Controlled release cgrp delivery composition for cardiovascular and renal indications

Abstract

The present invention provides methods of treating heart failure and improving renal function, and/or preventing the advancement of heart failure into advanced stages, and methods of counteracting ischemia due to a myocardial infarction by providing improved methods of administering a therapeutically effective amount CGRP as a controlled release formulation. The therapies can be administered on an outpatient or inpatient basis and can further be used as maintenance therapies.

1 .- 47 . (canceled) 
     
     
         48 . A method of counteracting ischemia due to a myocardial infarction in a heart failure patient, comprising the steps of:
 (a) identifying a patient that is suffering from heart failure; and   (b) delivering a treatment effective amount of a composition comprising CGRP to the heart failure patient so that ischemia due to a myocardial infarction in the heart failure patient is counteracted;   
       wherein the composition is a flowable thermoplastic polymer composition comprising a biocompatible polymer, a biocompatible solvent and CGRP, and the composition is delivered to a bodily tissue or fluid in the patient, wherein the amounts of the polymer and the solvent are effective to form a biodegradable polymer matrix containing CGRP in situ when the composition contacts the bodily tissue or fluid. 
     
     
         49 . The method of  claim 48 , wherein the ischemia is counteracted by a reduction in infarction size or reduction in reperfusion injury. 
     
     
         50 . The method of  claim 48 , wherein the composition is delivered to the heart failure patient prior to the myocardial infarction. 
     
     
         51 . The method of  claim 48 , wherein the composition is in the form of a conjugate comprising CGRP coupled to a polymer. 
     
     
         52 . The method of  claim 51 , wherein the polymer is a poly(alkylene glycol) or a polysaccharide. 
     
     
         53 . The method of  claim 48 , wherein the composition comprises a controlled release additive. 
     
     
         54 . The method of  claim 48 , wherein the composition comprises between about 0.56 and 290 mg CGRP and between about 0.01 and 5.8 mL of the composition is administered to the patient. 
     
     
         55 . The method of  claim 48 , wherein the composition comprises about 0.56 and 290 mg CGRP and between about 0.004 and 1.93 mL of the composition is administered to the patient. 
     
     
         56 . The method of  claim 48 , wherein the biocompatible polymer is selected from the group consisting of polylactides, polyglycolides, polyanhydrides, polyorthoesters, polycaprolactones, polyamides, polyurethanes, polyesteramides, polydioxanones, polyacetals, polyketals, polycarbonates, polyorthocarbonates, polyphosphazenes, polyhydroxybutyrates, polyhydroxyvalerates, polyalkylene oxalates, polyacrylates, polyalkylene succinates, poly(malic acid), poly(amino acids) and copolymers, terpolymers, cellulose diacetate, ethylene vinyl alcohol, and copolymers and combinations thereof. 
     
     
         57 . The method of  claim 48 , wherein the polymer matrix releases CGRP by diffusion, erosion, or a combination of diffusion or erosion as the polymer matrix biodegrades in the patient. 
     
     
         58 . The method of  claim 48 , wherein the CGRP is delivered via a puncture needle or catheter. 
     
     
         59 . The method of  claim 48 , further comprising administering one or more drugs selected from the group consisting of anti-proliferative agents, anti-clotting agents, vasodilators, diuretics, beta-blockers, calcium ion channel blockers, cardioprotectants, blood thinners, cardiotonics, ACE inhibitors, anti-inflammatories, and antioxidants. 
     
     
         60 . The method of  claim 59 , wherein the drug is added to the polymer composition prior to administration such that the solid polymer matrix further contains the drug. 
     
     
         61 . The method of  claim 59 , wherein the drug is administered as a separate formulation before, simultaneously with, or subsequently to administration of the polymer composition. 
     
     
         62 . The method of  claim 48 , wherein the controlled release composition comprises biodegradable microspheres incorporating CGRP. 
     
     
         63 . The method of  claim 62 , wherein the microspheres comprise poly(lactic-co-glycolic acid), poly(lactic acid), poly(caprolactone), polycarbonates, polyamides, polyanhydrides, polyamino acids, polyortho esters, polyacetals, polycyanoacrylates degradable polyurethanes, polyacrylates, ethylene-vinyl acetate copolymers, acyl substituted cellulose acetates, and derivatives and copolymers thereof.