Minoxidil Adjuvant Therapies

A method for increasing the efficacy of topical minoxidil, the method comprising:

• applying an effective amount of a nuclear receptor agonist topically to a portion of the skin that is suffering from alopecia and contains at least one hair follicle;
• and
• applying topical minoxidil to said portion of the skin.

A method for converting androgenetic alopecia patients who are non-responders to minoxidil into responders, the method comprising:

• applying an effective amount of a nuclear receptor agonist topically to a portion of the skin that is suffering from alopecia and contains at least one hair follicle;
• and
• applying topical minoxidil to said portion of the skin.

A method for improving hair growth of subjects using topical minoxidil, the method comprising:

• applying an effective amount of a nuclear receptor agonist topically to a portion of the skin that is suffering from alopecia and contains at least one hair follicle;
• and
• applying topical minoxidil to said portion of the skin.

A method for accelerating hair growth of subjects using topical minoxidil, the method comprising:

• applying an effective amount of a nuclear receptor agonist topically to a portion of the skin that is suffering from alopecia and contains at least one hair follicle;
• and
• applying topical minoxidil to said portion of the skin.

A method for increasing the metabolism of minoxidil within hair follicles of human subjects, the method comprising:

• applying an effective amount of a nuclear receptor agonist topically to a portion of the skin that is suffering from alopecia and contains at least one hair follicle;
• and
• applying topical minoxidil to said portion of the skin.

A method for increasing the bioavailable minoxidil sulfate within hair follicles of human subjects, the method comprising:

• applying an effective amount of a nuclear receptor agonist topically to a portion of the skin that is suffering from alopecia and contains at least one hair follicle;
• and
• applying topical minoxidil to said portion of the skin.

A method to enhance the appearance of minoxidil treatment of human hair loss, the method comprising:

• applying an effective amount of a nuclear receptor agonist topically to a portion of the skin that is suffering from alopecia and contains at least one hair follicle;
• and
• applying topical minoxidil to said portion of the skin.

A method for increasing the sulfonating capacity of a hair follicle cell and/or keratinocyte cell, the method comprising applying a composition including an effective amount of a nuclear receptor agonist topically to a portion of skin that includes at least one hair follicle cell and/or keratinocyte cell.

A method for inducing sulfotransferase in a hair follicle, the method comprising applying a composition including an effective amount of a nuclear receptor agonist topically to a portion of skin that includes at least one hair follicle cell and/or keratinocyte cell.

A method for inducing PAPSS in a hair follicle cell and/or keratinocyte cell, the method comprising applying a composition including an effective amount of a nuclear receptor agonist topically to a portion of skin that includes at least one hair follicle cell and/or keratinocyte cell.

A method for increasing the concentration of PAPS in a hair follicle cell and/or keratinocyte cell, the method comprising applying a composition including an effective amount of a nuclear receptor agonist topically to a portion of skin that includes at least one hair follicle cell and/or keratinocyte cell.

A composition for inducing expression of sulfotransferase, comprising an inducer of sulfotransferase and a carrier, the composition formulated as any one or combination of a shampoo, a foam, ointment, spray, solution, gel, slow release capsule, oral tablet, dry shampoo, hair styling product, exfoliating agent.

A composition for inducing expression of sulfotransferase, comprising an inducer of sulfotransferase and a carrier, the composition formulated as a cosmetic product.

A composition for inducing a SULT1A1 enzyme, a SULT1A3 enzyme, and/or a SULT1E1 enzyme in a human hair follicle cell and/or a keratinocyte cell, comprising an agonist of the AhR nuclear receptor.

A kit for inducing expression of sulfotransferase, comprising an applicator and an inducer of sulfotransferase.

17-47. (canceled)

A method for increasing the concentration of PAPS in a hair follicle, the method comprising applying a composition including an effective amount of a nuclear receptor agonist topically to a portion of skin containing at least one hair follicle.

A method for increasing the concentration of PAPS in a hair follicle, the method comprising:

• applying a composition including an effective amount of a nuclear receptor agonist topically to a portion of skin containing at least one hair follicle;
• and;
• applying an effective amount of a prodrug to the skin, the prodrug configured to be activated via sulfonation.

A method for increasing the concentration of PAPS in a hair follicle, the method comprising:

• applying a composition including an effective amount of a nuclear receptor agonist topically to a portion of skin containing at least one hair follicle;
• and;
• applying topical minoxidil to said portion of the skin.

A composition for up-regulating the sulfonating capacity of hair bearing skin, hair follicles, and/or keratinocyte cells;

• increasing minoxidil response;
• converting minoxidil non-responders to responders;
• and/or accelerating minoxidil response, comprising any one or combination of an activator of the Nrf2 nuclear factor, an inducer of the Nrf2 nuclear factor, agent that disassociates Nrf2 from Keap1, a direct or indirect inhibitor of Keap1, an agent that down-regulates Keap1, an agent that is an inducer of or increases the activity of p300/CBP, and an agent that increases the state of oxidative stress of a cell.

A method for up-regulating the sulfonating capacity of hair bearing skin, hair follicles, and/or keratinocyte cells, the method comprising:

• administering a composition including an activator of the Nrf2 nuclear factor to a hair follicle cell and/or a keratinocyte cell.

A method for up-regulating the sulfonating capacity of hair bearing skin, hair follicles, and/or keratinocyte cells, the method comprising:

• administering a composition including an inducer of the Nrf2 nuclear factor to a hair follicle cell and/or a keratinocyte cell.

A method of up-regulating the sulfonating capacity of hair bearing skin, hair follicles, and/or keratinocyte cells, the method comprising:

• administration of a composition including an agent that disassociates Nrf2 from Keap1 to a hair follicle cell and/or a keratinocyte cell.

A method for up-regulating the sulfonating capacity of hair bearing skin, hair follicles, and/or keratinocyte cells, the method comprising:

• administration of a composition including a direct or indirect inhibitor of Keap1 to a hair follicle cell and/or a keratinocyte cell.

A method for up-regulating the sulfonating capacity of hair bearing skin, hair follicles, and/or keratinocyte cells, the method comprising administration of a composition including an agent that down-regulates Keap1 expression to a hair follicle cell and/or a keratinocyte cell.

A method for up-regulating the sulfonating capacity of hair bearing skin, hair follicles, and/or keratinocyte cells, the method comprising administration of a composition including an inducer of the activity of, or an agent that increases the activity of, p300/CBP to a hair follicle cell and/or a keratinocyte cell.

A method for up-regulating the sulfonating capacity of hair bearing skin, hair follicles, and/or keratinocyte cells, the method comprising a composition including an agent that increases the state of oxidative stress of a cell, wherein the composition is applied to a hair follicle cell and/or a keratinocyte cell.

The methods of 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, or 93, wherein the administering or applying includes doing so:

• topically in the form of a shampoo, solution, foam, lotion, gel, spray, or gas;
• and/or
• orally, sublingually, by injection, as an implant, or by using a bacteria that secrets the agent.

A method of up-regulating the sulfonating capacity of hair bearing skin, hair follicles, and/or keratinocyte cells, increasing minoxidil response, converting minoxidil non-responders to responders, and/or accelerating minoxidil response by applying or administering the compositions of 13, 14, 15, 70, 71, 72, 73, or 76.

98-101. (canceled)

The method according to claim 125, wherein the topical solution containing the alkalinizing agent further comprises any one or a combination of:

• a retinoid X receptor (RXR) agonist, a retinoic acid receptor (RAR) agonist, an agonist of another nuclear receptor (NR) in an RXR−NR heterodimer, a CAR nuclear receptor agonist, a PXR nuclear receptor agonist, a PPARα nuclear receptor agonist, a Nrf2 nuclear receptor agonist, a GR nuclear receptor agonist, a FXR nuclear receptor agonist, and a LXRα nuclear receptor agonist, a VDR nuclear receptor agonist, a retinoid X receptor (RXR) agonist, and a retinoic acid receptor (RAR) agonist.

The method according to claim 125, wherein the method further comprises increasing hair growth, accelerating hair growth, arresting hair loss, accelerating minoxidil response, and/or up-regulating the sulfonating capacity of hair bearing skin, hair follicles, and/or keratinocyte cells.

A method of improving minoxidil response, converting minoxidil non-responders to responders, increasing hair growth, accelerating hair growth, arresting hair loss, accelerating minoxidil response, and/or up-regulating the sulfonating capacity of hair bearing skin, hair follicles, and/or keratinocyte cells, the method comprising:

• applying or administering a composition comprising any one or combination of:
• an activator of the Nrf2 nuclear factor, an inducer of the Nrf2 nuclear factor, agent that disassociates Nrf2 from Keap1, a direct or indirect inhibitor of Keap1, an agent that down-regulates Keap1, an agent that is an inducer of or increases the activity of p300/CBP, and an agent that increases the state of oxidative stress of a cell.

A method of improving minoxidil response, converting minoxidil non-responders to responders, increasing hair growth, accelerating hair growth, arresting hair loss, accelerating minoxidil response, and/or up-regulating the sulfonating capacity of hair bearing skin, hair follicles, and/or keratinocyte cells, the method comprising:

• applying or administering a composition or a buffer having alkaline pH within a range from pH 7.4 to 11.

The method according to claim 125, wherein the method further comprises up-regulating the sulfonating capacity of hair bearing skin, hair follicles, and/or keratinocyte cells.

The method according to claim 125, wherein the alkalinizing agent includes any one or combination of sodium bicarbonate, sodium citrate, potassium citrate, calcium carbonate, sodium lactate, and calcium acetate, carbicarb, and sodium citrate/citric acid.

The method according to claim 125, wherein the topical solution containing the alkalinizing agent further includes a penetration enhancer.

The method according to claim 125, further comprising:

• increasing transdermal penetration via a transdermal penetration device.

The method according to claim 125, wherein the method further comprises alkalizing the intracellular pH of cells is alkalinized by application of a topical proton pump agonist and/or by application of a topical proton pump agonist.

A method for treating alopecia, the method comprising:

• administering a topical solution containing an alkalinizing agent that will increase sulfotransferase activity and increase the sulfonation capacity of the outer root sheath of hair follicles;
• and
• applying a topical or oral dosage form of minoxidil with, prior or after application of the topical solution containing the alkalinizing agent.

126-133. (canceled)

135-136. (canceled)

A composition for treating alopecia, comprising:

• a topical solution containing an alkalinizing agent to increase sulfotransferase activity and increases the sulfonating capacity of the outer root sheath of hair follicles;
• wherein the alkalinizing agent includes any one or combination of sodium bicarbonate, sodium citrate, potassium citrate, calcium carbonate, sodium lactate, and calcium acetate, carbicarb, and sodium citrate/citric acid.

A method of improving minoxidil response, the method comprising:

• administering a topical solution containing an alkalinizing agent that will increase sulfotransferase activity and increases the sulfonating capacity of the outer root sheath of hair follicles;
• and
• applying a topical or oral dosage form of minoxidil with, prior or after application of the topical solution containing the alkalinizing agent.

A method for increasing sulfotrasnferase activity, the method comprising administering a topical solution containing an alkalinizing agent that will increase sulfotransferase activity and increases the sulfonating capacity of the outer root sheath of hair follicles.