KR102229943B1 - Composition for Skin-lightening and Improving Wrinkle Using an Extract of Maerua edulis - Google Patents

Abstract

The present invention relates to a composition for skin whitening using an extract of Maerua edulis having tyrosinase inhibitory activity.

Description

Composition for Skin-lightening and Improving Wrinkle Using an Extract of Maerua edulis}

The present invention relates to a composition for skin whitening using the Maerua edulis extract.

With the development of medical technology and the improvement of living standards, people's desire for beauty is strong, and the perception that appearance itself is a social competitiveness is increasing, so preference for skin whitening and skin wrinkle improvement is increasing, and the cosmetic market is expanding (J. .Korean Soc.Food Sci.Nutr., 42(3):355 (2013)).

The skin accounts for about 16% of the human body, and since it is in direct contact with the external environment, it plays an important role in protecting the human body from external harmful factors such as temperature, humidity, and ultraviolet rays. The skin consists of the epidermis, the dermis, and the subcutaneous tissue under the keratin. The epidermis is a thin protective layer composed of keratinocytes, mainly composed of keratin, immune cells such as melanocytes, langerhans cells, etc., and Merkel's copuscles that produce and secrete melanin. It prevents external irritation and invasion of pathogens, regulates body temperature, and maintains moisture and lipid components.

Melanin is a phenolic polymer natural pigment that is widely present in living organisms. In the human body, it is synthesized from melanosomes in melanocytes in the basement layer of the epidermis and is transferred to surrounding keratinocytes to represent the color of human skin. Abnormally low levels of melanin cause skin lesions such as vitiligo. Conversely, when excessively produced, acquired hyperpigmentation such as melanoderma, postinflammatory melanoderma, solar lentigo, etc. It can cause a variety of skin diseases, including.

The synthesis of melanin is made by making melanosomes from melanocytes in the base layer of the skin, and a series of processes by which melanin is synthesized is collectively referred to as melanogenesis. Melanin production is based on tyrosine, one of the amino acids, and DOPA (3,4-) by tyrosinase, tyrosinase related protein-1 (TRP-1), and tyrosinase related protein-2 (TRP-2). dihydroxyphenylalanine) to dopa quinone, followed by a non-enzymatic reaction, spontaneous oxidation, and then a polymerization reaction with amino acids or proteins to synthesize melanin (Korean J. FOOD SCI. TECHNOL., 2000. 32(3):736; Journal of Life Science, 2013. 23(12):1445; Pigment Cell Res. 1999. 12(1):4-12.). Recently, studies on inhibition of melanin synthesis have been conducted using proteins such as tyrosinase, TRP-1, and TRP-2 as well as microphtalmia associated transcription factor (MITF). The main intracellular signaling pathway is the cAMP/PKA (cyclic monophosphate/protein kinase A) pathway, where cAMP promotes the expression of MITF via PKA and CREB1 (cAMP responsive element binding protein 1), and MITF is important in the melanin synthesis process. It promotes transcription of tyrosinase, TRP-1, and TRP-2 as transcriptional regulators (Pharmazie. 2015 Oct;70(10):646-9.; Int J Mol Sci. 2015 Oct 13;16(10):24219- 42; Curr Pharm Biotechnol. 2015;16(12):1111-9.).

Since tyrosinase plays the most important role as the first step to produce melanin, research on whitening agents is mainly a tyrosinase activity inhibitor or an antagonist against the substrate of tyrosinase to regulate tyrosinase activity. Research has been conducted in the direction of developing (Kor. J. Pharmacogn., 44(3):220, 2013).

The present invention discloses the tyrosinase inhibitory activity of the extract of Maerua edulis.

An object of the present invention is to provide a composition for skin whitening using a Maerua edulis extract.

Other or specific objects of the present invention will be presented below.

The present invention was completed by confirming that the Maerua edulis extract has tyrosinase inhibitory activity, as confirmed in the following Examples and Experimental Examples.

In consideration of the above, the present invention can be understood as a composition for skin whitening comprising an extract of Maerua edulis.

Maerua edulis is a shrub widely distributed in South Africa and is a plant known to have antibacterial and insecticidal activity (Afrigriland 56:76-77, 2012; Ind. Crops Prod. 110:88-93, 2017; Ind. Crops) Prod. 110:36-44, 2017).

In the present specification, "Maerua edulis extract" refers to Maerua edulis leaves, stems, above-ground parts, rhizomes, roots, underground parts, or mixtures thereof, which are to be extracted into water, lower alcohols having 1 to 4 carbon atoms (methanol, ethanol, butanol, etc.) ), methylene chloride, ethylene, acetone, hexane, ether, chloroform, ethyl acetate, butyl acetate, N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), 1,3-butylene glycol, propylene glycol or It refers to an extract obtained by leaching using a mixed solvent thereof, an extract obtained by using a supercritical extraction solvent such as carbon dioxide, pentane, or a fraction obtained by fractionating the extract, and the extraction method includes the polarity of the active substance, the degree of extraction, and the degree of preservation. Considering this, arbitrary methods such as cold settling, reflux, warming, ultrasonic radiation, and supercritical extraction can be applied. In the case of a fractionated extract, a fraction obtained by suspending the extract in a specific solvent and mixing and policing with a solvent of a different polarity, the crude extract is adsorbed on a column filled with silica gel, etc., and then a hydrophobic solvent, a hydrophilic solvent, or a mixed solvent thereof It means including the fraction obtained as a mobile phase. In addition, the meaning of the extract includes a concentrated liquid extract or a solid extract from which the extraction solvent has been removed by a method such as freeze drying, vacuum drying, hot air drying, spray drying, or the like. Preferably, it means an extract obtained by using water, an alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof as an extraction solvent, more preferably an extract obtained by using a mixed solvent of water and an alcohol having 1 to 4 carbon atoms as an extraction solvent. do.

In addition, in the present specification, the term "active ingredient" refers to an ingredient that can exhibit a desired activity alone or exhibit activity with a carrier that is not itself active.

The composition of the present invention may contain the active ingredient in an arbitrary amount (effective amount) as long as it can exhibit a skin whitening effect, etc., depending on the use, formulation, and blending purpose, and the usual effective amount is based on the total weight of the composition. It will be determined within the range of 0.001% to 15% by weight. Here, "effective amount" refers to intended medical/cosmetic effects, such as skin whitening effect, when the composition of the present invention is administered to a mammal, preferably a human, to which the composition of the present invention is administered during the administration period as suggested by a medical expert, etc. Yes, it refers to the amount of the active ingredient contained in the composition of the present invention. Such effective amounts can be determined empirically within the range of ordinary skill in the art.

In a specific aspect, the composition of this invention can be grasped as a food composition.

The food composition of the present invention may be prepared in any form, such as beverages such as tea, juice, carbonated drinks, ion drinks, processed oils such as milk, yogurt, gums, rice cakes, Korean sweets, bread, snacks, noodles, etc. Foods, tablets, capsules, pills, granules, liquids, powders, flakes, pastes, syrup, gels, jelly, can be prepared in health functional food preparations such as bars.

In addition, the food composition of the present invention can be classified as a product as long as it conforms to the enforcement regulations at the time of manufacture and distribution in terms of legal and functional classification. For example, it is a health functional food according to the Korean 「Health Functional Food Act」, or confectionery, bean, tea, and beverages according to each food type according to the food code of the Korean 「Food Sanitation Act」 (``Food Standards and Standards'' notified by the Ministry of Food and Drug Safety). , Special use food, etc.

The food composition of the present invention may contain food additives in addition to the active ingredients. Food additives can generally be understood as substances that are added to food and mixed or infiltrated in manufacturing, processing, or preserving food. Since they are consumed daily and for a long time with food, their safety must be ensured. Food additives with guaranteed safety are limited in terms of ingredients or functions in the Food Additives Code according to the laws of each country governing the manufacture and distribution of food (the “Food Sanitation Act” in Korea). In the Korean Food Additives Code (“Food Additive Standards and Standards” notified by the Ministry of Food and Drug Safety), food additives are classified into chemical synthetic products, natural additives, and mixed preparations in terms of ingredients.These food additives are sweeteners and flavors in terms of function. It is categorized into agents, preservatives, emulsifiers, acidulants, and thickeners.

Sweeteners are used to impart an appropriate sweet taste to foods, and both natural and synthetic can be used in the composition of the present invention. Preferably, a natural sweetener is used, and examples of the natural sweetener include sugar sweeteners such as corn syrup solids, honey, sucrose, fructose, lactose, and maltose.

Flavoring agents can be used to enhance taste or aroma, and both natural and synthetic can be used. Preferably, it is the case of using a natural one. In the case of using natural ones, the purpose of nutrient enhancement can be combined in addition to flavor. As a natural flavoring agent, it may be obtained from apples, lemons, tangerines, grapes, strawberries, peaches, or the like, or from green tea leaves, roundtails, bamboo leaves, cinnamon, chrysanthemum leaves, jasmine, and the like. In addition, you can use those obtained from ginseng (red ginseng), bamboo shoots, aloe vera, and ginkgo. The natural flavoring agent may be a liquid concentrate or a solid extract. In some cases, synthetic flavoring agents may be used, and synthetic flavoring agents may include esters, alcohols, aldehydes, terpenes, and the like.

As a preservative, sodium calcium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate, EDTA (ethylenediaminetetraacetic acid), etc. can be used, and as an emulsifier, acacia gum, carboxymethylcellulose, xanthan gum, Pectin, etc. may be mentioned, and as the acidulant, arithmetic, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, phosphoric acid, and the like can be used. In addition to the purpose of enhancing taste, the acidulant may be added so that the food composition has an appropriate acidity for the purpose of inhibiting the growth of microorganisms.

As the thickening agent, a suspending agent, a settling agent, a gel-forming agent, a swelling agent, and the like may be used.

In addition to the food additives described above, the food composition of the present invention may include a physiologically active substance or minerals known in the art for the purpose of supplementing and reinforcing functionality and nutritional properties and ensuring stability as a food additive.

Examples of such physiologically active substances include catechins contained in green tea, vitamins such as vitamin B1, vitamin C, vitamin E, and vitamin B12, tocopherol, dibenzoyl thiamine, etc., and minerals include calcium preparations such as calcium citrate, magnesium stearate. Magnesium preparations such as, iron preparations such as iron citrate, chromium chloride, potassium iodide, selenium, germanium, vanadium, and zinc.

In the food composition of the present invention, the food additive described above may be included in an appropriate amount to achieve the purpose of addition according to the product type.

Regarding other food additives that may be included in the food composition of the present invention, reference may be made to the food code of each country or the food additive code.

The composition of the present invention may be understood as a pharmaceutical composition in other specific embodiments. When the composition for skin whitening of the present invention is understood as a pharmaceutical composition, its use may be understood as a composition for improving skin hyperpigmentation.

The pharmaceutical composition of the present invention may be prepared in an oral dosage form or a parenteral dosage form according to an administration route by a conventional method known in the art, including a pharmaceutically acceptable carrier in addition to the active ingredient. Here, the route of administration may be any suitable route including a local route, an oral route, an intravenous route, an intramuscular route, and direct absorption through mucosal tissue, and two or more routes may be used in combination. An example of a combination of two or more routes is a case in which two or more formulations of drugs are combined according to the route of administration, for example, when one drug is first administered by an intravenous route and the second drug is administered by a local route.

Pharmaceutically acceptable carriers are well known in the art depending on the route of administration or formulation, and specifically, reference may be made to the pharmacopoeia of each country, including the “Korean Pharmacopoeia”.

When the pharmaceutical composition of the present invention is prepared in an oral dosage form, powders, granules, tablets, pills, dragees, capsules, solutions, gels, syrups, suspensions, wafers according to a method known in the art together with a suitable carrier It can be prepared in a formulation such as. Examples of suitable carriers at this time include sugars such as lactose, glucose, sucrose, dextrose, sorbitol, mannitol, and xylitol, starches such as corn starch, potato starch, wheat starch, cellulose, methylcellulose, ethylcellulose, sodium carboxymethylcellulose, Celluloses such as hydroxypropylmethylcellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, magnesium stearate, mineral oil, malt, gelatin, talc, polyol, vegetable oil, ethanol, grease Serol, etc. are mentioned. In the case of formulation, appropriate binders, lubricants, disintegrants, colorants, and diluents may be included as needed. Suitable binders include starch, magnesium aluminum silicate, starch ferryst, gelatin, methylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, glucose, corn sweetener, sodium alginate, polyethylene glycol, wax, etc., and lubricants include oleic acid. Sodium, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, silica, talcum, stearic acid, magnesium salts and calcium salts thereof, polydecylene glycol, etc., and as disintegrating agents starch, methyl cellulose , Agar, bentonite, xanthan gum, starch, alginic acid, or a sodium salt thereof. Moreover, lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, glycine, etc. are mentioned as a diluent.

When the pharmaceutical composition of the present invention is prepared in a parenteral dosage form, it may be formulated in the form of an injection, a transdermal administration, a nasal inhalation and a suppository according to a method known in the art together with a suitable carrier. When formulated as an injection, an aqueous isotonic solution or suspension may be used as a suitable carrier, and specifically, triethanol amine-containing PBS (phosphate buffered saline), sterile water for injection, an isotonic solution such as 5% dextrose, etc. may be used. . When formulated as a transdermal administration, it can be formulated in the form of an ointment, cream, lotion, gel, external solution, pasta, liniment, air roll, and the like. In the case of nasal inhalants, suitable propellants such as dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, etc. can be used to form an aerosol spray.When formulated as a suppository, the carrier is Withepsol ( witepsol), tween 61, polyethylene glycols, cacao butter, laurin paper, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, sorbitan fatty acid esters, and the like.

The specific formulation of pharmaceutical compositions is known in the art, and for example, Remington's Pharmaceutical Sciences (19th ed., 1995) may be referred to. This document is considered as part of this specification.

The preferred dosage of the pharmaceutical composition of the present invention is in the range of 0.001 mg/kg to 10 g/kg per day, preferably 0.001 mg/kg to 1 g, depending on the patient's condition, weight, sex, age, patient severity, and route of administration. May be in the /kg range. Administration can be made once a day or divided into several times. Such dosage should not be construed as limiting the scope of the invention in any aspect.

The composition of the present invention can be understood as a cosmetic composition in another specific aspect. In particular, when the anti-inflammatory composition of the present invention is identified as a cosmetic composition, its use may be understood as a use for suppressing inflammatory skin troubles and alleviating inflammatory skin irritation.

Even if the composition of the present invention is identified as a cosmetic composition, the cosmetic composition can be classified as a product for its use and legally, and specifically, functional cosmetics with uses such as improving skin troubles and improving atopic dermatitis, non-functional It may be a general cosmetic or the like. The product form can also take any product form, specifically solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing, oils, powder foundations, emulsion foundations, waxes. It can take the form of a product such as a foundation or spray. In a specific product form, it may be a flexible lotion, a nutritional lotion, a nutritional cream, a massage cream, an essence, an eye cream, a cleansing cream, a cleansing foam, a cleansing water, a pack, a spray, or a powder formulation.

In addition to the active ingredient, the cosmetic composition of the present invention may include components commonly used in the cosmetic composition, such as stabilizers, solubilizers, surfactants, vitamins, conventional adjuvants such as pigments and perfumes, and carriers.

When the formulation of the present invention is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, or zinc oxide may be used as carrier components. I can.

When the formulation of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder may be used as a carrier component. In particular, in the case of a spray, additionally chlorofluorohydrocarbon, propane / May contain propellants such as butane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, a solubilizing agent or an emulsifying agent is used as a carrier component, specifically water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol, fatty acid ester of sorbitan, and the like may be used.

When the formulation of the present invention is a suspension, as a carrier component, a liquid diluent such as water, ethanol or propylene glycol, an ethoxylated isostearyl alcohol, a suspending agent such as polyoxyethylene sorbitol ester, polyoxyethylene sorbitan ester, and crystallites Castle cellulose, aluminum metahydroxide, bentonite, agar, and the like can be used.

When the formulation of the present invention is a surfactant containing cleansing, as a carrier component, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters may be used.

The cosmetic composition of the present invention can be prepared according to a method for preparing a cosmetic composition conventionally performed in the art, except for including the active ingredient that exhibits skin whitening activity and the like.

As described above, according to the present invention, it is possible to provide a composition for skin whitening using a Maerua edulis extract. The composition of the present invention can be commercialized as food, medicine or cosmetics.

1 is a result of tyrosinase inhibitory activity of Maerua edulis extract.

Hereinafter, the present invention will be described with reference to Examples and Experimental Examples. However, the scope of the present invention is not limited to these Examples and Experimental Examples.

<Example> Preparation of Maerua edulis extract

Maerua edulis leaf powder was added with 20 times the weight of 70% ethanol, leached for 24 hours, filtered through Whatman paper filter paper No.2, and the filtrate was concentrated under reduced pressure to prepare a Maerua edulis extract. .

<Experimental Example> Skin whitening activity-Tyrosinase inhibition activity test

A sample diluted by concentration in 0.1M potassium phosphate buffer (pH 6.5) and 1250 unit/ml mushroom tyrosinase were added, followed by 1.5 mM L-tyrosine as a substrate, mixed well, and reacted at 37°C for 20 minutes. Made it. The absorbance was measured at 490 nm using a microplate reader, and the tyrosinase inhibitory activity (%) was calculated by comparing with the sample untreated group. While the results are shown in Fig. 1, the IC ₅₀ , which is a 50% inhibitory concentration of tyrosinase, is shown in Table 1 below. The result is the result of repeated experiment 3 times for each concentration.

Tyrosinase inhibitory activity (IC ₅₀ , μg/ml) division Tyrosinase inhibition assay(㎍/ml)) Maerua edulis extract 28.65 Arbutin 179.42

As shown in Fig. 1 and the above table, the sample showed a concentration-dependent tyrosinase inhibitory activity, and the IC ₅₀ of the sample was 28.65 μg/ml. _{The IC 50} of arbutin, an existing skin whitening agent used as a positive control, was 179.42 μg/ml, respectively.

Claims (5)

A composition for skin whitening comprising an extract of Maerua edulis as an active ingredient.
The method of claim 1,
The composition, characterized in that the extract is water, an alcohol having 1 to 4 carbon atoms, or a mixed solvent extract thereof.
The method according to claim 1 or 2,
The composition is a composition, characterized in that the food composition.
The method according to claim 1 or 2,
The composition is a composition, characterized in that the cosmetic composition.
The method according to claim 1 or 2,
The composition is a pharmaceutical composition, characterized in that the composition.

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