KR101985886B1 - Composition comprising indole compound and panthenol for preventing and improving skin damage caused by UV radiation - Google Patents

Abstract

The present invention relates to a cosmetic composition or a pharmaceutical composition comprising (1) an indole compound or a pharmaceutically acceptable salt thereof and (2) a panthenol as an active ingredient, wherein (1) an indole compound or a pharmaceutically acceptable salt thereof and (2) a composition exhibiting an excellent effect in preventing and / or improving skin damage caused by ultraviolet rays due to the synergistic effect of panthenol.

Description

[0001] The present invention relates to a composition for preventing and improving skin damage caused by ultraviolet rays including indole compounds and panthenol,

The present invention relates to a cosmetic composition or a pharmaceutical composition for inhibiting skin damage caused by ultraviolet rays, and more particularly, to a cosmetic composition or cosmetic composition which can protect skin from ultraviolet rays to prevent skin damage due to ultraviolet rays, ≪ / RTI >

Humans in modern society are constantly exposed to ultraviolet rays, and the amount of ultraviolet rays exposed due to destruction of the ozone layer is increasing. Skin exposed to such ultraviolet rays will cause external and functional damage, aging, lipid peroxidation, and inflammatory reaction.

UVA (320 to 400 nm), UVB (280 to 320 nm), and UVB (280 to 320 nm) are the main influences on the skin because they are absorbed in air and do not reach the surface, ) to be. UVA causes pigmentation, phototoxicity, photoallergy, and penetrates into the dermal layer of the skin, causing skin aging. UVB promotes skin protein denaturation, cell keratinization, and causes sunburn, especially erythema and blistering.

When the skin is exposed to ultraviolet light, the reaction of the skin begins with the absorption of light energy by the ultraviolet absorbers present in the skin and undergoes a very complex multi-step reaction. Light absorbed into the skin transports energy to nucleic acids, amino acids, melanin, and various chromophores and interacts with free oxygen molecules in the body to produce harmful reactive oxygen species through various pathways. In addition, when keratinocytes and epidermal cells are irradiated with ultraviolet light, various inflammatory cytokines are secreted and the inflammation is induced in various cells by this stimulation, and the skin tissue is damaged.

Generally, as an antioxidant for inhibiting the generation of harmful reactive oxygen species, there are many ingredients used in cosmetics, but most of them have a disadvantage that they are not efficiently delivered to mitochondria and their efficacy is weak.

Accordingly, it is an object of the present invention to provide a cosmetic composition and / or cosmetic composition capable of preventing and / or improving skin damage caused by ultraviolet rays, that is, preventing and / or improving various skin diseases caused by ultraviolet rays To provide a pharmaceutical composition.

The present invention is to provide a cosmetic composition and / or a pharmaceutical composition which is excellent in antioxidative and anti-inflammatory effects and which not only inhibits skin damage due to ultraviolet rays but also exhibits excellent effects on skin improvement.

The present invention also provides a cosmetic composition and / or a pharmaceutical composition which is effective for maintaining the skin barrier function and has an excellent effect of improving the retention of moisture of the skin.

In order to solve the above problems, the present invention provides a cosmetic composition and / or a pharmaceutical composition comprising (1) an indole compound or a pharmaceutically acceptable salt thereof and (2) a panthenol as an active ingredient, preferably an indole compound or its pharmaceutical And a cosmetic composition and / or a pharmaceutical composition for prevention and improvement of skin damage caused by ultraviolet rays containing an acceptable salt and panthenol as an active ingredient.

The inventors of the present invention have found that when an indole compound or its pharmaceutically acceptable salt and panthenol are used together, they have an excellent effect for preventing and / or improving skin damage caused by ultraviolet rays, and have completed the present invention.

In other words, the inventors of the present invention have experimentally found that the indole compound or its pharmaceutically acceptable salt and panthenol act simultaneously to maximize the synergistic inhibition of skin damage due to ultraviolet rays.

Further, the composition of the present invention can enhance the skin barrier and enhance the moisture retention ability of the skin damaged by ultraviolet rays.

The indole compound included in the cosmetic composition or the pharmaceutical composition of the present invention as an active ingredient may preferably include a compound represented by the following general formula (1).

[Chemical Formula 1]

It is believed that the indole compound is excellent in protecting cells from free radical active oxygen.

The method of obtaining the compound represented by Formula 1 is not particularly limited. The indole compound according to the present invention may be chemically synthesized by a method known in the art, or a commercially available substance may be used.

The term " pharmaceutically acceptable salts " of the present invention refers to salts prepared with little or no toxicity or with acids or bases. When the compound of the present invention is relatively acidic, the base addition salts may be obtained by contacting a neutral form of such compound with a sufficient amount of the desired base and an appropriate inert solvent. Pharmaceutically acceptable base addition salts include, but are not limited to, salts formed with sodium, potassium, calcium, ammonium, magnesium or organic amino. Where the compounds of the present invention are relatively basic, acid addition salts can be obtained by contacting neutral forms of such compounds with a sufficient amount of the desired acid and a suitable inert solvent. Pharmaceutically acceptable acid addition salts include those derived from organic acids such as propionic acid, isobutyric acid, oxalic acid, malonic acid, malonic acid, succinic acid, suberic, fumaric acid, mandelic acid, phthalic acid, benzenesulfonic acid, Such as citric acid, tartaric acid, methanesulfonic acid, hydrochloric acid, bromic acid, nitric acid, carbonic acid, monohydrogencarbonic acid, phosphoric acid, monohydrogenphosphoric acid, dihydrogenphosphoric acid, sulfuric acid, monohydrogenphosphoric acid, hydrogen iodide, phosphorous acid ≪ / RTI > but are not limited to, the salts formed with Also included are salts of amino acids such as arginate and analogs of organic acids such as glucuronic acid or galacturonic acid, but are not limited thereto.

INDUSTRIAL APPLICABILITY The indole compound represented by formula (1) of the present invention may exist in unsolvated form as well as solvated form including form of hydrate, ethanol and the like. The indole compound represented by the formula (1) of the present invention may exist in a crystalline or amorphous form, and all such physical forms are included in the scope of the present invention.

The indole compounds represented by formula (I) of the present invention may also exist in the form of pro-drugs. In particular, prodrugs which can be separated into an indole compound which is in an active form by esterase or amidase present in the skin can be used. Specifically, in order to control the hydrophilicity / lipophilicity, the skin absorbency, the solubility and the in vivo dynamics of the indole compound, alkyl having 1 to 6 carbon atoms, alkenyl having 1 to 6 carbon atoms, haloalkyl having 1 to 6 carbon atoms, An alkoxyalkyl group having 1 to 6 carbon atoms, an alkoxyalkyl or alkoxyalkoxyalkyl group having 1 to 6 carbon atoms, a phenacyl group, a phenacyl group substituted with an alkyl having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, Substituents such as a carbonylalkyl group, a cyanoalkyl group having 1 to 6 carbon atoms, and an alkylthioalkyl group having 1 to 6 carbon atoms in each alkyl moiety may be linked to the -OH group of the indole compound by an ester bond or an amide bond. Such prodrugs can be made by methods well known in the art, such as those described in BURGER'S MEDICAL CHEMISTRY AND DRUG DISCOVERY, 172-178, 949-982 (Manfred E. Wolffed., 5th ed. .

The composition of the present invention may further comprise panthenol in addition to the indole compound.

The panthenol is absorbed into the body and becomes pantothenic acid. The pantothenic acid is a component of Coenzyme A, which plays an important role in metabolism of all cells, and regenerates damaged skin tissue and promotes its function.

Panthenol is also a precursor of vitamin B5 (pantothenic acid), so there is no fear of irritation or other side effects that may occur in steroids and other anti-inflammatory drugs.

The inventors of the present invention have conducted extensive research on various components and have found that when an indole compound represented by the formula (1) or a pharmaceutically acceptable salt thereof and panthenol are used together, skin damage caused by ultraviolet rays, preferably by ultraviolet rays Which is effective in blocking and inhibiting the generation of various inflammatory substances.

Accordingly, the present invention provides a cosmetic composition which suppresses skin inflammation reaction by ultraviolet rays, inhibits the generation of harmful reactive oxygen species by ultraviolet rays, and exerts an effect of enhancing skin barrier and / or improving skin damage and / .

The composition of the present invention may contain, in addition to the indole compound and panthenol of formula (1) for preventing and / or improving skin damage caused by ultraviolet rays, a moisturizing agent, a thickener, a surfactant, An alcohol, a flavor, a pH adjuster, a natural extract, and the like, as well as chemical and / or natural ingredients for improving the effect of the present invention.

The composition of the present invention can be manufactured in the form of medicines, functional foods and cosmetics. Such medicaments, functional foods and cosmetics may include pharmaceutically or cosmetically acceptable excipients or additives. The compositions of the present invention may be administered alone or in admixture with any convenient vehicle, excipient, or the like, and such dosage forms may be single-dose or multiple-dose formulations.

The composition of the present invention may be a solid preparation, a semi-solid preparation or a liquid preparation. Solid preparations include, but are not limited to, powders, granules, tablets, capsules, suppositories, and the like. Solid form preparations may include, but are not limited to, excipients, flavoring agents, binders, preservatives, disintegrants, lubricants, fillers, and the like. Examples of the semi-solid preparation include a cream, a lotion, an emulsifier, a liniment, and the like, but the present invention is not limited thereto, and can be produced by adding a suitable colorant, a flavoring agent, a stabilizer, a tackifier, a surfactant, and the like. Examples of the liquid preparation include water, alcohols, solutions such as solutions of propylene glycol, suspensions, emulsions and the like, but not limited thereto, and they can be prepared by adding appropriate coloring agents, flavoring agents, stabilizers, tackifiers and the like.

For example, powders can be prepared by simple mixing of the indole compound or its salt of the present invention and a suitable pharmaceutically acceptable excipient such as lactose, starch, microcrystalline cellulose, and panthenol. The granules may contain the indole compounds of the present invention or their salts and panthenol; Suitable excipients which are pharmaceutically acceptable; And a suitable pharmaceutically acceptable binder such as polyvinylpyrrolidone and hydroxypropylcellulose, followed by wet granulation using a solvent such as water, ethanol or isopropanol or dry granulation using a compressive force . Further, the tablet may be prepared by mixing the above granule with a suitable pharmaceutically acceptable salt such as magnesium stearate and then tableting it using a tablet machine. Also, for example, the external preparation for skin may be a pharmaceutically or cosmetically acceptable suitable substance such as vaseline, stearyl alcohol and the like; A suitable pharmaceutically or cosmetically acceptable surfactant such as polysorbate, sorbitan sesquioleate, and the like; Suitable pharmacologically or cosmetically acceptable moisturizing agents such as glycerin; A suitable pharmaceutically or cosmetically acceptable solvent; And a conventional external preparation for skin preparation in which a flavoring agent, a coloring agent, a stabilizer, a tackifier and the like are homogeneously mixed.

Meanwhile, the cosmetic composition containing the indole compound or its salt and the panthenol of the present invention can be manufactured into various formulations such as cosmetics, lotions, and creams, and specifically, various forms such as an emulsion, a cream, and a paste Can be applied, and can be produced by using a conventional method of making a cosmetic.

The cosmetic composition or the pharmaceutical composition of the present invention may contain 0.0001 to 0.5% by weight, preferably 0.001 to 0.3% by weight, of the indole compound represented by the formula (1) or a salt thereof, based on the total weight of the composition.

If the amount of the indole compound or its salt is less than 0.0001% by weight, it can not sufficiently attain an effect of improving the skin damage due to ultraviolet rays. If the amount exceeds 0.5% by weight, the stability of the formulation may be affected. There is concern and it is not desirable.

The amount of the panthenol to be used together with the indole compound or its salt of the present invention may be 0.1 to 7 wt%, preferably 1 to 5 wt%, based on the total weight of the composition.

If the content of the panthenol is less than 0.1% by weight, it can not sufficiently attain an effect of improving the skin damage due to ultraviolet rays. If the content of the panthenol exceeds 7% by weight, the cosmetic composition or the pharmaceutical composition And is not economical because it is not expected to increase the apparent effect as the increasing content.

In order to achieve the object of prevention and / or improvement of skin damage by ultraviolet ray blocking according to the present invention, the indole compound or its salt and panthenol of the present invention may be administered at about 0.001 mg / kg to about 10 g / kg each day , A daily dosage of about 0.01 mg / kg to about 1 g / kg is preferred. However, the dosage may vary depending on the route of administration and formulation, the patient's condition (age, sex, weight, etc.), severity of the condition being treated, and the like. For convenience, the total daily dose may be divided as needed and divided into several doses throughout the day.

INDUSTRIAL APPLICABILITY The cosmetic composition or pharmaceutical composition containing the indole compound and panthenol of the present invention exhibits an excellent effect for preventing and / or improving skin damage caused by ultraviolet rays.

In addition, the cosmetic composition or the pharmaceutical composition of the present invention has an effect of enhancing the water retention ability of the skin by strengthening the skin barrier damaged by ultraviolet rays.

The cosmetic composition or the pharmaceutical composition of the present invention can provide an excellent feeling without giving stimulation to the skin.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the embodiments according to the present invention can be modified into various other forms, and the scope of the present invention should not be construed as being limited to the embodiments described below. The embodiments of the present invention are provided by way of example to facilitate a specific understanding of the present invention.

[Preparation of Comparative Examples 1-3 and Example 1]

According to the composition shown in the following Table 1, Comparative Example 1 is a comparative sample containing no indole compound and panthenol, Comparative Example 2 contains an indole compound, Comparative Example 3 contains a panthenol, and Example 1 contains both an indole compound and panthenol By weight, and prepared by the following method.

First, the water phase and the oil phase were heated and dissolved at 70 to 75 DEG C, respectively. The oil phase was gradually added to the water phase, and the mixture was emulsified for 10 minutes under a homomixer at 5000 RPM, followed by cooling to 30 DEG C to produce an emulsion

(Unit weight%) Ingredients Comparative Example Example One 2 3 One Cetearyl alcohol 3 3 3 3 Hydrogenated lecithin One One One One Macadamia seed oil 5 5 5 5 glycerin 10 10 10 10 Indole compound - 0.1 - 0.1 Panthenol - - 3 3 Purified water To 100 To 100 To 100 To 100

[Evaluation of Comparative Examples 1-3 and Example 1]

The compositions of Comparative Examples 1-3 and Example 1 were evaluated in order to evaluate skin damaging effect by ultraviolet rays as follows.

Twenty women between 30 and 50 years old were applied twice a day for 4 weeks on the inner side of the hump for 4 weeks. After 4 weeks, UV irradiation was applied to the skin to cause skin damage. After 24 hours and 48 hours, , Skin barrier function (TEWL), and skin color (red tone). The compositions of Comparative Example 1 and Comparative Example 2 were applied to the inner surface of the left hump of the subject, and the composition of Comparative Example 3 and Example 1 was applied to the inner surface of the right hump.

Experimental Example  1: skin irritation index by ultraviolet irradiation ( EI ) Change measurement

The EI (Erythema Index) was measured using an optical instrument, using Mexameter MX18 as an index to measure the degree of skin erythema and burning.

Erythema index Erythema index change
(After 24 hours) Control group
(Comparative Example 1) Erythema index change
(After 48 hours) Control group
(Comparative Example 1) Comparative Example 1 142.53 - 128.60 - Comparative Example 2 118.82 23.71 103.25 25.35 Comparative Example 3 123.47 19.06 112.60 16.00 Example 1 88.54 53.99 63.55 65.05

As a result of measuring the skin erythema index (EI) change using the optical equipment of Table 2, it can be seen that the skin eruption index change amount in Example 1 is significantly lower than that of Comparative Example 2 and Comparative Example 3. Particularly, when comparing the difference value with the control (Comparative Example 1), it was found that there was a synergistic effect when the indole compound and the panthenol were treated together, compared with the case of treating the indole compound and the panthenol, respectively.

Experimental Example  2: by ultraviolet irradiation Percutaneous water loss ( TEWL ) Increase rate measurement

Percutaneous water loss (TEWL) is an index of skin barrier function that maintains skin moisturization. The higher the index, the greater the skin loss, which means that the function of the skin barrier is impaired. TEWL was measured using Vapometer®.

TEWL TEWL variation
(After 24 hours) Control group
(Comparative Example 1)
Tea with TEWL variation
(After 48 hours) Control group
(Comparative Example 1)
Tea with Comparative Example 1 3.07 - 3.00 - Comparative Example 2 2.52 0.55 2.28 0.72 Comparative Example 3 2.46 0.61 2.32 0.68 Example 1 1.51 1.56 1.26 1.74

As can be seen from the results of the measurement of the transdermal water loss (TEWL) in the above Table 3, it was found that the sample which was mixed with the indole compound and the panthenol alone had a smaller increase in the TEWL, The difference between the control and the control group shows that synergistic effect is better than that of the single application.

Experimental Example  3: Skin color by ultraviolet irradiation Red tone (a value) change measurement

After the compositions of Comparative Examples 1-3 and Example 1 were used for 4 weeks, ultraviolet rays were irradiated and the change in the skin color tone (a value) was measured using Spectrophotometer CM2600d.

Redness (a *) Redness (a *) Change
(After 24 hours) Control group
(Comparative Example 1)
Tea with Redness (a *) Change
(After 48 hours) Control group
(Comparative Example 1)
Tea with Comparative Example 1 4.34 - 3.90 - Comparative Example 2 3.99 0.35 3.55 0.35 Comparative Example 3 3.85 0.49 3.21 0.69 Example 1 3.04 1.30 2.45 1.45

As can be seen from the measurement results of the change amount of the skin color red tones (a value) in Table 4, it can be seen that the change in the skin color tones is less in Example 1 than in Comparative Example 1-3, It was confirmed that the skin color red tone change due to ultraviolet rays is small and synergistic effect is obtained in Example 1 in which both of them are contained compared to Comparative Example 2-3 containing only one.

As described above, the reduction of the skin erythema index change in Experimental Example 1, the increase of the transdermal water loss (TEWL) in Experimental Example 2, and the decrease of the skin tone of red tones in Experimental Example 3 in relation to skin damage after ultraviolet irradiation , The cosmetic composition comprising the indole compound and the panthenol according to the present invention showed the effect of suppressing the skin damage by ultraviolet rays, and the synergistic effect was confirmed in the application of the indole compound and the panthenol, and other skin side effects and irritation were not found I did.

Claims (6)

1. An indole compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof; And panthenol as an active ingredient. The cosmetic composition for prevention and improvement of skin damage caused by ultraviolet rays.
[Chemical Formula 1]

1. An indole compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof; And panthenol as an active ingredient.
[Chemical Formula 1]

The cosmetic composition according to claim 1 or 2, wherein the indole compound is contained in an amount of 0.0001 to 0.5% by weight based on the total weight of the composition, and the panthenol is contained in an amount of 0.1 to 7% by weight based on the total weight of the composition. 1. An indole compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof; And a pharmaceutical composition for preventing and improving skin damage caused by ultraviolet rays comprising panthenol as an active ingredient.
[Chemical Formula 1]

1. An indole compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof; And a panthenol as an active ingredient.
[Chemical Formula 1]

The pharmaceutical composition according to claim 4 or 5, wherein the indole compound is contained in an amount of 0.0001 to 0.5 wt% based on the total weight of the composition, and the panthenol is contained in an amount of 0.1 to 7 wt% based on the total weight of the composition.