Implant device release agents and methods of using same

• US 9,120,249 B2
• Filed: 04/25/2008
• Issued: 09/01/2015
• Est. Priority Date: 04/27/2007
• Status: Active Grant

• Current Assignee: ENDO USA Incorporated
• Original Assignee: Endo Pharmaceuticals Solutions Incorporated (Endo International PLC)
• Inventors: Kuzma, Petr, Decker, Stephanie, Quandt, Harry
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): HELM, CARALYNNE E
• Application Number:
  US12/109,852
• Publication Number:
  US 20080311170A1
• Time in Patent Office: 2,685 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/802 Additives, excipients, e.g. cyclodextrins, fatty acids, surfactants
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/02 of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
• CPC Class Codes: B29C 33/62 based on polymers or oligomers
• CPC Class Codes: B29C 41/085 by rotating the former around its axis of symmetry

Abstract

Medical implant devices are prepared from a polymeric material and a release agent, where the device is a molded, reservoir implant, and the release agent has a molecular weight (MW) of at least 1000. The release agent may be a non-ionic surfactant such as Brij 35, polyoxyetheylene(20)sorbitan trioleate, Tween 20, Tween 80, vitamin E TPGS, and a mixture of any two or more thereof. Hydrated implants may have a surface area of about 500 mm² or greater.

Claims

1. A device suitable for implantation into a subject for delivery of an active agent to the subject at a zero-order or near-zero order rate comprising:

a polymeric material comprising a polymer formed from one or more hydrophilic, ethylenically unsaturated monomers and a release agent;

wherein the device is a molded, reservoir implant comprising a hollow core for containing the active agent and an optional pharmaceutical carrier; and

the release agent comprises d-α

-tocopheryl polyethylene glycol 1000 succinate (Vitamin E TPGS).

2. The device of claim 1, wherein the reservoir implant is a dry implant.

3. The device of claim 2, wherein the dry implant has a surface area of about 350 mm² or greater.

4. The device of claim 2, wherein the dry implant has a surface area of from about 350 mm² to about 600 mm².

5. The device of claim 1, wherein the reservoir implant is a hydrated implant.

6. The device of claim 5, wherein the hydrated implant has a surface area of about 500 mm² or greater.

7. The device of claim 5, wherein the hydrated implant has a surface area of from about 500 mm² to about 800 mm².

8. The device of claim 1, wherein the polymeric material is prepared from a monomer mixture comprising two or more polymerizable monomers.

9. The device of claim 8, wherein the monomers are selected from 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, hydroxypropyl methacrylate, hydroxypropyl acrylate, hydroxybutyl methacrylate, hydroxybutyl acrylate, diethylene glycol methacrylate, diethylene glycol acrylate, propylene glycol methacrylate, propylene glycol acrylate, dipropylene glycol methacrylate, dipropylene glycol acrylate, glycidyl methacrylate, glycidyl acrylate, glyceryl methacrylate, glyceryl acrylate, N-methylmethacrylamide, N,N-dimethylmethacrylamide, N-vinylpyrrolidone N-vinylmethylpyrrolidone, N-vinylcaprolactam, N-vinyl-2-methylcaprolactam, N-vinyl-3,5-dimethylcaprolactam, or a mixture of any two or more thereof.

10. The device of claim 8, wherein the monomers are selected from methyl acrylate, methyl methacrylate, ethyl acrylate, ethyl methacrylate, propyl methacrylate, butyl acrylate, butyl methacrylate, methoxymethyl acrylate, methoxymethyl methacrylate, ethoxymethyl acrylate, ethoxymethyl methacrylate, methoxyethyl methacrylate, vinyl acetate, vinyl propionate, or a mixture of any two or more thereof.

11. The device of claim 8, wherein the polymerizable monomers are liquids.

12. A process comprising:

charging a polymerization column or a mold with a liquid comprising one or more hydrophilic, ethylenically unsaturated monomers and a release agent;

rotating the polymerization column or mold about its longitudinal axis at a speed sufficient to displace the monomer radially outward along the interior surfaces of the polymerization column or mold;

maintaining the polymerization column or mold at a position substantially parallel to the ground;

polymerizing the liquid polymerizable material; and

recovering a reservoir implant device;

wherein the release agent is Vitamin E TPGS.

13. The process of claim 12, wherein the reservoir implant is a dry implant.

14. The process of claim 13, wherein the dry implant has a surface area of about 350 mm² or greater.

15. The process of claim 13, wherein the dry implant has a surface area of from about 350 mm² to about 600 mm².

16. The process of claim 12, wherein the reservoir implant is a hydrated implant.

17. The process of claim 16, wherein the hydrated implant has a surface area of about 500 mm² or greater.

18. The process of claim 16, wherein the hydrated implant has a surface area of from about 500 mm² to about 800 mm².

19. The process of claim 12, wherein the liquid comprises two or more polymerizable monomers.

20. The process of claim 12, wherein the polymerization column or mold is further charged with a free-radical polymerization catalyst selected from organic peroxides, percarbonates, peroxycarbonates, peroxydicarbonates, hydroperoxides, alkali metal sulfates, benzoin methyl ether, or a mixture of any two or more thereof.