Compositions having enhanced pharmacokinetic characteristics
View Patent ↗Compositions comprising a therapeutic component and an efficacy enhancing component, that enhances the pharmacokinetic disposition of the therapeutic component, are disclosed. The therapeutic component may include an alpha-2-adrenergic agonist and the efficacy enhancing component may include fatty acids. In one embodiment, the therapeutic component and the efficacy enhancing component form a complex.
1. A liquid composition comprising:
an ophthalmically acceptable cationic therapeutic component selected from the group consisting of NMDA antagonists, antibacterials, antihistamines, decongestants, antiinflammatories, antiparasitics, miotics, anticholinergics, adrenergics, antivirals, local anesthetics, antifungals, amoebicidals, trichomonocidals, analgesics, mydriatics, antiglaucoma drugs, carbonic anhydrate inhibitors, ophthalmic diagnostic agents, ophthalmic agents used as adjuvants in surgery, chelating agents, antineoplastics, antihypertensives, muscle relaxants, diagnostics, and mixtures thereof in a therapeutically effective amount, and
an efficacy enhancing component having one, two or three negative charges provided in an amount greater than 0.2% (w/v) and less than about 10% (w/v) and being effective to enhance the pharmacokinetic disposition of the therapeutic component, to enhance the movement of the therapeutic component across a lipid membrane, or a biological membrane under physiological conditions, and to enhance the permeability of the therapeutic component, the efficacy enhancing component being present in an ion pair complex at a molar ratio of 1:3, 1:2, 1:1, 2:1 or 3:1 with the therapeutic component, from about 80% to about 100% of the therapeutic component present in complex with the efficacy enhancing component, the ion-pair complex remaining substantially intact in an aqueous environment, each of the enhanced effects being relative to the effect obtained with the therapeutic component without the efficacy enhancing component; and
a solubilizer component provided in an amount effective to enhance the solubility of the ion-pair complex in solution.
2. The composition of. claim 1 wherein the therapeutic component is selected from the group consisting of quinoxaline, (2-imidozolin-2-ylamino) quinoxaline, 5-bromo-6- (2-imidozolin-2-ylamino) quinoxaline, and mixtures thereof.
3. The composition of claim 1 wherein the solubilizer component is nonionic.
4. The composition of claim 1 wherein the efficacy enhancing component and the therapeutic component are present in amounts so that a ratio of electrical charge from the efficacy enhancing component to electrical charge from the therapeutic component is at least about 1:1.
5. The composition of claim 1 further comprising an effective amount of a nonionic tonicity component.
6. The composition of claim 1 further comprising an effective amount of a phosphate buffer component in concentration in a range of about 0.001 molar to about 0.1 molar in the composition.
7. A liquid composition comprising:
an ophthalmically acceptable cationic therapeutic component selected from the group consisting of NMDA antagonists, antibacterials, antihistamines, decongestants, antiinflammatories, antiparasitics, miotics, anticholinergics, adrenergics, antivirals, local anesthetics, antifungals, amoebicidals, trichomonocidals, analgesics, mydriatics, antiglaucoma drugs, carbonic anhydrase inhibitors, ophthalmic diagnostic agents, ophthalmic agents used as adjuvants in surgery, chelating agents, antineoplastics, antihypertensives, muscle relaxants, diagnostics, and mixtures thereof in a therapeutically effective amount;
an efficacy enhancing component having one, two or three negative charges provided in an amount greater than 0.2% (w/v) and less than about 10% (w/v) and being effective to enhance the pharmacokinetic disposition of the therapeutic component, to enhance the movement of the therapeutic component across a lipid membrane, or a biological membrane under physiological conditions, and to enhance the permeability of the therapeutic component, the efficacy enhancing component being present in an ion-pair complex at a molar ration of 3:1, 2:1, 1:1, 1:2 or 1:3 with the therapeutic component, from about 80% to about 100% of the therapeutic component present in complex with the efficacy enhancing component, the ion-pair complex remaining substantially intact in an aqueous environment, each of the enhanced effects being relative to the effect obtained with the therapeutic component without the efficacy enhancing component; and
an effective amount of a nonionic tonicity component.
8. The composition of claim 7 wherein the therapeutic component is selected from the group consisting of quinoxaline, (2-imidozolin-2-ylamino) quinoxaline, 5-bromo-6- (2-imidozolin-2-ylamino) quinoxaline, and mixtures thereof.
9. The composition of claim 7 wherein the efficacy enhancing component is selected from the group consisting of anionic polymers, saturated fatty acids and unsaturated fatty acids, and mixtures thereof.
10. The composition of claim 7 wherein the efficacy enhancing component and the therapeutic component are present in amounts so that a ratio of electrical charge from the efficacy enhancing component to electrical charge from the therapeutic component is at least about 1:1.
11. The composition of claim 7 further comprising an effective amount of a phosphate buffer component in a concentration range of about 0.001 molar to about 0.1 molar in the composition.
12. A liquid composition comprising:
an ophthalmically acceptable cationic therapeutic component selected from the group consisting of NMDA antagonists, antibacterials, antihistamines, decongestants, antiinflammatories, antiparasitics, miotics, anticholinergics, adrenergics, antivirals, local anesthetics, antifungals, amoebicidals, trichomonocidals, analgesics, mydriatics, antiglaucoma drugs, carbonic anhydrase inhibitors, ophthalmic diagnostic agents, ophthalmic agents used as adjuvants in surgery, chelating agents, antineoplastics, antihypertensives, muscle relaxants, diagnostics, and mixtures thereof provided in a therapeutically effective amount; and
an efficacy enhancing component having one, two, or three negative charges provided in an amount greater than 0.2% (w/v) and less than about 10% (w/v) and being effective to enhance the pharmacokinetic disposition of the therapeutic component, to enhance the movement of the therapeutic component across a lipid membrane, or a biological membrane under physiological conditions, and to enhance the permeability of the therapeutic component, from about 80% to about 100% of the therapeutic component present in complex with the efficacy enhancing component, the efficacy enhancing component being present in an ion-pair complex with the therapeutic component so that a ratio of electrical charge from the efficacy enhancing component to electrical charge from the therapeutic component is at least about 1:1 the complex remaining substantially intact in an aqueous environment, and each of the enhanced effects being relative to the effect obtained with the therapeutic component without the efficacy enhancing component.
13. The composition of claim 12 wherein the therapeutic component is selected from the group consisting of quinoxaline, (2-imidozolin-2-ylamino) quinoxaline, 5-bromo-6- (2-imidozolin-2-ylamino) quinoxaline, and mixtures thereof.
14. The composition of claim 12 wherein the efficacy enhancing component is selected from the group consisting of anionic polymers, saturated fatty acids and unsaturated fatty acids, and mixtures thereof.
15. The composition of claim 12 wherein the complex is not present in an emulsion.
16. The composition of claim 12 wherein the efficacy enhancing component and the therapeutic component are present in amounts so that a ratio of electrical charge from the efficacy enhancing component to electrical charge from the therapeutic component is in a range of about 1.1 to about 1.5.
17. The composition of claim 12 further comprising an effective amount of a phosphate buffer component in a range of about 0.01 molar to about 0.1 molar in the composition.
18. A liquid composition comprising:
an ophthalmically acceptable cationic therapeutic component selected from the group consisting of NMDA antagonists, antibacterials, antihistamines, decongestants, antiinflammatories, antiparasitics, miotics, anticholinergics, adrenergics, antivirals, local anesthetics, antifungals, amoebicidals, trichomonocidals, analgesics, mydriatics, antiglaucoma drugs, carbonic anhydrase inhibitors, ophthalmic diagnostic agents, ophthalmic agents used as adjuvants in surgery, chelating agents, antineoplastics, antihypertensives, muscle relaxants, diagnostics, and mixtures thereof in a therapeutically effective amount;
an efficacy enhancing component comprising a fatty acid provided in an amount greater than 0.2% (w/v) and less than about 10% (w/v) and being effective to enhance the pharmacokinetic disposition of the therapeutic component, to enhance the movement of the therapeutic component across a lipid membrane, or a biological membrane under physiological conditions, and to enhance the permeability of the therapeutic component; the efficacy enhancing component being present in an ionpair complex at a molar ratio of 1:3, 1:2, 1:1, 2:1 or 3:1 with the therapeutic component; from about 80% to about 100% of the therapeutic component present in complex with the efficacy enhancing component(s); the complex remaining substantially intact in an aqueous environment; and each of the enhanced effects being relative to the effect obtained with the therapeutic component without the efficacy enhancing component.