KR20150000391A - Cosmetic composition which has improved solubility comprising indole compound - Google Patents

Abstract

The present invention relates to a cosmetic composition with the improved solubility and dissolution stability of a specific indole compound of the chemical formula 1 using an alkali neutralizing agent. The cosmetic composition of the present invention has the excellent stability even while being stored for a long period. The solubility of a non-soluble indole compound is increased. Moreover, provided is a cosmetic composition having the solubility of an indole compound is increased thereby having the stability even while being stored for a long period. Also, the cosmetic composition overcomes the limitation in the application to products caused by low solubility of the indole compound, thereby providing a maximized effect of the products by being contained in a high concentration when mixed with cosmetics.

Description

[0001] The present invention relates to a cosmetic composition comprising an indole compound and an improved solubility-

The present invention relates to a cosmetic composition comprising an indole compound, and more particularly to a cosmetic composition having increased solubility of a poorly soluble indole compound and having stability with improved solubility even when stored for a long period of time.

In general, there are many theories to explain skin aging, but the free radical theory that skin is aged by free radicals caused by various causes outside the body is accepted as the most valid theory.

Free radicals are chemicals that are very chemically reactive. They occur when the skin is exposed to ultraviolet light or when the cells in the skin undergo respiration. Most of the free radicals associated with skin aging are Reactive Oxygen Species (ROS), which include superoxide radicals, hydrogen peroxide (H ₂ O ₂ ), hydroxy radicals, , Singlet oxygen (singlet oxygen), and the like.

The lipid peroxidation caused by these causes the generation of various reactive oxygen species of radicals, peroxides, aldehydes and epoxides, damaging DNA, RNA, proteins, cell membrane and cell structure, Are thought to be the main causes of cancer, tissue damage, and aging.

For example, the peroxidation of membrane lipids constituting cells can lead to changes in structure and fluidity of cell membranes, increased permeability of cytoplasmic substances, leakage of lysosomal enzymes, inactivation of membrane enzymes and transport proteins, It is known that peroxidation of skin constitutive membranes and deformation of dendritic proteins are most closely related to skin aging in these reactions.

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

As described above, since free radicals or reactive oxygen species are related to skin aging in the past, conventionally, superoxide dismutase (SOD), vitamin-E derivatives, vitamin C and derivatives thereof, flavonoids, There have been many attempts to obtain an anti-aging effect of the skin.

However, most of the conventional methods do not efficiently transfer to the mitochondria, and their efficacy is weak or does not appear well. Therefore, it is very important to transmit the antioxidant to the mitochondria in the skin aging.

As an antioxidant to be delivered to the mitochondria, there is an indole compound, which acts directly on the mitochondria to remove free radicals or reactive oxygen species, and is effective in preventing cell damage. Korean Patent Application No. 10-2010-0104175 .

However, the above-mentioned indole compounds are difficult to stabilize or have poor solubility, so that they are difficult to achieve a practical effect owing to the limitation of the concentration when they are applied to actual products and have problems in terms of solubility stability at the time of formulating cosmetics, and their use is limited .

Therefore, the inventors of the present invention have made various studies on the increase of the solubility of the poorly soluble indole compound and the stabilization of the compounding for the development of cosmetics for skin improvement having excellent antioxidant ability.

Accordingly, the present invention aims to solve the above problems and to increase the solubility of the poorly soluble indole compound.

Further, it is intended to provide a cosmetic composition which has increased solubility of the indole compound and has stability even when stored for a long period of time.

In addition, since the solubility of the indole compound is low, the problem that could not be applied to the product can be overcome, and it can be included at a high concentration when added to cosmetics, thereby providing a maximized product effect.

In order to solve the above problems, the present invention relates to a method for increasing the solubility and dissolution stability of a specific indole compound of formula (I) according to the present invention by using an alkaline neutralizing agent, preferably by increasing solubility of a specific indole compound of formula To improve the performance of the system.

The inventors of the present invention have found that the specific indole compounds of the general formula (1) are poor in solubility and thus have a limited application to a product in spite of the excellent antioxidative effects of the indole compounds. As a result, .

That is, the inventors of the present invention found that the addition of the specific indole compound of formula (1) and the alkaline neutralizing agent resulted in improved solubility of the poorly soluble indole compound of formula (1) .

In addition, when the indole compound, the alkaline neutralizing agent and the polyol are mixed together, it is found that the solubility of the poorly soluble indole compound of the formula (1) is further improved.

The indole compound of the present invention is a compound represented by the following formula (1).

[Chemical Formula 1]

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 indole compound of the present invention can be improved in solubility in a conventional pharmaceutical or cosmetic composition by mixing an alkaline neutralizing agent.

The alkaline neutralizing agent is a substance used for neutralization of an acidic substance, and may include carbonates, phosphates, ammonia or amines of sodium or potassium. The alkaline neutralizing agent is preferably selected from the group consisting of methylamine, ethylamine, propylamine, isopropylamine, butylamine, dimethylamine, diethylamine, diethanolamine, dipropylamine, diisopropylamine, But are not limited to, pyrrolidine, piperidine, morpholine, trimethylamine, triethylamine, tripropylamine, quinuclidine, pyridine, quinoline, isoquinoline, - (hydroxymethyl) -1,3-propanediol, potassium hydroxide (KOH), sodium hydroxide (NaOH), triethanolamine, tromethamine, methylglucamine But are not limited to, potassium hydroxide (KOH), sodium hydroxide (NaOH), sodium hydroxide (NaOH), and the like. , Triethanolamine (Tri ethanolamine, tromethamine, methylglucamine, arginine, and mixtures thereof may be used. For the purpose of the present invention mentioned above, it is most preferable to use any one selected from triethanolamine, tromethamine, and mixtures thereof.

The alkaline neutralizing agent according to the present invention preferably contains 0.001 to 40% by weight, more preferably 0.01 to 10% by weight, based on the total weight of the composition, of the composition in which the indole compound is contained in an amount of 0.00001 to 10% %, And most preferably 0.01 to 4 wt%.

When the content of the alkaline neutralizing agent is less than 0.001% by weight, preferably less than 0.01% by weight, the solubility of the indole compound is not affected, , There is an uneconomical problem because the increase in the effect is not expected to increase markedly.

That is, the present invention utilizes an alkaline neutralizing agent 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 may be used to dissolve the specific indole compound of the present invention, Lt; RTI ID = 0.0 > alkaline < / RTI > neutralizing agent.

Further, the present invention can provide a cosmetic composition having improved stability by increasing the solubility of the specific indole compound of formula (I) using an alkaline neutralizing agent.

In addition, the indole compounds of the present invention can be further improved in solubility in conventional pharmaceutical or cosmetic compositions by mixing polyols.

The polyol is selected from the group consisting of glycerin, butylene glycol, dipropylene glycol, pentylene glycol, hexylene glycol, diethylene glycol, propanediol, caprylyl glycol, methylpropanediol, polybutylene glycol- , Polyglycerin-4, polyglycerin-6, polyglycerin-10, polyglycerin-20, polyglycerin-40, sorbes-5, sorbes-6, sorbes-20, sorbes- , Dihydroxypropyl PG-glucoside, dithiaoctanediol, fructose, glucamine, methylglucamine, glucose, methylglucose-10, methylglucose-20, ozonized glycerin, At least one selected from the group consisting of glycerin, diglycerin, sorbitol, erythritol, pentaerythritol, inositol, mannitol, maltose, mannan, maltitol, mannose, lactitol, lactose, Can hamhal, not limited to this, it is possible to use the above-mentioned object of the present invention the, most preferably glycerin, butylene glycol, diethylene one selected from propylene glycol, and mixtures thereof.

The present invention utilizes a polyol in an amount sufficient to dissolve the particular indole compound of the present invention or to improve the solubility of the indole compound and the composition of the present invention may be used to dissolve the particular indole compound of the present invention or to improve solubility Lt; RTI ID = 0.0 > polyol. ≪ / RTI >

The cosmetic composition with improved stability of the indole compound of the present invention may contain, in addition to the above-described components, a moisturizing agent, a thickener, a surfactant, a oil base agent, a preservative, an antioxidant, an alcohol, a flavor, a pH adjuster, Of course, chemical and / or natural ingredients for doubling the effect of the present invention can be blended in an appropriate amount.

The composition containing the indole compound of the present invention can be produced in the form of medicines, health functional foods and cosmetics. Such medicaments, health functional foods and cosmetics may contain pharmaceutically acceptable excipients or additives. Compositions comprising the indole compounds of the present invention may be administered alone or in admixture with any convenient vehicle, excipient, etc., and such dosage forms may be single or multiple dose formulations.

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 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 active ingredient of the present invention with suitable pharmaceutically acceptable excipients such as lactose, starch, microcrystalline cellulose and the like. The granules may contain the active ingredient of the present invention; Suitable excipients which are pharmaceutically acceptable; And a suitable pharmaceutically acceptable binder such as polyvinylpyrrolidone or 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. For example, the external preparation for skin may be a pharmaceutically or cosmetically acceptable base such as vaseline or stearyl alcohol; 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.

However, the antioxidant activity of the indole compound according to the present invention is preferably a cosmetic composition, and the cosmetic composition can be used as cosmetics, cosmetics, oils, creams, powders, A foundation, a foundation, a makeup base, a stick, and the like. Such a cosmetic composition can also be applied in various forms such as a liquid, a cream, a paste and a solid, and can be produced by a conventional cosmetic preparation method.

For example, the composition of the present invention may be prepared as a softening agent using a carbomer, butylene glycol, glycerin, PEG, ethanol, polyoxyethylene hydrogenated castor oil, triethanolamine, purified water or the like, Alcohol, glyceryl stearate / phage-100 stearate, polysorbate 60, sorbitan sesquioleate, cetyl octanoate, squalane, apricot kernel oil, butylen glycol, carbomer, Preservative, purified water, arginine, etc., but the present invention is not limited to such a formulation.

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

That is, the present invention aims to increase the solubility of the specific indole compound of formula (1) by an alkaline neutralizing agent to improve the stability of the formulation even during long-term storage.

Further, the present invention can further improve the solubility of the indole compound by treating the alkaline neutralizing agent and the polyol together.

Further, the present invention provides a cosmetic composition blended at a high concentration by stably dispersing the specific indole compound of formula (1).

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 above-described embodiments. The embodiments of the present invention are provided by way of example to facilitate a specific understanding of the present invention.

<Experimental Example 1-4> Preparation of Essence Composition

In Experimental Example 1, raw material 2 was dispersed in raw material 1 at a composition ratio shown in the following Table 1, and then raw material 3 was added to dissolve. After confirming solubility, raw materials 5-8 were dissolved successively, and the raw material 9 was gradually added thereto and stirred uniformly. The raw materials 10-13 were weighed in a beaker, heated to 40-45 ° C and dissolved, and the mixture was gradually added to the water phase and uniformly stirred for 10 minutes to prepare an essence. Experimental Example 2-4 was prepared in the same manner as Experimental Example 1.

(Unit weight%) Ingredients Experimental Example One 2 3 4 One Purified water To 100 To 100 To 100 To 100 2 Indole compounds ^{1 )} 0.005 0.005 0.005 0.005 3 Tromethamine ^{2 )} - 0.28 - - 4 Triethanolamine ^{3 )} - - 0.30 0.30 5 Dipropylene glycol - - - 3 6 glycerin - - - 5 7 Chelating agent Suitable amount Suitable amount Suitable amount Suitable amount 8 antiseptic Suitable amount Suitable amount Suitable amount Suitable amount 9 Carbomer 0.3 0.3 0.3 0.3 10 Xanthan gum 0.5 0.5 0.5 0.5 11 Solubilizing agent 0.3 0.3 0.3 0.3 12 Phenyl trimecicone 0.5 0.5 0.5 0.5 13 ethanol 3 3 3 3 14 Spices Suitable amount Suitable amount Suitable amount Suitable amount

1) Indole compound: NecroX (LG LS)

2) Tromethamine: Tris Amino Ultra PC (DOW chem)

3) Triethanolamine: Triethanolamine (Unioncarbide)

&Lt; Experimental Example 5-8 > Preparation of cream cosmetic composition

In Experimental Example 5, raw materials 11 and 12 were sequentially added to the raw material 10 at the composition ratios shown in the following Table 2, and the raw material 13 was added thereto and dispersed. After the raw materials 16 to 18 were dissolved successively, the raw material 19 was gradually dispersed, stirred evenly and heated to 70 to 75 캜. The raw material 1-9 was weighed in a beaker, heated to 70-75 ° C and uniformly dissolved, slowly added to the water phase, and uniformly emulsified with a homomixer for 10 minutes. Then, the fragrance of the raw material 20 was added and the mixture was completely cooled to room temperature to prepare a cream containing a high content of the indole compound. Experimental Example 6-8 was prepared in the same manner as Experimental Example 5.

(Unit weight%) Ingredients Experimental Example 5 6 7 8 One Cetearyl alcohol 2 2 2 2 2 Glyceryl stearate 2 2 2 2 3 Glyceryl stearate,
FAGE -100 stearate 2 2 2 2 4 Cetearyl olivate,
Sorbitan olivate One One One One 5 Caprylic / capric triglyceride 5 5 5 5 6 Triethanolhexanone 5 5 5 5 7 Cyclopentasiloxane 5 5 5 5 8 Hydrogenated polydecene 10 10 10 10 9 Dimethicone One One One One 10 Purified water To 100 To 100 To 100 To 100 11 glycerin - - - 10 12 Dipropylene glycol - - - 5 13 Indole compounds ^{1 )} 0.2 0.2 0.2 0.2 14 Tromethamine ^{2 )} - 0.2 - - 15 Triethanolamine ^{3 )} - - 0.21 0.21 16 antiseptic Suitable amount Suitable amount Suitable amount Suitable amount 17 Chelating agent Suitable amount Suitable amount Suitable amount Suitable amount 18 Pigment Suitable amount Suitable amount Suitable amount Suitable amount 19 Carbomer 0.2 0.2 0.2 0.2 20 Spices Suitable amount Suitable amount Suitable amount Suitable amount

1) Indole compound: NecroX (LG LS)

2) Tromethamine: Tris Amino Ultra PC (DOW chem)

3) Triethanolamine: Triethanolamine (Unioncarbide)

&Lt; Evaluation of solubility and compatibility &

The solubility and usability of the cosmetic compositions of Experimental Examples 1 to 8 were evaluated. Specifically, the separation and precipitation of the phases were visually observed while being kept at 25 DEG C for 4 weeks and at 5 DEG C for 4 weeks, and are shown in Tables 3 and 4 below.

<Evaluation Criteria>

No abnormality: O, weak precipitation:?, Separation and precipitation: X

Solubility Experimental Example One 2 3 4 Room temperature (25 캜) X O O O Refrigerated (5 ℃) X O O O

As shown in Table 3, it was confirmed that indole compounds were soluble in green in reddish brown powder insoluble in water in Experimental Examples 2 to 4 using an alkaline neutralizing agent. In addition, in Experiment Example 1 in which no alkaline neutralizing agent was used, it was confirmed that the product was dispersed as a reddish brown powder and was not dissolved.

Solubility Example 6 7 8 9 Room temperature (25 캜) X O O O Refrigerated (5 ℃) X O O O

As shown in Table 4, in the case of Experimental Examples 7 to 9 using an alkaline neutralizing agent, it was confirmed that the indole compound was dissolved in green in a reddish brown powder insoluble in water, and the formulation was uniformly and stably maintained in a cream phase without precipitation Respectively. In Experimental Example 6 in which no alkaline neutralizing agent was used at all, the solubility of the indole compound was remarkably reduced and the reddish brown powder was dispersed in the form of a reddish brown powder. In the case of the cream phase, the insoluble powder itself was mixed. It was confirmed that even in Experimental Examples 7 and 8 in which no polyol was used, a uniform and stable formulation was maintained without precipitation.

From the above experimental results, it was confirmed that the alkaline neutralizing agent of the present invention affects the solubility of the indole compound and helps to be stably dispersed in the cosmetic. Experiments have shown that the content of alkaline neutralizer greatly affects the solubility of indole compounds.

In addition, it has been confirmed that the indole compound of the present invention can be stably dispersed in the cosmetic when the alkaline neutralizing agent and the polyol are treated together.

Claims (6)

An indole compound represented by the following formula (1); And
A composition having improved solubility or dissolution stability of an indole compound represented by the following formula (1), which comprises an alkaline neutralizing agent.
[Chemical Formula 1]

The method of claim 1, wherein the alkaline neutralizing agent is selected from the group consisting of methylamine, ethylamine, propylamine, isopropylamine, butylamine, dimethylamine, diethylamine, diethanolamine, dipropylamine, diisopropylamine, di- Butylamine, pyrrolidine, piperidine, morpholine, trimethylamine, triethylamine, tripropylamine, quinuclidine, pyridine, quinoline, isoquinoline, benzathine, N-methyl- Is selected from the group consisting of amino-2- (hydroxymethyl) -1,3-propanediol, potassium hydroxide, sodium hydroxide, triethanolamine, tromethamine, methylglucamine, arginine, lysine and mixtures thereof &Lt; / RTI &gt; The composition according to claim 2, wherein the alkaline neutralizing agent is any one selected from the group consisting of potassium hydroxide, sodium hydroxide, triethanolamine, tromethamine, methylglucamine, arginine, and mixtures thereof. The composition of claim 3, wherein the alkaline neutralizing agent is any one selected from the group consisting of triethanolamine, tromethamine, and mixtures thereof. The composition of claim 1, further comprising a polyol. 6. The composition of claim 5, wherein the polyol is selected from the group consisting of glycerin, butylene glycol, dipropylene glycol, pentaerythritol, hexylene glycol, diethylene glycol, propanediol, caprylyl glycol, 10, polyglycerin-3, polyglycerin-4, polyglycerin-6, polyglycerin-10, polyglycerin-20, polyglycerin-40, sorbes-5, sorbes-6, sorbes- 30, sorbes-40, dihydroxypropyl PG-glucoside, dithiaoctanediol, fructose, glucamine, methylglucamine, glucose, methylglucose-10, methylglucose-20, ozonized glycerin, Which is composed of at least one selected from the group consisting of atorvastatin, atorvastatin, atorvastatin, atorvastatin, atorvastatin, atorvastatin, atorvastatin, atorvastatin, atorvastatin, atorotriol, thioglycerin, diglycerin, sorbitol, erythritol, pentaerythritol, inositol, mannitol, maltose, mannan, maltitol, mannose, lactitol, Line in group The composition according to claim any one of.