Novel compositions and methods for prevention and treatment of protozoal disease

Abstract

A composition is provided that has been specially adapted for parenteral administration, e.g., intranasal, intramuscular, subcutaneous, transdermal or intraveneous administration, wherein the composition is comprised of at least one anti-protozoal drug in a therapeutically effective amount for the treatment or prevention of protozoan infections in man an in animals. In one embodiment, the anti-protozoal drug is a triazine-based anticoccidial agent, e.g., a triazinedione or triazinetrione such as diclazuril, toltrazuril, sulfonotoltrazuril or water-soluble sodium salts thereof. In a presently preferred embodiment, the triazine-based anticoccidial agent is sulfonototrazuril. Methods of treatment of protozoal infections in man and animals are also provided.

What is claimed is:  
     
         1 . A composition useful for the treatment and prevention of protozoan infections in man and in animals that is adapted for parenteral administration, comprising at least one anti-protozoal drug.  
     
     
         2 . The composition of  claim 1 , wherein the anti-protozoal drug is a triazine-based anticoccidial.  
     
     
         3 . The composition of  claim 2 , wherein the triazine-based anticoccidial is selected from the group consisting of clazuril, diclazuril, letrazuril, toltrazuril and mixtures thereof.  
     
     
         4 . The composition of  claim 2 , wherein the triazine-based anticoccidial is sulfonotoltrazuril.  
     
     
         5 . The composition of  claim 2 , wherein the triazine-based anticoccidial is toltrazuril sulfone.  
     
     
         6 . The composition of  claim 2 , further comprising a suitable solvent of the triazine-based anticocidial.  
     
     
         7 . The composition of  claim 6 , wherein the solvent is selected from the group consisting of DMSO, DMA and water.  
     
     
         8 . The composition of  claim 6 , wherein the triazine-based anticoccidial is selected from the group consisting of clazuril, diclazuril, letrazuril, toltrazuril and mixtures thereof and the solvent is DMSO.  
     
     
         9 . The composition of  claim 6 , wherein the triazine-based anticoccidial is diclazuril sulffone and the solvent is DMSO.  
     
     
         10 . The composition of  claim 6 , wherein the triazine-based anticoccidial is sulfonotoltrazuril and the solvent is DMSO.  
     
     
         11 . The composition of  claim 6 , wherein the triazine-based anticoccidial is toltrazuril sulfone and the solvent is DMSO.  
     
     
         12 . The composition of  claim 6 , wherein the triazine-based anticoccidial is water-soluble and the solvent is water.  
     
     
         13 . The composition of  claim 2 , wherein the triazine-based anticoccidial is a water-soluble salt of a triazine-based anticoccidial selected from the group consisting of clazuril, diclazuril, letrazuril, toltrazuril and mixtures thereof.  
     
     
         14 . The composition of  claim 13 , wherein the triazine-based anticoccidial is a sodium salt of a triazine-based anticoccidial selected from the group consisting of clazuril, diclazuril, letrazuril, toltrazuril and mixtures thereof.  
     
     
         15 . The composition of  claim 2 , wherein the triazine-based anticoccidial is a water-soluble salt of toltrazuril sulfone.  
     
     
         16 . The composition of  claim 15 , wherein the triazine-based anticoccidial is a sodium salt of toltrazuril sulfone.  
     
     
         17 . The composition of  claim 2 , wherein the triazine-based anticoccidial is a water-soluble salt of sulfonotoltrazuril.  
     
     
         18 . The composition of  claim 17 , wherein the triazine-based anticoccidial is a sodium salt of sulfonotoltrazuril.  
     
     
         19 . The composition of  claim 2 , wherein the triazine-based anticoccidial is a water-soluble salt of diclazuril.  
     
     
         20 . The composition of  claim 19 , wherein the triazine-based anticoccidial is a sodium salt of diclazuril.  
     
     
         21 . The composition of  claim 1 , wherein the composition is formulated for a parenteral administration selected from the group consisting of intraveneous, intramuscular, subcutaneous, intranasal, transdermal and transmucosal.  
     
     
         22 . The composition of  claim 2 , fruther comprising a drug selected from the group consisting of a sulfonamide, pyrimethamine, nitazoxanide, a non-steroidal anti-inflammatory agent, and mixtures thereof.  
     
     
         23 . A composition useful for the treatment and prevention of protozoan infections in man and in animals that is adapted for oral administration, comprising a water-soluble salt of a triazine-based anticoccidial.  
     
     
         24 . The composition of  claim 23 , wherein the triazine-based anticoccidial is selected from the group consisting of clazuril, diclazuril, letrazuril, toltrazuril and mixtures thereof.  
     
     
         25 . The composition of  claim 23 , wherein the triazine-based anticoccidial is sulfonotoltrazuril.  
     
     
         26 . The composition of  claim 23 , wherein the triazine-based anticoccidial is toltrazuril sulfone.  
     
     
         27 . The composition of  claim 23  wherein the water-soluble salt is a sodium salt of the triazine-based anticoccidial.  
     
     
         28 . The composition of  claim 23 , wherein the composition is adapted for oral administration such that the water soluable salt of the triazine-based anticoccidial is protected from precipitation in the acidic environment of the stomach.  
     
     
         29 . The composition of  claim 28 , wherein the composition formulated as a pill or capsule and said pill or capsule is enteric coated to protect said composition from the acidic pH of the stomach.  
     
     
         30 . A method of treating a protozoal infection in man or in animals, comprising the parenteral administeration of a therapeutically effective amount of a composition comprised of at least one triazine-based anticoccidial drug.  
     
     
         31 . The method of  claim 30 , wherein the triazine-based anticoccidial is selected from the group consisting of clazuril, diclazuril, letrazuril, toltrazuril and mixtures thereof.  
     
     
         32 . The method of  claim 30 , wherein the triazine-based anticoccidial is diclazuril.  
     
     
         33 . The method of  claim 30 , wherein the triazine-based anticoccidial is sulfonotoltrazuril.  
     
     
         34 . The method of  claim 30 , wherein the triazine-based anticoccidial is toltrazuril sulfone.  
     
     
         35 . The method of  claim 30 , wherein the triazine-based anticoccidial is a water-soluble salt of a triazine-based anticoccidial.  
     
     
         36 . The method of  claim 35 , wherein the water-soluble salt of the triazine based compound is a sodium salt of a trtiazine-based antioccidial selected from the group consisting of clazuril, diclazuril, letrazuril, toltrazuril and mixtures thereof.  
     
     
         37 . The method of  claim 30 , wherein the triazine-based anticoccidial is a water-soluble salt of a sulfonotoltrazuril.  
     
     
         38 . The method of  claim 30 , wherein the triazine-based anticoccidial is a water-soluble salt of toltrazuril sulfone.  
     
     
         39 . The method of  claim 30 , wherein the parenteral administration route is selected from the group consisting of intraveneous, intramuscular, subcutaneous, intranasal, transdermal and transmucosal.  
     
     
         40 . The method of  claim 30 , wherein the composition further comprises a suitable solvent of the triazine-based anticocidial.  
     
     
         41 . The method of  claim 30 , wherein the protozoal infection is selected from the group consisting of equine protozoal myeloencephalitis, equine piroplasmosis, and human cryptosporidiosis.  
     
     
         42 . The method of  claim 30  wherein the therapeutically effective amount of the triazine-based anticoccidial is from between about 0.01 mg/kg and about 20 mg/kg.  
     
     
         43 . The method of  claim 40 , wherein the protozoal infection is equine protozoal myeloencephalitis in an equid, the triazine based anticoccidial is diclazuril, the solvent is DMSO, the parenteral route is intraveneous and the therapeutically effective amount is from between about 0.01 mg/kg and about 20 mg/kg.  
     
     
         44 . The method of  claim 43  wherein the therapeutically effective amount is from between about 1 mg/kg and about 10 mg/kg.  
     
     
         45 . The method of  claim 43  wherein the therapeutically effective amount is from between about 3 mg/kg and about 6 mg/kg.  
     
     
         46 . The method of  claim 40 , wherein the protozoal infection is equine protozoal myeloencephalitis in an equid, the triazine based anticoccidial is sulfonotoltrazuril, the solvent is DMSO, the parenteral route is intraveneous and the therapeutically effective amount is from between about 0.01 mg/kg and about 20 mg/kg.  
     
     
         47 . The method of  claim 46  wherein the therapeutically effective amount is from between about 1 mg/kg and about 10 mg/kg.  
     
     
         48 . The method of  claim 46  wherein the therapeutically effective amount is from between about 3 mg/kg and about 6 mg/kg.  
     
     
         49 . The method of  claim 40 , wherein the protozoal infection is equine piroplasmosis in an equid, the triazine based anticoccidial is sulfonotoltrzuril, the solvent is DMSO, the parenteral route is intraveneous and the therapeutically effective amount is from between about 0.01 mg/kg and about 20 mg/kg.  
     
     
         50 . The method of  claim 49  wherein the therapeutically effective amount is from between about 1 mg/kg and about 10 mg/kg.  
     
     
         51 . The method of  claim 49  wherein the therapeutically effective amount is from between about 3 mg/kg and about 6 mg/kg.  
     
     
         52 . The method of  claim 40 , wherein the protozoal infection is equine piroplasmosis in an equid, the triazine based anticoccidial is diclazuril, the solvent is DMSO, the parenteral route is intraveneous and the therapeutically effective amount is from between about 0.01 mg/kg and about 20 mg/kg.  
     
     
         53 . The method of  claim 52  wherein the therapeutically effective amount is from between about 1 mg/kg and about 10 mg/kg.  
     
     
         54 . The method of  claim 52  wherein the therapeutically effective amount is from between about 3 mg/kg and about 6 mg/kg.  
     
     
         55 . The method of  claim 40 , wherein the protozoal infection is human cryptosporidiosis in a human subject, the parenteral route is intraveneous and the therapeutically effective amount is from between about 0.01 mg/kg and about 20 mg/kg.  
     
     
         56 . The method of  claim 52  wherein the therapeutically effective amount is from between about 1 mg/kg and about 10 mg/kg.  
     
     
         57 . The method of  claim 52  wherein the therapeutically effective amount is from between about 3 mg/kg and about 6 mg/kg.  
     
     
         58 . The method of  claim 30 , wherein the triazine based anticoccidial is a water -soluble salt of a triazine-based anticoccidial selected from the group consisting of clazuril, diclazuril, letrazuril, toltrazuril, sulfonotoltrazuril and mixtures thereof, and the therapeutically effective amount is from between about 0.01 mg/kg and about 20 mg/kg.  
     
     
         59 . The method of  claim 55  wherein the therapeutically effective amount is from between about 1 mg/kg and about 10 mg/kg.  
     
     
         60 . The method of  claim 55  wherein the therapeutically effective amount is from between about 3 mg/kg and about 6 mg/kg.