KR102139339B1 - Cosmetic composition which has improved solubility comprising indole compound - Google Patents

Abstract

The present invention relates to a cosmetic composition having increased solubility and dissolution stability of a specific indole compound of Formula 1 using polyol, and the cosmetic composition of the present invention is capable of exhibiting excellent stability even during long-term storage.

Description

Cosmetic composition which has improved solubility comprising indole compound

The present invention relates to a cosmetic composition comprising an indole compound, and more particularly, to a cosmetic composition having stability with improved solubility even during long-term storage by increasing the solubility of a poorly soluble indole compound.

In general, there are several theories explaining skin aging, but among them, the free radical theory that the skin is aged by free radicals caused by various causes inside and outside the body is accepted as the most valid theory.

Free radicals are chemically reactive chemicals that occur when the skin is irradiated with UV light or in the process of breathing cells in the skin. Most of the free radicals related to skin aging are reactive oxygen species (ROS), which include super oxide radical, hydrogen peroxide (H ₂ O ₂ ), and hydroxyl radical (Hydroxy radical). , Singlet oxygen, and the like.

The lipid peroxidation caused by them generates various free radical species of radicals, peroxides, aldehydes and epoxides, and damages DNA, RNA, proteins, cell membranes and cell structures, and these free radical species They are thought to be the main causes of cancer, tissue damage, and aging.

For example, peroxidation of membrane lipids that make up cells changes the structure and fluidity of cell membranes, increases permeability of cytoplasmic substances, leaks of lysosome enzymes, inactivation of membrane and transport proteins, and covalent crosslinking of lipids and proteins. It causes covalent crosslinking, protein chain cleavage, DNA damage and mutation, and it is known that during these reactions, peroxidation of the skin cell membrane and modification of dermal cell proteins are most closely associated with skin aging.

Aerobic organisms have protective mechanisms to prevent the formation of these oxidants and lipid peroxidation, which include enzymes such as superoxide dismutase (SOD) and catalase and α-tocopherol (α- Fat-soluble and water-soluble antioxidants or radical scavengers such as tocopherol, Vitamin E), β-carotene, ascorbic acid, Vitamin C, and glutathione.

As mentioned above, since free radicals or free radicals are so closely related to skin aging, superoxide dismunase (SOD), vitamin-E derivatives, vitamin C and its derivatives, flavonoids, and flavonoids are blended in cosmetics. By doing so, a lot of efforts have been made to obtain an anti-aging effect.

However, since most of the conventional methods are not efficiently delivered to the mitochondria, the efficacy is weak or poorly displayed, so it can be considered that the delivery to the mitochondria as an antioxidant is very important for skin aging.

As an antioxidant delivered to the mitochondria, there is an indole compound, which acts directly on the mitochondria to remove free radicals or free radicals, and confirms that it has an effect on preventing cell damage with Korean Patent Application No. 10-2010-0104175 Can.

However, the above indole compound is difficult to stabilize or has poor solubility, so it is difficult to obtain a practical effect due to a limitation in concentration when applying the actual product, and it has a problem in terms of dissolution stability when blending cosmetics, and thus its use is limited. .

Therefore, the present inventors have conducted various studies on the improvement of solubility of the poorly soluble indole compound and stabilization when compounding, in order to develop a cosmetic for skin improvement with excellent antioxidant ability.

Therefore, the present invention is to solve the above problems, and to provide a method for increasing the solubility of poorly soluble indole compounds.

In addition, by increasing the solubility of the indole compound to provide a cosmetic composition having stability even for long-term storage.

In addition, it is intended to provide a maximized product effect by overcoming the problem that the indole compound has a low solubility and thus could not be applied to a product in a limited manner, and can be included in a high concentration when blended in a cosmetic.

In order to solve the above problems, the present invention is a method of increasing the solubility and dissolution stability of a specific indole compound of Formula 1 according to the present invention by using an alkali neutralizing agent, preferably by increasing the solubility of a specific indole compound of Formula 1, stability It is intended to provide a way to improve.

The inventors of the present invention have limitations in applying a large amount to the product despite the excellent antioxidant effect of the indole compound because the specific indole compound of Formula 1 has poor solubility, and as a result of repeated research on a method capable of resolving it Was completed.

That is, as a result of adding the polyol when blending, the inventors of the present invention found that the solubility of the poorly soluble indole compound of Formula 1 is improved and have excellent stability, thereby completing the present invention.

The indole compound of the present invention is a compound of Formula 1 below.

[Formula 1]

The method for obtaining the compound represented by Chemical Formula 1 is not particularly limited. The indole compound according to the present invention can be chemically synthesized by a method known in the art or a commercially available material can be used.

The indole compound of the present invention can improve solubility in conventional pharmaceutical or cosmetic compositions by mixing polyols.

The polyol is glycerin, butylene glycol, dipropylene glycol, pentylene glycol, hexylene glycol, dietylene glycol, propanediol, caprylyl glycol, methyl propanediol, polybutylene glycol-10, polyglycerin-3 , Polyglycerin-4, Polyglycerin-6, Polyglycerin-10, Polyglycerin-20, Polyglycerin-40, Sorbet-5, Sorbet-6, Sorbet-20, Sorbet-30, Sorbet-40 , Dihydroxypropyl PG-glucoside, dithiooctanediol, fructose, glucamine, methylglucamine, glucose, methylglucose-10, methylgluceth-20, ozonized glycerin, phytantriol, thioglycerin , Diglycerin, sorbitol, erythritol, pentaerythritol, inositol, mannitol, maltose, mannan, maltitol, mannose, lactitol, lactose, thritol, trimethylolpropane, and xylitol. However, it is not limited thereto, and for the purpose of the present invention mentioned above, most preferably, any one selected from glycerin, butylene glycol, dipropylene glycol, and mixtures thereof may be used.

The polyol according to the present invention, in the indole compound is 0.000001% to 10% by weight based on the total weight of the composition, it is preferable to include 0.001 to 40% by weight based on the total weight of the composition, more preferably 0.01 to 10% by weight , Most preferably 0.01 to 4% by weight.

If the content of the polyol is less than 0.001% by weight, preferably less than 0.01% by weight, there is a problem that it does not properly dissolve because it does not affect the solubility improvement of the indole compound, 40% by weight, preferably exceeding 10% by weight In the case, there is an uneconomical problem because an increase in the effect is not expected as much as the increasing content.

That is, the present invention uses a polyol in an amount sufficient to dissolve the specific indole compound of the present invention or to improve the solubility of the indole compound, and the composition of the present invention is used to dissolve or dissolve the specific indole compound of the present invention. It contains an amount of polyol sufficient to improve.

In addition, the present invention can provide a cosmetic composition with improved stability by increasing the solubility of a specific indole compound of Formula 1 using polyol.

The cosmetic composition having improved stability of the indole compound of the present invention includes moisturizers, thickeners, surfactants, emulsifiers, preservatives, antioxidants, alcohols, fragrances, pH adjusting agents, natural extracts, etc. Of course, chemical and/or natural ingredients for doubling the effects of the present invention can be formulated in suitable amounts.

The composition containing the indole compound of the present invention may be prepared in the form of pharmaceuticals, health functional foods and cosmetics. Such pharmaceuticals, dietary supplements and cosmetics may contain pharmaceutically acceptable excipients or additives. The composition comprising the indole compound of the present invention may be administered alone or in combination with any convenient carrier, excipient, etc., and such a dosage form may be a single dosage form or a repeated dosage form.

The composition containing the indole compound 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 preparations may include, but are not limited to, excipients, flavoring agents, binders, preservatives, disintegrants, lubricants, fillers, and the like. Semi-solid formulations include, but are not limited to, creams, lotions, emulsifiers, linen agents, and the like, and may be prepared by adding a suitable colorant, flavoring agent, stabilizer, viscous agent, surfactant, and the like. Liquid preparations include, but are not limited to, solutions such as water, alcohol, propylene glycol solutions, suspensions, emulsions, etc., and may be prepared by adding suitable colorants, flavoring agents, stabilizers, viscous agents, and the like.

For example, powders can be prepared by simply mixing the active ingredients of the present invention with suitable pharmaceutically acceptable excipients such as lactose, starch, microcrystalline cellulose. Granules are active ingredients of the present invention; Suitable pharmaceutically acceptable excipients; And after mixing a suitable pharmaceutically acceptable binder such as polyvinylpyrrolidone, hydroxypropylcellulose, to be prepared using a wet granulation method using a solvent such as water, ethanol, isopropanol or a dry granulation method using a compressive force Can. In addition, tablets may be prepared by mixing the granules with a suitable pharmaceutically acceptable lubricant, such as magnesium stearate, and then tableting using a tableting machine. In addition, for example, the external preparation for skin may be a pharmaceutically or cosmetically acceptable suitable base such as vaseline and stearyl alcohol; Pharmaceutically or cosmetically acceptable suitable surfactants such as polysorbate and sorbitan sesquioleate; Suitable moisturizers that are pharmaceutically or cosmetically acceptable; Suitable pharmaceutically or cosmetically acceptable solvents; And it can be prepared by a conventional method for preparing external preparations for skin to homogeneously mix flavors, colorants, stabilizers, and viscous agents.

However, due to the antioxidant efficacy of the indole compound according to the present invention, it is preferable that the composition according to the present invention is a cosmetic composition, and these cosmetic compositions are cosmetic products, essences, oils, creams, powders, etc. It can be prepared and used in formulations such as packs, foundations, makeup bases, and sticks. The cosmetic composition may also be applied in various forms such as liquid, cream, paste, and solid phases, and may be prepared by a conventional cosmetic preparation method.

For example, the composition of the present invention may be prepared with softening agent using carbomer, butylene glycol, glycerin, PEG, ethanol, polyoxyethylene cured castor oil, triethanolamine, purified water, etc., or cetearyl Alcohol, glyceryl stearate/page-100 stearate, polysorbate 60, sorbitan sesquioleate, cetyl octanoate, squalane, apricode kernel oil, butylene glycol, carbomer, xanthan gum, It may be prepared in a lotion type using ingredients such as preservatives, purified water, and arginine, but the present invention is not limited to these formulations.

The present invention provides a cosmetic composition having increased solubility of a poorly soluble indole compound and improved stability.

That is, the present invention provides a cosmetic composition having improved formulation stability even during long-term storage by increasing the solubility of a specific indole compound of Formula 1 by polyol.

In addition, the present invention provides a cosmetic composition stably dispersed in a specific indole compound represented by Chemical Formula 1 and formulated at a high concentration.

Hereinafter, the following examples and the like will be described to more specifically describe the present invention. However, the embodiments according to the present invention can be modified in many different forms, and the scope of the present invention should not be interpreted as being limited to the embodiments described below. Embodiments of the present invention are provided by way of example to help a specific understanding of the present invention.

<Example 1-2 and Comparative Example 1-4> Comparison of solubility in polyol

Experiment method

In Example 1, in the composition ratio of Table 1, an indole compound was added to dipropylene glycol at 1% and stirred for 1 hour. Examples 2 to 6 were prepared in the same manner as in Example 1.

Compatibility evaluation

For the solubility experiments of Examples 1 to 6, after stirring for 1 hour, separation and precipitation were visually observed and shown in Table 1.

Evaluation standard

No abnormality: ◎, weak precipitation: ○, precipitation: X

Example One 2 3 4 5 6 Polyol Dipropylene glycol Butylene glycol glycerin Indole compound ^{1 )} One% 10% One% 10% One% 10% evaluation ◎ ◎ ◎ ○ ◎ ○

1) Indole compound: NecroX (LG LS)

As shown in the above table, it was confirmed that the poorly soluble indole compound that does not dissolve in a small amount of water and oil phase has a difference in solubility depending on the content, but is soluble in polyol.

<Example 7-9 and Comparative Example 1> Preparation of essence composition

Example 7 is the composition ratio shown in Table 2, and after dissolving raw material 4 in raw material 1, 5-8 was added to dissolve it. After checking the solubility, the raw materials 5-7 are sequentially dissolved, and then the raw materials 8 are slowly added to stir uniformly. Raw materials 9-12 were weighed in a beaker, heated and dissolved at 40-45°C, gradually added to the aqueous phase, and uniformly stirred for 10 minutes to prepare an essence. Examples 8-9 and Comparative Example 1 were prepared in the same manner as in Example 7.

(Unit weight%)
Ingredient name Example Comparative example 7 8 9 One One Dipropylene glycol 5 - - - 2 glycerin - 5 - - 3 Butylene glycol - - 5 - 4 Indole compound ^{1 )} 0.005 0.005 0.005 0.005 5 Purified water To 100 To 100 To 100 To 100 6 Chelating agent Proper Proper Proper Proper 7 antiseptic Proper Proper Proper Proper 8 Sodium polyacrylate 0.2 0.2 0.2 0.2 9 Solubilizer 0.3 0.3 0.3 0.3 10 Phenyl trimethicone 0.5 0.5 0.5 0.5 11 ethanol 3 3 3 3 12 Spices Proper Proper Proper Proper

<Example 10-12 and Comparative Example 2> Preparation of creamy cosmetic composition

Example 10 is the composition ratio of Table 3 below, and the raw material 13 is added to the raw material 13 to be dissolved, and then the raw material 14-18 is added to sequentially dissolve. The raw materials 19 are slowly added and dispersed, stirred evenly, and heated to 70-75°C. After weighing the raw materials 1-9 into a beaker, it is heated and uniformly dissolved at 70-75°C, and slowly added to the water phase to uniformly emulsify with a homomixer for 10 minutes. Thereafter, the fragrance of the raw material 20 was added and completely cooled to room temperature to prepare a cream containing a high content of indole compounds. Examples 11-12 and Comparative Example 2 were prepared in the same manner as in Example 10.

(Unit weight%)
Ingredient name Example Comparative example 10 11 12 2 One Cetearyl alcohol 2 2 2 2 2 Glyceryl stearate 2 2 2 2 3 Glyceryl stearate,
PG-100 Stearate 2 2 2 2 4 Cetearyl oleate,
Sorbitan Olive One One One One 5 Caprylic/Capric Triglyceride 5 5 5 5 6 Triethylhexanoin 5 5 5 5 7 Cyclopentasiloxane 5 5 5 5 8 Hydrogenated polydecene 10 10 10 10 9 Dimethicone One One One One 10 glycerin 10 - - - 11 Dipropylene glycol - 10 - - 12 Butylene glycol - - 10 - 13 Indole compound ^{1 )} 0.2 0.2 0.2 0.2 14 Purified water To 100 To 100 To 100 To 100 15 Tromethamine 0.15 0.15 0.15 0.15 16 antiseptic Proper Proper Proper Proper 17 Chelating agent Proper Proper Proper Proper 18 Coloring Proper Proper Proper Proper 19 Carbomer 0.2 0.2 0.2 0.2 20 Spices Proper Proper Proper Proper

<Evaluation of solubility and compatibility>

Solubility and usability of the cosmetic compositions of Examples 7 to 12 and Comparative Examples 1 to 2 were evaluated. Specifically, it was shown in Tables 4 and 5 by visually observing whether or not the phases were separated and whether they precipitated while storing at 25°C for 4 weeks and 5°C for 4 weeks.

<Evaluation criteria>

No abnormality: O, weak precipitation: △, separation and precipitation: X

Solubility Example Comparative example 7 8 9 One Room temperature (25℃) O O O X Refrigeration (5℃) O O O X

As shown in Table 4, it was confirmed that in the case of Examples 7 to 9, which were previously dissolved in polyol and dissolved, the indole compound was dissolved in green in a red-brown powder which was insoluble in water. However, in the case of Comparative Example 1 in which no polyol was used at all, the solubility of the indole compound was remarkably deteriorated and dispersed in the form of a red-brown powder.

Solubility Example Comparative example 10 11 12 2 Room temperature (25℃) O O O O Refrigeration (5℃) O O O △

As shown in Table 5, in the case of Examples 10 to 12 using polyol, it was confirmed that the indole compound was dissolved in green in a reddish brown powder insoluble in water, and a uniformly stable formulation was maintained without precipitation when prepared in a creamy form. . However, in the case of Comparative Example 2 in which no polyol was used at all, the appearance of precipitation was not observed well at room temperature when prepared in the form of a cream, but it was observed that a reddish brown powder precipitated at the temperature of refrigeration.

Through the above experimental results, it was confirmed that the polyol of the present invention influences the solubility of the indole compound and helps to stably disperse in the cosmetic. In addition, it was confirmed through experiments that the content of the polyol greatly influences the solubility of the indole compound.

Claims (3)

An indole compound represented by Formula 1 below; And it characterized in that it comprises a polyol, a cosmetic composition having improved solubility or dissolution stability of the indole compound of Formula 1,
The polyol is a cosmetic composition, characterized in that at least one selected from the group consisting of glycerin, butylene glycol and dipropylene glycol.
[Formula 1]

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