Method and device for long-term delivery of drugs

• US 5,629,008 A
• Filed: 06/07/1994
• Issued: 05/13/1997
• Est. Priority Date: 06/02/1992
• Status: Expired due to Term

• Current Assignee: C.R. Bard, Inc. (Becton Dickinson & Co)
• Original Assignee: C.R. Bard, Inc. (Becton Dickinson & Co)
• Inventors: Lee, Clarence C.
• Primary Examiner(s): Azpuru, Carlos A.
• Application Number:
  US08/255,343
• Time in Patent Office: 1,071 Days
• Field of Search: 424/423, 424/424, 424/426, 604/892.1
• US Class Current: 424/426
• 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 9/0092 Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
• CPC Class Codes: A61M 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50

Abstract

The present invention is an implantable device that is capable of delivering a therapeutic agent to a tissue or organ over a long period of time. The implantable device is especially suited for treating tissues and organs that are comprised of smooth muscle. The implantable device can deliver either a single therapeutic agent or a plurality of therapeutic agents to the tissue or organ at zero order kinetics.

Claims

1. An implant device for the long term delivery of a therapeutic agent to a tissue or organ, comprising:

a container for implantation within the tissue or organ; and

a therapeutic agent immobilized in a biodegradable matrix wherein said matrix is biodegradable by enzymatic or acid/base hydrolysis and contained within the container such that the therapeutic agent is released at a rate of at least approximately 0.1 μ

g/day over a period of at least approximately one month, said device having a diameter of between approximately 20 microns and approximately 3 cm.

2. The implant device of claim 1, wherein the container is comprised of a material which is impermeable to macromolecules.

3. The implant device of claim 2, wherein the rate of release of the therapeutic agent is controlled by a portion of the container being permeable to the therapeutic agent.

4. The implant device of claim 2, wherein the rate of release of the therapeutic agent is further controlled by controlling the permeability of the permeable portion.

5. The implant device of claim 2, wherein the rate of release of the therapeutic agent is further controlled by controlling the dimensions of the permeable portion.

6. The implant device of claim 1, wherein the rate of release is controlled by controlling the rate of biodegradation of the biodegradable matrix.

7. The implant device of claim 1, wherein the therapeutic agent is selected from the group consisting of antimuscarinic agents, anticholinergic agents, antispasmodic agents, calcium antagonist agents, potassium channel openers, musculotropic relaxants, polysynaptic inhibitors, beta-adrenergic stimulators and antitumor agents.

8. The implant device of claim 1, wherein the therapeutic agent is selected from the group consisting of propantheline bromide, imipramine, hyoscyamine sulfate, oxybutynin chloride, carmustine, dicyclomine and terodiline.

9. The implant device of claim 1, wherein the biodegradable matrix is selected from the group consisting of polylactide, polyanhydrides, polyglycolide, polylactide co-glycolide polypeptides, poly(ortho)esters, hyaluronic acid, collagen, chondroitin sulfate, carboxylic acids, phospholipids, polysaccharides, polyamino acids, nucleic acids, phenylalanine, tyrosine, isoleucine, polynucleotides, polyethylene glycol, polyvinyl propylene, polyvinylpyrrolidone and beeswax.

10. The implant device of claim 1, wherein the container is a cylinder.

11. The implant device of claim 2, wherein the material which is impermeable to macromolecules is selected from the group consisting of stainless steel, gold, titanium, platinum, metal alloys, silicone, silastic and plastics.

12. The implant device of claim 11, wherein the plastic is selected from the group consisting of polyethylene, polypropylene, polycarbonate, polystyrene, polyethylene terephthalates, polyurethane and parylene.

13. A method of treating a tissue or organ comprising the step of implanting an implant device into the tissue or organ, the implant device comprising:

a container for implantation within the tissue or organ; and

a therapeutic agent immobilized in a biodegradable matrix wherein said matrix is biodegradable by enzymatic or acid/base hydrolysis and contained within the container such that the therapeutic agent is released at a rate of at least approximately 0.1 μ

g/day over a period of at least approximately one month, said device having a diameter of between approximately 20 microns and approximately 3 cm.

14. The method of claim 13, wherein the container is comprised of a material which is impermeable to macromolecules.

15. The method of claim 13, wherein the rate of release of the therapeutic agent is controlled by a portion of the container being permeable to the therapeutic agent.

16. The method of claim 15, wherein the rate of release of the therapeutic agent is further controlled by controlling the permeability of the permeable portion.

17. The method of claim 15, wherein the rate of release of the therapeutic agent is controlled by controlling the dimensions of the permeable portion.

18. The method of claim 13, wherein the rate of release is controlled by controlling the rate of biodegradation of the biodegradable matrix.

19. The method of claim 13, wherein the therapeutic agent is selected from the group consisting of antimuscarinic agents, anticholinergic agents, antispasmodic agents, calcium antagonist agents, potassium channel openers, musculotropic relaxants, polysynaptic inhibitors, beta-adrenergic stimulators and antitumor agents.

20. The method of claim 19, wherein the therapeutic agent is propantheline bromide, imipramine, hyoscyamine sulfate, carmustine, oxybutynin chloride, dicyclomine and terodiline.

21. The method of claim 18, wherein the biodegradable matrix is selected from the group consisting of polylactide, polyanhydrides, polyglycolide, polylactide co-glycolide polypeptides, poly(ortho)esters, hyaluronic acid, collagen, chondroitin sulfate, carboxylic acids, phospholipids, polysaccharides, polyamino acids, nucleic acids, phenylalanine, tyrosine, isoleucine, polynucleotides, polyethylene glycol, polyvinyl propylene, polyvinylpyrrolidone and beeswax.

22. The method of claim 13, wherein the container is a cylinder.

23. The method of claim 14, wherein the material which is impermeable to macromolecules is selected from the group consisting of stainless steel, gold, titanium, platinum, metal alloys, silicone, silastic and plastics.

24. The implant device of claim 23, wherein the plastic is selected from the group consisting of polyethylene, polypropylene, polycarbonate, polystyrene, polyethylene terephthalates, polyurethane and parylene.