Transdermal delivery of beneficial substances effected by a hostile biophysical environment

Abstract

The present invention generally relates to the transdermal delivery of substances and, in some embodiments, to the transdermal delivery of beneficial substances by a hostile biophysical environment. In one aspect, various methods for the transdermal delivery of beneficial substances are disclosed. By creating a hostile biophysical environment, beneficial substances may be delivered, according to certain embodiments, through the stratum corneum of the skin into the body. Beneficial substances include, but are not limited to, pharmaceutical agents, drugs, vitamins, co-factors, peptides, dietary supplements, and others. The beneficial effects disclosed include, for instance, relief of pain and inflammation, prevention and healing of ulcers of the skin, relief of headache, improved sexual function and enjoyment, growth of hair on the scalp, improving muscle size and/or function, removing body fat and/or cellulite, treating cancer, treating viral infections and others. A hostile biophysical environment may also be used in conjunction with systems and methods for increasing local blood flow, according to one set of embodiments. For example, by using a nitric oxide donor such as L-arginine, local blood flow may be increased, e.g., by transdermally delivering the nitric oxide precursor. The nitric oxide donor may be the sole cause of increased blood flow, or it may be supplemented with an adjunct such as theophylline.

What is claimed is: 
     
         1 - 115 . (canceled) 
     
     
         116 . A topical delivery vehicle for treating a medical condition in a subject, comprising:
 an oil-based cream comprising a water-containing portion, the water-containing portion comprising: an ionic strength of between about 0.25 M and about 15 M, and ibuprofen, wherein the ibuprofen is present in the water-containing portion at a concentration of about 4% or more by weight.   
     
     
         117 . The topical delivery vehicle of  claim 116 , wherein the cream further comprises a nitric oxide donor. 
     
     
         118 . The topical delivery vehicle of  claim 117 , wherein the nitric oxide donor comprises L-arginine. 
     
     
         119 . The topical delivery vehicle of  claim 117 , wherein the nitric oxide donor comprises L-arginine hydrochloride. 
     
     
         120 . The topical delivery vehicle of  claim 117 , wherein the nitric oxide donor comprises an L-arginine salt. 
     
     
         121 . The topical delivery vehicle of  claim 117 , wherein the nitric oxide donor comprises an L-arginine derivative. 
     
     
         122 . The topical delivery vehicle of  claim 121 , wherein the L-arginine derivative is selected from the group consisting of D,L-arginine, D-arginine, an alkyl ester of L-arginine, an alkyl ester of D-arginine, an L-arginine salt, a D-arginine salt, an alkyl ester salt of L-arginine, an alkyl ester salt of D-arginine, L-arginine glutamate, L-arginine butyrate, L-arginine glycolate, D-arginine hydrochloride, D-arginine glutamate; L-homoarginine, N-hydroxy-L-arginine, nitrosylated L-arginine, nitrosylated L-arginine, nitrosylated N-hydroxy-L-arginine, nitrosylated N-hydroxy-L-arginine, and combinations thereof. 
     
     
         123 . The topical delivery vehicle of  claim 117 , wherein the nitric oxide donor is present at a concentration of at least 0.5% by weight. 
     
     
         124 . The topical delivery vehicle of  claim 117 , wherein the nitric oxide donor is present at a concentration of between about 0.5% and about 25% by weight/volume. 
     
     
         125 . The topical delivery vehicle of  claim 116 , wherein the water-containing portion comprises an ionic salt. 
     
     
         126 . The topical delivery vehicle of  claim 125 , wherein the ionic salt is present in a concentration of between about 5% and about 50% by weight/volume. 
     
     
         127 . The topical delivery vehicle of  claim 125 , wherein the ionic salt comprises one or more of lithium chloride, potassium chloride, calcium chloride, magnesium chloride, choline chloride, sodium fluoride and lithium bromide. 
     
     
         128 . The topical delivery vehicle of  claim 125 , wherein the ionic salt comprises sodium chloride. 
     
     
         129 . The topical delivery vehicle of  claim 116 , wherein the ionic strength is between about 1 M and about 15 M. 
     
     
         130 . The topical delivery vehicle of  claim 116 , wherein the topical delivery vehicle further comprises citric acid. 
     
     
         131 . A method, comprising:
 applying a topical delivery vehicle to the skin of a subject, wherein the topical delivery vehicle comprises an oil-based cream comprising a water-containing portion, the water-containing portion comprising: an ionic strength of between about 0.25 M and about 15 M, and ibuprofen, wherein the ibuprofen is present in the water-containing portion at a concentration of about 4% or more by weight.   
     
     
         132 . The method of  claim 131 , wherein the cream further comprises a nitric oxide donor. 
     
     
         133 . The method of  claim 132 , wherein the nitric oxide donor comprises L-arginine and/or L-arginine hydrochloride. 
     
     
         134 . The method of  claim 132 , wherein the nitric oxide donor is present at a concentration of at least 0.5% by weight. 
     
     
         135 . The method of  claim 131 , wherein the water-containing portion comprises an ionic salt comprising one or more of sodium chloride, lithium chloride, potassium chloride, calcium chloride, magnesium chloride, choline chloride, sodium fluoride and lithium bromide. 
     
     
         136 . The method of  claim 131 , wherein the ionic strength is between about 1 M and about 15 M. 
     
     
         137 . The method of  claim 131 , wherein the topical delivery vehicle further comprises citric acid. 
     
     
         138 . The method of  claim 131 , wherein the subject is human.