Methods and compositions for treating mammalian nerve tissue injuries

• US 9,687,502 B2
• Filed: 07/28/2004
• Issued: 06/27/2017
• Est. Priority Date: 04/24/2001
• Status: Active Grant

• Current Assignee: Purdue Research Foundation (The Trustees of Purdue University (d/b/a Purdue University)), University of Chicago
• Original Assignee: Purdue Research Foundation (The Trustees of Purdue University (d/b/a Purdue University)), University of Chicago
• Inventors: Shi, Riyi, Borgens, Richard B., Lee, Raphael C.
• Primary Examiner(s): Yu, Misook
• Assistant Examiner(s): AKHOON, KAUSER M
• Application Number:
  US10/901,481
• Publication Number:
  US 20050069520A1
• Time in Patent Office: 4,717 Days
• Field of Search: 424 7838, 424423, 424 7837, 424422, 424 7808, 424 7828
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/74 Synthetic polymeric materials
• CPC Class Codes: A61K 31/765 Polymers containing oxygen
• CPC Class Codes: A61K 31/77 of oxiranes
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

To achieve, an in vivo repair of injured mammalian nerve tissue, an effective amount of a biomembrane fusion agent is administered to the injured nerve tissue. The application of the biomembrane fusion agent may be performed by directly contacting the agent with the nerve tissue at the site of the injury. Alternatively, the biomembrane fusion agent is delivered to the site of the injury through the blood supply after administration of the biomembrane fusion agent to the patient. The administration is preferably by parenteral administration including including intravascular, intramuscular, subcutaneous, or intraperitoneal injection of an effective quantity of the biomembrane fusion agent so that an effective amount is delivered to the site of the nerve tissue injury.

Claims

1. A method for treating a mammalian patient having suffered an injury to nerve tissue of the central nervous system, the method comprising

administering an effective amount of a composition comprising an amphipathic polymer comprising a polar substructure and a non-polar substructure to the mammalian patient, wherein the administering is effected after the injury occurs via the mammalian patient'"'"'s vascular system, wherein the administration is effective in delivering the amphipathic polymer to the site of the injured nerve tissue in the mammalian patient'"'"'s central nervous system, wherein delivery is effected using a technique selected from the group consisting of intravascular, intramuscular, subcutaneous and intraperitoneal injection and wherein the effective amount is an amount that increases the conduction of action potentials in injured nerve tissue of the central nervous system and increases at least one of reflex behavior, motor function and sensation in the patient.

2. The method of claim 1, wherein said amphipathic polymer comprises a block copolymer.

3. The method of claim 2, wherein said block copolymer is taken from the group consisting of polyalkylene glycol block copolymers, mixtures of polyalkylene glycol block copolymers, and mixtures of polyalkylene glycols and polyalkylene glycol block copolymers.

4. The method of claim 2, wherein said block copolymer comprises at least one compound taken from the group consisting of polymethylene glycol, polyethylene glycol, polypropylene glycol, polybutylene glycol, polypentylene glycol, polyhexylene glycol, polyheptylene glycol, polyoctylene glycol, polynonylene glycol, and polydecylene glycol, and branched and structural isomers thereof.

5. The method of claim 1, wherein said amphipathic polymer is taken from the group consisting of polyethylene glycol/polypropylene glycol block copolymers, and mixtures of polyethylene glycol, polypropylene glycol, and polyethylene glycol/polypropylene glycol block copolymers.

6. The method of claim 1, wherein said amphipathic polymer is taken from the group consisting of poloxamers and poloxamines.

7. The method of claim 1, wherein said amphipathic polymer is in a pharmaceutically acceptable carrier.

8. The method of claim 6, wherein the poloxamer is poloxamer 188.

9. The method of claim 1, wherein the administering of said effective amount of said amphipathic polymer includes injecting said amphipathic polymer into a vascular system of the patient.

10. The method of claim 1, wherein the administering of said effective amount of amphipathic polymer includes injecting said amphipathic polymer subcutaneously into the patient.

11. The method of claim 1, wherein the delivery by way of the patient'"'"'s vascular system is effected by intraperitoneal injection.

12. The method of claim 1, wherein the delivery is to the spinal cord.

13. The method of claim of claim 1, wherein the injury comprises an injury selected from the group consisting of a mechanical injury, a biochemical injury and an ischemic injury.

14. The method of claim 13, wherein the injury comprises an ischemic injury.

15. The method of claim 14 wherein the ischemic injury is selected from the group consisting of a stroke and a head injury.

26. The method of claim 1, wherein the effective amount is an amount that increases conduction of action potentials through the injured nerve tissue by at least 10%.

27. The method of claim 1, wherein the effective amount is an amount that increases the area of cutaneous trunci muscle recovery by at least 10%.

28. The method of claim 1, wherein the effective amount is an amount that restores more than one spinal root level as determined by the American Spinal Injury Association.

16. A method for treating a mammalian patient having suffered an injury to nerve tissue of the central nervous system, the method comprising

administering an effective amount of a composition comprising a poloxamer or a poloxamine to the patient, wherein the poloxamer or poloxamine is delivered via the patient'"'"'s vascular system to a site of the injured nerve tissue of the mammalian patient'"'"'s central nervous system, wherein delivery of the effective amount of the composition is effected after the injury occurs using a technique selected from the group consisting of intravascular, intramuscular, subcutaneous and intraperitoneal injection, and wherein the effective amount is an amount that increases the conduction of action potentials in the central nervous system and increases at least one of reflex behavior, motor function and sensation in the patient.

17. The method of claim 16 wherein the injury comprises an injury selected from the group consisting of a mechanical injury, a biochemical injury and an ischemic injury.

18. A method for treating a mammalian patient having suffered an injury to nerve tissue of the central nervous system, the method comprising administering an effective amount of a composition comprising an amphipathic polymer comprising a polar substructure and a non-polar substructure wherein the administrating is effective in delivering the effective amount to a site of nerve tissue injury in the mammalian patient'"'"'s central nervous system by way of a vascular route, and wherein the effective amount is administered after the injury occurs and is an amount that increases the conduction of action potentials in injured nerve tissue and increases at least one of reflex behavior, motor function and sensation in the patient.

19. The method of claim 18, wherein the amphipathic polymer comprises a block copolymer.

20. The method of claim 19, wherein said block copolymer is taken from the group consisting of polyalkylene glycol block copolymers, mixtures of polyalkylene glycol block copolymers, and mixtures of polyalkylene glycols and polyalkylene glycol block copolymers.

21. The method of claim 19, wherein said block copolymer comprises at least one compound taken from the group consisting of polymethylene glycol, polyethylene glycol, polypropylene glycol, polybutylene glycol, polypentylene glycol, polyhexylene glycol, polyheptylene glycol, polyoctylene glycol, polynonylene glycol, and polydecylene glycol, and branched and structural isomers thereof.

22. The method of claim 18, wherein said amphipathic polymer is taken from the group consisting of polyethylene glycol/polypropylene glycol block copolymers, and mixtures of polyethylene glycol, polypropylene glycol, and polyethylene glycol/polypropylene glycol block copolymers.

23. The method of claim 18, wherein said amphipathic polymer is taken from the group consisting of poloxamers and poloxamines.

24. The method of claim 18, wherein said composition further comprises a pharmaceutically acceptable carrier.

25. The method of claim 18, wherein the amphipathic polymer is poloxamer 188.