Compositions for treatment of hair loss

Abstract

To provide pharmaceutical compositions for treatment of hair loss.SOLUTION: The present invention provides pharmaceutical compositions for treatment of hair loss, containing 0.06-0.08%w / v of latanoprost and 4-5%w / v of minoxidil as active ingredients.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Patent Application No. 62 / 883,809, filed August 7, 2019, U.S. Provisional Patent Application No. 62 / 895,869, filed September 4, 2019, and U.S. Provisional Patent Application No. 63 / 100,611, filed March 23, 2020, the disclosures of which are incorporated by reference in their entireties herein.

[0002] The present invention relates to the use of certain prostaglandin analogs, alone and in combination with other compounds, such as cyclosporine, to prevent hair loss and / or promote hair growth.The present invention also relates to formulations that contain prostaglandin analogs and cyclosporine to promote hair growth or prevent hair loss on the scalp and other parts of the body.The present invention also relates to formulations and methods for treating certain hair loss disorders, such as male pattern baldness and alopecia areata. [Background technology]

[0003] Hair loss is a psychologically disheartening condition that causes significant psychological stress in both men and women. Of all men, 30% will experience some hair loss by age 30, 50% by age 50, and 80% by age 70. Of women, 40% will experience some hair loss by age 60. The negative impact of hair loss on quality of life is reported by men, and especially by adolescents and women.

[0004] Hair growth is generally divided into four phases. Anagen is the phase of active hair growth, lasting 2-6 years, but generally 3-5 years for scalp hair. During anagen, the epithelial compartment of the hair follicle undergoes rapid proliferation, with the greatest proliferation in the hair bulb matrix cells, and the hair follicle assumes the morphology of the hair bulb anagen. In fact, by studying the morphology of the hair bulb of the hair follicle, it is possible to determine which phase the hair is in. Catagen is a short transitional phase between anagen and telogen, lasting 7-14 days for scalp hair. Telogen, referred to as the "resting phase", where hair growth stops before the hair is finally shed, generally lasts 4-8 weeks, and where the hair papilla separates completely from the hair follicle. The fourth phase, which is the end of telogen, or the beginning of anagen, is the shedding phase, where the old hair is shed. Anagen begins again with the hair papilla moving back up and making contact with the hair follicle, where new hair growth begins again, and the new hair expels the old hair.

[0005] In people without hair loss disorders, about 90% of scalp hairs are in anagen, about 1-2% of hairs are in catagen, and about 8-9% of scalp hairs are in telogen. With the onset of male pattern baldness, the percentage of hairs in telogen increases and the number of hairs in anagen decreases. Patients have significantly fewer hair follicles than people without hair loss disorders, with a typical balding person having about 300 hair follicles per square inch of scalp, compared to about 450 follicles per square inch in people without hair loss disorders. Perhaps more importantly, in the active hair follicles of people with male pattern baldness, many of the hairs in the follicles are vellus hairs rather than terminal hairs, which are long, thick, and dark in color. In addition, the number of hairs in telogen is increased. Summary of the Invention

[0006] Summary: The present invention includes the following embodiments. 1. A composition comprising about 0.05-0.1% w / w, w / v, or v / v of latanoprost or latanoprost acid, and 0.05-0.1% w / w, w / v, or v / v of cyclosporine A, and 1.0-15.0% w / w, w / v, or v / v of diethylene glycol monoethyl ether. 2. The composition of embodiment 1, wherein the composition comprises about 0.05% w / w, w / v, or v / v of latanoprost or latanoprost acid, and about 0.06% w / w, w / v, or v / v of cyclosporine A, and about 10% w / w, w / v, or v / v of diethylene glycol monoethyl ether. 3. The composition of embodiment 2, further comprising oleyl alcohol. 4. The composition further comprising polyethylene glycol or propylene glycol. 5. A composition for use in promoting hair growth in a patient experiencing hair loss comprising about 0.05-0.1% w / w, w / v, or v / v of latanoprost or latanoprost acid, and 0.05-0.1% w / w, w / v, or v / v of cyclosporine A, and 5.0-15.0% w / w, w / v, or v / v of CAPTEX 300 EP / NF. 6. The composition of embodiment 5, wherein the composition comprises 0.06% w / w, w / v, or v / v of latanoprost or latanoprost acid, and 0.08% w / w, w / v, or v / v of cyclosporine A. 7. The composition of embodiment 6, further comprising 10% w / w, w / v, or v / v of CAPTEX 300 EP / NF. 8. A composition for use in the treatment of hair loss comprising about 0.05-0.1% w / w, w / v, or v / v of travoprost or travoprost acid, and 0.05-0.1% w / w, w / v, or v / v of cyclosporine A. 9. The composition of embodiment 8, further comprising a member selected from the group consisting of diethylene glycol monoethyl ether, CAPTEX 300 EP / NF, propylene glycol, and polyethylene glycol. 10. The composition of embodiments 1, 5, 8 and 9, further comprising oleic acid.

[0007] 11. A method for preventing hair loss in a patient, comprising administering to a patient in need thereof a formulation according to one of embodiments 1, 5, 8 and 9. 12. The method of embodiment 11, wherein the patient is suffering from alopecia areata and the formulation is applied once a day to areas of the scalp experiencing hair loss. 13. The method of embodiment 12, wherein the formulation is applied twice daily. 14. A method for inducing hair growth in a patient suffering from hair loss, comprising administering to a patient in need thereof a formulation according to one of embodiments 1, 5, 8 and 9, which downregulates T cells that invade the area of ​​the hair follicle hair bulb. 15. The method according to embodiment 14, wherein by applying the formulation according to one of embodiments 1, 5, 8, and 9, the patient experiences hair growth to a greater extent than if the patient did not apply the formulation. 16. The method according to embodiments 10-15, wherein the formulation maintains the hair in the anagen phase longer than if the formulation was not applied. 17. The method of embodiment 14, wherein the patient cures a sufficient amount of hair loss. 18. The method of embodiment 14, wherein the formulation comprises 0.06% w / w, w / v, or v / v latanoprost acid and 0.08% w / w, w / v, or v / v cyclosporine A, and a pharma- ceutically acceptable solvent, and a penetration enhancer. 19. A method of growing hair on the scalp of a patient, wherein the formulation comprises 0.1% w / w, w / v, or v / v of latanoprost or latanoprost free acid and cyclosporine. 20. The method of embodiment 19, wherein the cyclosporine is cyclosporine A.

[0008] 21. A composition for use in the treatment of hair loss comprising about 0.05-0.1% w / w, w / v, or v / v of bimatoprost, and 0.05-0.1% cyclosporine A, and 1.0-25.0% w / w, w / v, or v / v of diethylene glycol monoethyl ether. 22. A composition for use in hair growth comprising about 0.05-0.1% w / w, w / v, or v / v of bimatoprost, and 0.05-0.1% cyclosporine A, and 1.0-15.0% w / w, w / v, or v / v of diethylene glycol monoethyl ether. 23. A composition for use in treating hair loss or promoting hair growth comprising about 0.05-0.5% w / w, w / v, or v / v of latanoprost or latanoprost acid and 1.0-7.0% w / w, w / v, or v / v of minoxidil or minoxidil sulfate. 24. The composition of embodiment 23, wherein the composition has about 0.1% or 0.3% w / w, w / v or v / v of latanoprost or latanoprost acid, and about 5.0% w / w of minoxidil or minoxidil sulfate. 25. The composition of embodiment 23, further comprising a member selected from the group consisting of oleyl alcohol, ethanol, oleic acid, and diethylene glycol monoethyl ether. 26. The composition of embodiment 23, wherein the composition comprises 0.1%, 0.2% or 0.3% w / w, w / v or v / v of latanoprost or latanoprost acid, and 4.0%, 5.0%, 6.0% and 7.0% w / w, w / v or v / v of minoxidil or minoxidil sulfate. 27. A composition for use in treating hair loss or promoting hair growth comprising about 0.05-0.1% w / w, w / v, or v / v of bimatoprost or bimatoprost acid and 1.0-5.0% w / w, w / v, or v / v of minoxidil or minoxidil sulfate. 28. The composition of embodiment 27, wherein the composition is selected from the group consisting of 0.1%, 0.2% and 0.3% w / w, w / v, or v / v bimatoprost, and 4.0%, 5.0%, 6.0% and 7.0% w / w, w / v, or v / v minoxidil. 29. The composition of embodiment 27, further comprising oleyl alcohol, oleic acid, or ethanol. 30. The composition of embodiment 27, further comprising propylene glycol or polyethylene glycol.

[0009] 31. A composition for use in treating hair loss or promoting hair growth comprising about 0.05-0.5% w / w, w / v, or v / v of travoprost or travoprost free acid and 1.0-7.0% w / w, w / v, or v / v of minoxidil or minoxidil sulfate. 32. The composition of embodiment 31, wherein the composition has about 0.1% w / w, w / v, or v / v of travoprost or travoprost free acid, and about 5.0% w / w, w / v, or v / v of minoxidil or minoxidil sulfate, and at least 5% w / w, w / v, or v / v of diethylene glycol monoethyl ether. 33. The composition of any of embodiments 1-10, and 20-32, wherein the composition is applied to the skin under the patient's eyebrows to grow eyebrows. 34. The composition of any of embodiments 1-10, and 20-32, wherein the composition is applied to the patient's upper or lower eyelid margin to grow eyelashes. 35. The composition of any of the preceding embodiments, wherein the composition is applied to the skin under the patient's moustache or beard to grow moustache or beard hair. 36. A method of converting vellus hair to terminal hair by applying the formulation described in embodiments 1-10, and 21-32 to the area of ​​vellus hair of a patient. 37. A method of converting intermediate hair to terminal hair by applying the formulation of embodiment 23 to an area of ​​vellus hair of a patient. 38. A method for increasing at least one selected from hair length, thickness and pigmentation by applying the composition described in embodiments 1-10, or 21-32 to the scalp of a patient. 39. The composition of embodiment 23, 27, 31, or 33, wherein the composition is a gel. 40. The composition of embodiment 39, wherein the gel is applied to the eyebrows one selected from the group consisting of once a day, twice a day, or three times a day.

[0010] 41. The composition of embodiment 39, wherein the gel comprises at least one selected from the group consisting of sodium carboxymethylcellulose, hyaluronic acid, or carbodiimide, and / or mixtures thereof. 42. The composition of embodiment 41, wherein the sodium carboxymethylcellulose is selected from the group consisting of low viscosity (90,000 Daltons), medium viscosity (250,000 Daltons), and high viscosity (700,000 Daltons) carboxymethylcellulose, and / or mixtures thereof. 43. The composition according to embodiments 40 and 41, wherein the gel is applied to the eyebrows once or twice a day. 44. A first composition comprising latanoprost or latanoprost acid and minoxidil or minoxidil sulfate, wherein application of the composition to the skin results in a more rapid onset of hair growth compared to when either the latanoprost or latanoprost acid and minoxidil or minoxidil sulfate are applied to the skin as monotherapy at the same concentrations as the first composition. 45. The composition of embodiment 44, wherein the first composition comprises latanoprost or latanoprost acid, and minoxidil, in the same individual concentrations as latanoprost or latanoprost acid and minoxidil applied alone as monotherapy. 46. ​​The composition of embodiment 44 or 45, wherein the composition is applied to selected from the group consisting of the scalp, the skin under the eyebrows, the upper eyelid margin, the lower eyelid margin, and the face. 47. A first composition comprising latanoprost or latanoprost acid and minoxidil or minoxidil sulfate, wherein application of the first composition to the skin results in greater hair growth compared to when either the latanoprost or latanoprost acid and the minoxidil or minoxidil sulfate are applied to the skin alone as monotherapy at the same individual concentrations as they are present in the first composition. 48. The first composition of embodiment 47, comprising latanoprost or latanoprost acid, and minoxidil or minoxidil sulfate, which when applied to the scalp, the skin under the eyebrows, the upper eyelid margin, the lower eyelid margin, and the face, results in hair growth and hair length greater than when either latanoprost or latanoprost acid and minoxidil are applied alone as monotherapy at the same concentrations as they are present in the first composition. 49. The first composition of embodiment 47, comprising latanoprost or latanoprost acid and minoxidil or minoxidil sulfate, wherein when applied to the skin, either the latanoprost or latanoprost acid and minoxidil cause the diameter or circumference of individual hairs to be greater than if the latanoprost or latanoprost acid and minoxidil were applied to the skin alone at the same concentration as monotherapy. 50. The first composition of embodiment 47, comprising latanoprost or latanoprost acid and minoxidil or minoxidil sulfate, which when applied to the skin, results in a greater concentration of melanin in individual hairs compared to when latanoprost or latanoprost acid and minoxidil or minoxidil sulfate are applied to the skin alone at the same concentration as monotherapy.

[0011] 51. A first composition comprising travoprost or travoprost free acid and minoxidil or minoxidil sulfate, which when applied to the skin results in hair growth and lengthening of hair more than when either travoprost or travoprost acid and minoxidil or minoxidil sulfate are applied alone at the same concentration of travoprost or travoprost acid and minoxidil or minoxidil sulfate compared to monotherapy of travoprost or travoprost acid and minoxidil or minoxidil sulfate. 52. The first composition according to embodiment 51, comprising travoprost or travoprost free acid and minoxidil or minoxidil sulfate, wherein application of the first composition to the skin results in greater hair growth compared to when either travoprost or travoprost acid and minoxidil or minoxidil sulfate are applied to the skin alone as monotherapy at the same individual concentrations as they are present in the first composition. 53. The first composition of embodiment 51, comprising travoprost or travoprost free acid, and minoxidil or minoxidil sulfate, which when applied to the skin causes a greater diameter or circumference of individual hairs compared to when either travoprost or travoprost free acid and minoxidil or minoxidil sulfate are applied to the skin alone as monotherapy at the same individual concentrations as they are present in the first composition. 54. The first composition of embodiment 47, comprising travoprost or travoprost free acid and minoxidil or minoxidil sulfate, which, when applied to the skin, results in greater melanin concentration in individual hairs compared to when travoprost or travoprost free acid and minoxidil or minoxidil sulfate are applied to the skin alone at the same concentration as monotherapy. 55. A method of stimulating hair growth on the scalp by applying to the scalp a composition selected from the group consisting of any of embodiments 1-10 or 21-32 or 39-54. 56. A method for stimulating hair growth on the scalp by applying to the scalp a composition selected from the group consisting of any of formulations I to XXXXX. 57. A method for stimulating hair follicles to increase hair growth and increase one or more characteristics selected from the group consisting of: individual hair length, individual hair diameter or circumference, individual hair density, individual hair melanin content, an increase in the ratio of terminal to vellus hairs per square inch of skin, and an increase in black to white hairs in the area of ​​application, comprising applying an effective amount of a composition comprising one selected from the group consisting of any of embodiments 1-10 or 21-32, 39, 41 or 42 or formulations I-XXXXX to mammalian skin at the site of the hair follicle. 58. A method for stimulating hair follicles to increase hair growth and increase one or more characteristics selected from the group consisting of: individual hair length, individual hair diameter or circumference, individual hair density, individual hair melanin content, an increase in the ratio of terminal to vellus hairs per square inch of skin, and an increase in black to white hairs in the area of ​​application, comprising applying an effective amount of a composition comprising one selected from the group consisting of any of formulations I-XXXXX to mammalian skin at the site of the hair follicle. 59. The method according to embodiments 57 and 58, wherein the composition is applied to one selected from the group consisting of the scalp, the epidermis layer under the eyebrows, the lower eyelid margin, the upper eyelid margin, and the face. 60. A method for increasing the number of terminal hairs on the skin by applying to the skin or epidermis an effective amount of a composition comprising one selected from the group consisting of any of embodiments 1-10 or 21-32 or 39, 41 or 42 or formulations I-XXXXX.

[0012] 61. A method for increasing the number of terminal hairs on the scalp by applying to the skin of a mammal an effective amount of a composition comprising one selected from the group consisting of any of embodiments 1-10 or 21-32 or 39, 41, 42 and 54, or formulations I-XXXXX. 62. A method for converting white hair to darker hair by applying to the skin of a mammal an effective amount of a composition comprising one selected from the group consisting of any of embodiments 1-10 or 21-32 or 39, 41, 42 and 54, or formulations I-XXXXX. 63. A method for converting white hair to darker hair or increasing the melanin content of hair by applying an effective amount of a composition comprising one selected from the group consisting of any of embodiments 1-10 or 21-32 or 39-54, or formulations I-XXXXX, to mammalian skin adjacent to a hair follicle. 64. A method for increasing the melanin content of individual hairs by applying an effective amount of a composition comprising one selected from the group consisting of any of embodiments 1-10 or 21-32 or 39-54, or formulations I-XXXXX to mammalian skin adjacent to the hair follicle. 65. A method of thickening individual hairs by applying to mammalian skin in areas of the skin having white hairs an effective amount of a composition selected from the group consisting of any of embodiments 1-10 or 21-32 or 39-54, or formulations I-XXXXX. 66. The method according to embodiments 64 and 65, increasing the melanin and keratin content of individual hairs. 67. A method for increasing the diameter or circumference of individual hairs by applying an effective amount of a composition comprising one selected from the group consisting of any of embodiments 1-10 or 21-32 or 39-54, or formulations I-XXXXX, to mammalian skin adjacent to the hair follicle. 68. A method for increasing the diameter, circumference or length of an individual hair by applying to a hair follicle an effective amount of a composition comprising one selected from the group consisting of any of embodiments 1-10 or 21-32 or 39-54, or formulations I-XXXXX. 69. The method of any one of embodiments 60 to 68, wherein the composition is applied to one selected from the group consisting of the scalp, the skin under the eyebrows, the upper eyelid margin, the lower eyelid margin, and the face. 70. The method of embodiment 69, wherein the mammal is a human.

[0013] 71. A method for preventing hair loss in a patient undergoing chemotherapy, comprising administering a formulation selected from the group consisting of formulations I-XXXXX, or embodiments 1-10 or 21-32 or 39-54, and applying the embodiment or formulation to one selected from the group consisting of the scalp, the epidermal layer under the eyebrows, the upper and lower eyelid margins, or the face before, during or after chemotherapy. 72. The method according to embodiment 71, wherein the formulation is applied before the patient undergoes chemotherapy treatment to reduce the amount of hair loss. 73. The method of embodiment 72, wherein the formulation is applied one selected from the group consisting of 45 days prior to chemotherapy treatment, 30 days prior to chemotherapy treatment, 25 days prior to chemotherapy treatment, 20 days prior to chemotherapy treatment, 15 days prior to chemotherapy treatment, 10 days prior to chemotherapy treatment, and any of 9, 8, 7, 6, 5, 4, 3, 2, 1 days prior to chemotherapy treatment. 74. The method according to embodiment 72 or 73, wherein the formulation is applied in one selected from the group consisting of three times a day, twice a day, and once a day. 75. The method of any one of embodiments 71 to 74, wherein the patient loses less hair from at least one selected from the group consisting of the scalp, eyebrows, eyelashes, and face, as compared to a patient to whom the formulation is not administered for the same period of time. 76. The method of embodiment 75, wherein at least one hair selected from the group consisting of scalp, eyebrows, eyelashes, and face becomes longer, darker, and thicker compared to a patient to whom the formulation is not administered. 77. The method of embodiment 75, wherein at least one hair selected from the group consisting of the scalp, eyebrows, eyelashes, and face becomes more numerous compared to a patient to whom the formulation is not administered. 78. The method according to embodiment 71, wherein the formulation is applied while the patient is undergoing chemotherapy treatment. 79. The method according to embodiment 78, wherein the formulation is applied to at least one selected from the group consisting of the scalp, eyebrows, eyelashes, and face at one selected from the group consisting of three times a day, twice a day, and once a day. 80. The method of embodiment 79, wherein the patient loses less hair selected from the group consisting of the scalp, eyebrows, eyelashes, and face, compared to a patient to which the formulation is not applied.

[0014] 81. The method of embodiments 78 and 79, wherein at least one hair selected from the group consisting of scalp, eyebrows, eyelashes, and face becomes longer, darker, more abundant, and thicker compared to a patient not receiving treatment. 82. The method according to embodiments 78-81, wherein the patient applies the formulation while undergoing chemotherapy treatment. 83. The method according to paragraph 82, wherein the patient applies the preparation after chemotherapy treatment has ended. 84. The method according to embodiment 83, wherein the patient applies the formulation from one selected from the group consisting of 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, and 24 months after the end of chemotherapy treatment. 85. The method according to embodiment 84, wherein at least one hair selected from the group consisting of scalp, eyebrows, eyelashes, and face becomes longer, darker, more abundant, and thicker after chemotherapy treatment compared to a patient not receiving the treatment. 86. The method according to embodiment 84, wherein applying formulation I-XXXXX, or embodiments 1-10 or 21-31 or 39-54 to one selected from the group consisting of the scalp, eyebrows, eyelashes, and face, causes the hair to enter the anagen phase sooner and / or for a longer period than if the patient did not apply the formulation. 87. The method according to embodiment 85, wherein applying the formulation to one selected from the group consisting of the scalp, eyebrows, eyelashes, and face causes the hair to enter the anagen phase for longer than if the patient does not apply the formulation. 88. Use of a combination of latanoprost or latanoprost acid and minoxidil or minoxidil sulfate for the treatment of hair loss in a patient suffering therefrom. 89. The use according to embodiment 88, wherein latanoprost or latanoprost acid is present in a concentration of about 0.08-0.5% w / v, w / w, or v / v, and minoxidil or minoxidil sulfate is present in a concentration of about 2-8% w / v, w / w, or w / v. 90. The use according to embodiment 89, wherein latanoprost or latanoprost acid is present in a concentration of about 0.1-0.3% w / v, w / w, or v / v, and minoxidil or minoxidil sulfate is present in a concentration selected from the group consisting of 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, and 10% w / v, w / w, or v / v.

[0015] 91. The use according to embodiment 90, wherein latanoprost or latanoprost acid is present in a concentration of about 0.2% w / v, w / w, or w / v, and minoxidil or minoxidil sulfate is present in a concentration of about 5% w / v, w / w, or v / v. 92. The use according to embodiment 90, wherein the latanoprost or latanoprost is present in a concentration of about 0.3% w / v, and the minoxidil or minoxidil sulfate is present in a concentration of about 5% w / v, w / w, or v / v. 93. The use according to embodiment 90, wherein latanoprost is present in a concentration of about 0.8% w / v and minoxidil is present in a concentration of about 4% w / v. 94. The use according to embodiments 88 to 93, wherein the hair loss is at least one selected from the group consisting of scalp hair, eyebrows, eyelashes, or facial hair. 95. Use of a combination of latanoprost or latanoprost acid and minoxidil or minoxidil sulfate for hair growth in a patient. 96. The use according to embodiment 95, wherein the patient is suffering from hair loss. 97. The use according to embodiment 95, wherein latanoprost or latanoprost acid is present in a concentration of about 0.08-0.5% w / v, w / w, or v / v, and minoxidil or minoxidil sulfate is present in a concentration of about 2-8% w / v, w / w, or v / v. 98. The use according to embodiment 95, wherein latanoprost or latanoprost acid is present in a concentration of about 0.1-0.3% w / v, w / w, or v / v, and minoxidil or minoxidil sulfate is present in a concentration of 4-7% w / v, w / w, or v / v. 99. The use according to embodiment 95, wherein latanoprost or latanoprost acid is present in a concentration of about 0.2% w / v, w / w, or v / v, and minoxidil or minoxidil sulfate is present in a concentration of about 4% w / v, w / w, or v / v. 100. The use according to embodiment 95, wherein latanoprost or latanoprost acid is present in a concentration of about 0.3% w / v, w / w, or v / v, and minoxidil or minoxidil sulfate is present in a concentration of about 5% w / v, w / w, or v / v.

[0016] 101. The use according to embodiment 95, wherein latanoprost or latanoprost acid is present in a concentration of about 0.1% w / v and minoxidil or minoxidil sulfate is present in a concentration of about 5% w / v, w / w, or v / v. 102. The use according to embodiments 88 to 93 and 97 to 100, wherein the hair loss is at least one selected from the group consisting of scalp hair, eyebrows, eyelashes, or facial hair. 103. Use of a combination of travoprost or travoprost free acid and minoxidil or minoxidil sulfate for the treatment of hair loss in a patient suffering therefrom. 104. The use according to embodiment 103, wherein travoprost or travoprost free acid is present in a concentration of about 0.08-0.5% w / v, w / w, or v / v, and minoxidil or minoxidil sulfate is present in a concentration of about 2-8% w / v, w / w, or v / v. 105. The use according to embodiment 103, wherein travoprost or travoprost free acid is present in a concentration of about 0.07-0.3% w / v, w / w, or v / v, and minoxidil or minoxidil sulfate is present in a concentration of 4-7% w / v, w / w, or v / v. 106. The use according to embodiment 103, wherein travoprost or travoprost free acid is present in a concentration of about 0.2% w / v, w / w, or v / v, and minoxidil or minoxidil sulfate is present in a concentration of about 5% w / v, w / w, or v / v. 107. The use according to embodiment 103, wherein travoprost or travoprost free acid is present in a concentration of about 0.3% w / v, w / w, or v / v, and minoxidil or minoxidil sulfate is present in a concentration of about 5% w / v, w / w, or v / v. 108. The use according to embodiment 103, wherein travoprost or travoprost free acid is present in a concentration of about 0.1% w / v, w / w, or v / v, and minoxidil or minoxidil sulfate is present in a concentration of about 5% w / v, w / w, or v / v. 109. The use according to embodiments 103 to 108, wherein the hair loss is at least one selected from the group consisting of scalp hair, eyebrows, eyelashes, or facial hair. 110. Use of a combination of travoprost or travoprost free acid and minoxidil or minoxidil sulfate for hair growth in a patient.

[0017] 111. The use according to embodiment 110, wherein the patient is suffering from hair loss. 112. The use according to embodiment 111, wherein travoprost or travoprost free acid is present in a concentration of about 0.08-0.5% w / v, w / w, or v / v, and minoxidil or minoxidil sulfate is present in a concentration of about 2-8% w / v, w / w, or v / v. 113. The use according to embodiment 111, wherein travoprost or travoprost free acid is present in a concentration of about 0.1-0.3% w / v, w / w, or v / v, and minoxidil or minoxidil sulfate is present in a concentration of 4-7% w / v, w / v, w / w, or v / v. 114. The use according to embodiment 95, wherein travoprost or travoprost free acid is present in a concentration of about 0.2% w / v, w / w, or v / v, and minoxidil or minoxidil sulfate is present in a concentration of about 5% w / v, w / w, or v / v. 115. The use according to embodiment 95, wherein travoprost or travoprost is present in a concentration of about 0.3% w / v, w / w, or v / v, and minoxidil is present in a concentration of about 5% w / v, w / w, or v / v. 116. The use according to embodiment 95, wherein travoprost or travoprost free acid is present in a concentration of about 0.07% or 0.08% w / v, w / w, or v / v, and minoxidil or minoxidil sulfate is present in a concentration of about 4%, 5% or 6% w / v, w / w, or v / v. 117. The use according to embodiments 103 to 108, wherein the hair loss is at least one selected from the group consisting of scalp hair, eyebrows, eyelashes, or facial hair. 118. Use of a combination of bimatoprost and minoxidil or minoxidil sulfate for the treatment of hair loss in a patient suffering therefrom. 119. The use according to embodiment 118, wherein bimatoprost is present in a concentration of about 0.08-0.5% w / v, w / w, or v / v, and minoxidil or minoxidil sulfate is present in a concentration of about 2-8% w / v, w / w, or v / v. 120. The use according to embodiment 119, wherein bimatoprost is present in a concentration of about 0.1-0.3% w / v, w / w, or v / v, and minoxidil or minoxidil sulfate is present in a concentration of 4-7% w / v, w / w, or v / v.

[0018] 121. The use according to embodiment 118, wherein bimatoprost is present in a concentration of about 0.2% w / v, w / v, w / w, or v / v, and minoxidil or minoxidil sulfate is present in a concentration of about 5% w / v, w / w, or v / v. 122. The use according to embodiment 90, wherein bimatoprost is present in a concentration of about 0.3% w / v, w / w, or v / v, and minoxidil or minoxidil sulfate is present in a concentration of about 5% w / v, w / w, or v / v. 123. The use according to embodiment 90, wherein bimatoprost is present in a concentration of about 0.1% w / v, w / w, or v / v, and minoxidil or minoxidil sulfate is present in a concentration of about 5% w / v, w / w, or v / v. 124. The use according to embodiments 119 to 123, wherein the hair loss is at least one selected from the group consisting of scalp hair, eyebrows, eyelashes, or facial hair. 125. Use of a combination of bimatoprost and minoxidil for hair growth in patients. 126. The use according to embodiment 95, wherein the patient is suffering from hair loss. 127. The use according to embodiment 119, wherein bimatoprost is present in a concentration of about 0.08-0.5% w / v, w / w, or v / v, and minoxidil is present in a concentration of about 2-8% w / v, w / w, or v / v. 128. The use according to embodiment 127, wherein bimatoprost is present in a concentration of about 0.08% w / v, w / w, or v / v, and minoxidil or minoxidil sulfate is present in a concentration of 4-7% w / v, w / w, or v / v. 129. The use according to embodiment 95, wherein bimatoprost is present in a concentration of about 0.9% w / v, w / w, or v / v, and minoxidil or minoxidil sulfate is present in a concentration of about 4% w / v, w / w, or v / v. 130. The use according to embodiment 127, wherein bimatoprost is present in a concentration of about 0.3% w / v, w / w, or v / v, and minoxidil or minoxidil sulfate is present in a concentration of about 5% w / v, w / w, or v / v.

[0019] 131. The use according to embodiment 127, wherein bimatoprost is present in a concentration of about 0.1% w / v, and minoxidil or minoxidil sulfate is present in a concentration of about 4% w / v, w / w, or v / v. 132. The use according to embodiments 126 to 131, wherein the hair loss is at least one selected from the group consisting of scalp hair, eyebrows, eyelashes, or facial hair. 133. A composition for use in treating hair loss comprising about 0.05-0.5% w / v, w / w, or v / v of one selected from the group consisting of latanoprost and latanoprost acid, and 1-8% w / v, w / w, or v / v of minoxidil. 134. The composition of embodiment 133, comprising about 0.3% w / v, w / w, or v / v of latanoprost or latanoprost acid, and about 5% w / v, w / w, or v / v of minoxidil or minoxidil sulfate. 135. The composition of embodiment 133, comprising about 0.07% w / v, w / w, or v / v latanoprost or latanoprost acid, and about 4-6% w / v, w / w, or v / v minoxidil or minoxidil sulfate. 136. The composition of embodiment 133, further comprising oleyl alcohol or ethanol. 137. The composition of embodiment 136, further comprising propylene glycol. 138. The composition of embodiment 133, wherein the hair loss is due to male pattern baldness. 139. The composition of embodiment 137, wherein the hair loss is due to alopecia areata. 140. The composition of embodiment 137, further comprising acetic acid and one selected from the group consisting of polysorbate 60 and polyoxyethylene lauryl alcohol.

[0020] 141. The composition of embodiment 134, further comprising: acetic acid; and one selected from the group consisting of polysorbate 60 and polyoxyethylene lauryl alcohol. 142. The composition of embodiment 137, further comprising ethanol; and at least one selected from the group consisting of propylene glycol and polysorbate 80. 143. The composition of embodiment 142, wherein ethanol is present at a concentration of about 25-50% w / v. 144. The composition of embodiment 143, wherein the composition further comprises oleyl alcohol. 145. The composition of embodiment 144, further comprising diethylene glycol monoethyl ether. 146. The composition of embodiment 134, further comprising ethanol, propylene glycol, water; and at least one selected from the group consisting of benzyl alcohol, oleic acid, oleyl alcohol and polyoxyethylene lauryl alcohol. 147. The composition of embodiment 135, wherein the composition comprises ethanol, propylene glycol, polysorbate, water; and at least one selected from the group consisting of acetic acid, oleic acid and oleyl alcohol. 148. The composition of embodiment 147, wherein the composition comprises about 0.1-0.5% w / v, w / w, or v / v acetic acid. 149. The composition of embodiment 147, wherein the composition comprises about 5-60% w / v, w / w, or v / v propylene glycol. 150. The composition of embodiment 133, wherein the composition comprises ethanol, propylene glycol, polysorbate, water; and at least one selected from the group consisting of acetic acid, oleic acid and oleyl alcohol.

[0021] 151. A method of growing hair on the scalp by applying the formulation of embodiment 134 to the scalp at least once a day, wherein the areas of the scalp to which the formulation is applied grow hair to a greater extent than areas of the scalp to which the formulation is not applied. 152. A method for growing hair, comprising administering to the skin the formulation of embodiment 135, wherein the formulation causes telogen hairs in the area of ​​the scalp where it is applied to enter the anagen phase more quickly than in areas of the scalp where the formulation is not administered. 153. A method of enhancing nail growth or treating brittle nail syndrome in a patient suffering therefrom, comprising administering a formulation selected from embodiments 1-10 or 21-31 or 35-54, and formulations I-XXXXX, as applied topically to the patient's fingernail or cuticle, at least once a day. 154. The method is for treating nail psoriasis, psoriatic nail dystrophy, brittle nail syndrome, increased nail length and thickness, onychomycosis, abnormal nail curvature, onychomycosis, onycholysis, onycholysis, macroonychia, onychomycosis, longitudinal onychomycosis, white nails, nail bed epithelial hyperplasia, onychomycosis, paronychia, Pseudomonas aeruginosa infection, pterygium and pterygium inversus, spoon nails, subungual hematomas and other trauma to the nail, folic acid deficiency, white nails The method of embodiment 153, which is useful for treating a toenail or fingernail disorder selected from the group consisting of plaque, nail-patella syndrome, melanonychia, protein deficiency, brittle and peeling nails, methyl methacrylate damaged nails, vitamin C deficiency, vitamin deficiency, white nails, thinning nails associated with lichen planus, Raynaud's disease, bleeding associated with rheumatoid arthritis, Beau's lines, and Mees' lines associated with certain toxins. 155. A method of stimulating melanogenesis in melanocytes within and surrounding or adjacent cells of a hair follicle and simultaneously causing hair growth by administering any one of embodiments 1-10 or 21-31 or 35-54, or formulations I-XXXXX, to a hair follicle, wherein the melanocytes begin melanogenesis more quickly compared to when the embodiment or formulation is not applied to the hair follicle. 156. The method of embodiment 155, wherein the melanosomes in the melanocytes produce more melanin compared to when the embodiment or formulation is not applied topically to the hair follicle. 157. The method of embodiment 155, wherein the melanosomes in the melanocytes produce more of one selected from the group consisting of black eumelanin, brown eumelanin, yellow pheomelanin, and reddish-brown pheomelanin, compared to when the embodiment or formulation is not applied to the hair follicle. 158. A method for growing hair, by applying one selected from the group consisting of embodiments 5, 6, 7, 18, 19, 20, 23, 24-26, 44, 45, 47, 48, 49, 50, 88-93, 95, 97-101, resulting in thicker new hair growth compared to when the formulation is not applied. 159. The method according to embodiment 158, wherein application of one selected from the group consisting of embodiments 5, 6, 7, 18, 19, 20, 23, 24-26, 44, 45, 47, 48, 49, 50, 88-93, 95, 97-101 results in thicker new hair growth compared to the compositions of embodiments 5, 6, 7, 18, 19, 20, 23, 24-26, 44, 45, 47, 48, 49, 50, 88-93, 95, 97-101 and, in individual embodiments, the same compositions except that bimatoprost is replaced with latanoprost at the same concentration. 160. The method according to embodiment 158, wherein application of one selected from the group consisting of embodiments 5, 6, 7, 18, 19, 20, 23, 24-26, 44, 45, 47, 48, 49, 50, 88-93, 95, 97-101 results in thicker new hair growth compared to the composition of embodiments 5, 6, 7, 18, 19, 20, 23, 24-26, 44, 45, 47, 48, 49, 50, 88-93, 95, 97-101 and, in individual embodiments, the same composition except that travoprost is replaced with latanoprost to provide the same concentration to the hair follicle.

[0022] 161. A method of stimulating keratinization in keratinocytes within and surrounding or adjacent cells of a hair follicle and simultaneously inducing hair growth by administering any one of embodiments 1-10 or 21-31 or 35-54 or formulations I-XXXXX to a hair follicle, wherein the keratinocytes begin keratinization more quickly and / or for a longer duration compared to when the embodiment or formulation is not applied. 162. The method according to embodiment 161, wherein the keratinocytes produce hair that is thicker or has a larger diameter and / or circumference compared to when the embodiment or formulation is not topically applied to the hair follicle. 163. A method of growing hair, by applying one selected from the group of embodiments 5, 6, 7, 18, 19, 20, 23, 24-26, 44, 45, 47, 48, 49, 50, 88-93, 95, 97-101, resulting in new hair growth that is one selected from the group of thicker, longer, larger in diameter, and larger in circumference compared to when the formulation is not applied. 164. The method according to embodiment 163, wherein application of one selected from the group of embodiments 5, 6, 7, 18, 19, 20, 23, 24-26, 44, 45, 47, 48, 49, 50, 88-93, 95, 97-101 results in new hair growth that is one selected from the group consisting of thicker, longer, larger in diameter, and larger in circumference compared to the composition of embodiments 5, 6, 7, 18, 19, 20, 23, 24-26, 44, 45, 47, 48, 49, 50, 88-93, 95, 97-101 and, in individual embodiments, the same composition except that bimatoprost is replaced with latanoprost at the same concentration. 165. The method according to embodiment 163, wherein application of one selected from the group of embodiments 5, 6, 7, 18, 19, 20, 23, 24-26, 44, 45, 47, 48, 49, 50, 88-93, 95, 97-101 results in new hair growth that is one selected from the group consisting of thicker, longer, larger in diameter, and larger in circumference compared to the composition of embodiments 5, 6, 7, 18, 19, 20, 23, 24-26, 44, 45, 47, 48, 49, 50, 88-93, 95, 97-101 and, in individual embodiments, the same composition except that travoprost is replaced with latanoprost at the same concentration. 166. A method for enhancing hair growth by applying one of embodiments 1-10 or 21-31 or 35-54, or formulations I-XXXXX, to a hair follicle and applying infrared radiation to the hair follicle. 167. The method according to embodiment 166, in which infrared radiation is applied after one of embodiments 1 to 10 or 21 to 31 or 35 to 54, or formulations I to XXXXX, is applied to the hair follicles. 168. The method of embodiment 167, wherein infrared radiation is applied to the hair follicle by the device for one time period selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24 hours. 169. A composition comprising tafluprost and minoxidil. 170. A composition for use in treating hair loss comprising about 0.05-0.3% w / w, w / v, or v / v of tafluprost and 1-5% w / w, w / v, or v / v of minoxidil.

[0023] 171. The composition according to embodiments 169 and 170, wherein the composition further comprises polyethylene glycol or propylene glycol and ethanol. 172. The composition of embodiments 169, 170 and 171, further comprising 0.1% w / v tafluprost and 5% w / v minoxidil. 173. A composition for use in the treatment of hair loss, comprising tafluprost and finasteride. 174. The composition of embodiment 173, comprising 0.05% w / v to 0.3% w / v of tafluprost and 0.05% w / v to 0.3% w / v of finasteride. 175. A composition for use in treating hair loss, comprising tafluprost and cyclosporine. 176. The composition of embodiment 175, comprising 0.05-0.1% w / w, w / v, or v / v tafluprost and 0.05-0.1% w / w, w / v, or v / v cyclosporine. 177. The composition of embodiment 176, wherein the cyclosporine is cyclosporine A. [Brief description of the drawings]

[0024] [Figure 1] 1 is a description of the anatomy of a hair follicle including the surrounding tissue. [Diagram 2] A description of the various stages of hair growth. [Diagram 3]1 is one proposed mechanism of action of the formulations of the present invention. [Figure 4] 1 shows hair growth in a 46 year old female patient who applied Formulation XX followed by Formulation XVIII. [Diagram 5] 1 shows hair growth in a 53 year old male patient who applied Formulation XX followed by Formulation XVIII. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0025] A. Prostaglandin analogues Prostaglandin analogs of the present invention include latanoprost, bimatoprost, travoprost, uenoprost isopropyl ester, the free acids of these compounds, and other prostaglandin analogs known in the literature.

[0026] The compounds of the present invention generally have the formula I: [ka] It can be expressed by wherein the dashed bond represents a single bond or a double bond which may be in a cis or trans configuration, A is an alkylene or alkenylene group having 2 to 6 carbon atoms, which may be interrupted by one or more oxide groups and which may be substituted with one or more hydroxy, oxo, alkyloxy, or alkylcarboxy groups, wherein the alkyl groups contain 1 to 6 carbon atoms; B is a cycloalkyl group having 3 to 7 carbon atoms, which may be unsubstituted or substituted with one selected from the group consisting of H, methyl, or perfluoromethyl, or an aryl group selected from the group consisting of hydrocarbylaryl and heteroaryl groups having 4 to 10 carbon atoms, the heteroatoms of which may be selected from the group consisting of nitrogen, oxygen, halogen atoms (e.g., fluorine), lower alkyl groups having 1 to 6 carbon atoms which may be optionally substituted with halogen, and sulfur atoms; X is -O(R 4 ), and -N(R 4 )2, wherein R 4 are the same or different, and are lower alkyl groups having 1 to 6 carbon atoms, optionally substituted with hydrogen, -CH3, H, or -CH3; R 5 -C- or R 5 -OC-, where R 5 is a lower alkyl group having 1 to 6 carbon atoms; Z is =O or represents two hydrogen groups; one of R1 and R2 is =O, -OH, or -O(CO)R6 group and the other is -OH or -O(CO)R6; or R1 is =O and R2 is H, where R6 is a saturated or unsaturated acyclic hydrocarbon group having 1 to about 20 carbon atoms, or -(CH2)mR7, where m is 0 or an integer of 1 to 10 and R7 is a cycloalkyl group having 3 to 7 carbon atoms, or a hydrocarbylaryl, or heteroaryl group as defined above, or a pharma- ceutically acceptable salt thereof, with the proviso that when B is not substituted with a pendant heteroatom-containing group and Z is =O, then X is -OR 4 That is, the cycloalkyl or hydrocarbyl aryl or heteroaryl group is not substituted with pendant groups having atoms other than carbon or hydrogen.

[0027] The compounds of the present invention also have the following general formula II: [ka] It can be expressed by wherein the dashed bond represents a single bond or a double bond which may be in a cis or trans configuration, where y is 0 or 1, x is 0 or 1, where x and y are not both 1, Y is a group selected from the group consisting of alkyl, halogen (e.g., fluoro, chloro, etc.), nitro, amino, thiol, hydroxy, alkyloxy, alkylcarboxy, halogen-substituted alkyl (e.g., perfluoromethyl, perfluoroethyl, and perfluoropropyl), where said alkyl group contains 1 to 6 carbon atoms, n is 0 or an integer from 1 to about 3, and R3 is =O, -OH, or -O(CO)R6, where R6 is as defined above. Preferably, n is 1 or 2. X is -O(R 4 ), and -N(R 4 )2, wherein R 4 are the same or different, and are lower alkyl groups having 1 to 6 carbon atoms, optionally substituted with hydrogen, -CH3, H, or -CH3; R 5 -C- or R 5 -OC-, where R 5 is a lower alkyl group having 1 to 6 carbon atoms; Z is =O or represents two hydrogen groups; one of R1 and R2 is =O, -OH, or -O(CO)R6 group and the other is -OH or -O(CO)R6; or R1 is =O and R2 is H, where R6 is a saturated or unsaturated acyclic hydrocarbon group having 1 to about 20 carbon atoms, or -(CH2)mR7, where m is 0 or an integer of 1 to 10 and R7 is a cycloalkyl group having 3 to 7 carbon atoms, or a hydrocarbylaryl, or heteroaryl group as defined above, or a pharma- ceutically acceptable salt thereof, with the proviso that when B is not substituted with a pendant heteroatom-containing group and Z is =O, then X is -OR 4 That is, the cycloalkyl or hydrocarbyl aryl or heteroaryl group is not substituted with pendant groups having atoms other than carbon or hydrogen.

[0028] The compound may also be represented by the general formula (III): [ka] It can be expressed as:

[0029] The compounds of the present invention also have the general formula (IV): [ka] Or, a compound of general formula V: [ka] It can be expressed as:

[0030] In all the above formulas, the dotted lines at the bonds between carbons 5 and 6 (C-5), between carbons 13 and 14 (C-13), between carbons 8 and 12 (C-8), and between carbons 10 and 11 (C-10) indicate a single bond or a double bond which may be in the cis or trans configuration. When two solid lines are used, it indicates a particular configuration of that double bond. The diagonal lines at the C-9, C-11, and C-15 positions indicate the α configuration. When drawing the β configuration, a solid triangular line is used. y is 0 or 1, x is 0 or 1, where x and y are not both 1, Y is a group selected from the group consisting of alkyl, halogen (e.g., fluoro, chloro, etc.), nitro, amino, thiol, hydroxy, alkyloxy, alkylcarboxy, halogen-substituted alkyl (such as perfluoromethyl, perfluoroethyl, and perfluoropropyl), where said alkyl group contains 1 to 6 carbon atoms, n is 0 or an integer from 1 to about 3, and R3 is =O, -OH, or -O(CO)R6, where R6 is as defined above. Preferably, n is 1 or 2. X is -O(R 4 ), and -N(R 4 )2, wherein R 4 are the same or different, and are lower alkyl groups having 1 to 6 carbon atoms, optionally substituted with hydrogen, -CH3, H, or -CH3; R 5 -C- or R 5 -OC-, where R 5 is a lower alkyl group having 1 to 6 carbon atoms; Z is =O or represents two hydrogen groups; one of R1 and R2 is =O, -OH, or -O(CO)R6 group and the other is -OH or -O(CO)R6; or R1 is =O and R2 is H, where R6 is a saturated or unsaturated acyclic hydrocarbon group having 1 to about 20 carbon atoms, or -(CH2)mR7, where m is 0 or an integer of 1 to 10 and R7 is a cycloalkyl group having 3 to 7 carbon atoms, or a hydrocarbylaryl, or heteroaryl group as defined above, or a pharma- ceutically acceptable salt thereof, with the proviso that when B is not substituted with a pendant heteroatom-containing group and Z is =O, then X is -OR 4 That is, the cycloalkyl or hydrocarbyl aryl or heteroaryl group is not substituted with pendant groups having atoms other than carbon or hydrogen.

[0031] In the compounds used according to the present invention, compounds having C-9 or C-11 or C-15 substituents in α or β configuration are contemplated.As stated above, in all formulas provided herein, the dashed bond to the cyclopentane ring indicates substitution in α-configuration.The thick solid bond to the cyclopentane ring indicates substitution in α-configuration.Also, the dashed bond of the hydroxyl group or other substituent to the C-11 and C-15 carbon atoms represents α-configuration.

[0032] For purposes of the present invention, and without further limitation, the term "alkyl" refers to an alkyl group having 1 to 10 carbon atoms, the term "cycloalkyl" refers to a cycloalkyl group having 3 to 7 carbon atoms, and the term "aryl" refers to an aryl group having 4 to 10 carbon atoms. The term "saturated or unsaturated acyclic hydrocarbon group" is used to mean a straight or branched chain saturated or unsaturated hydrocarbon group having 1 to about 6, preferably 1 to about 4, carbon atoms. Such groups include alkyl, alkenyl and alkynyl groups of appropriate length, preferably alkyl, such as methyl, ethyl, propyl, butyl, pentyl, or hexyl, or isomers thereof.

[0033] The definition of R6 may include a cyclic component, -(CH2)mR7, where n is 0 or an integer from 1 to 10, and R7 is an aliphatic ring of about 3 to about 7 carbon atoms, or an aromatic ring or a heteroaromatic ring. An "aliphatic ring" may be saturated or unsaturated, preferably a saturated ring having 3 to 7 carbon atoms. As an aromatic ring, R7 is preferably phenyl, and a heteroaromatic ring has oxygen, nitrogen or sulfur as a heteroatom, i.e., R7 may be thienyl, furanyl, pyridyl, etc. Preferably, m is 0 or an integer from 1 to 4. Z is =O or represents two hydrogen atoms. X is -O(R 4 ), and -N(R 4 ) 2, wherein R 4 are lower alkyl groups having 1 to 6 carbon atoms, which may be the same or different and may be optionally substituted with hydrogen, -CH3, H or -CH3; [ka] where R 5 is a lower alkyl group having 1 to 6 carbon atoms.

[0034] 1) Latanoprost Latanoprost has the following structure: [ka]

[0035] Latanoprost is a prostaglandin analog, and is, in fact, a prodrug, and is available in its acid form (latanoprost acid): [ka] However, it is biologically active.

[0036] Latanoprost is an isopropyl ester, a prodrug that is converted to latanoprost free acid by r[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]hept-5-enoic acid. The free acid form of latanoprost is 200 times more potent than latanoprost as an FP receptor ligand for human recombinant FP receptors. Latanoprost free acid is a potent FP receptor agonist, with an EC value of 1.28 for the human FP receptor. 50 is 3.6 nM, which is PGF 2α It is twice as effective as PG analog esters. The effectiveness of PG analog esters for treating glaucoma or elevated IOP is closely correlated with the FP receptor binding affinity of the free acid. Other forms of latanoprost that can be used in the present invention include 15-ketolatanoprost, 15(S)-latanoprost, 5-trans-latanoprost, latanoprost-d4, latanoprost-lactol, and latanoprost-ethylamide-d4.

[0037] Latanoprost is a molecule that is poorly soluble in water, but generally lipid soluble. Latanoprost is more lipid soluble than bimatoprost. If a solution of latanoprost without organic solvent is required, it can be prepared by evaporating the methyl acetate and dissolving the neat oil directly into an aqueous buffer. The solubility of latanoprost in PBS (pH 7.2) is approximately 50 μg / mL. To maximize solubility in aqueous buffers, latanoprost should first be dissolved in ethanol or propylene glycol and then diluted with the aqueous buffer of choice. Using this method, latanoprost is soluble at 400 μg / mL in a 1:4 ethanol:PBS (pH 7.2) solution. In acidic or basic aqueous solutions, latanoprost has been shown to be stable for 48 hours, and in neutral aqueous solutions for up to one month at room temperature. Latanoprost is the isopropyl ester of 17-phenyl-13,14-dihydroprostaglandin F2a (17-phenyl-13,14-dihydroPGF2a).

[0038] A sufficient amount of solubility is obtained even at the highest concentration (5%) that can be used in propylene glycol, methanol, ethanol, and 2-propanol.Furthermore, it is noted that latanoprost can be dissolved in suitable dissolving agents such as alcohol (propylene glycol, methanol, ethanol, 2-propanol) and other cosolvents such as some aromatic alcohols and polyhydric alcohols (cetyl alcohol, stearyl alcohol, benzyl alcohol, glyceryl monooleate, POE stearate, polyoxyethylene lauryl alcohol, 1,3 butylene glycol, glycerol).

[0039] Latanoprost, including 15-ketolatanoprost, 15(S)-latanoprost, 5-trans-latanoprost, latanoprost-d4, latanoprost-lactol, latanoprost-ethylamide-d4, and latanoprost acid, may be present in the formulations of the invention at the following concentrations: 0.001%, 0.002%, 0.003%, 0.004%, 0.005%, 0.006%, 0.007%, 0.008%, 0.009%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.11%, 0.12%, 0.13%, 0.14%, 0.15%, 0.16%, 0.17%, 0.18%, 0.19%, 0.2%, 0.21%, 0.22%, 0.23%, 0.24%, 0.25%, 0.26%, 0.27%, 0.28%, 0.29%, 0.3%, 0.31%, 0.32%, 0.33%, 0.34%, 0.35%, 0.36%, 0.37%, 0.38%, 0.39 %,0.4%,0.41%,0.42%,0.43%,0.44%,0.45%,0.46%,0.47%,0.48%,0.49%,0.5%,0.55%,0.6%,0.65%,0.7%,0.75%,0.8%,0.85%,0.9%,0.95%,1.0%,1.1%,1.2%,1.3%,1.4%,1.5%,1.6%,1.7%,1.8%,1.9%,2.0%,2.1%,2.2%,2.3%,2.4%,2.5%,2.6%,2.7%,2.8%, 2.9%, 3.0%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, 4.0%, 4.1%, 4.2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8%, 4.9%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24% and 25% w / w, w / v or v / v.

[0040] Latanoprost, including 15-ketolatanoprost, 15(S)-latanoprost, 5-trans-latanoprost, latanoprost-d4, latanoprost-lactol, latanoprost-ethylamide-d4, and latanoprost acid, may be present in the formulations of the present invention alone or in combination with other prostaglandin analogs.Latanoprost, including 15-ketolatanoprost, 15(S)-latanoprost, 5-trans-latanoprost, latanoprost-d4, latanoprost-lactol, latanoprost-ethylamide-d4, and latanoprost acid, may be present in the formulations of the present invention alone or in combination with topical minoxidil or minoxidil sulfate, or topical or oral finasteride. Latanoprost, including 15-ketolatanoprost, 15(S)-latanoprost, 5-trans-latanoprost, latanoprost-d4, latanoprost-lactol, latanoprost-ethylamide-d4, and latanoprost acid, may be present in the formulations of the invention either alone or in combination with cyclosporines of formulas I, II and III.

[0041] 2) Travoprost Travoprost is a synthetic prostaglandin F analogue and is the isopropyl ester of the biologically active free acid. Its chemical name is [1R-[1α(Z),2β(1E,3R * ),3α,5α]]-7-[3,5-dihydroxy-2-[3-hydroxy-4-[3-(trifluoromethyl)phenoxy]-1-butenyl]cyclopentyl]-5-heptenoic acid, 1-methylethyl ester. The molecular formula is C 26 H 35 It is F3O6 and has a molecular weight of 500.55. [ka]

[0042] Travoprost free acid has the following structure: [ka]

[0043] Travoprost and travoprost free acid may be present in the formulations of the invention in the following concentrations: 0.001%, 0.002%, 0.003%, 0.004%, 0.005%, 0.006%, 0.007%, 0.008%, 0.009%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.11%, 0.12%, 0.13%, 0.14%, 0.15%, 0.16%, 0.17%, 0.18%, 0.19%, 0.2%, 0.21%, 0.22%, 0.23%, 0.24%, 0.25%, 0.26%, 0.27%, 0.28%, 0.29%, 0.3%, 0.31%, 0.32%, 0.33%, 0.34%, 0.35%, 0.36%, 0.37%, 0.38%, 0.39%, 0.4%, 0.41%, 0.42%, 0.43%, 0.44%, 0.45%, 0.46%, 0 .47%, 0.48%, 0.49%, 0.5%, 0.55%, 0.6%, 0.65%, 0.7%, 0.75%, 0.8%, 0.85%, 0.9%, 0.95%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3.0%, 3.1%, 3.2%, 3. 3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, 4.0%, 4.1%, 4.2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8%, 4.9%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24% and 25% w / w, w / v or v / v.

[0044] Travoprost and travoprost free acid can be present in the formulation of the present invention alone or in combination with other prostaglandin analogs or other hair growth compounds.Travoprost and travoprost free acid can be present in the formulation of the present invention alone or in combination with topical minoxidil or minoxidil sulfate, or topical or oral finasteride.Travoprost and travoprost free acid can be combined with cyclosporine of formula I, II or III.

[0045] 3) Wenoprostone isopropyl ester Unoprostone isopropyl ester has the following structure: [ka]

[0046] Wenoprostone isopropyl ester is a prodrug that converts to wenoprostone free acid, having the following structure: [ka]

[0047] Wenoprostone isopropyl ester and wenoprostone free acid are effective in lowering intraocular pressure, but have not been shown to induce hair growth and may in fact inhibit hair growth (McCarey BE, Kapik BM, Kane FE

[2004] ). A low incidence of iris pigmentation and eyelash changes has been reported with wenoprostone isopropyl 0.15% in two randomized clinical trials (Ophthalmology 111, 1480-1488). This indicates that prostaglandin analogs for use in hair growth are unpredictable and that many prostaglandin analogs may not induce hair growth and may inhibit hair growth.

[0048] 4) Bimatoprost Bimatoprost is a prostamide, a group of biological lipids related to prostaglandins, but contains a terminal ethanolamide group and targets a different receptor than prostaglandin analogues such as latanoprost and travoprost. Technically, bimatoprost is not considered a prostaglandin analogue, but is a prostamide. Bimatoprost may be represented by the following formula: [ka]

[0049] Bimatoprost is not a prodrug and is not believed to be converted to another compound or only a small amount (less than 5%) is converted to bimatoprost free acid. Bimatoprost differs from other compounds in that it is an amide. [ka]

[0050] Bimatoprost free acid: [ka] On the other hand, bimatoprost is believed to exert its biological activity as a hair growth agent as an ethyl amide, not as a free acid. This is in contrast to latanoprost and travoprost, which are prodrugs and exert their physiological effects on different receptors than bimatoprost, which explains the lack of predictability of bimatoprost, latanoprost, travoprost, and wenoprostone isopropyl ester being used to stimulate hair growth. Bimatoprost and latanoprost have very different solubility and pharmacological properties. Bimatoprost salt forms include tromethamine salt forms. For example, LUMIGAN™ 0.03% w / v, a topical solution for reducing elevated intraocular pressure and treating glaucoma, the first approved use of bimatoprost, has a clinical concentration of bimatoprost of 0.03% w / v. Latanoprost's first approved use, as a topical solution to reduce elevated intraocular pressure and treat glaucoma, XALATAN™, has a clinical concentration of 0.005% w / v.

[0051] The action of prostamides such as bimatoprost involves a different mechanism than the prostanoid FP receptor-mediated response by ligands such as latanoprost and travoprost. The effect of bimatoprost in monkeys with an elevated intraocular pressure model of glaucoma has been shown to be additive to that of latanoprost ("Additivity of Bimatoprost or Travoprost to Latanoprost in Glaucomatous Monkey Eyes", Gagliuso et al., 2004). Pharmacological differences between latanoprost and bimatoprost have been demonstrated. Some human patients with glaucoma that are unresponsive to latanoprost have been found to respond to bimatoprost in reducing elevated intraocular pressure ("Effect of bimatoprost on patients with primary open-angle glaucoma or ocular hypertension who are nonresponders to latanoprost", Gandolfi 2003). It appears likely that latanoprost and bimatoprost interact with different receptors in the eye and hair follicles.

[0052] Bimatoprost and bimatoprost free acid may be present in the following concentrations: 0.001%, 0.002%, 0.003%, 0.004%, 0.005%, 0.006%, 0.007%, 0.008%, 0.009%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.11%, 0.12%, 0.13%, 0.14%, 0.15%, 0.16%, 0.17%, 0.18%, 0.19%, 0.20%, 0.21%, 0.22%, 0.23%, 0.24%, 0.25%, 0.26%, 0.27%, 0.28%, 0.29%, 0.30%, 0.31%, 0.32%, 0.33%, 0.34%, 0.35%, 0.36%, 0.37%, 0.38%, 0.39%, 0.40%, 0.41%, 0.42%, 0.43%, 0.44%, 0.45%, 0.46%, 0.47%, 0.48%, 0.49%, 0.50%, 0.51%, 0.52%, 0.53%, 0.54%, 0.55%, 0.56%, 0.57%, 0.58%, 0.59%, 0.60%, 0.61%, 0.62%, 0.63%, 0.64%, 0.65%, 0.66%, 0.67%, 0.68%, 0.69%, 0.70%, 0.71%, 0.7 .16%, 0.17%, 0.18%, 0.19%, 0.2%, 0.21%, 0.22%, 0.23%, 0.24%, 0.25%, 0.26%, 0.27%, 0.28%, 0.29%, 0.3%, 0.31%, 0.32%, 0.33%, 0.34%, 0.35%, 0.36%, 0.37%, 0.38%, 0.39%, 0.4%, 0.41%, 0.42%, 0.43%, 0.44%, 0.45%, 0.46%, 0.47% ,0.48%,0.49%,0.5%,0.55%,0.6%,0.65%,0.7%,0.75%,0.8%,0.85%,0.9%,0.95%,1.0%,1.1%,1.2%,1.3%,1.4%,1.5%,1.6%,1.7%,1.8%,1.9%,2.0%,2.1%,2.2%,2.3%,2.4%,2.5%,2.6%,2.7%,2.8%,2.9%,3.0%,3.1%,3.2%,3.3%, , 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, 4.0%, 4.1%, 4.2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8%, 4.9%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, and 25% w / w, w / v, or v / v.

[0053] Bimatoprost and bimatoprost free acid may be present in the formulations of the present invention alone or in combination with other prostaglandin analogs. Bimatoprost may be combined with topical minoxidil or minoxidil sulfate, or topical or oral finasteride, and may be combined with cyclosporine I, II, or III.

[0054] The following U.S. patents and patent publications are incorporated herein by reference in their entireties: Patent Nos.: 8,038,988; 6,262,105; 7,388,029; 6,403,649; 9,750,750; 9,149,484; 9,101,550; 9,700,503; 6,946,120; 5,030,442; 5,030,442; 4,828,837; 7,803,357; 7,749,489; 6,465,514; 4,596,812; 7,442,369; 5,620,980; 5,225,189; 4,820,512; 6,596,266; and 5,834,014. U.S. Patent Publications: 20160136071; 20160228345; 20050079139; 20100210720; 20050079139; 20080206156; 20080206156; and 20040082660.

[0055] B. Cyclosporine Cyclosporine occurs naturally and was isolated from the fungus Tolypocladium inflatum in 1971. Cyclosporine is an immunosuppressant and is used to treat Crohn's disease, nephrotic syndrome, rheumatoid arthritis, organ transplant rejection, and dry eye disease. Cyclosporines are a group of non-polar cyclic oligopeptides with known immunosuppressant activity. Cyclosporine A and several other minor metabolites, as well as cyclosporines B, C, D, E, F, G, H, I, J, K, L, M, N, O, P, Q, R, S, T, U, V, W, X, Y, and Z, have been identified. In addition, derivatives, salts, etc. of such cyclosporines, as well as several synthetic analogues, have been produced and may be useful in the present invention. The use of cyclosporine A and cyclosporine A derivatives to treat various eye conditions has been the subject of various patents, including, for example, U.S. Pat. Nos. 5,474,979; 6,254,860; 6,350,442; and 7,368,436, the disclosures of each of which are incorporated by reference in their entireties.

[0056] Generally, commercially available cyclosporines may contain a mixture of several individual cyclosporines, all having a cyclic peptide structure of 11 amino acid residues with a total molecular weight of about 1,200 daltons, but with different substitutions or configurations of some of the amino acids. Thus, the present invention also contemplates mixtures of different types of cyclosporines or cyclosporine components. The term "cyclosporine component" as used herein is intended to include any individual member of the cyclosporine group, its salts, its derivatives, its analogs, and mixtures thereof, as well as mixtures of two or more of the individual cyclosporines, their salts, their derivatives, their analogs, and mixtures thereof.

[0057] Particularly preferred cyclosporine moieties include, but are not limited to, cyclosporine A, derivatives of cyclosporine A, salts of cyclosporine A, and the like, and mixtures thereof. Cyclosporine A is a particularly useful cyclosporine moiety.

[0058] The chemical structure of cyclosporin A is represented by Formula 1. [ka]

[0059] As used herein, the term "derivative" of cyclosporine refers to a compound that has a structure sufficiently similar to cyclosporine such that it functions in the present compositions and methods in a substantially similar or substantially identical manner to cyclosporine, e.g., cyclosporine A. Useful cyclosporine A derivatives include, but are not limited to, ((R)-methylthio-Sar) 3 -(4'-Hydroxy-MeLeu)Cyclosporin A, ((R)-(Cyclo)alkylthio-Sar 3 -(4'-Hydroxy-MeLeu) 4 -Cyclosporin A, and ((R)-(cyclo)alkylthio-Sar) 3- cyclosporine A derivatives, which are described below.

[0060] These cyclosporin derivatives are represented by the following general formulas (II) and (III), respectively. [ka] [ka] In the above formula, Me is methyl; Alk is 2-6C alkylene or 3-6C cycloalkylene; R is OH, COOH, alkoxycarbonyl, -NR1R2, or N(R3)-(CH2)-NR1R2; where R1, R2 are H, alkyl, 3-6C cycloalkyl, phenyl (optionally substituted with halo, alkoxy, alkoxycarbonyl, amino, alkylamino, or dialkylamino), benzyl, or 5- or 6-membered saturated or unsaturated heterocyclyl having 1-3 heteroatoms; or NR1R2 is a 5- or 6-membered heterocycle which may further contain N, O, or S heteroatoms and may be alkylated; R3 is H or alkyl, n is 2-4; and the alkyl portion contains 1-4C.

[0061] The present compositions and methods can be practiced using any suitable composition or combination of compositions that includes a therapeutically effective amount of a cyclosporine component in combination with bimatoprost, latanoprost, latanoprost acid, and travoprost and travoprost free acid, which are useful for promoting hair growth. The cyclosporine component is present in an amount and / or concentration that is sufficiently effective to provide the desired therapeutic effect when the cyclosporine-containing composition is administered to a human or animal in accordance with the present invention. Mixtures of cyclosporine components are contemplated. In one embodiment of the present invention, the cyclosporine component is advantageously present in the composition in an amount ranging from about 0.01-0.05% w / v, 0.05-0.1% w / v, 0.1% to about 0.5% w / v, 0.5-5% w / v, 5-15% w / v, and 15% or about 20% or 25% w / v of the composition.

[0062] In another embodiment, the cyclosporine component is present in an amount of about 0.01% to about 5% or about 10% or about 15% by weight of the composition. Cyclosporine may be present in the following concentrations: 0.001%, 0.002%, 0.003%, 0.004%, 0.005%, 0.006%, 0.007%, 0.008%, 0.009%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.11%, 0.12%, 0.13%, 0.14%, 0.15%, 0.16%, 0.17%. ,0.18%,0.19%,0.2%,0.21%,0.22%,0.23%,0.24%,0.25%,0.26%,0.27%,0.28%,0.29%,0.3%,0.31%,0.32%,0.33%,0.34%,0.35%,0.36%,0.37%,0.38%,0.39%,0.4%,0.41%,0.42%,0.43%,0.44%,0.45%,0.46%,0.47%,0.48%, 0.49%, 0.5%, 0.55%, 0.6%, 0.65%, 0.7%, 0.75%, 0.8%, 0.85%, 0.9%, 0.95%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3.0%, 3.1%, 3.2%, 3.3%, 3.4 %, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, 4.0%, 4.1%, 4.2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8%, 4.9%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, and 25% w / w, w / v, or v / v.

[0063] Cyclosporine, in all its various forms, both topical and oral, can be present in combination with bimatoprost, latanoprost, latanoprost acid, travoprost, travoprost free acid, minoxidil, minoxidil sulfate, and oral or topical finasteride.

[0064] C. Other hair growth agents 1) Minoxidil [ka]

[0065] Minoxidil is thought to open adenosine triphosphate (ATP)-sensitive potassium channels, dilating blood vessels and allowing more nutrients, blood, and oxygen to reach the hair follicle. During the late telogen phase of the hair follicle growth cycle, stem cells in the region of the hair bulge differentiate and re-enter the anagen phase. In patients with male pattern baldness, hair follicles become smaller and the duration of the anagen phase shortens. Minoxidil increases intracellular Ca 2+ Minoxidil increases the amount of Ca, which upregulates the enzyme adenosine triphosphate (ATP) synthase and promotes stem cell differentiation, independent of its role in ATP synthesis. 2+ Influx can increase stem cell differentiation and is theorized to be a factor in the mechanism by which minoxidil promotes hair growth (Mechanism of Action of Minoxidil in the Treatment of Androgenetic Alopecia) A. Gren et al., J Biol Regul Homeost Agents 31(4):1049-1053 (2017).

[0066] There is some evidence that minoxidil may cause hairs in the telogen phase to fall out, which are replaced by new, thicker hairs in the anagen phase.Minoxidil is a prodrug that is converted to minoxidil sulfate by the sulfotransferase enzyme SULT1A1. [ka]

[0067] Furthermore, minoxidil sulfate is a much more potent hair growth agent compared to minoxidil. Some studies speculate that the amount of the enzyme SULT1A1 in and around the hair follicle is what determines whether an individual responds well to minoxidil. Minoxidil can be combined with bimatoprost, latanoprost, 15-ketolatanoprost, 15(S)-latanoprost, 5-trans-latanoprost, latanoprost-d4, latanoprost-lactol, latanoprost-ethylamide-d4, and latanoprost acid, travoprost, and travoprost free acid, which in theory would cause a more rapid transition to anagen and a longer anagen phase. Minoxidil can also be combined with cyclosporine.Minoxidil can be combined with these compounds in the following concentrations: 0.001%, 0.002%, 0.003%, 0.004%, 0.005%, 0.006%, 0.007%, 0.008%, 0.009%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.11%, 0.12%, 0.13%, 0.14%, 0.15%, 0.16%, 0.17%, 0.18%, 0.19%, 0.2%, 0.21%, 0.22%, 0.23%, 0.24%, 0.25%, 0.26%, 0.27%, 0.28%, 0.29%, 0.3%, 0.31%, 0.32%, 0.33%, 0.34%, 0.35%, 0.36%, 0.37%, 0.38%, 0.39%, 0.4%, 0.41%, 0.42%, 0.43%, 0.44%, 0.45%, 0.46%, 0.47%, 0.48%, 0.49% ,0.5%,0.55%,0.6%,0.65%,0.7%,0.75%,0.8%,0.85%,0.9%,0.95%,1.0%,1.1%,1.2%,1.3%,1.4%,1.5%,1.6%,1.7%,1.8%,1.9%,2.0%,2.1%,2.2%,2.3%,2.4%,2.5%,2.6%,2.7%,2.8%,2.9%,3.0%,3.1%,3.2%,3.3%,3.4%,3.5%,3.6%,3.7%, %, 3.8%, 3.9%, 4.0%, 4.1%, 4.2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8%, 4.9%, 5.0%, 5.5%, 6.0%, 6.5%, 7.0%, 7.5%, 8.0%, 8.5%, 9.0%, 9.5%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, and 25% w / w, w / v, or v / v.

[0068] 2) Finasteride [ka]

[0069] Finasteride (C 23 H 36N2O2), also known as (1S,3aS,3bS,5aR,9aR,9bS,11aS)-N-tert-butyl-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,5a,6,9b,10,11-dodecahydroindeno[5,4-f]quinoline-1-carboxamide, is a 5α-reductase inhibitor originally used to treat benign prostatic hyperplasia in men. Oral finasteride works by reducing dihydrotestosterone (DHT) production by about 70%, including in the prostate and scalp. There have been some reports of successful scalp hair growth using topical finasteride. Finasteride can be combined with the prostaglandin analogs of the present invention, including bimatoprost, latanoprost and travoprost, and their analogs.

[0070] Finasteride can be combined with bimatoprost, latanoprost, 15-ketolatanoprost, 15(S)-latanoprost, 5-trans-latanoprost, latanoprost-d4, latanoprost-lactol, latanoprost-ethylamide-d4, and latanoprost acid, travoprost, and travoprost acid, which in theory will cause a more rapid transition to anagen and a longer anagen phase.Finasteride can be combined with minoxidil, minoxidil sulfate, or cyclosporine.Finasteride can be combined with these compounds in the following concentrations: 0.001%, 0.002%, 0.003%, 0.004%, 0.005%, 0.006%, 0.007%, 0.008%, 0.009%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.11%, 0.12%, 0.13%, 0.14%, 0.15%, 0.16%. ,0.17%,0.18%,0.19%,0.2%,0.21%,0.22%,0.23%,0.24%,0.25%,0.26%,0.27%,0.28%,0.29%,0.3%,0.31%,0.32%,0.33%,0.34%,0.35%,0.36%,0.37%,0.38%,0.39%,0.4%,0.41%,0.42%,0.43%,0.44%,0.45%,0.46%,0.47%,0.48%,0.49 %,0.5%,0.55%,0.6%,0.65%,0.7%,0.75%,0.8%,0.85%,0.9%,0.95%,1.0%,1.1%,1.2%,1.3%,1.4%,1.5%,1.6%,1.7%,1.8%,1.9%,2.0%,2.1%,2.2%,2.3%,2.4%,2.5%,2.6%,2.7%,2.8%,2.9%,3.0%,3.1%,3.2%,3.3%,3.4%,3.5%,3.6%,3. 7%, 3.8%, 3.9%, 4.0%, 4.1%, 4.2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8%, 4.9%, 5.0%, 5.5%, 6.0%, 6.5%, 7.0%, 7.5%, 8.0%, 8.5%, 9.0%, 9.5%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, and 25% w / w, w / v, or v / v.

[0071] definition The term "aerosol foam" refers to a product that includes a liquid foamable composition and a liquid propellant that is filled into a pressurized container with a valve system and nozzle at the top of the container and a dip tube that extends from the valve system to the bottom of the container. When the valve is opened, the liquid propellant instantly loses pressure and begins to evaporate, forming a high pressure gas layer at the top of the container. This high pressure gas layer pushes some of the liquid product and liquid propellant up the dip tube and out the nozzle. As the liquid flows through the nozzle, the liquid propellant evaporates into a gas, forming propellant bubbles in the liquid product in the process, creating a foam.

[0072] An "effective amount" of a compound is an amount sufficient to contribute to the treatment, prevention, or alleviation of one or more symptoms of a disease. When described in terms of the treatment of a disease, an "effective amount" may also be referred to as a "therapeutically effective amount." A "relief" of one or more symptoms (and grammatical equivalents of this expression) refers to a reduction in the severity or frequency of the symptoms, or the elimination of the symptoms. A "prophylactically effective amount" of a drug or formulation is an amount of a drug or formulation that, when administered to a subject, has the intended prophylactic effect, e.g., preventing or delaying the onset (or recurrence) of a disease, disorder, or illness, or reducing the likelihood of the onset (or recurrence) of a disease, disorder, or illness or symptoms thereof. A complete prophylactic effect does not necessarily occur with the administration of a single dose, but may occur only after a series of multiple administrations. Thus, a prophylactically effective amount may be administered by one or multiple administrations.

[0073] "Emulsion" refers in its ordinary sense to a mixture of two or more immiscible liquid components, where one component (e.g., a therapeutic lipid as described herein, or a mixture thereof with a surfactant) is dispersed by another component (e.g., the aqueous component of the compositions described herein). The term "submicron emulsion" refers to an emulsion that includes components that have a range of their longest dimension that is less than about 1 micron.

[0074] "Hair growth" or "growing hair" means increasing hair growth (hair regrowth, hair growth) compared to the rate of hair growth when the drugs and / or formulations of the present invention are not applied.

[0075] "Hair" may be vellus, which is a fine, thin, unpigmented, short hair whose bulb lies at the surface of the dermis. Intermediate hair is in a stage of growth between that of vellus ("baby" or immature hair), such as on the face, and that of mature hair, such as on the scalp. Terminal hair is coarse, pigmented, long hair whose follicle bulb lies deep in the dermis. As alopecia progresses, a transition occurs in the area close to the bald spot, and the hair itself changes type from terminal to vellus.

[0076] "Hair loss" can mean alopecia areata, androgenic alopecia, male pattern baldness, female pattern baldness, telogen effluvium, anagen effluvium, tinea capitis, cicatricial alopecia, lichen planus pilaris, discoid lupus erythematosus, barbaric folliculitis, dissecting cellulitis of the scalp, parietal cicatricial alopecia, frontal fibrosing alopecia, loose anagen syndrome, hair shaft abnormalities, catagen effluvium, androgenic alopecia, trichotillomania, chemotherapy-induced hair loss, hair loss due to infectious agents, trichorrhoea nodosa, and age-related alopecia.

[0077] By "follicular site" is meant an area of ​​the skin that contains hair follicles (eg, scalp, eyebrows, eyelid margins, face, etc.).

[0078] "Non-aerosol, non-spray foam" is a product that includes a foamable liquid composition filled into a non-pressurized container with a mechanical pump, an air chamber, a mixing chamber, a foam-forming screen mesh, and a dip tube that extends from the mechanical pump to the bottom of the container. When the mechanical pump is actuated, the foamable liquid composition is forced up through the dip tube into the mixing chamber where it is mixed with air from the air chamber in a predetermined ratio to form a foam. Actuation of the pump applies pressure to cause turbulent mixing of the air and the liquid foamable composition, forming air bubbles in the foamable liquid composition to generate the foam. The foam is then homogenized into a fine, uniform foam as it passes through the screen mesh before being discharged from the mixing chamber through a nozzle. This is thus a non-propellant method of ejecting a liquid product from a container in the form of a foam. The primary difference in the continued condition of the container is that in an aerosol foam container, the propellant fluid (usually a compressed or liquefied gas) is pumped into the container under high pressure after the container is sealed and is continuously maintained under pressure; in stark contrast, in a non-aerosol, non-spray foam container, the air within the container is continuously at atmospheric pressure.

[0079] A "pharmaceutically acceptable carrier" or "pharmaceutically acceptable excipient" generally means a carrier or excipient that is safe, non-toxic, and not biologically or otherwise undesirable, useful in preparing a pharmaceutical composition, and includes carriers or excipients that are acceptable for veterinary and human pharmaceutical use. As used herein and in the claims, "pharmaceutically acceptable carrier / excipient" includes both one and more than one such excipient.

[0080] The term "pharmaceutical acceptable salt" is intended to include salts of active compounds prepared with relatively non-toxic acids or bases, depending on the specific substituents found in the compounds described herein.When a compound of the present invention contains a relatively acidic functional group, a base addition salt can be obtained by contacting a neutral form of such a compound with a sufficient amount of a desired base, either neat or in a suitable inert solvent.Pharmaceutical acceptable base addition salts include, for example, sodium salts, potassium salts, calcium salts, ammonium salts, organic amino salts, or magnesium salts, or similar salts.When a compound of the present invention contains a relatively basic functional group, an acid addition salt can be obtained by contacting a neutral form of such a compound with a sufficient amount of a desired acid, either neat or in a suitable inert solvent. Pharmaceutically acceptable acid addition salts include those derived from inorganic acids, such as, for example, hydrochloride, hydrobromide, nitrate, carbonate, monohydrogencarbonic, phosphate, monohydrogenphosphoric, dihydrogenphosphoric, sulfate, monohydrogensulfuric, hydroiodide, or phosphite, as well as salts derived from relatively non-toxic organic acids, such as acetate, propionate, isobutyrate, maleate, malonate, benzoate, succinate, suberate, fumarate, lactate, mandelate, phthalate, benzenesulfonate, p-tolylsulfonate, citrate, tartrate, oxalate, methanesulfonate, etc. Also included are salts of amino acids, such as alginate, and salts of organic acids, such as glucuronate or galacturonate. See, e.g., Berge et al., "Pharmaceutical Salts," Journal of Pharmaceutical Science, 1977, 66, 1-19.Further information regarding suitable pharma- ceutically acceptable salts is found in REMINGTON'S PHARMACEUTICAL SCIENCES, 17th ed., Mack Publishing Company, Easton, PA, 1985, which is incorporated herein by reference.Certain compounds of the present invention contain both basic and acidic functional groups that allow the compounds to be converted into either base or acid addition salts.

[0081] "Prevention of hair loss" means slowing or preventing hair loss that would occur compared to if the formulation of the invention was not applied. The methods and compositions of the invention can be used to prevent hair loss, treat hair loss, or treat or thicken thinning hair, eyebrow loss, eyelash loss, or facial hair, and can be used to treat all types of alopecia, convert vellus hair to terminal hair, or increase the melanin content of hair, thicken hair, or increase the ratio of black to white hair on the scalp, eyebrows, eyelashes, or facial hair.

[0082] The term "prodrug" is used according to its clear and ordinary meaning and is intended to mean a compound that requires chemical or enzymatic transformation in vivo to release the active parent drug prior to producing a pharmacological effect.

[0083] The term "solubility" refers to the ability of a solvent to dissolve an amount of an active pharmaceutical ingredient relevant to its pharmacological effect.

[0084] The terms "solvent" and "solvent system" define a component of a formulation, the liquid or semi-solid phase that contains the API.

[0085] As used herein, the terms "stable" and "stability" are used in relation to the shelf life of a pharmaceutical product and relate to physical changes, degradation, or chemical alterations of an active pharmaceutical ingredient or formulation that limit the shelf life of the product.

[0086] "Synergy" between two drugs can occur when, for example, in a fixed combination, the two drugs enhance or increase one or more effects, or interact in such a way that when combined, with two different mechanisms of action, they provide a greater therapeutic effect or efficacy than when the drug is applied alone or when the two drugs are applied separately, or they avoid or reduce undesirable side effects when the drugs are provided as monotherapy. Negative effects of synergy are in the form of contraindications, such as when multiple depressants that affect the central nervous system (CNS) are used, e.g., alcohol and Valium. "Synergy" is also noted in describing how complex systems work. For example, biological systems can respond nonlinearly to the actions of the mind, so that the outcome can be greater than the sum of the changes in the individual parts.

[0087] In the context of the present invention, synergy means that the combination of two active drugs utilized in the methods and compositions of the present invention achieves results, for example, in stimulating the growth of scalp hair, eyebrows, eyelashes, etc., in a mammal (e.g., human), that are greater than the results obtained when the active drugs are utilized alone as monotherapy under similar conditions. Thus, to determine which combinations are within the scope of the present invention, the results obtained by the combination of the two drugs can simply be compared to the results obtained by each of the individual drugs alone.

[0088] The term "topical" in the context of the methods described herein refers to the administration of a compound or pharmaceutical composition in its normal sense, which is incorporated into a suitable pharmaceutical carrier and administered to a localized treatment site of a subject. Thus, the term "topical pharmaceutical composition" includes pharmaceutical dosage forms in which the compound is administered externally by direct contact with a local treatment site, such as the skin, scalp, eyebrows, eyelid margins, face. The term "topical epidermal pharmaceutical composition" refers to a pharmaceutical composition suitable for administration to the epidermal layer of the skin, such as the eyelids, eyebrows, scalp, or body. The term "topical administration" refers to administration externally by direct contact with a local treatment site. The term "topical epidermal administration" refers to administration externally by direct contact with the epidermis.

[0089] The terms "treat", "treating" or "treatment" may refer to indications of success in treating or improving damage, condition or disease, including objective or subjective parameters such as relief; remission; reduction of symptoms or making the damage, condition or disease more tolerable to the patient; slowing the rate of change or progression of symptoms; making the end point of change less severe; improving the physical or mental health of the patient. The treatment or improvement of symptoms can be based on objective or subjective parameters, including the results of physical examinations, neuropsychiatric examinations, and / or computer imaging systems. For example, certain methods presented herein successfully treat hair loss by reducing the incidence of hair loss, suppressing its symptoms and / or causes, and causing new hair growth.

[0090] Hair anatomy and hair growth Although hair follicle openings account for only about 0.1% of the total surface area of ​​human skin, hair follicles may account for as much as 10% of the total surface area of ​​the human scalp (Schaefer, H., et. al. (1990) "Follicular penetration" (pgs. 163 - 173) (1990)). In general, hair follicle openings lead to an epithelial surface that lacks the protective stratum corneum of the skin surface. As a result, hair follicles and sebaceous glands contribute significantly to transdermal drug delivery. As a result, hydrophilic drugs can penetrate with high fluidity, usually via intrafollicular pathways along the junction of the inner and outer root sheaths, and can diffuse rapidly into the skin by the outer root sheath. The longer lag time for scalp skin penetration of hydrophilic drugs, compared to the shorter time for lipophilic drugs, suggests that penetration of hydrophilic drugs through the upper skin is the rate-limiting step. The route of penetration of lipophilic drugs is likely along the junction of the inner and outer root sheath.

[0091] The release of sebum by the sebaceous glands associated with the hair follicle forms a lipid pathway for lipophilic substances within the hair follicle (Ebling et al., 1991). Also, the permeation pathway for lipophilic penetrants is thought to be the transepidermal pathway. Thus, although passing through the stratum corneum of the scalp is also an important pathway, some drugs may use a pathway through the hair follicle. Sebum present in the hair follicle also plays an important role in drug penetration of the outer root sheath. Human hair follicles can vary in diameter from 5um to 80um, which may affect the permeation through the hair follicle.

[0092] Certain penetration enhancers and solvents help to mobilize lipids in the intercellular channels of the stratum corneum.It is believed that the permeation of permeants and drugs through the scalp is related to rapid penetration into hair follicles and rapid diffusion through the outer root sheath into the dermis, while the transepidermal permeation of drugs is mainly through microchannels.Hydrophilic drugs also diffuse rapidly through the outer root sheath into the dermis, but the permeation of hydrophilic drugs through the upper dermis may be the rate-limiting step and relatively slow.

[0093] It is believed that human scalp anagen hair follicles express prostanoid receptor genes and proteins in the hair papilla and CTS around the hair bulb, but not in epidermal keratinocytes or melanocytes in the hair bulb. One theory is that some prostaglandin analogs bind to specific receptors on the plasma membrane of cells of the regulating hair papilla of the hair bulb, which possibly stimulates intracellular signaling pathways, resulting in hair growth and reduced hair loss. For example, without being bound by any theory, prostaglandin analogs such as latanoprost can increase the number of anagen hairs by transitioning hair from resting telogen to anagen, shortening the time to start anagen, and lengthening the anagen phase, thereby allowing hair to grow longer. Patients with androgenetic alopecia have a shortened anagen phase period and hair follicles spend more time in telogen compared to patients without androgenetic alopecia. Latanoprost, travoprost, and bimatoprost stimulate, to varying degrees, melanogenesis in melanocytes and keratinization in the hair papilla, potentially resulting in more melanin in individual hairs, resulting in darker hairs, and may increase the diameter of individual hairs and the size of the hair papilla, resulting in a greater number of longer, darker, and thicker hairs than those not treated with latanoprost, travoprost, and bimatoprost. Bimatoprost has also been reported to induce certain signals in the hair papilla that are used to grow eyelashes, but bimatoprost is a prostamide and has a different receptor system than prostaglandin analogues, and is therefore thought to have a different mechanism of action (Khidir, "The Prostamide-related glaucoma therapy …" FASEB, 27[2]: 557-567 [Feb. 2013]).

[0094] Keratinocyte cells are found in the outermost layer of the skin, known as the epidermis. Keratinocyte cells are also found in the basal layer of the skin. Keratinocyte cells form about 95% of the epidermis. Keratinocytes undergo keratinization to form the superficial layer of the skin. These superficial keratinized cells are continually replaced by cells derived from mitotic cells in the lowest layer of the epidermis, the basal layer. The cells of the basal layer are sometimes referred to as basal keratinocytes or basal cells. The epidermis is about 0.2 mm thick. Within the epidermis, keratinocytes are arranged in four distinct layers, known as the basal, spinous, granular, and stratum corneum. Melanocytes in the basal layer do not undergo keratinization, but they do produce melanin. Melanin accumulates in small granules known as melanosomes, which are transported to dendrites and then transferred to keratinocytes. Keratinocytes and melanocytes reside in hair follicles along with dermal fibroblasts. Epidermal and hair follicle homeostasis is primarily regulated by cellular interactions between keratinocytes and melanocytes. Keratinocytes stimulate melanocyte functions, such as melanogenesis, proliferation, differentiation, and dendrite formation, through cell-to-cell paracrine signaling. Hirobe, "Keratinocytes Regulate the Function of Melanocytes" Dermatolgica Sinica, Vol. 32, pgs. 200 - 204 (2014). It is theorized that prostaglandin analogs, such as latanoprost and travoprost, may act on hair-forming keratinocytes and pigment-producing melanocytes. Prostaglandin analogs may act directly on keratinocytes to increase the diameter of individual hairs and on melanocytes to darken hairs or rather the normal hair color of the individual user. This may occur through indirect action via the dermal papilla, which is located in the center of the hair bulb at the base of the hair follicle, by paracrine signals to keratinocytes and / or melanocytes as a result of an as yet unclear hair follicle signaling system.

[0095] Eyebrows Eyebrow loss, also known as madarosis, is characterized by the absence or loss of eyebrow growth. Eyebrow loss can have cosmetic, functional, and social / psychological consequences. Studies have shown that scalp hairs are usually thicker in diameter than eyebrows in Asian patients, whereas the reverse is true in Caucasian patients (Gandelman M. A Technique for Reconstruction of Eyebrows and Eyelashes. Semin Plast Surg. 19:153-8 (2005)). Eyebrows are generally less dense on the lateral side than on the medial side, and when eyebrow hair loss occurs, it is more noticeable in the lateral side. Eyebrows can be broadly divided into three regions. The inner third is usually below the orbital rim, and the hairs in this region are oriented vertically. The middle third is along the orbital rim, and the hairs are oriented diagonally or horizontally. The outer third is usually above the orbital rim.

[0096] Eyebrow trichoanalysis can be caused by diseases such as skin disorders, endocrine disorders such as thyroid disorders, and psychiatric disorders such as trichotillomania and chemotherapy. Heredity can also be a factor in diseases such as congenital malformations. Eyebrow trichoanalysis can be caused by physical trauma such as burns, complications from cosmetic procedures such as tattoos, and complications from transplants.

[0097] Eyelashes Eyelashes provide a functional and protective mechanism by protecting the eye by preventing foreign objects and objects from entering the eye. Long eyelashes are generally considered more attractive than short eyelashes in most cultures. In most mammals, the nervous system around the eye is excitable to protect the eye. Eyelash loss is known as eyelash hypotrichosis, including idiopathic hypotrichosis, chemotherapy-induced hypotrichosis, alopecia areata, and hypothyroidism. Eyelash length is highly proportional to age, with younger people having longer eyelashes and older people having shorter eyelashes. Current treatments for eyelash hypotrichosis include LATISSE™, a 0.03% w / v solution of bimatoprost applied to the upper eyelid margin.

[0098] chemotherapy Chemotherapy-induced alopecia occurs primarily because chemotherapy agents damage hair follicles, resulting in complete or incomplete hair loss. Hair loss occurs in approximately 65% ​​of chemotherapy patients. Hair loss generally occurs over the entire body and includes not only the scalp but also eyelashes and eyebrows. Chemotherapy-induced hair loss can be psychologically devastating and is described by some patients as a constant reminder of their illness, which can lead to feelings of being out of control and increased social isolation (Beisecker, Analee et al., Side Effects of Adjuvant Chemotherapy, Pycho-Oncology, 1997, 83-93-6). Focus groups have also demonstrated that loss of eyelashes and eyebrows is more psychologically devastating than scalp hair loss.

[0099] Other non-chemotherapeutic drugs can also cause hair loss, such as anticoagulants, oral contraceptives, retinoids, antithyroid drugs, and interferons. Generally, chemotherapy-induced hair loss is brought about by toxicity to the rapidly dividing cells in the hair follicle. During the anagen phase, the epithelial portion of the hair follicle undergoes rapid proliferation, with the greatest proliferation occurring in the matrix cells of the hair bulb. When chemotherapy agents are administered to a patient, the mitosis of cells can suddenly stop, causing hair loss, as the partially keratinized hair shaft weakens, resulting in hair loss. This is known as anagen effluvium. Chemotherapeutic agents can also cause apoptosis (programmed cell death) in the cells of the hair follicle. Generally, once chemotherapy is terminated, hair growth is restored, but in some patients, it may take several years, or even several complete hair cycles, to reach the same level of hair growth that the patient experienced before chemotherapy. Generally, the new hair is vellus hair, not terminal hair. The formulations and methods described herein can be used on the scalp, face, eyebrows, eyelashes, and entire body prior to or during chemotherapy to prevent hair loss, and after chemotherapy to regrow hair, shift the hair cycle into the anagen phase, and lengthen the anagen phase, resulting in longer, darker, and thicker eyelashes, eyebrows, head hair, and facial hair.

[0100] Vehicle Table 1 provides a list of solvents and penetration enhancers. [Table 1-1] [Table 1-2]

[0101] Solvents and penetration enhancers may be present in the following concentrations: 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3.0%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9 ...0%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, 3.0%, 3.1%, 3 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3.0%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3 .9%, 4.0%, 4.1%, 4.2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8%, 4.9%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10%w / w, 11%, 1 2%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57% , 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% w / w, w / v, or v / v.

[0102] Carbomer may be at a concentration of about 0.05 to 3.0% w / w, isopropyl myristate may be at a concentration of about 0.1 to about 10% w / w; PEG 40 castor oil may be at a concentration of about 0.1 to 20% w / w; carboxymethylcellulose may be at 0.1 to 5.0% w / w, ethanol may be at a concentration of about 1 to about 70% w / w; diethylene glycol monoethyl ether may be at a concentration of about 1.0 to about 50% w / w; polysorbate 20 may be at a concentration of about 0.05 to 3.0% w / w. , may be at a concentration of about 0.1 to about 5.0% w / w; polysorbate 40 may be at a concentration of about 0.1 to about 5.0% w / w; polysorbate 60 may be at a concentration of about 0.1 to about 5.0% w / w; glycerin may be at a concentration of about 1.0 to about 30% w / w; polysorbate 80 may be at a concentration of about 0.1 to about 5.0% w / w; PPG-5 ceteth-20 may be at a concentration of about 0.1 to about 5.0% w / w; oleic acid may be at a concentration of about 0.1 to about 5.0% w / w. isostearyl isostearate may be at a concentration of about 0.1 to about 10% w / w; dipropylene glycol dimethyl ether may be at a concentration of about 1 to about 50% w / w; diethylene glycol may be at a concentration of about 1 to about 50% w / w; dipropylene glycol may be at a concentration of about 1 to about 50% w / w; caprylic / capric acid may be at a concentration of about 0.1 to about 10% w / w; benzyl alcohol may be at a concentration of about 0.1 to about 10% w / w. the silicone may be at a concentration of about 0.1 to about 10% w / w; the PEG 40 castor oil may be at a concentration of about 0.1 to 20% w / w; the PEG 35 castor oil may be at a concentration of about 0.1 to 20% w / w; the oleyl alcohol may be at a concentration of about 0.1 to 10% w / w; the glyceryl monooleate may be at a concentration of about 0.1 to 10% w / w; and / or the water may be at a concentration of about 0 to about 90% w / w. EXAMPLES

[0103] Formulation I 0.05% w / v Latanoprost; 0.06% w / v cyclosporine A; 10.0% w / v diethylene glycol monoethyl ether; 5.0% w / v oleyl alcohol; and 100% with adequate water.

[0104] Formulation II 0.08% w / v Latanoprost; 0.1% w / v cyclosporine A; 15.0% w / v diethylene glycol monoethyl ether; 5% w / v PEG; 6.0% w / v oleyl alcohol; and 100% with adequate water.

[0105] Preparation III 0.08% w / v Latanoprost; 0.1% w / v cyclosporine A; 15.0% w / v diethylene glycol monoethyl ether; 5% w / v PEG; 6.0% w / v oleyl alcohol; and 100% with adequate water.

[0106] Formulation IV 0.06% w / v bimatoprost; 0.08% w / v cyclosporine A; 10.0% w / v glyceryl monooleate; 5.0% w / v oleic acid; 5% w / v ethanol; and 100% with adequate water.

[0107] Formulation V 0.08% w / v bimatoprost; 0.1% w / v cyclosporine A; 10.0% w / v diethylene glycol monoethyl ether; 5.0% w / v oleic acid; 5.0% w / v oleyl alcohol; and 100% with adequate water.

[0108] Formulation VI 0.08% w / v latanoprost or latanoprost acid; 0.08% w / v cyclosporine A; 10.0% w / v polyethylene glycol; 10.0% w / v diethylene glycol monoethyl ether; 5.0% w / v oleyl alcohol; and 100% with adequate water.

[0109] Formulation VII 0.05% w / v bimatoprost; 0.07% w / v cyclosporine A; 10.0% w / v oleyl alcohol; 10.0% w / v diethylene glycol monoethyl ether; and 100% with adequate water.

[0110] Formulation VIII 0.05% w / v latanoprost or latanoprost acid; 0.08% w / v cyclosporine A; 5.0% w / v diethylene glycol monoethyl ether; 10.0% w / v CAPTEX 300 EP / NF; 10.0% w / v PEG; and 100% with adequate water.

[0111] Preparation IX 0.06% w / v wenoprostone isopropyl ester free acid; 0.08% w / v cyclosporine A; 5.0% w / v diethylene glycol monoethyl ether; 10.0% w / v CAPTEX 300 EP / NF; 10.0% w / v PEG; and 100% with adequate water.

[0112] Formulation X 0.07% w / v travoprost or travoprost free acid; 0.08% w / v cyclosporine A; 5.0% w / v diethylene glycol monoethyl ether; 10.0% w / v CAPTEX 300 EP / NF; 10.0% w / v PEG; and 100% with adequate water.

[0113] Preparation XI 0.1% w / v bimatoprost; 005% w / v cyclosporine A; 20% w / v 2-(2-ethoxyethoxy)-ethanol; 5% w / v propanediol; 3% w / v oleic acid; and 100% with adequate water.

[0114] Preparation XII 0.1% w / v latanoprost; 005% w / v cyclosporine A; 20% w / v 2-(2-ethoxyethoxy)-ethanol; 5% w / v propanediol; 3% w / v oleic acid; and 100% with adequate water.

[0115] Preparation XIII 0.1% w / v latanoprost; 5.0% w / v Minoxidil; 10% w / v 2-(2-ethoxyethoxy)-ethanol; 5% w / v propanediol; 3% w / v oleic acid; and 100% with adequate water.

[0116] Formulation XIV 0.1% w / v latanoprost; 5.0% w / v minoxidil or minoxidil sulfate; 20% w / v 2-(2-ethoxyethoxy)-ethanol; 5% w / v propanediol; 3% w / v oleic acid; and 100% with adequate water.

[0117] Formulation XV 0.1% w / v latanoprost; 2.0% w / v minoxidil or minoxidil sulfate; 20% w / v 2-(2-ethoxyethoxy)-ethanol; 5% w / v propanediol; 3% w / v oleic acid; and 100% with adequate water.

[0118] Formulation XVI 0.1% w / v bimatoprost; 5.0% w / v Minoxidil; 20% w / v 2-(2-ethoxyethoxy)-ethanol; 5% w / v propanediol; 3% w / v oleic acid; and 100% with adequate water.

[0119] Formulation XVII 0.1% w / v travoprost; 5.0% w / v Minoxidil; 20% w / v 2-(2-ethoxyethoxy)-ethanol; 5% w / v propanediol; 3% w / v oleic acid; and 100% with adequate water.

[0120] Preparation XVIII 0.1% w / v latanoprost; 5.0% w / v Minoxidil; 30.0% w / v ethanol; 50% w / v propylene glycol; and 100% with adequate water.

[0121] Preparation XVIIII 0.1% w / v latanoprost; 5.0% w / v Minoxidil; 30.0% w / v ethanol; 50% w / v propylene glycol; 3% w / v diethylene glycol monoethyl ether; 2% w / v oleyl alcohol; and 100% with adequate water.

[0122] Preparation XX 0.3% w / v latanoprost; 5.0% w / v Minoxidil; 30.0% w / v ethanol; 50% w / v propylene glycol; and 100% with adequate water.

[0123] Preparation XXI 5.0% w / v minoxidil or minoxidil sulfate; 0.05% w / v Latanoprost; 30.0% w / v ethanol; 50% w / v propylene glycol; and 100% with adequate water.

[0124] Preparation XXII 5.0% w / v Minoxidil; 0.05% w / v Latanoprost; 30.0% w / v ethanol; 50% w / v propylene glycol; and 100% with adequate water.

[0125] Preparation XXIII 5.0% w / v Minoxidil; 0.008% w / v Latanoprost; 30.0% w / v ethanol; 50% w / v propylene glycol; A moderate amount of water.

[0126] Preparation XXIV 5.0% w / v Minoxidil; 0.007% w / v Latanoprost; 30.0% w / v ethanol; 50% w / v propylene glycol; and 100% with adequate water.

[0127] Preparation XXV 5.0% w / v Minoxidil; 0.005% w / v Latanoprost; 30.0% w / v ethanol; 50% w / v propylene glycol; and 100% with adequate water.

[0128] Formulation XXVI 3.0% w / v finasteride; 0.1% w / v latanoprost; 30.0% w / v ethanol; 50% w / v propylene glycol; and 100% water with the right amount of water.

[0129] Preparation XXVII 5.0% w / v finasteride; 0.3% w / v latanoprost; 30.0% w / v ethanol; 50% w / v propylene glycol; and 100% with adequate water.

[0130] Preparation XXVIII 5.0% w / v finasteride; 0.3% w / v bimatoprost; 30.0% w / v ethanol; 50% w / v propylene glycol; and 100% with adequate water.

[0131] Preparation XXVIIII 5.0% w / v finasteride; 0.1% w / v bimatoprost; 30.0% w / v ethanol; 50% w / v propylene glycol; and 100% with adequate water.

[0132] Formulation XXX 5.0% w / v finasteride; 0.1% w / v travoprost; 30.0% w / v ethanol; 50% w / v propylene glycol; and 100% with adequate water.

[0133] Preparation XXXI 5.0% w / v finasteride; 0.3% w / v travoprost; 30.0% w / v ethanol; 50% w / v propylene glycol; and 100% with adequate water.

[0134] Preparation XXXII 0.1% w / v latanoprost; 47% w / v ethanol; 0.4% w / v polysorbate 60; 1% w / v polyethylene lauryl alcohol; 0.3% w / v acetic acid; 10% w / v propylene glycol; and 100% with adequate water.

[0135] Preparation XXXIII 0.3% w / v latanoprost; 47% w / v ethanol; 0.4% w / v polysorbate 60; 1% w / v polyethylene lauryl alcohol; 0.3% w / v acetic acid; 10% w / v propylene glycol; and 100% with adequate water.

[0136] Formulation XXXIV 0.08% w / v Latanoprost; 4.0% w / v Minoxidil; 50% w / v propylene glycol; 30% w / v ethanol; 3% w / v transcutol; 2% w / v oleyl alcohol; 0.5% w / v POE40; and 100% with adequate water.

[0137] Formulation XXXV 0.08% w / v Latanoprost; 4.0% w / v Minoxidil; 50% w / v propylene glycol; 30% w / v ethanol; 3% w / v transcutol; 2% w / v oleyl alcohol; and 100% with adequate water.

[0138] Formulation XXXVI 0.1% w / v latanoprost; 47% w / v ethanol; 0.4% w / v polysorbate 60; 1% w / v polyethylene lauryl alcohol; 0.3% w / v acetic acid; 2.0% w / v oleic acid; 10% w / v propylene glycol; and 100% with adequate water.

[0139] Non-aerosol - Non-spray foam - Pumps and containers In another embodiment, the final product of the liquid formulation containing the active ingredient combination of bimatoprost / minoxidil, or travoprost / minoxidil, or latanoprost / minoxidil, or bimatoprost / finasteride, or travoprost / finasteride, or latanoprost / finasteride, or pharma- ceutically acceptable salts thereof, is packaged in a non-pressurized container and dispensed using a non-aerosol non-spray foam pump. The non-aerosol non-spray foam pump provides a safe and easy dispensing of a measured dose of foam containing the liquid formulation containing the drug combination or its salt, which is easily applied to the scalp, eyebrows, eyelashes, or face. The non-aerosol non-spray foam pump is adjusted to deliver an appropriate amount of foam. An additional object disclosed herein is to provide a liquid formulation in a reusable, non-pressurized container that does not contain a propellant and can be manufactured in a cylindrical or non-cylindrical shape. Thus, the present embodiment does not employ the use of pressurized containers containing typical propellants such as liquefied petroleum gas (a mixture of propane, isobutene, and n-butane), chlorofluorocarbons (CFCs), and dimethyl ether, which are flammable, harmful, and toxic volatile organic compounds (VOCs). The present embodiment can be safely transported, stored, and dispensed in reusable containers. Reusing products and product parts is very important to the environment.

[0140] Foam formulation The foam formulation comprises the combination of active ingredients of bimatoprost / minoxidil, or travoprost / minoxidil, or latanoprost / minoxidil, or bimatoprost / finasteride, or travoprost / finasteride, or latanoprost / finasteride, or pharma- ceutically acceptable salts thereof. Preferably, the amount of surfactant is about 2-10%. Any combination of anionic, cationic, nonionic, or amphoteric surfactants, and nonionic block copolymers may be used. Preferably, ethoxylated glycerides, ethoxylated sorbitan esters, polyethoxylated and / or hydrogenated castor oil, nonionic block copolymers, and amphoteric surfactants may be used. Particularly preferred surfactants may be selected from PEG-40 hydrogenated castor oil; PEG 40 stearate; polysorbate 20; cocamidopropyl betaine; glyceryl cocoate; PEG 6 (caprylic / capric) glyceride; poloxamer F68; and saturated phospholipids C6-C10.

[0141] Formulation XXXVII (spray solution) Minoxidil 5.0% w / v (active ingredient); Latanoprost 0.1% w / v or 0.3% w / v (active ingredient); 1,2-propanediol 60.5% w / v (solvent); Ethyl alcohol 10.2% w / v (solvent); Lactic acid 2.5% w / v (acidifier); Essence (Fragrance) 0.06% w / v (aroma / essence); and 100% (solvent) with appropriate amount of deionized water.

[0142] The manufacturing flow scheme of Formulation XXXV is as follows: 1: prepare minoxidil, latanoprost, and other excipients by weighing separately;2: put 1,2-propanediol, lactic acid, ethyl alcohol, and deionized water, weighed separately, into the manufacturing vessel and mix for ≥5 minutes;3: put pre-weighed minoxidil into the stainless steel manufacturing vessel and mix for ≥15 minutes to dissolve, followed by adding pre-weighed latanoprost (in a pre-weighed syringe with proper oil transfer);4: add essence (fragrance) and mix;5: perform filling with target amount, package and box the final product.

[0143] Formulation XXXVIII; Minoxidil(2) / Latanoprost(0.1) Spray Minoxidil 2% w / v (active ingredient); Latanoprost 0.1% w / v or 0.3% w / v (active ingredient); 1,2-propanediol 65.9% w / v (solvent / excipient); Ethyl alcohol 5.2% w / v (solvent); Lactic acid 2.5% w / v (acidifier); Essence (Fragrance) 0.06% w / v (aroma / essence); and A suitable amount of deionized water (solvent). The manufacturing flow scheme of the formulation is the same as that of formulation XXXVII.

[0144] Formulation XXXIX: Minoxidil (5) / Latanoprost (0.1 or 0.3) Form Minoxidil 5.0% w / v (active ingredient); Latanoprost 0.1% w / v or 0.3% w / v (active ingredient); 1,2-propanediol 51.5% w / v (solvent / excipient); PEG20 oleyl ether 0.5% w / v (surfactant); Plantacare 1200 * 10.5% w / v (surfactant); Komperlan KD **3% w / v (surfactant); Ethyl alcohol 5.2% w / v (solvent) (EP); Lactic acid 2.4% w / v (acidifier) ​​(EP); Essence (Fragrance) 0.06% w / v (Aroma / Essence [EP]); and Deionized water 21.8% (solvent) (EP). *Lauryl glycoside **Cocamide DEA = Coconut fatty acid diethanolamine The manufacturing flow scheme for the formulation is as follows: Minoxidil, latanoprost, and other excipients are weighed separately and prepared. 1,2-propanediol, lactic acid, ethyl alcohol, and deionized water are weighed and mixed in a manufacturing vessel for more than 5 minutes, pre-weighed minoxidil is added to a stainless steel manufacturing vessel and mixed for more than 15 minutes to dissolve, and then pre-weighed latanoprost is added. Pre-weighed PEG20 oleyl ether, Plantacare1200, and komperlanKD are added to a stainless steel manufacturing vessel and dissolved, and essence (fragrance) is added and mixed. Filling is performed at the target amount, and the final product is packaged and boxed.

[0145] Formulation XXXX: Minoxidil 2.0% / Latanoprost 0.1% foam Minoxidil 2% w / v; Latanoprost 0.1% w / v or 0.3% w / v; 1,2-propanediol 51.% w / v (solvent / excipient); PEG20 oleyl ether 0.5% w / v (surfactant); Plantacare 1200 10.5% w / v (surfactant); Komperlan KD 3% w / v (surfactant); Ethyl alcohol 5.2% w / v (solvent); Lactic acid 2.4% w / v (acidifier); Essence (Fragrance) 0.06% w / v 9 w / v (Aroma / Essence); and A suitable amount of deionized water.

[0146] Formulation XXXXI (Lotion) Minoxidil 5% w / v; Latanoprost 0.1% or 0.3% w / v; Ethanol 60.3%w / v; Polysorbate 60 0.4% w / v; Polyoxyethylene lauryl alcohol 1.00% w / v; Acetic acid 0.6% w / v; and Purified water totals 100%. The apparent pH of the final formulated solution is 6.24.

[0147] Formulation XXXXII Minoxidil 5% w / v; Latanoprost 0.1% or 0.3% w / v; Cetyl alcohol 2.20% w / v; Stearyl alcohol 1.00% w / v; Ethanol 51.8%w / v; Polysorbate 60 0.4% w / v; Polyoxyethylene lauryl alcohol 1.00% w / v; Propylene glycol 5.00% w / v; Propellant P75 4.30%w / v; Acetic acid, pH 6.0; and Purified water totals 100%.

[0148] Formulation XXXXIII (Lotion) Minoxidil 8% w / v; Latanoprost 0.3% or 0.1% w / v; Ethanol 50.5%w / v; Polysorbate 60 0.4% w / v; Polyoxyethylene lauryl alcohol 1.00% w / v; Acetic acid, pH 6.0 with appropriate amount; Propylene glycol 7.3% w / v; Benzyl alcohol 5% w / v; and Purified water totals 100%.

[0149] Formulation XXXXIV (solution) Latanoprost 0.1%, 0.2%, or 0.3% w / v; Minoxidil 5% w / v; Ethanol 51%w / v; Polysorbate 60 0.4% w / v; Laureth-12 1% w / v; Glacial acetic acid 0.3%w / v; Propylene glycol 7.5% w / v; Benzyl alcohol 5% w / v; and Purified water totals 100%. The pH is approximately 6.24.

[0150] Formulation XXXXV Minoxidil 8% w / v; Latanoprost 0.3% or 0.1% w / v; Ethanol 50.0%w / v; Polysorbate 60 0.4% w / v; Polyoxyethylene lauryl alcohol 1% w / v; Acetic acid, pH 6.0 with appropriate amount; Propylene glycol 10% w / v; Benzyl alcohol 5% w / v; and Purified water totals 100%.

[0151] Formulation XXXXVI (Lotion) Minoxidil 5% w / v; Latanoprost 0.1% or 0.3% w / v; Ethanol 47.50%w / v; Polysorbate 60 0.4% w / v; Polyoxyethylene lauryl alcohol 1.00% w / v; Acetic acid, pH 6.0 with appropriate amount; Benzyl alcohol 5% w / v; and Purified water totals 100%.

[0152] Formulation XXXXVII Minoxidil 5% w / v; Latanoprost 0.1% w / v; Ethanol 47%w / v; Polysorbate 60 0.4% w / v; Polyoxyethylene lauryl alcohol 1% w / v; Acetic acid 1%w / v; Propylene glycol 10% w / v; Benzyl alcohol 5% w / v; and Purified water, 100% in moderation.

[0153] Formulation XXXXVIII Minoxidil 5% w / v; Latanoprost 0.3% w / v; Ethanol 44.2%w / v; Polysorbate 60 0.4% w / v; Polyoxyethylene lauryl alcohol 1% w / v; Acetic acid 0.3%w / v; Propylene glycol 30% w / v; Benzyl alcohol 2% w / v; and Purified water, 100% in moderation.

[0154] Formulation XXXXIX Minoxidil 5% w / v; Latanoprost 0.3% w / v; Ethanol 46%w / v; Polysorbate 60 0.4% w / v; Polyoxyethylene lauryl alcohol 1% w / v; Acetic acid 0.3%w / v; Propylene glycol 30% w / v; Benzyl alcohol 10% w / v; and Purified water, 100% in moderation.

[0155] Formulation XXXXX Minoxidil sulfate 4% w / v; Latanoprost 0.08% w / v; Ethanol 30% w / v; Propylene glycol 50% w / v; Oleyl alcohol 2% w / v; Transcutol 3%; and Purified water, 100% in moderation. The apparent pH of the final formulations XXXXIV-XXXXX is adjusted to 6.0-6.5 and the benzyl alcohol can be removed and replaced with propylene glycol in single-use formulations.

[0156] Other embodiments Other formulations include: a composition comprising up to 5% w / w minoxidil, about 0.1% w / w latanoprost, about 0.15% w / w carbomer; about 0.22% w / w triethylamine (TEA); about 15.0% w / w ethanol; about 10.0% w / w diethylene glycol monoethyl ether; about 4.0% w / w polysorbate 20; and about 70.5% w / w water.

[0157] A composition comprising up to 5% w / w minoxidil, about 0.1% w / w latanoprost, about 0.10% w / w carbomer; about 0.035% w / w NaOH; about 15.0% w / w ethanol; about 10.0% w / w diethylene glycol monoethyl ether; and about 74.8% w / w water.

[0158] A composition comprising up to 5% w / w minoxidil, about 0.1% w / w latanoprost, about 0.125% w / w carbomer; about 0.18% w / w TEA; about 30.0% w / w ethanol; about 20.0% w / w diethylene glycol monoethyl ether; and about 49.59% w / w water.

[0159] A composition comprising up to 5% w / w minoxidil, about 0.1% w / w latanoprost, about 0.10% w / w carbomer; about 0.15% w / w TEA; about 30.0% w / w ethanol; about 20% w / w propylene glycol; and about 49.7% w / w water.

[0160] A composition comprising up to 5% w / w minoxidil, about 0.1% w / w latanoprost, about 0.20% w / w carbomer; about 0.22% w / w TEA; about 60.0% w / w ethanol; about 5.0% w / w glycerin; and about 34.48% w / w water.

[0161] A composition comprising up to 5% w / w minoxidil, about 0.1% w / w latanoprost, about 0.25% w / w carbomer; about 0.38% w / w TEA; about 60.0% w / w ethanol; about 4.0% w / w polysorbate 20; and about 35.27% w / w water.

[0162] A composition or solution comprising 4% w / v minoxidil, 0.08% w / v latanoprost, 50% w / v propylene glycol, 30% w / v ethanol, 3% w / v transcutol, 2% w / v oleyl alcohol, 0.5% w / v polyoxyethylene 40, and water qs to 100%.

[0163] A composition or solution comprising 4% w / v minoxidil, 0.08% w / v latanoprost, 50% w / v propylene glycol, 30% w / v ethanol, 3% w / v transcutol, 2% w / v oleyl alcohol, and water sufficient to make up 100%.

[0164] A composition comprising up to 5% w / w minoxidil, about 0.1% w / w latanoprost, about 0.25% w / w carbomer; about 0.38% w / w TEA; about 50.0% w / w ethanol; about 10% w / w diethylene glycol monoethyl ether; about 4.0% w / w polysorbate 20; and about 35.27% w / w water.

[0165] It is very difficult to formulate two insoluble drugs together, such as minoxidil and latanoprost, into a single aqueous composition. Both compounds have low solubility in water, and high concentrations of solvents and / or co-solvents are required to keep both compounds in solution, especially at very high concentrations of minoxidil, often 2-7% w / v. Furthermore, it is noted that many consumers find the typical Rogaine™ formulation unpleasant or intolerable in that it is sticky, and many users perceive it as leaving a sticky or greasy residue that reduces patient compliance. This is believed to be primarily due to the propylene glycol present at 50% w / v, which is necessary to solubilize the very insoluble substance minoxidil at high concentrations (typically 5% w / v). The addition of low concentrations of diethylene glycol monoethyl ether and oleyl alcohol has been found to make the solution less sticky and more comfortable to the touch and feel of the solution. It has also been surprisingly found that the addition of these compounds not only results in a better textured formulation, but that the addition of these compounds, especially the low concentrations of diethylene glycol monoethyl ether and oleyl alcohol, results in a more effective formulation with better hair growth. Without being bound by any theory, it is believed that the combination of diethylene glycol monoethyl ether and oleyl alcohol acts synergistically at certain concentrations to increase the skin penetration of the active ingredients (e.g., latanoprost and minoxidil), mobilize the lipids of the hair follicle and stratum corneum, and make both active ingredients more soluble in vivo, thereby making the formulation more effective by increasing the bioavailability of the active ingredients. Latanoprost is mostly lipid soluble and can penetrate into the epidermis hair follicles. However, when used in combination with certain solvents such as diethylene glycol monoethyl ether and oleyl alcohol, the formulation becomes more effective at exfoliating the inside of the pores, loosening blockages, removing impurities, and allowing the formulation to penetrate more freely. By weakening cell adhesion, the exfoliation opens up the hair follicles and pores, so to speak.This explains the increased efficacy of these formulations compared to similar formulations containing diethylene glycol monoethyl ether and oleyl alcohol.

[0166] In some embodiments, the composition comprises water, minoxidil, latanoprost in a concentration of about 0.01% w / w to about 0.4% w / w, or about 0.05-0.3% w / w, or about 0.1-0.3% w / w, minoxidil is present in an amount of about 0.5-10% w / w, or about 1-6% w / w, or about 2-5% w / w, or about 5% w / w, cetostearyl alcohol in a concentration of about 0.5% w / w to about 1% w / w, glyceryl monooleate in a concentration of about 1% w / w to about 3% w / w, preferably about 2% w / w, oleyl alcohol in a concentration of about 1% w / w to about 3% w / w, preferably about 2% w / w, and oleyl alcohol in a concentration of about 30% w / w to about 75% w / w. The surfactant may include one or more selected from the group consisting of ethanol at a concentration of about 10% w / w to about 25% w / w, propylene glycol at a concentration of about 0.5% w / w to about 2% w / w, preferably about 1% w / w, benzyl alcohol at a concentration of about 0.5% w / w to about 2% w / w, preferably about 1% w / w, carbomer at a concentration of about 0.15% w / w, triethanolamine at a concentration of about 0.16% w / w, and glycerol at a concentration of about 0.5% w / w to about 10% w / w, preferably 2% w / w.

[0167] In some embodiments, the composition comprises water, minoxidil, latanoprost in a concentration of about 0.01-0.5% w / w, or about 0.05-4% w / w, or about 0.1-0.5% w / w, minoxidil is present in an amount of about 0.5-10% w / w, or about 1-6% w / w or more, or about 2-5% w / w, or about 5% w / w, transcutol in a concentration of about 1% w / w to about 25% w / w, preferably about 10% w / w, propylene glycol in a concentration of about 1% w / w to about 25% w / w, glycerol monooleate in a concentration of about 1% w / w to about 3% w / w, preferably about 2 ... The excipients include one or more selected from the group consisting of oleyl alcohol, ethanol at a concentration of about 30% w / w to about 75% w / w, propylene glycol at a concentration of about 10% w / w to about 25% w / w, benzyl alcohol at a concentration of about 0.5% w / w to about 2% w / w, preferably about 1% w / w, carbomer at a concentration of about 0.15% w / w to about 0.2% w / w, triethanolamine at a concentration of about 0.16% w / w, and glycerin at a concentration of about 0.5% w / w to about 10% w / w, preferably 2% w / w.

[0168] Some embodiments may also include one or more additional ingredients in addition to those set forth in the paragraph above, where the one or more ingredients are selected from the group consisting of linoleic acid at a concentration of about 1% w / w to about 5% w / w, preferably 2% w / w, sodium lauryl sulfate at a concentration of 0.1% w / w to about 0.5% w / w, preferably 0.2% w / w, and docusate sodium at a concentration of 0.1% w / w to about 0.5% w / w, preferably 0.2% w / w.

[0169] In some embodiments, the composition comprises water, minoxidil, latanoprost or travoprost in a concentration of about 0.01-5% w / w, or about 0.05-4% w / w, or about 0.1-0.3% w / w, or about 0.1% w / w, 0.2% w / w, or 0.3% w / w, minoxidil is present in an amount of about 0.5-10% w / w, or about 1-6% w / w, or about 2-5% w / w, or about 5% w / w, transcutol in a concentration of about 1% w / w to about 25% w / w, preferably about 10% w / w, propylene glycol in a concentration of about 1% w / w to about 25% w / w, glycerol monooleate in a concentration of about 1% w / w to about 3% w / w, preferably about 2% w / w, and glycerol monooleate in a concentration of about 1% w / w to about 3% w / w, preferably about 2% w / w. oleic acid at a concentration of about 3% w / w, preferably about 2% w / w; linoleic acid at a concentration of about 1% w / w to about 3% w / w, preferably about 2% w / w; ethanol at a concentration of about 30% w / w to about 75% w / w; propylene glycol at a concentration of about 10% w / w to about 25% w / w; benzyl alcohol at a concentration of about 0.5% w / w to about 2% w / w, preferably about 1% w / w; carbomer at a concentration of about 0.15% w / w to about 0.2% w / w; triethanolamine at a concentration of about 0.5% w / w to about 10% w / w, preferably about 2% w / w; glycerin at a concentration of about 0.05% w / w to about 5% w / w, preferably about 1% w / w; essential oil at a concentration of about 0.5% w / w to about 5% w / w, preferably about 1% w / w; limonene at a concentration of about 0.5% w / w to about 5% w / w, preferably about 1% w / w; nerol at a concentration of about 0.5% w / w to about 5% w / w, preferably about 1% w / w; cineole at a concentration of about 0.5% w / w to about 5% w / w, preferably about 2% w / w, octyl salicylate at a concentration of about 0.5% w / w to about 5% w / w, preferably about 2% w / w, DMSO at a concentration of about 0.5% w / w to about 5% w / w, preferably about 2% w / w, DDAB at a concentration of about 0.01% w / w to about 1% w / w, preferably about 0.2% w / w, sodium taurodeoxycholate at a concentration of about 0.01% w / w to about 5% w / w, preferably about 2% w / w, and sodium taurodeoxycholate at a concentration of about 0.01% w / w to about 1% w / w, preferably about 0.The composition may include one or more selected from the group consisting of docusate sodium at a concentration of about 2% w / w, myristyl myristate at a concentration of about 1% w / w to about 30% w / w, preferably about 25% w / w, polysorbate 80 at a concentration of about 1% w / w to about 5% w / w, preferably about 2% w / w, cyclomethicone with silicone elastomer at a concentration of about 40% w / w to about 80% w / w, preferably about 73.5% w / w, Dow Silky Wax 10 at a concentration of about 1% w / w to about 20% w / w, preferably about 8% w / w, and isopropyl myristate at a concentration of about 1% w / w to about 20% w / w, preferably about 8% w / w.

[0170] In some embodiments, the composition comprises water, minoxidil or finasteride, latanoprost or travoprost, for example, latanoprost or topical finasteride at a concentration of about 0.01% w / w to about 0.5% w / w, preferably about 0.05-0.45% w / w, or about 0.075-0.4% w / w, more preferably about 0.1-0.3% w / w, and most preferably 0.1% w / w, 0.2% w / w, or 0.3% w / w. Minoxidil or finasteride is present in an amount of about 0.5-10% w / w, or about 1-6% w / w, or about 2-5% w / w, or about 5% w / w, and includes one or more selected from ethanol, e.g., at a concentration of 0.01% w / w to about 89% w / w; propylene glycol, e.g., at a concentration of 0.01% w / w to about 89% w / w; diethylene glycol monoethyl ether, e.g., at a concentration of 0.01% w / w to about 89% w / w; benzyl alcohol, e.g., at a concentration of 0.01% w / w to about 89% w / w; and one or more fatty acid and / or fatty ester excipients, e.g., at a concentration of 0.01% w / w to about 10% w / w. In some embodiments, the fatty acid can include one or more C8-mC28 fatty acids, which can be saturated, monounsaturated, or polyunsaturated. In some embodiments, the saturated fatty acid can be stearic acid. In some embodiments, the monounsaturated fatty acid can be oleic acid. In some embodiments, the polyunsaturated fatty acid can be linoleic acid. In some embodiments, the fatty acid ester can include one or more C8-C28 fatty acids, which can be saturated, monounsaturated, or polyunsaturated. In some embodiments, the saturated fatty acid ester can be glyceryl monostearate. In some embodiments, the monounsaturated fatty acid ester can be glyceryl monooleate. In some embodiments, the polyunsaturated fatty acid ester can be the ethyl ester of linoleic acid.

[0171] A preferred composition includes minoxidil or finasteride, latanoprost or travoprost, oleyl alcohol, ethanol, and propylene glycol. Latanoprost or travoprost is present in an amount of about 0.01-0.5% w / w, or about 0.05-0.4% w / w, or about 0.1-0.3% w / w, or most preferably about 0.1% w / w, 0.2% w / w, or 0.3% w / w. Minoxidil or finasteride is present in an amount of about 0.5-10% w / w, or about 1-6% w / w, or about 2-5% w / w, or about 5% w / w. Oleyl alcohol is present in an amount of about 1-10% w / w. Ethanol is present in an amount of about 50-80% w / w. Propylene glycol is present in an amount of 15-15% w / w.

[0172] Particularly preferred examples of compositions for hair growth by topical application include minoxidil or finasteride, in free form, latanoprost or travoprost, or pharma- ceutically acceptable salts thereof, wherein latanoprost or travoprost is present in an amount of about 0.1% w / w to about 4% w / w; minoxidil or finasteride is present in an amount of about 0.5-10% w / w, preferably about 1-6% w / w, more preferably about 2-5% w / w, and most preferably 5% w / w; and at least one first compound selected from fatty acids, fatty acid alcohols, and fatty acid esters, wherein the composition is formulated for topical administration to the skin.

[0173] In some embodiments, the first compound is a fatty acid. The fatty acid may be saturated or unsaturated. In some embodiments, the fatty acid is selected from the group consisting of stearic acid, oleic acid, linoleic acid, and mixtures thereof. In some embodiments, the first compound is a fatty acid ester. The fatty ester may be saturated or unsaturated. The fatty ester may be selected from the group consisting of glyceryl monostearate, glyceryl monooleate, and ethyl ester of linoleic acid. In some embodiments, the composition comprises at least two first compounds. The composition may comprise a mixture of at least one fatty acid and at least one fatty acid ester. The first compound may have 12 to 24 carbon atoms. The composition may further comprise at least one second compound selected from the group consisting of ethanol, propylene glycol, diethylene glycol monoethyl ether, and benzyl alcohol. The composition may further comprise at least one third compound selected from the group consisting of terpenes, occlusive agents, surfactants, sulfoxides, cyclic ethers, amides, amines, and dimethylaminopropionic acid derivatives. In some embodiments, the terpene is selected from the group consisting of terpinolene, limonene, nerol, and cineol. In some embodiments, the occlusive agent is selected from the group consisting of silicone, mineral oil, and water-insoluble polymer. In some embodiments, the surfactant is selected from the group consisting of polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, sodium dodecyl sulfate, sodium lauryl sulfate, DMSO, and sodium docusate. In some embodiments, the dimethylaminopropionic acid derivative is 2-dimethylaminopropionic acid dodecyl ester. The composition may include latanoprost in an amount of about 0.01% w / w to about 4% w / w. More preferably, the composition may include latanoprost in an amount of about 0.05% w / w to about 0.5% w / w. Most preferably, the composition may include latanoprost in an amount of about 0.1% w / w.In some embodiments, minoxidil is present in an amount of about 0.5-10% w / w, preferably about 1-6% w / w, more preferably about 2-5% w / w, and most preferably 5% w / w. The composition is in the form of one selected from the group consisting of a solution, a gel, an ointment, a foam, a film, a liniment, a cream, a shampoo, a lotion, a paste, a jelly, a spray, and an aerosol. In some embodiments, the composition is packaged in a kit with an applicator for application to the skin.

[0174] The compositions and formulations of the invention can be prepared using the following general methods.

[0175] The non-aqueous components (e.g., latanoprost, travoprost, minoxidil, finasteride, ethanol, glycol) are mixed in a beaker and stirred using a propeller-type overhead mixer until the solution is clear. Water is added to the non-aqueous mixture, followed by the thickener. Once the thickener is dispersed, a base is added to neutralize the polymer and thicken the solution into a gel or other desired composition. For example, ethanol, minoxidil, and latanoprost are combined in a beaker and stirred using a propeller-type overhead mixer until the solution is clear. This mixture is then added to the non-aqueous components to form a non-aqueous mixture. In a separate container, the thickener is dispersed in water to form an aqueous mixture, which is then added to the non-aqueous mixture. The non-aqueous mixture and the aqueous mixture are mixed, and a base is added to neutralize the polymer and thicken the solution into a gel.

[0176] The compositions of the present invention can be prepared using the following general method.

[0177] Ethyl alcohol is weighed into a suitable media jar equipped with a mixer, then bimatoprost, latanoprost or travoprost is added to the ethyl alcohol and stirred at a moderate speed until dissolved. In a separate mixing tank, minoxidil, diethylene glycol monoethyl ether, oleyl alcohol, propylene glycol, and optionally POE40 are added and mixed until the solvent is dispersed. Then, the ethyl alcohol / (bimatoprost, latanoprost or travoprost) solution is added to the non-aqueous solution and mixed until the ingredients are uniformly mixed (about 5 minutes of mixing). For gels, the carbomer thickener, previously dispersed in water, is added to the above mixture and mixed until fully dispersed, and after dispersion, a base is added to thicken the solution into a gel.

[0178] A topical 0.05% w / w latanoprost / 5% w / w minoxidil cream is prepared as follows: Medium viscosity carboxymethylcellulose and spermaceti are dissolved together at a temperature of 70-80°C. Propylene glycol, polysorbate 80, latanoprost, minoxidil, and transcutol are added sequentially, maintaining the temperature at 75-80°C. A preservative (e.g., methylparaben) is added slowly to the carboxymethylcellulose and spermaceti melt with continued stirring. Addition continues for at least 30 minutes, with further stirring, until the temperature drops to 40-45°C. Finally, sufficient water is added to bring the final weight to 1000 g, and the formulation is stirred to maintain homogeneity until it cools and solidifies.

[0179] Once formulated, the formulations can be applied continuously, daily, monthly, or yearly.

[0180] Example I A 42-year-old Caucasian male with alopecia areata is given 2 ml / day of Formulation VIII twice daily, as a small patch of hair loss approximately the size of a quarter, and applied to the area of ​​scalp where hair loss is evident. Thirty days after application, the patient's scalp hair follicles become less infiltrated with T cells, and the patient's hair begins to grow in the patch.

[0181] Example II A 32-year-old male with androgenetic alopecia applies Formulation VI at least once daily (1 ml / day) to the balding areas of the scalp. After 45 days of continued application, the underlying autoimmune reaction causing hair loss decreases in severity and hair begins to regrow on the patient's scalp in the balding areas.

[0182] Example III A 43-year-old woman suffering from telogen effluvium applies a formulation of Formulation XVII to her scalp twice a day. After 35 days of daily application, the patient's hair begins to regrow on her scalp in the areas where she suffers from hair loss. The patient experiences no side effects from applying Formulation XVII to her scalp.

[0183] Example IV A 62-year-old woman with thinning eyebrows applies Formulation XXII to her eyebrows with an applicator once daily. Within 45 to 90 days, the patient notices increased eyebrow growth, with eyebrows that are longer, thicker, and darker than when Formulation XXII is not applied.

[0184] Example V A 53-year-old male shaved an area of ​​approximately 1 inch by 1 inch on the underside of both forearms. All hair above the epidermis was removed. The patient applied approximately 0.5 ml of Formulation XI once daily to the left forearm while the right forearm was left untreated. After 20 days, the hair on the right forearm was fewer, shorter, thinner and less thick compared to the hair on the left forearm which was more numerous, longer, darker and thicker. After 30 days, the hair on the right forearm was fewer, shorter, thinner and less thick compared to the hair on the left forearm which was more numerous, longer, darker and thicker. The patient experienced no side effects.

[0185] Example VI A 53-year-old male shaved a 4" x 2" area above both knees to remove all above-epidermal hair and applied Formulation XI formulation once daily to the shaved area above the left knee and 5% ROGAINE™ solution once daily to the area above the right knee. After 20 days, hair growth in the shaved area above the left knee was slightly greater (more hair, longer and thicker) than in the shaved area above the right knee. After 30 days, hair in the area above the left knee was longer, darker and thicker than the area above the right knee. After 45 days, hair on the left knee was significantly longer, larger in diameter, darker and more numerous than the area above the left knee treated with 5% ROGAINE™ solution. The patient experienced no side effects.

[0186] Example VII A 54 year old Caucasian male shaved three 1 inch by 1 inch square areas (areas #1-#3) on his thighs, two side by side and one below. All hair above the epidermis was removed. Areas #1 and #2 were treated and area #3 was the control with no formulation applied. The patient applied Formulation XX at approximately 1 / 3 ml per day to area #1 and Formulation XVIII at 1 / 3 ml per day to area #2. Area #3 was untreated and served as the control. After 30 days, both area 1 and area 2 showed significant hair growth, with hair longer, darker, and thicker compared to the control (area #3). No significant differences were observed between area #1 and area #2 in terms of hair length, darkness, or thickness after 30 days. However, areas #1 and #2 had significantly more hair growth than area #3. After 60 days, there was significant hair growth in both areas #1 and #2, with no significant difference between the two areas in terms of length, thickness, or density, although the hair in area #1 was approximately 10% longer than area #2. No difference was observed between areas #1 and #2 in terms of density or thickness.

[0187] Example VIII A 53-year-old white male with balding on the crown, roughly corresponding to stage IV on the Hamilton-Norwood scale, applied Formulation XX once daily at approximately 1 ml / day to the crown and front of the head. On the 75th day, the patient was switched to Formulation XVIII. After 90 days, the patient noticed significant regrowth on the crown, with approximately 40-50% of the bald areas being reduced to areas with new hair growth (see Figure 5). Most of the new hair growth was darker hair of the patient's natural hair color, and the overall ratio of dark to grey hair was significantly increased in the treated areas. The new hair was longer, darker, and thicker compared to vellus hair in the balding area on the crown. The patient also noticed significant regrowth on the front of the head where the formulation was applied. The patient experienced no side effects.

[0188] Example IX A 54-year-old male shaved three areas of his thighs above the knee, approximately 2 inches by 3 inches, with close shaving below the surface of the epidermis: two areas on the left thigh, several inches apart, and an area on the right thigh. The subject left area #1 untreated, applying no formulation to area #2, applying generic 5% minoxidil-Rogaine™ solution at approximately 0.3 ml / day, and applying a minoxidil / latanoprost formulation (Formulation XVIII) at approximately 0.3 ml / day to area #3. After approximately 15 days, the untreated area showed some hair growth, but areas #2 and #3 showed more significant hair growth compared to area #1. Areas #2 and #3 were very similar in number and length of hair, but the hair in area #3 appeared to be slightly darker and thicker. At day 30, all three areas showed regrowth, but areas #2 and #3 had significantly more hairs that were longer, darker, and larger in diameter compared to area #1. At day 30, the number of hairs in areas #2 and #3 was similar, but the hairs in area #3 appeared slightly darker and thicker than area #2. At day 45, area 1 showed regrowth, with about half of the hairs regrown, but significantly less than areas #2 and #3. At day 45, area #3 had significantly more hairs than area #2, and were longer, darker, and thicker compared to area #2.

[0189] Example X A 54 year old male patient shaved three areas (approximately 1 inch by 1 inch) of his thighs to remove all hair from the area above the dermis. The patient applied Formulation XXXV to area #1 once daily, an identical formulation (4% w / v minoxidil solution) to area #2 except that it did not contain latanoprost, and an identical formulation to Formulation XXXV (0.08% w / v latanoprost solution) to area #3 except that it did not contain minoxidil. After 15 days, area #1 had more hairs, thicker and darker hairs growing above the epidermis than areas #2 and #3, and hair growth began sooner, resulting in greater regrowth and faster hair growth compared to areas #2 and #3. At day 15, there was little difference in hair growth between areas #2 and #3 in terms of number of hairs, hair length, hair thickness, or hair density. By day 30, area #1 showed more regrowth compared to areas #2 and #3, and more hair, longer, thicker, and darker compared to area #3. Area #1 had earlier onset of hair growth and greater hair growth compared to areas #2 and #3. The patient experienced no side effects.

[0190] Example XI A 46-year-old Caucasian female with balding and thinning hair along the vertex, corresponding to stage I on the Ludwig scale, applied Formulation XX to her head twice daily, approximately 2 ml / day, along the vertex for approximately 30 days. Around day 31, the patient began applying Formulation XVIII to her head once daily (1 ml / day), along the vertex. By day 45, the patient's vertex had significantly filled in with newly grown hair of the original hair color, and the ratio of dark hair to grey hair had greatly increased, with more dark hair of the original hair color compared to the grey hair (see Figure 4). The newly grown individual hairs were also thicker compared to the existing hair. The patient experienced no side effects.

[0191] Example XII A 54 year old patient shaved three areas (approximately 1 inch by 1 inch) on her arm to remove all hair from the surface of the epidermis. Once daily, the patient applied Formulation XVIII to area #1, a solution identical to Formulation XVIII except that it did not contain latanoprost to area #2, and a solution identical to Formulation XVIII except that it did not contain minoxidil to area #3. After 15 days, area #1 had started to regrow hair earlier and had more hair growth (hair growing more above the epidermis, longer, darker, thicker) than areas #2 and #3. By day 30, this trend continued with area #1 showing significant regrowth compared to areas #2 and #3. By day 45, area #1 had almost complete regrowth compared to areas #2 or #3. Area #3 had slightly darker and thicker hair compared to area #2, but the hair that grew in area #2 was slightly longer than area #3. However, area #1 had longer, darker and thicker hair than area #3, and longer hair than area #2, and more growth.

[0192] Example XIII A 54 year old patient had hair removed by shaving three areas (approximately 1 inch by 1 inch) on the upper thighs to remove all hair from these areas. The patient applied Formulation XVIII to area #1, Formulation XXXV to area #2, and no formulation to area #3 once daily. After 15 days, both areas #1 and #2 had significant regrowth compared to area #3. The hair in areas #1 and #2 was longer, darker, thicker, and more numerous compared to area #3. By day 30, both areas #1 and #2 had significant regrowth compared to area #3, with more hair, longer, thicker, and darker compared to area #3. By day 45, both areas #1 and #2 had almost completely grown back, but area #3 had significantly less hair growth than areas #1 and #2. There was no difference in hair growth between areas #1 and #2. The patient experienced no side effects.

[0193] Example XIV A 54 year old patient had three areas (approximately 1 inch by 1 inch), two on the right calf and one on the left calf, removed by shaving to remove all hair above the epidermis in these areas. The patient applied Formulation XVIII to area #1 of the left calf, no formulation to area #2 of the lower calf, and Formulation XIX to area #3 once daily. After 15 days, areas #1 and #3 both showed significant regrowth compared to area #2, and area #3 showed more hair growth (more, longer, thicker hair) than area #2. By day 30, areas #1 and #3 both showed significant regrowth compared to area #2, and more, longer, thicker, and darker hair compared to area #3. By day 30, area #3 showed significant hair growth, with approximately 20% more hair, longer and darker than area #2. The patient experienced no side effects.

[0194] Example XV A 62 year old Caucasian female had thinning hair along the crown. The patient began application of Formulation XX twice daily at approximately 2 ml per day by spraying 1 ml along the crown twice daily. On day 27, the patient switched to application of Formulation XVIII once daily by spraying approximately 1 ml of the formulation on the crown each day. The patient sprayed Formulation XVIII for 30 days. On day 73, the patient's hair had grown back significantly along the crown and, although it was not yet completely filled in, hair had grown on the crown and was thick and full.

[0195] Example XVI A 59-year-old Caucasian female with thinning, long hair on the crown began application of Formulation XX twice daily, approximately 2 ml per day, by spraying 1 ml twice daily on balding areas of the scalp. After 31 days, the patient switched to application of Formulation XVIII once daily, by spraying approximately 1 ml of the formulation daily. The patient sprayed Formulation XVIII for 78 days. On day 108, the patient's hair had significantly regrown along the crown.

[0196] Example XVII A 64-year-old Caucasian female with hair loss along her forehead and temples was initiated on twice-daily application of Formulation XX by spraying 1 ml twice daily on the areas of hair loss on the scalp. On day 30, the patient switched to application of Formulation XVIII once daily by spraying approximately 1 ml of the formulation daily. By day 106, the patient had significant growth of new hair along her forehead and temples that was darker and thicker than the existing hair in those areas prior to treatment.

[0197] Example XVIII A 26 year old Caucasian male with slight balding on the crown began application of Formulation XX twice daily at approximately 2 ml per day by spraying 1 ml twice daily on the areas of hair loss on the scalp. On day 29, the patient switched to application of Formulation XVIII once daily by spraying approximately 1 ml of the formulation daily. On day 99, the patient noted increased hair growth on the crown, with the balding areas barely visible.

[0198] Example XIX A 44-year-old white male had significant baldness on the vertex, roughly corresponding to Norwood-Hamilton classification IV. The patient began application of Formulation XX twice daily, approximately 2 ml per day, by spraying 1 ml twice daily on the areas of hair loss on the scalp. On day 29, the patient switched to application of Formulation XVIII once daily, by spraying approximately 1 ml of the formulation daily. On day 118, the patient's hair had grown significantly on the vertex, and the hair was darker and thicker than in the same area prior to treatment. By day 108, approximately half of the vertex had grown terminal hair where previously there was no hair or vellus hair.

[0199] Example XX A 59-year-old female patient with thinning along the crown, roughly equivalent to I-2 or I-3 on the Ludwig scale, began application of Formulation XX twice daily at approximately 2 ml per day by spraying 1 ml twice daily onto the areas of hair loss on the scalp. On day 30, the patient switched to application of Formulation XX twice daily at approximately 2 ml per day by spraying 1 ml twice daily onto the areas of hair loss on the scalp. On day 99, the crown was darker and fuller, with much of the crown covered with new hair that was thicker than the hair in the same area prior to treatment.

Claims

1. A composition for use in treating hair loss comprising about 0.05-0.5% w / v of latanoprost and latanoprost acid, and 0.01-0.1% w / v of cyclosporine.

2. 10. The composition of claim 1 further comprising oleyl alcohol or ethanol.

3. 3. The composition of claim 2, further comprising a member selected from the group consisting of polyethylene glycol or propylene glycol.

4. 4. The composition of claim 3, further comprising: acetic acid; and a member selected from the group consisting of polysorbate 60 and polyoxyethylene lauryl alcohol.

5. 4. The composition of claim 3, further comprising: acetic acid; and a member selected from the group consisting of polysorbate 60 and polyoxyethylene lauryl alcohol.

6. 3. The composition of claim 2, further comprising ethanol; and at least one selected from the group consisting of propylene glycol and polysorbate 80.

7. The composition of claim 9, wherein the ethanol is present at a concentration of about 25-30% w / v.

8. The composition of claim 10 , wherein the composition further comprises oleyl alcohol.

9. The composition of claim 3 further comprising diethylene glycol monoethyl ether.

10. A composition for use in hair loss comprising about 0.05-0.3% w / v latanoprost and 2-7% minoxidil.

11. 11. The composition of claim 10, further comprising: ethanol, propylene glycol, water; and at least one selected from the group consisting of benzyl alcohol, oleic acid, and polyoxyethylene lauryl alcohol.

12. 11. The composition of claim 10, wherein the composition comprises ethanol, propylene glycol, polysorbate, water; and at least one selected from the group consisting of oleyl alcohol, oleic acid, and benzyl alcohol.

13. The composition of claim 12, wherein the composition comprises propylene glycol, ethanol, and about 0.1-0.5% w / v acetic acid.

14. 14. The composition of claim 13, wherein the composition comprises 50% w / v propylene glycol and 30% w / v ethanol.

15. 11. The composition of claim 10, wherein the composition comprises at least two selected from the group consisting of ethanol, propylene glycol, polyoxyethylene 80, and propanediol; and at least one selected from the group consisting of acetic acid, oleic acid, and oleyl alcohol.

16. 11. The composition of claim 10, further comprising about 0.1% w / v latanoprost and about 5% w / v minoxidil.

17. 17. The composition of claim 16, further comprising propylene glycol, ethanol, and diethylene glycol monoethyl ether.

18. 18. The composition of claim 17, wherein the composition comprises 50% w / v propylene glycol, 25% w / v ethanol, 2-5% w / v diethylene glycol monoethyl ether, and water.

19. 11. The composition of claim 10, consisting of 0.08% w / v latanoprost, 4% w / v minoxidil, 2% w / v oleyl alcohol, 50% w / v propylene glycol, 30% w / v ethanol, water, and 3% w / v diethylene glycol monoethyl ether.

20. 11. The composition of claim 10, consisting of 0.1% w / v latanoprost, 5% w / v minoxidil, 3% w / v oleic acid, 50% w / v propylene glycol, 30% w / v ethanol, water, and 2% w / v diethylene glycol monoethyl ether.

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