Composite absorbable/biodegradable rings for controlled drug delivery

• US 20040265355A1
• Filed: 06/03/2004
• Published: 12/30/2004
• Est. Priority Date: 06/26/2003
• Status: Active Grant

• Current Assignee: Poly-Med, Inc.
• Original Assignee: Poly-Med, Inc.
• Inventors: Shalaby, Shalaby W.
• Granted Patent: US 8,404,272 B2
• Time in Patent Office: Days
• US Class Current: 424/426
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 31/129 containing macromolecular fillers
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

A fiber-reinforced composite ring for the controlled release of at least one bioactive agent includes a biocompatible matrix reinforced with absorbable/biodegradable fibers capable of providing the mechanical properties needed for inserting and maintaining the ring in a body cavity for a desired period of time. Such ring system as can be used for the intravaginal, intraperitoneal, and subcutaneous delivery of at least one bioactive agent, including those used as contraceptives, antimicrobial agents, and/or antiviral agents, as well as those for the treatment of cancer.

Claims

1. A fiber-reinforced composite ring for the controlled release of at least one bioactive agent comprising a biocompatible matrix reinforced with absorbable/biodegradable fibers capable of providing the mechanical properties needed for inserting and maintaining said ring in a body cavity for a desired period of time.

2. A fiber-reinforced composite ring as in claim 1 wherein the absorbable/biodegradable reinforcing fibers are formed from at least one cyclic monomer selected from the group consisting of glycolide, l-lactide, ε

-caprolactone, p-dioxanone, and trimethylene carbonate.

3. A fiber-reinforced composite ring as in claim 1 wherein both the reinforcing fibers and matrix are absorbable/biodegradable.

4. A fiber-reinforced composite ring as in claim 1 wherein the reinforcing fibers are absorbable/biodegradable and the matrix is non-absorbable/non-biodegradable.

5. A fiber-reinforced composite ring as in claim 3 wherein the fibers are in the form of a circularly configured construct, with protruding side loops, of multifilament or monofilament yarn and wherein the matrix comprises an absorbable/biodegradable polymer comprising ester linkages.

6. A fiber-reinforced composite ring as in claim 5 wherein the matrix comprises an absorbable/biodegradable polymer comprising ester and urethane linkages.

7. A fiber-reinforced composite ring as in claim 4 wherein the non-absorbable matrix comprises a methacrylate polymer derived from at least one alkyl methacrylate monomer.

8. A fiber-reinforced composite ring as in claim 7 wherein the methacrylate polymer is derived from at least one alkyl methacrylate monomer and N-vinyl pyrrolidone.

9. A fiber-reinforced composite ring as in claim 1 wherein the reinforcing fibers are absorbable/biodegradable and the matrix comprises absorbable and non-absorbable components.

10. A fiber-reinforced composite ring as in claim 9 wherein the non-absorbable component of the matrix comprises polydimethylsiloxane and the absorbable/biodegradable component of the matrix comprises polymer chains with ester or ester-urethane linkages.

11. A fiber-reinforced composite ring as in claim 9 wherein the non-absorbable component of the matrix comprises methacrylate-derived chains.

12. A fiber-reinforced composite ring as in claim 1 further comprising a water-soluble excipient to aid the release of the bioactive agent.

13. A fiber-reinforced composite ring as in claim 1 further comprising a retardant additive to slow the release of the bioactive agent.

14. A fiber-reinforced composite ring as in claim 1 further comprising an absorbable polymeric outer coating to modulate the release of the at least one bioactive agent.

15. A fiber-reinforced composite ring as in claim 1 further comprising a bioadhesive coating.

16. A fiber-reinforced composite ring as in claim 1 wherein the matrix is microporous.

17. A fiber-reinforced composite ring as in claim 1 wherein the matrix comprises cyclodextrin or a cyclodextrin derivative.

18. A fiber-reinforced composite ring as in claim 1 wherein the body cavity comprises the vagina and wherein the at least one bioactive agent comprises a contraceptive agent selected from the group consisting of spermiostatic agents, spermicidal agents, hormonal agents, viscosity modifiers capable of increasing the viscosity of vaginal mucus.

19. A fiber-reinforced composite ring as in claim 1 wherein the body cavity comprises the vagina and wherein the at least one bioactive agent has contraceptive properties.

20. A fiber-reinforced composite ring as in claim 1 wherein the body cavity comprises the vagina and wherein the at least one bioactive agent has labor induction properties.

21. A fiber-reinforced composite ring as in claim 1 wherein the body cavity comprises the vagina and wherein the at least one bioactive agent is for intravaginal and transvaginal prevention or treatment of an infection selected from bacterial infections, fungal infections, viral infections and parasitic infections.

22. A fiber-reinforced composite ring as in claim 1 wherein the body cavity comprises the vagina and wherein the at least one bioactive agent is for the treatment of cervical or ovarian cancer.

23. A fiber-reinforced composite ring as in claim 1 wherein the body cavity comprises the vagina and wherein the at least one bioactive agent provides hormone replacement therapy.

24. A fiber-reinforced composite ring as in claim 1 wherein the body cavity comprises the vagina and wherein the at least one bioactive agent aids in achieving contraception.

25. A fiber-reinforced composite ring as in claim 1 wherein the body cavity comprises the vagina and wherein the at least one bioactive agent provides treatment for infertility.

26. A fiber-reinforced composite ring as in claim 1 wherein the body cavity comprises the vagina and wherein the at least one bioactive agent provides treatment for infectious diseases.

27. A fiber-reinforced composite ring as in claim 1 wherein the body cavity comprises the vagina and wherein the at least one bioactive agent provides treatment in gynecological cancer.

28. A fiber-reinforced composite ring as in claim 1 wherein the body cavity comprises the vagina and wherein the at least one bioactive agent is selected from the group consisting of antifertility drugs, testosterone, testosterone precursors, spermicidal agents, sperm immobilizers, and bisphosphonate.

29. A fiber-reinforced composite ring as in claim 1 wherein the body cavity comprises the vagina and wherein the at least one bioactive agent is selected from the group consisting of antiprogestinic agents, anesthetic agents, analgesic agents, anti-inflammatory agents, antimicrobial agents, antiviral agents, and antipsychotic agents.

30. A fiber-reinforced composite ring as in claim 1 wherein the body cavity comprises the vagina and wherein the at least one bioactive agent is selected from the group consisting of monoclonal antibodies, recombinant immunomodulator vaccines, and hematopoietic growth factors.

31. A fiber-reinforced composite ring as in claim 1 wherein the body cavity comprises the peritoneal cavity and wherein the at least one bioactive agent is selected from the group consisting of anesthetic agents, analgesic agents, anti-inflammatory agents, antimicrobial agents, antibacterial agents, antifungal agents, antiviral agents, antipsychotic agents, antiadhesion agents, and antineoplastic agents.

32. A fiber-reinforced composite ring as in claim 1 wherein the at least one bioactive agent is of modulated solubility in the polymeric matrix.

33. A fiber-reinforced composite ring as in claim 32 wherein the at least one bioactive agent is an ionic conjugate of a basic antimicrobial drug, the conjugate comprising an acid component and a basic component comprising the antimicrobial drug, the conjugate having lower solubility in the polymeric matrix than the antimicrobial drug.

34. A fiber-reinforced composite ring as in claim 33 wherein the basic drug is selected from the group consisting of metronidazole and miconazole.

35. A fiber-reinforced composite ring as in claim 34 wherein the acid component of the conjugate is selected from the group consisting of pamoic acid, monosodium pamoate, naphthoic acid, and dimethyl naphthoic acid.

36. A fiber-reinforced composite ring as in claim 1 as a component of an orthopedic prosthesis.

37. A fiber-reinforced composite ring as in claim 1 as a component of a subcutaneous device.