Method and composition for improving or maintaining skin, hair follicle, scalp or hair health

Abstract

Disclosed are a method and composition for improving or maintaining the skin, hair follicle, scalp or hair health of a subject and related use thereof in preparing a personal care product and cosmetic product for improving or maintaining the skin, hair follicle, scalp or hair health of a subject. The method and composition of the present invention can inhibit the growth of microorganisms that cause skin problems, and / or promote the growth of microorganisms beneficial to the skin, and / or eliminate or mitigate skin problems, and / or inhibit the growth of hair follicle, scalp or hair health-related microorganisms, and / or eliminate or mitigate hair follicle, scalp or hair problems.

Description

Methods and compositions for improving or maintaining skin, follicle, scalp or hair health Technical Field

[0001] The present invention belongs to the technical field of cosmetics and personal care products; in particular, it relates to methods and compositions for improving or maintaining the health of a subject's skin, hair follicles, scalp or hair, as well as related applications of the methods and compositions in preparing personal care products and cosmetics for improving or maintaining the health of a subject's skin, hair follicles, scalp or hair. Background Art

[0002] The microbiome is an ecosystem of trillions of microorganisms living within our bodies. It is composed of bacteria, viruses, fungi, and other microorganisms. The skin, the body's largest organ, is home to approximately 1,000 bacterial species. These interdependent and mutually restrictive bacteria form a stable and harmonious biological barrier, collectively maintaining the balance of the skin's microbiome and playing a vital physiological role. Furthermore, in vitro studies have shown that skin microbes can influence the structure and function of the skin without penetrating the epidermis. Therefore, maintaining a healthy microbiome plays a crucial role in maintaining skin health.

[0003] Generally speaking, bacteria and fungi are important components of the skin microbiome, working together to maintain the skin's functioning. However, the skin microbiome can abnormally increase, decrease, or even disappear due to uncontrollable factors. An imbalance in the microbiome can lead to skin problems, including eczema, atopic dermatitis, and psoriasis. For example, overgrowth of Malassezia, Propionibacterium acnes, Staphylococcus epidermidis, and Candida albicans can cause inflammation; an excess of Staphylococcus aureus can cause eczema. Candida albicans is a common fungus that may be associated with the scalp microbiome. Candida albicans is usually part of the body's normal microbiome and does not cause problems under normal circumstances. However, when a person's immune system is compromised, the scalp is moist, or they use excessive sugary or oily hair products, Candida albicans may overgrow, leading to candidal dandritis. Candidal dandritis is mainly manifested by symptoms such as itching, erythema, desquamation and burning sensation on the scalp. Propionibacterium grows in the hair follicles and sebaceous glands of the skin and may sometimes cause skin problems such as acne. Staphylococcus is a type of bacteria that is widely present on human skin. Some strains of it may cause skin infections such as cellulitis and boils. Malassezia is a type of fungus that is often found on the human epidermis and scalp. In some cases, Malassezia may cause problems such as dandruff and psoriasis. Lactic acid bacteria can help regulate the pH value of the skin, maintain skin health, and have antibacterial and anti-inflammatory effects. Bifidobacterium can enhance the skin barrier function, keep the skin hydrated and smooth, and inhibit the growth of harmful microorganisms. As we age, we lose our antioxidant capacity because the level of antioxidants in the skin is very low, and some beneficial bacteria also decrease. For example, young individuals or those with more elastic skin have a large number of Streptococcus species. The reduction of Streptococci such as Streptococcus pneumoniae, Streptococcus infantis, and Streptococcus thermophilus can lead to aging problems such as lack of skin elasticity and radiance, fine lines, sagging, and dryness. Therefore, inhibiting the growth of harmful microbial communities or promoting the increase of beneficial microorganisms can significantly improve skin condition and maintain skin health.

[0004] The scalp microbiome grows on the skin on the top of the head, with a variety of bacteria working together, each making its own contribution to scalp health. If this delicate balance is broken, the scalp microbiome will be abnormal, and then rashes, flaking scalp, itchy skin, androgenic alopecia, etc. will appear. Microbiological studies have shown that androgenic alopecia is related to bacteria on hair follicles, and subjects with androgenic alopecia have the same type of yeast (Malassezia) as subjects with dandruff. Malassezia accounts for 96% of the total scalp fungi, and the most abundant distribution on the scalp is Malassezia restricta (M. restricta) and Malassezia globosa (M. globosa). Reducing or inhibiting the growth of this type of microbiome can significantly improve scalp health and prevent hair loss.

[0005] Microbial imbalance can lead to damage to the skin, hair follicles, scalp, or hair, subsequently causing inflammation and problems such as dry skin, sagging, and aging, or leading to problems such as itchy scalp, oily scalp, rashes, hair loss, and hypotrichosis. Therefore, there is an urgent need to find a method to improve or maintain the microbial health of the subject. Alitretinoin (9-cis RA, CAS-5300-03-8) is a retinoid with excellent anti-inflammatory properties. Ergothioneine (EGT) is a safe natural compound with excellent anti-inflammatory and antioxidant properties. Currently, there are no studies on the interaction between alitretinoin and the skin microbiome, especially by inhibiting the excessive growth of harmful microorganisms, thereby alleviating or inhibiting problems with the skin, hair follicles, scalp, or hair; or promoting the growth of beneficial microorganisms, thereby protecting the health of the skin, hair follicles, scalp, or hair.

[0006] The present inventors have discovered that 9-cis RA, or a combination of 9-cis RA and EGT, can improve or maintain the health of the skin, hair follicles, scalp, or hair by improving or maintaining the health of the subject's microbiome. Summary of the Invention

[0007] In one aspect, the present invention provides a method for improving or maintaining the health of a subject's skin, hair follicles, scalp or hair, comprising administering to the subject a composition comprising an effective amount of alitretinoin or a pharmaceutically acceptable salt, hydrate, ester, analog or derivative thereof.

[0008] In some embodiments, the composition further comprises an effective amount of ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof.

[0009] In some embodiments, improving or maintaining the health of a subject's skin, hair follicles, scalp, or hair comprises inhibiting the growth of microorganisms that cause skin problems, and / or promoting the growth of microorganisms that are beneficial to the skin, and / or eliminating or alleviating skin problems, and / or inhibiting the growth of microorganisms associated with hair follicle, scalp, or hair health, and / or eliminating or alleviating hair follicle, scalp, or hair problems.

[0010] In some embodiments, the microorganisms that cause skin problems are selected from one or more of the following: Propionibacterium, Staphylococcus, Candida albicans and Malassezia; the microorganisms that are beneficial to the skin are selected from one or more of the following: Streptococcus, Lactobacillus, Bifidobacterium; and the skin problems are selected from one or more of the following: lack of skin elasticity, dry skin, desquamation, dull skin, fine lines, sagging, inflammation, peeling, acne, atopic dermatitis, eczema, melasma, erythema, papules, and itching.

[0011] In some embodiments, the microorganisms associated with hair follicle, scalp or hair health are selected from one or more of the following: Staphylococcus, Propionibacterium and Malassezia; hair follicle, scalp or hair problems include folliculitis or seborrheic dermatitis, itchy scalp, dandruff, oily scalp, rash, itchy skin, flaky scalp, hair loss, tinea capitis, hypotrichosis, hypotrichosis, and lichen planus.

[0012] In some embodiments, the composition is prepared as a personal care product, a cosmetic.

[0013] In some embodiments, the composition is in the form of a lotion, cream, ointment, serum, paste, gel, solution, dispersion, spray, suspension, emulsion, foam, patch, powder, film, spirit, tincture, and liniment.

[0014] In some embodiments, alitretinoin or a pharmaceutically acceptable salt, hydrate, ester, analog or derivative thereof is formulated for administration in an amount of 0.1-500 mg per day, or in an amount of 0.1 μM to 1 M, or 0.001 to 50.0% (w / w). In some embodiments, alitretinoin or a pharmaceutically acceptable salt, hydrate, ester, analog or derivative thereof is formulated for administration in an amount of 1 μM to 500 mM, or 10 to 300 mg, or 0.003 to 10% (w / w) per day. In some embodiments, alitretinoin or a pharmaceutically acceptable salt, hydrate, ester, analog or derivative thereof is formulated at 0.5-1500 mg, 1-1200 mg, 2-1000 mg, 3-800 mg, 5-600 mg, 8-500 mg, 10-300 mg, 15-200 mg, 20-100 mg, 0.1-400 mg, 0.5-300 mg, 1-200 mg, 2-200 mg, 5-200 mg, 10-200 mg, 3-150 mg, 10-150 mg, 3-100 mg, 10-100 mg, 5-90 mg, 8-80 mg, 10-80 mg, 15-70 mg, 20-60 mg or in an amount of 0.1 μM to 500 μM, 1 μM to 500 μM, 1 μM to 5mM, 1 μM to 500 mM, 5 μM to 500 μM, 5 μM to 5mM, 5 μM to 100 mM, 5 μM to 500 mM, 50 μM to 500 μM, 50 μM to 5 mM, or 0.001 to 45%, 0.002 to 40%, 0.002 to 30%, 0.003 to 20%, 0.003 to 10%, 0.005 to 5%, 0.005 to 2%, 0.01-1%, 0.01 to 0.5%, 0.02 to 0.2%, 0.05 to 0.1%, 0.0005% to 5%, 0.001% to 25%, 0.0 0.01% to 10%, 0.001% to 3%, 0.002% to 2%, 0.003% to 1%, 0.005% to 10%, 0.005% to 0.8%, 0.008% to 10%, 0.008% to 0.5%, 0.01% to 20%, 0.01% to 10%, 0.01% to 1%, 0.01% to 0.1%, 0.05% to 20%, 0.05% to 10%, 0.05% to 5% (w / w).

[0015] In some embodiments, thioneine or its pharmaceutically acceptable salt, acid, ester, analog or derivative is formulated to be used in an amount of 1-1500 mg per day. In some embodiments, thioneine or its pharmaceutically acceptable salt, acid, ester, analog or derivative can be formulated to be used in an amount of 1-1000 mg, 2-500 mg, 3-200 mg, 4-100 mg, 5-50 mg, 10-30 mg per day.

[0016] In some embodiments, the composition is administered topically, transdermally, or subcutaneously. In some embodiments, administration includes oral administration and external application. External application includes application and the like.

[0017] In another aspect, the present invention provides a composition comprising alitretinoin or a pharmaceutically acceptable salt, hydrate, ester, analog or derivative thereof, for improving or maintaining the health of a subject's skin, hair follicles, scalp or hair.

[0018] In some embodiments, the composition further comprises an effective amount of ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof.

[0019] In some embodiments, the composition inhibits the growth of microorganisms that cause skin problems, and / or promotes the growth of microorganisms that are beneficial to the skin, and / or eliminates or reduces skin problems, and / or inhibits the growth of microorganisms associated with hair follicle, scalp or hair health, and / or eliminates or reduces hair follicle, scalp or hair problems.

[0020] In some embodiments, the microorganisms that cause skin problems are selected from one or more of the following: Propionibacterium, Staphylococcus, Candida albicans and Malassezia; the microorganisms that are beneficial to the skin are selected from one or more of the following: Streptococcus, Lactobacillus, Bifidobacterium; and the skin problems are selected from one or more of the following: lack of skin elasticity, dry skin, desquamation, dull skin, fine lines, sagging, inflammation, peeling, acne, atopic dermatitis, eczema, melasma, erythema, papules, and itching.

[0021] In some embodiments, the microorganisms associated with hair follicle, scalp or hair health are selected from one or more of the following: Staphylococcus, Propionibacterium and Malassezia; hair follicle, scalp or hair problems include folliculitis or seborrheic dermatitis, itchy scalp, dandruff, oily scalp, rash, itchy skin, flaky scalp, hair loss, tinea capitis, hypotrichosis, hypotrichosis, and lichen planus.

[0022] In some embodiments, the composition is prepared as a personal care product, a cosmetic.

[0023] In some embodiments, the composition is in the form of a lotion, cream, ointment, serum, paste, gel, solution, dispersion, spray, suspension, emulsion, foam, patch, powder, film, spirit, tincture, and liniment.

[0024] In some embodiments, alitretinoin or its pharmaceutically acceptable salt, hydrate, ester, analog or derivative is formulated to be administered in an amount of 0.1-500 mg per day or in an amount of 0.1 μM to 1 M or 0.001 to 50.0% (w / w). In some embodiments, alitretinoin or its pharmaceutically acceptable salt, hydrate, ester, analog or derivative is formulated to be administered in an amount of 0.5-1500 mg, 1-1200 mg, 2-1000 mg, 3-800 mg, 5-600 mg, 8-500 mg, 10-300 mg, 15-200 mg, 20-100 mg, 0.1-400 mg, 0.5-300 mg, 1-200 mg, 2-200 mg, 5-200 mg, 10-200 mg, 3-150 mg, 10-150 mg, 3-100 mg, 10-100 mg, 5-90 mg, 8-80 mg, 10-80 mg, 15-70 mg, 20-60 mg or in an amount of 0.1 μM to 500 μM, 1 μM to 500 μM, 1 μM to 5mM, 1 μM to 500 mM, 5 μM to 500 μM, 5 μM to 5mM, 5 μM to 100 mM, 5 μM to 500 mM, 50 μM to 500 μM, 50 μM to 5 mM, or 0.001 to 45%, 0.002 to 40%, 0.002 to 30%, 0.003 to 20%, 0.003 to 10%, 0.005 to 5%, 0.005 to 2%, 0.01-1%, 0.01 to 0.5%, 0.02 to 0.2%, 0.05 to 0.1%, 0.0005% to 5%, 0.001% to 25%, 0.0 In some embodiments, the composition comprises alitretinoin or a pharmaceutically acceptable salt, hydrate, ester, analog or derivative thereof in an amount of 1 μM to 500 mM, or 10 to 300 mg, or 0.003 to 10% (w / w).

[0025] In some embodiments, thioneine or its pharmaceutically acceptable salt, acid, ester, analog or derivative is formulated to be used in an amount of 1-1500 mg per day. In some embodiments, thioneine or its pharmaceutically acceptable salt, acid, ester, analog or derivative can be formulated to be used in an amount of 1-1000 mg, 2-500 mg, 3-200 mg, 4-100 mg, 5-50 mg, 10-30 mg per day.

[0026] In another aspect, the present invention provides a composition for use in preparing a personal care product or cosmetic for improving or maintaining the health of a subject's skin, hair follicles, scalp or hair, wherein the composition comprises an effective amount of alitretinoin or a pharmaceutically acceptable salt, hydrate, ester, analog or derivative thereof.

[0027] In some embodiments, the composition further comprises an effective amount of ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof.

[0028] In some embodiments, the composition inhibits the growth of microorganisms that cause skin problems, and / or promotes the growth of microorganisms that are beneficial to the skin, and / or eliminates or reduces skin problems, and / or inhibits the growth of microorganisms associated with hair follicle, scalp or hair health, and / or eliminates or reduces hair follicle, scalp or hair problems.

[0029] In some embodiments, the microorganisms that cause skin problems are selected from one or more of the following: Propionibacterium, Staphylococcus, Candida albicans and Malassezia; the microorganisms that are beneficial to the skin are selected from one or more of the following: Streptococcus, Lactobacillus, Bifidobacterium; and the skin problems are selected from one or more of the following: lack of skin elasticity, dry skin, desquamation, dull skin, fine lines, sagging, inflammation, peeling, acne, atopic dermatitis, eczema, melasma, erythema, papules, and itching.

[0030] In some embodiments, the microorganisms associated with hair follicle, scalp or hair health are selected from one or more of the following: Staphylococcus, Propionibacterium and Malassezia; hair follicle, scalp or hair problems include folliculitis or seborrheic dermatitis, itchy scalp, dandruff, oily scalp, rash, itchy skin, flaky scalp, hair loss, tinea capitis, hypotrichosis, hypotrichosis, and lichen planus.

[0031] In some embodiments, the composition is in the form of a lotion, cream, ointment, serum, paste, gel, solution, dispersion, spray, suspension, emulsion, foam, patch, powder, film, spirit, tincture, and liniment. In some embodiments, the composition is administered by a route such as topical, transdermal, or subcutaneous administration.

[0032] In some embodiments, alitretinoin or a pharmaceutically acceptable salt, hydrate, ester, analog or derivative thereof is formulated for administration in an amount of 0.1-500 mg per day, or in an amount of 0.1 μM to 1 M, or 0.001 to 50.0% (w / w). In some embodiments, alitretinoin or a pharmaceutically acceptable salt, hydrate, ester, analog or derivative thereof is formulated for administration in an amount of 1 μM to 500 mM, or 10 to 300 mg, or 0.003 to 10% (w / w) per day. In some embodiments, alitretinoin or a pharmaceutically acceptable salt, hydrate, ester, analog or derivative thereof is formulated at 0.5-1500 mg, 1-1200 mg, 2-1000 mg, 3-800 mg, 5-600 mg, 8-500 mg, 10-300 mg, 15-200 mg, 20-100 mg, 0.1-400 mg, 0.5-300 mg, 1-200 mg, 2-200 mg, 5-200 mg, 10-200 mg, 3-150 mg, 10-150 mg, 3-100 mg, 10-100 mg, 5-90 mg, 8-80 mg, 10-80 mg, 15-70 mg, 20-60 mg or in an amount of 0.1 μM to 500 μM, 1 μM to 500 μM, 1 μM to 5mM, 1 μM to 500 mM, 5 μM to 500 μM, 5 μM to 5mM, 5 μM to 100 mM, 5 μM to 500 mM, 50 μM to 500 μM, 50 μM to 5 mM, or 0.001 to 45%, 0.002 to 40%, 0.002 to 30%, 0.003 to 20%, 0.003 to 10%, 0.005 to 5%, 0.005 to 2%, 0.01-1%, 0.01 to 0.5%, 0.02 to 0.2%, 0.05 to 0.1%, 0.0005% to 5%, 0.001% to 25%, 0.0 0.01% to 10%, 0.001% to 3%, 0.002% to 2%, 0.003% to 1%, 0.005% to 10%, 0.005% to 0.8%, 0.008% to 10%, 0.008% to 0.5%, 0.01% to 20%, 0.01% to 10%, 0.01% to 1%, 0.01% to 0.1%, 0.05% to 20%, 0.05% to 10%, 0.05% to 5% (w / w).

[0033] In some embodiments, thioneine or its pharmaceutically acceptable salt, acid, ester, analog or derivative is formulated to be used in an amount of 1-1500 mg per day. In some embodiments, thioneine or its pharmaceutically acceptable salt, acid, ester, analog or derivative can be formulated to be used in an amount of 1-1000 mg, 2-500 mg, 3-200 mg, 4-100 mg, 5-50 mg, 10-30 mg per day.

[0034] This Summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description. This Summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used to limit the scope of the claimed subject matter. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 is a graph showing the total number of Staphylococcus epidermidis recovered after treatment with various concentrations of 9-cis RA, 9-cis RA and EGT, and 1 μM α-GO.

[0036] Figure 2 is a graph showing the total number of Candida albicans recovered after treatment with various concentrations of 9-cis RA, 9-cis RA and EGT, and 1 μM α-GO.

[0037] FIG3 is a graph showing the total number of P. acnes recovered after treatment with various concentrations of 9-cis RA, 9-cis RA and EGT, and 1 μM α-GO.

[0038] Figure 4 is a graph showing the total number of Malassezia recovered after treatment with various concentrations of 9-cis RA, 9-cis RA and EGT, and 1 μM α-GO.

[0039] FIG5 is a graph showing the total number of Staphylococcus aureus recovered after treatment with various concentrations of 9-cis RA, 9-cis RA and EGT, and 1 μM α-GO.

[0040] FIG6 is an optical density graph at 600 nm of Malassezia globosa after being treated with various concentrations of alitretinoin.

[0041] FIG7 is an optical density graph at 600 nm of Malassezia restricta after being treated with various concentrations of alitretinoin.

[0042] FIG8 is a graph showing the optical density at 530 nm of Propionibacterium acnes after treatment with various concentrations of alitretinoin.

[0043] FIG9 is a graph showing the optical density at 530 nm of Staphylococcus aureus after treatment with various concentrations of alitretinoin.

[0044] FIG10 is an optical density graph at 530 nm of Staphylococcus epidermidis after being treated with various concentrations of alitretinoin. DETAILED DESCRIPTION

[0045] The preferred embodiments of the present invention will now be described in detail with reference to the embodiments thereof. Although the present invention will be described in conjunction with the preferred embodiments, it should be understood that they are not intended to limit the present invention to these embodiments. On the contrary, the present invention is intended to cover substitutions, modifications and equivalents, which may be included within the spirit and scope of the present invention as defined in the claims.

[0046] As used herein, the term "or" is intended to include "and" and "or." In other words, the term "or" can also be replaced with "and / or."

[0047] As used herein, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise.

[0048] As used herein, the term "comprises" or "includes" or variations thereof refers to instances where the term is used in its non-limiting sense, meaning that items following the term are included, but items not specifically mentioned are not excluded. It also includes the more restrictive verbs 'consisting essentially of' and 'consisting of.'

[0049] As used herein, the terms "mammal" or "subject" are used interchangeably to refer to any animal to which the methods and compositions of the present disclosure can be applied or administered. The animal may be suffering from an illness or other disease, but the animal does not need to be sick to benefit from the methods and compositions of the present disclosure. Thus, any animal can utilize the disclosed compositions or be a recipient of the disclosed methods. Although the animal subject is preferably a human, the methods and compositions of the present invention are also suitable for veterinary medicine, for example, for treating domesticated species such as canines, felines, murines, and various other pets; farm animals, such as cattle, horses, sheep, goats, pigs, etc.; and wild animals, such as non-human primates in the wild or in zoos, etc.

[0050] As used herein, the term "administer" refers to the process of delivering the disclosed composition or active ingredient to a subject. The composition of the present invention is preferably administered orally, intravenously, intramuscularly, intraperitoneally, topically, or sublingually, but may also be administered by other conventional routes to achieve the desired effect.

[0051] As used herein, the term "effective amount" refers to the amount required to achieve the effects taught herein. An effective amount herein includes, but is not limited to, an amount necessary to improve or maintain the health of a subject's skin, hair follicles, scalp, or hair, and / or inhibit the growth of microorganisms that cause skin problems, and / or promote the growth of microorganisms that are beneficial to the skin, and / or eliminate or alleviate skin problems, and / or inhibit the growth of microorganisms associated with hair follicle, scalp, or hair health, and / or eliminate or alleviate hair follicle, scalp, or hair problems. According to the present disclosure, a suitable single dose size is a dose that can achieve the above-mentioned effects when applied once or multiple times within an appropriate time period.

[0052] As used herein, the term "pharmaceutically acceptable" refers to pharmaceutically, physiologically, dietary acceptable, and refers to those compositions or agents, materials or combinations of compositions and / or dosage forms thereof that are within the scope of sound medical judgment, suitable for contact with the tissues of humans and animals, compatible with the other ingredients of the composition, without excessive toxicity, irritation, allergic response or other problems or complications, and commensurate with a reasonable benefit / risk ratio.

[0053] In some embodiments, the alitretinoin of the present invention or its pharmaceutically acceptable salt, hydrate, ester, analog or derivative and / or composition comprising the same can be prepared as a composition together with a dietary or pharmaceutically acceptable carrier. "Carrier" can include liquid or solid fillers, diluents, excipients, solvents, encapsulating materials, buffers, stabilizers, preservatives, oils, surfactants, gelling agents, antioxidants, chelating agents, viscosity enhancers, ultraviolet absorbers, pH regulators, pigments, spices, etc. The carrier used in the present invention is preferably a carrier suitable for personal care products, cosmetics, and beauty products.

[0054] The methods of the present invention comprise administering at least 0.1 mg per day, typically 0.1-2000 mg, 0.5-1500 mg, 1-1200 mg, 2-1000 mg, 3-800 mg, 5-600 mg, 8-500 mg, 10-300 mg, 15-200 mg, 20-100 mg, 0.1-400 mg, 0.5-300 mg, 1-200 mg, 2-200 mg, 5-200 mg, 10-200 mg, 3-150 mg, 10-150 mg, 3-100 mg, 10-100 mg, 5-90 mg, 8-100 mg, 10-2 ... -80 mg, 10-80 mg, 15-70 mg, 20-60 mg of alitretinoin or a pharmaceutically acceptable salt, hydrate, ester, analog or derivative thereof, or at 0.1 μM to 1 M or 0.001 to 50.0% (w / w), typically 0.1 μM to 500 μM, 1 μM to 500 μM, 1 μM to 5 mM, 1 μM to 500 mM, 5 μM to 500 μM, 5 μM to 5 mM, 5 μM to 100 mM, 5 μM to 500 mM, 50 μM to 500 μM, 50 μM to 5 mM, or 0.001 to 45%, 0.002 to 45%. 0%, 0.002 to 30%, 0.003 to 20%, 0.003 to 10%, 0.005 to 5%, 0.005 to 2%, 0.01-1%, 0.01 to 0.5%, 0.02 to 0.2%, 0.05 to 0.1%, 0.0005% to 5%, 0.001% to 25%, 0.001% to 10%, 0.001% to 3%, 0.002% to 2%, 0.003% to 1%, 0.005% to 10%, 0.005% to 0.8%, 0.008% to 10%, 0.008% to 0.5%, 0.01% to 20%, 0 In some embodiments, the amount of alitretinoin or its pharmaceutically acceptable salt, hydrate, ester, analog or derivative is used in an amount of 0.01% to 10%, 0.01% to 1%, 0.01% to 0.1%, 0.05% to 20%, 0.05% to 10%, 0.05% to 5% (w / w), and / or method of the present invention comprises using at least 1mg every day, typically 1-1500mg, preferably 1-1000mg, 2-500mg, 3-100mg, 4-50mg or 5-30mg ergothioneine or its pharmaceutically acceptable salt, acid, ester, analog or derivative, this depends on concrete preparation and form.Amount to be used can also change according to factors such as sensitivity, age, sex and body weight, idiosyncrasies of the experimenter.One or more dosages can be used once or repeatedly every day or with applicable frequency in any time period.For example, effective dose can be used every day, continue one day, several days, many days or use every day indefinitely.

[0055] The following examples are illustrative of selected embodiments of the present invention and are not intended to limit the scope of the invention.

[0056] Primary adult human dermal fibroblasts were embedded in a fibrin matrix to create dermal equivalents. The dermal equivalents were cultured to allow the fibroblasts to reconstitute the matrix. Primary neonatal human keratinocytes were applied to the surface of the dermal equivalents and cultured under liquid for 48 hours. Culture was performed at an air-liquid interface (ALI) until a stratified epidermis formed.

[0057] Malassezia, Propionibacterium acnes, Staphylococcus epidermidis, Candida albicans, and Staphylococcus aureus were cultured in appropriate culture medium and incubation conditions (37±2°C, 5±1% (v / v) CO2, ≥95% RH). Inoculation buffer (GS25) was used to prepare the above bacteria containing approximately 1.1×10 6 cfu·mL -1 Inoculum of microbial flora. 10 μL of the mixture was used to colonize the skin (epidermis), with each unit being equivalent to approximately 10 of each bacterium. 5 cfu cm -2 Afterwards, the stratified epidermis was incubated at 37±2°C, 5±1% (v / v) CO2, and ≥95% RH for 3±1 hours.

[0058] α-Glucan oligosaccharide (α-GO) is a well-known prebiotic that can protect skin health by maintaining the balance of microbiota and strengthening the skin's microbial barrier, so it was used as a control in the experiment. Different concentrations of alitretinoin (0μM, 0.1μM, 1μM, 10μM, 100μM), 9-cis RA (1μM) and EGT (1μM) (composition) and control (α-GO, 1μM) were applied to the above-mentioned stratified epidermis, and then incubated at 37±2°C, 5±1% (v / v) CO2, ≥95% RH for 24±2 hours. After incubation, the above-mentioned microorganisms were counted to evaluate the efficacy of alitretinoin, the composition and α-GO in inhibiting microbial growth: 8mm biopsy sections were taken from the skin, and the number of viable bacteria (cfu·cm -2 ). The choice of solid culture medium is based on the characteristics of the microorganism itself.

[0059] As shown in Figures 1-5, epidermal treatment with alitretinoin and its combination with EGT significantly inhibited the colonization of Staphylococcus epidermidis, Candida albicans, Propionibacterium acnes, Malassezia, and Staphylococcus aureus. This inhibitory effect increased with increasing alitretinoin concentration, maintaining a healthy microbial population. Furthermore, at the same concentration, alitretinoin exhibited a greater inhibitory effect than α-GO, and its combination with EGT was even more effective.

[0060] Experiments have confirmed that alitretinoin and its combination with EGT have a positive effect on regulating microbial flora, significantly inhibiting the levels of Staphylococcus epidermidis, Candida albicans, Propionibacterium acnes, Malassezia, and Staphylococcus aureus, alleviating or inhibiting skin problems, and thus repairing skin damage. By inhibiting the excessive growth of microorganisms, alitretinoin and its combination with EGT have a positive regulatory effect on skin health. Therefore, alitretinoin and its combination with EGT can inhibit the excessive growth of microorganisms, thereby maintaining or regulating skin microbial homeostasis and maintaining and improving skin health. Example 2

[0061] Thirty healthy women aged 20-59 years were randomly divided into three groups. The first group (G1, n = 10) applied a base cream as a control group, the second group (G2, n = 10) applied a base cream of 0.01% alitretinoin, and the third group (G3, n = 10) applied a base cream of 0.01% alitretinoin and 5% EGT. The cream was applied once a day for 4 weeks. Skin microorganisms were collected on day 0 and day 28, and the elasticity, moisture and desquamation of the subjects' skin were measured. The participants' faces were washed with sterile water and then smeared on solid tryptic soy agar (TSA) medium. Single colonies were collected and cultured in liquid tryptic soy broth (TSB) medium at 37°C for 72 hours.

[0062] Each sample was centrifuged and the pellet collected. Microbial DNA from the pellet was extracted using a specific kit. DNA purity and quantity were estimated using a spectrophotometer. The bacterial 16S rRNA gene was amplified using the following primers: forward, 5'-AGAGTTTGATCMTGGCTCAG-3'; reverse, 5'-TACGGYTACCTTGTTACGACTT-3'. PCR was performed in a 25-μL reaction vessel containing 2 μL of genomic DNA (10 ng / μL), 0.5 μL of each primer (10 μM), 12.5 μL of 2× KAPA HiFi HotStart Ready Mix, and 9.5 μL of distilled water. The following PCR conditions were used: initial denaturation at 95°C for 3 minutes; 30 cycles of denaturation at 95°C for 1 minute, annealing at 55°C for 1 minute, and extension at 75°C for 90 seconds; and a final extension at 72°C for 8 minutes. The PCR products were sequenced on an ABI-3730XL DNA sequencer and 16S rRNA fragments were identified using NCBI Microbial Nucleotide BLAST and Mega-BLAST.

[0063] The results showed that the Streptococcus in Group 2 and Group 3 was more abundant than that in the base cream group, that is, alitretinoin and its composition can promote the growth of microorganisms that are beneficial to the skin, such as Streptococcus. Streptococcus exists in large quantities in young individuals. In addition, Streptococcus has the potential to improve the elasticity of facial skin. Therefore, alitretinoin and its composition improve the skin condition by increasing the abundance of Streptococcus. In addition, alitretinoin and its composition can significantly increase the skin elasticity and moisture of the subjects and avoid the problem of skin desquamation. Skin elasticity was increased by about 9% and 13% and skin moisture by about 11% and 26% in Group 2 and Group 3, respectively. Therefore, alitretinoin and its composition can improve skin physiological functions and keep the skin young. Example 3

[0064] Forty volunteers with dandruff were recruited and randomly divided into four groups of 7-8 participants each. Each group used a shampoo containing or without 0.08% alitretinoin for 6 weeks. The number and area of ​​dandruff patches were recorded weekly. A skin irritation test kit was used to assess scalp reactions. Finally, a questionnaire was administered to collect participants' feedback on the product.

[0065] The results showed that the experimental group using shampoo containing 0.08% alitretinoin had a 55% reduction in dandruff, which was significantly better than the blank group. In addition, all participants in the alitretinoin group reported that the shampoo was mild and non-irritating, and that the itching sensation was reduced. Example 4

[0066] Growth inhibition of Malassezia globosa, Malassezia restricta, Propionibacterium acnes, Staphylococcus aureus, and Staphylococcus epidermidis was tested using 50 ml test tubes containing 10 ml of mDixon medium. The culture was first inoculated into a petri dish to an optical density (OD) of 0.2. Each petri dish was then loaded with the above microorganisms and challenged with the test material (control and various concentrations of alitretinoin: 0.001 μM, 0.01 μM, 0.1 μM, 1 μM, 10 μM, 100 μM, 1000 μM). After shaking at 30°C for 48 hours, the OD was measured and recorded using a spectrophotometer.

[0067] Figures 6 and 7 show the optical density at 600 nm of Malassezia globosa and Malassezia restrictosa after treatment with various concentrations of alitretinoin. After treatment with alitretinoin, the optical density of both Malassezia globosa and Malassezia restrictosa culture dishes decreased; the higher the alitretinoin concentration, the lower the optical density. At 1000 μM alitretinoin, the optical density of Malassezia globosa even decreased from 4.3 in the control to 0.3, while the optical density of Malassezia restrictosa also decreased from 6.7 in the control to 0.8, demonstrating that alitretinoin can significantly inhibit the growth of lipophilic fungi such as Malassezia globosa and Malassezia restrictosa. Figures 8 to 10 show the optical density at 530 nm of Propionibacterium acnes, Staphylococcus aureus, and Staphylococcus epidermidis after treatment with various concentrations of alitretinoin. After treatment with alitretinoin, the optical density of the culture dishes of Propionibacterium acnes, Staphylococcus aureus and Staphylococcus epidermidis all decreased; and the higher the concentration of alitretinoin, the lower the optical density; under treatment with 1000μM alitretinoin, the optical density of Propionibacterium acnes decreased from 2.7 in the control treatment to 0.4, while the optical density of Staphylococcus aureus and Staphylococcus epidermidis even decreased from 2.3 and 1.7 in the control treatment to 0.5 and 0.2, respectively, indicating that alitretinoin can significantly inhibit the growth of Gram-positive bacteria such as Propionibacterium acnes, Staphylococcus aureus and Staphylococcus epidermidis.

[0068] Experiments have confirmed that alitretinoin has a positive effect on regulating the scalp microbiome, significantly reducing the levels of Malassezia, Propionibacterium acnes, Staphylococcus aureus and Staphylococcus epidermidis, relieving or eliminating scalp inflammation such as folliculitis and seborrheic dermatitis, and then repairing scalp or subcutaneous barrier damage. It also has a positive therapeutic or inhibitory effect on itchy scalp, dandruff, oily scalp, rash, itchy skin, flaking scalp, hair loss, tinea capitis, hypotrichosis, hypotrichosis, and lichen planus, and has a positive regulatory effect on the health of hair follicles, scalp or hair.

[0069] Although specific embodiments and examples of the present invention have been described herein, it will be understood by those skilled in the art that any modifications and variations may be made without departing from the principles of the present invention. The above examples and descriptions do not limit the scope of the present invention. Any combination of the embodiments of the present invention, as well as any obvious extensions or analogs thereof, are within the scope of the present invention. Furthermore, the present invention encompasses any arrangement intended to achieve the same purpose, as well as all such variations and modifications that fall within the scope of the appended claims.

Claims

1. A method for improving or maintaining the health of a subject's skin, hair follicles, scalp or hair, the method comprising administering a composition to the subject, characterized in that: The composition comprises an effective amount of alitretinoin or a pharmaceutically acceptable salt, hydrate, ester, analog or derivative thereof.

2. The method according to claim 1, characterized in that: The composition also comprises an effective amount of ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog or derivative thereof.

3. The method according to claim 1 or 2, characterized in that: The improving or maintaining the health of the subject's skin, hair follicles, scalp or hair includes inhibiting the growth of microorganisms that cause skin problems, and / or promoting the growth of microorganisms that are beneficial to the skin, and / or eliminating or alleviating skin problems, and / or inhibiting the growth of microorganisms associated with hair follicles, scalp or hair health, and / or eliminating or alleviating hair follicles, scalp or hair problems.

4. The method according to claim 3, characterized in that: The microorganisms that cause skin problems are selected from one or more of the following: Propionibacterium, Staphylococcus, Candida albicans and Malassezia; the microorganisms that are beneficial to the skin are selected from one or more of the following: Streptococcus, lactic acid bacteria, and Bifidobacterium; the skin problems are selected from one or more of the following: lack of skin elasticity, dry skin, desquamation, dull skin, fine lines, sagging, inflammation, peeling, acne, atopic dermatitis, eczema, chloasma, erythema, papules, and itching.

5. The method according to claim 3, characterized in that: The hair follicle, scalp or hair health-related microorganisms are selected from one or more of the following: Staphylococcus, Propionibacterium and Malassezia; hair follicle, scalp or hair problems include folliculitis or seborrheic dermatitis, itchy scalp, dandruff, oily scalp, rash, itchy skin, flaking scalp, hair loss, tinea capitis, hypotrichosis, hypotrichosis, and hair lichen planus.

6. The method according to any one of claims 1 to 5, characterized in that The composition is prepared as personal care products and cosmetics.

7. The method according to any one of claims 1 to 6, characterized in that The composition is in the form of a lotion, cream, ointment, serum, paste, gel, solution, dispersion, spray, suspension, emulsion, foam, patch, powder, film, spirit, tincture and liniment.

8. The method according to any one of claims 1 to 7, characterized in that The alitretinoin or a pharmaceutically acceptable salt, hydrate, ester, analog or derivative thereof is formulated for administration in an amount of 0.1-500 mg per day or in an amount of 0.1 μM to 1 M or 0.001 to 50.0% (w / w).

9. The method according to any one of claims 1 to 8, characterized in that The alitretinoin or a pharmaceutically acceptable salt, hydrate, ester, analog or derivative thereof is formulated for administration in an amount of 1 μM to 500 mM, or 10 to 300 mg, or 0.003 to 10% (w / w) per day.

10. The method according to any one of claims 2 to 9, characterized in that The ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog or derivative thereof is formulated for administration in an amount of 1-1500 mg per day.

11. The method according to any one of claims 1 to 10, characterized in that The administration includes internal administration and external application.

12. A composition comprising alitretinoin or a pharmaceutically acceptable salt, hydrate, ester, analog or derivative thereof, characterized in that: The composition is used to improve or maintain the health of a subject's skin, hair follicles, scalp or hair.

13. The composition according to claim 12, characterized in that The composition also comprises an effective amount of ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog or derivative thereof.

14. The composition according to claim 12 or 13, characterized in that The composition inhibits the growth of microorganisms that cause skin problems, and / or promotes the growth of microorganisms that are beneficial to the skin, and / or eliminates or alleviates skin problems, and / or inhibits the growth of microorganisms associated with hair follicle, scalp or hair health, and / or eliminates or alleviates hair follicle, scalp or hair problems.

15. The composition according to claim 14, characterized in that The microorganisms that cause skin problems are selected from one or more of the following: Propionibacterium, Staphylococcus, Candida albicans and Malassezia; the microorganisms that are beneficial to the skin are selected from one or more of the following: Streptococcus, lactic acid bacteria, and Bifidobacterium; the skin problems are selected from one or more of the following: lack of skin elasticity, dry skin, desquamation, dull skin, fine lines, sagging, inflammation, peeling, acne, atopic dermatitis, eczema, chloasma, erythema, papules, and itching.

16. The composition according to claim 14, characterized in that The hair follicle, scalp or hair health-related microorganisms are selected from one or more of the following: Staphylococcus, Propionibacterium and Malassezia; hair follicle, scalp or hair problems include folliculitis or seborrheic dermatitis, itchy scalp, dandruff, oily scalp, rash, itchy skin, flaking scalp, hair loss, tinea capitis, hypotrichosis, hypotrichosis, and hair lichen planus.

17. The composition according to any one of claims 12 to 16, characterized in that The composition is prepared as personal care products and cosmetics.

18. The composition according to any one of claims 12 to 17, characterized in that The composition is in the form of a lotion, cream, ointment, serum, paste, gel, solution, dispersion, spray, suspension, emulsion, foam, patch, powder, film, spirit, tincture and liniment.

19. The composition according to any one of claims 12 to 18, characterized in that The alitretinoin or a pharmaceutically acceptable salt, hydrate, ester, analog or derivative thereof is formulated for administration in an amount of 0.1-500 mg per day or in an amount of 0.1 μM to 1 M or 0.001 to 50.0% (w / w).

20. The composition according to any one of claims 12 to 19, characterized in that The composition comprises alitretinoin or a pharmaceutically acceptable salt, hydrate, ester, analog or derivative thereof in an amount of 1 μM to 500 mM, or 10 to 300 mg, or 0.003 to 10% (w / w).

21. The composition according to any one of claims 12 to 20, characterized in that The ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog or derivative thereof is formulated for administration in an amount of 1-1500 mg per day.

22. Use of a composition in the preparation of a personal care product or cosmetic for improving or maintaining the health of a subject's skin, hair follicles, scalp or hair, characterized in that: The composition comprises an effective amount of alitretinoin or a pharmaceutically acceptable salt, hydrate, ester, analog or derivative thereof.

23. The use according to claim 22, characterized in that The composition also comprises an effective amount of ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog or derivative thereof.

24. The use according to claim 22 or 23, characterized in that The composition inhibits the growth of microorganisms that cause skin problems, and / or promotes the growth of microorganisms that are beneficial to the skin, and / or eliminates or alleviates skin problems, and / or inhibits the growth of microorganisms associated with hair follicle, scalp or hair health, and / or eliminates or alleviates hair follicle, scalp or hair problems.

25. The use according to claim 24, characterized in that The microorganisms that cause skin problems are selected from one or more of the following: Propionibacterium, Staphylococcus, Candida albicans and Malassezia; the microorganisms that are beneficial to the skin are selected from one or more of the following: Streptococcus, lactic acid bacteria, and Bifidobacterium; the skin problems are selected from one or more of the following: lack of skin elasticity, dry skin, desquamation, dull skin, fine lines, sagging, inflammation, peeling, acne, atopic dermatitis, eczema, chloasma, erythema, papules, and itching.

26. The use according to claim 24, characterized in that The hair follicle, scalp or hair health-related microorganisms are selected from one or more of the following: Staphylococcus, Propionibacterium and Malassezia; hair follicle, scalp or hair problems include folliculitis or seborrheic dermatitis, itchy scalp, dandruff, oily scalp, rash, itchy skin, flaking scalp, hair loss, tinea capitis, hypotrichosis, hypotrichosis, and hair lichen planus.

27. The use according to any one of claims 22 to 26, characterized in that The composition is in the form of a lotion, cream, ointment, serum, paste, gel, solution, dispersion, spray, suspension, emulsion, foam, patch, powder, film, spirit, tincture and liniment.

28. The use according to any one of claims 22 to 27, characterized in that The alitretinoin or a pharmaceutically acceptable salt, hydrate, ester, analog or derivative thereof is formulated for administration in an amount of 0.1-500 mg per day or in an amount of 0.1 μM to 1 M or 0.001 to 50.0% (w / w).

29. The use according to any one of claims 22 to 28, characterized in that The alitretinoin or a pharmaceutically acceptable salt, hydrate, ester, analog or derivative thereof is formulated for administration in an amount of 1 μM to 500 mM, or 10 to 300 mg, or 0.003 to 10% (w / w) per day.

30. The composition according to any one of claims 23 to 29, characterized in that The ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog or derivative thereof is formulated for administration in an amount of 1-1500 mg per day.

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