KR20240044913A - Composition for Preventing Hair Loss or Promoting Hair Growth Comprising Metal Thiooctoyl Hyaluronate Complex - Google Patents

Abstract

The present invention relates to a composition for preventing hair loss or promoting hair growth comprising a metal thioctoyl hyaluronate complex consisting of alpha-lipoic acid, a metal, and hyaluronic acid. Since the composition of the present invention has excellent hair loss prevention and hair growth promotion effects, it can be usefully used for patients with various types of hair loss, including genetic or non-genetic hair loss, alopecia areata, anti-cancer hair loss, etc.

Description

Composition for preventing hair loss or promoting hair growth comprising metal thiooctoyl hyaluronate complex {Composition for Preventing Hair Loss or Promoting Hair Growth Comprising Metal Thiooctoyl Hyaluronate Complex}

The present invention relates to a composition for preventing hair loss or promoting hair growth comprising a metal thioctoyl hyaluronate complex consisting of alpha-lipoic acid, a metal, and hyaluronic acid.

The average number of hairs in the human body is about 100,000 to 150,000, and there are three stages: a growth stage in which hair cells (keratinocytes) around the dermal papilla divide and proliferate, a catagen stage in which the hair stops growing and separates from the dermal papilla, and the hair cells do not grow. As the cell division and activity of the hair follicles cease in the process of repeating the resting phase, which falls out after a certain period of time, the existing hair is pushed out by the newly growing hair and falls out naturally. Usually, the hair growth period of adults varies from person to person, but it is generally 3 to 5 years for men and 4 to 6 years for women, and it is known that about 15% of hair is in the catagen and resting stages.

Each human hair has an independent growth cycle, falling out on one side and growing on the other side, maintaining the same number of hairs overall. This is called physiological natural hair loss. This natural hair loss phenomenon occurs with an average of about 100 hairs falling out per day. A larger amount of hair falls out than the natural hair loss described above, or hair does not exist in areas where hair should normally exist. When growth stops, hair loss occurs as a type of disease. Hair loss can occur during the natural aging process, but can also be caused by external environmental factors such as hormonal changes, stress, air pollution, and processed foods. However, in these cases, hair loss recovers once the cause is removed.

Types of hair loss include male pattern hair loss, female pattern hair loss, alopecia areata, and anticancer hair loss. First, male pattern hair loss is called 'androgenetic alopecia', and hair loss begins from the M-shaped area on the crown or forehead. The main cause is that testosterone, a male hormone, is converted to DHT by 5-alpha reductase (type 2), causing damage to DHT. It attacks sensitive hair follicles and causes hair loss.

Female pattern hair loss is characterized by diffuse hair loss, which is a form of overall thinning of the hair and a decrease in hair density. Hair loss usually begins with the hair falling out from the crown or above the parting, and worsens to the point where the scalp area on the crown is visible. The cause is the effect of DHT, a secondary metabolite of male hormones excessively secreted in women, and after menopause, due to a decrease in female hormones, the female hormone, estrogen, cannot suppress the function of the male hormone, androgen, as much as before, leading to hair loss. Other causes include poor blood circulation in the scalp due to stress, aging, Western diet, hyperlipidemia, dieting, lack of essential nutrients, accumulation of heavy metals, free radicals, chronic inflammation, etc., and decreased immunity due to lack of nutrition and accumulation of waste products. This can be an important cause.

Anti-cancer hair loss is caused by the cytotoxicity of anti-cancer drugs, and the biggest reason why anti-cancer drugs cause hair loss is because anti-cancer drugs affect cells that undergo a lot of cell division. Cytotoxic anticancer drugs are designed to prevent the rapid cell division and replication of cancer cells, so they affect bone marrow cells, intestinal epithelial cells, and hair follicle stromal keratinocytes that divide rapidly, causing hair loss, nausea, vomiting, anemia, and lymphocyte reduction. Side effects such as bleeding may occur, and since more than 85% of hair is in the growth stage, chemotherapy treatment causes the side effect of almost 100% of hair falling out.

Cancer cells have a fast cell division rate and a high metabolic rate, so they generate a lot of free radicals, and the free radicals generated in this way can induce the death of cancer cells. Many anticancer drugs can increase oxygen radicals in cancer cells and induce hair follicle cell death through the same mechanism.

Anticancer drugs increase oxygen radicals during high cell division of hair follicle cells, cause oxidative damage to mitochondria necessary for rapid energy metabolism, inhibit angiogenesis, and damage microcirculation of blood vessels around hair follicles, causing anticancer hair loss. As a result, in order to treat anticancer hair loss, it is possible to prevent the increase in free radicals and oxidative damage to mitochondria, which are side effects of cytotoxic anticancer drugs, and to activate the division of hair follicle stem cells and keratinocytes by supplying nutrients to hair follicle cells, activating mitochondria, and suppressing free radicals. A strong antioxidant effect and cell activity promotion effect are required.

As hair loss progresses, the dermal papilla present in the hair root becomes smaller, and accordingly, the thickness of the hair growing from the dermal papilla becomes thinner, and the hair cycle of growth, regression, and resting hair also becomes shorter, making the newly growing hair even thinner. As this phenomenon is repeated, the increasingly thinner hair turns into fluff, and the hair cycle gradually becomes shorter, causing the hair to grow less quickly and fall out, resulting in a decrease in the overall number of hairs. In the past, it was considered only a phenomenon or disease that mainly occurred in older men, but statistics show that close to half of all hair loss patients are young patients in their 20s and 30s, and the number of female patients is also gradually increasing. Hair loss causes major changes in the external aspect, so the cost of hair loss treatment, such as receiving transplant surgery or taking treatment for hair loss, is gradually increasing among young people who are interested in beauty and appearance.

Currently, many hair growth agents to prevent baldness and hair loss are being marketed around the world, but there are still few drugs or technologies that can satisfy the therapeutic effect. The only drug approved by the U.S. Food and Drug Administration (FDA) for hair growth after clinical trials is minoxidil, which was originally developed as a treatment for high blood pressure and was commercialized for hair growth, a type of side effect discovered, and the first in the world to be approved by the U.S. federal government. It is a treatment for baldness and alopecia. In addition, another currently used drug is finasteride, which is based on the hormonal theory of the cause of hair loss. Male hormones are converted into a metabolite, dihydrotestosterone (DHT), under the action of 5-alpha reductase. The substance is known to cause hair follicles to atrophy and disappear. The finasteride has the effect of slowing down the progression of male pattern hair loss as much as possible by inhibiting the production of DHT by blocking 5-alpha reductase. The effect of this drug is not on hair growth but on preventing further hair loss.

In addition, substances known to be effective in preventing hair growth and hair loss have been reported. For example, compounds include cyclosporine derivatives, N-heterocyclic carboxylic acids and carbamates, quinazolinone derivatives, chrysin 7-O-crotonate, and 1,2-disubstituted benzenecarboxamide derivatives. It has been reported that natural products with fewer side effects include ginseng extract, apricot seed oil, dendrobium extract, Baekdu extract, indigo extract, and Sanghwang mushroom extract (Patent Document 1). In addition, there are oral nutritional supplements such as Pancidil for hair loss treatment, which contain medicinal yeast, vitamins B1 (thiamine), B5 (pantothenic acid), and keratin that help with hair loss. These vitamins and yeast ingredients are known to help hair growth. It is known.

However, various side effects are known in the case of existing DHT inhibitors or steroid treatments. In the case of finasteride, hair loss occurs again when the medication is stopped, and in the case of minoxidil, people experience allergies such as itching and erythema and a shedding phenomenon in which weak telogen hair falls out again when the medication is stopped. Additionally, in the case of DHT inhibitors, there is fear of decreased sexual function such as decreased libido and psychological resistance to taking the drug (Non-patent Document 1). In the case of topical application of steroids, side effects such as scalp atrophy or permanent hair loss may occur due to a decrease in collagen at the injection site. Therefore, there is an urgent need to develop an agent that can effectively prevent hair loss and promote hair growth with fewer side effects.

Accordingly, the present inventors completed the present invention by confirming that a metal thioctoyl hyaluronate complex composed of hyaluronic acid, alpha-lipoic acid, and a metal such as magnesium can be usefully used for preventing hair loss and promoting hair growth. did.

Public Patent Publication No. 10-2019-0134114

Venkataram Mysore, Indian Dermatol. Online J., 3(1):62-65, 2012

The purpose of the present invention is to provide a composition for preventing hair loss or promoting hair growth comprising a metal thioctoyl hyaluronate complex consisting of hyaluronic acid, alpha-lipoic acid, and a metal such as magnesium.

In order to solve the above problems, the present invention provides a composition for preventing hair loss or promoting hair growth comprising a metal thioctoyl hyaluronate complex represented by the following formula (1).

[Formula 1]

In the above, n is an integer from 2 to 50, and Mt ²⁺ may be an alkaline earth metal or a divalent transition metal ion.

In one embodiment, the composition may be in the form of a pharmaceutical composition or a cosmetic composition, but is not limited thereto.

In one embodiment, n may be an integer from 2 to 10, and the metal is an alkaline earth metal, such as magnesium (Mg), beryllium (Be), calcium (Ca), strontium (Sr), barium (Ba), and radium. (Ra), or divalent transition metals such as iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), etc. may be used without limitation.

In a preferred embodiment, the composite may be a composite represented by Formula 2 in which the metal is magnesium.

[Formula 2]

In the above, n is an integer from 2 to 10.

In one embodiment, the composition may further include, but is not limited to, another anti-hair loss or hair growth promoting agent, such as choline alfoscerate.

In one embodiment, the composition may be in the form of a spray or injection. In a preferred embodiment, the spray or injection may be administered to the skin, subcutaneously, or dermis of the hair loss area, but is not limited thereto.

The composition containing the metal thioctoyl hyaluronate complex of the present invention has excellent hair loss prevention and hair growth promotion effects, so it is useful for patients with various types of hair loss, including genetic or non-genetic hair loss, alopecia areata, anti-cancer hair loss, etc. can be used

However, the effects of the present invention are not limited to the effects mentioned above, and other effects not mentioned will be clearly understood by those skilled in the art from the following description.

Figure 1 schematically shows the synthesis process of metal thioctoyl hyaluronate complex.
Figure 2a shows alpha-lipoic acid powder used as a raw material in the production of the metal thioctoyl hyaluronate complex, and Figure 2b is a photograph showing the synthesized magnesium thioctoyl hyaluronate complex aqueous solution.
FIGS. 3A to 3C and FIGS. 4A to 4C are photographs showing the effects of preventing hair loss and promoting hair growth over time after administering the composition of the present invention to various hair loss patients including normal hair loss and anti-cancer hair loss.

Hereinafter, the present invention will be described in detail.

1. Composition for preventing hair loss or promoting hair growth

One aspect of the present invention provides a composition that can be used to prevent hair loss or promote hair growth.

The composition for preventing hair loss or promoting hair growth of the present invention includes a metal thioctoyl hyaluronate complex represented by the following formula (1).

[Formula 1]

Here, n is an integer from 2 to 50, such as 2 to 30, 2 to 20, 2 to 10, or 2 to 5, and Mt ²⁺ is an alkaline earth metal or a divalent transition metal ion. The alkaline earth metal may include magnesium (Mg), beryllium (Be), calcium (Ca), strontium (Sr), barium (Ba), radium (Ra), etc., and the divalent transition metal may be iron (Fe). ), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), etc., but is not limited thereto.

The metal thioctoyl hyaluronate complex included in the composition of the present invention is magnesium thioctoyl hyaluronic acid, preferably represented by the following formula (2), which is a combination of magnesium and alpha-lipoic acid using hyaluronic acid, preferably a hyaluronic acid oligomer, as a support. It is preferable that it is a ronate complex.

[Formula 2]

Here, n is an integer from 2 to 50, such as 2 to 30, 2 to 20, 2 to 10, or 2 to 5.

In a preferred embodiment, the metal thioctoyl hyaluronate complex comprised in the composition of the present invention is

1) Preparing a hyaluronic acid polymer solution;

2) converting the hyaluronic acid polymer into a hyaluronic acid oligomer by treating the hyaluronic acid polymer with acid;

3) synthesizing hyaluronic acid metal salt by treating hyaluronic acid oligomer with metal hydroxide;

4) adding a base to the hyaluronic acid metal salt to dissociate the hyaluronic acid cross-linked side chains; and

5) forming a complex of hyaluronic acid metal salt and alpha-lipoic acid.

In one embodiment, the metal may be an alkaline earth metal or a divalent transition metal. The alkaline earth metal may include magnesium (Mg), beryllium (Be), calcium (Ca), strontium (Sr), barium (Ba), radium (Ra), etc., and the divalent transition metal may be iron (Fe). ), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), etc., but is not limited thereto. In a preferred embodiment, the metal is preferably, but not limited to, magnesium.

In step 1), the hyaluronic acid polymer solution has a concentration range of 1 to 10% (w/w), preferably 1 to 5% (w/w), but is not limited thereto. If the concentration of the hyaluronic acid polymer solution is less than 1% (w/w), stirring is difficult due to an increase in viscosity, making it difficult to operate the processing process, and if it is more than 10% (w/w), processing of processing raw materials is difficult. The capacity is small and the process is not economical.

In step 2), the acid may be any organic acid or an aqueous solution of an inorganic acid without limitation, but it is preferable to use an organic acid. The organic acids may include lactic acid, acetic acid, formic acid, citric acid, oxalic acid, malic acid, succinic acid, and tartaric acid, and the inorganic acids may include hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, boric acid, and carbonic acid, but are not limited thereto. .

The aqueous solution of the organic acid, such as lactic acid, has a concentration range of 1 to 5 N, preferably 1 to 3 N, but is not limited thereto. If the concentration of the organic acid is less than 1 N, the acid hydrolysis reaction is not performed smoothly, and if it is more than 5 N, a separate neutralization reaction may be required after the acid hydrolysis reaction.

The reaction temperature during the acid treatment may be 60 to 100°C, for example, 60 to 90°C, or 60 to 80°C, but is not limited thereto. If the reaction temperature is less than 60°C, the hydrolysis reaction may not be performed due to the low temperature, and if it exceeds 100°C, the reaction rate increases, but there is a problem of increased equipment costs due to the need for pressurized reaction equipment.

Additionally, the reaction time during the acid treatment may be 0.5 to 8 hours, preferably 1 to 6 hours, but is not limited thereto. If the reaction time is less than 1 hour, the conversion to hyaluronic acid oligomer may not be sufficiently performed, and if it is longer than 6 hours, the hyaluronic acid oligomer is hydrolyzed back to hyaluronic acid monomer, and the conversion rate of hyaluronic acid oligomer decreases. There is a risk that the conversion rate of monomers may increase.

In step 3), the metal hydroxide is preferably magnesium hydroxide, and the hyaluronic acid metal salt is preferably magnesium hyaluronic acid salt, but is not limited thereto.

The added mole number of metal hydroxide, such as magnesium hydroxide, relative to 1 mol of the hyaluronic acid oligomer may be in the range of 0.1 to 0.5 mol, preferably 0.1 to 0.3 mol, but is not limited thereto. If the number of moles of metal hydroxide relative to 1 mol of the hyaluronic acid oligomer is less than 0.1 mol, the number of ionic bonds between the hyaluronic acid oligomer and the metal, such as magnesium, may be small, which may lower the synthesis yield of metal salt of hyaluronic acid. If it is more than 0.5 mol, unreacted metal may be present. Oxides may remain in the hyaluronic acid compound, resulting in poor transparency and precipitation in aqueous solutions.

In step 4), the base may be any organic base or an aqueous solution of an inorganic base without limitation, but it is preferable to use an inorganic base. The organic base may be pyridine, imidazole, histidine, guanidine, etc., and the inorganic base may include magnesium hydroxide, calcium hydroxide, magnesium oxide, calcium oxide, calcium carbonate, etc., but is not limited thereto.

The aqueous solution of the inorganic base, such as sodium hydroxide, has a concentration range of 1 to 5 N, preferably 1 to 4 N, such as 1 to 3 N, but is not limited thereto. If the concentration of the inorganic base is less than 1 N, the side chain dissociation of the hyaluronic acid cross-link is not completely performed, which causes a problem in that the conversion rate of magnesium thioctoyl hyaluronate synthesis in the subsequent process is reduced, and if the concentration is more than 4 N, the hyaluronic acid cross-linking occurs. In addition to the side chain dissociation of the bond, it is substituted with sodium ions due to a substitution reaction with magnesium, which may cause a problem in that the conversion rate of magnesium thioctoyl hyaluronate synthesis in the subsequent process is reduced.

The reaction temperature during the base treatment may be 30 to 80°C, for example, 40 to 70°C, or 40 to 60°C, but is not limited thereto. If the reaction temperature is less than 30°C, the reaction may not be performed due to the low temperature, and if it is higher than 80°C, a substantially significant effect of increasing the reaction cannot be obtained.

Additionally, the reaction time during the base treatment may be 0.1 to 1 hour, preferably 0.2 to 0.5 hours, but is not limited thereto. If the reaction time is less than 0.1 hour, the reaction may not be sufficiently performed, and if it is longer than 1 hour, a substantially significant effect of increasing the reaction cannot be obtained.

In step 5), the added mole number of alpha-lipoic acid relative to 1 mol of the hyaluronic acid metal salt may be in the range of 0.1 to 0.8 mol, for example, 0.71 mol, preferably 0.1 to 0.5 mol, but is not limited thereto. When the molar number of alpha-lipoic acid relative to 1 mol of the hyaluronic acid oligomer is less than 0.1 mol, the yield of metal thioctoyl hyaluronate synthesis is low, and the properties of the metal thioctoyl hyaluronite complex desired in the present invention, such as transdermal absorption rate, are low. It may not show improvement or increase in bioavailability, and if it exceeds 0.8 mol, there is a high possibility that it will remain in the composite as free alpha-lipoic acid.

Additionally, the reaction temperature may be 40 to 120°C, for example, 50 to 100°C, or 60 to 90°C, but is not limited thereto. If the reaction temperature is less than 40℃, the reaction may not be carried out due to the low temperature, and if it exceeds 120℃, a side reaction due to the oxidation reaction of alpha-lipoic acid may occur, causing problems such as browning and off-odor in the final product. There is.

In one embodiment, the composition of the present invention may further include other anti-hair loss or hair growth promoting agents. The hair loss prevention or hair growth promoting agent may be any compound known to those skilled in the art, such as finasteride, minoxidil, choline alfoscerate, etc., but is not limited thereto.

In the present invention, the term "hair loss" means the absence of hair in areas where hair should normally exist, and includes a phenomenon in which the number of hairs decreases compared to the normal state. The hair loss is a concept that includes both non-scarring alopecia or cicatricial alopecia depending on whether the hair follicles are destroyed, for example, hereditary androgenetic alopecia, alopecia areata, tinea capitis due to fungal infection, telogen effluvium, hair growth wall, hair It includes, but is not limited to, dysgenerative diseases, hair loss due to lupus, toxic folliculitis, lichen planus pilaris, hair loss due to burns and/or trauma, etc.

Preventing hair loss means removing the cause of hair loss or suppressing the progression of hair loss, and may include promoting hair growth by suppressing hair loss or promoting hair formation.

The composition of the present invention, which contains the metal thioctoyl hyaluronate complex represented by Formula 1 as an active ingredient, did not show any unusual side effects when applied to the scalp in various clinical trials.

According to a specific embodiment of the present invention, the effect over time was examined after administering the composition of the present invention to patients with various types of hair loss, including genetic or non-genetic hair loss, alopecia areata, anti-cancer hair loss, etc. It was confirmed that the composition of the invention can achieve excellent hair loss prevention and hair growth promotion effects in a short period of time, which cannot be obtained with conventional hair loss treatment in both men and women (see FIGS. 3A to 3C and 4A to 4C) ).

2. Pharmaceutical composition for preventing or treating hair loss

Another aspect of the present invention provides a pharmaceutical composition for preventing or treating hair loss.

The pharmaceutical composition of the present invention contains a metal thioctoyl hyaluronate complex represented by Formula 1 as an active ingredient. A description of the metal thioctoyl hyaluronate complex represented by Formula 1 is given in '1.' It is the same as described in 'Composition for preventing hair loss or promoting hair growth', and hereinafter, only the composition specific to the pharmaceutical composition will be described.

In the present invention, the term "prevention" refers to any action that reduces the risk of developing a disease or disorder, and refers to the prevention of disease in subjects who are susceptible to exposure to the disease or who are susceptible to the disease but who do not yet have the disease or show signs of the disease. It is used to include, without limitation, all actions that suppress or delay the onset of a disease by preventing the progression of one or more clinical symptoms.

In the present invention, the term "treatment" means any action that alleviates a disease or disorder, and any action that improves or beneficially changes the symptoms of a disease by arresting or reducing the progression of the disease or one or more clinical signs thereof. It is used to include actions without limitation.

In the present invention, the prevention or treatment of hair loss may be removing the cause of hair loss as described above or suppressing the progression of hair loss, and may be promoting hair growth by suppressing hair loss or promoting hair formation.

Meanwhile, the pharmaceutical composition of the present invention is formulated using a pharmaceutically acceptable carrier and/or excipient according to a method that can be easily performed by a person skilled in the art to which the present invention pertains. It can be manufactured in dosage form or by placing it in a multi-dose container. At this time, the formulation may be in the form of a solution, suspension, or emulsion in an oil or aqueous medium, or may be in the form of an extract, powder, granule, tablet, capsule, or gel (e.g., hydrogel), and may additionally contain a dispersant or stabilizer. there is.

In addition, the metal thioctoyl hyaluronate complex represented by Formula 1 included in the pharmaceutical composition can be used in pharmaceutically acceptable forms such as colloidal suspension, powder, saline solution, lipid, liposome, microsphere, or nano-spherical particle. It can be transported on any carrier that can be used. They may form complexes or associate with the delivery vehicle and may be used in the field, such as lipids, liposomes, microparticles, gold, nanoparticles, polymers, condensation agents, polysaccharides, polyamino acids, dendrimers, saponins, adsorption enhancers or fatty acids. It can be transported in vivo using a known delivery system.

In addition, the pharmaceutically acceptable carriers include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia, gum, calcium phosphate, alginate, gelatin, calcium silicate, and microcrystalline cellulose, which are commonly used in preparation. , polyvinyl pyrolidone, cellulose, water, syrup, methyl cellulose, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, mineral oil, etc., but is not limited thereto. In addition, in addition to the above ingredients, lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, etc. may be additionally included.

The pharmaceutical composition according to the present invention can be administered orally or parenterally during clinical administration and can be used in the form of a general pharmaceutical preparation, but is preferably administered parenterally, especially in the form of a spray or injection. That is, the pharmaceutical composition of the present invention can be administered in various oral and parenteral dosage forms during actual clinical administration. When formulated, diluents such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants are used. Or it is prepared using excipients. The pharmaceutical composition of the present invention is preferably administered in a parenteral formulation, and preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, and freeze-dried preparations. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate.

The effective dosage of the composition of the present invention may vary depending on factors such as formulation method, administration method, patient's age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and reaction sensitivity. Generally, it is 1 to 20 mg/day per 1 kg of body weight of an adult patient, preferably 5 to 10 mg/day, several times a day at regular time intervals, preferably 2 to 3 times a day, depending on the judgment of a doctor or pharmacist. It may be administered in divided doses. In one embodiment, the composition of the present invention is preferably, but not limited to, sprayed onto the skin of the hair loss area.

Additionally, the pharmaceutical composition of the present invention may be an external skin preparation. The external skin preparation is a preparation that can be used by applying it to the outside of the skin. When the pharmaceutical composition of the present invention is used as an external skin preparation, it is applied to the scalp, specifically the scalp in the area where hair loss has occurred or the area where hair growth is to be promoted. It may be applied to the scalp. The external skin preparation may be a cream, gel, ointment, skin emulsifier, skin suspension, transdermal delivery patch, drug-containing bandage, lotion, or a combination thereof. The skin external preparation includes ingredients commonly used in skin external preparations such as cosmetics and medicines, such as aqueous ingredients, oil-based ingredients, powder ingredients, alcohols, moisturizers, thickening agents, ultraviolet ray absorbers, whitening agents, preservatives, antioxidants, surfactants, Fragrances, colorants, various skin nutrients, or combinations thereof may be appropriately mixed according to need. The skin external preparations include metal sequestrants such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, and gluconic acid, caffeine, tannin, belafamil, licorice extract, glablidin, and calin. Hot water extracts of fruit, various herbal medicines, drugs such as tocopherol acetate, glytylitinic acid, tranexamic acid and its derivatives or salts, vitamin C, magnesium ascorbate phosphate, ascorbate glucoside, arbutin, kojic acid, glucose, fructose, Sugars such as trehalose can also be appropriately mixed.

3. Cosmetic composition for preventing or improving hair loss

Another aspect of the present invention provides a cosmetic composition for preventing or improving hair loss.

The cosmetic composition of the present invention contains a metal thioctoyl hyaluronate complex represented by Chemical Formula 1 as an active ingredient. A description of the metal thioctoyl hyaluronate complex represented by Formula 1 is given in '1.' It is the same as described in 'Composition for preventing hair loss or promoting hair growth', and hereinafter, only the composition specific to the cosmetic composition will be described.

The term "prevention" means reducing the risk of developing a disease or disorder, and is defined as reducing the risk of developing one or more clinical signs of a disease in subjects who are susceptible to being exposed to the disease or contracting the disease but have not yet developed the disease or shown symptoms of the disease. It refers to all actions that suppress or delay the onset of a disease by preventing it from occurring.

The above “improvement” means any action that improves or benefits the symptoms of a disease or disorder.

The prevention or improvement of hair loss may be removing the cause of hair loss or suppressing the progression of hair loss, or may be promoting hair growth by suppressing hair loss or promoting hair formation.

The cosmetic composition may include, for example, the metal thioctoyl hyaluronate complex represented by Formula 1 in a cosmetically effective amount together with a cosmetically acceptable carrier, and the cosmetically effective amount refers to the hair loss prevention or hair growth promotion effect described above. means a sufficient amount to achieve.

The cosmetic composition of the present invention contains the metal thioctoyl hyaluronate complex represented by Chemical Formula 1 within the range that does not affect the hair loss prevention or hair growth promoting activity of the complex, for example, the metal thioctoyl hyaluronate complex represented by Chemical Formula 1. It may additionally contain other ingredients that have characteristics that can have a synergistic effect on the activity of the nate complex. For example, fatty substances, organic solvents, solubilizers, thickening and gelling agents, emollients, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants, water, ionic or non-ionic emulsifiers, fillers, metal ions. In the field of cosmetics or dermatology, such as sequestering and chelating agents, preservatives, vitamins, blocking agents, humectants, essential oils, dyes, pigments, fragrances, hydrophilic or lipophilic actives, lipid vesicles or any other ingredients commonly used in cosmetics. It may contain auxiliaries commonly used in cosmetics or dermatology, and the ingredients may be contained in amounts commonly used in the cosmetics or dermatological fields.

The cosmetic composition of the present invention can be prepared in any formulation commonly manufactured in the art, for example, solution, suspension, emulsion, gel, lotion, essence, cream, powder, soap, shampoo, rinse. , pack mask, surfactant-containing cleansing, cleansing foam, cleansing water, oil, liquid foundation, cream foundation, or spray.

When the formulation is a solution or emulsion, a solvent, solubilizing agent, or emulsifying agent may be used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol, or fatty acid ester of sorbitan can be used. If the formulation is a suspension, the carrier ingredients include water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, and aluminum metahydroxide. Seeds, microcrystalline cellulose, bentonite, agar, or tracant may be used. When the formulation is a cream or gel, wax, paraffin, tracant, animal oil, starch, cellulose derivatives, silicone, bentonite, polyethylene glycol, silica, zinc oxide, or talc may be used as carrier ingredients. When the formulation is a powder or spray, the carrier component may include a propellant such as silica, talc, aluminum hydroxyl group, lactose, calcium silicate, chlorofluorohydrocarbon, propane/butane, or dimethyl ether. When the formulation is a surfactant-containing cleansing, the carrier ingredients include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, imidazolinium derivative, isethionate, methyl taurate, sarcosinate, and fatty acid amide ether sulfate. , fatty alcohol, alkylamidobetaine, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative, or ethoxylated glycerol fatty acid ester can be used.

Specifically, the cosmetic composition of the present invention may be an external skin preparation. The external skin preparation is a preparation that can be used by applying it to the outside of the skin. When the cosmetic composition of the present invention is used as an external skin preparation, it is applied to the scalp, specifically the scalp in the area where hair loss has occurred or the area where hair growth is to be promoted. It may be applied to the scalp. The external skin preparation may be a cream, gel, ointment, skin emulsifier, skin suspension, transdermal delivery patch, drug-containing bandage, lotion, or a combination thereof. The skin external preparation includes ingredients commonly used in skin external preparations such as cosmetics and medicines, such as aqueous ingredients, oil-based ingredients, powder ingredients, alcohols, moisturizers, thickening agents, ultraviolet ray absorbers, whitening agents, preservatives, antioxidants, surfactants, Fragrances, colorants, various skin nutrients, or combinations thereof may be appropriately mixed according to need. The skin external preparations include metal sequestrants such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, and gluconic acid, caffeine, tannin, belafamil, licorice extract, glablidin, and calin. Hot water extracts of fruit, various herbal medicines, drugs such as tocopherol acetate, glytylitinic acid, tranexamic acid and its derivatives or salts, vitamin C, magnesium ascorbate phosphate, ascorbate glucoside, arbutin, kojic acid, glucose, fructose, Sugars such as trehalose can also be appropriately mixed.

Hereinafter, the present invention will be described in detail by examples.

However, the following examples only specifically illustrate the present invention, and the content of the present invention is not limited by the following examples.

Example 1. Preparation of magnesium thioctoyl hyaluronate complex

<1-1> Preparation of hyaluronic acid solution

After dispersing 0.0718 mol of hyaluronic acid in 60 g of 1,2-hexanediol, 510 g of purified water was added and completely dissolved to prepare a 5% hyaluronic acid solution.

<1-2> Conversion to hyaluronic acid oligomer

After adding 10 mL of 2.94 N aqueous lactic acid solution to the 5% hyaluronic acid solution prepared in Example <1-1>, acid hydrolysis reaction was performed at 80°C and 200 rpm for 4 hours to convert into hyaluronic acid oligomer. .

<1-3> Synthesis of hyaluronic acid metal salt

Magnesium hyaluronic acid metal salt was synthesized by adding 0.145 mol of magnesium hydroxide to the hydrolyzed hyaluronic acid oligomer prepared in Example <1-2>, and then allowed to cool to 45°C.

<1-4> Dissociation of hyaluronic acid cross-linked side chains

10 ml of a 3.25 N NaOH aqueous solution was added to the magnesium metal salt solution of hyaluronic acid prepared in Example <1-3>, and the mixture was heated and stirred at 45°C and 400 rpm for 10 minutes to perform a dissociation reaction of the hyaluronic acid cross-linked side chain. .

<1-5> Synthesis of magnesium thioctoyl hyaluronate complex

In Example <1-4>, 0.101 mol of alpha-lipoic acid was added in several installments to the magnesium hyaluronic acid metal salt solution in which the dissociation reaction was completed, and the reaction mixture was heated and stirred at 45°C and 400 rpm until it became transparent to produce magnesium thioctoyl hyaluronic acid. Ronate complex was synthesized.

The synthesis process is summarized in Figure 1, and the alpha-lipoic acid powder used as a raw material and the synthesized magnesium thioctoyl hyaluronate complex solution are shown in Figures 2a and 2b, respectively.

Example 2. Preparation of a composition for preventing hair loss or promoting hair growth containing magnesium thioctoyl hyaluronate complex

A scalp tonic formulation composition was prepared by mixing the ingredients listed in Table 1 below based on the emulsion composition consisting of the magnesium thioctoyl hyaluronate complex and choline alfoscerate prepared in Example 1.

division Ingredient name Composition content (wt%) Liquid crystal emulsion composition Magnesium thioctoyl hyaluronate complex 5 Choline Alfoscerate 5 ethanol 10 moisturizer glycerin 5 Butylene glycol 3 1,2-hexanediol 2 Betaine One functional ingredients Niacinamide 5 panthenol One salicylic acid 0.5 menthol 0.3 carnitine 5 vitamin complex 0.2 mineral complex 0.2 amino acid complex 0.2 glutathione 0.2 biotin 0.01 irritant reliever allantoin 0.2 Solubilizer PEG-60 Hydrogenated Castor Oil 1.5 antiseptic Caprylic hydroxamic acid 0.8 menstruum Purified water 53.89 Sum 100

Example 3. Effect of preventing hair loss and promoting hair growth of the composition of the present invention

The composition of the present invention was spray-applied to various hair loss patients, including androgenetic alopecia, alopecia areata, and anticancer alopecia, on skin where hair loss had occurred, and the hair loss prevention and hair growth promotion effects were confirmed. For patients who visited the hospital, the composition prepared in Example 2 was sprayed and applied to the scalp using a pressure spray laser. In the case of self-application, the composition was sufficiently applied to the scalp after washing and drying the hair every morning or evening. and was absorbed transdermally.

Figures 3A to 3C show the treatment results for 5 patients with normal hair loss, and Figures 4A to 4C show the treatment results for 6 patients with anti-cancer hair loss. From the above results, the composition of the present invention comprising the metal thioctoyl hyaluronate complex represented by Formula 1 has excellent hair loss prevention and hair growth promotion effects on various hair loss patients including androgenetic alopecia, alopecia areata, and anticancer alopecia. It was confirmed that there is.

In the above, the present invention has been described in detail only with respect to the described embodiments, but it is obvious to those skilled in the art that various changes and modifications are possible within the technical scope of the present invention, and it is natural that such changes and modifications fall within the scope of the appended claims.

Claims (9)

Pharmaceutical composition for preventing hair loss or promoting hair growth comprising a metal thioctoyl hyaluronate complex represented by Formula 1:
[Formula 1]

In the above, n is an integer from 2 to 50, and Mt ²⁺ is an alkaline earth metal or a divalent transition metal ion. In claim 1,
The n is an integer of 2 to 10, and the metal is magnesium (Mg), beryllium (Be), calcium (Ca), strontium (Sr), barium (Ba), radium (Ra), iron (Fe), cobalt ( A pharmaceutical composition selected from the group consisting of Co), nickel (Ni), copper (Cu), and zinc (Zn). In claim 1,
A pharmaceutical composition comprising a magnesium thioctoyl hyaluronate complex represented by Formula 2:
[Formula 2]

In the above, n is an integer from 2 to 10. In claim 1,
A pharmaceutical composition further comprising choline alfoscerate. In claim 1,
Pharmaceutical compositions in the form of sprays or injections. Cosmetic composition for preventing hair loss or promoting hair growth comprising a metal thioctoyl hyaluronate complex represented by Formula 1:
[Formula 1]

In the above, n is an integer from 2 to 50, and Mt ²⁺ is an alkaline earth metal or a divalent transition metal ion. In claim 6,
The n is an integer from 2 to 10, and the metals include magnesium (Mg), beryllium (Be), calcium (Ca), strontium (Sr), barium (Ba), radium (Ra), iron (Fe), and cobalt ( A cosmetic composition selected from the group consisting of Co), nickel (Ni), copper (Cu), and zinc (Zn). In claim 6,
A cosmetic composition comprising a magnesium thioctoyl hyaluronate complex represented by Formula 2:
[Formula 2]

In the above, n is an integer from 2 to 10. In claim 6,
A cosmetic composition further comprising choline alfoscerate.