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.

1 - 115 . (canceled) 
   
   
       116 . A topical delivery vehicle, comprising:
 a nitric oxide donor; and   an NSAID.   
   
   
       117 . The topical delivery vehicle of  claim 116 , wherein the nitric oxide donor comprises L-arginine. 
   
   
       118 . The topical delivery vehicle of  claim 116 , wherein the nitric oxide donor comprises L-arginine HCl. 
   
   
       119 . The topical delivery vehicle of  claim 116 , wherein the nitric oxide donor comprises an L-arginine salt. 
   
   
       120 . The topical delivery vehicle of  claim 116 , wherein the nitric oxide donor is present at a concentration of at least 0.5% by weight/volume. 
   
   
       121 . The topical delivery vehicle of  claim 116 , wherein the NSAID is acetylsalicylic acid. 
   
   
       122 . The topical delivery vehicle of  claim 116 , wherein the NSAID is naproxen. 
   
   
       123 . The topical delivery vehicle of  claim 116 , wherein the NSAID is celecoxib. 
   
   
       124 . The topical delivery vehicle of  claim 116 , wherein the NSAID is refecoxib. 
   
   
       125 . The topical delivery vehicle of  claim 116 , wherein the topical delivery vehicle further comprises a hostile biophysical environment containing the NSAID. 
   
   
       126 . The topical delivery vehicle of  claim 125 , wherein the hostile biophysical environment comprises an ionic salt. 
   
   
       127 . The topical delivery vehicle of  claim 125 , wherein the hostile biophysical environment has an ionic strength of at least about 1 M. 
   
   
       128 . The topical delivery vehicle of  claim 125 , wherein the hostile biophysical environment comprises a component having an octanol-water partition coefficient of at least about 1000. 
   
   
       129 . The topical delivery vehicle of  claim 125 , wherein the hostile biophysical environment has a pH between about 3 and about 11. 
   
   
       130 . The topical delivery vehicle of  claim 125 , wherein the hostile biophysical environment comprises one or more of sodium chloride, choline chloride, magnesium chloride, calcium chloride. 
   
   
       131 . The topical delivery vehicle of  claim 125 , wherein the hostile biophysical environment is capable of driving the NSAID through stratum corneum when applied topically to a subject. 
   
   
       132 . The topical delivery vehicle of  claim 116 , wherein the topical delivery vehicle is a cream. 
   
   
       133 . The topical delivery vehicle of  claim 116 , wherein the topical delivery vehicle is a gel. 
   
   
       134 . The topical delivery vehicle of  claim 116 , wherein the topical delivery vehicle is a lotion. 
   
   
       135 . A method, comprising:
 applying, to a portion of the skin of a subject, a delivery vehicle comprising NSAID in a hostile biophysical environment.