Transdermal delivery of cannabinoids

Abstract

The present invention overcomes the problems associated with existing drug delivery systems by delivering cannabinoids transdermally. Preferably, the cannabinoids are delivered via an occlusive body (i.e., a patch) to alleviate harmful side effects and avoid gastrointestinal (first-pass) metabolism of the drug by the patient. A first aspect of the invention provides a method for relieving symptoms associated with illness or associated with the treatment of illness in a mammalian subject, comprising the steps of selecting at least one cannabinoid from the group consisting of cannabinol, cannabidiol, nabilone, levonantradol, (−)-HU-210, (+)-HU-210, 11-hydroxy-Δ 9 -THC, Δ 8 -THC-11-oic acid, CP 55,940, and R(+)-WIN 55,212-2, selecting at least one permeation enhancer from the group consisting of propylene glycol monolaurate, diethylene glycol monoethyl ether, an oleoyl macrogolglyceride, a caprylocaproyl macrogolglyceride, and an oleyl alcohol, and delivering the selected cannabinoid and permeation enhancer transdermally to treat an illness.

1 . A method for relieving symptoms associated with illness or associated with the treatment of illness in a mammalian subject, comprising the steps of:
 selecting at least one cannabinoid from the group consisting of: cannabinol, cannabidiol, nabilone, levonantradol, (−)-HU-210, (+)-HU-210, 11-hydroxy-Δ 9 -THC, Δ 8 -THC-11-oic acid, CP 55,940, and R(+)-WIN 55,212-2;   selecting at least one permeation enhancer from the group consisting of: propylene glycol monolaurate, diethylene glycol monoethyl ether, an oleoyl macrogolglyceride, a caprylocaproyl macrogolglyceride, and an oleyl alcohol; and   delivering the selected cannabinoid and permeation enhancer transdermally to treat an illness.   
     
     
         2 . The method of  claim 1 , wherein the delivering step comprises: providing an occlusive body having the selected cannabinoid and permeation enhancer; and positioning the occlusive body on a patient. 
     
     
         3 . The method of  claim 2 , wherein the occlusive body comprises:
 an impermeable backing;   a rate-controlling microporous membrane, said backing and membrane defining a cavity therebetween;   the selected cannabinoid disposed within the cavity;   the selected permeation enhancer disposed within the cavity;   a viscous flowable gel confined between the backing and the membrane within the cavity for immobilizing the cannabinoid and the permeation enhancer; and   means for attaching the body to skin, wherein the selected cannabinoid and permeation enhancer are released through the membrane to the skin.   
     
     
         4 . The method of  claim 1 , wherein the illness is selected from AIDS, cancer, Huntington's disease, arthritis, nervous-tissue inflammation, vascular inflammation, inflammatory bowel disease, and other inflammation-related conditions. 
     
     
         5 . The method of  claim 1 , wherein the subject is selected from the group consisting of patients experiencing a loss of appetite, patients experiencing chronic pain, patients experiencing spasticity, patients experiencing dystonia, and patients experiencing nausea and vomiting. 
     
     
         6 . The method of  claim 1 , wherein the cannabinoid is a combination of cannabinoids selected from the group consisting of: cannabinol, cannabidiol, nabilone, levonantradol, (−)-HU-210, (+)-HU-210, 1]-hydroxy-Δ 9 -THC, Δ 8 -THC-11-oic acid, CP 55,940, and R(+)-WIN 55,212-2. 
     
     
         7 . The method of  claim 1 , wherein the permeation enhancer is a combination of permeation enhancers selected from the group consisting of: propylene glycol monolaurate, diethylene glycol monoethyl ether, an oleoyl macrogolglyceride, a caprylocaproyl macrogolglyceride, and an oleyl alcohol. 
     
     
         8 . The method of  claim 1 , wherein the cannabinoid is cannabidiol and the permeation enhancer is diethylene glycol monoethyl ether. 
     
     
         9 . The method of  claim 1 , wherein the selected cannabinoid is delivered via a topical formulation. 
     
     
         10 . The method of  claim 1 , wherein the selected cannabinoid and permeation enhancer are delivered via a patch. 
     
     
         11 . The method of  claim 1 , further comprising the steps of:
 selecting an opiate; and   delivering the selected opiate transdermally with the selected cannabinoid and permeation enhancer.   
     
     
         12 . An occlusive body for the delivery of cannabinoids, comprising:
 an impermeable backing;   a rate-controlling microporous membrane, said backing and membrane defining a cavity therebetween;   a cannabinoid disposed within the cavity;   a permeation enhancer disposed within the cavity; and   a viscous flowable gel confined between the backing and the membrane within the cavity for immobilizing the cannabinoid and the permeation enhancer.   
     
     
         13 . The occlusive body of  claim 12 , wherein the cannabinoid is selected from the group consisting of: Δ 9 -THC, Δ 8 -THC, cannabinol, cannabidiol, nabilone, levonantradol, (−)-HU-210, (+)-HU-210, 11-hydroxy-Δ 9 -THC, Δ 8 -THC-11-oic acid, CP 55,940, R(+)-WIN 55,212-2, or any combination thereof. 
     
     
         14 . The occlusive body of  claim 12 , wherein the permeation enhancer is selected from the group consisting of: propylene glycol monolaurate, diethylene glycol monoethyl ether, an oleoyl macrogolglyceride, a caprylocaproyl macrogolglyceride, and an oleyl alcohol. 
     
     
         15 . The occlusive body of  claim 12 , further comprising an adhesive for attaching the occlusive body to a patient's skin and wherein the cannabinoid and permeation enhancer are released through the membrane to the patient's skin. 
     
     
         16 . The occlusive body of  claim 12 , wherein the occlusive body is a patch. 
     
     
         17 . The occlusive body of  claim 12 , wherein the membrane has an exterior surface coated with an adhesive. 
     
     
         18 . The occlusive body of  claim 17 , wherein the adhesive is a silicone-based adhesive. 
     
     
         19 . The occlusive body of  claim 12 , wherein the membrane is hydrophobic and the cavity includes a hydrophilic wetting agent. 
     
     
         20 . The occlusive body of  claim 12 , wherein the cavity includes water and a surfactant selected from a viscosity modifier and a gelling agent. 
     
     
         21 . The occlusive body of  claim 20 , wherein the surfactant comprises methyl cellulose. 
     
     
         22 . The occlusive body of  claim 12 , further comprising an opiate confined in the cavity with the cannabinoid and permeation enhancer. 
     
     
         23 . A method for increasing the concentration of cannabinoids or cannabinoid metabolites in a subject, comprising:
 contacting the subject's skin with a compound selected from the group consisting of: cannabinol, cannabidiol, nabilone, levonantradol, (−)-HU-210, (+)-HU-210, 11-hydroxy-Δ 9 -THC, Δ 8 -THC-11-oic acid, CP 55,940, and R(+)-WIN 55,212-2; and   contacting the subject's skin with a permeation enhancer selected from the group consisting of: propylene glycol monolaurate, diethylene glycol monoethyl ether, an oleoyl macrogolglyceride, a caprylocaproyl macrogolglyceride, and an oleyl alcohol.   
     
     
         24 . The method of  claim 23 , further comprising contacting the subject's skin with a drug metabolism inhibitor. 
     
     
         25 . The method of  claim 23 , wherein the compound is a combination of compounds selected from the group consisting of: cannabinol, cannabidiol, nabilone, levonantradol, (−)-HU-210, (+)-HU-210, 1]-hydroxy-Δ 9 -THC, Δ 8 -THC-11-oic acid, CP 55,940, and R(+)-WIN 55,212-2.