Fragmented polymeric compositions and methods for their use

• US 6,063,061 A
• Filed: 07/31/1997
• Issued: 05/16/2000
• Est. Priority Date: 08/27/1996
• Status: Expired due to Term

• Current Assignee: Baxter Healthcare SA (Baxter International Inc.), Baxter International Inc.
• Original Assignee: Fusion Medical Technologies Inc. (Baxter International Inc.)
• Inventors: Osawa, A. Edward, Shargill, Narinder S., Wallace, Donald G., Vega, Felix, Reich, Cary J.
• Primary Examiner(s): Buiz, Michael
• Assistant Examiner(s): Woo, Julian W.
• Application Number:
  US08/903,674
• Time in Patent Office: 1,020 Days
• Field of Search: 424/423, 424/445, 514/21, 604/181
• US Class Current: 604/181
• CPC Class Codes: A61L 2300/418 Agents promoting blood coagulation, blood-clotting agents, embolising agents
• CPC Class Codes: A61L 24/0015 Medicaments; Biocides
• CPC Class Codes: A61L 24/0031 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents

Abstract

Molecular cross-linked gels comprise a variety of biologic and non-biologic polymers, such as proteins, polysaccharides, and synthetic polymers. Such molecular gels may be applied to target sites in a patient'"'"'s body by extruding the gel through an orifice at the target site. Alternatively, the gels may be mechanically disrupted and used in implantable articles, such as breast implants. When used in vivo, the compositions are useful for inhibiting post-surgical spinal and other tissue adhesions, for filling tissue divots, tissue tracts, body cavities, surgical defects, and the like.

Claims

1. A method for sealing a tissue tract, said method comprising at least partly filling a tissue tract with a fragmented hydrogel hydrated at less than its equilibrium swell, said fragmented hydrogel comprising subunits having sizes from 0.05 mm to 5 mm when fully hydrated and an equilibrium swell from 400% to 1300%, wherein said hydrogel degrades in the tissue tract after from 1 to 120 days.

6. A method as in any of claim 1, wherein the extrusion step comprises manually dispensing the hydrogel through a syringe having an orifice size in the range from 0.01 mm to 5.0 mm.

7. A method as in any of claim 1, wherein the hydrogel has been disrupted prior to the extrusion step.

13. A method as in any of claims 1-4, wherein the hydrogel is filled or delivered using a spatula, using a brush, by spraying, or manually.

14. A method as in claim 1, wherein the hydrogel has a degree of hydration in the range from 50% to 95% of the hydration at equilibrium swell.

15. A method as in any one of claims 1-4, wherein the hydrogel has been disrupted after cross-linking.

16. A method as in any one of claims 1-4, wherein the hydrogel has been disrupted before cross-linking.

17. A method as in any one of claims 1-4, wherein the hydrogel comprises a plasticizer.

18. A method as in claim 17, wherein the plasticizer is selected from the group consisting of polyethylene glycol, sorbitol, and glycerol.

19. A method as in claim 17, wherein the plasticizer is present at from 0.1% by weight to 30% by weight of the composition of the polymeric component.

22. A method as in any one of claims 1-4, wherein the hydrogel comprises a cross-linked protein hydrogel.

23. A method as in claim 22, wherein the protein is selected from the group consisting of gelatin, soluble collagen, albumin, hemoglobin, fibrogen, fibrin, casein, fibronectin, elastin, keratin, laminin, and derivatives and combinations thereof.

24. A method as in any one of claims 1-4, wherein the hydrogel comprises a cross-linked polysaccharide.

25. A method as in claim 24, wherein the polysaccharide is selected from the group consisting of glycosaminoglycans, starch derivatives, cellulose derivatives, hemicellulose derivatives, xylan, agarose, alginate, and chitosan and combinations thereof.

26. A method as in any one of claims 1-4, wherein the hydrogel comprises a cross-linked non-biologic polymer.

27. A method as in claim 26, wherein the polymer selected from the group consisting of polyacrylates, polymethacrylates, polyacrylamides, polyvinyl resins, polyactide-glycolides, polcaprolactones, polyoxyethlenes, and combinations thereof.

28. A method as in any one of claims 1-4, wherein the hydrogel comprises at least two components selected from the group consisting of cross-linked proteins, cross-linked polysaccharides, and cross-linked non-biologic polymers.

29. A method as in any one of claims 1-4, wherein the hydrogel comprises a polymer and a cross-linking agent, wherein the polymer and cross-linking agent have been reacted under conditions which yield cross-linking of polymer molecules.

30. A method as in any one of claims 1-4, wherein the molecular cross-linked hydrogel has been produced by irradiation of the polymer under conditions which yield cross-linking of polymer molecules.

31. A method as in any one of claims 1-4, wherein the molecular cross-linked hydrogel has been produced by reaction of monounsaturated and polyunsaturated monomers under conditions which yield cross-linking of polymer molecules.

2. A method for inhibiting bleeding at a target site in a patient'"'"'s body, said method comprising delivering a fragmented hydrogel hydrated at less than its equilibrium swell, said fragmented hydrogel comprising subunits having sizes from 0.05 mm to 5 mm when fully hydrated and an equilibrium swell from 400% to 1300%, wherein said hydrogel degrades in the tissue tract after from 1 to 120 days to the target site in an amount sufficient to inhibit bleeding.

3. A method for delivering a bioactive substance to a target site in a patient'"'"'s body, said method comprising delivering a fragmented hydrogel hydrated at less than its equilibrium swell, said fragmented hydrogel comprising subunits having sizes from 0.05 mm to 5 mm when fully hydrated and an equilibrium swell from 400% to 1300%, wherein said hydrogel degrades in the tissue tract after from 1 to 120 days in combination with the bioactive substance to the target site.

20. A method as in claim 3, wherein the bioactive substance is a hemostatic agent.

21. A method as in claim 20, wherein the bioactive substance is thrombin.

4. A method for delivering a swellable composition to a target site in tissue, said method comprising providing a fragmented hydrogel hydrated at less than its equilibrium swell, said fragmented hydrogel comprising subunits having sizes from 0.05 mm to 5 mm when fully hydrated and an equilibrium swell from 400% to 1300%, wherein said hydrogel degrades in the tissue tract after from 1 to 120 days, said composition being hydrated at less than its equilibrium swell and applying the composition to the target site, wherein it swells to an equilibrium swell value.

5. A method for applying a polymeric composition at a target site in a patient'"'"'s body, said method comprising:

providing a biocompatible resorbable molecular cross-linked hydrogel; and

extruding the gel through an orifice at the target site.

8. A method as in claim 5, wherein the target site is in tissue selected from the group consisting of muscle, skin, epithelial tissue, connective or supporting tissue, nerve tissue, ophthalmic and other sense organ tissue, vascular and cardiac tissue, gastrointestinal organs and tissue, pleura and other pulmonary tissue, kidney, endocrine glands, male and female reproductive organs, adipose tissue, liver, pancreas, lymph, cartilage, bone, oral tissue, and mucosal tissue, and spleen and other abdominal organs.

9. A method as in claim 8, wherein the target site is a void region within the selected tissue.

10. A method as in claim 9, wherein the void region is selected from the group consisting of tissue divots, tissue tracts, intravertebral spaces, and body cavities.

11. A method as in claim 9, further comprising immobilizing a barrier layer over the void after the gel has been extruded.

12. A method as in claim 5, wherein the extrusion step causes the hydrogel to fracture into sub-units having a size in the range from 0.05 mm to 3.0 mm.