BIOLOGIC MATRICES COMPRISING ANTI-INFECTIVE METHODS AND COMPOSITIONS RELATED THERETO

• US 20110070284A1
• Filed: 02/23/2009
• Published: 03/24/2011
• Est. Priority Date: 02/22/2008
• Status: Abandoned Application

• Current Assignee: Musculoskeletal Transplant Foundation
• Original Assignee: Musculoskeletal Transplant Foundation
• Inventors: Depaula, Carl Alexander, Sunwoo, Moonhae, Gertzman, Arthur A.
• Application Number:
  US12/918,991
• Publication Number:
  US 20110070284A1
• Time in Patent Office: Days
• US Class Current: 424/425
• CPC Class Codes: A61K 31/085 having an ether linkage to aromatic ring nuclear carbon
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/191 having two or more hydroxy groups, e.g. gluconic acid
• CPC Class Codes: A61K 9/70 Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug hollow drug-filled fibres A61K9/0092
• CPC Class Codes: A61L 2300/202 with halogen atoms, e.g. triclosan, povidone-iodine
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 27/3633 Extracellular matrix [ECM]
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 31/005 Ingredients of undetermined constitution or reaction products thereof
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents

Abstract

Described herein are methods and compositions related to biologic matrices comprising at least one anti-infective. In certain embodiments, the invention relates to a biologic matrix comprising a slowed release anti-infective agent. In a particular embodiment, the invention relates to an acellular dermal matrix comprising a slowed release antiinfective agent, wherein the anti-infective agent is triclosan. In further embodiments, the the biologic matrix is suitable for use in surgical procedures, such as, for example, for the replacement of damaged or inadequate integumental tissue or for the repair, reinforcement or supplemental support of soft tissue defects.

Claims

1. A biologic matrix comprising a slowed release anti-infective agent.

2. The biologic matrix of claim 1, wherein the biologic matrix is an acellular biologic matrix.

3. The acellular biologic matrix of claim 2, wherein the acellular biologic matrix is derived from tissue selected from the group consisting of:

dermal, fascia, dura, pericardia, tendons, ligaments, and muscle.

4. The acellular biologic matrix of claim 3, wherein the acellular biologic matrix is an acellular dermal matrix.

5. The acellular biologic matrix of claim 2, wherein the acellular biologic matrix is hydrated with a solution of specially denatured alcohol and water in a ratio of alcohol to water selected from the group consisting of:

20;

80;

25;

75;

30;

70;

35;

65;

40;

60;

45;

55;

50;

50;

55;

45;

60;

40;

65;

35;

70;

30;

75;

25;

80;

20;

85;

15;

90;

10; and

95;

05.

6. The acellular biologic matrix of claim 5, wherein the acellular biologic matrix is hydrated with a 70% specially denatured alcohol and 30% water solution.

7. The acellular biologic matrix of claim 6, wherein the anti-infective agent is triclosan.

8. The acellular biologic matrix of claim 5, wherein the acellular biologic matrix is hydrated with a 40% specially denatured alcohol and 60% water solution.

9. The acellular biologic matrix of claim 8, wherein the anti-infective agent is triclosan.

10. The acellular biologic matrix of claim 6, wherein the hydrated acellular biologic matrix is dipped in a triclosan solution.

11. The acellular biologic matrix of claim 6, wherein the hydrated acellular biologic matrix is soaked in a triclosan solution for at least about five seconds to less than about forty-five minutes.

12. The acellular biologic matrix of claim 6, wherein the hydrated acellular biologic matrix is sprayed with a triclosan solution.

13. The acellular biologic matrix of claim 10, wherein the triclosan solution comprises about 500 to about 4000 ppm triclosan.

14. The acellular biologic matrix of claim 11, wherein the triclosan solution comprises about 500 to about 4000 ppm triclosan.

15. The acellular biologic matrix of claim 12, wherein the triclosan solution comprises about 10 ppm to about 100,000 ppm triclosan.

16. The acellular biologic matrix of claim 10, wherein the acellular biologic matrix comprises a concentration of triclosan is about 50 to about 2000 ppm.

17. The The acellular biologic matrix of claim 11, wherein the acellular biologic matrix comprises a concentration of triclosan is about 50 to about 2000 ppm.

18. The acellular biologic matrix of claim 12, wherein the acellular biologic matrix comprises a concentration of triclosan is about 50 to about 2000 ppm.

19. The acellular biologic matrix of claim 14, wherein the hydrated biologic matrix comprising anti-infective is vacuum-dried from about one minute to about six minutes.

20. The acellular biologic matrix of claim 6, wherein the hydrated biologic matrix comprising anti-infective demonstrates anti-microbial activity in a zone-of-inhibition assay against gram positive bacteria.

21. The acellular biologic matrix of claim 20, wherein the zone-of-inhibition assay comprises an 8 mm diameter disc of the dermal material applied to an agar plate treated with 0.5 mL of a 1:

1000 dilution of Staphylococcus aureus and the zone-of-inhibition of the gram positive bacteria is at least 10 mm within about 48 hours.

22. The acellular biologic matrix of claim 6, wherein the treated acellular biologic matrix demonstrates toxicity against gram positive bacteria, wherein a log reduction of greater than 1.0 is observed within 24 hours.

23. The acellular biologic matrix of claim 22, wherein a log reduction greater than 2.0 is observed within 24 hours.

38. The biologic matrix of claim 2, wherein the anti-infective agent is encapsulated in a selectively degradable polymer affixed to the acellular biologic matrix.

39. The acellular biologic matrix of claim 38, wherein the selectively degradable polymer is selected from the group consisting of:

poly lactic glycolic acid copolymer, polycaprolactone,alginate, gelatin, collagen, carboxymethylcellulose, and hyaluronic

41. The acellular biologic matrix of claim 3, wherein the tissue is derived from a mammalian source selected from the group consisting of:

humans, non-human primates, pigs, cows, horses, goats, sheep, dogs, cats, rabbits, guinea pigs, gerbils, hamsters, rats, or mice.

42. The acellular biologic matrix of claim 41, wherein the human source is a living human donor.

43. The acellular biologic matrix of claim 41, wherein the human source is cadaveric.

44. The acellular biologic matrix of claim 41, wherein the source is porcine.

45. The acellular biologic matrix of claim 41, wherein the source is equine.

46. The acellular biologic matrix of claim 41, wherein the source is bovine.

47. The acellular biologic matrix of claim 2, wherein the acellular biologic matrix has been disinfected.

48. The acellular biologic matrix of claim 2, wherein the acellular biologic matrix has been sterilized.

24. A method of treating an acellular biologic matrix with an anti-infective agent, comprising:

(a) hydrating an acellular biologic matrix with a solution of about 30-70% specially denatured alcohol; and

(b) dipping the acellular biologic matrix in a solution comprising an anti-infective agent.

26. The method of claim 24 or claim 25, wherein the anti-infective agent is triclosan.

36. The method of claim 24, 25, 27, or 28, wherein the biologic matrix is an acellular dermal matrix.

40. The method of claim 24, 25, 27, or 28, further comprising lyophilizing the biologic matrix treated with an anti-infective agent.

49. The method of claim 24, 25, 26, or 28, wherein the biologic matrix in (a) is hydrated in a 40% specially denatured alcohol solution.

25. A method of treating an acellular biologic matrix with an anti-infective agent, comprising:

(a) hydrating an acellular biologic matrix with a solution of about 30-70% specially denatured alcohol; and

(b) soaking the acellular biologic matrix in a solution comprising an anti-infective agent for at least about five seconds and less than 1 hour.

27. A method of preparing an acellular biologic matrix for implantation into a subject, comprising:

(a) hydrating an acellular biologic matrix in a solution of about 30-70% specially denatured alcohol; and

(b) dipping the hydrated biologic matrix in a triclosan solution.

29. An acellular biologic matrix prepared according to the method of claim 27 or claim 28.

30. The acellular biologic matrix of claim 29, wherein the acellular biologic matrix is suitable for implantation into a human patient.

31. The acellular biologic matrix of claim 30, wherein the acellular biologic matrix is suitable for use in a surgical procedure selected from the group consisting of:

hernia repair, abdominal wall repair;

breast reconstruction, cranial reconstruction, maxillary reconstruction, facial reconstruction, urologic reconstruction, gynecologic reconstruction, pulmonary reconstruction, bladder neck suspension, tendon repair, chronic wound care, acute wound care, burn care, dura repair and replacement, gastrointestinal reconstruction;

parastomal reinforcement and repair, trauma repair, diabetic ulcer and chronic venous insufficiency ulcer.

32. The acellular biologic matrix of claim 31, wherein the hernia is selected from the group consisting of:

ventral, inguinal, paraesophageal, incisional, and hiatal

33. The acellular biologic matrix of claim 31, wherein the triclosan is slowly released from the acellular biologic matrix after implantation into the human patient.

34. The acellular biologic matrix of claim 29, further comprising at least one additional anti-infective agent.

35. The acellular biologic matrix of claim 34, wherein the at least one additional anti-infective agent is chlorhexidine gluconate.

37. The acellular biologic matrix of claim 29, wherein the biologic matrix is an acellular dermal matrix.

28. A method of preparing an acellular biologic matrix for implantation into a subject, comprising:

(a) hydrating an acellular biologic matrix in a solution of about 30-70% specially denatured alcohol; and

(b) spraying the hydrated biologic matrix with a triclosan solution.