JPH08310938A - Topical skin - Google Patents

Abstract

(57) [Summary] [Structure] An extract and / or a treated product thereof extracted from a milk fat globule membrane using a solvent consisting of a lower alcohol and water and / or a low polar solvent immiscible with water, and / or a treated product thereof is an active ingredient. External preparation for skin. [Effect] It is possible to obtain a safe external preparation for skin having excellent moisturizing property, high antioxidative property.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an external preparation for skin, more specifically, an extract of milk fat globule film as an active ingredient, which is excellent in moisturizing skin, emollient (softening) and antioxidation. The present invention relates to an extremely safe external preparation for the skin, which has the above effect and is derived from a natural product.

[0002]

2. Description of the Related Art With the progress of modern science such as synthetic chemistry, new materials have been developed, and functional materials and composite materials have been actively developed also in the fields of cosmetics and pharmaceuticals. Emollients and moisturizers developed by research on human dermatology are also positioned as one of them, and many raw materials have been commercialized so far. These internal emollients are transepidermal water loss (TWL)
It is used for the purpose of preventing oil, oils and fats such as olive oil, corn oil, coconut oil, beef tallow, mink oil, and the like, and hydrocarbon compounds such as petrolatum, liquid paraffin and squalane have been used. However, the effect was low when used in a small amount, and a sufficient effect was not obtained. In order to obtain a sufficient effect, the amount used must be increased, and as a result, discomfort such as stickiness cannot be avoided.

As a moisturizer, conventionally, natural polysaccharides such as hyaluronic acid, chondroitin sulfate, chitin, chitosan,
For synthetic polymer compounds such as pullulan, xanthan gum, and polysaccharides obtained from seaweed, carboxyvinyl polymer, sodium pyrrolidonecarboxylate (PCA soda), polyvinylpyrrolidone, polyvinyl alcohol, etc. are used. It was a matter of immediate and aging. Also, polyhydric alcohol glycerin, 1,3
-Butylene glycol, propylene glycol, etc. were used, and some effects were observed, but the moisturizing ability of itself was low, and sufficient moisturizing effect was not obtained when used in a small amount. Therefore, in order to obtain a sufficient effect, it is necessary to increase the amount used, and the adverse effects such as stickiness like fats and oils and hydrocarbon compounds have been recognized.

[0004] Glycolipids and phospholipids have been found to have a moisturizing effect by themselves, but they have not yet reached a sufficient effect.

On the other hand, regarding the milk fat globule coating, a bath agent containing a milk fat globule coating or buttermilk containing the same (JP-A-3-206027), and a milk fat globule coating are mixed with various HLB-valued oil layer components. There are known emulsion compositions (Japanese Patent Application Laid-Open No. 3-275611) that do not use the milk fat globule membrane extract according to the present invention, but use the milk fat globule membrane itself as an emulsifier. I'm just there.

In addition, buttermilk contains phospholipids of 50 to 75% by weight and gangliosides of at most 5% by weight.
A cosmetic or dermatological pharmaceutical composition containing a vesicle prepared from a complex lipid consisting of 50 to 25% by weight of the above glycolipid is known (JP-A-6-16536). However, this complex lipid is only disclosed to be useful for the production of vesicles of high quality, and the extraction solvent is completely different from the milk fat globule membrane extract of the present invention, and therefore the extract The composition is different, and there is no suggestion about the effect such as the moisturizing effect on the skin.

[0007]

DISCLOSURE OF THE INVENTION In view of the fact that the conventional external preparations for skin as described above cannot exert sufficient effects, the present invention can sufficiently exhibit moisturizing properties even when used in a small amount, and the skin The purpose of the present invention is to develop a novel external preparation for skin which is not sticky when applied and has an antioxidant property and is highly safe.

[0008]

The present invention has been made in order to achieve the above-mentioned object, and pays attention to milk from the viewpoint of safety, and a milk fat globule membrane extract and / or a processed product thereof. It has been completed as a result of obtaining new knowledge that it has an excellent effect and further researching on the basis of this new knowledge.

The active ingredient of the external preparation for skin according to the present invention is an extract of milk fat globule membrane. As the milk fat globule film as a raw material of the active ingredient, besides milk, dairy products containing a milk fat globule film can be used as they are or produced separately from them, for example, full-fat milk, buttermilk. Milk products containing milk fat globule membranes such as butter serum, whey protein concentrate and the like are preferably used.

In order to efficiently extract the extract of the present invention from the milk fat globule membrane, a mixed solvent of lower alcohol and water and / or a low polar solvent which is not further mixed with water is selected and used. At that time, the mixing ratio of the lower alcohol and water is usually 97: 3 to 70:30, preferably 95: 3.
5 to 75:25, more preferably 90:10 to 80: 2
0. Furthermore, when this mixed solvent and a low polar solvent which is immiscible with water are added, the mixing ratio of the mixed solvent and the low polar solvent is usually 90:10 to 50:50, preferably 8
0: 20-60: 40, more preferably 75: 25-6
It is good to set it to 5:35.

As the lower alcohol, methanol, ethanol, propanol and butanol are used in an appropriate combination. As low-polarity solvents, low-polarity solvents that are immiscible with water are widely used, including pentane, hexane, heptane,
Saturated hydrocarbons such as octane, nonane and decane; unsaturated hydrocarbons such as hexene and heptene are used alone or in combination of two or more.

In the external preparation for skin of the present invention, an extract obtained from a milk fat globule film with the above mixed solvent and / or a treated product thereof is used as an active ingredient. The extraction treatment is carried out by adding a mixed solvent to the milk fat globule membrane and stirring at 1 to 40 ° C., preferably at room temperature, if necessary. The amount of the mixed solvent to be used is not particularly limited, but as a tentative guideline, the mixed solvent is 1 to 20 times, preferably 5 to 10 parts, per 1 part of the milk fat globule film (powdered). Good.

The present invention is characterized in that it uses a mixed solvent of a specific combination of solvents having various polarities. The extract obtained as described above contains various polar lipids and minerals derived from milk. Also, it contains a non-protein nitrogen compound (NPN) in a well-balanced manner, and exhibits the excellent effect aimed at by the present invention.

As the polar lipid, phosphatidylethanolamine (PE), phosphatidylcholine (PC),
In addition to phospholipids such as sphingomyelin (SM), glycolipids such as glucosylceramide (Glu-Cer), lactosylceramide (Lac-Cer) and gangliosides are included. Minerals include calcium, magnesium, sodium, potassium and other minerals. Further, as the non-protein nitrogen compound (NPN),
Amino acids, peptides and nucleic acids are included.

In the external preparation for skin according to the present invention, the above-mentioned milk fat globule membrane extract can be used as an active ingredient as it is, or a treated product of the extract can be used as an active ingredient. As the processed product, a concentrate, a paste, a dried product and / or a diluted product of the extract are widely used.

For example, the extract is vacuum (freeze) dried as it is, or concentrated under reduced pressure and then vacuum (freeze) dried,
Alternatively, the treated product can be produced by concentrating under reduced pressure, adding acetone, collecting the formed precipitate, and vacuum (freezing) drying. Alternatively, after the extract is loaded onto the column, a low-polarity solvent such as hexane is passed through to collect the solvent-eluted fraction, which is concentrated under reduced pressure and then vacuum (freeze) dried. The treated product may be produced by a purification method. still,
As a processed product, without performing the final drying step,
It is also possible to stop the operation in each of the above-mentioned steps in the process up to that point and select and use one having a shape and a concentrate according to the purpose.

The external preparation for skin according to the present invention includes not only cosmetics but also quasi-drugs and pharmaceuticals for skin application, and the extract for milk fat globule membrane and / or its treated product is used as an active ingredient for external skin application. 0.05 to 10% by weight, preferably 0.1 to 5% by weight (as dry weight) of the agent, and formulated into a fluid form such as solid, semi-solid or liquid according to a conventional method. Good.

The external preparation for skin according to the present invention includes various optional ingredients (oil, moisturizer, thickener, preservative, antioxidant, emulsifier) used in ordinary cosmetics, quasi drugs, pharmaceuticals and the like. , Chelating agents, pigments, pH adjusters, medicinal components, ultraviolet absorbers, and fragrances) can be appropriately mixed, and the external preparation for skin according to the present invention can be produced according to a conventional method. In particular, when vitamin E is blended as an antioxidant, it exerts a synergistic effect with the milk fat globule membrane extract, which is the active ingredient according to the present invention, and / or a treated product thereof, and the antioxidant effect can be enhanced.

Further, the dosage form of the external preparation for skin according to the present invention is not particularly limited as long as it is acceptable as a skin application agent, and examples thereof include cream, emulsion, foundation, pack, lotion, essence, ointment. , Gel, powder, lip balm, lipstick, sun care, bath salt, shampoo, conditioner, etc., which can be arbitrarily selected according to the purpose, whitening, anti-inflammatory, anti-oxidation, moderate moisture absorption, moisturizing, etc. The necessary amount of the external preparation for skin may be applied appropriately times.

The present invention will be specifically described below with reference to examples, but the present invention is not limited thereto.

[0021]

Example 1 Production of Active Ingredient (1): 100 g of Batase rum powder (product of Coleman, Belgium), hexane-ethanol-water (30: 62: 8) mixed solvent 7
00 ml was added, and the mixture was extracted with stirring for 3 hours. (1) The extract was suction filtered, the filtrate was concentrated under reduced pressure, and then vacuum dried to obtain 23.8 g of a dried product (Product I of the present invention). (2) 5 times with respect to the liquid extracted in the same manner and concentrated under reduced pressure.
A double (w / v) amount of acetone was added to collect the formed precipitate, which was vacuum-dried to give 1 (1) of the dried product (product II of the present invention).
Obtained 1.4 g. (3) Silicic acid suspended in hexane after activation according to a conventional method (Wakogel C-200 manufactured by Wako Pure Chemical Industries, Ltd.)
1 L was packed in a glass column having a diameter of 12 cm and a length of 33 cm. On the other hand, the product I of the present invention obtained above was suspended in hexane, and the obtained suspension was loaded on a column.
Hexane (5 L) was passed through the column at a flow rate of / h, and the hexane-eluted fraction was concentrated under reduced pressure and then dried in a vacuum to obtain 7.0 g of a dried product (Product III of the present invention).

The phospholipid content of each sample was as shown in Table 1 below.

[0023]

[Table 1]

[0024]

[Example 2: Moisture retention test (1)] The product II of the present invention produced in Example 1 was subjected to a "moisture retention test for the effect of dry skin" by a high frequency impedance meter (manufactured by IBS). I did. (Method) The moisturizing ability of the product II of the present invention to acetone-ether-treated human dry skin was examined by changing the conductance value. A 10% solution of the product II of the present invention dissolved in squalane was used as a sample. Squalane was used as a control. Two circular compartments with a diameter of about 2 cm were set inside the forearm of the test subject, and each compartment had about 5 ml of acetone / ether.
Was soaked for 20 minutes. Two kinds of samples (the present invention product II and squalane) were allocated to each compartment, and the samples were applied twice a day (morning and night) from one day to seven days later. Before and after acetone / ether treatment 1,2,
After 4 and 7 days, the conductance value of each section was measured (measurement conditions: measurement nitrogen temperature 20 ° C., humidity 60%, number of measurements N = 5).

(Results) The results obtained (actually measured values of 5 measurements) are shown in FIG. As is clear from this result, after one day of the acetone / ether treatment, a sharp decrease in the conductance value was observed at the treated site. Two days after the acetone / ether treatment (one day after coating the sample), the product II of the present invention
The conductance value was observed to increase with time in the application site of the above, but no increase in conductance value was observed in the control squalane application site even one day after application of the sample. After that, it was confirmed that the conductance values of both sections increased with time, and that the product II of the present invention recovered to the normal conductance value before the acetone / ether treatment 6 days after application.

[0026]

[Example 3: Moisture retention test (2)] The product II of the present invention produced in Example 1 was subjected to a "moisture retention test for the effect of normal skin" by a high frequency impedance meter (manufactured by IBS). I did. (Method) The moisturizing effect of the product II of the present invention on human skin was examined by changing the conductance value. The sample of the invention II
Was used in a squalane to prepare a 5% solution. Squalane was used as a control. Two circular compartments with a diameter of about 2 cm were set on the inner side of the forearm of the test subject, and two kinds of samples (the present invention product II and squalane) were allocated to each compartment, 100 μl was applied, and after 30 seconds After wiping lightly with gauze (measurement time was 0 second), the conductance value of each section was measured (measurement condition: measurement room temperature 20 ° C., humidity 60%, number of measurements N = 10).

(Results) The obtained results (average value of 10 measurements) are shown in FIG. As is clear from this result,
The conductance value of the product II of the present invention was significantly different from that of the control squalane. In addition, the stickiness observed with squalane alone was not felt.

(Discussion) From the results of Examples 2 and 3, it was confirmed that the product II of the present invention had a clearly higher conductance value than the control squalane-applied site, had a good feeling in use, and had excellent moisturizing properties. Has been certified.

[0029]

[Example 4: Moisturizing test (3)] (Method) Various solvents 7 as shown in Table 2 were used with respect to 100 g of buttersrum powder (Pergie, product of Coleman).
00 ml was added, and the mixture was extracted with stirring for 3 hours. Then,
The extract was suction-filtered, the filtrate was concentrated under reduced pressure, 5 times (W / V) amount of acetone was added to the concentrated concentrate under reduced pressure, the generated precipitate was recovered, and this was vacuum dried to obtain a dried product ( Invention product I
V, V and comparative control products) were obtained. This dried product (invention product I
V, V and comparative control products) were subjected to a moisture retention test by a high frequency impedance meter in the same manner as in Example 2.

(Results) Table 2 shows the conductance values of the products IV and V of the present invention and the comparative control product 6 days after the application of the sample.

[0031]

[Table 2]

(Discussion) The products IV and V of the present invention restore the normal conductance value of the skin before the acetone / ether treatment,
It showed less stickiness than the comparative control product and showed excellent moisturizing properties.

[0033]

[Example 5: Antioxidant test] (Method) The antioxidant property of each sample in an emulsion system was measured under the following conditions. (1) Measurement sample Linoleic acid 0.5 g 0.1 M sodium phosphate buffer (pH 7.0) 50.0 ml 2% Tween20 15.0 ml distilled water 35.0 ml Antioxidant substances (each sample shown in Table 3) Test Concentration The sample was pre-emulsified with 2% Tween 20, and then the whole was mixed and emulsified at 5000 rpm for 3 minutes using Excel Auto Homogenizer DX-70 (manufactured by Nippon Seiki Co., Ltd.). Transfer the emulsion to a 100 ml Erlenmeyer flask with a stopper,
The mixture was left at 45 ° C. in the dark while stirring with a magnetic stirrer. Samples were sampled over time, thiobarbituric acid (TBA) was added to develop color, and the fading of peroxide was examined. The TBA value was determined according to the method of Tien et al. (Chemistry and Biology, 30, 9, 604 (1992)). The time until the TBA value (absorbance at 535 nm) rapidly increased was regarded as the induction period of the lipid peroxidation reaction, and the antioxidant properties of each sample were evaluated.

The results obtained are shown in Table 3.

[0035]

[Table 3]

(Discussion) As is clear from these results, the present invention product I, the present invention product II, and the present invention product III do not show antioxidant properties by themselves, but have a long induction period due to coexistence with vitamin E. became. Although the phospholipid (PL) content was equivalent to that derived from egg yolk or soybean, it was found that the synergistic effect (synergist) of the antioxidant was large.

In this example, the following commercial products were used as the reagents. Vitamin E: DL-α-tocopherol (Vitamin E)
Wako 1st grade (Assay 98.0%) Linoleic acid: Linoleic acid (Linoleic acid) Wako 1st grade for biochemistry (Asaay 99.0%) Egg yolk PL (Egg yolk phospholipid): Lecithin, Egg (Lecithi)
n, from Egg) Wako first grade soybean PL (soybean phospholipid): lecithin, soybean (Lecith
in, from Soybean) Wako first grade The composition of the commercially available phospholipid (PL) is as shown in Table 4 below.

[0038]

[Table 4]

[0039]

[Example 6: Production of active ingredient (2)] Buttermilk was filtered, sterilized, concentrated and spray-dried by a conventional method. 600 ml of hexane-ethanol-water (25:65:10) mixed solvent for 100 g of the buttermilk powder thus obtained.
Was added and the mixture was extracted with stirring for 3 hours. The extract was suction-filtered, the filtrate was concentrated under reduced pressure, and then vacuum dried to obtain 6.9 g of a dried product (invention product VI).

[0040]

[Example 7: Preparation of external preparation for skin] Using the product of the present invention obtained in Example as an active ingredient, an external preparation for skin was prepared with the composition shown below. In the formulation of prescription example, "appropriate amount" means 1 in total.
It means an amount of 100% by weight. Formulation Example 1 Cream (1) A (% by weight) Monostearate Polyethylene glycol (40.EO) 2.0 Self-emulsifying type glyceryl monostearate 5.0 Stearic acid 5.0 Behenyl alcohol 1.0 Liquid paraffin 10. 0 Glyceryl trioctanoate 10.0 Vitamin E 0.1 Inventive product I 0.5 Inventive product III 0.5 B Glycerin 5.0 Ethylparaben 0.1 Purified water Appropriate amount A component belonging to A is dissolved by heating. Separately, the components belonging to B are dissolved by heating. B was added to A, and the mixture was stirred, emulsified, and cooled to produce a cream.

Formulation Example 2 Cream (2) A (% by weight) Monostearate Polyethylene glycol (40.EO) 2.0 Self-emulsifying glyceryl monostearate 5.0 Stearic acid 5.0 Behenyl alcohol 1.0 Flow Paraffin 10.0 Glyceryl trioctanoate 10.0 Vitamin E 0.2 Inventive product II 0.5 B Glycerin 5.0 Ethylparaben 0.1 Purified water Appropriate amount A component belonging to A is dissolved by heating. Separately, the components belonging to B are dissolved by heating. B was added to A, and the mixture was stirred, emulsified, and cooled to produce a cream.

Formulation Example 3 Emulsion A (% by weight) Monostearic acid Polyoxyethylenesorbitan (20.EO) 1.0 Monostearic acid Polyoxyethylenesorbitan (60.EO) 0.5 Lipophilic mono Glycerin stearate 1.0 Stearic acid 0.5 Behenyl alcohol 0.5 Avocado oil 4.0 Glyceryl trioctanoate 4.0 Inventive product V 5.0 B 1,3-butylene glycol 5.0 Ethylparaben 0.1 Purified water A proper amount of the ingredients belonging to A are dissolved by heating. Separately, the components belonging to B are dissolved by heating. After adding B to A, stirring and emulsifying, cooling was performed to produce an emulsion.

Formulation Example 4 Lotion A (% by weight) Polyoxyethylene hydrogenated castor oil (60.EO) 8.0 Ethanol 15.0 Inventive product III 0.1 Ethylparaben 0.1 Citric acid 0. 1 Sodium citrate 0.3 1,3-butylene glycol 4.0 Disodium edetate 0.01 Purified water Appropriate amount The above components were mixed, uniformly stirred and dissolved to produce a lotion.

Formulation Example 5 Hydrophilic ointment A (% by weight) Polyoxyethylene cetyl ether 2.0 Glycerin monostearate 10.0 Liquid paraffin 10.0 Vaseline 4.0 Cetanol 5.0 Inventive product I 3.0 B Propylene glycol 10.0 Methylparaben 0.1 Purified water Appropriate amount The components belonging to A are dissolved by heating. Separately, the components belonging to B are dissolved by heating. After adding B to A, stirring and emulsifying, cooling was performed to produce a hydrophilic ointment.

Formulation 6 Hair shampoo A (wt%) Vitamin B ₁₂ 0.05 N-coconut oil fatty acid-L-glutamic acid 40.00 Triethanolamine (30%) Coconut oil fatty acid diethanolamide 3.00 Polyoxyethylenedio Methyl oleic acid glucoside (120EO) 2.00 Invention product IV 2.00 B Ethyl paraoxybenzoate 0.30 Purified water Appropriate amount (production method) A is uniformly stirred and dissolved. Separately, B, which had been uniformly dissolved by heating, was gradually added, and the mixture was stirred uniformly to prepare a hair shampoo.

Formulation Example 7 Hair rinse A (% by weight) Cetyl alcohol 5.00 Liquid paraffin 5.00 Lanolin 1.00 Isopropyl myristate 10.00 Invention product VI 10.00 B 60% Stearyltrimethylammonium chloride 5.00 Polyvinyl alcohol 0.50 1,3-butylene glycol 5.00 Purified water Appropriate amount (production method) A is uniformly stirred and dissolved, and B is heated separately,
Dissolve. B was added to A, emulsified, stirred, and cooled to produce a hair rinse. It was confirmed that each of the external preparations of Formulation Examples 1 to 7 had the effect of satisfying the purpose of the product of the present invention.

[0047]

The extract of milk fat globule film, which is the active ingredient of the external preparation for skin according to the present invention, not only has an excellent moisturizing effect, but also has an excellent feeling in use and is extremely safe without skin irritation. It is highly effective and is a skin external preparation suitable for long-term use. Further, the active ingredient of the present invention exerts an excellent antioxidative effect when used in combination with vitamin E, and therefore can be applied as a skin external preparation having a wide range of functionality.

[Brief description of drawings]

FIG. 1 shows the effect of the product II of the present invention on the change in conductivity of dry skin treated with acetone / ether.

FIG. 2 shows the effect of the product II of the present invention on the change in conductivity of dry skin.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Reference number within the agency FI Technical indication location A61K 35/20 ADA A61K 35/20 ADA (72) Inventor Tomoko Ueda 1-21 Sakaemachi, Higashimurayama-shi, Tokyo -3 Meiji Dairy Industry Co., Ltd. Nutrition Science Research Institute (72) Inventor Toshihiro Otsu 1-21 Sakaemachi, Higashimurayama City, Tokyo-3 Meiji Dairy Co., Ltd. Nutrition Science Research Institute (72) Inventor Haruo Negishi 1-21 Sakaemachi, Higashimurayama City, Tokyo -3 Meiji Dairy Industry Co., Ltd. Nutrition Science Research Institute (72) Inventor Yu Kuwata 1-21-3 Sakaemachi, Higashimurayama City, Tokyo Meiji Dairy Co., Ltd. Nutrition Science Research Institute

Claims (5)

[Claims] 1. A skin external preparation containing an extract extracted from a milk fat globule film using a solvent consisting of lower alcohol and water and / or a low polar solvent immiscible with water and / or a treated product thereof as an active ingredient. Agent. 2. The external preparation for skin according to claim 1, wherein the milk fat globule coating is a dairy product containing the milk fat globule coating. 3. The external preparation for skin according to claim 1, wherein the treated product is a concentrate, paste, dried product and / or diluted product of the extract. 4. The external preparation for skin according to any one of claims 1 to 3, wherein the extract contains polar lipids, minerals and non-protein nitrogen compounds. 5. The external preparation for skin according to any one of claims 1 to 4, wherein vitamin E is added to the extract and / or the treated product.