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, wherein the adjuvant gas consists of a gas selected from the group consisting of carbon dioxide, nitric oxide, nitrous oxide, and dilute acid gases.   
   
   
       2 . The method according to  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 . The method according to  claim 1 , wherein at least a portion of the adjuvant gas is suffused prior to contacting the agent. 
   
   
       4 . The method according to  claim 1 , wherein at least a portion of the agent is suffused prior to contacting the adjuvant gas. 
   
   
       5 . The method according to  claim 1 , wherein contacting comprises placing a solid, powder, or liquid form of the agent on or over the tissue surface. 
   
   
       6 . The method according to  claim 1 , wherein contacting comprises suffusing the physiologically active agent in a gaseous, vapor, mist, or powder form. 
   
   
       7 . The method according to  claim 1 , wherein the physiologically active agent comprises at least one drug selected from the group consisting of nitroglycerin, imidazopyridines, 5-HT3 antagonists, epinephrine, angiotensin II, atrophine, apomorphine, and opioids. 
   
   
       8 . The method according to  claim 1 , wherein the tissue surface comprises a mucosal surface. 
   
   
       9 . The method according to  claim 8 , wherein the mucosal surface is a nasal surface, an oral surface, an ocular tissue surface, or an auricular tissue surface. 
   
   
       10 . 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, wherein means 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.   
   
   
       11 . The system according to  claim 10 , wherein the delivering means comprises a hand-held dispenser. 
   
   
       12 . The system according to  claim 10 , wherein the physiologically active substance is dissolved or suspended in the pressurized adjuvant gas. 
   
   
       13 . The system according to  claim 10 , wherein the source of adjuvant gas comprises a first receptacle and the source of physiologically active substance comprises a second receptacle. 
   
   
       14 . The system according to  claim 13 , 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. 
   
   
       15 . The system according to  claim 10 , 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. 
   
   
       16 . The system according to  claim 15 , 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. 
   
   
       17 . A method for delivering a 5-HT3 antagonist to a patient, said method comprising:
 contacting a nasal mucosal surface with a 5-HT3 antagonist, while the 5-HT3 antagonist is in contact with the nasal mucosal tissue surface, suffusing the nasal mucosal surface with a gas containing at least 50% carbon by volume, wherein the carbon dioxide promotes uptake of the 5-HT3 antagonist into the mucosal tissue or promotes transmucosal delivery of the 5-HT3 antagonist into the vascular circulation and wherein the patient refrains from inhaling the gas while the carbon dioxide is being suffused.   
   
   
       18 . The method according to  claim 17 , wherein the 5-HT3 antagonist comprises ondansetron. 
   
   
       19 . The method according to  claim 17 , wherein the gas consists essentially of carbon dioxide.