KR20160057189A - Composition for stabilizing polyphenolic effective ingredient - Google Patents

Abstract

The present invention relates to a composition for stabilizing a poorly soluble polyphenol-based active ingredient and, more specifically, to a composition capable of stabilizing a poorly soluble polyphenol-based active ingredient in a formulation by comprising an amphiphilic block copolymer and powder. A cosmetic composition comprising a composition for stabilizing a poorly soluble polyphenol-based active ingredient has no irritation to a skin, and can stabilize the active ingredient in the cosmetic formulation by improving the solubility of the poorly soluble polyphenol-based active ingredient.

Description

TECHNICAL FIELD The present invention relates to a composition for stabilizing polyphenolic active ingredients,

The present invention relates to a composition for stabilizing a polyphenolic insoluble active ingredient, and more particularly, to a composition containing an amphiphilic block copolymer and a powder to stabilize a polyphenolic insoluble active ingredient in a formulation.

Among the ingredients that impart whitening, wrinkle, or other skin-improving effects to the skin, there are a number of poorly soluble materials that do not dissolve in either water or oil, such as polyphenolic systems. Therefore, various methods have been attempted to stabilize these efficacious ingredients in cosmetics in order to use them in high amounts.

In the case of a cream or spot exclusive cosmetic product (Korean Patent No. 10-0811465) using a water-free anhydrous formulation, it was intended to provide different advantages by providing stabilization and heat feeling of components which are easily oxidized or precipitated in water. However, it still has problems such as instability due to aging and heavy and frustrating feeling.

In addition to such a formulation technology, stabilization of an insoluble drug and optimization of its efficacy using polymeric micelles or nanoparticle formation techniques using an amphiphilic block copolymer (Korean Patent Publication No. 2003-0045611, 2007-0041185, Arch Pharm Res Vol 30, No. 9, 2007 ), optimization of efficacy of polyphenolic (genistein) active ingredients using nanostructured lipid carriers ( international journal of pharmaceutics, 453, 2013 ), and solubility enhancement methods using cyclodextrin and its derivatives , 10-1001287, 10-1128450, Bull. Korean Chem. Soc. Vol 29, No. 3, 2008 ). However, there is still a problem of precipitation due to aging in manufacturing cosmetic formulations by such an enclosing method, and there is a limit to use a poorly soluble component in a high content.

A problem to be solved by the present invention is to provide a composition capable of stabilizing a polyphenolic insoluble active ingredient in a cosmetic formulation.

Another object of the present invention is to provide a composition which is free from skin irritation when the composition is added to cosmetics.

The present invention relates to an amphiphilic block copolymer comprising polyethylene glycol as a hydrophilic group; And a powder comprising a porous polymer particle, a cyclodextrin or a derivative thereof, or a mixture thereof. The present invention also provides a composition for stabilizing a poorly soluble polyphenolic active ingredient.

The inventors of the present invention have been studying to stabilize a polyphenolic insoluble active ingredient in cosmetic formulations and found that when the cosmetic composition contains the amphiphilic block copolymer and the powder, the solubility of the poorly soluble polyphenolic active ingredient is remarkably high The present invention has been accomplished on the basis of these findings. This stabilizing effect is synergistically enhanced as compared with the case where the amphiphilic block copolymer and the powder are used alone, and the amphiphilic block copolymer forms polymer micelles to stabilize the polyphenolic insoluble active ingredient, And is trapped in the inside of the powder.

In the present invention, the composition for stabilizing the polyphenolic insoluble active ingredient may contain 0.01 to 10% by weight of an amphiphilic block copolymer and 0.1 to 20% by weight of a powder relative to the total weight of the composition.

In the present invention, the amphiphilic block copolymer is a hydrophilic group and may include polyethylene glycol. More specifically, in the present invention, the amphiphilic block copolymer is excellent in biocompatibility and has a relatively slow decomposition rate as compared with other biodegradable block copolymers and has a relatively stable methoxypolyethylene glycol-b-polycaprolactone Methoxypolyethylene glycol (mPEG-b-PCL-b-mPEG), methoxypolyethylene glycol-b-polycaprolactone (mPEG-b-PCL), methoxypolyethylene glycol-b Polypropylene glycol-b-methoxypolyethylene glycol (mPEG-b-PPG-b-mPEG), methoxypolyethylene glycol-b-poly (D, L-lactide- co- glycolide) (mPEG-b-PLGA), and methoxypolyethylene glycol-polylactide (mPEG-b-PLA).

In the present invention, the molecular weight of the methoxypolyethylene glycol (mPEG) in the amphiphilic block copolymer is not particularly limited, but preferably has a molecular weight of 500 to 100,000 Da, more preferably 500 to 20,000 Da Lt; / RTI > In the amphiphilic block copolymer, the molecular weight ratio of the hydrophilic group methoxypolyethylene glycol (mPEG) to the hydrophobic group may be 1:10 to 10: 1, and preferably has a molecular weight ratio of 1: 5 to 5: 1 . In addition, methoxy polyethylene glycol polypropylene glycol -b- -b- methoxy polyethylene glycol (mPEG-b-PPG-b -mPEG) is flocked yarn meoro preferably Nick ^® Pluronic F commercially available ^{-127 (Pluronic ® F-127,} BASF) may be used. Preferably, the mPEG-b-PPG-b-mPEG may be prepared by mixing with water during the preparation of the composition of the present invention, and the remaining amphiphilic block copolymer may be mixed with a polyol or the like.

In the present invention, the amphiphilic block copolymer may be contained in an amount of 0.01 to 10% by weight, preferably 0.1 to 5% by weight, more preferably 0.5 to 3% by weight based on the total weight of the composition. If the amount of the amphiphilic block copolymer is less than 0.01% by weight, the stability of the formulation is hardly affected. If the amount of the amphiphilic block copolymer is more than 10% by weight, the feeling of use such as stickiness and skin irritation may be reduced.

The powder is usually used for imparting a soft feel to a cosmetic composition, enhancing its absorbency, and functioning to prevent shine or tackiness. In the present invention, the powder is used to prevent precipitation of a poorly soluble polyphenolic active ingredient And may include a porous polymer particle, a cyclodextrin or a derivative thereof, or a mixture thereof. More specifically, the porous polymer particles that can be used as the powder include polyurethane derivatives, silica, porous cellulose, polymethylmethacrylate, allyl methacrylate crosspolymer, Polyamide, and the like, but is not limited thereto.

Preferably, the polyurethane derivative is selected from the group consisting of hexamethylene diisocyanate (HDI) / trimethylolhexyl lactone crosspolymer and silica (HDI) / trimethylol hexyllactone crosspolymer & Silica), HDI / trimethylolhexyl lactone & HDI / Trimethylol hexyllactone & silica & dimethicone, and HDI / PPG / polycaprolactone crosspolymer & silica, and more preferably, HDI / PPG / Polycaprolactone crosspolymer & Commercially available plastic powders D-400, D-800 (Plastic Powder D-400, D-800, Nikko Chemicals Co. Ltd) can be used. For the purpose of the present invention, when the polyurethane derivative hexamethylene diisocyanate (HDI) / trimethylolhexyl lactone cross-polymer and silica is used as the powder, the stability of the polyphenolic insoluble active ingredient in the formulation is the most excellent.

Further, the cyclodextrin is a cyclic oligosaccharide in which 6 to 12 glucose units each have an? -1,4-glycoside bond. Also, the cyclodextrin derivative may preferably be a hydroxypropyl -? - cyclodextrin in which seven molecules of dextrin substituted with a hydroxypropyl group are linked in a ring form.

The powder used in the composition of the present invention may be contained in an amount of 0.1 to 20% by weight, preferably 0.3 to 10% by weight, more preferably 0.5 to 5% by weight based on the total weight of the composition. When the amount of the powder is less than 0.1% by weight, the stability of the poorly soluble active ingredient is hardly affected. When the amount of the powder is more than 20% by weight, problems such as stiffness or warpage may occur.

The composition of the present invention may contain a polyphenolic insoluble active ingredient. Examples of the polyphenol-poor insoluble active ingredient include genistein, daidzein, flangenidin, polyadin, diosmetin, mace lignan, But is not limited to, at least one selected from the group consisting of ginsenoside alginate, ruthenium seed extract, glycitein, quercetin, resveratrol, hesperetin, catechin, and resperidin. The polyphenol may also contain a derivative of the polyphenol or an efficacy component derived from the polyphenol. For the purpose of the present invention, preferably, the polyphenolic insoluble active ingredient may contain genistein, and in such a case, the genistein can be remarkably stabilized in cosmetic formulations comprising the composition of the present invention.

The present invention also relates to the use of a composition comprising methoxypolyethylene glycol-b-polycaprolactone-b-methoxypolyethylene glycol (mPEG-b-PCL-b-mPEG), methoxypolyethylene glycol-b-polycaprolactone mPEG-b-PCL), methoxypolyethylene glycol-b-polypropylene glycol-b-methoxypolyethylene glycol (mPEG-b-PPG-b-mPEG), methoxypolyethylene glycol- At least one selected from the group consisting of poly (D, L-lactide- co -glycolide) (mPEG-b-PLGA) and methoxypolyethylene glycol-polylactide ; And hexamethylene diisocyanate (HDI) / trimethylolhexyl lactone crosspolymer & silica (HDI) / trimethylol hexyllactone crosspolymer & Silica). For purposes of the present invention, a composition comprising the amphiphilic block copolymer and the powder can most stabilize the polyphenolic insoluble active ingredient in the formulation.

The present invention also provides a composition for stabilizing the polyphenolic insoluble active ingredient and a cosmetic composition comprising the polyphenolic insoluble active ingredient. In the cosmetic composition, the polyphenolic insoluble active ingredient can be highly stabilized in the formulation. The present invention also provides a method for stabilizing a polyphenolic insoluble active ingredient in a cosmetic formulation by using the composition for stabilizing the polyphenolic insoluble active ingredient.

In the present invention, the composition for stabilizing the polyphenolic insoluble active ingredient may be added to any cosmetic formulations conventionally produced in the art and used in the form of solutions, suspensions, emulsions, pastes, gels, creams, lotions, But are not limited to, soaps, surfactant-containing cleansers, oils, powder foundations, emulsion foundations, wax foundations, or sprays. More specifically, it can be manufactured into a formulation such as lotion, lotion, nutritional cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray, or powder.

In the present invention, the composition for stabilizing a polyphenolic insoluble active ingredient may be prepared from a cosmetic composition by adding an additive such as a moisturizer, an oil, an ultraviolet screening agent, a flavoring agent, an antioxidant, or a pH adjuster commonly used in cosmetics , But is not limited thereto.

(S1) dissolving a polyphenolic insoluble active ingredient in a solvent; (s2) adding an amphiphilic block copolymer containing polyethylene glycol as a hydrophilic group to the solvent; And (s3) adding a powder containing a porous polymer particle, a cyclodextrin or a derivative thereof, or a mixture thereof to a solvent. The present invention also provides a method for preparing a polyphenolic insoluble active ingredient stabilizing composition.

The cosmetic composition comprising the composition for stabilizing the polyphenolic insoluble active ingredient of the present invention has no irritation to the skin and can be stabilized in the cosmetic formulation by improving the solubility of the polyphenol-based insoluble active ingredient.

Hereinafter, embodiments of the present invention will be described in detail to facilitate understanding of the present invention. 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 following embodiments. Embodiments of the invention are provided to more fully describe the present invention to those skilled in the art.

Preparation of cosmetic composition base (Examples 1 to 3 and Comparative Examples 1 to 5)

Using the ingredients and contents shown in Table 1 below, the cosmetic composition bases of Examples 1 to 3 and Comparative Examples 1 to 5 were prepared as follows. In Examples 1 and 2 and Comparative Examples 1 and 2, raw materials 1 to 4 were first dissolved in 50 wt% of ethanol by heating at 50 ° C, and then the solution was gradually added to the aqueous phase of raw materials 5 to 6 uniformly mixed. The ethanol solvent was evaporated by distillation under reduced pressure at 50 캜, 8 to 10 of the aqueous phase material was added, and the mixture was stirred for 4 minutes at a homomixer of 5,000 rpm, followed by defoaming. Example 3 and Comparative Examples 3 to 5 were prepared by dissolving the raw material 4 in the raw material 3, charging the homogeneously mixed raw materials 5 to 10, stirring the mixture at a homomixer at 5000 rpm for 4 minutes, and defoaming.

division Raw material name Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Polyol 1. mPEG-b-PCL-b-mPEG 15 - - 15 15 - - - 2. mPEG-b-PCL - 15 - - - - - - 3. Dipropylene glycol 10 10 10 10 10 10 10 10 4. Genistein 2.5 2.5 2.5 One 1.2 One 1.2 0.5 Awards 5. Purified water Balance
Balance
Balance
Balance
Balance
Balance
Balance
Balance
6. Hexylene glycol 2 2 2 2 2 2 2 2 7. Poloxamer 407 - - 15 - - - - - 8.Plastic Powder D-400 10 10 10 - - 10 10 - 9. Carbomer (2%) 7 7 7 7 7 7 7 7 10. Tromethamine (10%) 1.4 1.4 1.4 1.4 1.4 1.4 1.4 1.4

Preparation of cosmetic composition (Examples 4 to 6 and Comparative Examples 6 to 7)

In order to apply Examples 1 to 3 and Comparative Examples 1 and 3 prepared in Table 1 to general cosmetic formulations, cosmetic compositions were prepared by the following method using the composition components and contents shown in Table 2 below. First, the water phase and the oil phase were heated and dissolved, respectively. The oil phase was added to the water phase and emulsified for 5 minutes under the condition of a homomixer of 6000 rpm, followed by cooling. The mixture was heated at 55 to 50 DEG C with additives and Examples 1 to 3 and Fertilizer Examples 1, 3 was added and emulsified again for 5 minutes under the condition of homomixer 6000 rpm and cooled to 30 ° C.

division Raw material name Example 4 Example 5 Example 6 Comparative Example 6 Comparative Example 7 Paid Cetostearyl alcohol 1.5 1.5 1.5 1.5 1.5 Hydrogenated lecithin 1.5 1.5 1.5 1.5 1.5 Glyceryl stearate / phage-100 stearate One One One One One Glyceryl stearate One One One One One Polyglyceryl-3-methylglucose distearate 1.5 1.5 1.5 1.5 1.5 Hydrogenated polydecene 4.5 4.5 4.5 4.5 4.5 Caprylic / capric triglyceride 5 5 5 5 5 Dimethicone 0.5 0.5 0.5 0.5 0.5 Awards Purified water Balance Balance Balance Balance Balance glycerin 5 5 5 5 5 Dipropylene glycol 8 8 8 8 8 Hexylene glycol 1.5 1.5 1.5 1.5 1.5 Panthenol One One One One One Carbomer (2%) 8 8 8 8 8 Tromethamine (10%) 1.5 1.5 1.5 1.5 1.5 additive Example 1 10 - - - - Example 2 - 10 - - - Example 3 - - 10 - - Comparative Example 1 - - - 10 - Comparative Example 3 - - - - 10 incense Suitable amount Suitable amount Suitable amount Suitable amount Suitable amount

Experimental Example 1: Formulation stability evaluation

Stability was evaluated by observing stability after storage for 2 months at 0 ℃, 40 ℃ and 45 ℃ cycle chamber (-10 ℃ -> 45 ℃ -> -10 ℃). The evaluation was very good depending on whether or not precipitation occurred: O, trace precipitation: DELTA, precipitation: X.

As shown in Table 3, Examples 4 to 6, which included Examples 1 to 3, could stably contain a higher content of genistein than Comparative Examples 6 and 7 which included Comparative Examples 1 and 3. Furthermore, it was confirmed that the cream containing Examples 1 to 3 was stable without precipitation when the cream was prepared based on Examples 1 to 3 and Comparative Examples 1 and 3 that were stable over time.

Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 50 ℃ O O O O O O O X 45 ° C O O O O △ O △ X 40 ℃ O O O O △ O △ X 0 ℃ O O O O X O △ X Cycle O O O O X O △ X Room temperature O O O O X O △ X

Example 4 Example 5 Example 6 Comparative Example 6 Comparative Example 7 50 ℃ O O O O O 45 ° C O O O O O 40 ℃ O O O O O 0 ℃ O O O △ △ Cycle O O O △ △ Room temperature O O O △ △

Experimental Example 2: First Skin Irritation Test (Closed Patch Test)

In order to examine the skin irritation in the above Examples and Comparative Examples, a predetermined amount (0.2 g) of each sample was applied to the back of a healthy adult male and female for 24 hours, the pin chamber was removed, and after 4 hours, And the results are shown in Table 5 below. The criteria and the degree of stimulation were evaluated as follows.

Criteria

-; No erythema or unusual symptoms.

+ -; Slightly reddish than around

+; Remarkably reddened than surrounding

++; More reddened and swollen than the surrounding area.

sample Tested embroidery Judgment result Irritation degree ++ + + - - Example 4
Example 5
Example 6
Comparative Example 6
Comparative Example 7 50
50
50
50
50 -
-
-
-
- -
-
-
-
- -
One
One
2
One 50
49
49
48
49 0.00
0.02
0.02
0.04
0.02

As shown in Table 5, the stimulus intensity was similar in both Examples and Comparative Examples, and it was confirmed that the cosmetic composition of the present invention (Examples 4 to 6) was safe for skin.

Claims (9)

An amphiphilic block copolymer comprising polyethylene glycol as a hydrophilic group; And
A composition for stabilizing a poorly soluble polyphenolic active ingredient, comprising a powder comprising a porous polymer particle, a cyclodextrin or a derivative thereof, or a mixture thereof. The composition of claim 1, wherein the composition comprises from 0.01 to 10% by weight of an amphiphilic block copolymer and from 0.1 to 20% by weight of a powder relative to the total weight of the composition. The amphiphilic block copolymer of claim 1, wherein the amphiphilic block copolymer is selected from the group consisting of methoxypolyethylene glycol-b-polycaprolactone-b-methoxypolyethylene glycol (mPEG-b-PCL-b-mPEG), methoxypolyethylene glycol Methoxypolyethylene glycol (mPEG-b-PPG-b-mPEG), methoxypolyethylene glycol-b-polypropylene glycol- B-poly (D, L-lactide- co -glycolide) (mPEG-b-PLGA), and methoxypolyethylene glycol- polylactide (mPEG- ≪ RTI ID = 0.0 > and / or < / RTI > The porous polymer particle according to claim 1, wherein the porous polymer particle is selected from the group consisting of a polyurethane derivative, silica, porous cellulose, polymethylmethacrylate, allyl methacrylate crosspolymer, Wherein the composition comprises at least one selected from the group consisting of polyamides. 2. The composition according to claim 1, wherein the polyphenolic insoluble active ingredient is selected from the group consisting of genistein, daidzein, franganidine, polyhedin, diosmetin, mei lignan, asialicoside, ginsenoside alga, Wherein the composition comprises any one or more selected from the group consisting of tetanus, quercetin, catechin, resveratrol, hesperetin, and resperidin. Methoxypolyethylene glycol-b-polycaprolactone-b-methoxypolyethylene glycol (mPEG-b-PCL-b-mPEG), methoxypolyethylene glycol-b-polycaprolactone (mPEG- PCL), methoxypolyethylene glycol-b-polypropylene glycol-b-methoxypolyethylene glycol (mPEG-b-PPG-b-mPEG), methoxypolyethylene glycol- , L-lactide- co -glycolide) (mPEG-b-PLGA), and methoxypolyethylene glycol-polylactide (mPEG-b-PLA); And hexamethylene diisocyanate (HDI) / trimethylolhexyl lactone crosspolymer & silica (HDI) / trimethylol hexyllactone crosspolymer & silica). A cosmetic composition comprising the polyphenolic insoluble active ingredient stabilizing composition of claim 1 and a polyphenolic insoluble active ingredient. A method for stabilizing a polyphenolic insoluble active ingredient in a cosmetic formulation by using the composition for stabilizing the polyphenolic insoluble active ingredient of claim 1. (s1) dissolving the poorly soluble polyphenolic component in the solvent;
(s2) adding an amphiphilic block copolymer containing polyethylene glycol as a hydrophilic group to the solvent; And
(s3) adding a powder comprising a porous polymer particle, a cyclodextrin, or a mixture thereof to a solvent
Wherein the polyphenol compound is a polyphenol-based compound.