Method of administration and treatment
Provided herein are formulations for topical and/or transdermal administration, and methods of using these formulations for the treatment of proliferative diseases related to cancer such as cancers and related conditions, and solid tumors. Also provided are formulations for topical and/or transdermal administration, and methods of using these formulations for melasma, gout, skin disorders, and other diseases and disorders described herein as well as methods for modulating the pH (e.g. raising) of a tissue or microenvironment proximal to a tumor, modulating pH, or improving the effectiveness of know chemotherapeutic agents, immunotherapy and the like for the prevention, treatment of cancers and related conditions described herein.
1. A formulation suitable for transdermal delivery of active agents, wherein the active agents consist of a buffering agent and tranexamic acid, and the formulation further comprises a long chain fatty acid, a phosphatidylcholine (Phospholipon® 90G), and a fatty acid ester; and wherein the buffering agent comprises sodium carbonate and/or sodium bicarbonate.
2. The formulation of claim 1 , wherein the long chain fatty acids-comprises one or more of caprid acid, ethyloctadecanoic acid, lauric acid, a lecithin, linoelaidic acid, linoleic acid, linolenic acid, neodecanoic acid, oleic acid, palmitic acid, pelargonic acid, stearic acid, and vaccenic acid, wherein the lecithin is selected from an egg lecithin, a soy lecithin, and a synthetic lecithin.
3. The formulation of claim 1 , wherein the formulation further comprises glycolic acid.
4. The formulation of claim 1 , wherein the formulation further comprises one or both of an emulsifier and a surfactant.
5. The formulation of claim 4 , wherein the emulsifier comprises polyglyceryl-4 Laurate (Durosoft®).
6. The formulation of claim 4 , wherein the surfactant comprises one or more of a polyoxyethylated castor oil derivative, nonoxynol, octoxynol, phenylsulfonate, a poloxamer (e.g., Pluronic®), a polyoleates, sodium laurate, sodium lauryl sulfate (sodium dodecyl sulfate), sodium oleate, sorbitan dilaurate, sorbitan dioleate, a sorbitan monolaurate, a sorbitan monooleate; sorbitan trilaurate, sorbitan trioleate, a sorbitan monopalmitate, a sorbitan stearate; a polyethylene glycol, a nonylphenyl ether, p-(1,1,3,3-tetramethylbutyl)-phenyl ether (Triton™ X-100), or a polysorbate (e.g., a Tween®).
7. The formulation of claim 6 , wherein the surfactant is a poloxamer (e.g., Pluronic®).
8. The formulation of claim 1 , wherein the formulation comprises from about 1% w/w to about 50% w/w sodium carbonate and/or from about 1% w/w to about 50% w/w sodium bicarbonate.
9. The formulation of claim 8 , wherein the formulation comprises about 6% tranexamic acid.
10. The formulation of claim 9 , wherein the formulation further comprises a penetrant or penetration enhancer, and a polar solvent, and one or both of an emulsifier and a surfactant.
11. The formulation of claim 8 , wherein the formulation comprises less than about 10% tranexamic acid.
12. The formulation of claim 1 , wherein
the formulation further comprises benzyl alcohol, isopropyl palmitate (IPP), and a lecithin, wherein the lecithin is selected from an egg lecithin, a soy lecithin, and a synthetic lecithin; and
the formulation further comprises one or more of water, a poloxamer, and a polyglyceryl-4 Laurate (Durosoft®).
13. The formulation of claim 1 which is formulated as a cream, a lotion, or an ointment.
14. The formulation of claim 1 , wherein the fatty acid ester is selected from butyl acetate, cetyl lactate, decyl N,N-dimethylamino acetate, decyl N,N-dimethylamino isopropionate, diethyleneglycol oleate, diethyl sebacate, diethyl succinate, diisopropyl sebacate, dodecyl N,N-dimethyamino acetate, dodecyl (N,N-dimethylamino)-butyrate, dodecyl N,N-dimethylamino isopropionate, dodecyl 2-(dimethyamino) propionate, E0-5-oleyl ether, ethyl acetate, ethylaceto acetate, ethyl propionate, glycerol monoethers, glycerol monolaurate, glycerol monooleate, glycerol monolinoleate, isopropyl isostearate, isopropyl linoleate, isopropyl myristate, isopropyl myristate/fatty acid monoglyceride combination, isopropyl palmitate, methyl acetate, methyl caprate, methyl laurate, methyl propionate, methyl valerate, 1-monocaproyl glycerol, monoglycerides (medium chain length), nicotinic esters (benzyl), octyl acetate, octyl N,N-dimethylamino acetate, oleyl oleate, n-pentyl N-acetylprolinate, propylene glycol monolaurate, sorbitan dilaurate, sorbitan dioleate, sorbitan monolaurate, sorbitan monolaurate, sorbitan trilaurate, sorbitan trioleate, sucrose coconut fatty ester mixtures, sucrose monolaurate, sucrose monooleate, and tetradecyl N,N-dimethylamino acetate.
15. The formulation of claim 1 , wherein the formulation further comprises a penetrant or penetration enhancer selected from one or more of benzyl alcohol, cetyl alcohol, isododecane, isopropyl palmitate (IPP), isopropyl stearate, menthol, phosphatidyl choline, undecane, and/or a lecithin, wherein the lecithin is selected from an egg lecithin, a soy lecithin, and a synthetic lecithin.
16. The formulation of claim 1 , further comprising a detergent portion selected from poloxamer, propylene glycol, glycerin, ethanol, 50% w/v sodium hydroxide solution, or a combination thereof.
17. The formulation of claim 1 , further comprising a bile salt selected from salts of taurocholic acid, glycocholic acid, taurochenodeoxycholic acid, glycochenodeoxycholic acid, cholic acid, and deoxycholic acid.
18. The formulation of claim 1 , wherein the formulation further comprises a polar solvent selected from one or more of ethanol, isopropyl palmitate (IPP), and water.
19. The formulation of claim 3 , wherein the formulation further comprises benzyl alcohol, isopropyl palmitate (IPP), and a lecithin, wherein the lecithin is selected from an egg lecithin, a soy lecithin, and a synthetic lecithin; and the formulation further comprises one or more of water, a poloxamer, and a polyglyceryl-4 Laurate (Durosoft®).