METHOD OF TREATING CANDIDA ISOLATES
The present invention relates to methods of treatment of vulvovaginitis caused by nonspecified Candida isolates using controlled release antimycotic delivery systems. The invention utilizes a minimal number of administrations to obtain cessation of the condition. The methods and systems are especially effective against any Candida species causing vaginal irritation, and thus reduce the need for identification of the isolate prior to treatment.
1 . A method for the local treatment of a vulvovaginal candidiasis condition caused by Candia dubliniensis, Candia tropicalis, Candia glabrata, Candia parapsilosis, Candia krusei, Candia lusitaniae , or a mixture thereof the treatment comprising:
applying to the vaginal tissue of a human a single dose treatment formulation comprising:
about 35 to about 45% w/w sorbitol solution;
about 3 to about 8% w/w propylene glycol;
about 0.001 to about 1% w/w edetate disodium;
about 5 to about 11% w/w mineral oil;
about 0.5 to about 5% w/w polyglyceryl-3-oleate;
about 0.5 to about 5% w/w glyceryl monoisostearate;
about 0.001 to about 1% w/w microcrystalline wax;
about 0.5 to about 2% w/w silicon dioxide;
about 0.001 to about 1% w/w methylparaben;
about 0.001 to about 1% w/w propylparaben;
about 25 to about 45% w/w water; and
about 0.5 to about 5% w/w butoconazole nitrate.
2 . The method according to claim 1 , wherein said formulation comprises:
about 38 to about 40% w/w sorbitol solution;
about 4 to about 6% w/w propylene glycol,
about 0.01 to about 0.5% w/w edetate disodium;
about 6 to about 9% w/w mineral oil;
about 2 to about 3% w/w polyglyceryl-3-oleate;
about 2 to about 3% w/w glyceryl monoisostearate;
about 0.01 to about 0.8% w/w microcrystalline wax;
about 0.09 to about 0.9% w/w silicon dioxide;
about 0.01 to about 0.5% w/w methylparaben;
about 0.01 to about 0.5% w/w propylparaben;
about 30 to about 40% w/w water; and
about 1.5 to about 3.5% w/w butoconazole nitrate.
3 . The method according to claim 2 , wherein said formulation comprises:
about 39.978% w/w sorbitol solution;
about 5% w/w propylene glycol;
about 0.05% w/w edetate disodium;
about 8.032% w/w mineral oil;
about 2.713% w/w polyglyceryl-3-oleate;
about 2.713% w/w glyceryl monoisostearate;
about 0.452% w/w microcrystalline wax;
about 1.013% w/w silicon dioxide;
about 0.18% w/w methylparaben;
about 0.05% w/w propylparaben;
about 37.819% w/w water; and
about 2.0% w/w butoconazole nitrate.
4 . The method according to claim 3 , wherein the species is C. glabrata or C. tropicalis.
5 . A method for the treatment of an unidentified vulvovaginal fungal condition caused by Candia dubliniensis, Candia tropicalis, Candia glabrata, Candia parapsilosis, Candia krusei, Candia lusitaniae , or a mixture thereof, the treatment comprising administering to said fungal condition a bioadhesive, single dose treatment formulation comprising from about 0.500 to about 5.000% w/w butoconazole nitrate.
6 . The method according to claim 5 , wherein said formulation further comprises:
about 35 to about 45% w/w sorbitol solution;
about 3 to about 8% w/w propylene glycol;
about 0.001 to about 1% w/w edetate disodium;
about 5 to about 11% w/w mineral oil;
about 0.5 to about 5% w/w polyglyceryl-3-oleate;
about 0.5 to about 5% w/w glyceryl monoisostearate;
about 0.001 to about 1% w/w microcrystalline wax;
about 0.5 to about 2% w/w silicon dioxide;
about 0.001 to about 1% w/w methylparaben;
about 0.001 to about 1% w/w propylparaben; and
about 25 to about 45% w/w water.
7 . The method according to claim 5 , wherein the treatment provides peak plasma levels of the butoconazole nitrate at about 6 to about 48 hours after administration and retains activity for at least 4 days.
8 . A method for the treatment of a fungal condition caused by Candida dubliniensis, Candida tropicalis, Candida glabrata, Candida parapsilosis , mycelial Candida, Candida krusei, Candida lusitaniae or mixtures thereof, the treatment comprising,
applying to said fungal condition
about 35 to about 45% w/w sorbitol solution;
about 3 to about 8% w/w propylene glycol;
about 0.001 to about 1% w/w edetate disodium;
about 5 to about 11% w/w mineral oil;
about 0.5 to about 5% w/w polyglyceryl-3-oleate;
about 0.5 to about 5% w/w glyceryl monoisostearate;
about 0.001 to about 1% w/w microcrystalline wax;
about 0.5 to about 2% w/w silicon dioxide;
about 0.001 to about 1% w/w methylparaben;
about 0.001 to about 1% w/w propylparaben;
about 25 to about 45% w/w water; and
about 0.5 to about 5% w/w butoconazole nitrate.
9 . The method according to claim 8 , wherein the treatment is a single dose treatment.
10 . The method according to claim 8 wherein said fungal condition is unidentified.
11 . A method for the treatment of a fungal condition caused by a species selected from the group consisting of C. dubliniensis, C. tropicalis, C. glabrata, C. parapsilosis, C. krusei, C. lusitaniae , and mixtures thereof, the method comprising:
applying to the vaginal tissue a multiphase formulation in a single dose wherein the multiphase formulation comprises:
(i) a hydrophilic phase comprising
about 38 to about 40% w/w sorbitol solution;
about 3 to about 8% w/w propylene glycol;
about 0.001 to about 1% W/w edetate disodium;
about 25 to about 45% w/w water; and
about 0.5 to about 5% w/w butoconazole nitrate; and
(ii) a hydrophobic phase comprising
about 5 to about 1% w/w mineral oil;
about 0.5 to about 5% w/w polyglyceryl-3-oleate;
about 0.5 to about 5% w/w glyceryl monoisostearate;
about 0.001 to about 1% w/w microcrystalline wax;
about 0.5 to about 2% w/w silicon dioxide;
about 0.001 to about 1.000% w/w methylparaben; and
about 0.001 to about 1% w/w propylparaben.
12 . The method according to claim 11 , wherein the hydrophobic phase and hydrophilic stage for a bioadhesive dosage form provides peak plasma levels of butoconazole nitrate at about 6 to about 48 hours and retains activity for at least 4 days.
13 . A method for the treatment of an unidentified vulvovaginatis condition caused by a species of Candida selected from the group consisting of C. dubliniensis, C. tropicalis, C. glabrata, C. parapsilosis, C. krusei , and C. lusitaniae comprising treating said condition by applying to the vaginal tissue a multiphase formulation in a single dose to provide a Candida species kill rate of about 50 to about 100% for a period of at least about 4 days.
14 . The method according to claim 13 wherein the multiphase formulation is administered via an applicator device which is designed to apply the formulation evenly over the vaginal tissue of a human.
15 . A method for the local treatment of a vulvovaginal candidiasis condition caused by Candia dubliniensis, Candia tropicalis, Candia glabrata, Candia parapsilosis, Candia krusei, Candia lusitaniae , or a mixture thereof, over a treatment period reduced by at least 25%, the treatment comprising:
applying to the vaginal tissue of a human a single dose treatment formulation comprising:
about 35 to about 45% w/w sorbitol solution;
about 3 to about 8% w/w propylene glycol;
about 0.001 to about 1% W/w edetate disodium;
about 5 to about 11% w/w mineral oil;
about 0.5 to about 5% w/w polyglyceryl-3-oleate;
about 0.5 to about 5% w/w glyceryl monoisostearate;
about 0.001 to about 1% w/w microcrystalline wax;
about 0.5 to about 2% w/w silicon dioxide;
about 0.001 to about 1% w/w methylparaben;
about 0.001 to about 1% w/w propylparaben;
about 25 to about 45% w/w water; and
about 0.5 to about 5% w/w butoconazole nitrate.
16 . The method according to claim 15 , wherein said formulation comprises:
about 38 to about 40% w/w sorbitol solution;
about 4 to about 6% w/w propylene glycol;
about 0.01 to about 0.5% w/w edetate disodium;
about 6 to about 9% w/w mineral oil;
about 2 to about 3% w/w polyglyceryl-3-oleate;
about 2 to about 3% w/w glyceryl monoisostearate;
about 0.01 to about 0.8% w/w microcrystalline wax;
about 0.09 to about 0.9% w/w silicon dioxide;
about 0.01 to about 0.5% w/w methylparaben;
about 0.01 to about 0.5% w/w propylparaben;
about 30 to about 40% w/w water; and
about 1.5 to about 3.5% w/w butoconazole nitrate.
17 . The method according to claim 16 , wherein said formulation comprises:
about 39.978% w/w sorbitol solution;
about 5% w/w propylene glycol;
about 0.05% w/w edetate disodium;
about 8.032% w/w mineral oil;
about 2.713% w/w polyglyceryl-3-oleate;
about 2.713% w/w glyceryl monoisostearate;
about 0.452% w/w microcrystalline wax, about 1.013% w/w silicon dioxide;
about 0.18% w/w methylparaben;
about 0.05% w/w propylparaben;
about 37.819% w/w water; and
about 2.0% w/w butoconazole nitrate.
18 . The method according to claim 17 , wherein the species is C. glabrata or C. tropicalis.