Rate controlled release of a pharmaceutical agent in a biodegradable device

• US 20040253293A1
• Filed: 06/16/2003
• Published: 12/16/2004
• Est. Priority Date: 06/16/2003
• 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., Shafiee, Afshin, Jani, Dharmendra, Bartels, Stephen Paul
• Application Number:
  US10/462,184
• Publication Number:
  US 20040253293A1
• Time in Patent Office: Days
• US Class Current: 424/426
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid

Abstract

Chemical erosion controlled release 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 chemical erosion controlled release drug delivery systems are controlled through the hydrophobicity and load level of pharmaceutically active agent or drug. Such controlled solubility characteristics allow for manipulation of the drug release rates depending on the particular therapeutic use and the particular needs of the patient.

Claims

1. A chemical erosion controlled release drug delivery system comprising:

a biodegradable polymer with a therapeutically effective amount of at least one hydrophobic or hydrophobically-enhanced pharmaceutically active agent with rate of chemical erosion and release rate of said active agent controlled by said active agent.

3. The drug delivery system of claim 1 or 2 wherein said biodegradable polymer is selected from the group consisting of poly(lactide)s, poly(glycolide)s, poly(lactide-co-glycolide)s, poly(lactic acid)s, poly(lactic acid-co-glycolic acid)s, polycaprolactones, polycarbonates, poly(ester amide)s, polyanhydrides, poly(amino acid)s, polyorthoesters, polyacetals, polycyanoacrylates, poly(ether ester)s, polydioxanones, poly(alkylene alkylate)s, copolymers of poly(ethylene glycol) and polyorthoesters, biodegradable polyurethanes and blends and copolymers thereof.

4. The drug delivery system of claim 1 or 2 wherein said hydrophobically-enhanced pharmaceutically active agents are produced by admixing a hydrophilic pharmaceutically active agent or a pharmaceutically active agent of low hydrophobicity with a hydrophobic agent.

6. The drug delivery system of claim 4 wherein said hydrophobic agent is selected from the group consisting of glycerol triacetate, glycerol diacetate, diethyl phthalate, dimethyl phthalate, phthalate esters, phosphate esters, fatty acid esters, glycerol derivatives, acetyl triethyl citrate, dibutyl tartrate and combinations thereof.

8. The drug delivery system of claim 1 or 2 wherein said at least one pharmaceutically active agent is selected from the group consisting of ametantrone, amphotericin B, annamycin, cyclosporin, daunorubicin, diazepam, doxorubicin, elliptinium, etoposide, fluocinolone acetonide, ketoconazole, methotrexate, miconazole, mitoxantrone, nystatin, phenytoin, lodeprednol, triamcinolone acetonide and vincristine.

9. The drug delivery system of claim 1 or 2 wherein said at least one pharmaceutically active agent is selected from the group consisting of cytokines and steroidal hormones.

10. The 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, neuroprotection agents, beta blockers, mitotics, epinephrine, anti-diabetic edema agents, anti-vascular endothelial growth factors (VEGF) receptors, pyrrolyl-methylene-indolinones, C_6-45 phenyl amino alkoxy quinazolines, anti-proliferative vitreoretinopathy agents, anti-inflammatory agents, immunological response modifiers, anti-ocular angiogenesis agents, anti-mobility agents, steroids, matrix metalloproteinase (MMP) inhibitors, humanized antibodies, aptamers, peptides, antibiotics, angiogenesis targeting agents, anti-cataract and anti-diabetic retinopathy agents, thiol cross-linking agents, anticancer agents, immune modulators, anti-clotting agents, anti-tissue damage agents, proteins, nucleic acids, anti-fibrous agents, non-steroidal anti-inflammatory agents, antibiotics, antipathogens, piperazine derivatives, cycloplegic and mydriatic agents anticholinergics, anticoagulants, antifibrinolytics, antihistamines, antimalarials, antitoxins, chelating agents, hormones, immunosuppressives, thrombolytics, vitamins, salts, desensitizers, prostaglandins, amino acids, metabolites and antiallergenics.

11. The 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, trifluorothymidine, interferon, immune modulators and growth factors.

12. A method of making the drug delivery system of claim 1 or 2 comprising:

encapsulating in a biodegradable polymer a therapeutically effective amount of at least one pharmaceutically active agent.

13. The method of claim 12 wherein said biodegradable polymer is selected from the group consisting of poly(lactide)s, poly(glycolide)s, poly(lactide-co-glycolide)s, poly(lactic acid)s, poly(lactic acid-co-glycolic acid)s, polycaprolactones, polycarbonates, poly(ester amide)s, polyanhydrides, poly(amino acid)s, polyorthoesters, polyacetals, polycyanoacrylates, poly(ether ester)s, polydioxanones, poly(alkylene alkylate)s, copolymers of polyethylene glycol and polyorthoester, biodegradable polyurethanes and blends and copolymers thereof.

14. The method of claim 12 wherein said at least one pharmaceutically active agent is selected from the group consisting of ametantrone, amphotericin B, annamycin, cyclosporin, daunorubicin, diazepam, doxorubicin, elliptinium, etoposide, fluocinolone acetonide, ketoconazole, methotrexate, miconazole, mitoxantrone, nystatin, phenytoin, lodeprednol, triamcinolone acetonide and vincristine.

15. The method of claim 12 wherein said at least one pharmaceutically active agent is selected from the group consisting of cytokines and steroidal hormones.

16. The method of claim 12 wherein said at least one pharmaceutically active agent is selected from the group consisting of anti-glaucoma agents, neuroprotection agents, beta blockers, mitotics, epinephrine, anti-diabetic edema agents, anti-vascular endothelial growth factors (VEGF) receptors, pyrrolyl-methylene-indolinones, C_6-45 phenyl amino alkoxy quinazolines, anti-proliferative vitreoretinopathy agents, anti-inflammatory agents, immunological response modifiers, anti-ocular angiogenesis agents, anti-mobility agents, steroids, matrix metalloproteinase (MMP) inhibitors, humanized antibodies, aptamers, peptides, antibiotics, angiogenesis targeting agents, anti-cataract and anti-diabetic retinopathy agents, thiol cross-linking agents, anticancer agents, immune modulators, anti-clotting agents, anti-tissue damage agents, proteins, nucleic acids, anti-fibrous agents, non-steroidal anti-inflammatory agents, antibiotics, antipathogens, piperazine derivatives, cycloplegic and mydriatic agents anticholinergics, anticoagulants, antifibrinolytics, antihistamines, antimalarials, antitoxins, chelating agents, hormones, immunosuppressives, thrombolytics, vitamins, salts, desensitizers, prostaglandins, amino acids, metabolites and antiallergenics.

17. The method of claim 12 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, trifluorothymidine, interferon, immune modulators and growth factors.

18. A method of using the drug delivery system of claim 1 or 2 comprising:

creating an incision within an eye; and

implanting said drug delivery system within said eye through said incision.

19. A method of using the drug delivery system of claim 1 or 2 comprising:

creating an incision within an eye; and

implanting said drug delivery system within said eye through said incision using a cannula used along with a needle of a vitrectomy system.

2. A chemical erosion controlled release drug delivery system comprising:

a biodegradable polymer with a therapeutically effective amount of at least one hydrophobic or hydrophobically-enhanced pharmaceutically active agent present in an amount sufficient to control rate of said active agent release from said biodegradable polymer.

5. A method of producing a hydrophobically-enhanced pharmaceutically active agent comprising:

admixing a hydrophilic pharmaceutically active agent or a pharmaceutically active agent of low hydrophobicity with a hydrophobic agent.

7. The method of claim 5 wherein said hydrophobic agent is selected from the group consisting of glycerol triacetate, glycerol diacetate, diethyl phthalate, dimethyl phthalate, phthalate esters, phosphate esters, fatty acid esters, glycerol derivatives, acetyl triethyl citrate, dibutyl tartrate and combinations thereof.

20. A method of using a drug delivery system comprising:

creating an incision within an eye; and

implanting said drug delivery system within said eye through said incision using a cannula used along with a needle of a vitrectomy system.