Compositions and methods for the treatment of alopecia

Abstract

The embodiments relate to compositions and methods for treating hair loss, which may include treating alopecia, by application of a composition comprising an alkalizing agent and / or a sulfotransferase enzyme. The composition may be formulated to be an orally administered composition. In some embodiments, the composition is used to increase the response of minoxidil.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This patent application is related to and claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 490,939, filed March 17, 2023, U.S. Provisional Patent Application No. 63 / 489,499, filed March 10, 2023, U.S. Provisional Patent Application No. 63 / 488,045, filed March 2, 2023, and U.S. Provisional Patent Application No. 63 / 485,333, filed February 16, 2023, the contents of each of which are incorporated by reference in their entirety.

[0002] The embodiments may relate to compositions and methods for the treatment of hair loss, which may include the treatment of alopecia, by application of a composition comprising an alkalizing agent and / or a sulfotransferase enzyme. The composition may be formulated to be an orally administered composition. In some embodiments, the composition is used to increase the response of minoxidil. [Background technology]

[0003] A drug that can be used to treat alopecia is minoxidil. In order for minoxidil to exert its hair growth properties, it must be activated by the SULT1A1 (minoxidil sulfotransferase) enzyme. The enzyme is expressed in both the scalp and the liver. Different people express different amounts of the enzyme or have genetic variations that affect the activity of the enzyme. Therefore, the response to minoxidil treatment may vary from person to person and depends on the SULT1A1 enzyme.

[0004] Previous studies have demonstrated that alkalizing the intracellular pH of keratinocytes induces the expression of SULT1A1 enzyme in the scalp, which subsequently improves, increases, or enhances the minoxidil response. Therefore, topical alkalizing agents have been developed as minoxidil boosters. However, this topical minoxidil booster has only met with limited success because it is difficult to comply with twice-daily application, tends to change hair color, and tends to leave sodium bicarbonate residues on hair. Furthermore, minoxidil exerts its hair regenerative effects primarily through the dermal papilla and dermal sheath cells, which are difficult to treat with topical cosmetic products.

[0005] The dermal papilla has a rich blood supply, which may be easier to regulate with orally administered compositions (e.g., drugs, ingredients, supplements, etc.). Thus, an oral composition that increases SULT1A1 enzyme in the dermal papilla, dermal sheath, or outer root sheath of the hair follicle, and subsequently increases the response to minoxidil (which may be oral or topological) for the treatment of hair loss, would be advantageous.

[0006] Prior to this disclosure, it was not known whether oral forms of alkalizing agents could induce SULT1A1 enzyme in scalp tissue. Furthermore, the adverse effects of oral forms of alkalizing agents were not known, as it is known that patients who chronically use large amounts of oral alkalizing agents can develop metabolic alkalosis and other disorders. The inventors conducted studies to test these effects, the results of which are the basis of the innovations disclosed herein. Summary of the Invention

[0007] The embodiments relate to compositions and methods for treating hair loss, which may include treating alopecia, by application of a composition comprising an alkalizing agent and / or a sulfotransferase enzyme. The composition may be formulated to be an orally administered composition. In some embodiments, the composition is used to increase the response of minoxidil.

[0008] An exemplary embodiment may relate to a composition for improving, increasing, or enhancing the minoxidil response of a subject suffering from alopecia. The composition may include an alkalizing agent and a sulfotransferase enzyme.

[0009] In some embodiments, the composition may be formulated as a topological composition, an oral composition, an injectable composition, or a transdermal composition, and / or the composition may be formulated as a drug, a nutritional supplement, or a cosmetic.

[0010] In some embodiments, the composition may include minoxidil.

[0011] In some embodiments, the composition may include minoxidil. The composition may be formulated as a topological composition, an oral composition, an injectable composition, or a transdermal composition.

[0012] In some embodiments, the alkalinizing agent may include one or more of bicarbonate, citrate, a loop diuretic, MOPS, BES, TES, HEPES, DIPSO, TAPSO, acetamidoglycine, POPSO, HEPPSO, HEPPS, tricine, tris(tromethamine), glycineamide, glycylglycine, or bicine, TAPS.

[0013] In some embodiments, the sulfotransferase enzyme can include a human sulfotransferase enzyme and / or a non-human sulfotransferase enzyme.

[0014] In some embodiments, the sulfotransferase enzyme can include one or more of carbohydrate sulfotransferase, galactose-3-O-sulfotransferase, heparan sulfate 2-O-sulfotransferase, heparan sulfate 3-O-sulfotransferase, heparan sulfate 6-O-sulfotransferase, N-deacetylase / N-sulfotransferase, tyrosylprotein sulfotransferase, uronyl-2-sulfotransferase, estrone sulfotransferase, chondroitin 4-sulfotransferase, SULT1A1, SULT1A2, SULT1A3, SULT1A4, SULT1B1, SULT1C2, SULT1C3, SULT1C4, SULT1D1P, SULT1E1, SULT2A1, SULT2B1, SULT4A1, or SULT6B1.

[0015] In some embodiments, the composition comprises a natural level or extract of minoxidil sulfotransferase enzyme, a natural level or extract of phenol sulfotransferase enzyme, and / or a natural level or extract of any of the following: Populus trichocarpa, Populus x canescens, Salix sp., Arabidopsis thaliana, silver poplar (Populus alba), Simon's poplar (Populus simonii), S. purpurea, P. tremuloides, I. polycarpa, P. nigra, Oryza sativa, Salicaceae family, poplar (Populus sp.), Idesia polycarpa ... polycarpa-Japanese orange cherry, potato (Solanum tuberosum), cabbage (Brassica rapa), Populus trichocarpa (Black Cottonwood), Salix Sp. (Willow Tree), cotton (Gossypium), Olea europaea L., Brassica napus, Apium graveolens, Brassica oleracea, Saccharina japonica, Solanum tuberosum, and / or black cottonwood. Natural levels or extracts of minoxidil sulfotransferase enzyme, phenol sulfotransferase enzyme, and / or sulfotransferase enzyme are present in amounts ranging from 1% to 100% by weight.

[0016] In some embodiments, the sulfotransferase enzyme can include OeST1.

[0017] Exemplary embodiments may relate to a method for improving, increasing, or enhancing minoxidil response in a subject suffering from alopecia. The method may include administering to a subject suffering from alopecia a composition comprising an alkalizing agent and a sulfotransferase enzyme.

[0018] In some embodiments, administering the composition may include administering the composition topologically, orally, by injection, or transdermally, and / or administering the composition as a drug, nutritional supplement, or cosmetic.

[0019] In some embodiments, the methods may include administering the composition before, during, and / or after administration of minoxidil.

[0020] In some embodiments, the composition may include minoxidil.

[0021] In some embodiments, the alkalinizing agent may include one or more of bicarbonate, citrate, a loop diuretic, MOPS, BES, TES, HEPES, DIPSO, TAPSO, acetamidoglycine, POPSO, HEPPSO, HEPPS, tricine, tris(tromethamine), glycineamide, glycylglycine, or bicine, TAPS.

[0022] In some embodiments, the sulfotransferase enzyme can include a human sulfotransferase enzyme and / or a non-human sulfotransferase enzyme.

[0023] In some embodiments, the sulfotransferase enzyme can include one or more of carbohydrate sulfotransferase, galactose-3-O-sulfotransferase, heparan sulfate 2-O-sulfotransferase, heparan sulfate 3-O-sulfotransferase, heparan sulfate 6-O-sulfotransferase, N-deacetylase / N-sulfotransferase, tyrosylprotein sulfotransferase, uronyl-2-sulfotransferase, estrone sulfotransferase, chondroitin 4-sulfotransferase, SULT1A1, SULT1A2, SULT1A3, SULT1A4, SULT1B1, SULT1C2, SULT1C3, SULT1C4, SULT1D1P, SULT1E1, SULT2A1, SULT2B1, SULT4A1, or SULT6B1.

[0024] In some embodiments, the composition comprises a natural level or extract of minoxidil sulfotransferase enzyme, a natural level or extract of phenol sulfotransferase enzyme, and / or a natural level or extract of any of the following: Populus trichocarpa, Populus x canescens, Salix sp., Arabidopsis thaliana, silver poplar (Populus alba), Simon's poplar (Populus simonii), S. purpurea, P. tremuloides, I. polycarpa, P. nigra, Oryza sativa, Salicaceae family, poplar (Populus sp.), Idesia polycarpa ... polycarpa--contains natural levels or extracts of sulfotransferase enzyme derived from Japanese orange cherry, potato (Solanum tuberosum), cabbage (Brassica rapa), Populus trichocarpa (Black Cottonwood), Salix Sp. (Willow Tree), cotton (Gossypium), Olea europaea L., Brassica napus, Apium graveolens, Brassica oleracea, Saccharina japonica, Solanum tuberosum, and / or black cottonwood. Natural levels or extracts of minoxidil sulfotransferase enzyme, phenol sulfotransferase enzyme, and / or sulfotransferase enzyme are present in amounts ranging from 1% to 100% by weight.

[0025] In some embodiments, the sulfotransferase enzyme can include OeST1.

[0026] In some embodiments, the methods may include quantifying the activity of SULT1A1 in dermal papilla cells and / or dermal sheath of the subject.

[0027] In some embodiments, the methods may include determining a therapeutic treatment using a composition based on a quantitative measurement of SULT1A1 activity in dermal papilla cells and / or dermal sheath of the subject.

[0028] An exemplary embodiment may relate to a composition for increasing the activity of a sulfotransferase enzyme in the scalp and / or liver of a subject suffering from alopecia. The composition may include an alkalizing agent and a sulfotransferase enzyme.

[0029] Exemplary embodiments may relate to a method for increasing activity of a sulfotransferase enzyme in the scalp and / or liver of a subject suffering from alopecia. The method may include administering to a subject suffering from alopecia a composition comprising an alkalizing agent and a sulfotransferase enzyme.

[0030] As used herein, the term "prevent" or "prevention" and other derivatives of these terms, when used in relation to alopecia, e.g. androgenetic alopecia, may refer to a reduction in the likelihood of alopecia in an individual receiving a given treatment, compared to a similar individual at risk of alopecia but not receiving treatment. Thus, the terms "prevent" and "prevention" may encompass a treatment that results in a lesser degree of alopecia than would otherwise be expected for a given individual. The effectiveness of preventing alopecia may be established, for example, by a controlled study in which a subject is administered a treatment (e.g., topically, orally, transdermally, etc.) and another subject is administered a placebo. Under these circumstances, a treatment may be considered effective in preventing alopecia if subjects treated with the treatment experience less hair loss over time, e.g., at least 5% less, at least 10% less, at least 15% less, at least 20% less, at least 25% less, at least 30% less, at least 35% less, at least 40% less, at least 45% less, at least 50% less, or more.

[0031] As used herein, the term "subject" refers to a human or animal in need of therapeutic treatment of androgenetic alopecia or any other form of alopecia.

[0032] As used herein, the terms "treat", "treatment" or "treating" refer to therapeutic treatment, where the purpose is to reverse, alleviate, improve, inhibit, slow down or stop the progression or severity of a disease or condition, such as androgenetic alopecia or other forms of alopecia. The term "treating" may include alleviating or relieving at least one adverse effect or symptom of a disease or condition. A treatment may generally be considered to be "effective" if one or more symptoms are alleviated. Alternatively, a treatment may be "effective" if the progression of a disease is slowed or stopped. That is, "treatment" may include not only the improvement of symptoms, but also the cessation of symptoms, or at least the slowing down of the progression or worsening of symptoms, compared to what would be expected in the absence of treatment. Beneficial or desired clinical results may include, but are not limited to, alleviation of one or more symptoms, reduction in the extent of disease, stabilization (e.g., not worsening) state of disease, delay or slowing of disease progression, improvement or alleviation of disease state, remission (whether partial or total), and / or reduction in mortality.For example, treatment may be considered effective if the extent or amount of hair loss is reduced, or the progression of hair loss is slowed or stopped.The term "treatment" of a disease may also include providing relief from symptoms or side effects of the disease (including palliative treatment).

[0033] The effectiveness of a treatment for treating or preventing alopecia can be determined by monitoring the density of hair in a given area of ​​the subject's body, for example, a given area of ​​the scalp.For example, if the hair loss rate is reduced, for example, by 10% or more, after treatment, the treatment can be considered to be effective in preventing alopecia.Similarly, if the hair density remains the same, the treatment can be considered to be effective in preventing alopecia.If the hair density is increased, for example, by 5% or more, for example, by 10% or more, after treatment, the treatment can also be considered to be effective in treating and / or preventing androgenetic alopecia.The effectiveness of a treatment for treating or preventing androgenetic alopecia can be determined by monitoring overall photography.For example, a patient or a professional can utilize before and after overall photography to evaluate treatment response.

[0034] As used herein, the term "alopecia" refers to all forms of hair loss in both males and females humans or animals, including but not limited to traction alopecia, androgenetic alopecia, male pattern baldness, female pattern baldness, alopecia areata, alopecia universalis, telogen effluvium, chemotherapy-induced alopecia, hair shedding, eyebrow hair loss, beard hair loss, thinning of hair, etc. The term allows for the presence of factors that do not substantially affect the basic and novel or functional property(s) of the embodiment.

[0035] To utilize the compositions described herein, a subject may apply an effective amount of the composition to the scalp. The term "effective amount," as used herein, may be an amount effective to prevent or treat hair loss.

[0036] Further features, aspects, objects, advantages and possible applications of the present invention will become apparent from a study of the illustrative embodiments and examples described below in conjunction with the drawings and the appended claims. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0037] The following is a description of exemplary embodiments presently contemplated for carrying out the present invention. This description is not to be taken in a limiting sense, but is made merely for the purpose of illustrating the general principles and features of the present invention. The scope of the present invention is not limited by this description.

[0038] Alopecia, especially androgenetic alopecia, is a progressive shrinkage of hair follicles on the female scalp. It may be characterized by diffuse thinning of the crown area of ​​the scalp while the frontal hairline remains intact. Alopecia is generally hereditary, but may also be hormone-dependent, which may affect its development. Oral and / or topical minoxidil is a US FDA-approved drug for the treatment of alopecia. Its use may moderately increase hair regrowth. The risk of adverse events from such use of minoxidil is low. However, irritant dermatitis, allergic contact dermatitis, and hirsutism have been reported.

[0039] The embodiments may relate to compositions and methods for treating alopecia. For example, the compositions may be administered to induce SULT1A1 enzyme. The compositions may be formulated as topological compositions, oral compositions, injectable compositions, transdermal compositions, etc. In some embodiments, the compositions may be formulated and / or administered to induce scalp SULT1A1 enzyme. In some embodiments, the compositions may be formulated and / or administered to increase minoxidil response in subjects suffering from alopecia. As described herein, inducing SULT1A1 enzyme (which improves, increases, or enhances minoxidil response) may be achieved by a composition comprising an alkalizing agent and / or a sulfotransferase enzyme (e.g., an enzyme supplement extracted from a plant, bacteria, animal, fungus, etc.).

[0040] Although the embodiments disclosed herein may specifically discuss the treatment of forms of alopecia (e.g., androgenetic alopecia), it is understood that the disclosed compositions and methods may be applicable to the treatment of other forms of alopecia as well.

[0041] The composition may be administered with or without a minoxidil treatment. The minoxidil treatment may be a treatment that includes administration of a composition that contains minoxidil, where the minoxidil composition is a topological composition, an oral composition, an injectable composition, a transdermal composition, etc. If the composition is administered with a minoxidil treatment, the composition may be administered before the minoxidil treatment (e.g., before administering the minoxidil composition), during the minoxidil treatment (e.g., while the minoxidil composition is being administered), and / or after the minoxidil treatment (e.g., after administering the minoxidil composition). This may include administering the composition and minoxidil simultaneously, each being administered on the same day but at different times, etc. In some embodiments, the composition (e.g., a composition having an alkalizing agent and / or a sulfotransferase enzyme) may include minoxidil. In some embodiments, the composition does not include minoxidil, but the composition and minoxidil are administered together as part of the treatment.

[0042] The minoxidil composition or the minoxidil component of the composition can be minoxidil or its pharma- ceutically acceptable salt.Minoxidil is a prodrug that is converted to its active form, minoxidil sulfate, by sulfotransferase enzymes present in the outer root sheath (ORS) of hair follicles (see Buhl AE, Waldon DJ, Baker CA, Johnson GA.Minoxidil sulfate is the active metabolite that stimulates hair follicles.J Invest Dermatol.November 1990;95(5):553-7).It has been demonstrated that the activity of sulfotransferase in ORS determines clinical response to minoxidil (Goren A, Castano JA, McCoy J, Bermudez F, Lotti T.Novel enzymatic assay predicts minoxidil response in the treatment of androgenetic alopecia.Dermatol Ther.2014;27(3):171-3). Concentrations of minoxidil are contemplated to be from about 2 to about 20% by weight, although other concentrations may be used.

[0043] Minoxidil induces (upregulates) the expression of sulfotransferase in hairy skin, hair follicles, and / or keratinocyte cells, such as the scalp. This may include upregulating sulfonation capacity. Compositions and method embodiments disclosed herein may also induce the expression of sulfotransferase. However, composition embodiments may also improve, increase, or enhance a subject's response to minoxidil in this regard, for example, the composition may increase the rate, amount, duration, effect, etc. of upregulating the expression of sulfotransferase in hairy skin, hair follicles, and / or keratinocyte cells. For example, methods and composition embodiments disclosed herein may be used to increase the metabolism of minoxidil in hair follicles of subjects suffering from a form of alopecia, which may result in increased bioavailable minoxidil sulfate.

[0044] Any treatment disclosed herein may be administered at a predetermined frequency. This predetermined frequency may be once every 24 hours, twice every 24 hours, three times every 24 hours, four times every 24 hours, etc. For example, the composition may be formulated to be administered twice every 24 hours. Again, the treatment may include the use of the composition alone or the use of the composition with a separate administration of minoxidil. Thus, the treatment may include administering minoxidil at a predetermined frequency. The administration frequency of the composition may be the same as or different from the administration frequency of minoxidil. In some embodiments, the composition itself includes minoxidil.

[0045] Any of the compositions disclosed herein may be oral formulations, topological formulations, injectable formulations, transdermal formulations, and the like. Any of the compositions or oral formulations disclosed herein may be in tablet form, pill form, capsule form, gel form, liquid form, spray form, and the like. Any of the oral formulations or any one or combination of the components of the oral formulations may be dry, wet, lipolyzed, and the like. Any of the topological formulations disclosed herein may be aerosols, liquid solutions, gels, and the like for application as lotions, ointments, shampoos (wet or dry), foams, or mousses. These may be vehicles applied, for example, to the scalp. Any of the topological formulations or any one or combination of the components of the topological formulations may be dry, wet, lipolyzed, and the like. Any of the injectable formulations disclosed herein may be in intradermal injection form. Any of the injectable formulations or any one or combination of the components of the injectable formulations may be dry, wet, lipolyzed, and the like. Any of the transdermal formulations disclosed herein may be in the form of a controlled release vehicle, such as a patch. Any of the transdermal formulations or any one or combination of the components of a transdermal formulation can be dry, moist, lipoylated, or the like.

[0046] It is contemplated that the compositions disclosed herein are formulated as cosmetics (e.g., lotions, ointments, shampoos (wet or dry), foams, mousses, or aerosols for application as hair sprays, liquid solutions, gels, and the like. However, any of the compositions disclosed herein may be formulated in the form of a drug, nutritional supplement, cosmetic product, and the like.

[0047] Depending on the use and implementation, any topological formulation may include a solvent. The solvent may or may not be volatile. The solvent may be an alcohol, such as a polyhydric alcohol, benzyl alcohol, propylene glycol, water, etc. Any topological formulation may include starch (modified or unmodified starch). It is contemplated that the starch acts as a sebum absorbent. Non-limiting examples of suitable unmodified starch materials may include corn starch, potato starch, tapioca starch, rice starch, wheat starch, cassaya starch, etc. Modified starch materials are starches that have been derivatized or altered by processes known to those skilled in the art, such as esterification, etherification, oxidation, acid hydrolysis, crosslinking, enzymatic conversion, etc. Non-limiting examples of suitable modified starch materials include aluminum starch octenyl succinate, sodium starch octenyl succinate, calcium starch octenyl succinate, distarch phosphate, hydroxyethyl starch phosphate, hydroxypropyl starch phosphate, sodium carboxymethyl starch, and sodium starch glycolate. Any topological formulation may include oil absorbing agents and / or suspending agents, such as silica, cellulose, chalk, talc, fuller's earth, etc. Some embodiments may include other sebum absorbing agents, such as clay materials, which may be stearalkonium hectorite, stearalkonium bentonite, quaternium-18 bentonite, quaternium-18 hectorite, etc. The use of sebum absorbing agents, oil absorbing agents, and suspending agents may promote more pleasing aesthetics for the user when minoxidil is administered by reducing or eliminating the oily and / or unaesthetic appearance of hair.

[0048] Any topological formulation may include an embodiment of the composition formulated as a dry shampoo. By "dry shampoo" is meant that the composition is formulated to include a carrier material that evaporates by being a volatile liquid, and a powder that remains, the powder including starch. An exemplary starch may be aluminum starch octenyl succinate. Examples of suitable carrier materials that are volatile liquids may be lower alcohols, including but not limited to ethanol or isopropanol, volatile silicone compounds such as polydimethylsiloxane (e.g., having a viscosity of less than about 5 cSt at 25°C), cyclomethicone, cyclohexanesiloxane, decamethyltetrasiloxane, octamethyltrisiloxane, decamethylpentasiloxane, decamethylcyclopentasiloxane, octamethylcyclotetrasiloxane, trimethylsilylamodimethicone, phenyltrimethicone, hexamethydisiloxane, dimethylsiloxane / methylalkylsiloxane, etc. Other carrier materials known to those skilled in the art may also be used. Use of a dry shampoo may be preferred in some cases, as it helps keep the minoxidil from washing away, and embodiments of the composition are intended for use in conjunction with minoxidil treatment. Minoxidil itself may be formulated as a dry shampoo.

[0049] Any topological formulation may include an embodiment of the composition formulated as a spray, aerosol, etc. In this regard, any topological formulation may be a composition that includes a propellant (e.g., butane, isobutane, propane, A-46 (isobutane and propane), liquefied petroleum gas (e.g., propane), dimethyl ether, methyl ethyl ether, trichlorofluoromethane, dichlorodifluoromethane, dichlorotetrafluoroethane, monochlorodifluoromethane, trichlorotrifluoroethanepropane, carbon dioxide, nitrous oxide, 1,1,1,2,-tetrafluoroethane, 1,1,2,3,3,3-heptafluoropropane, etc.). The propellant may condense to a liquid state in the aerosol container at ambient temperature. In some embodiments, the propellant may have a lower specific gravity compared to the remainder of the composition, thus facilitating the ejection of the composition from the container (e.g., via a dip tube) compared to releasing the propellant.

[0050] Depending on the use and implementation, any formulation may be a composition that includes a carrier. For example, any formulation may be encapsulated in a pharma- ceutically acceptable carrier. A pharma- ceutically acceptable carrier may encapsulate the composition in liposomes, microbeads, and the like. In addition to being "pharmaceutically acceptable," each carrier may be "acceptable" in the sense of being compatible with other components of the formulation. A carrier may be used to temporarily encapsulate a composition until a condition that causes its release is met. In some embodiments, the carrier may be formulated to controllably release the composition, for example, in a time-dependent manner.

[0051] Depending on the use and implementation, any formulation may be a composition that includes a penetration enhancer, which may enhance the penetration of the composition and / or minoxidil into the skin (e.g., the scalp). Suitable penetration enhancers include alcohols (e.g., dodecanol, oleyl alcohol, and the like); amines (e.g., isopropylamine, diisopropylamine, triethylamine, triethanolamine, diisopropanolamine, ethylenediamine, and the like); carboxylic acids (e.g., oleic acid, linoleic acid, linolenic acid, and the like); esters (e.g., dibutyl sebacate, dibutyl phthalate, butyl benzoate, ethyl caprate, and the like); azone, N-methylpyrrolidone; bile salts; urea; glycols (e.g., diethylene glycol and tetraethylene glycol); fatty acids (e.g., lauric acid, myristic acid, and capric acid); fatty esters; fatty ethers; cyclodextrins; occlusive agents; surfactants; dimethylaminopropionic acid derivatives; terpenes; sulfoxides; cyclic ethers; amides; sulfoxides (e.g., dimethyl sulfoxide, DMSO, decyl metal sulfoxide, and the like); azones (e.g., 1-dodecylazacycloheptan-2-one, laurocapran, laurocapram; pyrrolidones (e.g., 2-pyrrolidone, 2P,N-methylpyrrolidone, N-methyl-2-pyrrolidone, NMP, 1-propyl-3-dodecyl-2-pyrrolidone, 1-butyl-3-dodecyl-2-pyrrolidone, etc.); surfactants (e.g., polyoxyethylene-2-oleyl ether, polyoxyethylene-2-stearyl ether, sodium dodecyl sulfate, SDS, sodium lauryl sulfate, SLS); oxazolidinones (e.g., 4-decyloxazolidinone, 2-one), urea, 2-(1-nonyl)-1,3-dioxolane; terpenes; polyester nanosponges; liposomes; phospholipids; cyclopentadecalactone; pentadecalactone; SNAC; sodium salcaprodinate N-[8-(2-hydroxybenzoyl)amino]caprylate; CNAC; 5-CNAC; 8-(N-2-hydroxy-5-chloro-benzyl)-amino-caprylic acid; sodium caprate; glyceryl triglyceride; peptides, and the like.

[0052] Depending on the use and implementation, any formulation may be a composition that includes an exfoliant to promote exfoliation of the surface of the skin (e.g., the surface of the scalp) and / or to promote absorption of the composition and / or components of the composition. Examples of exfoliants include: (1) inorganic and / or metallic particles, such as boron nitride in body-centered cubic form (Borazon®); aluminosilicates (e.g., nepheline); zircon; mixed oxides of aluminum, such as emery; zinc oxide; aluminum oxides, such as alumina or corundum; titanium oxide; titanium oxide-coated mica; carbides, especially silicon carbide (carborundum); or other metal oxides; metals and metal alloys, such as iron shot, steel shot, especially perlite; silicates, such as glass, quartz, sand, or vermiculite; calcium carbonate (e.g., Bora Bora sand or Rose de Brinox); Brignoles (sand) or magnesium carbonate; sodium chloride; pumice; amorphous silica; diamond; ceramics, (2) organic particles, for example fruit stones, especially apricot stones, for example Scrubami® apricots; wood cellulose, for example crushed bamboo stalks; coconut shells, for example coconut exfoliators; polyamides, in particular nylon-6; sugar; plastic microbeads, for example polyethylene or polypropylene; crushed walnuts; crushed apricot seeds; crushed shells, (3) mixed particles in association with organic and inorganic compounds, particles coated with the above compounds, etc.

[0053] Depending on the use and implementation, any formulation may be a composition that is incorporated into a controlled release vehicle (e.g., an encapsulation body) that allows the composition's ingredients or drugs to be controllably released to the dermis of the skin (e.g., the scalp). The capsule or vehicle that encapsulates the ingredients or drugs may include, but is not limited to, liposomes, non-ionic liposomes, niosomes, novasome I, erythromycin-Zn complexes, microspheres, nanoparticles, solid lipid nanoparticles, and nanoemulsions.

[0054] The embodiments of the treatment may include the use of one or more compositions. The compositions may include one or more alkalizing agents. For example, the treatment may include administering composition-1 and composition-2, where composition-1 has an alkalizing agent that is different from the alkalizing agent used in composition-2. Furthermore, one composition may have the same alkalizing agent(s) as another composition, but the concentration or amount of the alkalizing agent may differ. Furthermore, one composition may be administered before administration of minoxidil, while the other may be administered after administration of minoxidil. As described herein, some compositions may be formulated with penetrating agents, carrier materials, etc. The compositions used in the treatment may also differ based on the inclusion of these ingredients. The number of compositions used, the number of alkalizing agents used, when they are administered, and whether / when they are used with minoxidil may be determined based on the desired effect and / or design criteria.

[0055] Embodiments of the composition may include one or more alkalizing agents. Any alkalizing agent may include a bicarbonate or a combination of bicarbonates. Examples of bicarbonates may include sodium bicarbonate, potassium bicarbonate, magnesium bicarbonate, calcium bicarbonate, and the like. Other alkalizing agents may include a citrate or a combination of citrates. Examples of citrates may include potassium citrate, sodium citrate, citric acid, and the like. Other alkalizing agents may include a loop diuretic or a combination of loop diuretics. Examples of loop diuretics may include bumetanide (Bumex), ethacrynic acid (Edecrin), furosemide (Lasix), torasemide (Soaanz), and the like. Other alkalizing agents may include MOPS, BES, TES, HEPES, DIPSO, TAPSO, acetamidoglycine, POPSO, HEPPSO, HEPPS, tricine, tris(tromethamine), glycinamide, glycylglycine, bicine, TAPS, and the like.

[0056] Embodiments of the composition may include one or more sulfotransferase enzymes. Any sulfotransferase enzyme may be human or non-human. Examples of sulfotransferase enzymes include carbohydrate sulfotransferases (e.g., CHST1, CHST2, CHST3, CHST4, CHST5, CHST6, CHST7, CHST8, CHST9, CHST10, CHST11, CHST12, CHST13, CHST14, etc.), galactose-3-O-sulfotransferases (e.g., GAL3ST1, GAL3ST2, GAL3ST3, GAL3ST4, etc.), heparan sulfate 2-O-sulfotransferases (e.g., HS2ST1), heparan sulfate 3-O-sulfotransferases (e.g., HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, HS3ST4, HS3ST5, HS3ST6, etc.), heparan sulfate 6-O-sulfotransferases (e.g., HS3ST1, HS3ST2, HS3ST3A1, HS3ST3B1, HS3ST4, HS3ST5, HS3ST6, etc.), and the like. The enzyme may be an O-sulfotransferase (e.g., HS6ST1, HS6ST2, HS6ST3, etc.), an N-deacetylase / N-sulfotransferase (e.g., NDST1, NDST2, NDST3, NDST4, etc.), a tyrosylprotein sulfotransferase (e.g., TPST1, TPST2, etc.), an uronyl-2-sulfotransferase, an estrone sulfotransferase, a chondroitin 4-sulfotransferase, SULT1A1, SULT1A2, SULT1A3, SULT1A4, SULT1B1, SULT1C2, SULT1C3, SULT1C4, SULT1D1P, SULT1E1, SULT2A1, SULT2B1, SULT4A1, SULT6B1, etc.

[0057] In an exemplary embodiment, the sulfotransferase enzyme can be a phenol sulfotransferase extract (eg, a phenol sulfotransferase extracted from a plant that produces a sulfated salicinoid). Examples of plants that produce sulfated salicinoids include Populus trichocarpa, Populus x canescens, Salix sp., Arabidopsis thaliana, silver poplar (Populus alba), Simon's poplar (Populus simonii), S. purpurea, P. tremuloides, I. polycarpa, P. nigra, Oryza sativa, Salicaceae family, poplar (Populus sp.), Idesia polycarpa - Japanese orange cherry, cherry), potato (Solanum tuberosum), cabbage (Brassica rapa), Populus trichocarpa (Black Cottonwood), Salix Sp. (Willow Tree), cotton (Gossypium), Olea europaea L., Brassica napus, Apium graveolens, Brassica oleracea, Saccharina japonica, Solanum tuberosum, Black Cottonwood, and the like.

[0058] In another exemplary embodiment, the sulfotransferase enzyme can be OeST1 (Olive Tree SULT1A1). OeST1 is a sulfotransferase plant supplement that can be extracted from the olive tree. The human homolog of OeST1 is SULT1A1, which belongs to the cytosolic sulfotransferase family. Like OeST1, SULT1A1 catalyzes the transfer of a sulfonate group from PAPS to the hydroxyl group of various phenolic substrates, including flavonoids, catecholamines, and xenobiotics. The expression level of OeST1 can vary depending on the tissue, developmental stage, and environmental conditions of the olive plant. However, studies have shown that OeST1 is most abundant in olive fruits and leaves. In olive fruits, OeST1 is expressed at high levels during the early stages of development and ripening, when flavonoids and other phenolic compounds are synthesized and accumulated. The expression of OeST1 in olive fruits is controlled by various factors, including light, temperature, and water availability, which can affect the synthesis and accumulation of flavonoids and other phenolics in the fruit. In olive leaves, OeST1 is also expressed at high levels, especially in young and actively growing leaves. Expression of OeST1 in olive leaves is controlled by various factors, including light, temperature, and biotic and abiotic stresses, which may affect the biosynthesis and accumulation of flavonoids and other phenolics in leaves. Overall, the expression of OeST1 in olive fruits and leaves suggests that sulfated flavonoids and other phenolics may play an important role in olive plant physiology and adaptation and may contribute to the health benefits of olive fruits and leaves. There are studies that have measured the concentration of OeST1 (Olive Tree SULT1A1) in olive leaves. For example, a study published in 2014 in the Journal of Agricultural and Food Chemistry used quantitative real-time polymerase chain reaction (qPCR) analysis to measure the expression levels of various sulfotransferase genes, including OeST1, in olive leaves.The study found that OeST1 is expressed at a relatively high level in olive leaves compared to other sulfotransferase genes. Another study published in the same journal in 2018 used a radiolabeled assay to measure the activity of sulfotransferases, including OeST1, in olive leaf extracts. The study found that sulfotransferase activity in olive leaf extracts was mainly due to OeST1, and that the activity was higher in young compared to older leaves. These studies suggest that OeST1 is present in significant amounts in olive leaves and is likely involved in the sulfation of various phenolic compounds in this plant tissue. However, it is important to note that the concentration of OeST1 or any other enzyme in olive leaves may vary depending on several factors, such as cultivar, growing conditions, and leaf age. Therefore, further studies may be needed to determine the concentration of OeST1 in different types of olive leaves and under different growing conditions.

[0059] It is understood that any plant that produces flavonoids or has minoxidil sulfotransferase enzyme, phenol sulfotransferase enzyme, and / or sulfotransferase enzyme can be used. Any method and composition can use the natural concentration of enzyme found in the plant or its extract. Furthermore, any enzyme can be from an animal.

[0060] Table 1 shows the results of the minoxidil response assay for 8 uL of each plant ingredient diluted in a 100 uL reaction tube incubated overnight. A result >0.4 means it has activity against minoxidil. [Table 1]

[0061] Exemplary Formulations

[0062] An exemplary formulation may include a composition comprising an alkalizing agent (1,000 mg sodium bicarbonate) and a sulfotransferase enzyme (300 mg Olea Europea leaf extract).

[0063] Another exemplary formulation may include a composition comprising an alkalizing agent (375 mg sodium bicarbonate + 375 mg potassium bicarbonate + 150 mg calcium (as calcium citrate / malate) + 100 mg magnesium (as magnesium aspartate)) and a sulfotransferase enzyme (500 mg minoxidil sulfotransferase enzyme complex (Olea europaea L leaf, Brassica napus, Brassica oleracea, Saccharina japonica, Oryza sativa, Brassica Oleracea). It is contemplated that this formulation would be administered twice daily.

[0064] Embodiments of the composition may include an alkalizing agent in an amount ranging from 1% to 100% by weight and / or a sulfotransferase enzyme in an amount ranging from 1% to 100% by weight, which may induce the SULT1A1 enzyme in the scalp and subsequently increase the minoxidil response.

[0065] Method for quantifying SULT1A1 activity

[0066] The embodiment may further relate to a method for determining or quantifying the activity of SULT1A1 in dermal papilla cells and / or dermal sheath. This may be performed to determine whether and to what extent a subject will benefit from the treatments disclosed herein, particularly treatments for increasing, improving, or enhancing minoxidil response. The method may include, for example, using the results of sulfotransferase activity from a colorimetric assay to predict minoxidil response, for example, SULT1A1 activity may be used as an indicator of minoxidil response.

[0067] The method may include obtaining a sample from a subject (e.g., plucked hair with hair follicles, a biopsy sample, etc.). A colorimetric assay may be performed to measure sulfotransferase enzyme activity in the sample, thereby generating an activity value indicative of the level of sulfotransferase activity in the sample. The assay may include placing the sample in a reaction mixture including an indicator dye and minoxidil. During the assay, the indicator dye undergoes a color change that correlates with the amount of sulfotransferase activity level in the sample, and the activity value correlates with the color change. The activity value may be compared to one or more standardized activity values. Each standardized activity value may represent the degree of minoxidil response expected for hair regrowth or retention at a particular dosage and form of minoxidil.

[0068] As a non-limiting example, the sulfotransferase can be SULT1A1. A sample (e.g., 1 to n hair follicles) can be placed in a reaction mixture containing about 50 mM potassium phosphate buffer (pH approximately 6.5), about 5 mM magnesium chloride, about 20 μM adenosine 3',5'-diphosphate (PAP) or adenosine 3'-phosphate,5'-phosphosulfate (PAPS), about 5 mM p-nitrophenyl sulfate, and about 0.1 mM minoxidil. The reaction can be performed in a transparent container with a lid or other opening into which the hair follicle sample can be inserted. The total amount of liquid in the assay container can be about 0.2 ml. It is understood that as part of the reaction, in the presence of minoxidil sulfotransferase activity, p-nitrophenyl sulfate is converted to p-nitrophenol for colorimetry. The reaction can be mixed and then incubated at 37° C. for approximately 4 to 16 hours, depending on the number of hair follicles used in the assay. Mixing can be by any mixing means known in the art (e.g., mechanical mixing, magnetic mixing, acoustic mixing, etc.). The more hair follicles there are, the shorter the incubation time can be, e.g., an assay using one hair follicle can be incubated for approximately 16 hours, while an assay using two hair follicles can be incubated for approximately 4 hours.

[0069] After incubation of the sample, the reaction may be stopped by adding about 1 / 10 volume of approximately 0.25 M Tris-HCl buffer (pH 8.7) and mixed. The pH may be varied (e.g., between 8.5 and 9.0). The absorbance at about 405 nm may then be read on a spectrophotometer or compared to a reference color card having a range of intensities corresponding to minoxidil sulfotransferase activity. Subjects with relatively high levels of sulfotransferase activity have relatively strong colorimetric readings, resulting in relatively significant color changes. In comparison, subjects with relatively low levels of sulfotransferase activity have relatively weak colorimetric readings, correspondingly with relatively minimal color changes. Subjects with a strong colorimetric assay response are expected to respond to minoxidil in terms of hair regrowth or retention. Subjects with a weak colorimetric assay response are expected to respond poorly to minoxidil.

[0070] It is understood that this minoxidil response test can be used to determine whether, when, and to what extent a subject can benefit from any treatment disclosed herein.For example, a subject with low or poor minoxidil response based on the diagnostic test can use an embodiment of the composition to improve, increase, or enhance the minoxidil response.Furthermore, the diagnostic test result can be used to determine the optimal treatment regime.This can include modifying the concentration and / or frequency of treatment (which can include administration of the composition and / or minoxidil) to match the subject's minoxidil sulfotransferase activity.

[0071] example

[0072] The following examples provide results of testing embodiments of the compositions and methods disclosed herein.

[0073] Example 1

[0074] In a study of 40 subjects, 20 subjects used 6% TRIS (oral) in combination with 0.05% hSULT1A1 topical and 20 subjects used a vehicle solution without TRIS or hS1ULT1A1. In the TRIS group, 70% of subjects had increased SULT1A1 activity compared to 0% in the vehicle group.

[0075] Example 2

[0076] In a study of 60 subjects, 30 subjects used 10% sodium bicarbonate (oral) combined with 0.05% hSULT1A1 topical and 30 subjects used vehicle solution. In the sodium bicarbonate and hSULT1A1 group, 68% of subjects had increased SULT1A1 activity compared to 0% in the vehicle group.

[0077] Example 3

[0078] In a study of 24 subjects, 12 subjects used 500 mg sodium bicarbonate (oral) daily in combination with 0.5 mg hSULT1A1 and 12 subjects used placebo. In the sodium bicarbonate and hSULT1A1 group, 50% of subjects had increased SULT1A1 activity compared to 0% in the vehicle group.

[0079] Example 4

[0080] In a study of 28 subjects, 14 subjects used 500 mg of sodium bicarbonate (oral) daily in combination with OeST1 (olive tree SULT1A1 extract) and 14 subjects used a placebo. In the sodium bicarbonate and OeST1 (olive tree SULT1A1) group, 60% of subjects had increased SULT1A1 activity compared to 5% in the vehicle group.

[0081] Example 5

[0082] One dose-ranging study included 20 subjects. They found that oral sodium bicarbonate, calcium bicarbonate, or magnesium bicarbonate at doses less than 500 mg qd induced scalp SULT1A1 enzyme. Doses greater than 1,000 mg qd induced scalp SULT1A1 enzyme in 18% of subjects, while doses greater than 2,000 mg qd induced scalp SULT1A1 enzyme in more than 30% of subjects.

[0083] Example 6

[0084] Sixty subjects were randomly assigned to receive an alkalizing agent (375 mg sodium bicarbonate + 375 mg potassium bicarbonate + 150 mg calcium (as calcium citrate / malate) + 100 mg magnesium (as magnesium aspartate)) and sulfotransferase enzymes (500 mg minoxidil sulfotransferase enzyme complex (Olea europaea L leaves, Brassica napus, Brassica oleracea, Saccharina japonica, Oryza sativa, Brassica When using an oral pill formulation containing Oleracea, 30 subjects used the pill formula and 30 subjects used a placebo pill. In the group using the pill formula, 77% of subjects had increased scalp SULT1A1 activity compared to 5% in the group using the placebo pill.

[0085] Example 7

[0086] A study was conducted using the following formulations in Table 2, with two pills given twice daily for seven days. Hair was plucked at baseline and on day 7. Minoxidil sulfotransferase activity in hair was measured using the Minoxidil Response Test. In Table 3 (Results), OD indicates activity. The increase across the cohort was 720%. [Table 2] [Table 3]

[0087] It should be understood that the disclosure of a range of values ​​is a disclosure of all numerical values ​​within that range, including the endpoints. It should also be understood that while some components, features, and / or configurations may be described in connection with only one particular embodiment, these same components, features, and / or configurations may be applied or used in many other embodiments and should be considered applicable to other embodiments unless otherwise stated or unless such components, features, and / or configurations are technically impossible to use in other embodiments. Thus, the components, features, and / or configurations of the various embodiments may be combined together in any manner, and such combinations are expressly contemplated and disclosed by this description.

[0088] In view of the above teachings of the present disclosure, it will be apparent to those skilled in the art that many modifications and variations of the described examples and embodiments are possible. The disclosed examples and embodiments are presented for illustrative purposes only. Other alternative embodiments may include some or all of the features disclosed herein. Accordingly, it is intended to cover all such modifications and alternative embodiments that may fall within the true scope of the present invention and should be given its full breadth.

[0089] It is to be understood that modifications to the embodiments disclosed herein may be made to satisfy a particular set of design criteria. Thus, while certain exemplary embodiments of the compositions and methods of using and making the same disclosed herein have been described and illustrated, it is to be clearly understood that the invention is not limited thereto and may be otherwise embodied and variously practiced within the scope of the following claims.

Claims

1. 1. A composition for improving, increasing, or enhancing minoxidil response in a subject suffering from alopecia, comprising: Alkalizing Agents and Sulfotransferase Enzymes A composition comprising:

2. the composition is formulated as a topological composition, an oral composition, an injectable composition, or a transdermal composition; and / or The composition is formulated as a drug, a nutritional supplement, or a cosmetic. The composition of claim 1.

3. Contains minoxidil, The composition of claim 1.

4. The composition comprises minoxidil, The composition is formulated as a topological composition, an oral composition, an injectable composition, or a transdermal composition; The composition of claim 1.

5. the alkalinizing agent comprises one or more of bicarbonate, citrate, loop diuretics, MOPS, BES, TES, HEPES, DIPSO, TAPSO, acetamidoglycine, POPSO, HEPPSO, HEPPS, tricine, tris(tromethamine), glycineamide, glycylglycine, or bicine, TAPS; The composition of claim 1.

6. The sulfotransferase enzyme comprises a human sulfotransferase enzyme and / or a non-human sulfotransferase enzyme. The composition of claim 1.

7. the sulfotransferase enzyme comprises one or more of carbohydrate sulfotransferase, galactose-3-O-sulfotransferase, heparan sulfate 2-O-sulfotransferase, heparan sulfate 3-O-sulfotransferase, heparan sulfate 6-O-sulfotransferase, N-deacetylase / N-sulfotransferase, tyrosylprotein sulfotransferase, uronyl-2-sulfotransferase, estrone sulfotransferase, chondroitin 4-sulfotransferase, SULT1A1, SULT1A2, SULT1A3, SULT1A4, SULT1B1, SULT1C2, SULT1C3, SULT1C4, SULT1D1P, SULT1E1, SULT2A1, SULT2B1, SULT4A1, or SULT6B1; The composition of claim 1.

8. The composition further comprises a natural level or extract of minoxidil sulfotransferase enzyme, a natural level or extract of phenol sulfotransferase enzyme, and / or a natural level or extract of phenol sulfotransferase enzyme from Populus trichocarpa, Populus x canescens, Salix sp., Arabidopsis thaliana, silver poplar (Populus alba), Simon poplar (Populus simonii), S. purpurea, P. tremuloides, I. polycarpa, P. nigra, Oryza sativa, Salicaceae family, Poplar (Populus sp.), Idesia polycarpa - Japanese orange cherry, Potato (Solanum tuberosum), Cabbage (Brassica rapa), Populus trichocarpa (Black Cottonwood), Salix sp. (Willow Tree), Cotton (Gossypium), Olea europaea L. europaea L), Brassica napus, Apium graveolens, Brassica oleracea, Saccharina japonica, Solanum tuberosum, and / or black cottonwood; the minoxidil sulfotransferase enzyme, phenol sulfotransferase enzyme, and / or natural levels or extracts of sulfotransferase enzyme are present in an amount ranging from 1% to 100% by weight; The composition of claim 1.

9. the sulfotransferase enzyme comprises OeST1; The composition of claim 1.

10. 1. A method of improving, increasing, or enhancing minoxidil response in a subject suffering from alopecia, comprising: administering to a subject suffering from alopecia a composition comprising an alkalizing agent and a sulfotransferase enzyme; A method comprising:

11. administering the composition comprises administering the composition topically, orally, by injection, or transdermally; and / or Administering the composition as a drug, nutritional supplement, or cosmetic. The method of claim 10, comprising:

12. administering said composition before, during, and / or after administration of minoxidil. The method of claim 10 further comprising:

13. The composition comprises minoxidil. The method of claim 10.

14. the alkalinizing agent comprises one or more of bicarbonate, citrate, loop diuretics, MOPS, BES, TES, HEPES, DIPSO, TAPSO, acetamidoglycine, POPSO, HEPPSO, HEPPS, tricine, tris(tromethamine), glycineamide, glycylglycine, or bicine, TAPS; The method of claim 10.

15. The sulfotransferase enzyme comprises a human sulfotransferase enzyme and / or a non-human sulfotransferase enzyme. The method of claim 10.

16. the sulfotransferase enzyme comprises one or more of carbohydrate sulfotransferase, galactose-3-O-sulfotransferase, heparan sulfate 2-O-sulfotransferase, heparan sulfate 3-O-sulfotransferase, heparan sulfate 6-O-sulfotransferase, N-deacetylase / N-sulfotransferase, tyrosylprotein sulfotransferase, uronyl-2-sulfotransferase, estrone sulfotransferase, chondroitin 4-sulfotransferase, SULT1A1, SULT1A2, SULT1A3, SULT1A4, SULT1B1, SULT1C2, SULT1C3, SULT1C4, SULT1D1P, SULT1E1, SULT2A1, SULT2B1, SULT4A1, or SULT6B1; The method of claim 10.

17. The composition further comprises a natural level or extract of minoxidil sulfotransferase enzyme, a natural level or extract of phenol sulfotransferase enzyme, and / or a natural level or extract of phenol sulfotransferase enzyme from Populus trichocarpa, Populus x canescens, Salix sp., Arabidopsis thaliana, silver poplar (Populus alba), Simon poplar (Populus simonii), S. purpurea, P. tremuloides, I. polycarpa, P. nigra, Oryza sativa, Salicaceae family, Poplar (Populus sp.), Idesia polycarpa - Japanese orange cherry, Potato (Solanum tuberosum), Cabbage (Brassica rapa), Populus trichocarpa (Black Cottonwood), Salix sp. (Willow Tree), Cotton (Gossypium), Olea europaea L. europaea L), Brassica napus, Apium graveolens, Brassica oleracea, Saccharina japonica, Solanum tuberosum, and / or black cottonwood; the minoxidil sulfotransferase enzyme, phenol sulfotransferase enzyme, and / or natural levels or extracts of sulfotransferase enzyme are present in an amount ranging from 1% to 100% by weight; The method of claim 10.

18. the sulfotransferase enzyme comprises OeST1; The method of claim 10.

19. Quantifying the activity of SULT1A1 in the dermal papilla cells and / or dermal sheath of said subject. The method of claim 10 further comprising:

20. determining a therapeutic treatment using said composition based on said quantitative measurement of SULT1A1 activity in dermal papilla cells and / or dermal sheath of said subject; 20. The method of claim 19, further comprising:

21. A composition for increasing the activity of a sulfotransferase enzyme in the scalp and / or liver of a subject suffering from alopecia, comprising: Alkalizing Agents and Sulfotransferase Enzymes A composition comprising:

22. 1. A method for increasing sulfotransferase enzyme activity in the scalp and / or liver of a subject suffering from alopecia, comprising: administering to a subject suffering from alopecia a composition comprising an alkalizing agent and a sulfotransferase enzyme; A method comprising:

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