MUCOSALLY NON-IRRITATIVE AMPHOTERICIN B FORMULATIONS AND METHODS FOR TREATING NON-INVASIVE FUNGUS-INDUCED MUCOSITIS
The present invention is directed to compositions and methods for non-irritatively treating and preventing non-invasive fungus-induced mucositis. Specifically, the invention involves compositions including a mucosally non-irritative mixture of amphotericin B and a pharmaceutically acceptable carrier. Such compositions can be non-irritatively mucoadministered to prevent, reduce, or eliminate chronic non-invasive fungus-induced mucositis conditions.
1 . A composition for mucoadministration comprising: a mucosally non-irritative mixture of amphotericin B and a pharmaceutically acceptable carrier.
2 . The composition of claim 1 , wherein the mixture is a universally mucosally non-irritative mixture.
3 . The composition of claim 1 , wherein the pharmaceutically acceptable carrier comprises sodium phosphate dibasic and sodium phosphate monobasic.
4 . The composition of claim 3 wherein the composition is a powder.
5 . The composition of claim 4 , wherein the amphotericin B is present in an amount of between about 0.27% and about 0.50% by weight of the total composition.
6 . The composition of claim 3 , further comprising water.
7 . The composition of claim 6 , wherein the amphotericin B is present in an amount of about 0.01% by weight of the total composition.
8 . The composition of claim 1 , wherein the pharmaceutically acceptable carrier comprises sodium phosphate dibasic, sodium phosphate monobasic and water.
9 . The composition of claim 1 , wherein the composition consists essentially of amphotericin B, sodium phosphate dibasic, sodium phosphate monobasic and water.
10 . The composition of claim 1 , wherein the composition is in a solid form, and wherein the solid form is suitable for incorporation into a solution or suspension.
11 . The composition of claim 1 , comprising:
between about 0.27% and about 0.50% by weight amphotericin B;
between about 45% and about 70% by weight sodium phosphate dibasic; and
between about 30% and about 55% by weight sodium phosphate monobasic.
12 . The composition of claim 11 , wherein the composition is a powder.
13 . The composition of claim 12 , wherein the composition is suitable for incorporation into a solution or suspension.
14 . The composition of claim 1 , comprising:
amphotericin B;
sodium phosphate dibasic;
sodium phosphate monobasic; and
at least about 96.25% by weight water.
15 . The composition of claim 14 , wherein the composition comprises:
about 0.01% by weight amphotericin B;
about 1.59% by weight sodium phosphate dibasic;
about 0.96% by weight sodium phosphate monobasic; and
about 97.44% by weight water.
16 . The composition of claim 1 , wherein the composition is free or essentially free of one or more of the following: propylene glycol and/or sodium metabisulfate, carboxymethylcellulose sodium, methylparaben, propylparaben, sodium desoxycholate.
17 . The composition of claim 1 , wherein the composition further comprises a polysaccharide degrading enzyme.
18 . The composition of claim 1 , wherein the composition is at least about 90% stable for up to 18 months under a nitrogen atmosphere.
19 . The composition of claim 1 , wherein the composition is at least about 95% stable for up to 18 months under a nitrogen atmosphere.
20 . The composition of claim 1 , wherein the composition is at least about 20% more stable under a nitrogen atmosphere than under an oxygen atmosphere.
21 . A method of treating a subject having non-invasive fungus-induced mucositis, comprising mucoadministering an effective amount of a composition to the subject, wherein the composition comprises a mucosally non-irritative mixture of amphotericin B and a pharmaceutically acceptable carrier.
22 . The method of claim 21 , wherein the composition comprises between about 50 μg to about 1000 μg of amphotericin B per milliliter of sterile water.
23 . The method of claim 21 , wherein the composition comprises between about 100 μg to about 500 μg of amphotericin B per milliliter of sterile water.
24 . The method of claim 21 , wherein the composition provides a low maximum plasma concentration.
25 . The method of claim 21 , wherein polyposis is improved in the subject.
26 . The method of claim 21 , wherein sinus inflammation is improved in the subject.
27 . The method of claim 21 , wherein the composition comprises about 100 μg of amphotericin B per milliliter of aqueous carrier and wherein 20 ml of the composition is administered in each nostril twice daily.
28 . A method for reducing eosinophil in a subject comprising: non-irritatively mucoadministering a composition comprising an effective amount of amphotericin B and a pharmaceutically acceptable carrier.
29 . A method for reducing the amount of major basic protein in the mucosa of a subject comprising: non-irritatively mucoadministering a composition comprising an effective amount of amphotericin B and a pharmaceutically acceptable carrier.