Methods and apparatus for the enhanced delivery of physiologic agents to tissue surfaces

Abstract

Apparatus and methods deliver physiologically active agents in the presence of adjuvant gases. The adjuvant gases can enhance the effectiveness of the drug, lower the dosage of drug or concentration of drug necessary to achieve a therapeutic result, or both. Exemplary adjuvant gases include carbon dioxide, nitric oxide, nitrous oxide, and dilute acid gases.

1 . A method for delivering physiologically active agents to tissue, said method comprising: 
 contacting a tissue surface with a physiologically active agent; and    suffusing the tissue surface with an adjuvant gas which promotes uptake of the agent by the tissue or vascular circulation and/or which promotes an activity of the agent.    
   
   
       2 . A method as in  claim 1 , wherein at least a portion of the adjuvant gas is suffused simultaneously with contacting of at least a portion of the agent.  
   
   
       3 . A method as in  claim 1 , wherein at least a portion of the adjuvant gas is suffused prior to contacting the agent.  
   
   
       4 . A method as in  claim 1 , wherein at least a portion of the agent is suffused prior to contacting the adjuvant gas.  
   
   
       5 . A method as in any one of  claims 1  to  4 , wherein contacting comprises placing a solid, powder, or liquid form of the agent on or over the tissue surface.  
   
   
       6 . A method as in any one of  claims 1  to  4 , wherein contacting comprises suffusing the physiologically active agent in a gaseous, vapor, mist, or powder form.  
   
   
       7 . A method as in any one of  claims 1  to  4 , wherein the adjuvant gas is selected from the group consisting of carbon dioxide, nitric oxide, nitrous oxide, and dilute acid gases.  
   
   
       8 . A method as in any one of  claims 1  to  4 , wherein the physiologically active agent comprises at least one drug selected from the group consisting of nitroglycerin, triptans, imidazopyridines, 5-HT3 antagonists, epinephrine, angiotensin II, atrophine, apomorphine, and opioids.  
   
   
       9 . A method as in any one of  claims 1  to  4 , wherein the tissue surface comprises a mucosal surface.  
   
   
       10 . A method as in  claim 4 , wherein the mucosal surface is a nasal surface, an oral surface, an ocular tissue surface, or an auricular tissue surface.  
   
   
       11 . A system for infusing a mucosal surface with a physiologically active substance, said system comprising: 
 a source of an adjuvant gas;    a source of the physiologically active substance in a fluid form; and    means for delivering both the adjuvant gas and the physiologically active substance to the mucosal surface.    
   
   
       12 . A system as in  claim 11 , wherein the delivering means comprises a hand-held dispenser.  
   
   
       13 . A system as in  claim 12 , wherein the hand-held dispenser comprises a receptacle of pressurized adjuvant gas and a valve assembly for releasing the gas at a controlled flow rate in the range from 0.5 cc/sec to 20 cc/sec.  
   
   
       14 . A system as in  claim 13 , wherein the physiologically active substance is dissolved or suspended in the pressurized adjuvant gas.  
   
   
       15 . A system as in  claim 11 , wherein the source of adjuvant gas comprises a first receptacle and the source of physiologically active substance comprises a second receptacle.  
   
   
       16 . A system as in  claim 15 , wherein the means for delivering both the adjuvant gas and the physiologically active substance comprises a common conduit and nozzle for delivering the gas and substance simultaneously.  
   
   
       17 . A system as in any one of  claims 11  to  16 , wherein the source of adjuvant gas comprises a gas selected from the group consisting of carbon dioxide, nitric oxide, nitrous oxide, and dilute acid gases.  
   
   
       18 . A system as in  claim 17 , wherein the physiologically active agent comprises at least one drug selected from the group consisting of nitroglycerin, triptans, imidazopyridines, 5-HT3 antagonists, epinephrine, angiotensin II, atrophine, apomorphine, and opioids.