Antifungal composition
AssigneeGist-Brocades N.V.
InventorsFerdinand Theodorus Van Rijn, Jacobus Stark, Hong Sheng Tan, Willem Johan Van Zoest, Nicolaas Cornelis Barendse
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Abstract
Novel compositions that comprise solvates, salts, or other modified crystalline forms of polyene-type antifungal compounds are provided. Representative of such compositions are formulations that comprise the novel cystalline substances .delta.-natamycin and .gamma.-natamycin. Additionally, there are provided methods of preparing or storing such compositions, and also methods of use whereby an enhanced rate of release of antifungal compound, in a pharmaceutical or food products application is achieved.
Claims44
A method of preparing a modified form of a polyene type antifungal compound selected from the group consisting of natamycin, lucensomycin, nystatin and amphotericin B, comprising the steps of:
- a) contacting said antifungal compound with a substantially non-aqueous solvent, so as to convert said antifungal compound into a solvated form;
- b) removing said solvent from said solvated antifungal compound under anhydrous conditions;
- c) contacting said antifungal compound of step (b) with a humid environment;
- and
- d) recovering said antifungal compound as a hydrated form.
A method of preparing a modified form of natamycin, comprising the steps of:
- a) contacting said natamycin with methanol so as to convert said natamycin into a solvated form;
- b) removing said solvent from said solvated natamycin by subjecting said solvated natamycin to diminished pressure over a drying agent;
- c) contacting said natamycin of step (b) with a humid environment;
- d) recovering said antifungal compound as .gamma.-natamycin trihydrate.
A method of preparing a polyene type antifungal compound selected from the group consisting of natamycin, lucensomycin, nystatin and amphotericin B, with increased activity comprising the steps of:
- a) adding said polyene type antifungal compound to a saturated water solution of an alkaline earth salt;
- b) recovering the alkaline earth salt of said antifungal compound from said saturated solution.
A method of preparing a polyene type antifungal compound selected from the group consisting of natamycin, lucensomycin, nystatin and amphotericin B, with increased stability comprising the steps of:
- a) contacting said antifungal compound with a substantially non-aqueous solvent so as to convert said antifungal compound into a solvated form;
- b) recovering solvated crystals of said antifungal compound;
- and
- c) storing said solvated crystals under an inert gas.
A method of preparing a polyene type antifungal compound selected from the group consisting of natamycin, lucensomycin, nystatin and amphotericin B, with increased stability comprising the steps of:
- a) contacting said antifungal compound with a substantially non-aqueous solvent so as to convert said antifungal compound into a solvated form;
- b) adding fumed silica to said solvent/antifungal mixture of step (a);
- and
- c) removing said solvent.
An antifungal natamycin composition which exhibits a natamycin release rate of at least about 3 .mu.g/24 hours over the first 24 hours when contacted on a carrier with an agar surface of 0.6 cm diameter at 6.degree. C., and a carrier loading of 40 .mu.g of natamycin.
An antifungal natamycin composition which exhibits a natamycin release rate of 4 to 20 .mu.g/24 hours over the first 24 hours when contacted on a carrier with an agar surface of 0.6 cm diameter, and a carrier loading of 40 .mu.g of natamycin.
An orthorhombic crystal form of hydrated natamycin.
An alkaline earth salt of natamycin in solid form.
An antifungal composition that comprises natamycin on fumed silica.
A method of preparing a modified form of a polyene type antifungal compound selected from the group consisting of natamycin, lucensomycin, nystatin and amphotericin B, comprising the steps of:
- a) contacting said antifungal compound with a substantially non-aqueous solvent, so as to convert said antifungal compound into a solvated form;
- and
- b) removing said solvent from said solvated antifungal compound under anhydrous conditions.
Dependencies are inferred from the claim text.