WO2025080263A1

WO2025080263A1 - Methods and compositions for treatment of hair re-pigmentation

Info

Publication number: WO2025080263A1
Application number: PCT/US2023/076470
Authority: WO
Inventors: Ofer A. Goren
Original assignee: Individual
Current assignee: Individual
Priority date: 2023-10-10
Filing date: 2023-10-10
Publication date: 2025-04-17
Anticipated expiration: 2026-04-10

Abstract

Embodiments can relate to a method for coloring or re-pigmenting hair by administering a composition containing an alkalizing agent to a subject, wherein the alkalizing agent increases melanin production in a hair bulb of the subject. Additional embodiments can relate to inducing redness in skin, wherein the alkalizing agent increases melanin production of the subject to increase redness of the skin. Additional embodiments can relate to treating vitiligo, wherein the alkalizing agent increases melanin production of the subject. Additional embodiments can relate to treating metabolic acidosis, wherein the alkalizing agent reduces blood acidity of the subject.

Description

Methods And Compositions For Treatment Of Hair Re-Pigmentation

FIELD OF THE INVENTION

[0001] Embodiments of the present disclosure can relate to use of compositions having alkalizing agent formulations that re-pigment gray hair and/or to change the color of hair (e.g., make the hair blonder, redder, etc.). The composition can be administered as an oral treatment, a topical treatment, or injectable treatment, transdermal treatment, etc.

BACKGROUND OF THE INVENTION

[0002] A common way to address discoloring hair, change hair color, obtain a desired aesthetic, etc. is to use hair dye. Synthetic hair dye (such as permanent hair dyes) is relatively inexpensive and relatively easy to apply at home or at a hair salon. However, synthetic hair dye use chemicals designed to alter the hair strand to color the hair via chemical reactions that tend to damage protective proteins of the hair. This can result in a weakening of the strength of the hair, which can make it more vulnerable to damage from the sun, etc. In addition, synthetic hair dye often causes scalp irritation, allergic reaction, permanent damage to the hair shaft, etc.

Moreover, some dye chemicals contain carcinogens. Temporary hair dye and semipermanent hair dye often cause less irritation, but they tend to not be as effective. A treatment that induces hair follicles to naturally produce hair color pigment would be desirable.

[0003] Canities or achromotrichia is a natural graying of hair with age, which is generally due to loss of pigmentation. Currently, no medical treatment is available for hair re-pigmentation. Ideally, a treatment for gray hair would be to reverse gray hair back to its original color by naturally stimulating the melanin producing cells in the hair follicle. Yet, no such treatments currently exist.

SUMMARY OF THE INVENTION

[0004] An exemplary embodiment can relate to a method for coloring or re-pigmenting hair. The method can involve administering a composition containing an alkalizing agent to a subject, wherein the alkalizing agent increases melanin production in a hair bulb of the subject.

[0005] In some embodiments, the alkalizing agent is tris(hydroxymethyl)aminomethane, sodium bicarbonate, TRC101, or an alkalizing agent suitable for treating metabolic acidosis. [0006] In some embodiments, the composition is administered orally, topically, transdermally, and/or via injection.

[0007] In some embodiments, the composition is formulated as a time-dependent release composition that controllably releases the alkalizing agent.

[0008] In some embodiments, the composition is administered via injection into the scalp of the subject.

[0009] In some embodiments, the alkalizing agent increases eumelanin production and/or pheomelanin production.

[0010] In some embodiments, the alkalizing agent increases black eumelanin, brown eumelanin, yellow pheomelanin, and/or red pheomelanin.

[0011] In some embodiments, the increase of melanin production in the hair bulb of the subject re-pigments at least a portion of a hair strand associated with the hair bulb or changes a color of at least a portion of a hair strand associated with the hair bulb.

[0012] In some embodiments, the increase of melanin production in the hair bulb of the subject re-pigments a gray colored portion of at least a portion of a hair strand associated with the hair bulb, changes a color of at least a portion of the hair strand associated with the hair bulb to a red color or a blonde color, or changes a color of at least a portion of a hair strand associated with the hair bulb to a redder color or a blonder color.

[0013] An exemplary embodiment can relate to a method for inducing redness in skin. The method can involve administering a composition containing an alkalizing agent to a subject, wherein the alkalizing agent increases melanin production of the subject to increase redness of the skin.

[0014] In some embodiments, the increasing redness of the skin includes increasing redness of at least a portion of: a lip, a nipple, a vagina, or a penis.

[0015] In some embodiments, the composition is administered orally, topically, transdermally, and/or via injection.

[0016] An exemplary embodiment can relate to a method of treating vitiligo. The method can involve administering a composition containing an alkalizing agent to a subject suffering from vitiligo, wherein the alkalizing agent increases melanin production of the subject.

[0017] In some embodiments, the composition is administered orally, topically, transdermally, and/or via injection. [0018] An exemplary embodiment can relate to method of treating metabolic acidosis. The method can involve administering a composition containing an alkalizing agent to a subject suffering from metabolic acidosis, wherein the alkalizing agent reduces blood acidity of the subject.

[0019] In some embodiments, reducing blood acidity restores or maintains acid-base homeostasis for the subject.

[0020] In some embodiments, the composition is administered orally, topically, transdermally, and/or via injection.

[0021] An exemplary embodiment can relate to a method for canities or achromotrichia. The method can involve administering a composition containing an alkalizing agent to a subject suffering from canities or achromotrichia, wherein the alkalizing agent increases melanin production in a hair bulb of the subject.

DETAILED DESCRIPTION OF THE INVENTION

[0022] The following description is of exemplary embodiments that are 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 describing the general principles and features of the present invention. The scope of the present invention is not limited by this description.

[0023] Human hair color is the pigmentation of human hair strands due to two types of melanin (e.g., eumelanin and pheomelanin) produced in the hair bulb. Generally, if more melanin is produced by the hair bulb, the color of the hair strand associated with the hair bulb is darker; if less melanin is produced, the hair strand is lighter. The tone of the hair strand is dependent on the ratio of black or brown eumelanin to yellow or red pheomelanin. Two types of pigment give hair its color: black-brown eumelanin and reddish-brown/reddish-yellow pheomelanin. These pigments are synthesized by melanocytes. Inside the melanocytes, tyrosine is converted into L- DOPA and then L-dopaquinone, which in turn is formed into pheomelanin or eumelanin. Regarding the darkness of the hair color, more black eumelanin leads to blacker hair, and more brown eumelanin to browner hair. All human hair has some amount of both pigments. Over 95% of melanin content in black and brown hair is eumelanin. Pheomelanin is generally found in elevated concentrations in blond and red hair, representing about one-third of total melanin content. If there is no black eumelanin, the result is strawberry blond. Blond hair results from small amounts of brown eumelanin with no black eumelanin.

[0024] Embodiments can relate to a method for coloring or re-pigmenting hair. This can be done to treat for graying hair (e.g., canities or achromotrichia), provide a means to alter hair color without the use of chemical dye, provide an alternative or a supplement to aesthetic medicine application, etc. As will be explained herein, additional embodiments can relate to treating vitiligo and treating metabolic acidosis.

[0025] The method can involve administering a composition containing an alkalizing agent to a subject. The alkalizing agent can increase melanin (e.g., eumelanin and/or pheomelanin) production in one or more hair bulbs of the subject. This can include increasing black eumelanin, brown eumelanin, yellow pheomelanin, and/or red pheomelanin in one or more hair bulbs of the subject. The increase of melanin production in the hair bub of the subject can repigment at least a portion of a hair strand associated with the hair bulb. In addition, or in the alternative, the increase of melanin production in the hair bulb of the subject can change a color of at least a portion of a hair strand associated with the hair bulb. For instance, the increase of melanin production in the hair bulb of the subject can re-pigment a gray colored portion of at least a portion of a hair strand associated with the hair bulb. The increase of melanin production in the hair bulb of the subject can change a color of at least a portion of the hair strand associated with the hair bulb to a red color or a blonde color. The increase of melanin production in the hair bulb of the subject can change a color of at least a portion of a hair strand associated with the hair bulb to a redder color or a blonder color. Test results indicate that those with naturally red or blonde hair may experience a stronger response to the alkalizing agent. As can be appreciated, embodiments of the composition can color or re-pigment hair naturally (e.g., without the use of chemical dyes or other synthetic chemicals).

[0026] Embodiments of the composition can include one or more alkalizing agents. The alkalizing agent can be any suitable compound that modifies blood pH of the subject’s body or modifies blood pH of a portion (e.g., in or around the hair follicle, the hair bulb, etc.) of a subject’s body. The change in pH can facilitate production or an increase in production of melanin. Any of the alkalizing agents can include a bicarbonate or a combination of bicarbonates. Examples of bicarbonates can include sodium bicarbonate, potassium bicarbonate, magnesium bicarbonate, calcium bicarbonate, etc. Other alkalizing agents can include a citrate or a combination of citrates. Examples of citrates can include potassium citrate, sodium citrate, citric acid, etc. Other alkalizing agents can include a loop diuretic or a combination of loop diuretics. Examples of loop diuretics can include Bumetanide (Bumex), Ethacrynic acid (Edecrin), Furosemide (Lasix), Torsemide (Soaanz), etc. Other alkalizing agents can include MOPS, BES, TES, HEPES, DIPSO, TAPSO, Acetamidoglycine, POPSO, HEPPSO, HEPPS, Tricine, Tris (tromethamine), Glycinamide, Glycylglycine, Bicine, TAPS, etc. Preferred alkalizing agents can be tris(hydroxymethyl)aminomethane, TRC101, or any alkalizing agent suitable for treating metabolic acidosis.

[0027] Embodiments of the method can involve the use of one or more compositions. The composition can include one or more alkalizing agents. For instance, the treatment might involve administering composition-1 and composition-2, wherein composition- 1 has an alkalizing agent that differs from an alkalizing agent used in composition-2. In addition, one composition might have the same alkalizing agent(s) as another composition, but the concentration or amounts of alkalizing agents may differ. In addition, composition-] might be administered before or after administration of composition-2, might be administered at the same time, etc. Composition-1 might be administered orally, while composition-2 is administered topically, etc. As explained herein, some compositions can be formulated with penetration agents, carrier material, etc. The compositions used might also differ based on the inclusion of these ingredients. How many compositions to use, how many alkalizing agents to use, when to administer them, etc. can be determined based on desired effects and/or design criteria.

[0028] Any of the compositions disclosed herein can be an oral formulation, a topological formulation, an injectable formulation, a transdermal formulation, etc. Any of the oral formulations disclosed herein can be in tablet form, pill form, capsule form, gel form, liquid form, spray form, etc. Any of the oral formulations or any one or combination of ingredients of the oral formulation can be in dry, wet, lypolized, etc. Any of the topological formulations disclosed herein can be a lotion, an ointment, a shampoo (wet or dry), an aerosol for application as a foam or mousse, a liquid solution, a lip balm, a gel, etc. These can be mediums applied to the scalp, for example. Any of the topological formulations or any one or combination of ingredients of the topological formulation can be in dry, wet, lypolized, etc. Any of the injectable formulations disclosed herein can be in intradermal injection form. Any of these mediums can be injected into the scalp or other portions of the body. Any of the injectable formulations or any one or combination of ingredients of the injectable formulation can be in dry, wet, lypolized, etc. Any of the transdermal formulations disclosed herein can be in the form of controlled release vehicle, such as a patch for example. Any of the transdermal formulations or any one or combination of ingredients of the transdermal formulation can be in dry, wet, lypolized, etc.

[0029] Embodiments of the compositions disclosed herein to be formulated as a cosmetic (e.g., lotion, ointment, shampoo (wet or dry), aerosol for application as a foam, mousse, or hairspray, a liquid solution, a gel, etc. Any of the compositions disclosed herein can be formulated in the form of a drug, a nutritional supplement, cosmetic product, etc.

[0030] Depending on the use and implementation, any of the topological formulations can include a solvent. The solvent may or may not be volatile. The solvent can be an alcohol, such as a polyhydric alcohol, benzyl alcohol, propylene glycol, water, et. Any of the topological formulations can include a starch (modified or unmodified starch). It is contemplated for the starch to act as a sebum absorber. Non-limiting examples of suitable unmodified starch materials can include cornstarch, potato starch, tapioca starch, rice starch, wheat starch, cassaya starch, etc. A modified starch material is a starch which has been derivatized or altered by processes known to those of ordinary skill in the art, such as esterification, etherification, oxidation, acid hydrolysis, crosslinking, enzyme conversion, etc. Non-limiting examples of suitable modified starch materials can include aluminum starch octenyl succinate, sodium starch octenyl succinate, calcium starch octenyl succinate, di starch phosphate, hydroxy ethyl starch phosphate, hydroxypropyl starch phosphate, sodium carboxymethyl starch, sodium starch glycolate, etc. Any of the topological formulations can include oil-absorbing agent and/or suspending agent, such as silica, cellulose, chalk, talc, fuller's earth, etc. Some embodiments can include other sebum absorbers, such as a clay material, which may be stearalkonium hectorite, stearalkonium bentonite, quaternium-18 bentonite, quaternium-18 hectorite, etc. Use of a sebum absorber, oil-absorbing agent, or suspending agent can facilitate a more pleasing aesthetic to a user by reducing or eliminating an oily and/or unaesthetic appearance of hair.

[0031] Any of the topological formulations can include embodiments of the composition formulated as a dry shampoo. By “dry shampoo,” it is meant that the composition is formulated to include a earner material that is a volatile liquid and therefore evaporates and a powder that remains, wherein the powder contains a starch. An exemplary starch can be aluminum starch octenyl succinate. Examples of suitable carrier materials that are volatile liquids can be lower alcohols including without limitation ethanol or isopropanol, a volatile silicone compound such as polydimethylsiloxanes (e.g., having a viscosity less than about 5 cSt at 25°C), cyclomethicone, cyclohexane siloxane, decamethyltetrasiloxane, octam ethyltri siloxane, decamethylpentasiloxane, decamethylcyclopentasiloxane, octam ethylcy cl otetrasil oxane, trimethylsilylamodimethicone, phenyl trimethicone, hexamethyidisiloxane, 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 instances because dry shampoo tends to not wash away the composition.

[0032] Any of the topological formulations can include embodiments of the composition formulated as a spray, aerosol, etc. In this regard, any of the topological formulations can be a composition including a propellant (e g., butane, isobutane, propane, A-46 (isobutane and propane), liquefied petroleum gas (e.g., propane), dimethyl ether, methyl ethyl ether, tri chi orofluorom ethane, dichlorodifluoromethane, dichlorotetrafluorothane, monochlorodifluoromethane, trichlorotrifluoroethane propane, carbon dioxide, nitrous oxide, 1,1, 1,2, -tetrafluoroethane, 1,1,2,3,3,3-heptafluoropropane, etc.). A propellant may condense to a liquid state in an aerosol container at ambient temperatures In some embodiments, the propellant may have a lower specific gravity as compared to the rest of the composition, thus facilitating propelling the composition from a container (e.g., through a dip tube) as compared to expelling the propellant.

[0033] Depending on the use and i mplementation, any of the formulations can be a composition including a carrier. For instance, any of the formulations can be encapsulated in a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier can encapsulate the composition in liposomes, microbeads, etc. In addition to being “pharmaceutically acceptable,” a carrier can be “acceptable” in the sense of being compatible with the other ingredients of the formulation. The carrier can be used to temporarily encapsulate the composition until a condition is met that causes its release. In some embodiments, the carrier can be formulated to controllably release the composition - e.g., a time-dependent release.

[0034] Depending on the use and implementation, any of the formulations can be a composition including a penetration enhancer. The penetration enhancer can enhance penetration of the composition in the skin (e.g , the scalp). Suitable penetrating enhancer agents can include alcohols (e.g., dodecanol, oleyl alcohol, etc.); amines (e.g., isopropyl amine, diisopropyl amine, triethyl amine, triethanol amine, diisopropanolamine, ethylene diamine, etc.); carboxylic acids (e.g., oleic acid, linoleic acid, linolenic acid, etc ); esters (e.g., dibutyl sebacate, dibutyl phthalate, butyl benzoate, ethyl caprate, etc.); Azone, N methyl pyrollidone; 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; cyclodextrines; occlusive agents; surface active agents; dimethylaminopropionic acid derivatives; terpenes; sulfoxides; cyclic ethers; amides; sulphoxides (e.g., dimethylsulphoxide, DMSO, decylmethalsulfoxide, etc.); Azones (e.g., 1- dodecylazacycloheptan-2-one, laurocapran, laurocapram); pyrrolidones (e.g., 2-pyrrolidone, 2P, N-methylpyrrilidone, N-methyl-2-pyrrolidone, NMP, l-propyl-3-dodecyl-2-pyrrolidone, 1-butyl- 3-dodecyl-2-pyrrolidone, etc.); surfactants (e.g., polyoxyethylene-2-oleyl ether, polyoxy ethylene-2-stearly ether, sodium dodecyl sulfate, SDS, sodium lauryl sulfate, SLS); oxazolidinones (e.g., 4-decyloxazolidin-2-one), urea, 2-(l -nonyl)- 1,3 -di oxolane; terpenes; polyester nanosponges; liposomes; phospholipids; cyclopentadecalactone; pentadecalactone; SNAC; salcaprozate sodium Sodium N-[8-(2-hydroxybenzoyl) amino] capryl ate; CNAC; 5- CNAC; 8-(N-2-hydroxy-5-chloro-benzyl)-amino-caprylic acid; sodium caprate; glyceryl triglyceride; peptides; etc.

[0035] Depending on the use and implementation, any of the formulations can be a composition including an exfoliating agent to promote abrasion of the surface of the skin (e g., surface of the scalp) and/or promote absorption of a composition and/or an ingredient of a composition.

Examples of exfoliating agents can include (1) inorganic and/or metallic particles such as: boron nitride, in body-centered cubic form (Borazon®); aluminosilicate (e.g. nepheline); zircon; mixed oxides of aluminum such as emery; zinc oxide; aluminum oxides such as aluminas or corundum; titanium oxide; titanium oxide coated mica; carbides, in particular silicon carbide (carborundum); or other metal oxides; metals, and metal alloys such as iron shot, steel shot, and in particular perlite; silicates such as glass, quartz, sand, or vermiculite; calcium carbonate (e.g. Bora-Bora sand or Rose de Brignoles sand) or magnesium carbonate; sodium chloride; pumice stone; amorphous silica; diamond; ceramics, (2) organic particles such as: fruit stones, in particular apricot stones, e.g. Scrubami® apricot; wood cellulose, e.g. ground bamboo stem; coconut shell, e.g. coconut exfoliator; polyamides, in particular Nylon-6; sugars; plastic microbeads, e g. polyethylenes or polypropylenes; ground walnut; ground apricot seed; ground shells, (3) mixed particles associating organic and inorganic compounds, particles coated in the compounds identified above, etc.

[0036] Depending on the use and implementation, any of the formulations can be a composition incorporated into a controlled release vehicle (e.g., an encapsulation) that would allow an ingredient or agent of the composition to be controllably released into the dermis of the skin (e.g., scalp). Capsules or vehicles that encapsulate the ingredient or agent can include, but are not limited to, liposomes, non-ionic liposomes, niosomes, novasome I, erythromycin-Zn complex, microspheres, nanoparticles, solid lipid nanoparticles, and nanoemulsions.

[0037] Any of the compositions disclosed herein can be administered at a predetermined frequency. This predetermined frequency can be once every 24 hours, twice every 24 hours, three times every 24 hours, four times every 24 hours, etc. Again, the treatment can involve use of the one or more compositions. Thus, composition-] administration frequency can be the same or different from composition-2 administration frequency.

[0038] As the alkal izing agent increases melanin production, embodiments of the composition can be used to for other aesthetic medicine applications and treatments. For instance, embodiments can relate to a method for inducing redness in skin. The method can involve administering a composition containing an alkalizing agent to a subject, wherein the alkalizing agent increases melanin production in the epidermis of the subject to increase redness of the skin. This can be done to increasing redness of at least a portion of a lip, at least a portion of a nipple, at least a portion of a vagina, at least a portion of a penis, etc. of the subject. As another example, embodiments can relate to administering a composition containing an alkalizing agent to a subject suffering from vitiligo, wherein the alkalizing agent increases melanin production in the epidermis of the subject.

[0039] Another application can be treatment for metabolic acidosis. Metabolic acidosis occurs when a person cannot maintain normal acid-base homeostasis. The inability to maintain normal acid-base homeostasis can be due to a physiological condition, due to medication the person is taking that causes a deviation in the homeostasis, etc. An alkalizing agent, via its ability to change blood pH, can be used to treat for metabolic acidosis. Thus, embodiments can relate to a method of treating metabolic acidosis. The method can involve administering a composition containing an alkalizing agent to a subject suffering from metabolic acidosis, wherein the alkalizing agent reduces blood acidity of the subject. Reducing blood acidity can restore or maintain acid-base homeostasis for the subject.

[0040] Several treatments and medical applications for embodiments of the compositions are disclosed herein. Any of the methods herein can involve a treatment and/or an application of one or more of the compositions discloses herein. Thus, a subject may be administered composition- 1 for treating graying hair, composition-2 for treating vitiligo, etc.

[0041] EXAMPLES

[0042] The following discussion below describes exemplary compositions and methods of use that were tested to demonstrate effectiveness of use of an alkalizing agent for the treatments discussed herein.

[0043] The pathogenesis of gray hair is not well understood, but it can be partially attributable to oxidative stress in the hair follicle leading to reduction of melanocytes or the ability of melanocytes to produce hair color pigment. During a clinical study of a topical drug used to induce a metabolizing enzyme (SULT 1 Al), a significant number of patients with gray hair reported hair pigment changed as an adverse event of the drug. Typical pigment changes occurred within 3-4 months of treatment, but some patients experienced pigment change in as little as 2-3 weeks. The most common pigments were red, yellow, and black. The pigment change was reversible upon discontinuation of the treatment. The reported hair pigment change was surprising since it was expected that: 1) no pigment change would occur; or 2) that more gray hair would result due the mechanism of action of the drug - i .e., the drug increases the follicular and intracellular pH leading to the SULT1A1 enzyme induction. Upon further research, it was discovered that altering intracellular pH of melanocyte stem cells could amplify melanocyte differentiation via histone acetylation; thus, presenting a plausible mechanism of action for the findings.

[0044] An open label study of AG-001 was conducted on eleven subjects. The results are shown in Table 1. Eight of the eleven subjects experienced hair pigment change within 3-4 months of applying AG-001 twice daily. The one subject that had 100% gray hair, experienced repigmentation with black hair within 3 weeks of commencing AG-001 treatment. The pigment change was reversible in all subjects upon discontinuation of the treatment with AG-001.

Table 1: Study of AG-001 on Eleven Subjects

[0045] It should be understood that the disclosure of a range of values is a disclosure of every numerical value within that range, including the end points. It should also be appreciated that some components, features, and/or configurations may be described in connection with only one particular embodiment, but these same components, features, and/or configurations can be applied or used with many other embodiments and should be considered applicable to the other embodiments, unless stated otherwise or unless such a component, feature, and/or configuration is technically impossible to use with the other embodiment. Thus, the components, features, and/or configurations of the various embodiments can be combined together in any manner and such combinations are expressly contemplated and disclosed by this statement.

[0046] It will be apparent to those skilled in the art that numerous modifications and variations of the described examples and embodiments are possible considering the above teachings of the disclosure. The disclosed examples and embodiments are presented for purposes of illustration only. Other alternate embodiments may include some or all of the features disclosed herein. Therefore, it is the intent to cover all such modifications and alternate embodiments as may come within the true scope of this invention, which is to be given the full breadth thereof.

[0047] It should be understood that modifications to the embodiments disclosed herein can be made to meet a particular set of design criteria. Therefore, while certain exemplary embodiments of the compositions and methods of using and making the same disclosed herein have been discussed and illustrated, it is to be distinctly understood that the invention is not limited thereto but may be otherwise variously embodied and practiced within the scope of the following claims.

Claims

WHAT IS CLAIMED IS:

1. A method for coloring or re-pigmenting hair, the method comprising: administering a composition containing an alkalizing agent to a subject; wherein the alkalizing agent increases melanin production in a hair bulb of the subject.

2. The method of claim 1, wherein: the alkalizing agent is tris(hydroxymethyl)aminomethane, sodium bicarbonate, TRC101, or an alkalizing agent suitable for treating metabolic acidosis.

3. The method of claim 1, wherein: the composition is administered orally, topically, transdermally, and/or via injection.

4. The method of claim 1, wherein: the composition is formulated as a time-dependent release composition that controllably releases the alkalizing agent.

5. The method of claim 1, wherein: the composition is administered via injection into the scalp of the subject.

6. The method of claim 1, wherein: the alkalizing agent increases eumelanin production and/or pheomelanin production.

7. The method of claim 1, wherein: the alkalizing agent increases black eumelanin, brown eumelanin, yellow pheomelanin, and/or red pheomelanin.

8. The method of claim 1, wherein: the increase of melanin production in the hair bulb of the subject re-pigments at least a portion of a hair strand associated with the hair bulb or changes a color of at least a portion of a hair strand associated with the hair bulb.

9. The method of claim 1, wherein: the increase of melanin production in the hair bulb of the subject re-pigments a gray colored portion of at least a portion of a hair strand associated with the hair bulb, changes a color of at least a portion of the hair strand associated with the hair bulb to a red color or a blonde color, or changes a color of at least a portion of a hair strand associated with the hair bulb to a redder color or a blonder color.

10. A method for inducing redness in skin, the method comprising: administering a composition containing an alkalizing agent to a subject; wherein the alkalizing agent increases melanin production of the subject to increase redness of the skin.

11. The method of claim 10, wherein: the increasing redness of the skin includes increasing redness of at least a portion of: a lip, a nipple, a vagina, or a penis.

12. The method of claim 10, wherein: the composition is administered orally, topically, transdermally, and/or via injection.

13. A method of treating vitiligo, the method comprising: administering a composition containing an alkalizing agent to a subject suffering from vitiligo; and wherein the alkalizing agent increases melanin production of the subject.

14. The method of claim 13, wherein: the composition is administered orally, topically, transdermally, and/or via injection.

15. A method of treating metabolic acidosis, the method comprising: administering a composition containing an alkalizing agent to a subject suffering from metabolic acidosis; and wherein the alkalizing agent reduces blood acidity of the subject.

16. The method of claim 13, wherein: reducing blood acidity restores or maintains acid-base homeostasis for the subject.

17. The method of claim 15, wherein: the composition is administered orally, topically, transdermally, and/or via injection.

18. A method for canities or achromotrichia, the method comprising: administering a composition containing an alkalizing agent to a subject suffering from canities or achromotrichia; wherein the alkalizing agent increases melanin production in a hair bulb of the subject.