Compositions and methods for preventing or treating muscle conditions

Abstract

Provided herein are compositions for preventing or treating muscle conditions such as muscle damage, injury, or atrophy. In some embodiments, the compositions comprise a prostaglandin E2 (PGE2) compound and a myotoxin. In some embodiments, the muscle damage, injury, or atrophy is the result of a nerve injury, a surgical procedure, or a traumatic injury. Methods of promoting muscle regeneration and methods of increasing muscle mass are also provided herein.

What is claimed is: 
     
         1 . A method of treating a muscle condition, the method comprising:
 (a) administering a prostaglandin E2 (PGE2) compound to a subject in need thereof and   (b) administering a myotoxin to the subject,   wherein the administering is by intramuscular administration.   
     
     
         2 . The method of  claim 1 , wherein the PGE2 compound is selected from the group consisting of PGE2, a PGE2 derivative, a PGE2 prodrug, a PGE2 receptor agonist, a compound that attenuates PGE2 catabolism, a compound that neutralizes PGE2 inhibition, a derivative thereof, an analog thereof, and a combination thereof. 
     
     
         3 . The method of  claim 2 , wherein the PGE2 compound is PGE2. 
     
     
         4 . The method of  claim 2 , wherein the PGE2 compound is a PGE2 derivative, and the PGE2 derivative comprises 16,16-dimethyl prostaglandin E2. 
     
     
         5 . The method of  claim 2 , wherein the PGE2 compound is a compound that attenuates PGE2 catabolism, and the compound that attenuates PGE2 catabolism comprises a compound, neutralizing peptide, or neutralizing antibody that inactivates or blocks 15-hydroxyprostaglandin dehydrogenase (15-PGDH) or inactivates or blocks a prostaglandin transporter (PGT or SLCO2A1). 
     
     
         6 . The method of  claim 1 , wherein the myotoxin is selected from the group consisting of an anesthetic, a divalent cation, snake venom, lizard venom, bee venom, and a combination thereof. 
     
     
         7 . The method of  claim 6 , wherein the myotoxin is an anesthetic, and the anesthetic is selected from the group consisting of an amino-amide anesthetic, an amino-ester anesthetic, and a combination thereof. 
     
     
         8 . The method of  claim 6 , wherein the anesthetic is an amino-amide anesthetic, and the amino-amide anesthetic is selected from the group consisting of bupivacaine, levobupivacaine, articaine, ropivacaine, butanilicaine, carticaine, dibucaine, etidocaine, lidocaine, mepivacaine, prilocaine, trimecaine, and a combination thereof. 
     
     
         9 . The method of  claim 6 , wherein the anesthetic is an amino-ester anesthetic, and the amino-ester anesthetic is selected from the group consisting of an aminobenzoic acid ester anesthetic, a benzoic acid ester anesthetic, and a combination thereof. 
     
     
         10 . The method of  claim 9 , wherein the amino-ester anesthetic is an aminobenzoic acid ester anesthetic, and the aminobenzoic acid ester anesthetic is selected from the group consisting of benzocaine, butacaine, butamben, chloroprocaine, dimethocaine, lucaine, meprylcaine, metabutethamine, metabutoxycaine, nitracaine, orthocaine, propoxycaine, procaine, proxymetacaine, risocaine, tetracaine, and a combination thereof. 
     
     
         11 . The method of  claim 9 , wherein the amino-ester anesthetic is a benzoic acid ester anesthetic, and the benzoic acid ester anesthetic is selected from the group consisting of amylocaine, cocaine, cyclomethycaine, α-eucaine, β-eucaine, hexylcaine, isobucaine, piperocaine, and a combination thereof. 
     
     
         12 . The method of  claim 6 , wherein the myotoxin is a snake venom or a lizard venom, and the snake venom or the lizard venom is selected from the group consisting of notexin, cardiotoxin, bungarotoxin, and a combination thereof. 
     
     
         13 . The method of  claim 6 , wherein the myotoxin is a divalent cation, and the divalent cation is selected from the group consisting of Ba 2+ , Sr 2+ , Mg 2+ , Ca 2+ , Mn 2+ , Ni 2+ , Co 2+ , a salt thereof, and a combination thereof. 
     
     
         14 . The method of  claim 1 , wherein the PGE2 compound is PGE2 and/or 16,16-dimethyl prostaglandin E2, and the myotoxin is bupivacaine. 
     
     
         15 . The method of  claim 1 , wherein the muscle condition comprises muscle damage, injury, or atrophy. 
     
     
         16 . The method of  claim 1 , wherein the intramuscular administration comprises an intramuscular injection into a skeletal muscle. 
     
     
         17 . The method of  claim 1 , wherein intramuscular administration comprises an acute exposure, an intermittent exposure, a chronic exposure, or a continuous exposure, to the subject. 
     
     
         18 . The method of  claim 1 , wherein the intramuscular administration comprises an intramuscular injection into a muscle that is injured, damaged or atrophied. 
     
     
         19 . The method of  claim 1 , wherein the method comprises administering the prostaglandin E2 (PGE2) compound and administering the myotoxin together in a single formulation to the subject. 
     
     
         20 . The method of  claim 1 , wherein the method comprises administering the prostaglandin E2 (PGE2) compound and administering the myotoxin sequentially in separate formulations to the subject. 
     
     
         21 . The method of  claim 20 , wherein the method comprises administering the prostaglandin E2 (PGE2) compound before administering the myotoxin to the subject. 
     
     
         22 . The method of  claim 20 , wherein the method comprises administering the prostaglandin E2 (PGE2) compound after administering the myotoxin to the subject. 
     
     
         23 . The method of  claim 1 , the method comprising administering the prostaglandin E2 (PGE2) compound with a pharmaceutically suitable excipient and administering the myotoxin with a pharmaceutically suitable excipient to the subject in need thereof by intramuscular administration. 
     
     
         24 . The method of  claim 1 , the method comprising administering the prostaglandin E2 (PGE2) compound and the myotoxin with the pharmaceutically suitable excipient in a single formulation to the subject in need thereof by intramuscular administration. 
     
     
         25 . The method of  claim 1 , the method comprising administering the prostaglandin E2 (PGE2) compound with a pharmaceutically suitable excipient and administering the myotoxin with a pharmaceutically suitable excipient sequentially in separate formulations to the subject in need thereof by intramuscular administration. 
     
     
         26 . The method of  claim 1 , wherein the intramuscular administration comprises an intramuscular injection into the muscle with the muscle condition.