Fluorosiloxane matrix controlled diffusion drug delivery systems

• US 20040043067A1
• Filed: 06/19/2002
• Published: 03/04/2004
• Est. Priority Date: 06/19/2002
• Status: Abandoned Application

• Current Assignee: Bausch & Lomb Incorporated (Bausch Health Cos., Inc.)
• Original Assignee: Bausch & Lomb Incorporated (Bausch Health Cos., Inc.)
• Inventors: Kunzler, Jay F., Salamone, Joseph C., Ammon, Daniel M. Jr.
• Application Number:
  US10/175,716
• Publication Number:
  US 20040043067A1
• Time in Patent Office: Days
• US Class Current: 424/468
• CPC Class Codes: A61K 31/357 having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
• 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: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: C08G 77/14 containing silicon bound to oxygen-containing groups C08G77/045 takes precedence
• CPC Class Codes: C08G 77/20 containing silicon bound to unsaturated aliphatic groups C08G77/045 takes precedence
• CPC Class Codes: C08G 77/24 halogen-containing groups
• CPC Class Codes: C08G 77/42 Block-or graft-polymers containing polysiloxane sequences polymerising aliphatic unsaturated monomers on to a polysiloxane C08F283/12
• CPC Class Codes: C08G 77/70 Siloxanes defined by use of the MDTQ nomenclature
• CPC Class Codes: C08L 83/04 Polysiloxanes

Abstract

Fluorinated side-chain siloxane copolymeric matrix controlled diffusion drug delivery systems are provided that allow controlled release of sustained concentrations of therapeutic agents within a treated area for a prolonged period of time. The favorable solubility characteristics of the fluorinated side-chains of the siloxane copolymeric matrix controlled diffusion drug delivery systems allow for manipulation of drug release rates depending on the particular therapeutic use and the particular needs of the patient.

Claims

1. A matrix controlled diffusion drug delivery system comprising:

a fluorinated side-chain siloxane copolymer polymerized with a therapeutically effective amount of at least one pharmaceutically active agent and optionally one or more monomers.

3. The matrix controlled diffusion drug delivery system of claim 1 or 2 wherein said at least one pharmaceutically active agent is selected from the group consisting of anti-glaucoma agents, anti-cataract agents, anti-diabetic retinopathy agents, thiol cross-linking agents, anti-cancer agents, immune modulators, anti-clotting agents, anti-tissue damage agents, anti-inflammatory agents, anti-fibrous agents, non-steroidal anti-inflammatory agents, antibiotics, anti-pathogen agents, piperazine derivatives, cycloplegic agents and mydriatic agents.

4. The matrix controlled diffusion drug delivery system of claim 1 or 2 wherein said at least one pharmaceutically active agent is selected from the group consisting of anticholinergics, anticoagulants, antifibrinolytics, antihistamines, antimalarials, antitoxins, chelating agents, hormones, immunosuppressives, thrombolytics, vitamins, salts, desensitizers, prostaglandins, amino acids, metabolites and antiallergenics.

5. The matrix controlled diffusion drug delivery system of claim 1 or 2 wherein said at least one pharmaceutically active agent is selected from the group consisting of hydrocortisone, gentamycin, 5-fluorouracil, sorbinil, interleukin-2, phakan-a, thioloa-thiopronin, bendazac, acetylsalicylic acid, fluocinolone acetonide, trifluorothymidine, interferon, immune modulators and growth factors.

6. The matrix controlled diffusion drug delivery system of claim 1 or 2 wherein said one or more monomers are selected from the group consisting of methyl methacrylate, N,N-dimethylacrylamide, acrylamide, N-methylacrylamide, 2-hydroxyethyl methacrylate, hydroxyethoxyethyl methacrylate, hydroxydiethoxyethyl methacrylate, methoxyethyl methacrylate, methoxyethoxyethyl methacrylate, methoxydiethoxyethyl methacrylate, poly(ethylene glycol) methacrylate, methoxy-poly(ethylene glycol) methacrylate, methacrylic acid, sodium methacrylate, glycerol methacrylate, hydroxypropyl methacrylate, N-vinylpyrrolidione and hydroxybutyl methacrylate.

15. A method of using the matrix controlled diffusion drug delivery system of claim 1 or 2 comprising:

creating an incision within an eye and

implanting said matrix controlled diffusion drug delivery system within said eye through said incision.

2. A matrix controlled diffusion drug delivery system comprising:

a fluorinated side-chain siloxane copolymer represented by

wherein the R₁ groups may be the same or different selected from the group consisting of C_1-7 alkyl and C_6-10 aryl;

the R₂ group is a C_1-7 alkylene;

x is a natural number less than 26;

p and q may be the same or different natural numbers less than 100 and z is a natural number less than 11, polymerized with a therapeutically effective amount of at least one pharmaceutically active agent and optionally one or more monomers.

7. A fluorinated side-chain siloxane copolymer comprising:

8. A method of making a matrix controlled diffusion drug delivery system comprising:

polymerizing a fluorinated side-chain siloxane copolymer with a therapeutically effective amount of at least one pharmaceutically active agent and optionally one or more monomers.

9. A method of making a matrix controlled diffusion drug delivery system comprising:

polymerizing a fluorinated side-chain siloxane copolymer represented by

wherein the R₁ groups may be the same or different selected from the group consisting of C_1-7 alkyl and C_6-10 aryl;

the R₂ group is a C_1-7 alkylene;

x is a natural number less than 26;

p and q may be the same or different natural numbers less than 100 and z is a natural number less than 11, with a therapeutically effective amount of at least one pharmaceutically active agent and optionally one or more monomers.

10. A method of making a matrix controlled diffusion drug delivery system comprising:

preparing a methacrylate-capped siloxane with a perfluorinated side-chain copolymer;

copolymerizing said methacrylate-capped siloxane with a perfluorinated side-chain copolymer with one or more monomers and a therapeutically effective amount of at least one pharmaceutically active agent.

11. The method of claim 8, 9 or 10 wherein said at least one pharmaceutically active agent is selected from the group consisting of anti-glaucoma agents, anti-cataract agents, anti-diabetic retinopathy agents, thiol cross-linking agents, anti-cancer agents, immune modulators, anti-clotting agents, anti-tissue damage agents, anti-inflammatory agents, anti-fibrous agents, non-steroidal anti-inflammatory agents, antibiotics, anti-pathogen agents, piperazine derivatives, cycloplegic agents and mydriatic agents.

12. The method of claim 8, 9 or 10 wherein said at least one pharmaceutically active agent is selected from the group consisting of anticholinergics, anticoagulants, antifibrinolytics, antihistamines, antimalarials, antitoxins, chelating agents, hormones, immunosuppressives, thrombolytics, vitamins, salts, desensitizers, prostaglandins, amino acids, metabolites and antiallergenics.

13. The method of claim 8, 9 or 10 wherein said at least one pharmaceutically active agent is selected from the group consisting of hydrocortisone, gentamycin, 5-fluorouracil, sorbinil, interleukin-2, phakan-a, thioloa-thiopronin, bendazac, acetylsalicylic acid, fluocinolone acetonide, trifluorothymidine, interferon, immune modulators and growth factors.

14. The method of claim 8, 9 or 10 wherein said one or more monomers are selected from the group consisting of methyl methacrylate, N,N-dimethylacrylamide, acrylamide, N-methylacrylamide, 2-hydroxyethyl methacrylate, hydroxyethoxyethyl methacrylate, hydroxydiethoxyethyl methacrylate, methoxyethyl methacrylate, methoxyethoxyethyl methacrylate, methoxydiethoxyethyl methacrylate, poly(ethylene glycol) methacrylate, methoxy-poly(ethylene glycol) methacrylate, methacrylic acid, sodium methacrylate, glycerol methacrylate, hydroxypropyl methacrylate, N-vinylpyrrolidione and hydroxybutyl methacrylate.