Cytotoxin (non-neurotoxin) for the treatment of human headache disorders and inflammatory diseases

Abstract

Pharmaceutical applications of a chemodenervating agent reduce pain by altering release of pain- and inflammation-mediating autocoids, with a duration of action between 12-24 weeks. The limiting factor in dosing for this application is weakness and paralysis created by higher doses of the chemodenervating pharmaceutical mediated by action of the neurotoxin component of this chemodenervating pharmaceutical. The invention described herein represents a novel mechanism and pharmaceutical formulation which eliminates the neurotoxin component of the chemodenervating pharmaceutical, while retaining the cytotoxin component which provides an essential bioeffect for the relief of pain and inflammation. The invention allows for improvement in administering the pharmaceutical agent for the reduction of pain and/or inflammation without causing muscular weakness and paralysis.

I claim:  
     
         1 . A pharmaceutical composition for treatment of inflammation or pain comprising purified protein, 
 wherein said purified protein is derived from  Clostridium botulinum,  and    wherein said purified protein substantially lacks neurotoxin properties.    
     
     
         2 . The pharmaceutical composition of  claim 1 , 
 wherein said purified protein is derived from  Clostridium botulinum  type C.    
     
     
         3 . The pharmaceutical composition of  claim 1 , 
 wherein said purified protein comprises  botulinum  toxin C2.    
     
     
         4 . The pharmaceutical composition of  claim 3 , 
 wherein said  botulinum  toxin C2 is purified from a bacterial strain expressing at least one cloned gene encoding a protein component of said  botulinum  toxin C2.    
     
     
         5 . A method for treatment of a disorder comprising the steps of, 
 selecting a region of a patient for treatment, and    administering a therapeutically effective amount of a pharmaceutical composition to said region,    wherein said pharmaceutical composition comprises a purified protein derived from  Clostridium botulinum,  and    wherein said purified protein substantially lacks neurotoxin properties.    
     
     
         6 . The method of  claim 5 , wherein said administration of said pharmaceutical composition to said region produces substantially no muscular weakening.  
     
     
         7 . The method of  claim 5 , wherein said therapeutic effect is mediated by inhibition of secretion of autocoids from mast cells, without antagonizing neuromuscular transmission.  
     
     
         8 . The method of  claim 5 , wherein said purified protein is derived from  Clostridium botulinum  type C.  
     
     
         9 . The method of  claim 5 , wherein said purified protein comprises botulinum toxin C2.  
     
     
         10 . The method of  claim 9 , wherein said  botulinum  toxin C2 is purified from a bacterial strain expressing at least one cloned gene encoding a protein component of said  botulinum  toxin C2.  
     
     
         11 . The method of  claim 5 , wherein said administration is by injection into said region.  
     
     
         12 . The method of  claim 5 , wherein said administration is by topical application to said region.  
     
     
         13 . The method of  claim 5 , wherein said application is of a dose of between approximately 5 and approximately 20 LD 50 units, as measured using the Swiss Webster mouse bioassay.  
     
     
         14 . The method of  claim 5 , wherein said application is of a dose of between approximately 20 and approximately 40 LD 50 units, as measured using the Swiss Webster mouse bioassay.  
     
     
         15 . The method of  claim 5 , wherein the disorder is selected from the group consisting of tension headache, migraine headache, and essential headache.  
     
     
         16 . The method of  claim 15 , wherein said region is the head.  
     
     
         17 . The method of  claim 15 , wherein said region is the neck.  
     
     
         18 . The method of  claim 5 , wherein the disorder is regional muscle pain or inflammation.  
     
     
         19 . The method of  claim 5 , wherein the disorder is selected from the group consisting of inflammation, pain, edema, redness, and itching.  
     
     
         20 . The method of  claim 5 , wherein the disorder is selected from the group consisting of asthma, eczema, hay fever, excessive salivation, tearing, otitis, anal fissures, and cystitis.  
     
     
         21 . The method of  claim 5 , wherein the disorder is selected from the group consisting of gastrointestinal ulceration and gastrointestinal inflammation.  
     
     
         22 . The method of  claim 5 , wherein the disorder is selected from the group consisting of myofascial pain, spasmodic torticollis, blepharospasm, and hemifacial spasm.  
     
     
         23 . The method of  claim 5 , wherein the disorder is rheumatoid arthritis.  
     
     
         24 . The method of  claim 5 , wherein the disorder is vasculitis.  
     
     
         25 . The pharmaceutical composition of  claim 1 , wherein said purified protein is prepared by biochemical separation to remove substantially all neurotoxin properties.  
     
     
         26 . The method of  claim 5 , wherein the disorder is selected from the group consisting of allergic conjunctivitis and allergic blepharoconjunctivitis.