AQUEOUS BASED CAPSAICINOID FORMULATIONS AND METHODS OF MANUFACTURE AND USE
Capsaicinoid formulations and methods of treatment are disclosed herein which can be utilized to treat/attenuate pain in mammals. Typically, administration is via injection at a discrete site to provide pain relief for an extended period of time. The formulations are administered in a pharmaceutically acceptable vehicle. The formulations include an analgesic agent in an amount sufficient to attenuate the burning and hyperalgesic effects of capsaicinoid administration. The invention also includes a method of treating pain by administering a corticosteroid followed by administration of a capsaicinoid.
1 . An aqueous pharmaceutical solution in unit dose form for injection in a mammal comprising:
0.001 to 1 mg capsaicin,
an aqueous vehicle comprising a solubilizing agent to solubilize said capsaicin, and hyaluronic acid,
wherein said aqueous vehicle reduces or eliminates the burning and stinging created by said capsaicin upon injection.
2 . An aqueous pharmaceutical solution as in claim 1 , wherein said solubilizing agent is polyethylene glycol.
3 . An aqueous pharmaceutical solution as in claim 1 , wherein said capsaicin is trans-capsaicin.
4 . An aqueous pharmaceutical solution as in claim 1 , wherein said capsaicin is in the form of a concentrate with a nonionic surfactant.
5 . An aqueous pharmaceutical solution as in claim 1 , wherein said solubilizing agent is selected from the group consisting of polyethylene glycol-300, polyethylene glycol-400, and polypropylene glycol.
6 . An aqueous pharmaceutical solution as in claim 1 , wherein solubilizing agent is polyethylene glycol-300.
7 . An aqueous pharmaceutical solution as in claim 6 , wherein said hyaluronic acid is 0.25-1.5% by weight of said solution.
8 . An aqueous pharmaceutical solution as in claim 6 , wherein said hyaluronic acid has an average molecular weight of 1000 kDaltons.
9 . An aqueous pharmaceutical solution as in claim 6 , wherein said hyaluronic acid is in the form of a hydrogel.
10 . An aqueous pharmaceutical solution as in claim 1 , wherein said hyaluronic acid is 800 to 1,200 kDaltons.
11 . An aqueous pharmaceutical solution, wherein said solution is
5-25% by weight polyethylene glycol, and
0.2-1% by weight hyaluronic acid.
12 . An aqueous pharmaceutical solution as in claim 1 further comprising a nonionic surfactant.
13 . An aqueous pharmaceutical solution as in claim 12 , wherein the nonionic surfactant is polyoxy 40 hydrogenated castor oil.
14 . An aqueous pharmaceutical solution as in claim 12 , wherein the nonionic surfactant is polysorbate 80.
15 . An aqueous pharmaceutical solution as in claim 14 , wherein the weight ratio of capsaicin to polysorbate 80 is 1 to 5.
16 . An aqueous pharmaceutical solution as in claim 1 further comprising an anti-inflammatory agent.
17 . An aqueous pharmaceutical solution as in claim 16 , wherein said anti-inflammatory agent is a corticosteroid.
18 . An aqueous pharmaceutical solution as in claim 1 , further comprising an analgesic agent.
19 . An aqueous pharmaceutical solution as in claim 18 , wherein said analgesic agent is one or more selected from the group consisting of phenol, menthol and eugenol.
20 . An aqueous pharmaceutical solution as in claim 1 further comprising an anesthetic agent.
21 . An aqueous pharmaceutical solution as in claim 1 , comprising:
0.005-0.05% by weight capsaicin,
0.025-0.15% by weight polysorbate 80 or polyoxy 40 hydrogenated castor oil,
0-25% by weight polyethylene glycol 300 or 400, and
0.2-1% by weight hyaluronic acid.
22 . A method for treating pain at a site in a mammal comprising:
administering to said site in said mammal an aqueous pharmaceutical solution comprising 0.001-1 mg capsaicin, a solubilizing agent to solubilize said capsaicin, and hyaluronic acid.
23 . A method as in claim 22 wherein said mammal is a human.
24 . A method as in claim 22 wherein an anesthetic is administered prior to the administration of said aqueous pharmaceutical solution.
25 . A method as in claim 24 , wherein the anesthetic agent is administered in a pharmaceutically acceptable vehicle in a volume from about 0.1 ml to 25 ml.
26 . A method as in claim 22 wherein during the first minute after administering said aqueous pharmaceutical solution, the joint is repeatedly flexed and extended.
27 . A method as in claim 22 wherein prior to, during and/or after administering said aqueous pharmaceutical solution, cooling means is applied to said site.
28 . A method as in claim 22 wherein said aqueous pharmaceutical solution is administered by injection.
29 . A method as in claim 22 wherein said aqueous pharmaceutical solution is administered by infiltration.
30 . A method as in claim 22 wherein the pain is from a wound or surgical site.
31 . A method as in claim 22 , wherein the capsaicin is trans-capsaicin dose level ranges from 0.001 mg to 0.5 mg.
32 . A method as in claim 22 , wherein said aqueous pharmaceutical solution is administered in a volume from about 0.1 ml to 25 ml.
33 . A method as in claim 22 wherein said aqueous pharmaceutical solution comprises a capsaicin, hyaluronic acid, and polyethylene glycol.
34 . A kit for administering a capsaicinoid by intra articular injection comprising:
a) at least one unit dose of an anesthetic agent
b) at least one unit dose of a capsaicinoid solution containing a capsaicinoid and hyaluronic acid,
wherein said kit is arranged such that said anesthetic agent is administered prior to said capsaicinoid solution.
35 . A kit as in claim 34 further comprising a means for administration of a) and b).
36 . A kit as in claim 34 further comprising instructions for administration.
37 . A kit as in claim 34 wherein the capsaicinoid, hyaluronic acid and anesthetic are formulated together.
38 . A kit as in claim 34 wherein said unit dose of a capsaicinoid is 0.001-1 mg capsaicin.
39 . A kit as in claim 34 wherein said anesthetic is lidocaine.
40 . A method as in claim 24 wherein said anesthetic is lidocaine.
41 . A method as in claim 22 , wherein said aqueous pharmaceutical solution is administered in a volume from about 0.5 ml to 10 ml.
42 . A method as in claim 22 wherein said site is a joint.
43 . A method as in claim 22 wherein said administration to said site is by intra articular injection to the knee.
44 . An aqueous solution as in claim 1 comprising 0.2-0.4 mg capsaicin.
45 . An aqueous solution as in claim 1 comprising 0.2-0.5 mg capsaicin in 5 ml aqueous vehicle.
46 . An aqueous solution as in claim 1 comprising 0.2 mg capsaicin in 5 ml aqueous vehicle.
47 . An aqueous solution as in claim 1 comprising 0.3 mg capsaicin in 5 ml aqueous vehicle.
48 . An aqueous solution as in 1 comprising 0.001-0.5 mg capsaicin.