JP5177338B2 - L-ascorbic acid glucoside-containing liposome solution - Google Patents

Description

  The present invention relates to a liposome liquid containing L-ascorbic acid glucoside, and more particularly to a cosmetic containing L-ascorbic acid glucoside in the liposome.

  Liposomes are closed vesicles composed of a lipid bilayer membrane and an aqueous layer inside. Liposomes are widely used and studied in the fields of bioscience basics and applications. Liposomes are composed of phospholipids, which are components similar to biological membranes, so that they easily bind to cell membranes and can transport moisture and various medicinal ingredients to the stratum corneum when applied to the skin. In addition, by being encapsulated in liposomes, a medicinal component that is inherently unstable and easily deactivated can be kept stable for a long period of time.

Ascorbic acid and its derivatives are blended in cosmetics as a whitening agent. L-ascorbic acid (hereinafter referred to as “ascorbic acid”) suppresses the production of melanin by suppressing the conversion reaction from dopaquinone, which is a metabolic intermediate in the melanin production process, to dopachrome, It has the action of converting oxidized melanin to colorless reduced melanin, and is effective in the treatment and improvement of skin whitening effects, spots, freckles, melanosis, liver spots and the like. However, since ascorbic acid is a chemically unstable compound, various ascorbic acid derivatives have been developed. In particular, among various ascorbic acid derivatives, L-ascorbic acid glucoside, which is excellent in stability, durability, and blending properties in cosmetics and has a whitening effect, has attracted attention. However, some ascorbic acid derivatives may have slightly poor immediate permeability to the skin, and when used in cosmetics, some types of derivatives may be irritating and may have poor compatibility between the water phase and the oil phase. In addition, there is a demand for cosmetics that are easy to use because coloring may occur over time due to the effects of the ingredients and pH. For example, cosmetics using ascorbic acid glucoside, lecithin and a chelating agent are disclosed (for example, Patent Document 1). Although this cosmetic maintained the durability of L-ascorbic acid glucoside and the problem of coloring over time was improved, satisfactory results were not obtained with respect to immediate penetration. In particular, the border between the sunscreened part that is covered with clothes and swimwear after suntanning and the part that is not covered with sunscreen is very different and stands out, so the development of a post-treatment agent was desired. Conventional whitening agents whiten the sunburned part and the non-tanned part in the same way, so that the boundary remains forever.
JP 2002-265344 A

In order to solve these problems, an external preparation for skin in which ascorbic acids are encapsulated in a lamellar structure composed of a fatty acid monoglyceride is disclosed (for example, Patent Document 2). Furthermore, studies have been made on liposomes containing ascorbic acid and its derivatives. For example, whitening cosmetics in which ascorbic acids are encapsulated in phospholipid liposomes are disclosed (for example, Patent Document 3). Further, a method is disclosed in which ascorbic acids are encapsulated in liposomes in combination with a solubilizing agent such as carbon dioxide gas in a critical or subcritical state and a lower alcohol (for example, Patent Document 4).
JP 2002-145751 A JP-A 56-120612 JP 2003-119120 A

  However, in the thing of patent document 3, when a whitening effect is anticipated locally, such as the boundary of a sunburn, a local specific effect is hard to be obtained, the stability of prescription itself is bad, and there are problems with coloring, odor, etc. For this reason, there are problems such as restrictions on the formulation of cosmetics. Moreover, in the thing of patent document 4, coloring, odor, etc. were strong, and there existed a fault that the mixing | blending prescription of cosmetics was restrict | limited.

  Moreover, when manufacturing liposomes, polyhydric alcohols such as glycerin and organic solvents such as ethanol may be used. However, residual polyhydric alcohols such as glycerin may cause stickiness and are not preferable for use. was there. Moreover, even when a volatile solvent such as ethanol is used, if it remains, there is a problem that it is restricted in terms of formulation.

  The present invention is more excellent in immediate permeability, high whitening effect, excellent in blending characteristics to various compounding agents, hardly colored or smelled over time due to the influence of the compounding agent, and can be used in various compounding forms. -It aims at providing the liposome liquid containing ascorbic-acid glucoside and liposome containing cosmetics.

That is, the present invention is an L-ascorbic acid glucoside-containing liposome solution listed in (1) to (4) below, a whitening cosmetic listed in (5), and an after sun lotion listed in (6).
(1) A liposome solution in which the phosphatidylcholine content in the phospholipid constituting the liposome is 70% by weight or more and 0.1 to 1 part by weight of L-ascorbic acid glucoside is blended with 1 part by weight of phospholipid. The ratio of the phospholipid to the liposome liquid is 0.1 to 20% by weight, the encapsulation rate of L-ascorbic acid glucoside is 50% by weight or more, and the average particle size of the liposome is 100 to 100%. L-ascorbic acid glucoside-containing liposome solution which is 800 nm.
(2) The L-ascorbic acid glucoside-containing liposome solution according to claim 1, wherein the ratio of the unsaturated fatty acid of the acyl group in the phosphatidylcholine in the phospholipid constituting the liposome is 70% or more.
(3) The L-ascorbic acid glucoside-containing liposome solution according to claim 1 or 2, wherein the ratio of the linoleic acid of the acyl group in the phosphatidylcholine in the phospholipid constituting the liposome is 50% or more.
(4) The L-ascorbic acid glucoside-containing liposome solution according to claim 3, wherein the liposome has an average particle size of 100 to 300 nm.
(5) A whitening cosmetic comprising 50% by weight or less of the L-ascorbic acid glucoside-containing liposome solution according to any one of claims 1 to 4.
(6) An after-sun lotion containing 50% by weight or less of the L-ascorbic acid glucoside-containing liposome solution according to any one of claims 1 to 4.

  According to the present invention, the cosmetic contains a liposome complex that encapsulates an ascorbic acid derivative in the liposome, thereby enhancing the whitening effect of the ascorbic acid derivative, and is less likely to cause coloration and odor over time. I will provide a. The present invention blends L-ascorbic acid glucoside with a specific liposome having a high phosphatidylcholine purity of phospholipid and a high unsaturated fatty acid content of phospholipid acyl group, and by controlling the particle size, particularly after sunburn. Since it has good permeability to rough skin, it is more effective to apply to after-sun lotion that does not leave behind a swimsuit after sunburn. The present invention provides a cosmetic that is excellent in light color improvement effects such as pigmentation and stains on the skin after sunburn, freckles, and liver spots, and also has an excellent whitening effect.

  The L-ascorbic acid glucoside encapsulated in the liposome of the present invention is a compound produced by enzymatic reaction of ascorbic acid and glucose with a glycosyltransferase. Specific examples include 2-O-α-D-glucosyl-L-ascorbic acid, which is α-D-glucosyl-L-ascorbic acid, 5-O-α-D-glucosyl-L-ascorbic acid, 6-O. -Α-D-glucosyl-L-ascorbic acid is excellent from the viewpoint of stability, and 2-O-α-D-glucosyl-L-ascorbic acid is particularly preferable.

  The L-ascorbic acid glucoside-containing liposome solution of the present invention can be obtained by mixing a phospholipid and a water-soluble substance encapsulated in the liposome by a known technique. For example, ultrasonic treatment method, French press method, reverse phase evaporation method, surfactant method, extrusion method, Manton Gorin method, calcium-EDTA chelate method, freezing and thawing method, and jetting a dispersion under a pressure of 150 MPa or more The jet flow collides with the wall surface arranged with respect to the injection port and is reversed in the direction substantially opposite to the jet flow direction. The pressurized sample is placed in the chamber under ultra-high pressure, passed through the narrow tube at high speed, and subjected to strong shearing force. Further, the fluid accelerated at the confluence receives a frontal impact and receives a strong impact. A method of obtaining liposomes by receiving strong cavitation due to pressure drop (microfluidizer method), using a vacuum emulsifier How to obtain the beam can be selected according to the purpose from a method of obtaining a liposome, or the like using a high pressure homomixer.

  The phospholipid constituting the liposome of the present invention is a compound having two or more hydrophobic groups composed of a phosphate group and an acyl group and / or an alkyl group in the molecule, such as phosphatidylcholine (PC), phosphatidylethanolamine (PE). ), Phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylglycerol (PG), phosphatidic acid (PA), sphingomyelin (SPM), cardiolipin, and mixtures thereof, soy lecithin, corn lecithin, cottonseed oil lecithin, egg yolk Natural lecithins such as lecithin and hydrogenated soybean lecithin, hydrogenated egg yolk lecithin, phospholipid derivatives in which polyethylene glycol or aminoglycan is introduced into these phospholipids, etc., of which one or more are mixed Used Te.

  Here, by setting the phosphatidylcholine content in the phospholipids constituting the liposome to 70% or more, the L-ascorbic acid glucoside-containing liposome can be stably prepared, and by imparting immediate permeability, the ascorbic acid glucoside has It is possible to further enhance the whitening effect. In addition, it is extremely useful industrially in that coloring and odor over time can be suppressed and it can be widely used as a cosmetic material. When the phosphatidylcholine content in the phospholipid constituting the liposome is less than 70%, there are problems such as coloring and odor, and the stability of the liposome is deteriorated.

  From the said viewpoint of this invention, it is still more preferable that the phosphatidylcholine content in the phospholipid which comprises a liposome shall be 75% or more.

  The acyl group constituting the phosphatidylcholine in the phospholipid is preferably an acyl group composed of a residue of an unsaturated fatty acid having 8 to 22 carbon atoms, such as 2-lauroleic acid, Linderic acid, succinic acid, and 5-laurolenic acid. , 11-lauroleic acid, tuzuic acid, 5-myristoleic acid, myristoleic acid, 2-palmitoleic acid, 7-palmitoleic acid, cis-9-palmitoleic acid, trans-9-palmitoleic acid, petroceric acid, petrocereidine Acid, cis-7-octadecenoic acid, trans-7-octadecenoic acid, cis-8-octadecenoic acid, trans-8-octadecenoic acid, oleic acid, elaidic acid, basenic acid, gondoic acid, trans-gondoic acid, erucic acid, Brassic acid, linoleic acid, linoelaidic acid, α-eleostearic acid, β-eleostearic acid, linolenic acid, linolenic elaidic acid, Psoi Examples include acyl groups derived from linear unsaturated carboxylic acids such as doereostearic acid, α-parinaric acid, β-parinaric acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, preferably linoleic acid, oleic acid, linolenic acid , An acyl group derived from eicosapentaenoic acid and docosahexaenoic acid.

  In particular, when the unsaturated fatty acid content in the acyl group is 70% by weight or more, the whitening effect of L-ascorbic acid glucoside can be further enhanced. Further, when the linoleic acid content is 50% by weight or more, the whitening effect of L-ascorbic acid glucoside can be further enhanced even when the unsaturated fatty acid content is less than 70% by weight. Particularly preferably, the unsaturated fatty acid content in the acyl group is 70% by weight or more, and the linoleic acid content is 50% by weight or more.

  The proportion of phospholipid in the L-ascorbic acid glucoside-containing liposome solution of the present invention is preferably 0.1 to 20% by weight, and the blending ratio of phospholipid and L-ascorbic acid glucoside is a whitening effect or From the viewpoint of stability during storage and the like, 0.1 to 1 part by weight of L-ascorbic acid glucoside is preferable with respect to 1 part by weight of phospholipid. If the amount of L-ascorbic acid glucoside is less than 0.1 part by weight relative to 1 part by weight of the phospholipid, the whitening effect is not sufficient, and if it exceeds 1 part by weight, preparation of the liposome becomes difficult.

  The average particle size of the liposome of the present invention is preferably 100 to 800 nm, more preferably 100 to 300 nm. When the average particle size is smaller than 100 nm, L-ascorbic acid glucoside cannot be sufficiently contained in the liposome, and the whitening effect of the liposome cannot be sufficiently obtained. When the average particle size is larger than 800 nm, the absorption rate from the skin is deteriorated. The whitening effect cannot be obtained sufficiently. Liposomes are prone to phase separation and aggregation, and become unstable during storage or skin retention.

  The mixing ratio of L-ascorbic acid glucoside in the liposome of the present invention is preferably 0.1 to 1 part by weight with respect to 1 part by weight of phospholipid, and the L-ascorbic acid glucoside compounded at this time is encapsulated in the liposome. The encapsulation rate is desirably 50% by weight or more. The encapsulation rate here means the ratio of L-ascorbic acid glucoside encapsulated in the liposome with respect to the total amount of L-ascorbic acid glucoside contained in the liposome liquid. For example, when 0.6 part by weight of L-ascorbic acid glucoside is blended with 1 part by weight of phospholipid, 0.3 part by weight or more of L-ascorbic acid glucoside out of 0.6 part by weight of L-ascorbic acid glucoside. It is desirable that the glucoside is encapsulated in the liposome. This encapsulation rate was determined by separating and removing L-ascorbic acid glucoside that was not encapsulated in liposomes using a gel filtration column, adding methanol, chloroform and water, and adding phospholipid to chloroform and L-ascorbic acid glucoside to methanol. It can be obtained by extracting into a water mixture and performing quantification. Moreover, L-ascorbic acid glucoside can be quantified by HPLC method (UV detection wavelength 240 nm) using a reverse phase column. If the encapsulation rate of L-ascorbic acid glucoside in the liposome is less than 50% by weight or more, the whitening effect on the tanned skin is diminished, and the boundary between the tanned part and the non-tanned part becomes difficult to disappear.

  The phosphatidylcholine content in the phospholipid constituting the liposome of the present invention is 70% or more, and the production process is performed even when two or more phospholipids are mixed by producing at a temperature higher than the phase transition temperature of the phospholipid. Can obtain a uniform and stable liposome without using an organic solvent. Therefore, the organic solvent removal step is unnecessary and industrially very advantageous. Moreover, since the manufactured liposome does not contain an extra compound such as an organic solvent, the degree of freedom of compounding is large. The liposome of the present invention comprises (A) a step of adding 80 to 99.9% by weight of water to 0.1 to 20% by weight of phospholipid and emulsifying at a temperature equal to or higher than the phase transition temperature of phospholipid, (B) L -It can manufacture from the process of mixing the ascorbic-acid glucoside aqueous solution and the emulsion obtained by (A).

  Cosmetics can be prepared by mixing the liposome of the present invention with an existing preparation. As a method of inclusion, they may be mixed at the final stage of the preparation, or may be mixed during the preparation, for example, when an aqueous phase is added. As the mixing conditions, the conditions for producing ordinary cosmetics can be applied as they are. The liposome encapsulating L-ascorbic acid glucoside in the liposome according to the present invention can be stably maintained even when mixed with an existing preparation, and the stability of L-ascorbic acid glucoside is not impaired.

  In addition, in cosmetics containing the liposome liquid of the present invention, alcohols, aqueous bases, oily bases, surfactants, pigments, dyes, pH adjusters, preservatives are commonly used additives for cosmetics. In addition, a bactericidal agent, a chelating agent, an antioxidant, an ultraviolet absorber, natural extracts derived from animals and plants, fragrances, inorganic salts and the like can be blended within a range that does not impair the performance of the present invention.

  The cosmetic dosage form to which the present liposome liquid can be incorporated in the present invention is a dosage form usually used for pharmaceuticals, quasi drugs and cosmetics, that is, the dosage form is in the form of liquid, gel, paste, cream, etc. It is applicable to.

  Furthermore, the present liposome solution can be applied to a powdery or solid form by mixing after removing water by known means such as freeze-drying and spray-drying, and is not particularly limited to these forms. Absent. Thus, the present invention also provides a powder obtained by drying the liposome liquid according to any one of claims 1 to 4. In this powder, the phosphatidylcholine content in the phospholipid constituting the liposome is 70% by weight or more, and 0.1 to 1 part by weight of L-ascorbic acid glucoside is blended with respect to 1 part by weight of the phospholipid. The average particle size of the liposome is 100 to 800 nm. Preferably, the ratio of the unsaturated fatty acid of the acyl group in the phosphatidylcholine in the phospholipid constituting the liposome is 70% or more, and / or the linoleic acid of the acyl group in the phosphatidylcholine in the phospholipid constituting the liposome The ratio is 50% or more, and / or the average particle size of the liposome is 100 to 300 nm.

  The present invention includes L-ascorbic acid glucoside in a specific liposome formulation having a high phosphatidylcholine purity of phospholipids and a high unsaturated fatty acid content of phospholipid acyl groups, and further controlling the particle size, thereby tanning in particular. Since it is a liposome formulation that has good penetration into rough skin afterwards and is not tanned or difficult to penetrate into rough skin, it can be applied to after-sun lotions that do not leave behind after sunburn. Is more effective. According to the present invention, it is possible to provide a cosmetic that is excellent in light color improvement effects such as pigmentation and stains on the skin after sunburn, freckles, and liver spots, and also has an excellent whitening effect.

Hereinafter, the present invention will be described in more detail based on examples.
Example 1
[Preparation of liposome containing L-ascorbic acid glucoside]
84.9 g of purified water and 10 g of unhydrogenated soybean lecithin (COATSOME NC-20, manufactured by NOF Corporation) (phosphatidylcholine purity 92.6%, unsaturated acyl group content 80.5%, of which linoleate acyl group 65.2%, see Table 1 for details of fatty acid composition), 5 g of L-ascorbic acid glucoside (2-O-α-D-glucosyl-L-ascorbic acid), 0.1 g of dl-α-tocopherol Using a Polytron (manufactured by Kinematica, rotor-stator type homogenizer), the mixture was stirred at room temperature for 10 minutes at 20,000 rpm to prepare a lipid-containing crude dispersion. This lipid-containing crude dispersion was subjected to micronization treatment 5 times at a pressure of 10,000 psi using DeBEE2000 (manufactured by BEE International Co., Ltd., ultra-high pressure emulsification dispersion crusher) to give L-ascorbic acid glucoside-encapsulated liposomes (particle size: 183 nm). Obtained. At this time, the encapsulation rate of L-ascorbic acid glucoside in the liposome encapsulating L-ascorbic acid glucoside was measured by gel filtration. As a result, the encapsulation rate of L-ascorbic acid glucoside in the liposome encapsulating L-ascorbic acid glucoside was measured. Was 80%.

  Here, a method for measuring the encapsulation rate will be described. The liposome complex was subjected to gel filtration through a gel filtration column (carrier: Pharmacia, Sephadex G50; column diameter 16 mm; column height 300 mm), and the eluate was fractionated (2.5 mL / fraction). 0.8 mL was collected from each fraction, 2 mL of methanol was added and stirred, then 1 mL of chloroform was added and stirred, and the whole was once dissolved transparently. Chloroform (3500 rpm, 10 minutes) was added to 1 mL of chloroform and stirred, 1.2 mL of distilled water was further added thereto, and the mixture was stirred and cooled with a cooling centrifuge (model KR-702 manufactured by Kubota Corporation). Room temperature), and the amount of L-ascorbic acid glucoside recovered in the separated upper two layers (water and methanol phase) was measured by high performance liquid chromatography (column: Wako Pure Chemical Industries, Wakosik-II 5C18 HG 4.6 mm × 250 nm, column temperature: 35 ° C., mobile phase: 0.02 M potassium dihydrogen phosphate (2.722 g / L) -water (pH 2.0), flow rate: 1.0 mL / min).

(Example 2)
[Preparation of liposome containing L-ascorbic acid glucoside]
Hydrogenated soybean lecithin (manufactured by NOF Corporation, COATSOME NC-61) 10 g (phosphatidylcholine purity 75.3%, no unsaturated acyl group, no linoleate acyl group, see Table 2 for details of fatty acid composition) The liposomes were prepared in the same manner as in Example 1 (particle size: 220 nm). At this time, the encapsulation rate of L-ascorbic acid glucoside in the liposome encapsulating L-ascorbic acid glucoside was measured by gel filtration. As a result, the encapsulation rate of L-ascorbic acid glucoside in the liposome encapsulating L-ascorbic acid glucoside was measured. Was 75%.

(Example 3)
[Preparation of liposome containing L-ascorbic acid glucoside]
Hydrogenated soybean lecithin (Nippon Yushi Co., Ltd., COATSOME NC-21) 10 g (phosphatidylcholine purity 95.1%, no unsaturated acyl group, no linoleic acid acyl group) in diethyl ether / ethanol mixed solution (9/1, v / v) After adding 1000 ml and dissolving, 200 ml of water was added, stirred with a magnetic stirrer, and then subjected to ultrasonic treatment with a sonicator for 30 minutes. Thereafter, diethyl ether and ethanol were distilled off with a rotary evaporator, and after adjusting the concentration, the mixture was filtered through a polycarbonate filter (pore size 0.6 μm) to prepare liposomes (particle size 504 nm). At this time, the encapsulation rate of L-ascorbic acid glucoside in the liposome encapsulating L-ascorbic acid glucoside was measured by gel filtration. As a result, the encapsulation rate of L-ascorbic acid glucoside in the liposome encapsulating L-ascorbic acid glucoside was measured. Was 78%.

(Comparative Example 1)
5 g of L-ascorbic acid glucoside (2-O-α-D-glucosyl-L-ascorbic acid) was added to 95 g of purified water, and the mixture was stirred and dissolved with a magnetic stirrer.

(Comparative Example 2)
[Preparation of L-ascorbic acid glucoside-encapsulating liposome complex]
79.9 g of purified water, 10 g of hydrogenated soybean lecithin (manufactured by NOF Corporation, COATSOME NC-21) (phosphatidylcholine purity 95.1%, no unsaturated acyl group, no linoleic acid acyl group), dl-α-tocopherol 0.1 g was added, and the mixture was stirred for 10 minutes at room temperature using a Polytron (manufactured by Kinematica, rotor-stator type homogenizer) at a rotation speed of 20,000 rpm to prepare a lipid-containing coarse dispersion. This lipid-containing crude dispersion is subjected to microparticulation treatment 5 times at a pressure of 10,000 psi using DeBEE2000 (manufactured by BEE International Co., Ltd.) to obtain empty liposomes that do not contain L-ascorbic acid glucoside. It was. Thereto, 5 g of L-ascorbic acid glucoside (2-O-α-D-glucosyl-L-ascorbic acid) was added and stirred with a magnetic stirrer for 30 minutes. The particle size of the liposome at this time was 247 nm. Further, the encapsulation rate of L-ascorbic acid glucoside in the liposome was 1% as a result of measurement by gel filtration.

(Comparative Example 3)
[Preparation of L-ascorbic acid glucoside-encapsulating liposome complex]
79.9 g of purified water, 10 g of hydrogenated soybean lecithin (manufactured by Nikko Chemicals, Resinol S-10) (phosphatidylcholine purity 31.8%, no unsaturated acyl group, no linoleic acid acyl group), L-ascorbic acid glucoside (2- 5 g of O-α-D-glucosyl-L-ascorbic acid) and 0.1 g of dl-α-tocopherol were added, and using a polytron (manufactured by Kinematica, rotor-stator homogenizer) at a rotation speed of 20,000 rpm for 10 minutes at room temperature. Stirring to prepare a lipid-containing crude dispersion. This lipid-containing crude dispersion was subjected to micronization treatment at a pressure of 10,000 psi with DeBEE2000 (produced by BEE International Co., Ltd., ultra-high pressure emulsification dispersion crusher) to give L-ascorbic acid glucoside-encapsulated liposomes (particle size: 161 nm). Obtained. At this time, the encapsulation rate of L-ascorbic acid glucoside in the liposome encapsulating L-ascorbic acid glucoside was measured by gel filtration. As a result, the encapsulation rate of L-ascorbic acid glucoside in the liposome encapsulating L-ascorbic acid glucoside was measured. Was 68%.

(Comparative Example 4)
[Preparation of L-ascorbic acid glucoside-encapsulating liposome complex]
79.9 g of purified water and 10 g of unhydrogenated soybean lecithin (manufactured by NOF Corporation, COATSOME NC-20) (phosphatidylcholine purity 92.6%, unsaturated acyl group content 80.5%, of which linoleate acyl group 65.2%), 5 g of L-ascorbic acid glucoside (2-O-α-D-glucosyl-L-ascorbic acid) and 0.1 g of dl-α-tocopherol were added, and Polytron (manufactured by Kinematica, rotor-stator type) The mixture was stirred at room temperature for 10 minutes using a homogenizer to prepare a lipid-containing crude dispersion (particle size: 604 nm). At this time, the encapsulation rate of L-ascorbic acid glucoside in the liposome encapsulating L-ascorbic acid glucoside was measured by gel filtration. As a result, the encapsulation rate of L-ascorbic acid glucoside in the liposome encapsulating L-ascorbic acid glucoside was measured. Was 16%.

(Examples 1-3 and Comparative Examples 1-4)
(Evaluation of cosmetics)
Using the L-ascorbic acid glucoside-containing liposome dispersion liquid obtained in the above Examples and Comparative Examples, cosmetics as skin lotions shown in Table 3 were prepared. The preparation method used a propeller mixer. However, four components shown in Table 3 were used as additive components as common additive components.
(1) Inhibition of melanin production using guinea pigs in brown guinea pigs
The melanin production inhibitory effect in vivo was evaluated. That is, the back of a brown guinea pig was shaved, covered with an ultraviolet shielding plate having a rectangular hole of 5 × 10 cm, and irradiated with ultraviolet rays (0.5 J / cm ² ). After the pigmentation was formed, 50 μL of the cosmetic material shown in Table 1 was applied twice a day. Then, the degree of blackening before application and after 20 days and 40 days after application was measured with a color difference meter (manufactured by Minolta, spectrocolorimeter CM-2600d). The results are shown in Table 3.

(2) Whitening effect 20 females (25 to 40 years old) are panelists and use the cosmetics shown in Table 3 twice a day for two months each day, followed by “spots” and “sobacas” on the skin. The degree of improvement was determined with the naked eye as follows, the average value of 20 people was obtained, and an average value of 7 or more was evaluated as a skin external preparation with a high whitening effect. The results are shown in Table 3.
10 points: When clearly determined to be effective.
5 points: When judged to have some effect.
0 point: When it is judged that there is no effect at all.

20 women (25 to 40 years old) are panelists, apply adhesive bandages to the upper arm of their right arm, sunbathe on the summer beach for 4 hours, peel off the adhesive bandages, and take up the morning twice a day for 5 days. 3 cosmetics were applied to the peeled part of the bandage. The degree of improvement after sunburn was determined with the naked eye as follows for the wrinkled part of the peeled part of the adhesive bandage.
○: After sunburn is inconspicuous ×: After sunburn remains

(3) Stability over time (degree of coloring)
The cosmetic was sealed in a transparent glass container and stored at 0 ° C., 25 ° C. and 40 ° C. for 3 months. The appearance was observed and evaluated in the following three stages. The results are shown in Table 4.
○: Good stability (no change in appearance at any temperature)
Δ: Slightly inferior (slightly colored at any temperature)
X: Stability failure (coloring occurs at any temperature)

(4) Stability over time (odor)
The cosmetic is sealed in a transparent glass container and stored at 0 ° C, 25 ° C and 40 ° C for 3 months, and its odor is evaluated in two stages as shown below with 20 women (25 to 40 years old) as panelists. did. The results are shown in Table 3.
○: Fewer than 4 panelists out of 20 felt that the smell was strong.
X: More than 5 panelists out of 20 felt that the smell was strong.

(5) Stability over time (degree of precipitation)
The cosmetic was sealed in a transparent glass container and stored at 0 ° C., 25 ° C. and 40 ° C. for 3 months. The appearance was observed and evaluated in the following two stages. The results are shown in Table 4.
○: Good stability (no change in appearance at any temperature)
X: Stability failure (at any temperature, causing precipitation or separation)

Note 1: 2-O-α-D-glucosyl-L-ascorbic acid (manufactured by Hayashibara Biochemical Research Institute)
Note 2; ΔL *: L * value (brightness) of a color difference meter, where 0 is before irradiation and the difference from L ^* value after UV irradiation is blackness. That is, the lower the value, the higher the degree of blackening.

  From Tables 3 and 4, it can be seen that the cosmetics (Examples 1 to 3), which are the skin lotions of the present invention, markedly suppress melanin production in brown guinea pigs as compared with Comparative Examples 1 to 4, both of which are whitening. The effect was excellent and the stability over time was also excellent. On the other hand, in Comparative Examples 1-4, sufficient performance is not obtained in all of these effects. That is, in Comparative Examples 1 to 4, L-ascorbic acid glucoside is blended in a specific liposome formulation having high phosphatidylcholine purity of phospholipid and high unsaturated fatty acid content of acyl group of phospholipid, and further controlling the particle size. Therefore, sufficient performance satisfying both the whitening effect and the temporal stability is not obtained.

Example 4
(Emollient cream)
(Prescription)
Oil phase wt%
Polyoxyethylene monostearate 40 2.0
Self-emulsifying glyceryl monostearate 5.0
Stearic acid 2.0
Cetanol 2.0
Squalane 12.0
Macadamia nut oil 4.0
Methylpolysiloxane 0.2
Preservative Appropriate amount of water phase 1,3-butanediol 7.0
Purified water Residual liposomes Example 3 liposomes 50.0

(Preparation method)
Both the oil phase and the aqueous phase are dissolved by heating at 80 ° C., and the aqueous phase is gradually added to the oil phase while stirring to emulsify. Furthermore, stirring was continued and the mixture was cooled, liposomes were added at 40 ° C. or lower, and further stirred to mix uniformly.

(Example 5)
Latex (prescription)
Oil phase wt%
Polyoxyethylene 20 sorbitan monostearate 1.0
Tetraoleic acid polyoxyethylene 40 sorbitol 0.5
Sorbitan monostearate 1.0
Stearic acid 0.5
Behenyl alcohol 0.5
Beeslow 0.5
Squalane 10.0
Glyceryl triisooctanoate 10.0
Decaoleic acid decaglyceryl 3.0
1,3-butanediol 7.0
Preservative Appropriate amount of water phase Xanthan gum 0.04
Triethanolamine 0.05
Purified water Residual liposomes Example 3 liposomes 50.0
(Preparation method)
Prepared according to the method of Example 4.

  About these Examples 4-5, the test of (1) melanin production inhibitory effect using a guinea pig and (2) whitening effect was done like Examples 1-3. The test results are shown in Table 5.

As can be seen from the results in Table 5, in Example 4 and Example 5, melanin production in brown guinea pigs was remarkably suppressed, and both were excellent in whitening effect.

Claims (4)

L-ascorbic acid glucoside-containing liposome in which the phosphatidylcholine content in the phospholipid constituting the liposome is 70% by weight or more and 0.1 to 1 part by weight of L-ascorbic acid glucoside is blended with 1 part by weight of phospholipid The ratio of the phospholipid to the liposome liquid is 0.1 to 20% by weight, the encapsulation rate of L-ascorbic acid glucoside is 50% by weight or more, and the average particle size of the liposomes L-ascorbic acid glucoside-containing liposome solution , wherein the ratio of unsaturated fatty acid in the acyl group in phosphatidylcholine in the phospholipid constituting the liposome is 70% or more, and the liposome In the acyl group of phosphatidylcholine in phospholipids And the proportion of 50% or more, and does not include the polyhydric alcohol and ethanol, L- ascorbic acid glucoside-containing liposome solution. The L-ascorbic acid glucoside-containing liposome solution according to claim 1 , wherein the liposome has an average particle size of 100 to 300 nm. A whitening cosmetic comprising 50% by weight or less of the L-ascorbic acid glucoside-containing liposome solution according to claim 1 or 2 . An after-sun lotion containing 50% by weight or less of the L-ascorbic acid glucoside-containing liposome solution according to claim 1 or 2 .