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 . A method, comprising an act of:
 applying, to a portion of the skin of a subject, a delivery vehicle comprising a pharmaceutical agent in a hostile biophysical environment.   
     
     
         2 . The method of  claim 1 , wherein the hostile biophysical environment has an ionic strength of at least about 1 M. 
     
     
         3 - 4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the hostile biophysical environment has a pH of at least about 9. 
     
     
         6 . The method of  claim 1 , wherein the hostile biophysical environment has a pH of less than about 5. 
     
     
         7 . The method of  claim 1 , wherein the hostile biophysical environment comprises a component having an octanol-water partition coefficient of at least about 1000. 
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein the act of applying occurs for a duration sufficient to transport an effective dosage of the pharmaceutical agent to treat a medical condition. 
     
     
         10 . The method of  claim 1 , wherein the pharmaceutical agent is one or more of naproxen, celecoxib, refecoxib, morphine, propoxyphene, oxycodone, hydrocodon, yohimbie, alprostadil, sildenafil, cialis, uprima, vardenaifl, dihydroergotamine, ergotamine, surnatripan, rizatriptan, zolmitriptan, finasteride, eflornithine, minoxidil, niacin, lidocaine, or benzocaine. 
     
     
         11 . The method of  claim 1 , wherein the hostile biophysical environment is capable of driving the pharmaceutical agent through stratum corneum. 
     
     
         12 . The method of  claim 1 , wherein the hostile biophysical environment has a pH between about 3 and about 11. 
     
     
         13 . The method of  claim 1 , wherein the hostile biophysical environment comprises an ionic salt. 
     
     
         14 . The method of  claim 1 , wherein the hostile biophysical environment comprises one or more of sodium chloride, choline chloride, magnesium chloride, calcium chloride. 
     
     
         15 . The method of  claim 1 , wherein the hostile biophysical environment has an ionic strength of between about 0.25 M and about 15 M. 
     
     
         16 - 22 . (canceled) 
     
     
         23 . The method of  claim 1 , wherein the hostile biophysical environment comprises a silicon-containing substance. 
     
     
         24 - 25 . (canceled) 
     
     
         26 . The method of  claim 9 , wherein the medical condition is selected from the group consisting of cramps, pain, and arthritis. 
     
     
         27 - 29 . (canceled) 
     
     
         30 . The method of  claim 26 , wherein the pharmaceutical agent is one or more of ibuprofen, naproxen, celecoxib, refecoxib, morphine, propoxyphene, oxycodone, or hydrocodon. 
     
     
         31 . The method of  claim 26 , wherein the medical condition is pain, and wherein the pharmaceutical agent comprises an NSAID. 
     
     
         32 . The method of  claim 31 , wherein the NSAID comprises ibuprofen. 
     
     
         33 - 56 . (canceled) 
     
     
         57 . The method of  claim 1 , wherein the delivery vehicle further comprises a nitric oxide donor. 
     
     
         58 . The method of  claim 57 , wherein the nitric oxide donor comprises L-arginine. 
     
     
         59 . The method of  claim 57 , wherein the nitric oxide donor is present in an amount effective to increase blood flow within the skin. 
     
     
         60 - 115 . (canceled)