Use of dibutyl adipate and isopropyl myristate in topical and transdermal products
First Claim
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1. A single or multiple phase topical composition for enhancing skin penetration of a pharmacologically active agent comprising:
- a pharmacologically effective amount of a pharmacologically active agent, such agent being an oil-soluble steroid, retinoid or aretinoid or a water-soluble α
- or β
-hydroxycarboxylic acid, ketocarboxylic acid or ester, lactone or salt thereof; and
(1) when the active agent is oil-soluble, an oil phase containing as a first solvent system, dibutyl adipate or a mixture of dibutyl adipate and isopropyl myristate, the oil-soluble active agent being solutiblized in the first solvent system, the first solvent system being present in an amount such that the oil-phase has a degree of unsaturation of 1 to 1.5 with respect to the oil-soluble active agent, any excess oil-soluble active agent not solubilized in the oil-phase being suspended in the composition;
or(2) when the active agent is water-soluble,(i) a second oil phase containing as a second solvent system, dibutyl adipate or a mixture of dibutyl adipate and isopropyl myristate; and
(ii) a water phase, the water-soluble active agent being solubilized in the water phase, any excess water-solublle active agent not solubilized in the water phase being solubilized in the second oil phase and/or suspended in the composition.
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Abstract
The present invention relates to composition and methods for enhancing and/or controlling epidermal, dermal and transdermal penetration of topically applied pharmacologically active agents by use of dibutyl adipate, or a mixture of dibutyl adipate and isopropyl myristate.
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Citations
17 Claims
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1. A single or multiple phase topical composition for enhancing skin penetration of a pharmacologically active agent comprising:
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a pharmacologically effective amount of a pharmacologically active agent, such agent being an oil-soluble steroid, retinoid or aretinoid or a water-soluble α
- or β
-hydroxycarboxylic acid, ketocarboxylic acid or ester, lactone or salt thereof; and(1) when the active agent is oil-soluble, an oil phase containing as a first solvent system, dibutyl adipate or a mixture of dibutyl adipate and isopropyl myristate, the oil-soluble active agent being solutiblized in the first solvent system, the first solvent system being present in an amount such that the oil-phase has a degree of unsaturation of 1 to 1.5 with respect to the oil-soluble active agent, any excess oil-soluble active agent not solubilized in the oil-phase being suspended in the composition;
or(2) when the active agent is water-soluble, (i) a second oil phase containing as a second solvent system, dibutyl adipate or a mixture of dibutyl adipate and isopropyl myristate; and (ii) a water phase, the water-soluble active agent being solubilized in the water phase, any excess water-solublle active agent not solubilized in the water phase being solubilized in the second oil phase and/or suspended in the composition. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
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13. A method of obtaining in a warm blooded mammal an enhanced rate of skin penetration of a pharmacologically active agent selected from the group consisting of oil-soluble steroids, retinoids and aretinoids and water-soluble α
- - or β
hydroxycarboxylic acid, ketocarboxylic acids, esters, lactones and salts thereof, comprising(a) contacting the sin of said mammal with a single or multiple phase topical composition comprising; a pharmacologically effective amount of said active agent; and when the active agent is oil-soluble, an oil phase containing as a solvent system, dibutyl adipate or a mixture of dibutyl adipate and isopropyl myristate, the oil-soluble active agent being solubilized in the oil phase, any excess oil-soluble active agent not solubilized in the oil phase being suspended in the composition;
orwhen the active agent is water-soluble, (i) a second oil phase containing as a second solvent system, dibutyl adipate or a mixture of dibutyl adipate and isopropyl myristate; and (ii) a water phase, the water-soluble active agent being solubilized in the water phase, any excess water-soluble active agent not solubilized in the water phase being solubilized in the second oil phase and/or suspended in the composition; and (b) when the active agent is oil-soluble, adjusting the amount of the solvent system and/or the relative amounts of dibutyl adipate and isopropyl myristate, when the solvent system is said mixture of dibutyl adipate and isopropyl myristate, so that the oil phase has a degree of unsaturation of 1 to 1.5 with respect to the oil-soluble active agent and the composition provides during said contacting an enhanced rate of skin penetration of the oil-soluble active agent;
orwhen the active agent is water-soluble, adjusting the amount of the second solvent system and/or the relative amount of dibutyl adipate and isopropyl myristate, when the second solvent system is said mixture of dibutyl adipate and isopropyl myristate, so that the composition provides during said contacting an enhanced rate of skin penetration of the water-soluble active agent. - View Dependent Claims (14, 15, 16)
- - or β
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17. A method for enhancing skin penetration of a pharmacologically active agent selected from the group consisting of water-soluble α
- -hydroxycarboxylic acids and dermatologically acceptable salts thereof and oil-soluble, halobetasol propionate, tretinoin, and 11-cis, 13-cis- 12-hydroxymethyl retionic acid delta lactone, the active agent being present in a dermatologically acceptable topical composition which, when the active agent is oil-soluble, has an oil phase or a water phase and an oil phase, or when the active agent is water-soluble, has an oil phase and a water phase, the active agent being solubilized in the oil phase when the active agent is halobetasol propionate, tretinoin, or 11-cis, 13-cis-12-hydroxymethyl retionoic acid delta lactone or solubilized in the water phase when the active agent is an α
-hydroxycarboxylic acid or a dermatologically acceptable salt thereof;
which method comprises;incorporating in said composition a skin penetration enhancing amount of dibutyl adipate or a mixture of isopropyl myristate and dibutyl adipate, provided that, when the active agent is halobetasol propionate, tretinoin, or 11-cis, 13-cis-12-hydroxymethyl retionic acid delta lactone, the amount of the dibutyl adiptate, or the mixture of isopropyl myristate and dibutyl adipate, employed results in the oil phase of the composition having an unsaturation of 1 to 1.5 with respect to the oil-soluble active agent and the composition having an enhanced rate of skin penetration of the oil-soluble active; and
when the active agent is an α
-hydroxycarboxylic acid or a dermatologically acceptable salt thereof, the amount of the dibutyl adipate, or the mixture of isopropyl myristate and dibutyl adipate, results in the composition having an enhanced rate of skin penetration of the water-soluble active agent.
- -hydroxycarboxylic acids and dermatologically acceptable salts thereof and oil-soluble, halobetasol propionate, tretinoin, and 11-cis, 13-cis- 12-hydroxymethyl retionic acid delta lactone, the active agent being present in a dermatologically acceptable topical composition which, when the active agent is oil-soluble, has an oil phase or a water phase and an oil phase, or when the active agent is water-soluble, has an oil phase and a water phase, the active agent being solubilized in the oil phase when the active agent is halobetasol propionate, tretinoin, or 11-cis, 13-cis-12-hydroxymethyl retionoic acid delta lactone or solubilized in the water phase when the active agent is an α
Specification