# US 11,026,903 B2 · Methods and compositions for treatment of pain using capsaicin > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,026,903 B2 - Document ID: US11026903B2 - Status: Granted - Kind: B2 - Application number: 16/984,384 - Filed: 2020-08-04 - Published: 2020-11-19 - Granted: 2021-06-08 - Earliest claimed: 2017-07-20 - Assignees: Centrexion Therapeutics Corporation - Applicants: Centrexion Therapeutics Corporation - Inventors: James N. Campbell; Peter D. Hanson; Randall Stevens - Web page: https://patentgrep.com/patent/US11026903B2 ## CPC - A61K 31/167: having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol - A61F 7/10: Cooling bags, e.g. ice-bags - A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)} - 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)} - A61K 31/165: having aromatic rings, e.g. colchicine, atenolol, progabide - A61P 19/02: for joint disorders, e.g. arthritis, arthrosis - A61P 29/02: without antiinflammatory effect - A61F 2007/0042: {Knee} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61F: FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS (dental prosthetics A61C) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The invention provides methods and compositions for treatment of pain, such as joint pain, using capsaicin in a procedure that attenuates transient burning sensation experienced by patients due to capsaicin administration. The methods desirably provide relief from joint pain, such as osteoarthritic knee joint pain, for an extended duration, such as at least about 3 months, 6 months, 9 months, or 1 year. To attenuate the adverse side effect of a transient burning sensation caused by capsaicin-induced neuronal excitation, the methods utilize a cooling article, such as a material wrap cooled via a circulating fluid, to reduce the temperature of tissue to be exposed to capsaicin to within a certain range for certain durations of time, optionally in combination with administering a local anesthetic agent, resulting in the substantial reduction or even elimination of transient burning sensation caused by capsaicin. ## Claims ### Claim 1 A method of ameliorating joint pain in a human patient, comprising: a. optionally applying a cooling article to a human patient's skin in proximity to a joint in need of pain relief therapy; then b. optionally administering a local anesthetic agent into said joint; then c. applying a cooling article to the patient's skin in proximity to said joint to achieve a temperature in the range of from 28° C. to 30° C. for tissue or fluid in the interior of the joint; then d. administering by injection into said joint 2 mL of a pharmaceutical composition comprising capsaicin in order to deliver a dose of capsaicin in an amount of 1 mg; and then e. optionally applying a cooling article to the patient's skin in proximity to said joint; to thereby ameliorate joint pain in the human patient, wherein the joint pain is osteoarthritic joint pain, the joint is a knee joint, and after administration of the pharmaceutical composition comprising capsaicin in step (d) but prior to step (e) said joint is flexed 5 times; and the following additional step is performed between steps (c) and (d): administering into said joint 15 mL of a pharmaceutical composition comprising a single pain-relief local anesthetic agent selected from the group consisting of lidocaine and a pharmaceutically acceptable salt thereof, in order to deliver a dose of lidocaine in an amount ranging from about 0.1 g to about 0.5 g; wherein other than administration of (i) a local anesthetic agent and (ii) the pharmaceutical composition comprising capsaicin, the patient does not receive any other pain-relief medicine. ### Claim 2 (depends on 1) The method of claim 1, wherein the method does not contain step (a). ### Claim 3 (depends on 2) The method of claim 2, wherein the method does not contain step (b). ### Claim 4 (depends on 3) The method of claim 3, wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature of 28° C. for tissue or fluid in the interior of the joint. ### Claim 5 (depends on 3) The method of claim 3, wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature of 29° C. for tissue or fluid in the interior of the joint. ### Claim 6 (depends on 3) The method of claim 3, wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature of 30° C. for tissue or fluid in the interior of the joint. ### Claim 7 (depends on 3) The method of claim 3, wherein the method comprises step (e) in which a cooling article is applied to the patient's skin in proximity to the joint to achieve a temperature in the range of from 28° C. to 30° C. for tissue or fluid in the interior of the joint for a duration of at least 15 minutes. ### Claim 8 (depends on 3) The method of claim 3, wherein the dose of lidocaine is about 0.3 g. ### Claim 9 (depends on 3) The method of claim 3, wherein the dose of lidocaine is about 0.15 g. ### Claim 10 (depends on 3) The method of claim 3, wherein the pharmaceutical composition comprising lidocaine is an aqueous mixture containing lidocaine at a concentration of about 2% w/w. ### Claim 11 (depends on 3) The method of claim 3, wherein the pharmaceutical composition comprising lidocaine is an aqueous mixture containing lidocaine at a concentration of about 1% w/w. ### Claim 12 (depends on 3) The method of claim 3, wherein the cooling article has an exterior surface temperature in the range of from about 5° C. to about 15° C. for application to the human patient's skin in proximity to said joint. ### Claim 13 (depends on 3) The method of claim 3, wherein the cooling article has an exterior surface temperature in the range of from about 8° C. to about 10° C. for application to the human patient's skin in proximity to said joint. ### Claim 14 (depends on 3) The method of claim 3, wherein the cooling article has an exterior surface temperature of about 9° C. for application to the human patient's skin in proximity to said joint. ### Claim 15 (depends on 12) The method of claim 12, wherein step (c) comprises applying for a duration of about 30 minutes the cooling article to an exterior surface of said joint. ### Claim 16 (depends on 12) The method of claim 12, wherein the method comprises step (e) in which the cooling article is applied for a duration of from about 30 minutes to about 60 minutes to the exterior surface of the patient's knee. ### Claim 17 (depends on 1) The method of claim 1, wherein other than the procedures set forth in the steps in claim 1, the method does not contain any procedure that reduces transient burning sensation experienced by the patient due to administration of capsaicin. ### Claim 18 (depends on 3) The method of claim 3, wherein other than the procedures set forth in the steps in claim 3, the method does not contain any procedure that reduces transient burning sensation experienced by the patient due to administration of capsaicin. ### Claim 19 (depends on 15) The method of claim 15, wherein other than the procedures set forth in the steps in claim 15, the method does not contain any procedure that reduces transient burning sensation experienced by the patient due to administration of capsaicin. ### Claim 20 (depends on 3) The method of claim 3, wherein the patient experiences transient burning sensation no greater than level two on a visual analog scale ranging from zero to four, due to administering the pharmaceutical composition comprising capsaicin. ### Claim 21 (depends on 18) The method of claim 18, wherein the patient experiences transient burning sensation no greater than level two on a visual analog scale ranging from zero to four, due to administering the pharmaceutical composition comprising capsaicin. ### Claim 22 (depends on 3) The method of claim 3, wherein transient burning sensation is evaluated at about 30 minutes after administration of the pharmaceutical composition comprising capsaicin, and said transient burning sensation is no greater than level one on a visual analog scale ranging from zero to four, due to administering the pharmaceutical composition comprising capsaicin. ### Claim 23 (depends on 18) The method of claim 18, wherein transient burning sensation is evaluated at about 30 minutes after administration of the pharmaceutical composition comprising capsaicin, and said transient burning sensation is no greater than level one on a visual analog scale ranging from zero to four, due to administering the pharmaceutical composition comprising capsaicin. ### Claim 24 (depends on 3) The method of claim 3, wherein transient burning sensation is evaluated at about 60 minutes after administration of the pharmaceutical composition comprising capsaicin, and said transient burning sensation is no greater than level one on a visual analog scale ranging from zero to four, due to administering the pharmaceutical composition comprising capsaicin. ### Claim 25 (depends on 3) The method of claim 3, wherein the method is characterized by achieving a reduction in joint pain for a duration of at least 6 months. ### Claim 26 (depends on 18) The method of claim 18, wherein the method is characterized by achieving a reduction in joint pain for a duration of at least 6 months. ### Claim 27 (depends on 22) The method of claim 22, wherein the method is characterized by achieving a reduction in joint pain for a duration of at least 6 months. ### Claim 28 (depends on 23) The method of claim 23, wherein the method is characterized by achieving a reduction in joint pain for a duration of at least 6 months.