Injectable implant composition having improved intrudability

• US 4,803,075 A
• Filed: 06/25/1986
• Issued: 02/07/1989
• Est. Priority Date: 06/25/1986
• Status: Expired due to Term

• Current Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Original Assignee: Collagen Corp. (Abbvie Incorporated)
• Inventors: Reihanian, Hertsel, Braun, William G., Wallace, Donald G., Pharriss, Bruce B.
• Primary Examiner(s): Page, Thurman K.
• Application Number:
  US06/878,418
• Time in Patent Office: 958 Days
• Field of Search: 424/423, 424/499, 424/500, 424/501, 424/400, 514/18, 514/801, 514/802
• US Class Current: 424/423
• CPC Class Codes: A61F 2/0059 Cosmetic or alloplastic implants A61F2/10 - A61F2/16, A61F2/28 take precedence
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61K 38/39 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• 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

Abstract

Injectable aqueous suspensions of biomaterials, such as cross-linked collagen, that contain a biocompatible fluid lubricant, such as glycogen or maltose, are disclosed. The inclusion of the lubricant significantly improves the intrusion of the suspension into soft tissue.

Claims

1. An injectable implant composition for soft tissue augmentation comprising an aqueous suspension of a particulate biomaterial containing a sufficient amount of a biocompatible fluid lubricant to significantly improve the intrudability of the composition, wherein said particles of biomaterial are fibrils or beads comprising natural or synthetic polymers, and wherein said fluid lubricant comprises a non-fibrillar high molecular weight charged polymer, a high molecular weight neutral polymer, or a low molecular weight neutral molecule.

2. The composition of claim 1 wherein the particulate biomaterial is fibrillar cross-linked collagen, or beads of a synthetic or natural polymer.

3. The composition of claim 1 wherein the particles of biomaterial are (a) generally spherical in shape and have diameters in the range of about 1 to 30 microns or (b) are 500-800 microns in length and less than 30 microns in width.

4. The composition of claim 1 wherein the concentration of particulate biomaterial in the suspension is in the range of 1% to 20% W/V.

5. The composition of claim 1 wherein the concentration of particulate biomaterial in the suspension is in the range of 3% to 6% W/V.

6. The composition of claim 1 wherein the concentration of said lubricant in the suspension is about 0.01% to 40% W/V.

7. The composition of claim 1 wherein the lubricant is a charged polymer.

8. The composition of claim 7 wherein the charged polymer is methylated collagen, succinylated collagen, or dextran sulfate.

9. The composition of claim 1 wherein the lubricant is an uncharged polymer selected from the group consisting of dextran, heparin, and glycogen, and the concentration of lubricant in the suspension is 10% to 40% W/V.

10. The composition of claim 1 wherein the lubricant is neutral, has a low molecular weight, and is present in the suspension at 10% to 40% W/V.

11. The composition of claim 10 wherein the lubricant is maltose, dextrose, a triglyceride of a fatty acid, egg yold phospholipid, or glycerol.

12. The composition of claim 1 wherein the lubricant is hyaluronic acid.

13. The composition of claim 1 wherein the lubricant is soluble in the suspending medium.

14. The composition of claim 8 wherein the biomaterial is cross-linked collagen and the concentration of biomaterial in the suspension is 3% to 6% W/V.

15. The composition of claim 9 wherein the biomaterial is cross-linked collagen and the concentration of biomaterial in the suspension is 3% to 6% W/V.

16. The composition of claim 11 wherein the biomaterial is cross-linked collagen and the concentration of biomaterial in the suspension is 3% to 6% W/V.

17. The composition of claim 12 wherein the biomaterial is cross-linked collagen and the concentration of biomaterial in the suspension is 3% to 6% W/V.

26. A method for augmenting soft tissue in a living mammal comprising injecting the composition of claim 1 into the mammal at the augmentation site.

27. A method for augmenting soft tissue in a living mammal comprising injecting the composition of claim 8 into the mammal at the augmentation site.

28. A method for augmenting soft tissue in a living mammal comprising injecting the composition of claim 9 into the mammal at the augmentation site.

29. A method for augmenting soft tissue in a living mammal comprising injecting the composition of claim 11 into the mammal at the augmentation site.

30. A method for augmenting soft tissue in a living mammal comprising injecting the composition of claim 12 into the mammal at the augmentation site.

31. The composition of claim 1 wherein said biomaterial is selected from fibrillar crosslinked collagen, gelatin beads, polytetrafluoroethylene beads, silicone rubber beads, hydrogel beads, silicon carbide beads, and glass beads.

32. The composition of claim 1 wherein said fluid lubricant is selected from hyaluronic acid, dextran sulfate, dextran, succinylated non-crosslinked collagen, methylated non-cross-linked collagen, glycogen, glycerol, dextrose, maltose, triglycerides of fatty acids, egg yolk phospholipids, and heparin.

18. A method of improving the intrudability of a particulate biomaterial into soft tissue comprising

incorporating a sufficient amount of a biocompatible fluid lubricant in the suspension to enhance the intrudability of the suspension into the tissue, wherein said particles of biomaterial are fibrils or beads comprising natural or synthetic polymers, and wherein said fluid lubricant comprises a non-fibrillar high molecular weight charged polymer, a high molecular weight neutral polymer, or a low molecular weight neutral molecule.

19. The method of claim 18 wherein the concentration of said lubricant in the suspension is about 0.01% to 40% W/V.

20. The method of claim 18 wherein the lubricant is a charged polymer.

21. The method of claim 20 wherein the charged polymeric methylated collagen, succinylated collagen, or dextran sulfate.

22. The method of claim 18 wherein the lubricant is an uncharged polymer selected from the group consisting of dextran, heparin, and glycogen and the concentration of lubricant in the suspension is 10% to 40% W/V.

23. The method of claim 18 wherein the lubricant is neutral, has a low molecular weight and is present in the suspension at 10% to 40% W/V.

24. The method of claim 23 wherein the lubricant is maltose, dextrose, a triglyceride of a fatty acid, egg yolk phospholipid, or glycerol.

25. The method of claim 18 wherein the lubricant is hyaluronic acid.

33. The method of claim 18 wherein said biomaterial is selected from fibrillar cross-linked collagen, gelatin beads, polytetrafluoroethylene beads, silicone rubber beads, hydrogel beads, silicon carbide beads, and glass beads.

34. The method of claim 18 wherein said fluid lubricant is selected from hyaluronic acid, dextran sulfate, dextran, succinylated non-cross-linked collagen, methylated non-cross-linked collagen, glycogen, glycerol, dextrose, maltose, triglycerides of fatty acids, egg yolk phospholipids, and heparin.