KR20160136494A - Genistein methyl ether-containing nanoliposome, method for preparing the same, and cosmetic composition comprising the same - Google Patents

Abstract

The present invention relates to a nanoliposome containing genistein methyl ether which shows excellent whitening activity; and to a cosmetic composition. More specifically, the present invention relates to a genistein methyl ether-containing nanoliposome, a manufacturing method thereof, and a cosmetic composition including the genistein methyl ether-containing nanoliposome. The genistein methyl ether-containing nanoliposome is manufactured by: completely dissolving poorly-soluble genistein methyl ether using polyol and ethanol; and making the dissolved genistein methyl ether into a nanoliposome using a glyceryl ester vesicle. Accordingly, the genistein methyl ether-containing nanoliposome has excellent storage stability and can maximize a whitening effect. Furthermore, according to the present invention, the genistein methyl ether-containing nanoliposome can protect active ingredients in shade cosmetics such as blemish balm and sun block, which are a formulation with high salinity, and can effectively deliver the active ingredients to the human skin.

Description

TECHNICAL FIELD [0001] The present invention relates to a method for preparing a nano-liposome, and more particularly, to a method for preparing the same,

The present invention relates to a nanoliposome and a cosmetic composition containing genistein methyl ether (GME) exhibiting excellent whitening activity. More particularly, the present invention relates to a nanoliposome and a cosmetic composition, Containing nanoliposome, which is excellent in storage stability and can maximize the whitening improving effect by dissolving it into glyceryl ester bejjicronanol liposomes, a process for producing the same, and a cosmetic composition containing the same.

Currently, whitening functional substances, which show the whitening efficacy determined by the Ministry of Food and Drug Administration, can be largely divided into oil-soluble substances and water-soluble substances. As water-soluble whitening functional substances, arbutin, niacinamide, and ascorbyl glucoside may be mentioned. As an oil-soluble whitening functional substance, alpha-safflower or licorice extract may be mentioned.

Arbutin, a water-soluble substance, has poor storage stability. When used in a cosmetic composition, arbutin is very irritating to skin due to hydroquinone remaining in discoloration and synthesis, and niacinamide has an unreacted prinicotonic acid, It is well known that it induces stimulation. Ascorbyl glucoside is a vitamin derivative, and it is one of the substances which is difficult to use because it can not be universally used in a formulation due to its high polarity. On the other hand, in the case of alpha-bisabolol or licorice extract, which is an oil-soluble substance, unlike arbutin or niacinamide, there is no residual unreacted substance and thus it can be safely used for skin. However, it has high instability for heat and light, Even if they make cosmetics, there is a unique color of the material itself, which causes the user to avoid use.

In particular, the whitening raw materials are those having skin whitening activity through inhibition of tyrosinase activity, an enzyme involved in melanin synthesis, and inhibit the expression of tyrosinase by inhibiting the expression of MITF (microphtalmia associated transcription factor) It is a reality that the effect is not remarkable as compared with a substance having a whitening activity by inhibiting the production. On the other hand, it has recently been confirmed that whitening activity of the genistein methyl ether (biochanin A) is observed by Park, Sung Ha et al. (Journal of the Society of Cosmetic Scientists, Vol. 39, No. 4, December 2013, 289 -294), which discloses that biocanin A inhibits tyrosinase expression through inhibition of MITF expression and further inhibits melanin production. However, since genistein methyl ether has such excellent whitening activity, it is difficult to handle because it is an insoluble substance which is insoluble in a solvent. Even if a cosmetic preparation is made, since the storage stability is not good, It is required to develop a cosmetic preparation technology optimized for ether.

In order to stabilize the conventional unstable active ingredients and effectively deliver the effect into the skin, a method of utilizing lecithin, which is a substance in the form of triglyceride composed of two hydrophilic fatty acids and one hydrophilic group, as a vesicle is mainly used. International Patent Publication WO / 2011/129588 discloses a polymer-liposome nanocomposite composition for percutaneous absorption using lecithin (phosphatidylcholine) derived from egg yolk as a vesicle and a method for producing the same. However, since phosphatidylcholine, which is a lecithin derived from egg yolk, has a high unit price and is derived from an animal, the tendency to avoid consumers is increasing, and there is a problem that storage stability, in particular, stability against heat and light, , The technique utilizing the conventional lecithin bezle can not be regarded as a technique suitable for stabilizing the active ingredient and delivering effective efficacy.

WO / 2011/129588 (Published on February 2, 2012)

Journal of the Society of Cosmetic Scientists of Korea, Vol. 39, No. 4, December 2013, 289-294

Accordingly, the present inventors confirmed that the production of tyrosinase can be prevented by inhibiting the expression of MITF by the genistein methyl ether, and stabilizing the genistein methyl ether using a technique of completely dissolving the whitening active substance and a glyceryl ester vesicle To thereby effectively transmit the efficacy to the cells. Thus, the present invention has been completed.

Accordingly, it is a first object of the present invention to provide a nano-liposome containing a genistein methyl ether-containing nanoliposome, which is excellent in storage stability and can maximize the whitening improving effect, by converting the genistein methyl ether having excellent whitening activity into glyceryl ester bejjicronanol liposomes .

A second object of the present invention is to provide a process for preparing the above-mentioned nenoliposome.

Further, it is a third object of the present invention to provide a cosmetic composition comprising the above-mentioned nenoliposome.

In order to achieve the first object, the present invention provides a genistein methyl ether and a glyceryl ester, and a genistein methyl ether-containing nanoliposome.

The genistein methyl ether may be included in an amount of about 0.0001 wt% to about 50 wt%.

The glyceryl ester may include an alpha hydroxy acid derivative having both a hydrophilic group and a lipophilic group.

The glyceryl ester may be one or more selected from the group consisting of glyceryl citrate / lactate / linolate / oleate, glyceryl stearate citrate, and glyceryl cocoate / citrate / lactate .

The glyceryl ester may be included in an amount of about 0.5 wt% to about 10 wt%.

Wherein the genistein methyl ether-containing nanoliposome comprises from about 50% to about 70% by weight of a water phase component, from about 0.1% to about 5% by weight of a surfactant, from about 0.1% to about 20% % ≪ / RTI > by weight to about 12% by weight.

The genistein methyl ether-containing nanoliposome may further comprise polyols and ethanol in a ratio of about 3: 1.

The polyols include at least one selected from the group consisting of glycerin, butylene glycol, propylene glycol, dipropylene glycol, methylpropanediol, isoprene glycol, pentylene glycol and polyethylene glycol .

The genistein methyl ether-containing nanoliposome may have a particle size of about 110 nm to about 180 nm.

According to another aspect of the present invention, there is provided a method for manufacturing a magnetic recording medium, comprising: forming a first mixture by mixing an aqueous phase component and an aqueous phase component; Mixing the first mixture with genistein methyl ether to form a second mixture; And applying pressure to the second mixture. ≪ Desc / Clms Page number 5 >

Wherein the first mixture comprises about 0.5 wt.% To about 10 wt.% Glyceryl ester, about 50 wt.% To about 70 wt.% Water component, about 0.1 wt.% To about 5 wt.% Surfactant, By weight, and from about 8% to about 12% by weight of the softening agent.

The glyceryl ester may include an alpha hydroxy acid derivative having both a hydrophilic group and a lipophilic group.

The glyceryl ester may be one or more selected from the group consisting of glyceryl citrate / lactate / linolate / oleate, glyceryl stearate citrate, and glyceryl cocoate / citrate / lactate .

The first mixture may further comprise polyols and ethanol in a ratio of about 3: 1.

The polyols include at least one selected from the group consisting of glycerin, butylene glycol, propylene glycol, dipropylene glycol, methylpropanediol, isoprene glycol, pentylene glycol and polyethylene glycol .

And about 0.0001% to about 50% by weight of the genistein methyl ether.

The step of applying pressure to the second mixture may be performed using a microfluidizer at a pressure of from about 1000 bar to about 1500 bar.

Furthermore, in order to achieve the third object, the present invention provides a cosmetic composition comprising a genistein methyl ether-containing nanoliposome containing genistein methyl ether and glyceryl ester.

The cosmetic composition may be an oil in water type.

According to the present invention, it is possible to make nanoliposomes by using glyceryl ester bezac, which is a poorly soluble substance showing whitening activity, and to apply it to a functional cosmetic composition to maximize whitening activating function. Can be provided. In particular, the inventive nenoliposomes of the present invention contain glyceryl ester as a vesicle, thereby securing the stability of the material and improving the instability of the nanoliposome including phospholipid vesicles such as lecithin , It is possible to apply universally within a formulation of a weakly soluble adult genistein methyl ether. Further, by maximizing the skin whitening improving effect according to the whitening active ingredient, genistein methyl ether, it is possible to provide an effective skin improving effect even with a small amount of the active substance.

In addition, according to the present invention, it is possible to provide a cosmetic composition which can satisfy the needs of consumers who pay attention to actual efficacy in use of cosmetics by providing higher stability and efficacy than arbutin, which is a conventional functional whitening active ingredient, The stability with time can be improved.

FIG. 1 illustrates a process for preparing a genistein methyl ether-containing nanoliposome according to an embodiment of the present invention.
Fig. 2 shows the inhibitory effect on melanin biosynthesis of the genistein methyl ether.
3 shows the emulsified state of the cosmetic composition according to one embodiment of the present invention.
4 shows the dispersion state of the cosmetic composition according to one embodiment of the present invention.
5 shows the stability with time of the cosmetic composition according to one embodiment of the present invention.
6A and 6B show the whitening effect of the cosmetic composition according to an embodiment of the present invention in an in vivo clinical practice.
7A and 7B show the whitening effect of the cosmetic composition according to an embodiment of the present invention in an in vivo clinical practice.
Figure 8 shows the whitening effect of the cosmetic composition according to an embodiment of the present invention in an in vivo clinical practice.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings, which will be readily apparent to those skilled in the art. The present invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. In order to clearly illustrate the present invention, parts not related to the description are omitted, and similar parts are denoted by like reference characters throughout the specification.

It is to be understood that the terms or words used in the specification and claims are not to be construed in a conventional or dictionary sense and that the inventor may properly define the concept of a term in order to best describe its invention And should be construed in accordance with the principles and meanings and concepts consistent with the technical idea of the present invention.

In the specification of the present invention, when a component is referred to as "comprising ", it means that it can include other components as well as other components, .

Throughout the specification of the present invention, "A and / or B" means A or B, or A and B.

Hereinafter, the present invention has been specifically described with reference to the accompanying drawings, but the present invention is not limited thereto.

A first aspect of the present invention provides a genistein methyl ether-containing nanoliposome comprising a genistein methyl ether and a glyceryl ester.

In one embodiment of the present invention, the genistein methyl ether is involved in the action of melanocyte stimulating hormone (MSH) and expresses a microphtalmia associated transcription factor (MITF), a gene regulating the function of the melanin producing gene Inhibiting the production of tyrosinase and further inhibiting melanin biosynthesis. Compared to whitening raw materials which inhibit the activity of tyrosinase or remove the stratum corneum and whiten skin, genistein methyl ether inhibits the melanin biosynthesis of tyrosine in melanocytes and dermal epithelium, thereby achieving an excellent whitening effect. More specifically, the melanin biosynthesis signaling pathway is involved in a wide variety of signaling pathways, and melanin is synthesized through several intracellular signaling pathways, of which the cAMP / PKA pathway is the main pathway for melanin synthesis, Upon exposure, melanocyte cAMP (cyclic adenosine monophosphate) is increased, PKA (protein kinase A) is activated, and CREB (cyclic AMP response element binding protein) is increased to increase MITF expression. MITF promotes transcription of tyrosinase, TRP-1, and TRP-2 as important transcription factors in melanin synthesis. Genistein methyl ether inhibits tyrosinase, TRP-1, and TRP- -2 protein expression, thereby inhibiting the production of melanin. Thus, melanin biosynthesis can be inhibited more effectively than conventional arbutin.

Since the compound of the flavonoid such as the above-mentioned genistein methyl ether is a poorly soluble substance, it is very important to improve the solubility in the cosmetic application. If the dissolution is not properly carried out, foreign matter may be generated, which may cause dissatisfaction to the user in using the cosmetic product, and a case may occur in which the solubility over time is deteriorated and re-determined.

In one embodiment of the present invention, the genistein methyl ether may be dissolved using a polyol and an alcohol. The genistein methyl ether may be dissolved in a mixed solution containing about 1.5% to about 4.5% by weight of polyol and about 0.5% to about 1.5% by weight of ethanol. For example, the genistein methyl ether may be completely dissolved in a mixed solution containing the polyol and the ethanol at a ratio of about 3: 1 (w / w), but may not be limited thereto.

The polyol may serve as a skin softening agent and may help dissolve in water. Examples of the polyol include glycerin, butylene glycol, propylene glycol, dipropylene glycol, methylpropanediol, isoprene Polyethylene glycol, polyethylene glycol, polyethylene glycol, polyethylene glycol, and the like.

In one embodiment of the present invention, the genistein methyl ether may be contained in an amount of about 0.0001 wt% to about 50 wt%, but is not limited thereto. For example, the genistein methyl ether-containing nanoliposomes may contain from about 0.0001% to about 50%, from about 0.0001% to about 30%, from about 0.0001% to about 10%, from about 0.0001% From about 0.0001% to about 0.01%, from about 0.0001% to about 0.001%, from about 0.001% to about 50%, from about 0.01% to about 0.01% To about 50 wt%, about 0.1 wt% to about 50 wt%, about 1 wt% to about 50 wt%, or about 0.0025 wt% to about 0.05 wt%. In the present invention, 0.0001% by weight means 1 ppm.

When the total weight of the genistein methyl ether-containing nanoliposome is 1 Kg, it may exhibit whitening efficacy even if the genistein methyl ether-containing nanoliposome contains only about 25 ppm of the genistein methyl ether. However, the present invention is not limited thereto. It is necessary to prescribe a blending amount of at least 2.0% by weight (20000 ppm) of whitening active substances (for example, arbutin, niacinamide, ascorbyl glucoside, etc.) Very high reality. However, in the present invention, even when a small amount of genistein methyl ether is blended, excellent whitening effect due to inhibition of tyrosine in the melanin biosynthetic process can be exhibited as described above, and the manufacturing cost of the cosmetic preparation can be expected to be reduced.

The genistein methyl ether-containing nanoliposomes can be emulsified by glyceryl esters.

In one embodiment of the present invention, the glyceryl ester may include an alpha hydroxy acid (AHA) derivative having both a hydrophilic group and a lipophilic group, and may be an ethylene oxide (EO) free form, .

The glyceryl ester may be one or more selected from the group consisting of glyceryl citrate / lactate / linolate / oleate, glyceryl stearate citrate, and glyceryl cocoate / citrate / lactate .

In one embodiment of the present invention, the glyceryl ester may be included in an amount of about 0.5% by weight to about 10% by weight, but the present invention is not limited thereto. For example, the genistein methyl ether-containing nanoliposomes may contain from about 0.5% to about 10%, from about 0.5% to about 5%, from about 0.5% to about 1%, from about 1% To about 10 wt%, about 5 wt% to about 10 wt%, or about 3 wt% to about 7 wt%. At this time, if the genistein methyl ether-containing nanoliposome contains less than about 0.5% by weight of glyceryl ester, emulsification is difficult, and if more than about 10% by weight of glyceryl ester is contained, the stability of the active ingredient may be impaired.

Wherein the genistein methyl ether-containing nanoliposome comprises from about 50% to about 70% by weight of a water phase component, from about 0.1% to about 5% by weight of a surfactant, from about 0.1% to about 20% % ≪ / RTI > by weight to about 12% by weight.

The water-based ingredients may include polyols such as purified water to help soften and moisturize the skin.

The surfactant may include at least one selected from the group consisting of polysorbate 20, polysorbate 60, and polysorbate 80. If the surfactant is included in the genistein methyl ether-containing nanoliposome at less than about 0.1 wt%, it is difficult to serve as a surfactant. If the surfactant is present at about 5 wt% or more, it may interfere with the formation of nanoliposome.

The oils may be included to improve usability and include paraffins having unsaturated groups; And natural oils such as olive oil, avocado oil, and sunflower oil. The oil may be included in the genistein methyl ether-containing nanoliposome in an amount of about 0.1 wt% to about 20 wt%, and preferably about 1 wt% to about 10 wt%. If the amount of the oil stream is less than about 0.1 wt%, it is not effective in improving usability. If the oil flow is more than about 20 wt%, the usability is deteriorated and the stability of the genistein methyl ether may be impaired.

The softening agent may include ethanol. The softening agent may be included in the genistein methyl ether-containing nanoliposome in an amount of about 8% by weight to about 12% by weight, and preferably about 10% by weight. If the amount of the softening agent is less than about 8.0 wt%, the effect of softening is small. If the amount of the softening agent is more than about 12 wt%, stability and skin irritation may be caused.

In one embodiment of the present invention, the genistein methyl ether-containing nanoliposome may further include, but is not limited to, a stability enhancer for effective penetration of the skin and stability of the genistein methyl ether. The stability improving agent may be at least one selected from the group consisting of ceramides and cholesterol.

In one embodiment of the present invention, the genistein methyl ether-containing nanoliposomes may have a particle size of about 110 nm to about 180 nm, but are not limited thereto. For example, the particle size of the genistein methyl ether-containing nanoliposomes may range from about 110 nm to about 180 nm, from about 110 nm to about 170 nm, from about 110 nm to about 150 nm, from about 110 nm to about 130 nm, from about 130 nm to about 180 nm, from about 150 nm to about 180 nm, from about 170 nm to about 180 nm, or from about 150 nm to about 170 nm.

The genistein methyl ether-containing nanoliposome can improve the stability of genistein methyl ether and effectively penetrate the skin, and thus can be used in various fields such as cosmetics as well as health food.

A second aspect of the present invention is a method for producing a water-soluble polymer, comprising: mixing an aqueous phase component and an aqueous phase component to form a first mixture; Mixing the first mixture with genistein methyl ether to form a second mixture; And applying pressure to the second mixture. ≪ Desc / Clms Page number 5 >

In the step of forming the first mixture according to the present invention, the first mixture comprises about 0.5 wt.% To about 10 wt.% Glyceryl ester, about 50 wt.% To about 70 wt.% Water component, about 0.1 wt.% Surfactant, About 5 wt.% Oil, about 0.1 wt.% To about 20 wt.% Oil, and about 8 wt.% To about 12 wt.% Of a softening agent.

The glyceryl ester may include an alpha hydroxy acid derivative having both a hydrophilic group and a lipophilic group, and may be an ethylene oxide (EO) -free form. The glyceryl ester may be one or more selected from the group consisting of glyceryl citrate / lactate / linolate / oleate, glyceryl stearate citrate, and glyceryl cocoate / citrate / lactate . At this time, emulsification is difficult if less than about 0.5% glyceryl ester is mixed, and stability of the active ingredient may be impaired if more than about 10% glyceryl ester is mixed.

The water-based ingredients may include polyols such as purified water to help soften and moisturize the skin. At this time, the purified water is not necessarily included, and may be mixed in a residual amount in consideration of usability and the like.

The surfactant may include at least one selected from the group consisting of polysorbate 20, polysorbate 60, and polysorbate 80. When the surfactant is mixed at less than about 0.1 wt%, it is difficult to serve as a surfactant. If the surfactant is mixed at more than about 5 wt%, it may interfere with the formation of nanoliposome.

The oils may be included to improve usability and include paraffins having unsaturated groups; And natural oils such as olive oil, avocado oil, and sunflower oil. The oil streams may be mixed at about 0.1 wt.% To about 20 wt.%, And preferably at about 1 wt.% To about 10 wt.%. If the amount of the oil stream is less than about 0.1 wt%, it is not effective in improving usability. If the oil flow is more than about 20 wt%, the usability is deteriorated and the stability of the genistein methyl ether may be impaired.

The softening agent may include ethanol. The softening agent may be mixed at about 8 wt.% To about 12 wt.%, And preferably at about 10 wt.%. If the amount of the softening agent is less than about 8.0 wt%, the effect of softening is small. If the amount of the softening agent is more than about 12 wt%, stability and skin irritation may be caused.

In one embodiment of the present invention, the first mixture may further include a stability improving agent, but the present invention is not limited thereto. The stability improving agent may be at least one selected from the group consisting of ceramides and cholesterol.

In one embodiment of the present invention, the first mixture may comprise polyols in a ratio of about 3: 1 and ethanol. The about 3: 1 ratio of polyols and ethanol may be, but not limited to, to completely dissolve the genistein methyl ether to be mixed in the subsequent step.

The first mixed liquor may be cooled before it is mixed with the genistein methyl ether. At this time, the temperature may be room temperature to about 50 캜, but may not be limited thereto.

In the step of forming the second mixture according to the present invention, the first mixture is mixed with the genistein methyl ether. At this time, the genistein methyl ether may be the undissolved substance itself, or may be one which is dispersed in alcohol, or completely dissolved by using polyol and alcohol. For example, the genistein methyl ether may be dissolved in a mixture of about 1.5 wt% to about 4.5 wt% polyol and about 0.5 wt% to about 1.5 wt% ethanol. For example, the genistein methyl ether may be completely dissolved in a mixed solution containing the polyol and the ethanol at a ratio of about 3: 1 (w / w), but may not be limited thereto.

The polyol may serve as a skin softening agent and may help dissolve in water. Examples of the polyol include glycerin, butylene glycol, propylene glycol, dipropylene glycol, methylpropanediol, isoprene Polyethylene glycol, polyethylene glycol, polyethylene glycol, polyethylene glycol, and the like.

In one embodiment of the present invention, the genistein methyl ether may be contained in an amount of about 0.0001 wt% to about 50 wt%, but is not limited thereto. For example, the genistein methyl ether-containing nanoliposomes may contain from about 0.0001% to about 50%, from about 0.0001% to about 30%, from about 0.0001% to about 10%, from about 0.0001% From about 0.0001% to about 0.01%, from about 0.0001% to about 0.001%, from about 0.001% to about 50%, from about 0.01% to about 0.01% To about 50 wt%, about 0.1 wt% to about 50 wt%, about 1 wt% to about 50 wt%, or about 0.0025 wt% to about 0.05 wt%. In the present invention, 0.0001% by weight means 1 ppm.

The second mixed liquid may be first cooled before the step of applying pressure. At this time, the temperature may be room temperature to about 50 캜, but may not be limited thereto.

In the present invention, the step of applying pressure can be performed by applying a pressure from about 1000 bar to about 1500 bar using a microfluidizer, and passing the fluid through three passes or more. The microtubulized zenithane methyl ether-containing nanoliposome may have a particle size of about 110 nm to about 180 nm.

In this regard, FIG. 1 illustrates a process for preparing a genistein methyl ether-containing nanoliposome according to an embodiment of the present invention, but is not limited thereto. Referring to Figure 1, a first mixture is prepared by mixing purified water, polysorbate 60, and glyceryl citrate / lactate / linolate / oleate, followed by addition of paraffin oil, ceramide, cholesterol, .

The first mixture is uniformly stirred using a homomixer at about 70 ° C at a speed of about 6000 rpm to about 7000 rpm for about 5 minutes to about 7 minutes, and then slowly cooled to about 50 ° C.

The second mixture is prepared by adding the genistein methyl ether to the cooled first mixture, followed by homogeneous stirring for about 5 minutes at a speed of about 4000 rpm to about 5000 rpm, followed by cooling to room temperature. At this time, the genistein methyl ether may be a pure substance itself or may be completely dissolved in a mixed solution containing polyol and ethanol in a ratio of about 3: 1 (w / w).

The cooled second mixture may be pressurized to about 1000 bar with a microfluidizer over three passes to form a nanoliposome composition having an average particle size of about 110 nm to about 180 nm.

A third aspect of the present invention provides a cosmetic composition comprising a genistein methyl ether-containing nanoliposome containing genistein methyl ether and glyceryl ester.

In one embodiment of the present invention, the cosmetic composition may be an oil in water type.

An underwater type cosmetic composition according to an embodiment of the present invention comprises an aqueous phase comprising purified water, an aging agent, and a powder; An oil phase part including a surfactant and an oil phase; And an active ingredient moiety comprising genistein methyl ether. In addition, the underwater type cosmetic composition may further include a preservative to enhance the preservability of the cosmetic composition, if necessary.

The water receiving part may include purified water, polyols that help soften and moisturize the skin, and a water-dispersible powder that can improve the feeling of use and improve the feeling of care during application of the skin. Here, the purified water may be mixed in a residual amount in consideration of usability and the like.

The oily portion includes a surfactant, an oil, and the like, and may further include an oil dispersing stimulant and an antioxidant. Examples of the surfactant include a polyethylene oxide emulsifier having a polyethylene oxide (PEG) added thereto, a glyceride fatty acid emulsifier wherein the hydroxy group of the glyceride is substituted with a fatty acid, and a glucose emulsifier But it is not limited thereto.

The active ingredient part may contain 5 wt% of the genistein methyl ether-containing nanoliposome according to the first aspect of the present invention, but is not limited thereto. At this time, for example, it may contain about 25 ppm to about 500 ppm of the genistein methyl ether for 1 Kg of the genistein methyl ether-containing nanoliposome. In one embodiment of the present invention, when the total weight of the genistein methyl ether-containing nanoliposome is 1 Kg, it may exhibit whitening effect even when the genistein methyl ether-containing nanoliposome contains only about 25 ppm of the genistein methyl ether (high efficiency). Wherein the concentration of the genistein methyl ether in the genistein methyl ether-containing nanoliposome ranges from about 25 ppm to about 10,000 ppm, from about 25 ppm to about 5000 ppm, from about 25 ppm to about 1000 ppm, from about 25 ppm to about 500 ppm, About 100 ppm, about 100 ppm, about 25 ppm to about 50 ppm, about 50 ppm to about 10000 ppm, about 100 ppm to about 10000 ppm, about 500 ppm to about 10000 ppm, about 1000 ppm to about 10000 ppm, 10000 ppm, or from about 25 ppm to about 500 ppm.

According to an embodiment of the present invention, there is provided an underwater type cosmetic composition, comprising: mixing an aqueous phase component contained in the upper part of the water and an oil phase component contained in the oil phase part; And then adding the mixture to the mixture with a genistein methyl ether-containing nanoliposome.

At this time, in the step of mixing the water phase component and the oil phase component, a water phase mixture prepared by mixing purified water, polyol, xanthan gum and hyarronic acid is first prepared, heated to a temperature of about 70 ° C to about 80 ° C, (PEG) -100 stearate, glyceryl monostearate, dimethicone, and tocopheryl acetate are mixed and heated to a temperature of about 70 ° C to about 80 ° C to prepare an oily portion, And the upper part are mixed to prepare a mixture. The mixture is then uniformly mixed using a homomixer at about 70 DEG C at a rate of about 6000 rpm to about 7000 rpm for about 6 minutes to about 8 minutes and then slowly cooled to a temperature of about 50 DEG C. [

In the step of adding the genistein methyl ether-containing nanoliposome, the genistein methyl ether-containing nanoliposome is added to the cooled mixture, and the mixture is homogenized in a homomixer at about 50 ° C for about 3 minutes at a rate of about 4000 rpm to about 5000 rpm To about 5 minutes, and then slowly cooled to about 30 DEG C to prepare a cosmetic composition.

Hereinafter, the present invention will be described in more detail with reference to examples and drawings. It is to be understood that both the foregoing description and drawings are for explaining the present invention only in detail. It should be understood that the scope of the present invention is not limited by these embodiments or drawings in accordance with the gist of the present invention, It will be obvious to those who have.

[ Example ]

As used in Tables 1 and 2 below, (DAICEL CHEMICAL, JAPAN), Liquid paraffin / Olive oil (SEOJIN CHEMICAL, KOREA), Ceramide (EVONIK, GERMANY), Cholesterol (DOOSAN, KOREA), Ethanol (KOREA ALCOHOL, KOREA) (CREMER, GERMANY), lecithin (LIPOID, USA), ammonium acryloyldimethylsiloxane (DSM, GERMANY), polysorbate 60 (CRODA, UK), glyceryl citrate / lactate / linoleate / (CLARIANT, SWISS), silica (PTL, KOREA), xanthan gum (AJINOMOTO, JAPAN), phage-100 stearate (CRODA, UK), glyceryl stearate (CRODA, UK) Hydroxypropyl acrylate / sodium acryloyldimethylsiloxane (DSM, GERMANY), hydroxyethyl acrylate / sodium acryloylmethyldimethylsilyl chloride (BASF, GERMANY), capric / caprylic triglyceride (EVONIK, GERMANY), cetanol Taurate copolymer / squalane / polysorbate 60 (SEPPIC, SINGAPORE) (BIOLAND, KOREA), 1,2- hexanediol (SYMMRISE, GERMANY), and phenoxyethanol (YOKKAICHI, JAPAN) was purchased.

Experimental Example 1 : Genistein Whitening activity of methyl ether

To measure the activity of whitening, B16F1 (mouse melanoma: ATCC, USA) cells were used. To determine the degree of inhibition of melanin biosynthesis of the genistein methyl ether, the following experiment was conducted .

First, B16F1 cells were cultured in 10% FBS-DMEM (Dulbeco's modified Eagle's medium; Gibco, USA) and the cell concentration was adjusted to 5.0 × 10 4 cells / ml. The cell lysate was dispensed in 2-ml portions into a 6-well plate, and then cultured in a 5% CO ₂ incubator at 37 ° C for 24 hours. After culturing for 24 hours, the medium was removed, and 1.8 ml of the medium prepared with 0.2 μM α-MSH (Sigma, USA) and 200 μl of the concentration-adjusted sample were mixed and cultured for 72 hours under the same conditions. In the case of the negative control, bacillus without α-MSH was added, and 500 μg / ml of arbutin was used as the positive control. After incubation for 72 hours, trypsin-EDTA solution (Sigma, USA) was washed twice with phosphate buffered saline (1 × PBS (-), Sigma, USA) 200 μl / well, and the cells were separated. This was obtained in a microtube, and after centrifugation, the supernatant was removed to obtain pellets. The obtained pellet was washed again with 1 x PBS (-) twice and dried at 70 캜 for 1 hour. To this was added 10% DMSO (dimethyl sulfoxide; in 1 M NaOH, Sigma, USA) was dissolved in 200 μl of each well, and the solution was dispensed into 96-well plates. The absorbance was measured at 490 nm using a microplate counter (microplate reader (Biorad, USA)). The results are shown in Fig.

Referring to FIG. 2, it can be seen that genistein methyl ether (GME) shows an inhibitory effect on melanin biosynthesis. Especially, at the concentration of 2.5 ㎍ / ㎖, it was confirmed that melanin biosynthesis inhibition effect was higher than 500 ㎍ / ㎖ of arbutin, which is a positive control.

Example : Genistein methyl  Ether-containing Nanoliposome  Produce

The nenoliposome containing the genistein methyl ether was prepared in the composition shown in Table 1.

[Table 1]

<Manufacturing Method>

1. A phase is precisely weighed for base production and weighed in a container and dispersed uniformly in water using an Agi-Mixer (SSC812CA, MATSUSHITA, JAPAN) and heated to 70 ° C to 80 ° C to prepare an A phase .

2. Weigh accurately the C phase on the B phase, mix it uniformly and warm to 70 ~ 80 ℃.

3. Prepare D phase in a separate container at room temperature by uniformly mixing and warming to 50 ° C.

4. B phase and C phase prepared at 70 ° C to 80 ° C are gradually mixed in phase A and dispersed uniformly at 6000 rpm to 7000 rpm for 7 minutes using a homomixer (TK HOMO MARK II, PRIMIX JAPAN) to form an emulsion And cooled to 50 DEG C, the prepared D phase is slowly mixed and homogeneously dispersed at 4000 rpm to 5000 rpm for 5 minutes using a homomixer to form a pre-emulsion and cooled to room temperature.

5. The pre-emulsion formed is passed through the microfluidics (MN250A, MICRONOX KOREA) at a pressure of 1000 bar to 1500 bar for 3 times to form a nanoliposome.

Example : Preparation of Underwater Type Cosmetic Composition

An underwater type cosmetic composition was prepared with the composition shown in Table 2.

[Table 2]

<Manufacturing Method>

1. The A phase is weighed precisely and weighed in a container, and the water phase is uniformly dispersed using an Agi mixer and heated to 70 ° C to 80 ° C to prepare the A phase.

2. Precisely weigh the B phase, disperse the thickener uniformly in the polyol, uniformly mix it in the A phase, and heat it to 70 ℃ ~ 80 ℃.

3. C-phase is weighed precisely in a separate vessel and heated to 70-80 ° C.

4. The prepared C phase was gradually mixed into phases A and B and homogeneously dispersed at 6000 rpm to 7000 rpm for 7 minutes using a homomixer to form an emulsion. After cooling to 50 캜, the prepared D phase was slowly mixed And homogeneously dispersed at 4000 rpm to 5000 rpm for 5 minutes using a homomixer to form an emulsion.

5. The E phase at 50 ° C was slowly mixed into the A-phase, B-phase, C-phase and D-phase in which the emulsion was formed and homogeneously dispersed for 5 minutes at 4000 rpm to 5000 rpm using a homomixer. After further dispersing for an additional 2 minutes, the process is completed.

<Result>

In the present embodiment, when the upper part corresponding to the upper part of water is not used in line dispersion with polyols, physical properties of the emulsion such as foreign matters and viscosity and hardness of the formulation may not properly come out due to agglomeration of the thickening agent. This phenomenon can be confirmed through Example 3 and Comparative Example 10.

In the case of a surfactant, a hydrophilic surfactant, which is a hydrophilic-substituted fatty acid having an HLB value of about 10 to 11, and a glyceryl-type fatty acid surfactant having an HLB value of about 2 to 4, The system was reinforced. In order to improve the stability of emulsions, the combination of hydrophilic surfactant having a relatively high HLB value and a lipophilic surfactant having a low HLB value in the formation of an emulsion of an underwater type makes the packing of the interfacial membrane tight, Height system. However, when the hydrophilic surfactant was used in an amount less than 0.1% by weight (Comparative Example 7), the emulsion was not easily formed and the emulsion was easily separated. When 8% by weight or more of the hydrophilic surfactant was used (Comparative Example 8) The results showed that the emulsion was not only poor in stability but also had a feeling of use that was very poor in feeling. Further, when 2% by weight or more of a glyceryl fatty acid surfactant having an HLB value of about 2 to 4 was used, the emulsification was not performed properly (see FIG. 3).

The HLB value is a numerical value of the degree of hydrophilicity and affinity of the surfactant. The HLB value can be calculated by the following equation, and the lower the HLB value of the surfactant, the more effective it is to lower the interfacial tension.

Equation

(M_w는 친수기의 분자량이고, M_o는 친유기의 분자량임)

(M _w and the molecular weight of the hydrophilic group, M _o is the molecular weight of the chinyugi Im)

In the case of Example 3, it was confirmed that it was clearly dispersed without aggregation and the dispersion time was also shortened. On the other hand, in the case of Comparative Example 10, it can be confirmed that there is a foreign object (see Fig. 4).

&Lt; Comparison with Conventional Whitening Active Ingredient (Arbutin) Using Type Underwater Type Cosmetic Composition >

The viscosity of the cosmetic composition of Example 3 and Comparative Example 11 was measured by using the following apparatus to test the change in physical properties by temperature.

The statistical comparative evaluation was conducted for one day after manufacture, and then the specific points of each temperature were visually evaluated. The evaluation results are shown in Table 3.

[Table 3]

Referring to Table 3, the underwater type cosmetic composition using genistein methyl ester showed excellent stability over time, and the base using arbutin showed poor results in high temperature stability and color change for one month (see Fig. 5 Reference).

&Lt; Comparison with Conventional Vetch (Lecithin) Underwater Type Cosmetic Composition >

For the comparison of the viscosity and the properties of the cosmetic composition of Example 3 and Comparative Example 12, the specific points of temperature for 30 days after the production were visually evaluated, and the results are shown in Table 4.

[Table 4]

&Lt; Potency test of genistein methyl ether using HPLC >

In order to confirm that the genistein methyl ether used in Example 3 was uniformly dispersed, a certain amount of sample was taken out and a comparative analysis with a standard substance was carried out by HPLC (AGILENT 1200, AGILENT JAPAN). The results are shown in Table 5.

[Table 5]

Referring to Table 5, the degree of dispersion of the whitening active ingredient, genistein methyl ether, in the water-based cosmetic composition was 99% to 101% relative to the standard sample.

Experimental Example  2: whitening activity of an underwater type composition Invivo  Test

The composition of the water-in-water type cosmetic composition according to Example 3 (test group) is as shown in Table 5 below, and the concentration of the composition is 25 ppm (the concentration of GME-containing nanoliposome is 500 ppm based on the total composition) . An in-vivo clinical trial was conducted on 24 adult women between the ages of 30 and 50 years. The subjects were self-applied twice a day to artificially induced pigmentation sites. After 2 weeks, 4 weeks, and 4 weeks after application of the sample, device evaluation using Mexameter (MX-18, CK ELECTRONIC GMBH GERMANY) Visual evaluation, safety evaluation, and questionnaire evaluation were conducted.

[Table 6]

First, according to the clinical results, changes in visual evaluation values and changes in values using Mexameter are shown in Tables 7 and 8 and FIGS. 6A, 6B, 7A and 7B, respectively.

[Table 7] Visual evaluation Degree of pigmentation reduction

From 2 weeks after the application of the sample, the whitening effect at a statistically significant level as compared with that of the control group at the site of the test group was visually confirmed by the expert. The p-value is the probability that the test statistic is obtained as a scarcity or extreme value in the hypothesis of truth set by the researcher. The lower the calculated p value, the stronger the evidence to reject the hypothesis from the sample data.

[Table 8] Apparatus evaluation Melanin pigment reduction degree

At 8 weeks after application of the sample, a statistically significant decrease in melanin pigment was observed at the site of test group use compared to the control group site. In addition, tests on the dermatological symptoms that occurred during the test period using the test group samples were conducted in parallel, and the results are shown in Table 9.

[Table 9] Dermatological conditions during the test period

No abnormal symptoms occurred during the test period. As a result, whitening test products using 25 ppm of genistein methyl ether showed a statistically significant whitening improvement effect compared with the control, and it was evaluated as a safe and effective whitening functional product because it did not cause any adverse reaction during the use period.

It will be understood by those of ordinary skill in the art that various changes in form and details may be made therein without departing from the spirit and scope of the present invention as defined by the appended claims and their equivalents. You will understand. It is therefore to be understood that the embodiments described above are illustrative in all aspects and not restrictive. For example, each component described as a single entity may be distributed and implemented, and components described as being distributed may also be implemented in a combined form.

The scope of the present invention is defined by the appended claims rather than the detailed description and all changes or modifications derived from the meaning and scope of the claims and their equivalents are to be construed as being included within the scope of the present invention do.

Claims (19)

A genistein methyl ether-containing nanoliposome, comprising genistein methyl ether and a glyceryl ester.
The method according to claim 1,
Wherein the genistein methyl ether-containing nanoliposome comprises 0.0001% to 50% by weight of the genistein methyl ether.
The method according to claim 1,
Wherein the glyceryl ester comprises an alpha hydroxy acid derivative having both a hydrophilic group and a lipophilic group.
The method according to claim 1,
Wherein the glyceryl ester comprises at least one member selected from the group consisting of glyceryl citrate / lactate / linolate / oleate, glyceryl stearate citrate, and glyceryl cocoate / citrate / lactate. Genistein methyl ether-containing nanoliposome.
The method according to claim 1,
Wherein the glyceryl ester is comprised between 0.5% and 10% by weight.
The method according to claim 1,
Wherein the composition further comprises 50 wt% to 70 wt% of a water phase component, 0.1 wt% to 5 wt% of a surfactant, 0.1 wt% to 20 wt% of an oil, and 8 wt% to 12 wt% Liposome.
The method according to claim 1,
Containing nanoliposome further comprising polyols and ethanol in a 3: 1 ratio.
8. The method of claim 7,
The polyols include at least one selected from the group consisting of glycerin, butylene glycol, propylene glycol, dipropylene glycol, methylpropanediol, isoprene glycol, pentylene glycol and polyethylene glycol &Lt; / RTI &gt; wherein the ninoliposome is a &lt; RTI ID = 0.0 &gt;
The method according to claim 1,
A genistein methyl ether-containing nanoliposome having a size of 110 nm to 180 nm.
Mixing the water phase component and the water phase component to form a first mixture;
Mixing the first mixture with genistein methyl ether to form a second mixture; And
Applying pressure to the second mixture
Containing nanoliposomes. &Lt; RTI ID = 0.0 &gt; 8. &lt; / RTI &gt;
11. The method of claim 10,
Wherein the first mixture comprises from 0.5% to 10% by weight of glyceryl ester, from 50% to 70% by weight of a water phase component, from 0.1% to 5% by weight of a surfactant, from 0.1% to 20% % &Lt; / RTI &gt; to 12% by weight of the composition.
12. The method of claim 11,
Wherein the glyceryl ester comprises an alpha hydroxy acid derivative having both a hydrophilic group and a lipophilic group.
12. The method of claim 11,
Wherein the glyceryl ester comprises at least one member selected from the group consisting of glyceryl citrate / lactate / linolate / oleate, glyceryl stearate citrate, and glyceryl cocoate / citrate / lactate. Containing nanoliposomes.
11. The method of claim 10,
Wherein the first mixture further comprises polyols and ethanol in a ratio of 3: 1. &Lt; RTI ID = 0.0 &gt; 21. &lt; / RTI &gt;
15. The method of claim 14,
The polyols include at least one selected from the group consisting of glycerin, butylene glycol, propylene glycol, dipropylene glycol, methylpropanediol, isoprene glycol, pentylene glycol and polyethylene glycol Containing nanoliposome. &Lt; / RTI &gt;
11. The method of claim 10,
Wherein said genistein methyl ether is mixed in an amount of 0.0001% by weight to 50% by weight.
11. The method of claim 10,
Wherein the step of applying pressure to the second mixture is carried out using a microfluidizer under a pressure of 1000 bar to 1500 bar.
Genistein methyl ether-containing nanoliposome containing genistein methyl ether and glyceryl ester
Wherein the cosmetic composition is a cosmetic composition.
19. The method of claim 18,
Wherein the cosmetic composition is an oil in water type.

Images