Proteinaceous gels having visualization agents and methods of use thereof

• US 20030077272A1
• Filed: 11/13/2002
• Published: 04/24/2003
• Est. Priority Date: 09/23/1996
• Status: Active Grant

• Current Assignee: Incept LLC
• Original Assignee: Incept LLC
• Inventors: Pathak, Chandrashekhar P.
• Granted Patent: US 7,211,651 B2
• Time in Patent Office: Days
• US Class Current: 424/94.64
• CPC Class Codes: A61K 47/42 Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• 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 24/106 Fibrin; Fibrinogen
• CPC Class Codes: A61P 7/08 Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock artificial tears A61P27/04
• CPC Class Codes: C07K 1/30 by precipitation
• CPC Class Codes: C07K 14/745 Blood coagulation or fibrinolysis factors
• CPC Class Codes: C07K 14/75 Fibrinogen
• CPC Class Codes: C08L 2666/02 Organic macromolecular compounds, natural resins, waxes or and bituminous materials
• CPC Class Codes: C08L 89/00 Compositions of proteins; Compositions of derivatives thereof foodstuff preparations A23J3/00
• CPC Class Codes: G06K 2207/1016 Motor control or optical moving unit control
• CPC Class Codes: G06K 7/10831 Arrangement of optical elements, e.g. lenses, mirrors, prisms optical elements per se G02B
• CPC Class Codes: Y10S 435/81 Packaged device or kit

Abstract

Proteinaceous gels having visualization agents and methods of use thereof are disclosed herein. Further, polymeric crosslinking agents are disclosed that have an inert water soluble polymeric component, biodegradable components, functional components reactive with chemical groups on a protein, for example, amine or thiol groups. The inert polymeric component may be flanked at each end with a biodegradable component which is flanked at each end with a protein reactive functional component. A polymeric crosslinking agent is disclosed having a biodegradable component, polyalkylene oxide, and at least three reactive functional groups that are each capable of forming a covalent bond in water with at least one functional group such as an amine, thiol, or carboxylic acid.

Claims

1. An adhesive system for use with a patient said adhesive system comprising a fibrinogen rich composition, a visualization agent, and a device for applying said fibrinogen rich composition or a reaction product of said fibrinogen rich composition to the patient.

2. The adhesive system of claim 1 wherein said fibrinogen rich composition comprises at least 1 mg/ml fibrinogen.

3. The adhesive system of claim 1 wherein said fibrinogen rich composition comprises about 1 mg/ml to about 100 mg/ml fibrinogen.

4. The adhesive system of claim 1 wherein said fibrinogen rich composition comprises about 1 mg/ml to about 30 mg/ml fibrinogen.

5. The adhesive system of claim 1 wherein said fibrinogen rich system comprises about 30 mg/ml to about 60 mg/ml fibrinogen.

6. The adhesive system of claim 1 wherein said visualization agent is blood compatible.

7. The adhesive system of claim 1 wherein said visualization agent is blue.

8. The adhesive system of claim 1 wherein said visualization agent is green.

9. The adhesive system of claim 1 wherein said visualization agent comprises at least one member of the group consisting of chromogenic dye, non-toxic fluorescent compound, indocyanine green, FD&

C no. 1, FD&

C no. 6, eosin, and fluorescein.

10. The adhesive system of claim 1 further comprising a coagulation component.

11. The adhesive system of claim 10 wherein said coagulation component comprises thrombin.

12. The adhesive system of claim 10 wherein said coagulation component further comprises calcium ions.

13. The adhesive system of claim 1 further comprising a synthetic cross-linker for cross-lining proteins of the fibrinogen rich composition.

14. The adhesive system of claim 13 wherein said cross-linker is water soluble.

15. The adhesive system of claim 13 wherein said cross-linker is biodegradable.

16. The adhesive system of claim 13 wherein said cross-linker is multi-functional.

17. The adhesive system of claim 13 wherein said cross-linker further comprises a biologically inert polymeric core.

18. The adhesive system of claim 17 wherein said biologically inert polymeric core further comprises a polyakyleneoxide.

19. The adhesive system of claim 17 wherein said cross-linker further comprises a biodegradable polymeric unit extension at each end of said biologically inert polymeric core.

20. The adhesive system of claim 17 wherein said cross-linker further comprises a reactive moiety end cap on each said biodegradable polymeric unit extension.

21. A biocompatible material comprising a fibrin glue and a visualization agent.

22. The biocompatible material of claim 21 wherein said fibrin glue comprises at least 1 mg/ml fibrinogen.

23. The biocompatible material of claim 21 wherein said fibrin glue comprises about 1 mg/ml to about 100 mg/ml fibrinogen.

24. The biocompatible material of claim 21 wherein said fibrin glue comprises about 1 mg/ml to about 30 mg/ml fibrinogen.

25. The biocompatible material of claim 21 wherein said fibrin glue comprises about 30 mg/ml to about 60 mg/ml fibrinogen.

26. The biocompatible material of claim 21 wherein said visualization agent is blood compatible.

27. The biocompatible material of claim 21 wherein said visualization agent is blue.

28. The biocompatible material of claim 21 wherein said visualization agent is green.

29. The biocompatible material of claim 21 wherein said visualization agent comprises at least one member of the group consisting of chromogenic dye, non-toxic fluorescent compound, indocyanine green, FD&

C no. 1, FD&

C no. 6, eosin, and fluorescein.

30. The biocompatible system of claim 21 further comprising a coagulation component.

31. The biocompatible material of claim 30 wherein said coagulation component comprises thrombin.

32. The biocompatible material of claim 30 wherein said coagulation component further comprises calcium ions.

33. The biocompatible material of claim 21 further comprising a synthetic crosslinker for cross-lining proteins of the fibrin glue.

34. The biocompatible material of claim 33 wherein said cross-linker is water soluble.

35. The biocompatible material of claim 33 wherein said cross-linker is biodegradable.

36. The biocompatible material of claim 33 wherein said cross-linker is multifunctional.

37. The biocompatible material of claim 33 wherein said cross-linker further comprises a biologically inert polymeric core.

38. The biocompatible material of claim 37 wherein said biologically inert polymeric core further comprises a polyakyleneoxide.

39. The biocompatible material of claim 37 wherein said cross-linker further comprises a biodegradable polymeric unit extension at each end of said biologically inert polymeric core.

40. The biocompatible material of claim 37 wherein said cross-linker further comprises a reactive moiety end cap on each said biodegradable polymeric unit extension.

41. A kit comprising a fibrin glue and a visualization agent.

42. The kit of claim 41 wherein said fibrin glue comprises at least 1 mg/ml fibrinogen.

43. The kit of claim 41 wherein said fibrin glue comprises about 1 mg/ml to about 100 mg/ml fibrinogen.

44. The kit of claim 41 wherein said fibrin glue comprises about 1 mg/ml to about 30 mg/ml fibrinogen.

45. The kit of claim 41 wherein said fibrin glue comprises about 30 mg/ml to about 60 mg/ml fibrinogen.

46. The kit of claim 41 wherein said visualization agent is blood compatible.

47. The kit of claim 41 wherein said visualization agent is blue.

48. The kit of claim 41 wherein said visualization agent is green.

49. The kit of claim 41 wherein said visualization agent further comprises at least one member of the group consisting of chromogenic dye, non-toxic fluorescent compound, indocyanine green, FD&

C no. 1, FD&

C no. 6, eosin, and fluorescein.

50. The kit of claim 41 further comprising a dual syringe.

51. The kit of claim 41 further comprising thrombin.

52. A method of preparing a biocompatible material said method comprising providing a fibrinogen rich composition and mixing said fibrinogen rich composition with a visualization agent.

53. The method of claim 52 wherein said visualization agent is blood compatible.

54. The method of claim 52 wherein said visualization agent is blue.

55. The method of claim 52 wherein said visualization agent is green.

56. The method of claim 52 wherein said visualization agent further comprises at least one member of the group consisting of chromogenic dye, non-toxic fluorescent compound, indocyanine green, FD&

C no. 1, FD&

C no. 6, eosin, and fluorescein.

57. The method of claim 52 further comprising mixing thrombin with said fibrinogen rich composition and said visualization agent.

58. The method of claim 52 further comprising mixing a synthetic cross-linker with said fibrinogen rich composition and said visualization agent.