Compositions comprising rifabutin, clarithromycin, and clofazimine and uses thereof

Abstract

Oral administration of a solid dosage form of the present invention comprising an effective amount of rifabutin, an effective amount of clarithromycin, an effective amount of clofazimine, and an effective amount of an absorption enhancer, is used to treat a subject suffering from, or susceptible to, Mycobacterium avium subspecies paratuberculosis infection. In an embodiment, the solid dosage form is sufficiently designed to result in a reduction in the increased metabolism of clarithromycin caused by rifabutin. In an embodiment, the solid dosage form is sufficiently designed to result in a reduction in the metabolism of rifabutin caused by clarithromycin. In an embodiment, the solid dosage form is sufficiently designed to result in a reduction in risk of a subject developing leucopenia or uveitis as a result of rifabutin.

What is claimed is: 
     
         1 . A method of treating a  mycobacterium avium  subspecies paratuberculosis infection comprising orally administering to a subject a solid oral dosage form, the solid dosage form comprising an effective amount of rifabutin; an effective amount of clarithromycin; an effective amount of clofazimine; and polyethylene glycol having an average molecular weight of between 1000-15000 Daltons and between 300% and 700% w/w relative to the amount of clofazamine. 
     
     
         2 . The method of  claim 1  wherein the rifabutin, clarithromycin, and clofazimine are present in a 9±0.5:19±0.5:2±0.5 w/w/w ratio. 
     
     
         3 . The method of  claim 1  wherein the polyethylene glycol has an average molecular weight of between 5000-12000 Daltons. 
     
     
         4 . The method of  claim 1  wherein the polyethylene glycol has an average molecular weight of 7000-9000 Daltons. 
     
     
         5 . The method of  claim 1  wherein the polyethylene glycol is between 400% and 600% w/w relative to the amount of clofazimine. 
     
     
         6 . The method of  claim 1  wherein an amount of clofazimine is 10-15% w/w relative to an amount of clarithromycin and 20-25% w/w relative to an amount of rifabutin. 
     
     
         7 . The method of  claim 1  wherein the  mycobacterium avium  subspecies paratuberculosis infection is associated with an autoimmune disease. 
     
     
         8 . A method of treating a subject infected with  mycobacterium avium  subspecies paratuberculosis comprising:
 orally administering to the subject for an effective treatment period, a solid oral dosage form comprising:
 an effective amount of rifabutin; 
 an effective amount of clarithromycin; 
 an effective amount of clofazimine; and 
 an effective amount of an absorption enhancer, wherein the absorption enhancer is a polyethylene glycol, and the polyethylene glycol: (i) has an average molecular weight of between 1000-15000 Daltons, and (ii) is between 200% and 700% w/w relative to the amount of clofazamine, wherein an amount of clofazimine is 10-15% w/w relative to an amount of clarithromycin and 20-25% w/w relative to an amount of rifabutin, 
   wherein the effective treatment period is suitable to halt or reduce progression of the infection.   
     
     
         9 . The method of  claim 8  wherein the rifabutin, clarithromycin, and clofazimine are present in a 9±0.5:19±0.5:2±0.5 w/w/w ratio. 
     
     
         10 . The method of  claim 8  wherein the polyethylene glycol has an average molecular weight of between 5000-12000 Daltons. 
     
     
         11 . The method of  claim 8  wherein the polyethylene glycol has an average molecular weight of 7000-9000 Daltons. 
     
     
         12 . The method of  claim 8  wherein the polyethylene glycol is between 400% and 600% w/w relative to the amount of clofazimine. 
     
     
         13 . The method of  claim 8  wherein the  mycobacterium avium  subspecies paratuberculosis infection is associated with an autoimmune disease. 
     
     
         14 . A method of treating a subject having an autoimmune disease comprising:
 orally administering to the subject for an effective treatment period, a solid oral dosage form comprising:
 an effective amount of rifabutin; 
 an effective amount of clarithromycin; 
 an effective amount of clofazimine; and 
 an effective amount of an absorption enhancer, wherein the absorption enhancer is a polyethylene glycol, and the polyethylene glycol: (i) has an average molecular weight of between 1000-15000 Daltons, and (ii) is between 200% and 700% w/w relative to the amount of clofazamine, wherein an amount of clofazimine is 10-15% w/w relative to an amount of clarithromycin and 20-25% w/w relative to an amount of rifabutin, 
   wherein the effective treatment period is suitable to halt or reduce progression of the disease.   
     
     
         15 . The method of  claim 14  wherein the rifabutin, clarithromycin, and clofazimine are present in a 9±0.5:19±0.5:2±0.5 w/w/w ratio. 
     
     
         16 . The method of  claim 14  wherein the polyethylene glycol has an average molecular weight of between 5000-12000 Daltons. 
     
     
         17 . The method of  claim 14  wherein the polyethylene glycol has an average molecular weight of 7000-9000 Daltons. 
     
     
         18 . The method of  claim 14  wherein the polyethylene glycol is between 400% and 600% w/w relative to the amount of clofazimine.