Delivery of Active Agents

Abstract

A method of introducing a physiologically-active agent into the circulatory system of a mammal is disclosed herein. The method utilizes a rapid drug delivery system which prevents deactivation or degradation of the active agent being administered to a patient in need of treatment. In particular, the drug delivery system is designed for pulmonary drug delivery such as by inhalation, for delivery of the active agents such as proteins and peptides to the pulmonary circulation in a therapeutically effective manner avoiding degradation of the active agents in peripheral and vascular tissue before reaching the target site.

We claim: 
     
         1 . A method of administering a labile active agent to a patient comprising:
 administering to said patient in need thereof an effective amount of a pharmaceutical composition comprising a diketopiperazine and one or more active agents by pulmonary inhalation;   wherein the one or more active agents is sensitive to enzymatic deactivation or degradation when in contact with local peripheral and vascular tissue, and said pharmaceutical composition provides avoidance of enzymatic deactivation or degradation of the one or more active agents.   
     
     
         2 . The method of  claim 1 , wherein said diketopiperazine is 2,5-diketo-3,6-di(4-X-aminobutyl)piperazine; wherein X is selected from the group consisting of succinyl, glutaryl, maleyl, and fumaryl; or a pharmaceutically acceptable salt thereof. 
     
     
         3 . The method of  claim 1 , wherein the pharmaceutical composition is a dry powder formulation. 
     
     
         4 . The method of  claim 3 , wherein said dry powder formulation further comprises a pharmaceutically acceptable carrier or excipient. 
     
     
         5 . The method of  claim 3 , wherein the dry powder formulation is administered using a dry powder inhalation system. 
     
     
         6 . The method of  claim 1 , wherein the at least one of the one or more active agents is a vasoactive agent. 
     
     
         7 . The method of  claim 6 , wherein the vasoactive agent is a prostaglandin. 
     
     
         8 . The method of  claim 7 , wherein the prostaglandin is PG 12. 
     
     
         9 . The method of  claim 6 , wherein the at least one vasoactive agent is administered at dosages ranging from about 0.01 mg to about 3 mg. 
     
     
         10 . The method of  claim 1 , wherein said patient is in need of treatment with a vasodilator. 
     
     
         11 . The method of  claim 1 , wherein the step of administering said pharmaceutical composition to said patient comprises administering said pharmaceutical composition using a breath-powered dry powder inhaler comprising a cartridge. 
     
     
         12 . A method of improving the effectiveness of a labile active agent in a patient comprising:
 administering by inhalation a pharmaceutical composition comprising a diketopiperazine microparticle and one or more active agents, wherein about 35% to about 75% of the microparticles have an aerodynamic diameter of less than 5.8 μm;   wherein the labile active agent when administered by injection is subject to degradation in the patient as a result of exposure to peripheral tissue, vascular venous tissue, or liver metabolism, and said labile active agent effectiveness is reduced by said degradation prior to reaching a site of action.   
     
     
         13 . The method of  claim 12 , wherein said diketopiperazine is 2,5-diketo-3,6-di(4-X-aminobutyl)piperazine; wherein X is selected from the group consisting of succinyl, glutaryl, maleyl, and fumaryl; or a pharmaceutically acceptable salt thereof. 
     
     
         14 . The method of  claim 12 , wherein the pharmaceutical composition is a dry powder formulation. 
     
     
         15 . The method of  claim 12 , wherein said labile active agent is a prostaglandin. 
     
     
         16 . The method of  claim 15 , wherein the prostaglandin is PG 12. 
     
     
         17 . A method of administering a prostaglandin to a patient in need thereof comprising:
 administering to said patient an inhalable dry powder pharmaceutical composition comprising diketopiperazine microparticles and said prostaglandin, wherein about 35% to about 75% of the diketopiperazine microparticles have an aerodynamic diameter of less than 5.8 μm,   wherein the prostaglandin is subject to degradation in a patient as a result of exposure to peripheral tissue, vascular venous tissue, or liver metabolism when administered by other routes of administration.   
     
     
         18 . The method of  claim 17 , wherein the inhalable dry powder further comprises an additional vasoactive agent. 
     
     
         19 . The method of  claim 17 , wherein the diketopiperazine microparticles comprise 2,5-diketo-3,6-di(4-X-aminobutyl)piperazine and X is fumaryl. 
     
     
         20 . A method of treating pulmonary disease to a patient in need thereof comprising:
 administering to said patient an inhalable dry powder formulation comprising a therapeutically effective amount of a prostaglandin using a breath-powered dry powder inhaler, wherein said formulation comprises from about 0.01 mg to about 3 mg of said prostaglandin.   
     
     
         21 . The method of  claim 20 , wherein said prostaglandin is PG I2.