Val (8) GLP-1 Composition and Method for Treating Functional Dyspepsia and/or Irritable Bowel Syndrome

Abstract

A method of treating functional dyspepsia and/or irritable bowel syndrome in mammals in need of treatment is disclosed herein. The method comprises administering to the mammal a formulation by inhalation, wherein the formulation avoids first pass metabolism of the active ingredient. The method comprises administering a formulation by pulmonary inhalation comprising a diketopiperazine and a glucagon-like peptide (GLP-1), analog, ROSE-010.

We claim: 
     
         1 . A process for forming a particle comprising Val (8) GLP-1 and a diketopiperazine comprising the steps of:
 providing a Val (8) GLP-1;   providing a diketopiperazine in a form selected from particle-forming diketopiperazine, diketopiperazine particles, and combinations thereof; and   combining said Val (8) GLP-1 and said diketopiperazine in the form of a co-solution, wherein said particle comprising said Val (8) GLP-1 and said diketopiperazine is formed.   
     
     
         2 . The process of  claim 1 , further comprising removing a solvent from said co-solution by lyophilization, filtration, or spray drying. 
     
     
         3 . The process of  claim 2 , wherein said particle comprising said Val (8) GLP-1 and said diketopiperazine is formed by removing said solvent. 
     
     
         4 . The process of  claim 2 , wherein said particle comprising said Val (8) GLP-1 and said diketopiperazine is formed prior to removing said solvent. 
     
     
         5 . The process of  claim 1 , wherein said Val (8) GLP-1 is provided in the form of a solution comprising a Val (8) GLP-1 concentration of about 0.001 mg/ml-50 mg/ml. 
     
     
         6 . The process of  claim 5 , wherein said Val (8) GLP-1 is provided in the form of a solution comprising a Val (8) GLP-1 concentration of about 0.1 mg/ml-10 mg/ml. 
     
     
         7 . The process of  claim 5 , wherein said Val (8) GLP-1 is provided in the form of a solution comprising a Val (8) GLP-1 concentration of about 0.25 mg/ml. 
     
     
         8 . The process of  claim 7 , wherein said diketopiperazine is provided in the form of a suspension of diketopiperazine particles. 
     
     
         9 . The process of  claim 7 , wherein said diketopiperazine is provided in the form of a solution comprising particle-forming diketopiperazine, the process further comprising adjusting the pH of said solution to form diketopiperazine particles. 
     
     
         10 . The process of  claim 8 , further comprising adding an agent to said suspension, wherein the agent is selected from the group consisting of salts, surfactants, ions, osmolytes, chaotropes and lyotropes, acids, bases, and organic solvents. 
     
     
         11 . The process of  claim 10  wherein said agent promotes association between said Val (8) GLP-1 and said diketopiperazine particles. 
     
     
         12 . The process of  claim 11 , wherein said agent is sodium chloride. 
     
     
         13 . A method of administering an effective amount of a Val(8) GLP-1 to a subject in need thereof by pulmonary delivery, said method comprising providing to said subject an inhalable dry powder formulation comprising Val(8) GLP-1 and a diketopiperazine. 
     
     
         14 . The method of  claim 13 , wherein said pulmonary delivery is obtained using a dry powder inhalation system. 
     
     
         15 . The method of  claim 13 , wherein the dry powder inhalation system comprises a cartridge. 
     
     
         16 . The method of  claim 13 , wherein said dry powder formulation further comprises a pharmaceutically acceptable carrier or excipient. 
     
     
         17 . The method of  claim 13 , wherein said need comprises the treatment of diabetes, ischemia, reperfused tissue injury, dyslipidemia, diabetic cardiomyopathy, myocardial infarction, acute coronary syndrome, obesity, catabolic changes after surgery, hyperglycemia, irritable bowel syndrome, functional dyspepsia, stroke, neurodegenerative disorders, memory and learning disorders, islet cell transplant or regenerative therapy. 
     
     
         18 . The method of  claim 17 , wherein said need comprises the treatment of irritable bowel syndrome. 
     
     
         19 . The method of  claim 13 , wherein a dosage of from about 10 μg to about 900 μg of Val(8) GLP-1 is administered per administration. 
     
     
         20 . The method of  claim 13 , wherein a dosage of from about 25 μg to about 500 μg of Val(8) GLP-1 is administered per administration. 
     
     
         21 . The method of  claim 13 , wherein a dosage of from about 50 μg to about 300 μg of Val(8) GLP-1 is administered per administration. 
     
     
         22 . A method of administering an effective amount of a GLP-1 molecule or a GLP-1 analog to a subject in need of treatment of irritable bowel syndrome by pulmonary delivery, said method comprising providing to said subject an inhalable dry powder formulation comprising a GLP-1 molecule or GLP-1 analog and a diketopiperazine. 
     
     
         23 . A method of forming a powder composition with an improved GLP-1 pharmacokinetic profile, comprising the steps of:
 providing a Val (8) GLP-1;   providing a particle-forming diketopiperazine in a solution;   forming diketopiperazine particles;   combining said Val (8) GLP-1 and said solution to form a co-solution; and   removing solvent from said co-solution by spray-drying to form a powder with an improved GLP-1 pharmacokinetic profile.