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US-12616675-B1 - Antifungal liquid and antifungal gel

US12616675B1US 12616675 B1US12616675 B1US 12616675B1US-12616675-B1

Abstract

A composition includes a microemulsion. The microemulsion includes an aqueous phase, an oil phase, and a surface-active agent. The aqueous phase includes water and at least one polyol. The oil phase includes a therapeutically effective amount of tolnaftate and a carrier including Jojoba oil. The microemulsion includes a disperse phase having a particle size of 50 nm or less. A method for making a composition includes forming a first mixture by combining water and at least one polyol; forming a second mixture by combining Jojoba oil, a surface-active agent, and a therapeutically effective amount of tolnaftate; and combining and mixing the first mixture and the second mixture to form a microemulsion. A method of using a composition includes applying the composition to a site of treatment.

Inventors

  • George A. Cioe
  • Matthew W. Zoeller

Assignees

  • George A. Cioe
  • The Tetra Corporation

Dates

Publication Date
20260505
Application Date
20230804

Claims (20)

  1. 1 . An antifungal liquid comprising: a surface-active agent comprising at least one of a homolog series of mono-unsaturated oleyl alcohol ethers or at least one of an alkyl and oleic homolog series of phosphate esters, which are anionic in character; an aqueous phase comprising water, N-acetyl-L Cysteine, urea, and one or more of an alcohol and a polyol, wherein the one or more of an alcohol and a polyol comprises one or more of butylene glycol, propylene glycol, glycerin, xylitol, ethylhexylglycerin, caprylyl glycol, sorbitol, phenoxyethanol, aminomethylpropanol, aminomethylpropanediol, and ethoxydiglycol; and an oil phase comprising Simmondsia chinensis Oil, 0.5 to 2.0 w/w % tolnaftate, and at least one aromatic alkyl ester selected from C12-15 alkyl benzoates, the antifungal liquid comprising a microemulsion including a continuous phase and a disperse phase, the continuous phase comprising the aqueous phase and the disperse phase comprising the oil phase.
  2. 2 . The antifungal liquid according to claim 1 , wherein the surface-active agent comprises one or more of Oleth-5, Oleth-10, and Oleth-3 Phosphate.
  3. 3 . The antifungal liquid according to claim 1 , wherein the surface-active agent comprises Oleth-5, Oleth-10, and Oleth-3 Phosphate.
  4. 4 . The antifungal liquid according to claim 1 , further comprising Melaleuca alternifolia oil.
  5. 5 . The antifungal liquid according to claim 1 , wherein the antifungal liquid comprises: water in an amount ranging from 20 to 70% w/w, one or more of butylene glycol, propylene glycol, glycerin, xylitol, ethylhexylglycerin, caprylyl glycol, sorbitol, phenoxyethanol, aminomethylpropanol, aminomethylpropanediol, and ethoxydiglycol in an amount ranging from 10.0 to 35.0% w/w, Simmondsia Chinensis Oil in an amount ranging from 3.0 to 15.0 w/w %, and at least one C12-15 alkyl benzoate in an amount ranging from 5.0 to 20.0 w/w %.
  6. 6 . The antifungal liquid according to claim 1 , further comprising tocopherol acetate.
  7. 7 . The antifungal liquid according to claim 1 , wherein the disperse phase has a particle size of less than 25 nm.
  8. 8 . The antifungal liquid according to claim 1 , further comprising an electrolyte in an amount ranging from 0.1 to 2.0 w/w %.
  9. 9 . An antifungal gel comprising: a surface-active agent comprising at least one of a homolog series of mono-unsaturated oleyl alcohol ethers or at least one of an alkyl and oleic homolog series of phosphate esters, which are anionic in character; an aqueous phase comprising water, N-acetyl-L Cysteine, urea, and one or more of an alcohol and a polyol, wherein the one or more of an alcohol and a polyol comprises one or more of butylene glycol, propylene glycol, glycerin, xylitol, ethylhexylglycerin, caprylyl glycol, sorbitol, phenoxyethanol, aminomethylpropanol, aminomethylpropanediol, and ethoxydiglycol; and an oil phase comprising Simmondsia Chinensis Oil, 0.5 to 2.0 w/w % tolnaftate, and at least one aromatic alkyl ester selected from C12-15 alkyl benzoates, the antifungal gel comprising a microemulsion including a continuous phase and a disperse phase, the continuous phase comprising the aqueous phase and the disperse phase comprising the oil phase.
  10. 10 . The antifungal gel according to claim 9 , wherein the surface-active agent comprises one or more of Oleth-5, Oleth-10, and Oleth-3 Phosphate.
  11. 11 . The antifungal gel according to claim 9 , wherein the surface-active agent comprises Oleth-5, Oleth-10, and Oleth-3 Phosphate.
  12. 12 . The antifungal gel according to claim 9 , further comprising Melaleuca alternifolia oil.
  13. 13 . The antifungal gel according to claim 9 , wherein the antifungal gel comprises: water in an amount ranging from 20 to 70% w/w, one or more of butylene glycol, propylene glycol, glycerin, xylitol, ethylhexylglycerin, caprylyl glycol, sorbitol, phenoxyethanol, aminomethylpropanol, aminomethylpropanediol, and ethoxydiglycol in an amount ranging from 10.0 to 35.0% w/w, Simmondsia Chinensis Oil in an amount ranging from 3.0 to 15.0 w/w %, and at least one C12-15 alkyl benzoate in an amount ranging from 5.0 to 20.0 w/w %.
  14. 14 . The antifungal gel according to claim 9 , further comprising tocopherol acetate.
  15. 15 . The antifungal gel according to claim 9 , wherein the disperse phase has a particle size of less than 50 nm.
  16. 16 . The antifungal gel according to claim 9 , wherein the one or more of an alcohol and a polyol comprises one or more of butylene glycol, glycerin, ethylhexylglycerin, caprylyl glycol, phenoxyethanol, aminomethylpropanol, and ethoxydiglycol.
  17. 17 . The antifungal gel according to claim 9 , wherein the one or more of an alcohol and a polyol comprises a combination of butylene glycol, glycerin, aminomethylpropanol, and ethoxydiglycol.
  18. 18 . The antifungal gel according to claim 17 , wherein the one or more of an alcohol and a polyol further comprises a combination of ethylhexylglycerin, caprylyl glycol, and phenoxyethanol.
  19. 19 . The antifungal gel according to claim 9 , wherein the one or more of an alcohol and a polyol comprises a combination of ethylhexylglycerin, caprylyl glycol, and phenoxyethanol.
  20. 20 . The antifungal liquid according to claim 1 , wherein the one or more of an alcohol and a polyol comprises one or more of butylene glycol, glycerin, ethylhexylglycerin, caprylyl glycol, phenoxyethanol, aminomethylpropanol, and ethoxydiglycol.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This present application is a continuation application under 35 U.S.C. § 120 of U.S. Ser. No. 17/185,576 filed on Feb. 25, 2021, which is a continuation application under 35 U.S.C. § 120 of U.S. Ser. No. 16/023,824 filed on Jun. 29, 2018, which claims priority of U.S. provisional application No. 62/580,689 filed on Nov. 2, 2017, and U.S. provisional application No. 62/618,289 filed on Jan. 17, 2018, the entire content of each of which is incorporated herein by reference. FIELD The present disclosure generally relates to compositions for treatment of fungal infections, methods for making such compositions, and methods of using such compositions. BACKGROUND Tolnaftate is an antifungal compound that is effective against an array of organisms including Microsporum gypseum, M. canis, M. audouinii, M. japonicum, Trichophyton Rubrum, T. mentagrophytes, T. schoenleinni, T. tonsurans, Epidermophyton floccosum, Candida albacans, and Malassezia furfur. Tolnaftate is the only monographed antifungal indicated for prophylaxis. Tolnaftate is well tolerated with a very minor adverse effect, i.e., a hypersensitivity to tolnaftate could cause pruritus and contact dermatitis. Resistance to tolnaftate has been reported only rarely. However, the potential to develop resistance by the action of multidrug efflux transporters does exist. Tolnaftate is soluble in some solvents and chemicals. Many solvents are either not appropriate or do not serve as an effective vehicle for tolnaftate in medicines. For instance, a composition including formaldehyde as a tolnaftate vehicle was often prescribed for antipruritic and antifungal therapy. Dermatologists often used this medication as a treatment for pruritus because it gave the patient quick relief. Subsequently, the product was removed from the market when formaldehyde was identified as a carcinogen. As a result, many of the products available today are suspensions of tolnaftate. Jojoba oil is extracted from the seed of the Simmondsia chinensis (Jojoba) plant. Jojoba oil is a natural source of liquid wax esters, like sperm whale oil. Jojoba oil contains an array of monounsaturated liquid wax esters including long chains of fatty acids and alcohols, whereas all other known seed oils are branched triglycerides. Jojoba oil has been widely used in cosmetics since the ban on the use of sperm whale oil in 1978. Jojoba oil is lipophilic and chemically similar to the sebum produced by human sebaceous glands. As humans age, the production of sebum decreases and skin can dry and crack. Jojoba oil is capable of reconditioning skin for a natural luster and shine. Jojoba oil is also capable of dissolving excess sebum and allowing pores to transpire normally in younger humans. The safety of natural Jojoba oil is well established. Jojoba oil is generally considered to not be allergenic, comedogenic, or an irritant to the eyes or skin. Jojoba is also generally considered not to promote contact sensitization. It has been found that bacteria including Staphylococcus aureus and Pseudomonas as well as the yeast Candida albicans are not capable of growing in Jojoba oil. Jojoba oil is generally understood to have a wide use and long history of not producing adverse effects. The unique properties of Jojoba oil are suited to hold tolnaftate in solution. U.S. Pat. No. 4,810,498 to Paul J. DiMeglio, issued on Mar. 7, 1989, relates to a nail oil composition containing Jojoba oil and tolnaftate. See also U.S. RE36,253 reissued on Jul. 13, 1999. When applied to the body, Jojoba oil is miscible with sebum which makes Jojoba oil an effective vehicle for transporting tolnaftate to sequestered pathogens in pores and hair follicles. The properties of Jojoba oil made it the perfect vehicle for Tetra Corporation's Formula 3 R antifungal. Formula 3R is a mixture of 5 oils. One of the oils, Jojoba oil, is the vehicle that holds tolnaftate in solution. Jojoba oil's moisture control and emollient qualities helped meet a requirement for simpler ingredients by replacing combinations of mineral oil, triglycerides, lanolin, squalene and synthetic esters. Jojoba oil's oxidative stability, thermal stability and lack of support for microbial growth allowed a decrease in dependence on antioxidants, preservatives, stabilizers and special handling requirements for tolnaftate in Formula 3 R. SUMMARY A composition can generally include a microemulsion comprising an aqueous phase, an oil phase, and a surface-active agent. An aqueous phase can generally comprise water and at least one polyol. An oil phase can comprise a therapeutically effective amount of tolnaftate and a carrier comprising Jojoba oil. The microemulsion can be stabilized by the surface-active agent and generally comprise a disperse phase having a particle size of 50 nm or less. A method for making a composition can generally comprise forming a first mixture by combining water and at least one polyol; forming a second mixture by combi