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.

What is claimed is: 
     
         1 . A method of administering a labile active agent to a patient in need thereof comprising:
 administering by inhalation a pharmaceutical composition comprising the labile active agent associated with a diketopiperazine microparticle wherein the active agent is subject to degradation in a patient as a result of exposure to peripheral tissue, vascular venous tissue, or liver metabolism, and wherein the effectiveness of said active agent is reduced by said degradation prior to reaching the agent's site of action.   
     
     
         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 active agent is a protein, a peptide, or an analog thereof. 
     
     
         7 . The method of  claim 1 , wherein the active agent is an endocrine hormone or an analog thereof. 
     
     
         8 . The method of  claim 7 , wherein the endocrine hormone is a hormone associated with diabetes, hyperglycemia and/or obesity. 
     
     
         9 . The method of  claim 8 , wherein the diabetes is type 2 diabetes mellitus. 
     
     
         10 . The method of  claim 9 , wherein the step of administering said composition to said patient comprises administration of said composition using a dry powder inhaler comprising a cartridge. 
     
     
         11 . The method of  claim 10  wherein about 35% to about 75% of the microparticles have an aerodynamic diameter of less than 5.8 um. 
     
     
         12 . The method of  claim 10  wherein said composition comprises GLP-1. 
     
     
         13 . The method of  claim 1  wherein the labile active agent is not GLP-1. 
     
     
         14 . A method of improving the effectiveness of a labile active agent comprising:
 administering by inhalation a pharmaceutical composition comprising the labile active agent associated with a diketopiperazine microparticle; wherein the labile active agent is recognized as being subject to degradation in the patient as a result of exposure to peripheral tissue, vascular venous tissue, or liver metabolism, and wherein the effectiveness of said agent is reduced by said degradation prior to reaching a site of action of the labile active agent.   
     
     
         15 . The method of  claim 14 , 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. 
     
     
         16 . The method of  claim 14 , wherein the pharmaceutical composition is a dry powder formulation. 
     
     
         17 . The method of  claim 16 , wherein said dry powder formulation further comprises a pharmaceutically acceptable carrier or excipient. 
     
     
         18 . The method of  claim 16 , wherein the dry powder formulation is administered using a dry powder inhalation system. 
     
     
         19 . The method of  claim 14 , wherein the labile active agent is a protein, a peptide, or an analog thereof. 
     
     
         20 . The method of  claim 14  wherein the labile active agent is GLP-1.