Injectable or implantable biomaterials for filling or blocking lumens and voids of the body

• US 5,752,974 A
• Filed: 12/18/1995
• Issued: 05/19/1998
• Est. Priority Date: 12/18/1995
• Status: Expired due to Term

• Current Assignee: Angiotech Pharmaceuticals Incorporated
• Original Assignee: Collagen Corp. (Abbvie Incorporated)
• Inventors: McCullough, Kimberly A., Jolivette, Dan M., Rhee, Woonza M., Chu, George H., Berg, Richard A., DeLustro, Frank A.
• Primary Examiner(s): SCHMIDT, JEFFREY
• Application Number:
  US08/574,050
• Time in Patent Office: 883 Days
• Field of Search: 606/213, 606/214, 606/215, 606/216, 606/1
• US Class Current: 606/214
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61L 24/043 Mixtures of macromolecular materials
• CPC Class Codes: A61L 24/102 Collagen
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• 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 26/0033 Collagen
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• 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 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 31/041 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 31/044 Collagen
• CPC Class Codes: A61P 15/18 Feminine contraceptives
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: C08L 5/10 Heparin; Derivatives thereof
• CPC Class Codes: C08L 71/02 Polyalkylene oxides
• CPC Class Codes: C08L 89/00 Compositions of proteins; Compositions of derivatives thereof foodstuff preparations A23J3/00
• CPC Class Codes: C08L 89/06 derived from leather or skin , e.g. gelatin

Abstract

Methods for completely or partially blocking, augmenting, sealing, or filling various biological lumens and voids within the body of a patient are disclosed. Lumens include arteries, veins, intestines, Fallopian tubes, and trachea. Voids include various lesions, fissures, diverticulae, cysts, fistulae, aneurysms, or other undesirable voids that may exist within a patient'"'"'s body. In the most general method of the invention, an effective amount of a biomaterial is administered (e.g., via injection, catheter, or surgical implantation) into the lumen or void. Preferred biomaterial compositions for use in the present invention are disclosed.

Claims

1. A method for completely or partially blocking, augmenting, sealing, or filling a lumen or void within the body comprising the steps of:

a) providing a polymer and a hydrophilic crosslinking agent in suspension or solution to form an injectable or implantable biomaterial;

b) injecting or implanting the biomaterial into a lumen or void within the body; and

c) allowing the biomaterial to anchor to body tissue surrounding the lumen or void to totally or partially block or fill the lumen or void.

2. The method of claim 1 wherein the polymer is selected from the group consisting of a protein, a synthetic polypeptide, a glycosaminoglycan, a proteoglycan, a polymeric hydrogel, and mixtures thereof.

3. The method of claim 2, wherein the polymer is crosslinked with the crosslinking agent prior to step b), thereby to form a biomaterial which is crosslinked.

4. The method of claim 3, wherein the crosslinked biomaterial is dehydrated prior to step b), and wherein, in step c), the biomaterial rehydrates and swells, thereby allowing the biomaterial to anchor to body tissue surrounding the lumen or void to totally or partially block or fill the lumen or void.

5. The method of claim 4, wherein the dehydrated crosslinked biomaterial is present in particulate form, suspended in a pharmaceutically acceptable nonaqueous carrier, and administered by injection into the lumen or void.

6. The method of claim 4, wherein the dehydrated crosslinked biomaterial is present in rod form and administered into the lumen or void via a catheter or an endoscope.

7. The method of claim 3, wherein the crosslinking agent is selected from the group consisting of aldehydes, carbodiimides, epoxides, and imidazoles.

8. The method of claim 3, wherein the crosslinking agent is a synthetic hydrophilic polymer.

9. The method of claim 8, wherein the synthetic hydrophilic polymer is a functionally activated polyethylene glycol.

10. The method of claim 9, wherein the synthetic hydrophilic polymer is a difunctionally activated polyethylene glycol.

11. The method of claim 2, wherein the polymer is a protein.

12. The method of claim 11, wherein the protein is collagen.

13. The method of claim 12, wherein the collagen is fibrillar collagen.

14. The method of claim 13, wherein the collagen comprises a mixture of particulate crosslinked fibrillar collagen and noncrosslinked fibrillar collagen.

15. The method of claim 14, wherein the particulate crosslinked fibrillar collagen comprises between about 25% to about 95% and the noncrosslinked fibrillar collagen comprises between about 5% to about 75% by weight of the composition.

16. The method of claim 12, wherein the collagen is nonfibrillar collagen.

17. The method of claim 16, wherein the nonfibrillar collagen is methylated collagen.

18. The method of claim 12, wherein the collagen is denatured collagen.

19. The method of claim 2, wherein the polymer is a glycosaminoglycan selected from the group consisting of hyaluronic acid, chondroitin sulfate A, chondroitin sulfate C, dermatan sulfate, keratan sulfate, keratosulfate, chitin, chitosan, heparin, and derivatives thereof.

20. The method of claim 19, wherein the glycosaminoglycan is hyaluronic acid.

21. The method of claim 1, wherein the polymer comprises a crosslinked mixture of collagen and one or more species of glycosaminoglycan.

22. The method of claim 1, wherein the biomaterial further comprises one or more biocompatible fluid lubricant selected from the group consisting of hyaluronic acid, dextran sulfate, dextran, succinylated noncrosslinked collagen, methylated noncrosslinked collagen, glycogen, glycerol, dextrose, maltose, triglycerides of fatty acids, and egg yolk phospholipid.

23. The method of claim 1, wherein the biomaterial further comprises a particulate material selected from the group consisting of ceramic particles, crosslinked or noncrosslinked particulate fibrillar collagen, gelatin beads, polytetrafluoroethylene beads, silicone rubber beads, beads of various hydrogel polymers, silicon carbide beads, glass beads, and mixtures thereof.

24. The method of claim 1, wherein the biomaterial further comprises an effective amount of one or more biologically active agent selected from the group consisting of a wound healing agent, an antibiotic, and an antimicrobial agent.

25. The method of claim 24, wherein the biologically active agent is a wound healing agent selected from the group consisting of:

transforming growth factors (TGFs), fibroblast growth factors (FGFs), platelet derived growth factors (PDGFs), epidermal growth factors (EGFs), connective tissue activated peptides (CTAPs), osteogenic factors, and biologically active analogs, fragments, and derivatives thereof.

26. The method of claim 1, wherein the method further comprises the step of selecting a lumen from the group consisting of a Fallopian tube, a trachea, an artery, a vein, and an intestine prior to step b).

27. The method of claim 1, wherein the method further comprises the step of selecting a void from the group consisting of aneurysms, lesions, fissures, fistulae, cysts, and diverticulae of any organ prior to step b).

28. The method of claim 1, wherein the method further comprises selecting a void caused by a surgical, chemical, or biological removal of growths, fluids, cells, or tissues prior to step b).

29. The method of claim 1, wherein the polymer and the crosslinking agent are administered by injection into the lumen or void before substantial crosslinking has occurred between the polymer and the crosslinking agent, and wherein crosslinking of the polymer and crosslinking agent is completed after administration to the lumen or void, thereby permitting the biomaterial to anchor to body tissue surrounding the lumen or void.

30. The method of claim 1 wherein the polymer and the hydrophilic crosslinking agent are crosslinked after injection or implantation of the biomaterial into the lumen or void, thereby permitting the biomaterial to anchor to body tissue surrounding the lumen or void.

31. The method of claim 1 wherein the polymer is a synthetic polymer.

32. The method of claim 1 wherein the polymer comprises polyethylene glycol.

33. The method of claim 32 wherein the hydrophilic crosslinking agent comprises a functionally activated polyethylene glycol.

34. The method of claim 1 wherein the biomaterial is injected or implanted within a lumen in the body.

35. A method for completely or partially blocking, augmenting, sealing, or filling a biological lumen or void within the body of a patient comprising administering an effective amount of a biomaterial into the lumen or void;

wherein the biomaterial is crosslinked using a mixture of hydrophilic and hydrophobic crosslinking agents.

36. The method of claim 35, wherein the hydrophilic crosslinking agent is a functionally activated polyethylene glycol.

37. The method of claim 35, wherein the hydrophobic crosslinking agent is a hydrophobic polymer which contains two or more succinimidyl groups prior to bonding with the biomaterial.

38. The method of claim 37, wherein the hydrophobic polymer is selected from the group consisting of:

disuccinimidyl suberate, bis(sulfosuccinimidyl) suberate, dithiobis(succinimidylpropionate), bis(2-succinimidooxycarbonyloxy)ethyl sulfone, 3,3'"'"'-dithiobis(sulfosuccinimidyl)propionate, and analogs and derivatives thereof.

39. The method of claim 35, wherein the biomaterial is a protein.

40. The method of claim 39, wherein the protein is collagen.

41. The method of claim 40, wherein the collagen is fibrillar collagen.

42. The method of claim 35, wherein the biomaterial comprises a glycosaminoglycan.

43. The method of claim 35, wherein the biomaterial further comprises an effective amount of one or more biologically active agent.

44. The method of claim 35, wherein the method further comprises the step of selecting a lumen from the group consisting of a Fallopian tube, a trachea, an artery, a vein, and an intestine prior to step b).

45. The method of claim 35, wherein the biomaterial and the crosslinking agent are administered by injection into the lumen or void before substantial crosslinking has occurred between the biomaterial and the crosslinking agent.

46. A method for completely or partially blocking, augmenting, sealing, or filling a biological lumen or void within the body of a patient comprising administering an effective amount of a biomaterial into the lumen or void;

wherein the biomaterial is a polymeric hydrogel which comprises a first synthetic polymer crosslinked using a second synthetic polymer, wherein the first synthetic polymer contains two or more nucleophilic groups, and the second synthetic polymer contains two or more electrophilic groups capable of forming covalent bonds with the nucleophilic groups on the first synthetic polymer.

47. The method of claim 46, wherein the biomaterial comprises collagen.

48. The method of claim 46, wherein the biomaterial further comprises a biologically active agent.