Claims for Patent: 8,367,733

Summary for Patent: 8,367,733

Title:	Infiltration of capsaicin into surgical sites and open wounds
Abstract:	The present invention is directed to methods for attenuating pain associated with a surgical site or an open wound by administration of single doses of a capsaicinoid formulation in proximity to a surgical site or wound opening.
Inventor(s):	Burch; Ronald (Wilton, CT), Carter; Richard B. (Washington Crossing, PA), Lazar; Jeff (Austin, TX)
Assignee:	Vallinex, Inc. (Baltimore, MD)
Application Number:	11/499,989
Patent Claims:	1. A method for attenuating pain associated with a surgical site or an open wound in a human or animal, comprising: administering by infiltration directly into tissue around an open wound or surgical incision a therapeutically effective amount of a single dose of a capsaicinoid in proximity to the site of incision or wound opening to produce a selective, highly localized destruction or incapacitation of C-fiber and/or A-delta fibers (nociceptors) in a discrete localized area responsible for the initiation of pain and thereby attenuating pain emanating from the site of incision or open wound. 2. The method of 1, wherein said dose of capsaicin is from about 1 .mu.g to about 15,000 .mu.g or a therapeutically equivalent does of a capsaicinoid other than capsaicin. 3. The method of 1, wherein said dose of capsaicin is from about 600 to 10,000 .mu.g or a therapeutically equivalent dose of a capsaicinoid other than capsaicin. 4. The method of 1, wherein said dose of capsaicinoid is administered in a pharmaceutically acceptable vehicle in a volume from about 0.1 to about 1000 ml. 5. The method of 1, wherein said dose of capsaicinoid is administered in a pharmaceutically acceptable vehicle in a volume from about 1 ml to about 100 ml. 6. The method of 1, wherein said dose of capsaicinoid is administered in a pharmaceutically acceptable vehicle in a volume from about 5 ml to about 30 ml. 7. The method of 4, wherein said pharmaceutically acceptable vehicle is an aqueous vehicle selected from the group consisting of Sodium Chloride Injection, Ringers Injection, Isotonic Dextrose Injection, Sterile Water Injection, Dextrose, Lactated Ringers Injection and any combination of mixtures thereof. 8. The method of 7, wherein said pharmaceutically acceptable vehicle comprises an agent selected from the group consisting of antimicrobial agents, isotonic agents, buffers, antioxidants, local anesthetics, suspending and dispersing agents, emulsifying agents, sequestering, chelating agents and any combination thereof. 9. The method of 5, wherein said pharmaceutically acceptable vehicle comprises about 20% PEG 300, about 10 mM histidine and about 5% sucrose in water for injection. 10. The method of 1, wherein said dose of capsaicinoid is administered in the form of microparticles selected from the group consisting of microcapsules and microspheres. 11. The method of 1, further comprising administering a local anesthetic prior to or concurrently with said dose of capsaicinoid in an amount and location effective to attenuate an initial hyperalgesic effect of said administered dose of capsaicinoid. 12. The method of claim 11, wherein said local anesthetic is selected from the group consisting of dibucaine, bupivacaine, ripivacaine, etidocaine, tetracaine, procaine, chlorocaine, prilocaine, mepivacaine, lidocaine, 2-chloroprocaine, and acid addition salts or mixtures thereof. 13. The method of 11, wherein said local anesthetic is administered to the surgical or wound site. 14. The method of 1, further comprising administering general anesthesia to the human or animal prior administration of said dose of capsaicinoid. 15. The method of 1, wherein said administration of capsaicinoid at the site provides attenuation of pain in proximity to the surgical or wound site for at least about 48 hours. 16. The method of 1, wherein said administration of capsaicinoid at the site provides attenuation of pain in proximity to the surgical or wound site for at least about one week. 17. The method of 1, wherein said capsaicinoid is selected from the group consisting of capsaicin, resiniferatoxin, N-vanillylnonanamides, N-vanillylsulfonamides, N-vanillylureas, N-vanillylcarbamates, N[(substituted phenyl)methyl]alkylamides, methylene substituted N[(substituted phenyl)methyl]alkanamides, N[(substituted phenyl)methyl]-cis-monosaturated alkenamides, N[(substituted phenyl)methyl]diunsaturated amides, 3-hydroxyacetanilide, hydroxyphenylacetamides, pseudocapsaicin, dihydrocapsaicin, nordihydrocapsaicin anandamide, piperine, zingerone, warburganal, polygodial, aframodial, cinnamodial, cinnamosmolide, cinnamolide, isovelleral, scalaradial, ancistrodial, .beta.-acaridial, merulidial, scutigeral, and any combinations thereof. 18. The method of 17, wherein said capsaicinoid is capsaicin. 19. The method of 18, wherein said capsaicin consists essentially of trans-capsaicin. 20. The method of 1, wherein said capsaicinoid administration provides an effect selected from the group consisting of: a) producing a selective, highly-localized destruction or incapacitation of C-fibers and/or A-delta fibers (nociceptors) in a localized area responsible for the initiation of pain for the purpose of reducing or eliminating pain arising from the area, and b) minimizing potential adverse consequences of C-fiber and/or A-delta activation and or damage outside of the locus of pain. 21. The method of 1, wherein said pain is associated with a median sternotomy, and the method further comprises administering said dose of capsaicinoid to sternal edges in an amount effective to denervate said sternal edges. 22. The method of 1, wherein said wound is a long bone fracture. 23. The method of 1, wherein said pain is associated with a laparoscopy, an anthroplasty, an anthroscopy, an arthrodesis, a synovectomy, a plantar fasciotomy, an Incision and Drainage (I and D), an osteotomy, and cancer surgery. 24. The method of 1, wherein said pain is associated with a mastectomy and the method further comprises administering said dose of capsaicinoid to the muscle, tissue or bone surrounding the surgical site. 25. The method of 1, wherein said dose of capsaicinoid is from about 500 .mu.g to about 5000 .mu.g capsaicin, or a therapeutically equivalent dose of another capsaicinoid. 26. The method of 1, wherein said surgical site is a bunionectomy, and said dose of capsaicinoid is from about 500 .mu.g to about 2000 .mu.g capsaicin, or a therapeutically equivalent dose of another capsaicinoid. 27. The method of 1, wherein said surgical site is associated with an injury selected from the group consisting of a tear of the anterior cruciate ligament, a tear of the posterior cruciate ligament, a tear of the medial collateral ligament, a tear of the lateral collateral ligament; a meniscal cartilage tear; a cartilage defect of the knee; and combinations of any of the foregoing. 28. The method of 1, wherein said surgical site or open wound pain is associated with an orthopedic disorder of the shoulder, knee, back, hip, spine, elbow, ankle, wrist, foot, pelvis, leg or hand, and combinations of any of the foregoing. 29. The method of 28, wherein said pain is associated with tendonitis, bursitis, osteoarthritis, rheumatoid arthritis or bursitis injury. 30. The method of 1, wherein the capsaicinoid is a purified capsaicin. 31. The method of 30, wherein the capsaicinoid is at least about 97% trans-capsaicin. 32. The method of 9, wherein said capsaicinoid comprises greater than 500 .mu.g to about 15,000 .mu.g capsaicin, a therapeutically equivalent amount of one or more other capsaicinoids, and therapeutically equivalent combinations thereof. 33. The method of 1, wherein said pain is associated with a median sternotomy, and the method further comprises administering said dose of capsaicinoid in an amount effective to the musle or tissue surrounding the surgical site to denervate said site. 34. The method of 1, wherein said pain is associated with a median sternotomy, and the method further comprises administering said dose of capsaicinoid to the sternum in an amount effective to denervate said site. 35. The method of 23, wherein said arthroplasty is a total knee arthroplasty. 36. The method of 23, wherein said aarthroplasty is a total hip arthroplasty. 37. The method of 23, wherein said arthroplasty is a total shoulder arthroplasty. 38. The method of 1, wherein said pain is associated with a laparoscopic cholecystectomy and the method further comprises administering said dose of capsaicinoid to the surgical site in an amount effective to denervate the surgical site. 39. The method of 38, wherein said capsaicin is administered to the muscle, tissue or bone surrounding the surgical site. 40. The method of 1, wherein said dose of capsaicin is from about 500 to about 5,000 .mu.g or a therapeutically equivalent dose of a capsaicinoid other than capsaicin. 41. The method of 1, wherein said dose of capsaicin is from about 500 to about 5,000 .mu.g or a therapeutically equivalent dose of a capsaicinoid other than capsaicin. 42. The method of 1, wherein said dose of capsaicin is from about 1,000 .mu.g or a therapeutically equivalent dose of a capsaicinoid other than capsaicin. 43. The method of 1, further comprising administering to said patent an effective amount of an analgesic. 44. The method of 43, wherein the analgesic is selected from the group consisting of sodium aurothiomalate, nonsteroidal anti-inflammatory agents (NSAID), opioid analgesics, para-aminophenol derivatives and salicylates. 45. The method of 44, wherein the NSAID is selected from the group consisting of naproxen, diclofenac, fluriprofen, ibuprofen, ketoprofen, ketorolac and pharmaceutically acceptable salts thereof. 46. The method of 44, wherein the opioid is selected from the group consisting of codeine, dextropropoxyphene, dihydrocodeine, morphine, diamorphine, hydromorphone, hydrocodone, methadone, pethidine, oxycodone, levorphanol, fentanyl, alfentanil and pharmaceutically acceptable salts thereof. 47. The method of 1, further comprising administering phenol prior or concurrently with said dose of capsaicinoid in an amount and location effective to attenuate an initial hyperalgesic effect of said administered dose of capsaicinoid. 48. The method of 1, wherein said dose of capsaicinoid is administered in a pharmaceutically acceptable vehicle in a volume of about 4 ml. 49. The method of 1, further comprising administering local anesthesia to the human or animal prior to administration of said dose of capsacinoid. 50. The method of 1, comprising administering anesthesia to the human or animal prior to administration of said dose of capsacinoid, wherein said anesthesia is selected from the group consisting of a regional block, a proximal block, a somatic block, a neuroaxial block, a spinal block, an epidural block, and a nerve block. 51. The method of claim 1 wherein the capsaicin is administered at the time of surgery. 52. The method of claim 1 wherein the capsaicin is administered into the tissue around a surgical incision immediately before, during or after surgery.

Details for Patent 8,367,733

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	ZOSTAVAX	zoster vaccine live	For Injection	125123	05/25/2006		2022-12-18