Partially absorbable fiber-reinforced composites for controlled drug delivery

• US 20050053639A1
• Filed: 09/08/2004
• Published: 03/10/2005
• 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 8,399,013 B2
• Time in Patent Office: Days
• US Class Current: 424/426
• CPC Class Codes: A61F 2250/0031 made from both resorbable and non-resorbable prosthetic parts, e.g. adjacent parts
• CPC Class Codes: A61K 31/375 Ascorbic acid, i.e. vitamin C; Salts thereof
• CPC Class Codes: A61K 31/4164 1,3-Diazoles
• CPC Class Codes: A61K 31/7135 Compounds containing heavy metals
• CPC Class Codes: A61K 9/0002 Galenical forms characterised by the drug release technique; Application systems commanded by energy
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61K 9/0036 Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms
• CPC Class Codes: A61K 9/0046 Ear
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61L 15/44 Medicaments
• CPC Class Codes: A61L 15/64 specially adapted to be resorbable inside the body
• CPC Class Codes: A61L 2300/222 Steroids, e.g. corticosteroids
• CPC Class Codes: A61L 2300/256 Antibodies, e.g. immunoglobulins, vaccines
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/408 Virucides, spermicides
• CPC Class Codes: A61L 2300/43 Hormones, e.g. dexamethasone
• 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 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 : Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

This invention describes a partially absorbable, fiber-reinforced composite in the form of a ring, or a suture-like thread, with modified terminals for use as a controlled delivery system of at least one bioactive agent, wherein said composite comprising an absorbable fiber construct capable of providing time-dependent mechanical properties of a biostable elastomeric matrix containing an absorbable microparticulate ion-exchanger to modulate the release of the bioactive agent(s) for a desired period(s) of time at a specific biological site; this can be a vaginal canal, peritoneal cavity, scrotum, prostate gland, an ear loop or subcutaneous tissue. Such drug delivery systems can be used for the local administration of at least one bioactive agent, including those used as contraceptive, antimicrobial, anti-inflammatory and/or antiviral agents as well as for cancer treatment.

Claims

1. A partially absorbable, fiber-reinforced composite for the controlled delivery of at least one bioactive agent comprising an absorbable fiber construct within a biostable elastomeric, copolymeric matrix, the matrix further containing an absorbable microparticulate ion-exchanging polymer to modulate the release of said bioactive agent for a desired period of time at a specific biological site, the fiber construct capable of providing time-dependent mechanical properties.

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

-caprolactone, p-dioxanone, trimethylene carbonate, and a morpholine-2,5-dione.

3. A partially absorbable, fiber-reinforced composite as in claim 1 wherein the biostable matrix comprises a polyether urethane elastomer.

4. A partially absorbable, fiber-reinforced composite as in claim 1 wherein the biostable matrix comprises a silicone elastomer.

5. A partially absorbable, fiber-reinforced composite as in claim 4 wherein the silicon elastomer comprises copolymeric polysiloxane having dimethyl siloxane sequences.

6. A partially absorbable, fiber-reinforced composite as in claim 5 wherein the matrix further contains a microparticulate silica.

7. A partially absorbable, fiber-reinforced composite as in claim 1 wherein the absorbable microparticulate ion-exchanging polymer comprises a carboxyl-bearing polyester based on at least one of the cyclic monomer selected from the group consisting of glycolide, l-lactide, and a morpholine-2,5-dione.

8. A partially absorbable, fiber-reinforced composite as in claim 1 in the form of an intravaginal ring, wherein the biological site is the vagina.

9. A partially absorbable, fiber-reinforced composite as in claim 8 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 polymer comprising ester linkages.

10. A partially absorbable, fiber-reinforced composite as in claim 5 wherein the absorbable reinforcing fibers are formed from at least one cyclic monomer selected from the group consisting of glycolide, l-lactide, ε

-caprolactone, p-dioxanone, trimethylene carbonate, and a morpholine-2,5-dione.

11. A partially absorbable, fiber-reinforced composite as in claim 5 wherein the absorbable microparticulate ion-exchanging polymer comprises a carboxyl-bearing polyester based on at least one of the cyclic monomer from the group consisting of glycolide, l-lactide, and a morpholine-2,5-dione.

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

13. A partially absorbable, fiber-reinforced composite as in claim 1 further comprising a bioadhesive coating.

14. A partially absorbable, fiber-reinforced composite as in claim 1 wherein the matrix is microporous.

15. A partially absorbable, fiber-reinforced composite as in claim 8 wherein the at least one bioactive agent comprises a contraceptive agent selected from the group consisting of spermiostatic agents, spermicidal agents, hormonal agents, non-steroidal agents, and viscosity modifiers capable of increasing the viscosity of vaginal mucus.

16. A partially absorbable, fiber-reinforced composite as in claim 8 wherein the at least one bioactive agent comprises a combination of ascorbic acid and iron gluconate.

17. A partially absorbable, fiber-reinforced composite as in claim 8 wherein the at least one bioactive agent comprises a non-steroidal compound comprising tanaproget.

18. A partially absorbable, fiber-reinforced composite as in claim 8 wherein the at least one bioactive agent has labor induction properties.

19. A partially absorbable, fiber-reinforced composite as in claim 8 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.

20. A partially absorbable, fiber-reinforced composite as in claim 8 wherein the at least one bioactive agent is for the treatment of cervical or ovarian cancer.

21. A partially absorbable, fiber-reinforced composite as in claim 8 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.

22. A partially absorbable, fiber-reinforced composite as in claim 1 wherein the biological site 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.

23. A partially absorbable, fiber-reinforced composite as in claim 1 wherein the at least one bioactive agent is selected from the group consisting of monoclonal antibodies, recombinant immunomodulator vaccines, and hematopoietic growth factors.

24. A partially absorbable, fiber-reinforced composite as in claim 1 in the form of a filament having a practically spherical head for outward retrieval from the biological site.

25. A partially absorbable, fiber-reinforced composite as in claim 24 wherein the biological site is a human peritoneal cavity with the head being placed subcutaneously.

26. A partially absorbable, fiber-reinforced composite as in claim 24 wherein the biological site is in a human scrotum with the head being placed subcutaneously.

27. A partially absorbable, fiber-reinforced composite as in claim 24 wherein the biological site is the ear loop of an animal or human, with the head remaining ex vivo.

28. A partially absorbable, fiber-reinforced composite as in claim 1 in the form of a suture-like strand for threading through a biological site.

29. A partially absorbable, fiber-reinforced composite as in claim 28 wherein the biological site is an animal skin or muscle wherein the end of the suture-like filament is knotted at the entrance and exit point of the skin for ease of removal after the required period of time.

30. A partially absorbable, fiber-reinforced composite as in claim 28 wherein the biological site is human skin or muscle wherein the end of the suture-like filament is knotted at the entrance and exit point of the skin for ease of removal after the required period of time.