KR102228039B1 - Cosmetic or pharmaceutical composition for skin whitening comprising Astragaloside I or a pharmaceutically acceptable salt thereof - Google Patents

Abstract

The present invention provides a composition for skin whitening, particularly a cosmetic composition, a pharmaceutical composition, and a health food comprising a compound represented by the following Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient. The cosmetic or pharmaceutical composition of the present invention has few side effects, so it is safe for the human body and has an excellent skin whitening effect.
[Formula 1]

Description

A cosmetic or pharmaceutical composition for skin whitening comprising Astragaloside I or a pharmaceutically acceptable salt thereof

The present invention relates to a cosmetic composition, a pharmaceutical composition, and a health food having an excellent effect on whitening, in particular, having an excellent effect related to the skin. The present invention also relates to a cosmetic composition, a pharmaceutical composition and a health food that can exert the above effect even in a small amount.

It is a common desire to have white and fair skin. The color or brightness of the skin is genetically determined according to the concentration and distribution of melanin in human skin, but is also affected by environmental or physiological conditions such as solar ultraviolet rays, fatigue or stress. Melanin is produced through a non-enzymatic oxidation reaction after being sequentially changed into dopa and dopaquinone by an enzyme called tyrosinase acting as a catalyst in tyrosine, a kind of amino acid. As such, the pathway by which melanin is produced is known, but the cause of the triggering of tyrosinase in the mechanism that induces melanin synthesis is still not elucidated in detail.

Meanwhile, as a commonly known whitening component, substances that inhibit tyrosinase enzyme activity such as Kojic acid or arbutin, hydroquinone, vitamin C (L-Ascorbic acid), or derivatives thereof, and various There are plant extracts. By inhibiting the synthesis of melanin pigments, they can not only realize skin whitening by brightening skin tone, but also improve skin hyperpigmentation such as spots and freckles caused by ultraviolet rays, hormones or genetics. However, when applied to the skin, there is a problem in that the amount of use is limited due to safety problems such as irritation and redness, or the effect is insignificant, so that a practical effect cannot be expected.

Therefore, there is an urgent need for the development of a component that is safe for the living body, has a stable active ingredient, and, above all, has a skin whitening effect that is superior to an existing material that is effective for skin whitening.

Accordingly, the present invention solves the above problems and provides a new active ingredient, that is, a useful use of the active ingredient, which has few side effects and is safe for the human body and has excellent skin whitening effect.

In other words, the problem to be solved by the present invention is to provide a composition comprising an active ingredient having excellent efficacy as an active ingredient.

In order to solve the above problems, the present invention provides a composition for skin whitening, preferably a cosmetic composition, a pharmaceutical composition, or a health food comprising Astragaloside I or a pharmaceutically acceptable salt thereof as an active ingredient. to provide.

That is, the present invention provides a new use of astragalloside I or a pharmaceutically acceptable salt thereof for skin whitening.

The inventors of the present invention confirmed that astragalloside I exhibits a whitening effect by inhibiting melanin synthesis, and completed the present invention.

In the present invention, the "whitening effect" refers to not only brightening skin tone by inhibiting the synthesis of melanin pigment, but also improving skin hyperpigmentation such as spots and freckles caused by ultraviolet rays, hormones, or genetics.

The present invention provides a composition comprising a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof in order to solve the above problems and achieve the object of the present invention.

[Formula 1]

The compound represented by Chemical Formula 1 has a molecular formula of C ₄₃ H ₆₈ O ₁₆ and a molecular weight of 840.99, and includes Astragaloside I, ASTRAGALOSIDE I (SH); It is named Cyclosiversioside B, etc.

The present invention is not particularly limited to the method of obtaining the astragalloside I, and chemically synthesized by a method known in the art, or a commercially available material may be used.

In the cosmetic composition, pharmaceutical composition and health food according to the present invention, the content of the astragalloside I is preferably 0.00001 to 10% by weight based on the total weight of the cosmetic composition, pharmaceutical composition and health food.

The "pharmaceutically acceptable salt" of the present invention preferably includes a base addition salt, and the base addition salt includes a salt consisting of sodium, potassium, calcium, ammonium, magnesium or organic amino, but is limited thereto. no.

Astragalloside I of the present invention may exist in unsolvated as well as solvated forms, including forms such as hydrates, ethanolates, and the like. Astragalloside I of the present invention may exist in crystalline or amorphous form, and all such physical forms are included within the scope of the present invention.

The cosmetic composition for skin whitening according to the present invention is a solution, external ointment, cream, foam, nutrient lotion, softening lotion, pack, softening water, emulsion, makeup base, essence, soap, liquid cleanser, bathing agent, sunscreen cream, sun oil , Suspension, emulsion, paste, gel, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation, patch and spray can be prepared in a formulation selected from the group consisting of, It is not limited thereto.

In addition, the cosmetic composition of the present invention may additionally include one or more cosmetically acceptable carriers blended in general skin cosmetics, and as common ingredients, for example, oil, water, surfactants, moisturizers, lower alcohols, A thickener, a chelating agent, a colorant, a preservative, a fragrance, and the like may be appropriately blended, but the present invention is not limited thereto.

The cosmetically acceptable carrier included in the cosmetic composition of the present invention varies depending on the formulation. When the formulation of the present invention is an ointment, paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide or Mixtures of these can be used.

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder, or mixtures thereof may be used as a carrier component. In particular, in the case of a spray, additional chloro Propellants such as fluorohydrocarbon, propane/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, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl benzoate, propylene glycol, 1,3 -Butylglycol oil, in particular cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil and sesame oil, glycerol aliphatic ester, polyethylene glycol or fatty acid ester of sorbitan.

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 and polyoxyethylene sorbitan ester, micro Crystalline cellulose, aluminum metahydroxide, bentonite, agar or tracant, and the like may be used.

When the formulation of the present invention is a soap, an alkali metal salt of a fatty acid, a fatty acid hemiester salt, a fatty acid protein hydrolyzate, isethionate, a lanolin derivative, an aliphatic alcohol, vegetable oil, glycerol, sugar, etc. may be used as a carrier component. I can.

The present invention also provides a skin whitening method comprising the step of applying the compound represented by Formula 1 to the skin of an individual. The subject includes, without limitation, mammals including mice, livestock, humans, and the like.

According to another embodiment of the present invention, the present invention provides a pharmaceutical composition for skin whitening containing the compound of Formula 1 as an active ingredient.

The composition containing the compound of the present invention may be in various oral or parenteral formulations, but preferably may be a parenteral formulation. In the case of formulation, it is prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants that are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and these solid preparations include at least one excipient in one or more compounds, such as starch, calcium carbonate, sucrose, or lactose ( lactose), gelatin, etc. In addition, in addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, syrups, etc., but may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to water and liquid paraffin, which are commonly used simple diluents. have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, and emulsions. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used.

The present invention can also be provided as a formulation of a skin external preparation for skin whitening effect comprising the compound of Formula 1 as an active ingredient.

When the compound of Formula 1 is used for external skin, additionally fatty substances, organic solvents, solubilizers, thickening and gelling agents, emollients, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants , Water, ionic or nonionic emulsifiers, fillers, sequestering and chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic activators, lipid vesicles or external preparations for skin It may contain adjuvants commonly used in the field of dermatology, such as any other ingredients used as. In addition, the above ingredients may be introduced in an amount generally used in the field of dermatology.

When the compound of Formula 1 is provided in a formulation for external application for skin, it is not limited thereto, but may have a formulation such as an ointment, patch, gel, cream, or spray.

The pharmaceutical composition of the present invention may be particularly preferably used as a parenteral preparation. For example, the external preparation for skin may include a suitable pharmaceutically acceptable base such as petrolatum and stearyl alcohol; Suitable pharmaceutically acceptable surfactants such as polysorbate and sorbitan sesquioleate; Suitable pharmaceutically acceptable moisturizers such as glycerin; Suitable pharmaceutically acceptable solvents; And a flavoring agent, a colorant, a stabilizer, a viscous agent, and the like are homogeneously mixed.

In addition, when the compound of Formula 1 of the present invention is used as a pharmaceutical, it may further contain one or more active ingredients exhibiting the same or similar function. For example, it may contain known skin whitening ingredients. When the additional skin whitening component is included, the skin whitening effect of the composition of the present invention may be further enhanced. When the above ingredients are added, skin safety, ease of formulation, and stability of active ingredients can be considered in combination with use. In one embodiment of the present invention, the composition is a whitening component known in the art, a substance that inhibits tyrosinase enzyme activity such as Kojic acid and arbutin, hydroquinone, vitamin-C (L-Ascorbic acid); And it may further include one or two or more components selected from the group consisting of derivatives thereof and various plant extracts. Additional ingredients may be included in an amount of 0.0001% to 10% by weight based on the total weight of the composition, and the content range may be adjusted according to requirements such as skin safety and ease of formulation of the compound of Formula 1 .

When the pharmaceutical composition of the present invention contains an effective amount of the compound of Formula 1, it can provide a desirable skin whitening effect. In the present invention, the term "effective amount" means an amount of a compound capable of exhibiting a skin whitening effect.

The effective amount of the compound of Formula 1 included in the composition of the present invention will vary depending on the form in which the composition is commercialized, the method in which the compound is applied to the skin, and the time it stays on the skin. For example, when the composition is commercialized as a pharmaceutical product, it may contain the compound of Formula 1 at a higher concentration than when it is commercialized as a cosmetic product that is routinely applied to the skin. Therefore, the daily dosage is 0.1 to 100 mg/kg, preferably 30 to 80 mg/kg, more preferably 50 to 60 mg/kg, based on the amount of the compound of Formula 1, and 1 to It can be administered 6 times.

Another embodiment of the present invention provides a health food for skin whitening effect comprising the compound of Formula 1 above.

In the present specification, the term'health food' refers to a food prepared by adding the compound of Formula 1 to food materials such as beverages, teas, spices, gums, confectionery, or encapsulating, powdering, and suspending. It means that it brings a specific effect, but unlike general drugs, it has the advantage of not having side effects that may occur when taking drugs for a long time by using food as a raw material. Since the health food of the present invention obtained in this way can be consumed on a daily basis, a high skin whitening effect can be expected, and it is very useful.

When the compound of Formula 1 is used as a food additive, the compound of Formula 1 may be added as it is or may be used with other foods or food ingredients, and may be appropriately used according to a conventional method. The mixing amount of the active ingredient may be appropriately determined according to the purpose of use (prevention, health or therapeutic treatment). In general, when preparing food or beverage, the composition of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less based on the raw material. However, in the case of long-term intake for the purpose of health and hygiene or for the purpose of health control, the amount may be less than the above range, and there is no problem in terms of safety, so the active ingredient may be used in an amount above the above range. . There is no particular limitation on the type of the food. Examples of foods to which the above substances can be added include meat, sausage, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, There are alcoholic beverages and vitamin complexes, and all health foods in the usual sense are included. The health beverage composition of the present invention may contain various flavoring agents or natural carbohydrates as an additional component, like a conventional beverage. The natural carbohydrates described above are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As the sweetener, natural sweeteners such as taumatin and stevia extract, and synthetic sweeteners such as saccharin and aspartame can 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 health food of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols. , Carbonated beverages, and the like. In addition, the health food of the present invention may contain pulp for the manufacture of natural fruit juice, fruit juice beverage, and vegetable beverage. These ingredients may be used independently or in combination. Although the proportion of these additives is not very important, it is generally selected from 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

Although not limited thereto, in one embodiment of the present invention, the composition may include the compound of Formula 1 in an amount of 0.00001% to 10% by weight based on the total weight of the composition.

A composition containing astragalloside I or a pharmaceutically acceptable salt thereof of the present invention exhibits a skin whitening effect.

The composition containing astragalloside I or a pharmaceutically acceptable salt thereof of the present invention can be used as a safe and excellent cosmetic raw material and pharmaceutical ingredient.

Hereinafter, in order to describe the present invention in more detail, it will be described with reference to the following examples. However, the embodiments according to the present invention may be modified in various forms, and the scope of the present invention should not be construed as being limited to the embodiments described below. Embodiments of the present invention are provided by way of example to aid in a specific understanding of the present invention.

Reference example One: Astragalloside I( Astragaloside I) substance information

[Formula 1]

Name of substance: Astragaloside I

CAS No. : 84680-75-1

Molecular Formula: C ₄₃ H ₆₈ O ₁₆

Molecular Weight: 840.99

Where to buy: Tauto Biotech (China)

Example 1: whitening effect-reducing the total amount of melanin

The whitening effect was confirmed by measuring the total amount of melanin at the cell level by adding the compound of Formula 1 to the culture medium of mouse melanoma cells (B-16 mouse melanoma cells) (Lotan R., Lotan D. Cancer) Res . 40:3345-3350, 1980). Before the experiment, toxicity was evaluated for the melanoma cells of mice, and a non-toxic concentration was selected to perform whitening evaluation.

The final concentration of the compound of Formula 1 was 1 ppm and 10 ppm in the culture solution, and arbutin, a control, was added to the medium to be 100 ppm, and each treated with B-16 melanoma cells was cultured for 3 days.

Thereafter, the cells were treated with trypsin, removed from the culture vessel, centrifuged, and melanin was extracted. The detached cells were boiled for 10 minutes by adding 1 ml of sodium hydroxide solution (1N concentration) to dissolve melanin, and the absorbance was measured at 400 nm using a spectrophotometer to measure the amount of melanin produced.

The amount of melanin was measured by a method expressed by absorbance per unit cell count (1×10 ⁶ cells), and the total amount of melanin relative to the control was calculated as an inhibition rate (%), and the results are summarized in Table 1.

The effect of reducing the total amount of melanin at the cellular level according to the concentration

sample Melanin production
(abs) Inhibition rate (%) Control (DMSO, 10ppm) 0.33 - Positive control (Arbutin, 100ppm) 0.228 31.06 Compound of Formula 1 (10ppm) 0.213 35.35 Compound of Formula 1 (1ppm) 0.279 15.46

As can be seen from the results of Table 2, when compared to arbutin, which is known as a whitening material, the compound of Formula 1 exhibits superior melanin production inhibition even when a lower concentration is applied to the cultured mouse melanoma cells. , It was confirmed that the total amount of melanin was less.

Therefore, it was found that the compound of Formula 1 can be used for whitening purposes.

Claims (5)

A cosmetic composition for skin whitening comprising a compound represented by the following Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
[Formula 1]

delete The cosmetic composition according to claim 1, wherein the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof is contained in an amount of 0.00001 to 10% by weight based on the total weight of the cosmetic composition. A health food composition for skin whitening comprising a compound represented by the following Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
[Formula 1]

A pharmaceutical composition for improving skin hyperpigmentation, comprising a compound represented by the following Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
[Formula 1]