Methods and compositions for oral supplements of oral minoxidil for treatment of alopecia

Abstract

The present invention may be directed to compositions and methods for the treatment of alopecia / epilation, which may include the treatment of alopecia conditions. Compositions and methods relate to oral supplements of oral minoxidil, including an SLC22A9 inducer, an HIF-alpha inducer, and / or an acidulant. Acidification of blood in patients with alopecia may cause mild acidosis, which may up-regulate SLC22A9 and / or down-regulate AABC3. Inducing SLC22A9, inducing HIF-alpha, and / or acidifying the patient's blood can promote oral form of minoxidil into hair follicles.

Description

Technical Field

[0001] Embodiments may relate to methods and compositions for treating hair loss, which may include treating alopecia. Specifically, the compositions and methods relate to oral supplements for oral minoxidil. Background Art

[0002] A drug that can be used to treat alopecia is minoxidil. In order for minoxidil to exert its hair growth properties, minoxidil must be activated by the enzyme SULT1A1 (minoxidil sulfotransferase). This 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 is variable among people and depends on the SULT1A1 enzyme.

[0003] Previous studies have shown that alkalizing the intracellular pH of keratinocytes induces expression of the SULT1A1 enzyme in the scalp and subsequently improves, increases, or enhances minoxidil response. Therefore, topical alkalizing agents have been developed as minoxidil enhancers; however, such topical minoxidil enhancers have had limited success because twice-daily application is difficult to comply with, it tends to change hair color, and it tends to leave a residue of sodium bicarbonate on the hair. In addition, minoxidil primarily exerts its hair regenerative effects through the dermal papilla and dermal sheath cells, which are difficult to treat with topical cosmetics. The dermal papilla has a rich blood supply, which makes it more susceptible to modulation by orally administered compositions (e.g., drugs, ingredients, supplements, etc.). Therefore, an oral composition that increases the SULT1A1 enzyme in the dermal papilla, dermal sheath, or outer root sheath of the hair follicle and subsequently increases the response to minoxidil for the treatment of hair loss / hair removal would be advantageous.

[0004] Sulfation of oral minoxidil occurs in the liver; it does not occur at the hair follicles. Therefore, oral minoxidil does not enter the hair follicles. As will be explained in this disclosure, the inventors have discovered that expression of SLC22A9 can promote the entry of oral minoxidil into the hair follicles. Summary of the invention

[0005] Embodiments relate to methods and compositions for oral supplementation of oral minoxidil. As described above, sulfation of oral minoxidil occurs in the liver; it does not occur at the hair follicles, which results in oral minoxidil not entering the hair follicles. However, the expression of SLC22A9 can promote the entry of oral minoxidil into the hair follicles. The expression of SLC22A9 can be achieved by inducing SLC22A9, HIF-1-A and / or acidifying the patient's blood.

[0006] Exemplary embodiments relate to an oral supplement for oral administration of minoxidil. The oral supplement may include an SLC22A9 inducer, a HIF-α inducer, and / or an acidifier.

[0007] In some embodiments, the acidifying agent may upregulate SLC22A9 and / or downregulate AABC3.

[0008] In some embodiments, the HIF-α inducer may include Juniperus cummunis extract, Green Tree Extract, Glycyrrhiza glabra, o-phenanthroline, iodochlorohydroxyquinoline, and / or cobalt sulfate heptahydrate.

[0009] In some embodiments, the oral supplement may include an oral minoxidil therapeutic composition comprising minoxidil or a pharmaceutically acceptable salt thereof.

[0010] In some embodiments, minoxidil or a pharmaceutically acceptable salt thereof may be present in the oral minoxidil therapeutic composition in a dosage ranging from 0.125 mg to 10 mg.

[0011] In some embodiments, the acidulant may include ammonium chloride, methanol, salicylates, biguanides, alcohols, polysaccharides, cyanides, and / or carbon monoxide.

[0012] Exemplary embodiments relate to methods for treating alopecia. The method may involve treating alopecia by administering oral minoxidil to a patient suffering from alopecia; and administering an oral supplement before, during, and / or after administering the oral minoxidil, the oral supplement comprising an SLC22A9 inducer, an HIF-α inducer, and / or an agent that acidifies the patient's blood. Alternatively, the method may involve treating alopecia by administering an oral supplement comprising oral minoxidil, the oral supplement additionally comprising an SLC22A9 inducer, an HIF-α inducer, and / or an agent that acidifies the patient's blood.

[0013] In some embodiments, the acidifying agent may upregulate SLC22A9 and / or downregulate AABC3.

[0014] In some embodiments, the acidifying agent may cause mild acidosis in the patient.

[0015] In some embodiments, the HIF-α inducer may include arachis oleifera extract, green tree extract, Glycyrrhiza glabra, o-phenanthroline, iodochlorohydroxyquinoline, and / or cobalt sulfate heptahydrate.

[0016] In some embodiments, oral minoxidil may include minoxidil or a pharmaceutically acceptable salt thereof.

[0017] In some embodiments, minoxidil or a pharmaceutically acceptable salt thereof may be present in an oral minoxidil in a dosage ranging from 0.125 mg to 10 mg.

[0018] In some embodiments, the acidulant may include ammonium chloride, methanol, salicylates, biguanides, alcohols, polysaccharides, cyanides, and / or carbon monoxide.

[0019] Exemplary embodiments relate to an oral composition for treating alopecia. The composition may include a SLC22A9 inducer, a HIF-α inducer, and / or an acidifying agent.

[0020] In some embodiments, the acidifying agent may upregulate SLC22A9 and / or downregulate AABC3.

[0021] In some embodiments, the HIF-α inducer may include arachis oleifera extract, green tree extract, Glycyrrhiza glabra, o-phenanthroline, iodochlorohydroxyquinoline, and / or cobalt sulfate heptahydrate.

[0022] In some embodiments, the acidulant may include ammonium chloride, methanol, salicylates, biguanides, alcohols, polysaccharides, cyanides, and / or carbon monoxide.

[0023] Exemplary embodiments relate to methods for treating alopecia. The methods involve administering an oral composition comprising a SLC22A9 inducer, a HIF-α inducer, and / or an acidifying agent to a patient suffering from alopecia.

[0024] In some embodiments, the acidifying agent may upregulate SLC22A9 and / or downregulate AABC3.

[0025] In some embodiments, the HIF-α inducer includes lavender extract, green tree extract, Glycyrrhiza glabra, o-phenanthroline, iodochlorohydroxyquinoline, and / or cobalt sulfate heptahydrate.

[0026] In some embodiments, the acidulant may include ammonium chloride, methanol, salicylates, biguanides, alcohols, polysaccharides, cyanides, and / or carbon monoxide.

[0027] As used herein, the term "prevent" or "prevention" and other derivatives of the term, when used to refer to alopecia, such as androgenetic alopecia, may refer to a reduced likelihood of alopecia in an individual receiving a given treatment relative to a similar individual at risk for alopecia but not receiving such a treatment. Thus, the term "prevent" or "prevention" may encompass treatments that result in a lower degree of alopecia than would be expected for a given individual. The efficacy of preventing alopecia may be determined by controlled studies, such as where a treatment (e.g., topical, oral, transdermal, etc.) is given to a subject and a placebo is given to another subject. In these cases, if a subject receiving the treatment experiences less alopecia over a period of time relative to a subject receiving a placebo, such as at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50% or more, then the treatment may be considered effective in preventing alopecia.

[0028] As used herein, the term "subject" refers to a human or animal in need of therapeutic treatment for androgenetic alopecia or any other form of hair loss.

[0029] As used herein, the term "treat / treatment / treating" refers to a therapeutic treatment, wherein 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 "treatment" may include reducing or alleviating at least one side effect or symptom of a disease or condition. If one or more symptoms are reduced, treatment may generally be considered "effective". Alternatively, if the progression of the disease is reduced or stopped, treatment may be "effective". 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 development or deterioration 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, relief of one or more symptoms, relief of the extent of the disease, stabilization of the disease state (e.g., no deterioration), delay or slowing of disease progression, improvement or relief of the disease state, alleviation (whether partially or completely) and / or reduced mortality. For example, if the extent or amount of hair loss / hair loss is reduced, or the progression of hair loss / hair loss is slowed down or stopped, treatment may be considered effective. The term "treatment" of a disease may also include alleviating the symptoms or side effects of the disease (including palliative care).

[0030] The efficacy of a treatment for the treatment or prevention of alopecia can be determined by monitoring the hair density on a given area of ​​the subject's body, such as a given area of ​​the scalp. For example, if the rate of hair loss / hair loss decreases after treatment, such as by more than 10%, the treatment can be considered effective for the prevention of alopecia. Similarly, if the hair density remains the same, the treatment can be considered effective for the prevention of alopecia. If the hair density increases after treatment, such as by more than 5%, such as by more than 10%, the treatment can also be considered effective for the treatment and / or prevention of androgenic alopecia. The efficacy of a treatment for the treatment or prevention of androgenic alopecia can be determined by monitoring global photography. For example, a patient or a specialist can use global photos before and after to evaluate the treatment response.

[0031] As used herein, the term "alopecia" refers to all forms of hair loss / hair loss in humans or animals (male / male and female / female), including but not limited to traction alopecia, androgenic alopecia, male pattern baldness, female pattern hair loss, alopecia areata, alopecia universalis, telogen effluvium, chemotherapy-induced alopecia, hair loss, eyebrow hair loss, beard hair loss, hair thinning, etc. The term permits the presence of elements that do not materially affect the basic and novel or functional characteristics of the embodiment.

[0032] 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 for preventing or treating hair loss / hair loss.

[0033] Further features, aspects, objects, advantages and possible applications of the present invention will become apparent from a study of the exemplary embodiments and examples described below, taken in conjunction with the accompanying drawings and appended claims. Specific implementation plan

[0034] The following description is an exemplary embodiment currently considered for implementing the present invention. This description should not be understood in a limiting sense, but is only 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.

[0035] Alopecia, especially androgenetic alopecia, is the progressive miniaturization of hair follicles on the scalp. It can be characterized by diffuse thinning in the top area of ​​the scalp, while the frontal hairline remains intact. Alopecia is usually hereditary, but may also be dependent on hormones that may affect its development. Oral and / or topical minoxidil is a drug approved by the U.S. FDA for the treatment of alopecia. Its use can provide a modest increase in hair regrowth. The risk of adverse events with the use of this minoxidil is low; however, irritant dermatitis, allergic contact dermatitis, and hirsutism have been reported.

[0036] Although the embodiments disclosed herein may specifically discuss the treatment of one form of hair loss (eg, androgenetic alopecia), it should be understood that the disclosed compositions and methods may be similarly applicable to the treatment of other forms of hair loss.

[0037] Embodiments may be directed to methods for treating alopecia. The method may include treating alopecia by administering oral minoxidil to a patient suffering from alopecia. The method may involve administering an oral supplement before, during, and / or after administering the oral minoxidil. The oral supplement may include an SLC22A9 inducer, a HIF-1-A inducer, and / or an agent that acidifies the patient's blood.

[0038] Embodiments may be directed to compositions for treating alopecia. For example, embodiments may be directed to compositions related to oral supplements for oral administration of minoxidil. The compositions may be administered to induce solute carrier family 22 (e.g., SLC2A9), induce hypoxia-inducible factor 1-alpha (e.g., HIF-1-A), and / or acidify the blood of a patient suffering from alopecia (e.g., using ammonium chloride). Acidifying the patient's blood may upregulate SLC22A9 and / or downregulate AABC3. Upregulating SLC22A9 and / or downregulating AABC3 may allow or facilitate access of orally administered minoxidil to hair follicles.

[0039] The composition is an oral supplement for oral minoxidil. Therefore, it is contemplated that the composition is used in conjunction with oral minoxidil treatment. Minoxidil treatment may be a treatment involving the administration of a composition comprising minoxidil. The oral supplement may be administered before (e.g., before administering the minoxidil composition), during (e.g., when administering the minoxidil composition) and / or after (e.g., after administering the minoxidil composition) the oral supplement. This may include administering the oral supplement and the minoxidil simultaneously, each on the same day but at different times, etc. The oral supplement may be separate from the oral minoxidil composition (e.g., a separate oral supplement composition taken in conjunction with an oral form of minoxidil), may be a part of a minoxidil composition (e.g., a component of an oral form of minoxidil), or minoxidil may be a part of an oral supplement composition (e.g., an oral supplement composition may include minoxidil).

[0040] The minoxidil composition or the minoxidil component of the composition can be minoxidil or a pharmaceutically acceptable salt thereof. Minoxidil is a prodrug that is converted into its active form, minoxidil sulfate, by sulfotransferases 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. 1990 November; 95(5): 553-7). It has been confirmed that the activity of sulfotransferases in ORS determines the clinical response to minoxidil (see Goren A, Castano JA, McCoy J, Bermudez F, Lotti T. Novel enzymatic assay predicts minoxidil response in the treatment of androgeneticalopecia. Dermatol Ther. 2014; 27(3): 171-3). It is contemplated that dosages of minoxidil are from about 0.125 mg to about 10 mg per day. However, other dosages may also be used.

[0041] By using an embodiment of the oral supplement composition in combination with minoxidil, minoxidil can enter the hair follicles. When entering the hair follicles, minoxidil induces (upregulates) the expression of sulfotransferases in the skin, hair follicles, and / or keratinocytes (e.g., scalp) bearing hair. This can include upregulating sulfonation capacity. Thus, an embodiment of the oral supplement composition having minoxidil as a component of the oral supplement composition can induce the expression of sulfotransferases.

[0042] The oral supplement composition and / or the minoxidil composition may be administered at a predetermined frequency. The predetermined frequency may be once per 24 hours, twice per 24 hours, three times per 24 hours, four times per 24 hours, etc. The frequency of administration of the oral supplement composition may be the same as or different from the frequency of minoxidil.

[0043] The form of the oral supplement composition may be in tablet form, pill form, capsule form, gel form, liquid form, spray form, etc. The form of the minoxidil composition may be in tablet form, pill form, capsule form, gel form, liquid form, spray form, etc. The form of the oral supplement composition may be the same as or different from the form of the minoxidil composition.

[0044] Any formulation of the oral supplement composition and / or the minoxidil composition may include a carrier. For example, any formulation may be encapsulated in a pharmaceutically acceptable carrier. A pharmaceutically acceptable carrier may encapsulate the composition in liposomes, sodium alginate, gum arabic, chitosan, cellulose, pectin, etc. In addition to being "pharmaceutically acceptable", each carrier is also "acceptable" in the sense of being compatible with the other ingredients of the formulation. The carrier may be used to temporarily encapsulate the composition until the conditions that cause its release are met. In some embodiments, the carrier may be formulated to release the composition in a controlled manner, for example, time-dependent release.

[0045] Exemplary embodiments of oral supplement compositions can be formulated as oral supplements for oral minoxidil. For example, the oral supplement can be administered in conjunction with oral minoxidil treatment - for example, a patient with alopecia can take the oral supplement composition before, during and / or after taking an oral minoxidil composition. The oral supplement may include an agent constructed to express SLC22A9, thereby upregulating SLC22A9. Therefore, the oral supplement may include a SLC22A9 inducer as a medicament. In addition, or in an alternative, the oral supplement may include an agent constructed to express HIF-1-A, thereby upregulating HIF-1-A. Therefore, the oral supplement may include a HIF-1-A inducer as an agent. Examples of HIF-1-A inducers may include European arabica extract, green tree extract, licorice, o-phenanthroline, iodochlorohydroxyquinoline, cobalt sulfate heptahydrate, etc. The oral supplement may include an agent constructed to acidify the patient's blood, thereby upregulating SLC22A9 and / or downregulating AABC3. It is contemplated that blood acidifiers acidify the blood, thereby inducing mild acidosis. An example of a blood acidifier may be ammonium chloride. For example, oral administration of 0.1 g / kg (1.9 mEq / kg) of ammonium chloride may induce metabolic acidosis in a patient. Other acidosis agents may include methanol, salicylates, biguanides, alcohols, polysaccharides, cyanides, carbon monoxide, and the like. Oral supplements may include SLC22A9 inducers, HIF-1-A inducers, and / or acidifiers. Oral supplements may include one or more SLC22A9 inducers, one or more HIF-1-A inducers, or one or more acidifiers.

[0046] The oral supplement may include one or more compositions and may also include an oral minoxidil therapeutic composition. The oral minoxidil therapeutic composition may include minoxidil or a pharmaceutically acceptable salt thereof. Minoxidil or a pharmaceutically acceptable salt thereof may be present in the oral minoxidil therapeutic composition at a dosage ranging from 0.125 mg to 10 mg per day. Minoxidil may be included in a composition separate from the oral supplement or as part of the oral supplement.

[0047] As described herein, the oral supplement may include an SLC22A9 inducer, a HIF-1-A inducer, and / or an acidifier. The oral supplement may be a single composition comprising one or more of an SLC22A9 inducer, a HIF-1-A inducer, or an acidifier. The oral supplement may be two or more compositions, for example, one composition may include an SLC22A9 inducer or a HIF-1-A inducer, and another composition may include an acidifier. The two compositions may be administered to the patient alone, but both may be administered in combination with minoxidil. It should be understood that more or less compositions may be used, and other combinations of inducers / agents in the composition may be used.

[0048] As another example, the oral supplement composition may include one or more SLC22A9 inducers, one or more HIF-1-A inducers, and / or one or more acidifiers. For example, treatment may involve administering Composition-1 and Composition-2, wherein Composition-1 has a first inducer or acidifier that is different from the inducer or acidifier used in Composition-2, or Composition-1 has a first concentration of an inducer or acidifier and Composition-2 has a different concentration of the same inducer or acidifier, etc. In addition, one composition may be administered before administering minoxidil, while the other composition may be administered after administering minoxidil.

[0049] How much composition(s) to use, how much inducer(s) or acidifier(s) to use, when to apply them, etc. can be determined based on the desired effect and / or design criteria.

[0050] Exemplary formulations of embodiments of the oral supplement compositions include the following:

[0051]

[0052] A placebo-controlled study was conducted using 268 mg ammonium chloride oral supplementation to determine increases in SLC22A9 upregulation. 10 subjects were administered placebo and 10 subjects were administered ammonium chloride daily for 5 days. SLC22A9 expression from hair follicles was measured at baseline and day 5. SLC22A9 increased 3-fold with a statistically significant p=0.01 increase in the active group versus the placebo group.

[0053] Embodiments of the oral supplement composition may include one or more sulfotransferases. Any of the sulfotransferases may be human or non-human. Examples of sulfotransferases may be 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.), sulfotransferases (e.g., HS2ST2, HS3ST3A1, HS3ST3B1, HS3ST4, HS3ST5, HS3ST6, etc.), sulfotransferases (e.g., HS2ST3, HS2ST4, etc.), sulfotransferases (e.g., HS2ST5, HS2ST6, etc.), sulfotransferases (e.g., HS2ST2, HS3ST3A1, HS3ST3B1, HS3ST4, HS3ST5, HS3 ... acetyl) heparan 6-O-sulfotransferase (e.g. HS6ST1, HS6ST2, HS6ST3, etc.), N-deacetylase / N-sulfotransferase (e.g. NDST1, NDST2, NDST3, NDST4, etc.), tyrosyl protein sulfotransferase (e.g. TPST1, TPST2, etc.), uridine-2-sulfotransferase, estrone sulfotransferase, chondroitin 4-sulfotransferase, SULT1A1, SULT1A2, SULT1A3, SULT1A4, SULT1B1, SULT1C2, SULT1C3, SULT1C4, SULT1D1P, SULT1E1, SULT2A1, SULT2B1, SULT4A1, SULT6B1, etc.

[0054] The sulfotransferase may be a phenolsulfotransferase extract (eg, a phenolsulfotransferase extracted from a plant that produces sulfated salicinoids). Examples of plants producing sulfated salicinoids may include Populus trichocarpa, Populus x canescens, Salix sp., Arabidopsis thaliana, Populus alba, Populus simonii, S. purpurea, P. tremuloides, I. polycarpa, P. nigra, Oryza sativa, Salicaceae family, Populus (Populus sp.), Idesia polycarpa - Japanese orange cherry, Solanum tuberosum, Brassica rapa, Populus trichocarpa, Salix (willow), Gossypium, Olea europaea L, Brassica napus, Apium graveolens), cabbage (brassicaoleracea), kelp (Saccharina japonica), potato (Solanum tuberosum), American black poplar, etc.

[0055] The sulfotransferase may be OeST1 (olive SULT1A1). OeST1 is a sulfotransferase plant supplement that can be extracted from olive trees. The human homolog of OeST1 is SULT1A1, which belongs to the cytoplasmic 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 the fruit and leaves of olives. In olive fruit, OeST1 is expressed at high levels during the early stages of development and maturation, when flavonoids and other phenolic compounds are synthesized and accumulated. The expression of OeST1 in olive fruit is regulated by a variety of factors, including light, temperature, and water availability, which can affect the synthesis and accumulation of flavonoids and other phenolic substances in the fruit. In olive leaves, OeST1 is also expressed at high levels, particularly in young and actively growing leaves. The expression of OeST1 in olive leaves is regulated by multiple factors, including light, temperature, and biotic and abiotic stresses, which can affect the biosynthesis and accumulation of flavonoids and other phenolics in the leaves. Overall, the expression of OeST1 in olive fruit and leaves suggests that sulfated flavonoids and other phenolics may play an important role in the physiology and adaptation of olive plants and may contribute to the health benefits of olive fruit and leaves. Studies have measured the concentration of OeST1 (OLIVE SULT1A1) in olive leaves. For example, a study published in the Journal of Agricultural and Food Chemistry in 2014 measured the expression levels of different sulfotransferase genes, including OeST1, in olive leaves using quantitative real-time polymerase chain reaction (qPCR) analysis. The study found that OeST1 was expressed at relatively high levels in olive leaves compared to other sulfotransferase genes. Another study published in the same journal in 2018 measured the activity of sulfotransferases, including OeST1, in olive leaf extracts using a radiolabeled assay. The study found that the sulfotransferase activity in olive leaf extracts was mainly attributed to OeST1, with activity being higher in young leaves than in older leaves. These studies suggest that OeST1 is present in large quantities in olive leaves and may be 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 variety, growing conditions, and leaf age. Therefore, additional studies may be needed to determine the concentration of OeST1 in different types of olive leaves and under different growing conditions.

[0056] Although some embodiments use the composition of the present invention as an oral supplement for oral minoxidil, the composition of the present invention can be used to treat alopecia in the absence of minoxidil. For example, an embodiment may be directed to an oral composition for treating alopecia, wherein the composition includes an SLC22A9 inducer, a HIF-α inducer, and / or an acidifier. Thus, by administering a composition of the present invention that will induce SLC22A9, induce HIF-α, and / or acidify the patient's blood, hair growth can be promoted, hair loss / hair loss can be prevented, and / or the rate of hair loss / hair loss can be reduced. Again, the acidifier can upregulate SLC22A9 and / or downregulate AABC3. The acidifier can include ammonium chloride, methanol, salicylates / esters, biguanides, alcohols, polysaccharides, cyanides, and / or carbon monoxide. The HIF-α inducer can include araucaria extract, green tree extract, glycyrrhiza glabra, o-phenanthroline, iodochlorohydroxyquinoline, and / or cobalt sulfate heptahydrate.

[0057] It should be understood that any plant that produces flavonoids or has minoxidil sulfotransferase, phenol sulfotransferase and / or sulfotransferase can be used. Any method and composition can use the natural concentration of enzymes found in plants or extracts thereof. In addition, any enzyme can also be derived from animals.

[0058] It should be understood that the disclosure of a range of values ​​is a disclosure of each value within the range, including the endpoints. It should also be appreciated that some components, features, and / or configurations may be described in conjunction with only one particular embodiment, but these same components, features, and / or configurations may be applied or used with 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 with other embodiments. Therefore, 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 statement.

[0059] It will be apparent to those skilled in the art that, in view of the above teachings of the present disclosure, many modifications and variations of the described embodiments and embodiments are possible. The disclosed embodiments and embodiments are presented for illustrative purposes only. Other alternative embodiments may include some or all of the features disclosed herein. It is therefore intended to encompass all such modifications and alternative embodiments that may be within the true scope of the present invention, which will be given its full breadth.

[0060] It should be understood that the embodiments disclosed herein may be modified to meet a specific set of design criteria. Therefore, although certain exemplary embodiments of the compositions disclosed herein and methods of using and making the compositions have been discussed and described, it should be clearly understood that the invention is not limited thereto, but may be variously implemented and practiced within the scope of the following claims.

Claims

1. An oral supplement for oral administration of minoxidil, the oral supplement comprising: SLC22A9 inducers, HIF-α inducers and / or acidifying agents.

2. The oral supplement of claim 1, wherein: The acidifying agent upregulates SLC22A9 and / or downregulates AABC3.

3. The oral supplement of claim 1, wherein: The HIF-α inducers include arachis oleifera extract, green tree extract, licorice, o-phenanthroline, iodochlorohydroxyquinoline and / or cobalt sulfate heptahydrate.

4. The oral supplement of claim 1, further comprising: An oral minoxidil therapeutic composition comprising minoxidil or a pharmaceutically acceptable salt thereof.

5. The oral supplement of claim 4, wherein: Minoxidil or a pharmaceutically acceptable salt thereof is present in the oral minoxidil therapeutic composition in a dosage ranging from 0.125 mg to 10 mg.

6. The oral supplement of claim 1, wherein: Acidifying agents include ammonium chloride, methanol, salicylates, biguanides, alcohols, polysaccharides, cyanide and / or carbon monoxide.

7. A method for treating alopecia, comprising: Treat hair loss by: Oral minoxidil is administered to patients suffering from alopecia; and administering an oral supplement before, during, and / or after the administration of oral minoxidil, the oral supplement comprising an SLC22A9 inducer, a HIF-α inducer, and / or an agent that acidifies the patient's blood, or Alopecia is treated by administering an oral supplement comprising oral minoxidil, which additionally includes a SLC22A9 inducer, a HIF-α inducer, and / or an agent that acidifies the patient's blood.

8. The method according to claim 7, wherein: Acidifiers upregulate SLC22A9 and / or downregulate AABC3.

9. The method according to claim 7, wherein: Acidifiers cause mild acidosis in patients.

10. The method according to claim 7, wherein: HIF-α inducers include arachis oleifera extract, green tree extract, glycyrrhiza glabra, o-phenanthroline, iodochlorohydroxyquinoline and / or cobalt sulfate heptahydrate.

11. The method according to claim 7, wherein: Oral minoxidil includes minoxidil or a pharmaceutically acceptable salt thereof.

12. The method according to claim 11, wherein: Minoxidil or a pharmaceutically acceptable salt thereof is present in oral minoxidil at a concentration ranging from 0.125 mg to 10 mg.

13. The method according to claim 7, wherein: Acidifying agents include ammonium chloride, methanol, salicylates, biguanides, alcohols, polysaccharides, cyanide and / or carbon monoxide.

14. An oral composition for treating alopecia, the composition comprising: SLC22A9 inducers, HIF-α inducers and / or acidifying agents.

15. The oral composition according to claim 14, wherein: Acidifiers upregulate SLC22A9 and / or downregulate AABC3.

16. The oral composition according to claim 14, wherein: HIF-α inducers include arachis oleifera extract, green tree extract, glycyrrhiza glabra, o-phenanthroline, iodochlorohydroxyquinoline and / or cobalt sulfate heptahydrate.

17. The oral composition according to claim 14, wherein: Acidifying agents include ammonium chloride, methanol, salicylates, biguanides, alcohols, polysaccharides, cyanide and / or carbon monoxide.

18. A method for treating alopecia, the method comprising: An oral composition comprising a SLC22A9 inducer, a HIF-α inducer and / or an acidifying agent is administered to a patient suffering from alopecia.

19. The method of claim 18, wherein: Acidifiers upregulate SLC22A9 and / or downregulate AABC3.

20. The method of claim 18, wherein: HIF-α inducers include arachis oleifera extract, green tree extract, glycyrrhiza glabra, o-phenanthroline, iodochlorohydroxyquinoline and / or cobalt sulfate heptahydrate.

21. The method of claim 18, wherein: Acidifying agents include ammonium chloride, methanol, salicylates, biguanides, alcohols, polysaccharides, cyanide and / or carbon monoxide.

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