KR102550913B1 - Composition for preventing or treating hair loss comprising the extract of Sargassum horneri as an active ingredient - Google Patents

Abstract

Since the extract of thorax chinensis and the rolliolide derived from thoracic chinensis can restore the expression of beta-catenin decreased by UVB irradiation, it can be used for preventing or treating hair loss.

Description

Composition for preventing or treating hair loss comprising the extract of Sargassum horneri as an active ingredient}

The present invention relates to a composition for the prevention or treatment of hair loss comprising an extract of black capsular capillaries as an active ingredient.

In general, there are many causes of alopecia, but there are genetic and acquired factors. Genes directly involved in the cause of hair loss in genetic factors have not been identified, but several genes have been reported to be involved. The degree of hair loss due to genetic factors can predict the progress of hair loss to some extent by comprehensively determining the congenital history, the current hair loss condition, and the progress of hair loss. Causes of acquired hair loss include alopecia areata, androgenetic alopecia, female pattern alopecia, juvenile alopecia, drug-induced alopecia, traumatic alopecia, alopecia caused by skin disease, and scarring alopecia.

Alopecia areata is a circular or oval shape of various sizes, with clear borders of hair loss, single hair or multiple hair loss, and in severe cases, it can spread to the entire head, and it is difficult to detect hair loss progress and has a high recurrence rate. Recent research results have revealed that alopecia areata is a kind of autoimmune disease. In other words, lymphocytes that can damage hair follicles are concentrated around the hair follicle, and the main targets are known to be the cause of melanocytes, keratinocytes, dermal papilla, and vascular endothelium. .

Recently, hair loss symptoms are common due to environmental factors, mental stress, and excessive use of shampoo or cosmetic soap. Therefore, it is desirable to diagnose and treat hair loss symptoms at an early stage because hair loss symptoms not only give severe stress to the person, but also cause loss of self-confidence and interfere with smooth interpersonal relationships. In particular, when the factors of genetic hair loss and the cause of acquired hair loss are combined, the symptoms of hair loss appear more severe, so it is important to diagnose and prevent it at an early stage.

Currently, many products are circulated on the market as hair loss treatment and hair growth agents, but there are many products whose effect is insignificant or the effect of hair loss and hair growth treatment has not been verified.

Sargassum horneri is a brown algae belonging to the family Sargassum horneri, which lives in the southern coast of Korea and all the coasts of Japan, and is mainly used as feed. It has been reported that the extract of oxen cape has the function of preventing osteoporosis (Yakugaku Zasshi. 2006, 126, 1117-1137) and the effect of preventing blood coagulation (Bioresour. Technol. 2007, 98, 1711-1716). In addition, it has been reported that the hot water extract of oxensis japonica has an inhibitory effect on Herpes simplex virus type 1 (Chem. Pharm. Bull. 2001, 49, 484-485. ; Biol. Pharm. Bull. 1998, 21 , 730-734). However, nothing is known about the hair loss improvement effect of hoesaeng cap.

Republic of Korea Publication No. 10-2014-0016057 (2014.02.07)

The present invention provides a composition for preventing, improving, or treating hair loss containing, as an active ingredient, an extract of capsular thorax, which increases the expression of β-catenin, a loliolide derived from capsicum culata, or both of them as active ingredients.

One aspect provides a pharmaceutical composition for preventing or treating hair loss comprising an extract of capsular capillaries, rolliolide, or a combination thereof as an active ingredient.

The extract of the thoracic capitis may be obtained by extracting water, C1 to C4 alcohol, or a mixture thereof using a solvent. For example, the solvent may be 30% to 100% ethanol, 40 to 90% ethanol, 50 to 80% ethanol, or 70% ethanol.

According to one embodiment, the extract of the thorax capitula may be extracted by heating. The warming may be 60 °C to 80 °C, or 65 °C to 75 °C, and according to one embodiment, it may be 70 °C.

The roliolide may be a compound represented by Chemical Formula 1 below.

[Formula 1]

The rolliolide may be extracted from hoesaeng hatban. For example, it can be washed and freeze-dried, then pulverized and stored, immersed in a solvent mixed with water and ethanol, and extracted at room temperature or at elevated temperature.

The roliolide may be in the form of a pharmaceutically acceptable salt. As the salt, an acid addition salt formed by a pharmaceutically acceptable free acid may be used. The acid addition salt may be prepared by a conventional method, for example, by dissolving a compound in an excess acid aqueous solution and precipitating it with a water-miscible organic solvent (eg, methanol, ethanol, acetone or acetonitrile). Alternatively, an equimolar amount of the compound and an acid or alcohol (eg, glycol monomethyl ether) in water may be heated, and the mixture may be evaporated to dryness or the precipitated salt may be suction filtered. Organic acids and inorganic acids may be used as the free acid. For example, the inorganic acid may be hydrochloric acid, hydrobromic acid, sulfuric acid, or phosphoric acid, and the organic acid may be citric acid, acetic acid, lactic acid, tartaric acid, maleic acid, fumaric acid, formic acid, or propionic acid. acid), oxalic acid, trifluoroacetic acid, benzoic acid, gluconic acid, methane sulfonic acid, glycolic acid, succinic acid, 4-toluenesulfonic acid, benzenesulfonic acid, salicylic acid, nicotinic acid, isonicotinic acid, picolinic acid, glutamic acid Or it may be aspartic acid, but is not limited thereto.

The "improvement" may refer to any activity that at least reduces a parameter related to alleviation or treatment of a condition, for example, the severity of a symptom.

The term "treatment" may comprehensively mean a process of treating, alleviating, alleviating a hair loss condition, or an effect thereof, and includes, for example, hair follicle cell regeneration, hair follicle cell activity recovery, hair follicle cell death inhibition, DKK It may mean any action that suppresses the progress of hair loss, such as suppression of the expression of hair loss inducing factors such as -1.

The hair loss refers to a state in which there is no hair in an area where hair should normally exist or is less than normal, and specifically, it may mean that the terminal hair (thick and black hair) of the scalp is lost. The cause of hair loss can be caused by various eating habits and environmental influences such as genetic causes, hormonal imbalance, mental stress, exposure to air pollution, ultraviolet rays, and intake of processed foods. For example, hair loss includes hereditary androgenic "alopecia" (baldness), circular "hair loss, ringworm of the head caused by fungal infection, telogen" hair loss, hair growth, hair growth disorders, etc., and scarring "hair loss" caused by lupus It may be alopecia, toxic folliculitis, lichen planus pilaris, hair loss caused by burns and trauma. In one embodiment, the hair loss may be hair loss induced by ultraviolet rays.

The pharmaceutical composition may be administered to a subject through various routes to prevent or treat hair loss. The subject may be a mammal, such as a human, cow, horse, pig, dog, sheep, goat, or cat, and the mammal may be a human. An effective dosage of the compound of the present invention for the human body may vary depending on the patient's age, weight, sex, dosage form, health condition and disease severity. The administration may be administered in various formulations for oral administration or parenteral administration such as intravenous, intraperitoneal, transdermal, intradermal, subcutaneous, epithelial, rectal, inhalation, nasal, sublingual, or intramuscular administration. It is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.

The pharmaceutical composition may be for oral administration. Solid preparations for oral administration may include tablets, pills, powders, granules, fine granules, capsules, suspensions, oral preparations, rapidly disintegrating tablets, syrups, chewing agents, troches, etc. It may be prepared by mixing the compound of the invention with at least one excipient, for example, starch, calcium carbonate, sucrose, lactose, or gelatin. In addition, lubricants may also be used in addition to simple excipients. Liquid formulations for oral administration may include suspensions, internal solutions, emulsions, or syrups. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, and preservatives are used. can be included

The pharmaceutical composition may be for parenteral administration. Formulations for parenteral administration may include sterilized aqueous solutions, injections, non-aqueous solutions, suspensions, emulsions, lyophilized formulations, aerosols, nasal administration, emulsions, suppositories, and the like. 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 paper, glycerol, gelatin, and the like may be used.

The pharmaceutical composition may be an external agent. External preparations can be applied in the form of patches, bands, emulsions, ointments, packs, gels, creams, lotions, liquids or powders, and as cosmetics, softening lotion, nutrient lotion, massage cream, nutrient cream, moisturizing cream, functional lotion, mist , It can be applied as a pack, gel or skin adhesive type formulation. Therefore, in order to be used as the external preparation, components commonly used in external preparations such as cosmetics or pharmaceuticals, such as aqueous components, oily components, powder components, alcohols, moisturizers, thickeners, ultraviolet absorbers, whitening agents, preservatives, antioxidants, surfactants, and fragrances , Colorants, various skin nutrients, etc. may be appropriately incorporated into the composition as needed. The external preparations include metal sequestering agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, and gluconic acid, caffeine, tannin, bellapamil, licorice extract, glabridin, and calin fruit hot water extract, various herbal medicines, tocopherol acetate, glycylitnic acid, tranexamic acid and its derivatives or salts, vitamin C, magnesium ascorbate, ascorbic acid glucoside, arbutin, kojic acid, glucose, fructose, trehalose Sugars such as can also be blended appropriately.

Another aspect provides a cosmetic composition for preventing or improving hair loss, comprising an extract of capricorn chinensis as an active ingredient.

The cosmetic composition may include the black capsular capricorn extract at a concentration of 1 to 100 μg/mL based on the total weight of the composition. For example, the oxen capsular extract is 10 to 90 μg/mL, 15 to 85 μg/mL, 20 to 85 μg/mL, 20 to 80 μg/mL, 25 to 80 μg/mL, 30 to 80 μg/mL mL, or at a concentration of 35 to 80 μg/mL. The cosmetic composition may include, without limitation, ingredients commonly accepted in addition to the active ingredients, and may include, for example, antioxidants, stabilizers, solubilizers, vitamins, pigments, and conventional adjuvants such as fragrances, and carriers. Components such as surfactants, antioxidants, preservatives, pH regulators, humectants, and lubricants may be further added as needed. In addition, the cosmetic composition further includes a substance capable of supplementally providing essential nutrients to the skin, for example, it may contain auxiliary agents such as natural fragrance, cosmetic fragrance, or plant extract. The cosmetic composition may be used as a cosmetic or quasi-drug formulation. The formulation of the composition may be any form of formulation capable of blending the black capsicum extract as an active ingredient. Preferably, the above cosmetic or quasi-drug formulations include hair tonic, hair cream, hair lotion, hair shampoo, hair rinse, hair conditioner, hair spray, hair aerosol, pomade, powder, gel, hair pack, hair treatment, eyebrow hair growth agent, and eyelashes. It can be manufactured in various forms such as solutions, brush gels, emulsions, oils, waxes, aerosols, etc., such as hair growth agents, eyelash nutrients, or shampoos for pets and rinses for pets, and manufacturing or processing of devices for scalp or hair such as wigs or hats It may be used for, but is not limited thereto. The cosmetic composition may contain various ingredients formulated in conventional cosmetics according to various formulations or to suit the final purpose. For example, in the case of having a shampoo formulation, it may contain any one or more of synthetic surfactants and preservatives, thickeners, viscosity modifiers, pH modifiers, fragrances, dyes, hair conditioning agents, and water as cleaning ingredients. Among the synthetic surfactants, synthetic anionic surfactants are alkyl and alkyl ether sulfates, and representative examples include sodium lauryl sulfate, ammonium lauryl sulfate, triethanolamine lauryl sulfate, polyoxyethylene sodium lauryl sulfate, and polyoxyethylene ammonium lauryl sulfate. there is In addition, among the synthetic surfactants, synthetic amphoteric surfactants are alkyl betamine and alkyl amidopropyl betaine, representative examples of which are cocodimethyl carboxymethyl betaine, lauryldimethyl carboxymethyl betaine, lauryl dimethyl alpha-carboxyethyl betaine , cetyl dimethyl carboxymethyl betaine, and cocamido propyl betaine. The nonionic surfactants include alkanol amides and amine oxides, such as lauryl diethyl amine oxide, coconut oil alkyldimethyl amine oxide, lauric acid diethanolamide, coconut oil fatty acid diethanolamide, and coconut oil fatty acid monoethanolamide. In addition, the cosmetic composition may be used for pets in different formulations. It can be prepared in the form of "shampoo" containing the composition, and can be prepared by adding a neutral detergent that is less irritating to the pet's skin and has excellent moisturizing power.

According to one embodiment, a composition containing an extract of thorax chinensis, rolliolide, or a combination thereof as an active ingredient can effectively prevent, improve, or treat hair loss.

1 is a result of confirming the effect of 5 types of capsular extracts extracted by different extraction methods on the β-catenin expression level of HaCaT cells irradiated with UVB.
Figure 2 is the result of confirming the effect of rolliolide extracted from thoracic capitis on the amount of β-catenin expression in the cytoplasm of HaCaT cells irradiated with UVB.

Hereinafter, one or more specific examples will be described in more detail through examples. However, these examples are intended to illustrate one or more specific examples, and the scope of the present invention is not limited to these examples.

Example 1: Material preparation

Sargassum horneri, Sargassum fulvellum, Sargassum tortile, Sargassum sagamianum, and Sargassum confusum used in this experiment were washed three times with water and washed with salt and sand. has been removed. And after freezing at -70 ℃ for 2 hours, it was lyophilized for 3 days. Each dried hat half was stored in a refrigerator until use. DMEM used in the experiment was a product of Hyclone, and fetal bovine serum (FBS), penicillin, and NE-PER nuclear and cytoplasmic extraction kit were a product of Thermo Fisher Scientific. For all other analytical reagents, special grade or HPLC grade reagents were used.

Example 2: Extract preparation

2-1. Room temperature water extract preparation

Five types of capsular powder were extracted with distilled water at a ratio of 1:50 at 37 ° C for 24 hours, centrifuged (4000 rpm, 20 min), filtered with filter paper (Whatman No. 6), lyophilized, and used for the test.

2-2. Preparation of hot water extract

The five capsular powders were extracted with distilled water at a ratio of 1:50 at 100 ° C for 4 hours, centrifuged (4000 rpm, 20 min), filtered with filter paper (Whatman No. 6), lyophilized, and used for the test.

2-3. Ethanol extract preparation

Five capsular powders were extracted with 70% ethanol at a ratio of 1:50 at 70 °C for 24 hours, centrifuged (4000 rpm, 20 min), and filtered with filter paper (Whatman No.6). The prepared 70% ethanol extract was concentrated under reduced pressure and lyophilized and used in the experiment.

Example 3: Separation of useful components

Loliolide, a useful ingredient, was isolated and purified from the ethanol extract of the black cocker spaniel and used in the experiment. The structural formula of rolliolide is shown in Formula 1 below.

[Formula 1]

Example 4: Effect of Mojaban extract on skin keratinocytes irradiated with UVB

4-1. HaCaT cell preparation

HaCaT cells used in the experiment were prepared by adding 10% heat-inactivated FBS and penicillin (100 unit/ml) to DMEM, and maintained at 37° C. and 5% CO ₂ using an incubator.

4-2. western blot

HaCaT cells were dispensed and attached to a 6cm culture dish, and then treated with the extract of Example 2 (room temperature, hot water, or ethanol extraction of 5 types of capsular caps) and rolliolide obtained from capsular caps, respectively, and cultured for 1 hour did

Cultured HaCaT cells were irradiated with UVB (40 mJ/cm ² ). After culturing for 24 hours after UVB irradiation, the supernatant was removed, and cytoplasmic and nuclear proteins were obtained from the cells using NE-PER® Nuclear and Cytoplasmic Extraction Kit (Thermo).

After mixing the obtained protein concentration (40 μg/ml) and a sample buffer, protein denaturation was induced by boiling at 100° C. for 3 minutes. After separating the proteins by 10% SDS-PAGE, the proteins were transferred to a PVDF membrane. Non-specifically bound proteins were blocked by reacting with 0.1% Tween 20 and Tris-buffered saline (TBS) containing a blocking buffer for 2 hours.

Thereafter, the solution to which the primary antibody (1:1000) for β-catenin was added was mixed for 12 hours, and then washed three times for 10 minutes with TBST. Then, the membrane was reacted with a solution to which secondary antibodies goat anti-rabbit and goat anti-mouse were added at room temperature for 1 hour and 30 minutes, and then washed three times with TBST for 10 minutes. The expression of the target protein was measured through luminescence by an enzymatic reaction using electrochemiluminescence (ECL).

4-3. Therapeutic effect of hair loss treatment of hoesaeng capban extract

The effect of various capsular extracts prepared in Example 2 on the expression of hair loss-related protein (β-catenin) in UVB-irradiated HaCaT cells was evaluated.

According to FIG. 1, it was confirmed that the experimental group treated with the A. moth extract (room temperature water, hot water, and ethanol) had a higher level of expression of β-catenin protein than the experimental groups treated with other extracts. In particular, the increase in β-catenin expression was the highest in the experimental group treated with the ethanol extract of A. Therefore, it is considered that the hair loss improvement effect of the hoesaeng capricorn extract is excellent.

4-4. Hair loss treatment effect of rolliolide

Western blotting was performed to confirm the effect of roliolide, a useful component derived from thoracic capitis, on β-catenine protein activity.

According to Figure 2, HaCaT cells irradiated with UVB decreased the amount of β-catenin expression in the cytoplasm, but treated with loliolide increased the expression of β-catenine in the cytoplasm in a concentration-dependent manner.

In summary, it is expected that rolliolide derived from thorax can increase or restore the cytoplasmic expression of β-catenin, which is suppressed by UV light, and thereby have a hair loss treatment effect.

Claims (5)

A pharmaceutical composition for the prevention or treatment of hair loss comprising an extract of black capped capillaries as an active ingredient. Regarding paragraph 1,
The hoesaeng hatban extract is extracted with ethanol as a solvent,
pharmaceutical composition. Regarding paragraph 1,
The hoesaeng hatban extract is extracted by heating,
pharmaceutical composition. A cosmetic composition for preventing or improving hair loss, comprising an extract of black capped capillaries as an active ingredient. A food composition for preventing or improving hair loss, comprising an extract of thorax chinensis as an active ingredient.

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