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 system for administering to a patient a labile active agent subject to degradation as a result of exposure to peripheral tissue, vascular venous tissue, or the liver, the system comprising:
 a dry powder inhalation device comprising a formulation of microparticles comprising a diketopiperazine and the labile active agent, wherein about 35% to about 75% of the microparticles have an aerodynamic diameter of less than 5.8 micrometer;   wherein inhalation of the formulation results in a greater therapeutic effect from a lower exposure of the labile active agent than oral, subcutaneous and intravenous administration of the labile active agent.   
     
     
         2 . The system of  claim 1 , wherein said diketopiperazine is 2,5-diketo-3,6-di(4-X-aminobutyl)piperazine, and X is selected from the group consisting of succinyl, glutaryl, maleyl, and fumaryl; or a pharmaceutically acceptable salt thereof. 
     
     
         3 . The system of  claim 1 , wherein the formulation further comprises a pharmaceutically acceptable carrier or excipient. 
     
     
         4 . The system of  claim 1 , wherein the labile active agent comprises a vasoactive agent, a neuroactive agent, a hormone, an anticoagulant, an immune-modulating agent, a cytotoxic agent, an antibiotic, an antiviral agent, an antigen, or an antibody. 
     
     
         5 . The system of  claim 4 , wherein the vasoactive agent is a prostaglandin. 
     
     
         6 . The system of  claim 5 , wherein the prostaglandin is PG 12. 
     
     
         7 . The system of  claim 4 , wherein the vasoactive agent is administered at dosages ranging from about 0.01 mg to about 3 mg. 
     
     
         8 . The system of  claim 1 , wherein said patient is in need of treatment with a vasodilator. 
     
     
         9 . The system of  claim 1 , wherein the dry powder inhalation system comprises a cartridge. 
     
     
         10 . The system of  claim 2 , wherein X is fumaryl. 
     
     
         11 . The system of  claim 4 , wherein said labile active agent does not bind receptors in the lung. 
     
     
         12 . The system of  claim 2 , wherein said diketopiperazine comprises a pharmaceutically acceptable salt.