Growth control of oral and superficial microorganisms using gallium compounds

Abstract

The present invention provides methods for treating or preventing diseases and disorders caused by iron-dependent pathogenic microorganisms, such as bacteria, fungi, and parasites, by applying a gallium compound to an affected area. In particular, the present invention provides methods for treating or preventing dental caries, vaginal infections, skin infections, and so forth. Gallium compounds can be formulated as toothpaste, mouthwash, cream, ointment, gel, solution, eye drops, suppository, and the like. Furthermore, the invention provides methods for controlling microbial growth on environmental surfaces, including those of toothbrush, denture, dental retainer, contact lens, catheter, food stuff, and so forth. In addition, the present invention provides animal feeds which contain gallium compounds that promote the animal growth and prevent the animals from infections as well as protect consumers from post processing infections.

1 . A toothpaste comprising a gallium compound. 
     
     
         2 . The toothpaste of  claim 1 , wherein the gallium compound is at least one selected from the group consisting of gallium nitrate, gallium maltolate, gallium citrate, gallium phosphate, gallium chloride, gallium fluoride, gallium carbonate, gallium formate, gallium acetate, gallium sulfate, gallium tartrate, gallium oxalate, gallium, and gallium oxide. 
     
     
         3 . The toothpaste of  claim 1 , wherein the gallium compound is a gallium complex selected from the group consisting of gallium pyrones, gallium pyridones, gallium hydroxymates, gallium aminocarboxylates, gallium oximes, and gallium complexed with transferrin and lactoferrin. 
     
     
         4 . The toothpaste of  claim 1 , wherein the concentration of the gallium compound is at least about 1 μM. 
     
     
         5 . The toothpaste of  claim 4 , wherein the concentration of the gallium compound is at least about 500 μM. 
     
     
         6 . The toothpaste of  claim 5 , wherein the concentration of the gallium compound is at least about 1 mM. 
     
     
         7 . A mouthwash comprising a gallium compound. 
     
     
         8 . The mouthwash of  claim 7 , wherein the gallium compound is at least one selected from the group consisting of gallium nitrate, gallium maltolate, gallium citrate, gallium phosphate, gallium chloride, gallium fluoride, gallium carbonate, gallium formate, gallium acetate, gallium sulfate, gallium tartrate, gallium oxalate, gallium, and gallium oxide. 
     
     
         9 . The mouthwash of  claim 7 , wherein the gallium compound is a gallium complex selected from the group consisting of gallium pyrones, gallium pyridones, gallium hydroxymates, gallium aminocarboxylates, gallium oximes, and gallium complexed with transferrin and lactoferrin. 
     
     
         10 . The mouthwash of  claim 7 , wherein the concentration of the gallium compound is at least about 1 μM. 
     
     
         11 . The mouthwash of  claim 10 , wherein the concentration of the gallium compound is at least about 500 μM. 
     
     
         12 . The mouthwash of  claim 11 , wherein the concentration of the gallium compound is at least about 1 mM. 
     
     
         13 . A method of preventing dental cavity, comprising applying a prophylactically effective amount of a gallium compound to a tooth surface and/or an oral cavity of a subject. 
     
     
         14 . The method of  claim 13 , wherein the gallium compound is formulated as a toothpaste or a mouthwash. 
     
     
         15 . A method of treating a vaginal infection, comprising applying a therapeutically effective amount of a gallium compound to the vagina. 
     
     
         16 . The method of  claim 15 , wherein the gallium compound is formulated as a cream, ointment, solution, gel, or suppository. 
     
     
         17 . The method of  claim 15 , wherein the gallium compound is at least one selected from the group consisting of gallium nitrate, gallium maltolate, gallium citrate, gallium phosphate, gallium chloride, gallium fluoride, gallium carbonate, gallium formate, gallium acetate, gallium sulfate, gallium tartrate, gallium oxalate, gallium, and gallium oxide. 
     
     
         18 . The method of  claim 15 , wherein the gallium compound is a gallium complex selected from the group consisting of gallium pyrones, gallium pyridones, gallium hydroxymates, gallium aminocarboxylates, gallium oximes, gallium complexed with transferrin, lactoferrin, and heme. 
     
     
         19 . The method of  claim 15 , wherein the concentration of the gallium compound is at least about 1 μM. 
     
     
         20 . The method of  claim 19 , wherein the concentration of the gallium compound is at least 500 μM. 
     
     
         21 . The method of  claim 20 , wherein the concentration of the gallium compound is at least 1 mM. 
     
     
         22 . The method of  claim 15 , wherein the gallium compound is applied in combination with a probiotic. 
     
     
         23 . The method of  claim 22 , wherein the probiotic is a non-pathogenic species of genus  Lactobacillus.    
     
     
         24 . The method of  claim 23 , wherein the probiotic microorganism is at least one selected from the group consisting of  Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus leichmannii, Lactobacillus johnsonni, Lactobacillus  and  delbrueckii.    
     
     
         25 . A method of treating or preventing oral thrash caused by  Candida albicans , comprising applying a therapeutically effective amount of a gallium compound to an oral cavity of a subject in need thereof. 
     
     
         26 . A method of controlling a growth of microorganisms on a surface of an inanimate object, comprising applying an effective amount of a gallium compound to a surface of the object. 
     
     
         27 . The method of  claim 26 , wherein the object is selected from the group consisting of a contact lens, a denture, a dental retainer, a toothbrush, an implant, a bandage, a wound dressing, and a medical device. 
     
     
         28 . An animal feed comprising a gallium compound. 
     
     
         29 . The animal feed of  claim 28  further comprising a probiotic. 
     
     
         30 . A contact-lens disinfecting solution comprising a gallium compound. 
     
     
         31 . A method of controlling a growth of microorganisms in food, comprising applying a gallium compound to the food. 
     
     
         32 . The method of  claim 31 , wherein the food is a grain or a vegetable. 
     
     
         33 . The method of  claim 31 , wherein the food is an animal product selected from the group consisting of fish, eggs, dairy products and meat. 
     
     
         34 . A method of controlling the growth of pathogenic microorganisms on a skin surface of a subject comprising applying a therapeutically effective amount of a gallium compound to the skin surface of the subject. 
     
     
         35 . A method of treating or preventing a skin infection comprising applying a therapeutically effective amount of a gallium compound to a skin wound of a subject in need thereof. 
     
     
         36 . A method of disinfecting a skin surface of a subject comprising applying a therapeutically effective amount of a gallium compound to the skin surface of the subject. 
     
     
         37 . The method of  claim 34 , wherein the gallium compound is formulated as a cream, a lotion, a solution, an aerosol, an ointment, or a gel.