Methods of Treatment of Opioid Tolerance, Physical Dependence, Pain and Addiction With Inhibitors of Certain Growth Factor Receptors

• US 20100210709A1
• Filed: 10/08/2008
• Published: 08/19/2010
• Est. Priority Date: 10/09/2007
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Howard, Gutstein B.
• Granted Patent: US 8,501,740 B2
• Time in Patent Office: Days
• US Class Current: 514/44.A
• 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 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 47/40 Cyclodextrins; Derivatives thereof
• CPC Class Codes: A61K 47/6951 using cyclodextrin cyclodextrins used as simple excipients A61K47/40
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• 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: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

Methods of preventing the development and reversing or partially reversing opioid tolerance in a subject are provided herein. Such methods include the step of administering to a subject in need thereof a therapeutically effective amount of a PDGFR modulator or EGFR modulator alone or together with an opiate analgesic. The methods can also be used for the treatment of refractory neuropathic pain, physical dependence or addiction.

Claims

1. A method of treating opioid tolerance comprising the step of administering to a subject in need thereof a therapeutically effective amount of a PDGFR modulator wherein said modulator is administered to the subject in an aqueous pharmaceutical formulation comprising cyclodextrin, cyclodextran, or other cycloamyloses.

2. A method of claim 1 wherein the PDGFR modulator is adminstered to the subject in combination with an opioid.

3. The method of claim 1, wherein the modulator is a tyrosine kinase specific small molecule antagonist, PDGF receptor specific antisense nucleotide or siRNA.

4. The method of claim 1, wherein the modulator is an inhibitor.

5. The method of claim 1, wherein the modulator is imatinib.

6. The method of claim 1, wherein the modulator is spinally, intravenously, intraperitoneally, intramuscularly, subcutaneously, or orally administered.

7. A method of treating pain comprising the step of administering to a subject in need thereof a therapeutically effective amount of Imatinib wherein Imatinib is provided in an aqueous pharmaceutical formulation.

8. A method of treating opioid tolerance comprising the step of administering to a subject in need thereof a therapeutically effective amount of a EGFR modulator wherein said modulator is administered to the subject in an aqueous pharmaceutical formulation comprising cyclodextrin, cyclodextran, or other cycloamyloses.

10. The method of claim 8, wherein the modulator is a tyrosine kinase specific small molecule antagonist, EGF receptor specific antisense nucleotide or siRNA.

11. The method of claim 8, wherein the modulator is an inhibitor

12. The method of claim 8, wherein the modulator is gefitinib, lapatinib or erlotinib.

13. The method of claim 8, wherein the modulator is spinally, intravenously, intraperitoneally, intramuscularly, subcutaneously, or orally administered.

9. The method of claim 9 wherein the subject is administered the EGFR modulator in combination with an opioid.

14. A pharmaceutical aqueous formulation comprising:

cyclodextrin; and

an EGFR small molecule inhibitor.

16. A method of administering an EGFR inhibitor to a subject in need thereof comprising the step of administering to the subject by injection, intravenous infusion, or orally a liquid formulation according to claim 14.

15. A pharmaceutical aqueous formulation comprising:

cyclodextrin; and

a PDGFR small molecule inhibitor.

17. A method of administering an PDGFR inhibitor to a subject in need thereof comprising the step of administering to the subject by injection, intravenous infusion, or orally a liquid formulation according to claim 15.