KR20230102912A - Composition for prevention of hair loss or improvement of hair growth - Google Patents

Abstract

The present invention relates to a composition for preventing hair loss or stimulating hair growth. It has an excellent effect of promoting the activity of the wind/beta-catenin signaling pathway, and thus can be usefully used as a composition for preventing hair loss or promoting hair growth.

Description

Composition for prevention of hair loss or improvement of hair growth}

The present invention relates to a composition for preventing hair loss or stimulating hair growth, and specifically, by containing a sialic acid derivative or a pharmaceutically acceptable salt thereof as an active ingredient, inducing proliferation of dermal papilla cells to promote hair growth and 5 alpha- The present invention relates to a composition for preventing hair loss or stimulating hair growth, which has an excellent effect of suppressing the production of dihydrotestosterone by inhibiting the activity of reductase and promoting the activity of the wint/beta-catenin signaling pathway.

In addition to the simple function of biologically protecting the scalp, hair has been considered important as a means of expressing beauty and individuality in terms of beauty. In particular, in a modern society that values beauty, hair occupies the most important part in satisfying the desire for individual expression regardless of age or gender.

In recent years, not only male pattern baldness, but also a change in dietary habits and an increase in stress caused by social environments have led to an increase in the number of female hair loss populations, and their age is also decreasing regardless of age or gender. Moreover, in recent years, as the regulation or restriction of internal and external activities has been followed by the prolonged corona pandemic, the number of hair loss population due to increased stress, lack of exercise, irregular lifestyle, etc. is rapidly increasing.

There are about 100,000 to 150,000 hairs in the human body, and each hair has a different cycle and repeats growth and shedding through anagen, catagen, and telogen. This hair growth cycle is repeated over 3 to 6 years. As a result, it is a natural phenomenon that about 50 to 70 hairs fall out per day, but if the number of hairs that fall out exceeds 100, it is likely to be a symptom of hair loss.

In general, 'alopecia' refers to an increase in the number of abnormally falling hairs due to a decrease in the proportion of hair in the growth phase and an increase in hair in the catagen or telogen phase during this cycle. Alopecia, in which hair is lost from the scalp, is caused by various factors, and is usually divided into congenital genetic predisposition and acquired alopecia formed by receiving other environments. Currently, the causes of hair loss include internal factors such as the action of male hormones or external factors such as mental stress in daily life and accumulation of lipid peroxide in the scalp. there is.

Specifically, in terms of the hair growth cycle, alopecia refers to an increase in the number of hairs that fall out abnormally due to a shortened hair growth rate in the hair growth cycle and an increased number of hairs in the catagen or telogen phase. Hair loss is a normal phenomenon, but normal people have a lot of hair in the growth phase, whereas people with alopecia have a lot of hair in the resting phase. In other words, the characteristic of people exhibiting alopecia is miniaturization of the hair. As hair loss progresses, the period of the growth phase is shortened, the transition to the catagen phase and the telogen phase is promoted, and the volume of the subsequent hair dermal papilla is reduced, so the hair follicles are gradually miniaturized. Therefore, for the treatment of hair loss, it can be said that a more desirable method is to make the hair follicles in the telogen phase go quickly to the anagen phase and to extend the shortened anagen phase.

Hair loss prevention agents that can improve or treat alopecia that are currently widely used include minoxidil and oral finasteride, which are external skin preparations approved by the US Food and Drug Administration (FDA), and approved by the Ministry of Food and Drug Safety (MFDS) in Korea. There is an oral dutasteride that has been received. Minoxidil, which has been used as a treatment for hypertension, has been known to promote hair growth through a mechanism that expands blood vessels through hyperpolarization of cell membranes and supplies nutrients to hair follicles, but recent studies have shown that minoxidil promotes hair growth by acting directly on hair follicle cells. It has been reported to activate the signaling pathway of Wnt/βcatenin, which is a mechanism. Finasteride is the ingredient name of Propecia, which was developed as a treatment for benign prostatic hyperplasia and then introduced to the treatment of alopecia. ) is known to inhibit the production of DHT, which causes hair loss. However, hair loss inhibitors such as minoxidil, finasteride, dutasteride, etc. show a temporary great effect in terms of efficacy, but the fact is that the effect varies greatly between individuals, and the effect disappears immediately when discontinued, and various dermatitis or As many side effects, such as loss of sexual desire and induction of gynecomastia, are concerned, it is difficult to maintain these effects for a long period of time.

Sialic acid is a generic term for N-acyl and O-acyl derivatives of neuraminic acid, and about 50 types are known. , A keto acid refers to an organic compound containing a carboxylic acid group and a ketone group. Acetic acid (CH ₃ COOH) is additionally attached to neuraminic acid composed of nine carbons or the position of the hydroxyl group (-OH) attached to the carbon is changed to form various types of sialic acids. Typical sialic acids include N-acetylneuraminic acid (Neu5Ac or NANA), N-glycolneuraminic acid (Neu5Gc), and 2-keto-3-deoxynonic acid (2-keto-3-deoxynonic acid). acid, Kdn), etc., and especially N-acetylneuraminic acid is more distributed than other sialic acids. In addition, there are derivatives in which the hydroxyl group is modified with an acetyl group, sulfate group, phosphoric acid group, etc., and specific sugar chains including sialic acid have been found to be involved in cell adhesion and cell recognition.

Sialic acid is not detected in celiacs, but is mainly detected in bacteria, echinoderms, and stellate animals. In mammals, it is produced from N-acetylmannosamine 6-phosphate and phosphoenolpyruvic acid. In particular, sialic acid is part of the metabolism. Except for processes, it does not exist in a glassy state in nature. It is widely present as a component of oligosaccharides, polysaccharides, glycoproteins, and glycolipids in animal organs, tissues, blood, mucus, milk, etc., and is not found in plants, but is relatively widely distributed in microorganisms.

In higher animals, sialic acid is linked by an a-glycosidic bond by the action of Gal, GlcNAc, and GalNAc of glycoproteins, glycolipids, and oligosaccharide sugar chains, and sialytransferase specific for sialic acid, respectively. In other words, it only temporarily exists in a free form during the metabolic process, and most of it exists in the form of an oligosaccharide attached to the non-reducing end of the sugar chain as a glycoside.

Sialic acid is a component of glycoproteins or glycolipids on the cell surface of cell membranes and can perform various biological functions by being located at the terminal. In particular, sialic acid is a present component of human milk, and there are sources of sialic acid in various conjugated forms associated with various oligosaccharides and glycoproteins. These include free N-acetylneuraminic acid (or sialic acid), sialyllactose, sialic acid-containing ganglioside, glycomacropeptide (GMP, glycomacropeptide), and caseinoglycopeptide (cGMP, caseinomacropeptide) at a certain content or higher. This is included.

In addition, sialic acid is a component of ganglioside or glycoprotein in the brain and is particularly abundant in the brain or central nervous system, and its amount increases rapidly during infancy. It is known. And as an indispensable component of mucoprotein, antiviral function to block the hemolysis of influenza virus, anticancer function, neutralization of toxin component, anti-inflammatory function, defense function in case of bacterial infection, immune regulation function, suppression of pigmentation It is known to exhibit various functions such as function and nerve cell signaling function.

Regarding the efficacy of the sialic acid derivative or a pharmaceutically acceptable salt thereof, Korean Registered Patent Registration No. 10-1773067 Preventive effect of degenerative arthritis, Registered Patent No. 10-2019676 Preventive effect of prostatic hyperplasia, Registered Patent No. 10 -1873527 endometriosis prevention effect, Registration Patent No. 10-1112051 Hypertrophic scar or keloid prevention effect, Registration Patent No. 10-2092435 Skin pigmentation reduction effect, Publication Patent No. 10-2019-0067499 Acne improvement effect, registered patent No. 10-2204367 discloses a skin wrinkle improvement effect and Registered Patent No. 10-1386979 discloses a hair removal effect, but no example of use for hair loss prevention or hair growth promotion efficacy has been known yet.

The inventors of the present invention have made diligent efforts to develop a composition that can prevent hair loss, induce hair growth, and effectively act in safe hair loss prevention or hair growth promotion without side effects even when used on the human body for a long time. It was confirmed that possible salts had an efficacy as an agent for preventing hair loss, and the present invention was completed.

Accordingly, the technical problem to be achieved by the present invention relates to a composition for preventing hair loss or stimulating hair growth, which contains a sialic acid derivative or a pharmaceutically acceptable salt thereof as an active ingredient to promote hair growth by inducing proliferation of dermal papilla cells. It is to provide a composition for preventing hair loss or stimulating hair growth, which has an excellent effect of suppressing the production of dihydrotestosterone by inhibiting the activity of 5-alpha-reductase and promoting the activity of the wint/beta-catenin signaling pathway.

In order to achieve the above object, the present invention provides a composition for preventing hair loss or promoting hair growth containing a sialic acid derivative or a pharmaceutically acceptable salt thereof as an active ingredient,

In order to achieve the above object, the present invention contains a sialic acid derivative or a pharmaceutically acceptable salt thereof as an active ingredient, thereby inducing proliferation of dermal papilla cells to promote hair growth and inhibiting the activity of 5-alpha-reductase. Provided is a composition for preventing hair loss or promoting hair growth that inhibits the production of dihydrotestosterone and promotes the activity of the wint/beta-catenin signaling pathway.

By containing the sialic acid derivative or a pharmaceutically acceptable salt thereof of the present invention as an active ingredient, there is no skin irritation and cytotoxicity, so it has excellent human safety, induces the proliferation of dermal papilla cells, promotes hair growth, and promotes hair growth. Since it inhibits the production of dihydrotestosterone by inhibiting its activity and is very effective in promoting the activity of the Wint/beta-catenin signaling pathway, it can be usefully used as an active ingredient in sialic acid derivatives or pharmaceutically acceptable salts thereof. can

1 is a graph showing the analysis results of the activity promoting effect of the wint/beta-catenin signaling pathway by 2,3-sialyllactose and 2,6-sialyllactose of the present invention.

The present invention relates to a composition for preventing hair loss or promoting hair growth containing a sialic acid derivative or a pharmaceutically acceptable salt thereof as an active ingredient.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In general, the nomenclature used herein is one well known and commonly used in the art.

Hereinafter, the present invention will be described in more detail.

In the present invention, sialic acid is a generic term for N-acyl and O-acyl derivatives of neuraminic acid, and about 50 types are known, and α-keto acids composed of 9 carbons A keto acid is an organic compound containing a carboxylic acid group and a ketone group. Acetic acid (CH ₃ COOH) is additionally attached to neuraminic acid composed of nine carbons or the position of the hydroxyl group (-OH) attached to the carbon is changed to form various types of sialic acids. Typical sialic acids include N-acetylneuraminic acid (Neu5Ac or NANA), N-glycolneuraminic acid (Neu5Gc), and 2-keto-3-deoxynonic acid (2-keto-3-deoxynonic acid). acid, Kdn), etc., and N-acetylneuraminic acid is more distributed than other sialic acids. In addition, there are derivatives in which the hydroxyl group is modified with an acetyl group, a sulfuric acid group, or a phosphoric acid group.

In the present invention, the sialic acid derivative is preferably α2,3-sialylgalactose, α2,6-sialylgalactose, α2,3-sialyllactose ( α2,3-sialyllactose), α2,6-sialyllactose, α2,3-sialyl N-acetyllactosamine, α2,6-sialyl N-acetyllactosamine (α2,6-sialyl N-acetyllactosamine), disialyllactose, Stn epitope (STnepitope or 2-acetamido-6-O-(a-2-N--acetylneuraminyl)-2-deoxyl -a-D-galactopyranosyl serine), but is not limited thereto.

Preferably, in the present invention, sialic acid may be N-acetylneuraminic acid, and a composition for preventing hair loss or stimulating hair growth comprising a compound represented by the following general formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient is provided.

[Formula 1]

Sialic acid (Neu5Ac) - Galactose (Gal) - Glucose (Glc)

In the compound of Formula 1, sialic acid may be bonded to galactose in various ways, preferably through an α-2,3 bond or an α-2,6 bond, and sialic acid may be a modified sialic acid. can be acid For example, the OH group on carbon 4 of the sialic acid can be modified (eg, replaced with a C1-C4 alkyl group).

In the compound of Formula 1, any monosaccharide compound known in the art may be used as the monosaccharide compound located in galactose and glucose, and for example, tetrasaccharides (eg, erythose and threose), pentoses (eg, ribose, arabinose, xylose and lysose) and hexoses (allose, altrose, glucose, mannose, gulose, idose, galactose and talose). Preferably, the monosaccharide compound located in galactose and glucose is a pentose or hexose sugar, more preferably a hexose sugar, even more preferably glucose, mannose or galactose, most preferably glucose or galactose. there is.

In addition, the monosaccharide compound may have a D- or L-form stereoisomer, and most preferably a D-form stereoisomer. The same or different monosaccharide compounds may be bound to galactose and glucose, and preferably different monosaccharide compounds may be bound to each other.

In Formula 1, galactose or glucose is bonded to galactose, and glucose or galactose is bonded to glucose. Most preferably, galactose is bonded to galactose, and glucose is bonded to glucose. When galactose is joined to galactose and glucose to glucose, a disaccharide compound, lactose, is formed. Monosaccharide compounds located in galactose and glucose are either modified or unmodified. For example, in the case of a modified monosaccharide compound, an acetyl group or an N-acetyl group may be bonded to the -OH group. Preferably, the monosaccharide compound located on galactose and glucose may be an unmodified monosaccharide compound.

In addition, the galactose and glucose may be connected by a glycosidic bond, and the glycosidic bond may be an α- or β-glycosidic bond, but preferably may be a β-glycosidic bond.

According to a preferred embodiment of the present invention, the compound of Formula 1 may be sialyllactose. Sialyllactose is a compound in which galactose bound to sialic acid and glucose are linked by a β-1,4 glycosidic bond.

According to a preferred embodiment of the present invention, the sialyllactose of the present invention is 2,3-sialyllactose (Neu5Ac-α-2-3-Gal-β1-4-Glc, NANA-Lactose, 3-N-Acetylneuraminyl-D-lactose) and 2,6-sialyllactose (Neu5Ac-a-2-6-Gal-β1-4-Glc).

In the present invention, 2,3-sialyllactose and 2,6-sialyllactose are present on the surface of various animal cells and are a type of sialic sugar that plays an important role in cell recognition, recognition and adsorption of bacteria and viruses, Natural 2,3-sialyllactose and 2,6-sialyllactose are components of human milk oilgosaccharides (HMOs) present in large quantities in human milk components. There may be several methods by which 2,3-sialyllactose and 2,6-sialyllactose can be obtained. For example, 2,3-sialyllactose and 2,6-sialyllactose may be obtained from the precursors through an enzyme synthesis method using a glycosyltransferase derived from a specific microorganism, but is not limited thereto.

The above sialic acid derivatives may be prepared by a known method or purchased and used by a known method. The experiment on the sialic acid derivative presented in the present invention was carried out using 2,3-sialyllactose purchased from Jinchem Co., Ltd. and 2,6-sialyllactose, and the 2,3-sialyllactose and 2,6-sialyllactose are represented by Chemical Formulas 1 and 2, respectively.

Formula 1

Formula 2

In the present invention, sialic acid derivatives can be used in the form of "pharmaceutically acceptable salts thereof", and unless otherwise stated, all salts, hydrates and solvents that can exist in sialic acid derivatives prepared by conventional methods. Freight is included.

As used herein, the term "pharmaceutically acceptable salt" refers to a formulation of a compound that does not cause serious irritation to the organism to which the compound is administered and does not impair the biological activity and physical properties of the compound.

The pharmaceutical salt is an acid that forms a non-toxic acid addition salt containing a pharmaceutically acceptable anion, for example, inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrobromic acid, hydroiodic acid, tartaric acid, formic acid, citric acid, Organic carbonic acids such as acetic acid, trichloroacetic acid, trifluoroacetic acid, gluconic acid, benzoic acid, lactic acid, fumaric acid, maleic acid, salicylic acid, etc., sulfonic acids such as methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, etc. Acid addition salts formed by and the like are included. For example, pharmaceutically acceptable carboxylic acid salts include metal salts or alkaline earth metal salts formed by lithium, sodium, potassium, calcium, magnesium, etc., amino acid salts such as lysine, arginine, guanidine, dicyclohexylamine, N organic salts such as -methyl-D-glucamine, tris(hydroxymethyl)methylamine, diethanolamine, choline and triethylamine; and the like.

As the salt, an acid addition salt formed by a pharmaceutically acceptable free acid is useful. Acid addition salts are prepared by conventional methods, for example, by dissolving the compound in an excess of an aqueous acid solution and precipitating the salt using a water-miscible organic solvent, such as methanol, ethanol, acetone or acetonitrile. Equimolar amounts of the compound and an acid or alcohol (eg, glycol monomethyl ether) in water may be heated, and then the mixture may be evaporated to dryness, or the precipitated salt may be suction filtered. At this time, organic acids and inorganic acids can be used as the free acid, and hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, etc. can be used as the inorganic acid, and methanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, and maleic acid can be used as the organic acid. , succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, citric acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, Vanillic acid, hydroiodic acid, and the like may be used, but are not limited thereto.

In addition, a pharmaceutically acceptable metal salt may be prepared using a base. The alkali metal or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and then evaporating and drying the filtrate. At this time, as the metal salt, it is particularly suitable for preparing a sodium, potassium or calcium salt, but is not limited thereto. In addition, the corresponding silver salt can be obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (eg, silver nitrate).

Although many studies on the cause of hair loss or promoting hair growth are continuously and actively conducted, the exact biological mechanism related to hair loss is still very complicated.

Hair repeats the hair cycle of growth, catagen, rest, and growth, and alopecia refers to a state in which the resting period is long and the growth period is short. It has been believed that hair regeneration is almost impossible until now because hair follicles atrophy when the resting period is long, and most of the hair loss prevention agents currently on the market expect only the hair loss prevention effect of growing hair.

Hereinafter, the invention for preventing hair loss or promoting hair growth of the present invention will be described in detail.

In the present invention, "hair loss" refers to a state in which there is no hair in an area where hair should normally exist, and specifically means that the terminal hair (thick and black hair) of the scalp is lost, and various forms from slight thinning of hair to complete baldness appears as The cause of hair loss is not limited, but examples include hereditary androgenetic alopecia (baldness), alopecia areata, ringworm of the head (tinea capitis) caused by fungal infection, telogen effluvium, hair growth, hair production disorders, etc. Scarring alopecia may mean that it appears in various forms due to various causes, such as hair loss caused by lupus, idiopathic folliculitis, lichen planus pilaris, hair loss caused by burns and trauma.

In the present invention, the types of hair loss include scarring alopecia in which hair is not regenerated due to the destruction of hair follicles due to scarring, and non-scarring alopecia in which hair is regenerated after the symptomatic site is razed by maintaining hair follicles without forming scars. Scarring alopecia is caused by trauma, burns, leprosy or bacterial infection, and non-scarring hair loss includes alopecia areata, hair growth, telogen effluvium, drug-induced alopecia, secondary syphilis, dermatophytosis, endocrine disorders, and dermatomyositis. which is caused by, etc.

The term "prevention" of the present invention refers to preventing something or a phenomenon from occurring, that is, preventing hair loss from occurring, and a product that prevents hair loss along with hair growth is called an anti-hair loss agent. In addition, it is divided into a hair growth agent that nourishes the hair roots to grow hair, a hair growth agent that promotes blood circulation in the scalp to help prevent hair loss, and a hair growth agent that turns thinned vellus hair into healthy terminal hair.

In the present invention, the target of application of the anti-hair loss agent means that the focus is on scarring hair loss. Among scarring alopecia, androgenetic alopecia, in which male hormones act as an important etiology, accounts for about 80% of all hair loss symptoms. Genetic factors, the concentration of androgen, a male hormone in the blood, and a high concentration of dihydrotestosterone (DHT: dihydrotestosterone), which binds to androgen receptors present in scalp hair follicles, are known to be the main causes. DHT regulates hair growth by binding to androgen receptors in the scalp dermal papilla. At this time, the binding of DHT transmits a cell destruction signal to the genes of keratinocyte cells to produce apoptosis factors, DKK-1 and TGF-β1. This means that hair loss occurs due to the destruction of hair cells.

In addition, in the present invention, 5 alpha-reductase (5α-reductase), an enzyme that catalyzes the irreversible reduction of testosterone to DHT, together with nicotinamide adenine dinucleotide phosphate (NADPH) as a hydrogen donor. reductase) is associated with hair loss. That is, DHT produced in this way inhibits protein synthesis around the hair follicle, thereby reducing cell proliferation of hair cells, shrinking scalp hair follicles, and converting thick and long healthy hair into thin and short hair to progress hair loss.

In the present invention, "hair growth" means that hair grows in a hair follicle, and the hair includes hair roots and hair follicles of the head, hair, eyelashes, eyebrows, beard, armpits, pubic hair, and all parts of the body with hair roots and hair follicles do.

In the present invention, "acceleration" means supplying nutrients to the root of the hair so that the hair grows quickly, thereby controlling the growth cycle of the hair. At this time, the activity of outer root sheath cells, including dermal papilla cells and hair follicle stem cells constituting hair follicles, and various cytokines and growth factors produced by these cells play an important role. In particular, regeneration of hair follicles and activation of stem cells are followed for periodic hair growth, which is achieved through activation of the Wnt/β catenin signaling pathway. In addition, growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and fibroblast growth factor (FGF) promote the growth phase of hair, and transforming growth factor (TGFβ-1) , Epidermal growth factor (EGF), etc. means to regulate the hair growth cycle by inducing the catagen phase of the hair follicle.

Therefore, in the present invention, the hair loss prevention or hair growth promotion effect is to promote dermal papilla cell proliferation, inhibit the activity of 5 alpha-reductase, and wint/beta-catenin by the sialic acid derivative or a pharmaceutically acceptable salt thereof. It may be achieved by promoting the activity of a signaling pathway.

In an embodiment, the composition for preventing hair loss or promoting hair growth (or for promoting hair growth) of the present invention may be used as a cosmetic composition, a pharmaceutical composition (pharmaceutical composition, quasi-drug) and food composition. The composition of the present invention may be formulated in any form that can be applied to the skin in general, but may be formulated in the form of an external preparation for skin. The composition of the present invention may be formulated into a formulation that can be applied to the skin, such as, for example, liquid, cream, paste, or solid.

The sialic acid derivative or a pharmaceutically acceptable salt thereof of the present invention may be included in the composition or formulation as an agent for preventing hair loss or a hair growth promoter.

In one embodiment of the present invention, in the cosmetic composition for preventing hair loss or stimulating hair growth, the content of the sialic acid derivative or a pharmaceutically acceptable salt thereof is not particularly limited, but is contained in an amount of 0.001 to 30.0% by weight based on the total weight of the composition. it is desirable More preferably, it is contained in an amount of 0.1 to 10% by weight based on the total weight of the composition, and may be more preferably 1.0 to 5% by weight. However, when the amount of the sialic acid derivative or a pharmaceutically acceptable salt thereof is less than 0.001% by weight, the effect of promoting hair growth is insignificant, and when it exceeds 30% by weight, stability of the formulation is impaired and skin irritation may occur.

In the present invention, when the sialic acid derivative or its pharmaceutically acceptable salt is 0.1 to 5% by weight based on the total weight of the composition, it has been clinically shown to have an effect of preventing hair loss or stimulating hair growth. More preferably, the content of the sialic acid derivative or a pharmaceutically acceptable salt thereof may be 1 to 5.0% by weight, most preferably 2 to 5% by weight, based on the total weight of the composition. In the present invention, it was confirmed through test examples that the effect of preventing hair loss or stimulating hair growth was remarkably excellent when the sialic acid derivative or its pharmaceutically acceptable salt was within the above content range.

The cosmetic composition containing the sialic acid derivative or a pharmaceutically acceptable salt thereof of the present invention is not particularly limited in dosage form, and may be appropriately selected according to the purpose. For example, softening lotion (skin lotion and milk lotion), nourishing lotion, essence, nourishing cream, massage cream, pack, gel, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing water, pack, powder, Body lotion, body cream, body oil, body essence, hair tonic, hair conditioner, hair essence, hair lotion, hair nutrition lotion, hair shampoo, hair conditioner, hair treatment, hair cream, hair nutrition cream, hair moisture cream, hair Massage cream, hair wax, hair aerosol, hair pack, hair nutrition pack, hair soap, hair cleansing foam, hair oil, hair drying agent, hair preservative, hair dye, hair waving agent, hair bleach, hair gel, hair glaze, hair dressing , hair lacquer, hair moisturizer, hair mousse and hair spray, but may be prepared in any one or more formulations selected from the group consisting of, but not limited thereto, preferably hair tonic, hair conditioner, hair essence, hair lotion, hair Nutrition lotion, hair shampoo, hair rinse, hair treatment, hair cream, hair nutrition cream, hair moisture cream, hair massage cream, hair wax, hair aerosol, hair pack, hair nutrition pack, hair soap, hair cleansing foam, hair oil, hair It can be formulated as a drying agent, hair preservative, hair dye, hair waving agent, hair bleach, hair gel, hair glaze, hair dresser, hair lacquer, hair moisturizer, hair mousse or hair spray.

When the composition containing the sialic acid derivative or pharmaceutically acceptable salt thereof of the present invention is formulated as a cosmetic formulation, the composition of the present invention may include all components commonly used in cosmetics in addition to the extract, such as It may contain a component selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymeric peptides, polymeric polysaccharides, sphingolipids, and seaweed extracts.

In the present invention, any polymeric peptide can be selected as long as it can be incorporated into cosmetics, but preferably collagen, hydrolyzed collagen, gelatin, elastin, hydrolyzed elastin, keratin and the like can be selected. Polymer peptides can be purified and obtained by conventional methods such as a purification method from a culture medium of microorganisms, an enzyme method, or a chemical synthesis method, or can be used after being purified from natural products such as pig or cow dermis or silkworm silk fibers.

In the present invention, as the polymeric polysaccharide, any polysaccharide that can be blended with cosmetics can be selected, but hydroxyethyl cellulose, xanthan gum, sodium hyaluronate, chondroitin sulfate or a salt thereof (sodium salt, etc.) is preferably selected. can For example, chondroitin sulfate or a salt thereof can be used after being purified from mammals or fish.

In the present invention, any sphingolipid can be selected as long as it can be blended with cosmetics, but ceramide, phytosphingosine, sphingoglycolipid and the like can be preferably selected. Sphingolipids can be purified by conventional methods or obtained by chemical synthesis from mammals, fish, shellfish, yeast, or plants.

In the cosmetic composition of the present invention, in addition to the above essential ingredients, other ingredients commonly used in cosmetic preparations may be incorporated as needed. In this case, the ingredients include oil and fat components, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, bactericides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, fragrances, and blood circulation promoters. , cooling agents, antiperspirants, purified water and the like can be used.

Ingredients included in the composition formulated as a cosmetic formulation of the present invention may include ingredients commonly used in cosmetics in addition to the extract as an active ingredient, for example, stabilizers, solubilizers, vitamins, pigments, and fragrances Such conventional adjuvants and carriers are included.

The pharmaceutical composition in the present invention means prepared for the purpose of preventing or treating a disease, and the pharmaceutical composition containing the sialic acid derivative or a pharmaceutically acceptable salt thereof of the present invention is commonly used in the preparation of the pharmaceutical composition. It may further include suitable carriers, excipients and diluents.

A pharmaceutical composition containing a sialic acid derivative or a pharmaceutically acceptable salt thereof according to the present invention may be formulated according to conventional methods, such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, sprays, and external preparations. , It can be formulated and used in the form of suppositories and sterile injection solutions, preferably in the form of powders, granules, tablets or sprays, more preferably in the form of nasal sprays, lubricants, wetting agents, flavoring agents, emulsifying agents, suspending agents , It may be formulated into a parenteral formulation using diluents or excipients such as preservatives and surfactants.

In addition, it may be formulated and used in the form of external preparations, suppositories, external preparations for the skin, and sterile injection solutions. Specifically, the composition of the present invention can be used by a method such as directly applying or spreading to the hair or scalp. The hair to which the composition of the present invention is applied includes hair roots and hair follicles of the head, hair, eyelashes and eyelashes, beard, armpits, pubic hair, hair roots throughout the body, and all parts with hair follicles.

In addition, according to each formulation, pharmaceutically acceptable carriers such as buffers, analgesics, solubilizers, isotonic agents, stabilizers, and bases may be prepared by further including carriers known in the art. As used herein, the term "pharmaceutically acceptable carrier" may refer to a carrier or diluent that does not inhibit the biological activity and characteristics of an active ingredient to be injected without stimulating living organisms. The type of the carrier that can be used in the present invention is not particularly limited, and any carrier commonly used in the art and pharmaceutically acceptable can be used. Non-limiting examples of the carrier include saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and the like. These may be used alone or in combination of two or more. The carrier is a non-natural carrier

(non-naturally occurring carrier).

Carriers, excipients and diluents that may be included in the composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. When formulated, it may be prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations contain at least one excipient such as starch, calcium carbonate, sucrose or lactose, gelatin, etc. in the complex. mixed and prepared In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use include suspensions, solutions for oral use, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included. . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin fat, glycerogeratin, etc. may be used.

The pharmaceutical composition containing the sialic acid derivative of the present invention or a pharmaceutically acceptable salt thereof can be administered in a pharmaceutically effective amount. The pharmacologically effective amount means an amount that is sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment and does not cause side effects. It may be determined according to the activity of the drug, sensitivity to the drug, method of administration, time of administration, route of administration and excretion rate, duration of treatment, factors including drugs used in combination or concurrently, and other factors well known in the medical field.

Specifically, it is generally 0.01 mg to 5000 mg per day per 1 kg of body weight of the subject to be administered, and may be administered once or several times a day at regular time intervals according to the judgment of a doctor or pharmacist, but is not limited thereto. That is, the preferred dosage of the pharmaceutical composition containing the sialic acid-containing whey protein of the present invention varies depending on the condition and body weight of the patient, the severity of the disease, the type of drug, the route and duration of administration, but can be appropriately selected by those skilled in the art. . However, for desirable effects, the complex of the present invention is preferably administered at 0.2 to 200 mg per day, preferably 2 to 100 mg.

Administration may be administered once a day, or may be administered in several divided doses. The dosage is not intended to limit the scope of the present invention in any way.

The sialic acid derivative or pharmaceutically acceptable salt thereof of the present invention can be administered to mammals such as rats, mice, livestock, and humans through various routes. All modes of administration can be envisaged, for example by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.

In addition, since the pharmaceutical composition containing the sialic acid derivative or the pharmaceutically acceptable salt thereof of the present invention has little toxicity and side effects (Registration Patent No. 10-1873527, Registration Patent 10-2204367, etc.), it is used for the purpose of prevention or treatment. It can be used safely even for long-term use.

In addition, the pharmaceutical composition of the present invention may be used alone or in combination with other pharmaceutically active compounds exhibiting an effect of preventing or improving hair loss-related diseases or in a suitable set.

The pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. And it can be single or multiple administrations. It is important to administer the amount that can obtain the maximum effect with the minimum amount without causing side effects in consideration of all of the above factors, and can be easily determined by those skilled in the art.

For example, but not limited thereto, in addition to a pharmaceutical composition containing the sialic acid derivative of the present invention or a pharmaceutically acceptable salt thereof as an active ingredient, minoxidil, finasteride or spironolactone ( spironolactone) and dutasteride can be selected and administered additionally.

As used herein, the term "administration" means introducing the pharmaceutical composition of the present invention to a subject by any suitable method, and the route of administration of the composition of the present invention can be various oral or parenteral routes as long as it can reach the target tissue. can be administered through

The administration method of the pharmaceutical composition according to the present invention is not particularly limited, and may follow a method commonly used in the art. As a non-limiting example of the administration method, the composition may be administered by oral administration or parenteral administration.

Specifically, the composition of the present invention can be used by a method such as directly applying or spreading to the hair or scalp.

The pharmaceutical composition according to the present invention may be prepared in various formulations depending on the desired administration method.

The frequency of administration of the composition of the present invention is not particularly limited thereto, but may be administered once a day or administered several times by dividing the dose.

As another aspect, the present invention provides a method for preventing or treating hair loss-related diseases comprising administering a pharmaceutical composition containing a sialic acid derivative or a pharmaceutically acceptable salt thereof.

In the present invention, diseases related to causes of hair loss include Alopecia Areata, Androgenetic Alopecia, Telogen Efffluvium, Traumatic, Trichoti lomania, Pressure Alopecia, etc. It may include, but is not limited to, nasal congestion, syphilitic (Alopecia syphlltiac), seborrheic alopecia (Alopecia seborrhecia), symptomatic, scarring, congenital alopecia, etc., and may refer to all diseases caused by hair loss from the hair follicle. there is

In the present invention, the subject of hair loss may refer to all animals, including humans, having or are likely to have a hair loss-related disease. The animal may be not only humans but also mammals such as cattle, horses, sheep, pigs, goats, camels, antelopes, dogs, and cats that require treatment for similar symptoms, but are not limited thereto.

Specifically, the preventive or therapeutic method of the present invention may include administering the composition in a pharmaceutically effective amount to a subject having or at risk of developing a hair loss-related disease. The administration method is as described above.

The prevention may mean any act of suppressing or delaying the onset of hair loss-related diseases by administering the composition for preventing hair loss or stimulating hair growth according to the present invention to a subject.

In addition, the treatment may refer to any action that improves or benefits the symptoms of a hair loss-related disease by administering the composition of the present invention to a subject suspected of having a hair loss-related disease.

For administration, the composition of the present invention may contain pharmaceutically acceptable carriers, excipients or diluents in addition to the above-described active ingredients. The carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

An appropriate dosage of the composition of the present invention varies depending on the condition and weight of the patient, the severity of the disease, the type of drug, and the time, but can be appropriately selected by those skilled in the art. Specifically, the dose of the sialic acid derivative or a pharmaceutically acceptable salt thereof may be 50 to 500 mg.

The amount of the composition of the present invention can be appropriately adjusted according to individual differences such as age, severity of lesions, etc., or formulation, and it is preferable to apply an appropriate amount to the scalp once or several times a day and use it for one week to several months. In an embodiment of the present invention, the composition for preventing hair loss or stimulating hair growth was used 7 times a week for 3 months, and as a result, it was confirmed that an excellent effect of preventing hair loss or stimulating hair growth appeared (Formulation Example 2 and Test Example 5).

In the present invention, the term "food" refers to the food that people consume on a daily basis, and is a concept including health functional food.

The health functional food refers to food having bioregulatory functions such as disease prevention and improvement, biodefense, immunity, recovery after illness, and aging suppression, and should be harmless to the human body when taken for a long period of time.

The sialic acid derivative or a pharmaceutically acceptable salt thereof of the present invention may be added to a food composition for the purpose of preventing hair loss or promoting hair growth. When the sialic acid derivative or acceptable salt thereof of the present invention is used as a food additive, the compound may be added as it is or used together with other foods or food ingredients, and may be appropriately used according to conventional methods. The mixing amount of the active ingredient may be appropriately determined depending on the purpose of use (prevention, health or therapeutic treatment). In general, when preparing food or beverage, the compound of the present invention is added in an amount of 0.01 to 10% by weight, preferably 0.05 to 1% by weight of the raw material composition. However, in the case of long-term intake for the purpose of health and hygiene or health control, the amount below the above range may be used.

The food of the present invention can be prepared in all forms, such as functional food, nutritional supplement, health food and food additives, and there are no particular restrictions on the type of food. there is no Examples of foods to which the above substances can be added include meat, sausages, bread, chocolates, candies, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice creams, various soups, beverages, tea, drinks, There are alcoholic beverages, vitamin complexes, and the like, and includes all foods in a conventional sense.

The beverage composition of the present invention may contain various flavoring agents or natural carbohydrates as additional components. The aforementioned natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As the sweetener, natural sweeteners such as thaumatin and stevia extract, or synthetic sweeteners such as saccharin and aspartame may be used.

The proportion of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 ml of the composition of the present invention.

In addition to the above, the composition of the present invention contains various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, A carbonation agent used in carbonated beverages and the like may be contained. The ratio of these additives is not very important, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention. In addition, the composition of the present invention may contain fruit flesh for preparing natural fruit juice, fruit juice beverages and vegetable beverages. The ratio of such flesh is not very important, but is generally selected in the range of 0.01 to 10 parts by weight per 100 parts by weight of the composition of the present invention. These components may be used independently or in combination.

[Production Example 1] Preparation of 2,3-sialyllactose and 2,6-sialyllactose

In general, in the production method of sialic acid derivatives, sialic acid derivatives or pharmaceutically acceptable salts thereof have a large difference in content or components depending on the type of strain, microbial fermentation, etc., and their functional, nutritional and Since the bioactive properties may be different, in the present invention, 2,3-sialyllactose and 2,6-sialyllactose purchased from Jinchem Co., Ltd. are commercially available as more purified sialic acid derivatives or pharmaceutically acceptable salts thereof. This experiment was performed using sialyllactose.

[Test Example 1] Proliferative effect of dermal papilla cells

To investigate the effect of 2,3-sialyllactose and 2,6-sialyllactose on the proliferation of human hair follicle dermal papilla cell (HHFDPC), which is the main cell of hair growth, the proliferation ability of dermal papilla cells was investigated. measured. Human dermal papilla cells were purchased from PromoCell, and the HHFDPC was supplemented with a culture medium additive (Supplement Mix; PromoCell, Heidelberg, Germany), 100 units/mL of penicillin, and 100 μg of streptomycin. Cell Growth Medium; PromoCell, Heidelberg, Germany) was cultured at 37°C and 5% CO ₂ conditions. Specifically, after culturing HFDPC, it is inoculated into a 96-well plate (1.5 x 10 ⁴ cells/well), and incubated at 37°C for 24 hours in a 5% CO ₂ incubator, and the 4th to 6th subcultured HFDPC Cells were used for this test.

DMSO (Dimethylsulfoxide) diluted 1:1000 in DMEM (Dulbecco's modified Eagle's medium) containing 1% fetal bovine serum (FBS), penicillin 100 units/mL and streptomycin 100 μg 1 ng/mL βFGF to the cultured cells as a control, 0.1 μg of minoxidil as a positive control, 0.1, 0.5, and 1 μg concentrations for each concentration for 2,3-sialyllactose (Example 1) and 2,6-sialyllactose (Example 2), respectively Each treatment was then incubated again for 48 hours under the conditions of 37°C and 5% CO ₂ . After 72 hours, the cell culture supernatant was removed by centrifugation, washed once with PBS (Phosphate Buffer Saline) solution, and MTT (3-[4,5-dimethylthiazol-2-yl]-2 dissolved in 1 mg/mL ,5-diphenyltetrazolium bromide) was diluted 10 times, mixed with the medium, treated, and incubated for 1-2 hours, after which the MTT reagent was removed. When formazan crystals are observed in each well, 200 μl of DMSO per well is added and gently shaken for 30 minutes in a light-shielded state to dissolve the formazan crystals. The degree of cell proliferation was evaluated. CCK-8 was treated in a culture solution at a ratio of 1:10 and incubated for 1 hour, and then the absorbance at 450 nm was repeatedly measured three times using a spectrophotometer for each well, and the average of the absorbance values was calculated.

Table 1

The measurement results of the dermal papilla cell proliferation rate are shown in Table 1, and the results confirm that the dermal papilla cell proliferation effect is shown in all treatments at the concentrations of 0.1, 0.5, and 1 μg, respectively, for Examples 1 and 2. . Even at the same 0.1 μg treatment concentration as the positive control minoxidil, Examples 1 (142.26%) and 2 (142.16%) showed a relatively higher dermal papilla cell proliferation rate than Minoxidil (129.37%), and dermal papilla cells between Examples 1 and 2 The difference in growth rate was almost similar and did not show a significant difference. In addition, it was shown that the pattern of dermal papilla cell proliferation rate was not significantly different from the result of 0.1 μg treatment concentration even at the treatment concentrations of 0.5 and 1 μg for Examples 1 and 2, respectively.

Accordingly, it can be confirmed that both 2,3-sialyllactose and 2,6-sialyllactose are superior to minoxidil in promoting the proliferation of dermal papilla cells.

[Test Example 2] Inhibitory effect of 5-alpha-reductase activity

In order to evaluate the activity of 5 alpha-reductase in dermal papilla cells, dermal papilla cells were dispensed at 0.8 x 10 ⁶ cells/dish in a 60 mm cell culture dish. After 24 hours of culture, the existing culture medium was removed, and no additives were added (0 mg/mL) as a control for each dish, finasteride (1 mg/mL) as a positive control, Examples 1 and 2 (1 mg/mL) were treated, respectively, and exchanged again with the culture medium containing each of them, and cultured for 24 hours. After culturing, the existing culture medium was removed, washed with 1 x PBS, and treated with Trypsin/EDTA to make each single cell. After centrifugation, the cells were lysed using an extraction buffer (880 mM Sucrose, 1.5M CaCl ₂ ), and then the supernatant obtained by centrifugation was taken and used as a crude enzyme solution for the measurement test of 5-alpha-reductase activity inhibition ability. used The measurement and analysis method calculated the activity of 5-alpha-reductase by measuring the change in the amount of NADPH, a substrate used when testosterone is converted to dihydrotestosterone, by absorbance, and the crude enzyme solution (protein 35 μg), 20 μM testosterone (Sigma, USA) and 320 μM NADPH (Sigma, USA) were mixed and incubated for 30 minutes, and then the absorbance of the mixture was measured at 340 nm using a spectrophotometer to obtain 5 alpha -The activity of the reductase was analyzed.

Table 2

As shown in Table 2, when finasteride, known to inhibit the activity of 5-alpha-reductase, was treated at a concentration of 1 mg/mL, the relative activity was 76.18±2.81%, whereas the treatment of Examples 1 and 2 The activity of 5 alpha-reductase in one test group was 52.19 ± 2.14% in Example 1 and 53.14 ± 1.16% in Example 2, respectively. It can be seen that Examples 1 and 2 inhibit the activity of 5-alpha-reductase more effectively than finasteride.

Therefore, it can be confirmed that both 2,3-sialyllactose and 2,6-sialyllactose are superior to finasteride in their inhibitory effect on the activity of 5-alpha-reductase.

[Test Example 3] Wint/beta-catenin signaling pathway activation effect

The method for measuring the activation level of dermal papilla cells, which are critically involved in hair follicle formation and regeneration, starts with a protein called Wnt, which is known to play an important role in maintaining and activating genes expressed during the growth of the hair cycle. Beta-catenin/TCF (T-cell factor) was measured using the TCF reporter luciferase system, which is a method for evaluating the activation of the wint/beta-catenin signaling pathway that is transferred to transcription factors.

As for human dermal papilla cells (HHFDPC), HFDPC cells cultured in the same way as in Test Example 1 were used in this experiment, and Wnt3a protein was used as a positive control to activate the wint/beta-catenin signaling pathway, and as a negative control. used DMSO. About 3×10 ⁴ of the Wnt reporter HEK293A cells were dispensed into each well in a 96-well plate, and 18 hours later, Example 5 was treated at a concentration of 5 μg, 10 μg, and 20 μg, respectively. Then, Wint reporter analysis was performed according to the protocol using Promega's Luciferase assay kit, and Wint/beta-catenin promoter activity was measured using PerkinElmer's luminometer Victor.

As shown in Figure 1, in Examples 1 and 2, compared to the untreated negative control group, the wint / beta-catenin signal was amplified by about 9.35 and 9.29 times, respectively, and did not show a concentration-dependent pattern, but 20 μg / mL It was confirmed that there was a repeatable effect near the concentration. It can be seen that both Examples 1 and 2 exhibit slightly superior effects compared to the positive control Wnt3a protein (8.6 times) binding to the direct receptor of wint/beta-catenin.

Therefore, both 2,3-sialyllactose and 2,6-sialyllactose promote excellent hair growth by activating the TCF transcription factor by promoting the activity of the wint/beta-catenin signaling pathway, which is a hair growth promoting signal of hair follicle stem cells. It can be confirmed that there is a stimulating effect.

From the results of Test Examples 1, 2, and 3 above, both 2,3-sialyllactose and 2,6-sialyllactose have an effect of promoting proliferation of dermal papilla cells, an effect of inhibiting the activity of 5 alpha-reductase, and It was confirmed that the effect of promoting the activation of the beta-catenin signaling pathway was remarkably excellent.

[Formulation Example 1] Hair Essence

In order to confirm whether the composition containing 2,3-sialyllactose and 2,6-sialyllactose according to the present invention is safe for human skin when used, a skin irritation test was performed as part of skin safety verification.

The test subjects of the present invention divided a panel of 60 men and women composed of Catholic University students into two groups and selected 30 people each, and for the test subjects, the hair essence of Examples 1 and 2 and Comparative Example 1 in Table 3 above made to use Specifically, after washing the back skin, the water was wiped off, and it was allowed to wait for 15 minutes in a constant temperature and humidity room (temperature 24 ± 4 ° C. relative humidity 40-45%). The same amount of the scalp essence of Examples 1 and 2, respectively, was sufficiently applied to the cotton wool so that it did not flow, and it was attached to the position of the skin on the back. After 24 hours and 48 hours after attaching the test substance, the subject indicated the degree of stimulation from 0 to 4 points (0 = no stimulation, 1 = very weak, 2 = weak, 3 = moderate, 4 = severe). (measured twice in total), stimuli such as stinging and burning were evaluated.

Table 4 below shows the number of subjects who complained of irritation according to the rating for each time period, and the average value was calculated to derive a mean score for skin irritation.

Table 4

From the results in Table 4, the 10%-containing hair essence compositions of Examples 1 and 2 were found to have no skin irritation as in Comparative Example 1 that did not contain 2,3-sialyllactose and 2,6-sialyllactose. appear.

Therefore, it was confirmed that 2,3-sialyllactose and 2,6-sialyllactose are safe to the human body and do not irritate the scalp even in a composition containing 10.0% by weight based on the total weight of the composition, and there are no side effects even when used for a long period of time. did

[Formulation Example 2] Hair Tonic

In this formulation example, the composition content of Examples 1 and 2 was 0.1, 0.5, 1.0, 2,.0 and 5.0% by weight of Examples 1-1 to 1-5 and Examples 2-1 to 2-5 and Comparison The hair tonic of Example 2 was prepared by a conventional method according to the prescription shown in Table 5 below.

table 5

[Test Example 5] Confirmation of the effect of promoting hair growth

From the results of Test Examples 1, 2, and 3, both 2,3-sialyllactose and 2,6-sialyllactose have an effect of promoting proliferation of dermal papilla cells, an effect of inhibiting the activity of 5 alpha-reductase, and beta -The activation promoting effect of the catenin signaling pathway was excellent, and the skin safety was confirmed from Test Example 4. Preferably, in the present invention, Examples 1-1 to 1-5 and Example 2-1 in Table 5 A hair growth stimulating effect test was conducted on the hair tonic compositions of 2-5.

For the human body application test, the Ministry of Food and Drug Safety's "Guidelines for human application test of cosmetics that help alleviate hair loss symptoms" were applied, and the test subjects for the present invention were found to have significantly less hair than normal or hair loss through a questionnaire. A total of 60 men and women in their 20s to 50s who were recognized to have symptoms were divided into two groups consisting of 50 experimental groups and 10 non-control groups, and the purpose and purpose of the present invention was explained to all of them, and After receiving the consent to participate in the application experiment, an experiment to verify the effect of the present invention on the improvement of hair growth was conducted centering on the subjects.

Specifically, the test subjects were a panel consisting of 20 students and 60 of their direct descendants, 120 adult men and women, composed of Catholic University students and their direct descendants, and the experimental group was the hair tonic composition of Formulation Example 2, the above Example 1-1, 5- According to 2, 5-3, 5-4, and 1-5 and Examples 2-1, 2-2, 2-3, 2-4, and 2-5, each group was divided into 5 groups, each having a total of 10 people. 100 people were selected, and a total of 20 people were selected as a control group in two groups of 10 people each. Examples 1-1 to 1-5, Examples 2-1 to 2-5, and Comparative Example 2 were used to confirm the hair growth promoting effect, and were used on hair and scalp 7 times a week for 3 months.

After use, it was evaluated by dividing it into three stages according to the degree of improvement or damage as an evaluation criterion for four evaluation items such as thickness of hair, degree of denseness, volume and elasticity, respectively, and for each of Examples 2-1 to 2-5 An overall evaluation was judged (degree of improvement: +5, +4, +3, +2, +1, no improvement: 0, degree of impairment: -1, -2, -3, -4, -5). After 3 months from the start of use, the evaluation of the thickness and density of hair was carried out using a hair diagnostic device IS-3000C (Besutopia, Korea) to measure the change in hair diameter and number of hairs in the phototrichogram And, together with the results, the evaluation of the thickness, density, volume and elasticity of the hair was added together with the results of the user questionnaire in the form of a questionnaire survey, and the overall evaluation was calculated and determined.

table 6

From the results of Table 6, Comparative Examples 1 and 2 that do not contain 2,3-sialyllactose and 2,6-sialyllactose Examples 1-3 to 1-5 and Examples 2-3 and 2 It was evaluated that the effect of promoting hair growth was very high in the -5 section. In addition, the average value between Examples 1-1 to 1-5 and Examples 2-1 to 2-5 was higher as the content of Examples 1 and 2 in Formulation Example 2 increased.

Therefore, it was confirmed that both 2,3-sialyllactose and 2,6-sialyllactose can be effectively used to promote hair growth when preparing a hair tonic composition of 1% or more.

In summary, by containing the sialic acid derivatives or pharmaceutically acceptable salts thereof according to 2,3-sialyllactose and 2,6-sialyllactose of the present invention as an active ingredient, proliferation of dermal papilla cells is induced and hair It was confirmed that the effect of promoting growth and inhibiting the activity of 5-alpha-reductase to inhibit the production of dihydrotestosterone as well as promoting the activity of the wint/beta-catenin signaling pathway was excellent.

Having described specific parts of the present invention in detail above, it is clear that these specific techniques are only preferred embodiments for those skilled in the art, and the scope of the present invention is not limited thereto. Accordingly, the substantial scope of the present invention will be defined by the appended claims and equivalents thereof.

Hereinafter, formulation examples of cosmetic and pharmaceutical compositions for preventing hair loss and promoting hair growth containing sialic acid derivatives or pharmaceutically acceptable salts thereof according to 2,3-sialyllactose and 2,6-sialyllactose of the present invention are given. However, this is not intended to limit the cosmetic composition and pharmaceutical composition for preventing hair loss and promoting hair growth of the present invention to the following formulations, but is only intended to be specifically described.

[Formulation Example 3-1] Hair shampoo

Hair shampoo was prepared in a conventional manner according to the composition shown in Table 7 below.

table 7

[Formulation Example 3-2] Hair Treatment

Hair treatment was prepared in a conventional manner according to the composition shown in Table 8 below.

Table 8

[Formulation Example 3-3] Hair nutrient lotion

According to the composition shown in Table 9 below, a hair nourishing lotion was prepared in a conventional manner.

Table 9

[Formulation Example 4] Pharmaceutical formulation

[Formulation Example 4-1] Preparation of powder

Powders were prepared by a conventional method according to the compositions shown in Table 10 below.

Table 10

[Formulation Example 4-2] Preparation of capsule formulation

According to the composition shown in Table 11 below, capsules were prepared by filling gelatin capsules in a conventional manner.

Table 11

[Formulation Example 4-3] Preparation of ointment

An ointment was prepared by a conventional method according to the composition shown in Table 12 below.

Table 12

[Formulation Example 5] Food formulation

[Formulation Example 5-1] Production of Drinking Agent

After mixing 80 mg of 2,3-sialyllactose and 2,6-sialyllactose, 9 mg of vitamin E, 9 mg of vitamin C, 10 g of glucose, 0.6 g of citric acid, and 25 g of liquid oligosaccharide, 300 ml of purified water was added to each bottle. It was filled so that it was ㎖ each. After filling the bottle, the beverage was prepared by sterilizing at 130 ° C. for 4 to 5 seconds.

[Formulation Example 5-2] Preparation of granules

80 mg of 2,3-sialyllactose and 2,6-sialyllactose, 9 mg of vitamin E, 9 mg of vitamin C, 250 mg of anhydrous crystalline glucose and 550 mg of starch were mixed and formed into granules using a fluidized bed granulator. After that, it was prepared by filling the bag.

[Prior art literature]

Patent literature

(Patent Document 0001) Republic of Korea Patent Registration No. 10-1112051

(Patent Document 0002) Republic of Korea Patent Registration No. 10-1386979

(Patent Document 0003) Republic of Korea Patent Registration No. 10-1773067

(Patent Document 0004) Republic of Korea Patent Registration No. 10-1873527

(Patent Document 0005) Republic of Korea Patent Publication No. 10-2019-0067499

(Patent Document 0006) Republic of Korea Patent Registration No. 10-2019676

(Patent Document 0007) Republic of Korea Patent Registration No. 10-2204367

Claims (6)

A composition for preventing hair loss or promoting hair growth, comprising a sialic acid derivative or a pharmaceutically acceptable salt thereof as an active ingredient. According to claim 1,
The sialic acid derivatives or pharmaceutically acceptable salts thereof are α2,3-sialyllactose, α2,6-sialyllactose, α2,3-sialylgalactose, α2,6-sialylgalactose, α2,3-sialyllactose. A composition for preventing hair loss or stimulating hair growth, which comprises N-acetyllactosamine, α2,6-sialyl N-acetyllactosamine, disilyllactose, and a Stn epitope. According to claim 1,
The composition promotes hair growth by inducing the proliferation of dermal papilla cells, inhibits the activity of 5-alpha-reductase to inhibit the production of dihydrotestosterone, and promotes the activity of the wint/beta-catenin signaling pathway. A composition for preventing hair loss or promoting hair growth. According to claim 1,
The composition is a composition for preventing hair loss or promoting hair growth, characterized in that for increasing the thickness, density, volume and elasticity of the hair. According to claim 1,
The composition for preventing hair loss or stimulating hair growth, characterized in that the content of the sialic acid derivative or a pharmaceutically acceptable salt thereof is contained in 0.001 to 30.0% by weight based on the total weight. According to any one of claims 1 to 5,
The composition is a composition for preventing hair loss or promoting hair growth, characterized in that the cosmetic composition, pharmaceutical composition and food composition.

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