the composition to a vascular site, a solid, coherent mass forms which embolizes said vascular site and wherein the viscosity of said composition is at least about 150 centistokes at 40°

C.

51. A method for embolizing a vascular site, said method comprising:

(a) selecting the embolic composition of claim 17, wherein said embolic composition has a viscosity of at least 150 centistokes at 40°

C;

(b) transferring the embolic composition to a delivery catheter having a proximal end and a distal end, wherein the distal end of the delivery catheter is positioned at the vascular site to be embolized; and

(c) injecting the heated embolic composition into said vascular site in sufficient amounts to embolize said vascular site.

52. The method according to claim 51, wherein, prior to (b), the embolic composition is heated and mixed to at least 40°

C. to form a uniform suspension.

18. A composition comprising hydroxyethyl methacrylate and tantalum, such that upon delivery of the composition to a vascular site, a solid, coherent mass forms which embolizes said vascular site and wherein the viscosity of said composition is at least about 150 centistokes at 40°

C.

53. A method for embolizing a vascular site, said method comprising:

(a) selecting the embolic composition of claim 18, wherein said embolic composition has a viscosity of at least 150 centistokes at 40°

C.;

(b) transferring the embolic composition to a delivery catheter having a proximal end and a distal end, wherein the distal end of the delivery catheter is positioned at the vascular site to be embolized; and

(c) injecting the heated embolic composition into said vascular site in sufficient amounts to embolize said vascular site.

54. The method according to claim 53, wherein, prior to (b), the embolic composition is heated and mixed to at least 40°

C. to form a uniform suspension.

19. A method for embolizing a vascular site, said method comprising:

(a) selecting an embolic composition comprising a biocompatible prepolymer and a biocompatible contrast agent, wherein said embolic composition has a viscosity of at least 150 centistokes at 40°

C.;

(b) transferring the embolic composition to a delivery catheter having a proximal end and a distal end, wherein the distal end of the delivery catheter is positioned at the vascular site to be embolized; and

(c) injecting the embolic composition into said vascular site in sufficient amounts to embolize said vascular site.

21. The method according to claim 19, wherein the embolic composition further comprises a thickening agent.

23. The method according to claim 19, wherein the embolic composition further comprises a biocompatible solvent.

25. The method according to claim 19, wherein the embolic composition further comprises a thickening agent and a biocompatible solvent.

27. The method according to any one of claims 19-26, wherein the composition transferred is maintained at a temperature above 40°

C.

28. The method according to any one of claims 19-26, wherein, prior to the embolic composition being injected, a blood flow attenuating device is insert immediately upstream the ejection port of said catheter.

29. The method according to claim 28, wherein said blood flow attenuating device is an inflatable microballoon which permits both normal and attenuated blood flow depending upon whether the microballoon is deflated or inflated.

30. The method according to any one of claims 19-26, wherein said composition has a viscosity of at least 200 centistokes at 40°

C.

31. The method according to any one of claims 19-26, wherein said composition has a viscosity of at least 500 centistokes at 40°

C.

32. The method according to any one of claims 19-26, wherein said composition has a viscosity of from at least 500 to 5,000 centistokes at 40°

C.

33. The method according to claim 19, wherein said biocompatible prepolymer is selected from the group comprising acrylates and silicone prepolymers.

35. The method according to claim 33, wherein said biocompatible prepolymer is cyanoacrylate.

37. The method according to claim 19, wherein said biocompatible contrast agent is a water insoluble contrast agent.

39. The method according to claim 37, wherein said water insoluble contrast agent is selected from the group comprising tantalum, tantalum oxide, tungsten, barium sulfate, gold, and platinum.

41. The method according to claim 39, wherein said water insoluble contrast agent is tantalum.

43. The method according to claim 21, wherein said thickening agent is selected from the group comprising polymethyl methacrylate and silica gel.

45. The method according to claim 43, wherein said thickening agent is polymethyl methacrylate.

47. The method according to claim 23, wherein said biocompatible solvent is selected from the group comprising ethyl lactate, dimethylsulfoxide, ethanol, acetone, Ethiodol®

, Lipiodol®

, iodinated poppy seed oil, iodinated soy bean oil, water, and hexamethyldisiloxane.

49. The method according to claim 47, wherein said biocompatible solvent is dimethylsulfoxide.

20. A method for embolizing a vascular site, said method comprising:

(a) selecting an embolic composition comprising a biocompatible prepolymer and a biocompatible contrast agent, wherein said embolic composition has a viscosity of at least 150 centistokes at 40°

C.;

(b) heating and mixing the embolic composition to at least 40°

C. to form a uniform suspension;

(c) transferring the embolic composition to a delivery catheter having a proximal end and a distal end, wherein the distal end of the delivery catheter is positioned at the vascular site to be embolized; and

(d) injecting the embolic composition into said vascular site in sufficient amounts to embolize said vascular site.

22. The method according to claim 20, wherein the embolic composition further comprises a thickening agent.

24. The method according to claim 20, wherein the embolic composition further comprises a biocompatible solvent.

26. The method according to claim 20, wherein the embolic composition further comprises a thickening agent and a biocompatible solvent.

34. The method according to claim 20, wherein said biocompatible prepolymer is selected from the group comprising acrylates and silicone prepolymers.

36. The method according to claim 34, wherein said biocompatible prepolymer is cyanoacrylate.

38. The method according to claim 20, wherein said biocompatible contrast agent is a water insoluble contrast agent.

40. The method according to claim 38, wherein said water insoluble contrast agent is selected from the group comprising tantalum, tantalum oxide, tungsten, barium sulfate, gold, and platinum.

42. The method according to claim 40, wherein said water insoluble contrast agent is tantalum.

44. The method according to claim 22, wherein said thickening agent is selected from the group comprising polymethyl methacrylate and silica gel.

46. The method according to claim 44, wherein said thickening agent is polymethyl methacrylate.

48. The method according to claim 24, wherein said biocompatible solvent is selected from the group comprising ethyl lactate, dimethylsulfoxide, ethanol, acetone, Ethiodol®

, Lipiodol®

, iodinated poppy seed oil, iodinated soy bean oil, water, and hexamethyldisiloxane.

50. The method according to claim 48, wherein said biocompatible solvent is dimethylsulfoxide.