Biomaterials for preventing post-surgical adhesions comprised of hyaluronic acid derivatives

• US 6,723,709 B1
• Filed: 02/27/1998
• Issued: 04/20/2004
• Est. Priority Date: 08/29/1995
• Status: Expired due to Term

• Current Assignee: Anika Therapeutics Incorporated
• Original Assignee: Fidia Advanced Biopolymers S.R.L. (Anika Therapeutics Incorporated)
• Inventors: Pressato, Daniele, Callegaro, Lanfranco, Pavesio, Alessandra
• Primary Examiner(s): Wilson, James O.
• Assistant Examiner(s): Maier, Leigh C.
• Application Number:
  US09/031,835
• Time in Patent Office: 2,244 Days
• Field of Search: 514/56, 514/62, 514/54, 536/18.7, 536/53, 536/55, 536/55.2, 424/423, 424/443, 424/488
• US Class Current: 514/54
• CPC Class Codes: A61L 31/042 Polysaccharides
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/129 containing macromolecular fillers
• 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: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

New biomaterials essentially constituted by esterified derivatives of hyaluronic acid or by cross-linked derivatives of hyaluronic acid for use in the surgical sector, particularly for use in the prevention of post-surgical adhesion.

Claims

1. A composite biomaterial comprised of:

a benzyl ester of hyaluronic acid, wherein 80% of the carboxyl groups of hylauronic acid are esterified with a benzyl radical and up to 20% of the carboxyl groups are esterified with the alkyl radical of a C10 to C20 aliphatic alcohol, and

wherein said biomaterial is in the form of a gel, a flat membrane or mesh, a woven or non-woven tissue, or combinations thereof and wherein said biomaterials prevent the surgical adhesion of tissue.

2. The composite material according to claim 1 wherein said alcohol is stearyl or palmitic alcohol.

3. The composite material according to claim 1 which further comprises a non-biodegradable synthetic polymer.

4. The composite material according to claim 3, wherein said synthetic polymer is a member selected from the group consisting of polypropylene, polyethylene, polyester and polytetrafluoroethylene.

5. The biomaterial of claim 1 further comprising a biologically active agent.

6. The biomaterial of claim 5 wherein the biologically active agent is selected from the group consisting of steroidal and non-steroidal antiinflammatories, fibrinolytics, hemostatics, antithrombotics, growth factors, antitumorals, antibacterials, antivirals and antifungals.

7. The composite biomaterial according to claim 1, further comprising an auto-crosslinked derivative hyaluronic acid wherein 0.5 to 20% of the carboxyl groups of hyaluronic acid are cross-linked to the hydroxyl group of the same or different hyaluronic acid molecule.

8. The composite biomaterial according to claim 7, wherein said auto-crosslinked derivative has 4.5 to 5.0% of the carboxyl groups of the hyaluronic acid molecule cross-linked.

9. A method for preventing surgical adhesions of tissue which comprises applying to tissue involved in surgery a biomaterial comprised of:

a benzyl ester of hyaluronic acid wherein 80% of the carboxyl groups of hyaluronic acid are esterified with a benzyl radical and up to 20% of the carboxyl groups are esterified with the alkyl radical of a C₁₀ to C₂₀ aliphatic alcohol.

10. The method according to claim 9, wherein said alcohol is stearyl or palmitic alcohol.

11. The method according to claim 9 wherein said biomaterial further comprises a non-biodegradable synthetic polymer.

12. The method according to claim 11, wherein said synthetic polymer is a member selected from the group consisting of polypropylene, polyethylene, polyester and polytertrafluoroetheylene.

13. The method of claim 9 wherein said surgery is selected from the group consisting of abdominal, laparoscopic, laparotomic, intestinal, gynecologic, abdominalpelvic, peritoneal, urogenital, orthopedic, spinal/dura mater, tendon/nerve, including carpal tunnel, cardiovascular, thoracic, ophthalmic, oncologic, plastic, esthetic, ENT, paranasal sinuses, and transplantation.

14. The method of claim 9, wherein said biomaterial further comprises an auto-crosslinked derivative hyaluronic acid wherein 0.5 to 20% of the carboxyl groups of hyaluronic acid are crosslinked to the same or different hyaluronic acid molecule.

15. The method according to claim 14, wherein said cross-linked derivative has 4.5 to 5% of the carboxyl groups of the hyaluronic acid molecule cross-linked.