Biodegradable neurotoxin implant

• US 6,383,509 B1
• Filed: 08/07/2001
• Issued: 05/07/2002
• Est. Priority Date: 06/02/2000
• Status: Expired due to Fees

• Current Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Original Assignee: Allergan Sales LLC (Abbvie Incorporated)
• Inventors: Brady, Daniel G., Donovan, Stephen
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): FUBARA, BLESSING M
• Application Number:
  US09/923,631
• Publication Number:
  US 20020028244A1
• Time in Patent Office: 273 Days
• Field of Search: 424/423, 424/422, 424/484, 424/486, 424/236.1, 424/247.1, 514/964
• US Class Current: 424/423
• CPC Class Codes: A61K 38/4893 Botulinum neurotoxin (3.4.24.69)
• 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: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia

Abstract

A biocompatible implant for continuous in vivo release of a neurotoxin over a treatment period extending from one month to five years. The implant can be made of casting a solution of a polymer, such as an ethyl vinyl acetate copolymer and the neurotoxin. The neurotoxin can be a botulinum toxin.

Claims

1. A controlled release system, comprising:

(a) a biodegradable polymer, and;

(b) a quantity of neurotoxin located within the biodegradable polymer, wherein fractional amounts of the neurotoxin can be released from the biodegradable polymer over a prolonged period of time, without a significant immune response.

2. The controlled release system of claim 1, wherein neurotoxin is released from the polymer in a continuous or monophasic manner.

3. The controlled release system of claim 1, wherein the prolonged period of time during which neurotoxin is released from the polymer extends over a period of time of from about 10 days to about 6 years.

4. The controlled release system of claim 1, wherein the neurotoxin comprises a polypeptide.

5. The controlled release system of claim 1, wherein the neurotoxin comprises a presynaptic neurotoxin.

6. The controlled release system of claim 1, wherein the neurotoxin is a Clostridial neurotoxin.

7. The controlled release system of claim 1, wherein the neurotoxin is a botulinum toxin.

8. The controlled release system of claim 1, wherein the neurotoxin is a botulinum toxin selected from the group consisting of botulinum toxin types A, B, C₁, D, E, F and G.

9. The controlled release system of claim 1, wherein the neurotoxin is a botulinum toxin type A.

10. The controlled release system of claim 1, wherein the biodegradable polymer is selected from the group consisting of poly(lactides), poly(glycolides), poly(lactide-co-glycolides), poly(lactic acid)s, poly(glycolic acid)s, poly(lactic acid-co-glycolic acid)s, polycaprolactone, polycarbonates, polyesteramides, polyanhydrides, poly(amino acids), polyorthoesters, polycyanoacrylates, poly(p-dioxanone), poly(alkylene oxalates), biodegradable polyurethanes, blends and copolymers thereof.

11. The controlled release system of claim 1, wherein the quantity of the neurotoxin is between about 1 unit and about 50,000 units of a botulinum toxin.

12. The controlled release system of claim 1, wherein the quantity of the neurotoxin is between about 10 units and about 2,000 units of a botulinum toxin type A.

13. The controlled release system of claim 1, wherein the quantity of the neurotoxin is between about 100 units and about 30,000 units of a botulinum toxin type B.

14. The controlled release system of claim 1 wherein the neurotoxin is a botulinum toxin which is released in an amount effective to cause flaccid muscular paralysis of a muscle or muscle group at or in the vicinity of the implanted system.

15. A controlled release system, comprising:

(a) a biodegradable polymeric matrix, and;

(b) between about 10 units and about 20,000 units of a botulinum toxin within the biodegradable polymeric matrix, wherein fractional amounts of the botulinum toxin can be released from the polymeric matrix over a prolonged period of time extending from about 2 months to about 5 years, without a significant immune response.

16. A method for making a controlled release system which will not induce a significant immune response, the method comprising the steps of:

(a) dissolving a biodegradable polymer in a solvent to form a polymer solution;

(b) mixing or dispersing a neurotoxin in the polymer solution to form a polymer-neurotoxin mixture, and;

(c) allowing the biodegradable polymer-neurotoxin mixture to set or cure, thereby making a controlled release system which will not induce a significant immune response.

17. The method of claim 16, further comprising the step after the mixing step of evaporating solvent.

18. A method for using a continuous release system, the method comprising injection or implantation of a controlled release system which includes a biodegradable polymeric matrix and a neurotoxin, thereby treating a movement disorder or a disorder influenced by cholinergic innervation, without causing a significant immune response.