JP2005047904A - External preparation composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an external preparation excellent in preventing effect on skin-aging. <P>SOLUTION: The subject external preparation composition contains a lamella vehicle having 0.05-5μm average particle size and a lamella vehicle having 6-30μm average particle size. The lamella vehicles comprise fatty acid monoglycerides as their principal ingredients. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to an external preparation composition excellent in the effect of suppressing skin thickening and elasticity reduction.

Human skin undergoes thickening and a decrease in elasticity with ultraviolet rays and aging, resulting in wrinkles, sagging, dullness, and the like. For such skin aging, cosmetics containing synthetic or natural moisturizing ingredients, various plant extracts, rutin sugar derivatives, proteins such as sericin, α-hydroxy acids and the like have been proposed.
Moreover, the lamellar structure which has a fatty acid monoglyceride as a main component (patent document 1), the lamellar structure which has a fatty acid monoglyceride as a main component, and the skin external preparation containing vitamin A (patent document 2), and a fatty acid monoglyceride as a main component It is known that a skin external preparation (Patent Document 3) containing a lamellar structure and ascorbic acid encapsulated in the lamellar structure has excellent moisturizing action and anti-aging effect.
Japanese Patent No. 2606761 JP 2000-239140 A JP 2002-145751 A

  However, the effects of these lamella structures are not yet satisfactory, and there is a demand for an external preparation material that is further excellent in the effect of preventing skin aging.

  Thus, the present inventors have searched for a material excellent in the effect of preventing skin aging, and surprisingly, mainly, a lamellar vesicle mainly composed of a fatty acid monoglyceride having a large average particle diameter and a fatty acid monoglyceride having a small average particle diameter are mainly used. It has been found that when a lamellar vesicle as a component is used in combination, extremely remarkable skin thickening suppression effect and elasticity reduction suppression effect can be obtained, and the present invention has been completed.

  In addition, as a result of studying the production method of lamellar vesicles with a small average particle diameter, the lipid component containing fatty acid monoglyceride was used in a specific concentration range, and the water phase was added to the oil phase, so that the particle size distribution could be easily operated. It has been found that fine lamella vesicles having a narrow average particle diameter of 0.05 to 1 μm can be obtained efficiently.

That is, the present invention is a lamellar vesicle mainly composed of a fatty acid monoglyceride and containing a lamellar vesicle having an average particle size of 0.05 to 5 μm and a lamellar vesicle having an average particle size of 6 to 30 μm. A composition is provided.
The present invention also provides a lamella having an average particle diameter of 0.05 to 1 μm, wherein 60 to 80 parts by weight of an aqueous phase component is added to 20 to 40 parts by weight of a lipid component mainly composed of a fatty acid monoglyceride and stirred. A method for producing vesicles is provided. Here, the average particle size refers to the median value (median) of the particle sizes obtained from the particle size distribution.

  The external preparation composition of the present invention exhibits an excellent effect of suppressing skin thickening and improving skin elasticity, and is useful for comprehensive skin improvement. Furthermore, there is no irritation | stimulation with respect to skin, By using this, the outstanding skin cosmetics can be obtained.

  The main component of the lamellar vesicle used in the present invention is a fatty acid monoglyceride. However, from the viewpoint of moisturizing effect, transglutaminase 1 activation effect, skin thickening, and elasticity reduction inhibiting effect, it is particularly saturated or unsaturated with 8 to 20 carbon atoms. Saturated fatty acid monoglycerides are preferred. Specific examples of constituent fatty acids of fatty acid monoglycerides include caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, palmitooleic acid, etc., and these monoglycerides are of two or more types May be used in combination. In particular, when trying to obtain a small lamella vesicle having an average particle size of 0.05 to 1 μm, the average particle size is 0.05 to 1 μm, more preferably by using a fatty acid monoglyceride having monopalmitic acid as a constituent fatty acid. Fine lamella vesicles having a particle diameter of 0.1 to 1 μm and a substantially uniform particle diameter can be obtained. As the monoglyceride to be combined therewith, it is preferable that the fatty acid composition is stearic acid or myristic acid.

  Moreover, cholesterol, an alkyl, or an alkenyl monoglycerol ether etc. are mentioned as another structural component of this lamella vesicle. Cholesterol is particularly preferred because it improves the stability of the lamellar vesicles. As the alkyl or alkenyl monoglycerin ether, an alkyl or alkenyl monoglycerin ether having 8 to 20 carbon atoms is preferable. The total amount of cholesterol and monoglycerin ether added is preferably 1 to 100 parts by weight, particularly 5 to 25 parts by weight, based on 100 parts by weight of the fatty acid monoglyceride.

  In this invention, it is a lamella vesicle which has such a fatty acid monoglyceride as a main component, Comprising: The lamella vesicle with an average particle diameter of 0.05-5 micrometers and the lamella vesicle with an average particle diameter of 6-30 micrometers are used together. To do. A preferred combination is a lamellar vesicle having an average particle size of 0.05 to 5 μm and a lamellar vesicle having an average particle size of 6 to 20 μm, and a particularly preferred combination is a lamellar vesicle having an average particle size of 0.1 to 5 μm and a lamellar vesicle having 6 to 20 μm. By using these two types of lamellar vesicles having different particle diameters in combination, it is possible to obtain a skin thickening inhibitory effect and a skin elasticity reduction inhibitory effect which are so excellent that they cannot be predicted at all from a single action.

  Such lamellar vesicles with different average particle diameters can be produced by preparing lamellar vesicles with a wide particle size distribution, followed by gel filtration, centrifugation, and successive filtration using filtration membranes of different pore sizes. It may be manufactured separately.

  Such lamellar vesicles are prepared, for example, by physically stirring an oil phase mixture containing fatty acid monoglycerides in an aqueous phase. As such a method, for example, a fatty acid monoglyceride or an oil phase mixture containing the fatty acid monoglyceride is dissolved in an organic solvent such as dichloromethane, chloroform or acetone, and then the solvent is distilled off in a rotating container to dry the fat layer. (Oil phase), water or a suitable aqueous solution (aqueous phase) is added, and the oil phase is gradually dispersed and mixed in the aqueous phase by physically stirring, thereby dispersing the lamella vesicle dispersion used in the present invention. Can be prepared (thin phase method). Alternatively, after the water phase is heated and melted and mixed, a fatty acid monoglyceride having a concentration of about 0.1 to 15%, which is kept at the same temperature and dissolved, or an oil phase mixture containing the same is added, A dispersion of lamellar vesicles used in the present invention can be prepared by physically dispersing and mixing an oil phase in an aqueous phase. As said heating temperature, 40-100 degreeC, Furthermore, 45-80 degreeC is preferable, and 50-70 degreeC is especially preferable.

  In order to obtain a lamellar vesicle having a small particle size, it has been conventionally preferred to increase the rotational speed and shearing force during physical stirring, that is, to apply higher energy. Thus, fine particle lamellae having an average particle diameter of 0.05 to 1 μm, further 0.05 to 0.5 μm, particularly 0.1 to 0.5 μm could not be obtained.

On the other hand, by using a specific lipid as a membrane constituent, particularly a fatty acid monoglyceride having monopalmitic acid as a constituent fatty acid, and adjusting by the above thin film method in the absence of Ca ²⁺ , an average particle size of 0.5 μm Although it was known that the following fine particle lamellae could be obtained, the process was complicated and a special device such as a rotating container capable of distilling off the solvent was required. It wasn't.

  As a result of studying a method for preparing a fine particle lamella more easily, the present inventors have not unexpectedly conducted a method for dispersing a small oil phase in a large amount of water phase, but surprisingly a larger amount of oil phase than in the past. A method in which the aqueous phase is added to the mixture and stirred. More specifically, after heating and melt-mixing a large amount of the oil phase mixture, an aqueous phase kept at the same level or at a lower temperature than the oil phase is added, and the physical phase is added. By stirring and stirring, the aqueous phase is gradually dispersed and mixed in the oil phase so that a fine particle lamellar dispersion of 0.05 to 1 μm, further 0.05 to 0.5 μm, especially 0.1 to 0.5 μm can be obtained. It was found that it can be prepared.

  The oil phase concentration in the preparation method is preferably about 20 to 40% of the total amount. Therefore, 60 to 80 parts by weight of the water phase component is added to 20 to 40 parts by weight of the oil phase component. Moreover, as an oil phase, the fatty acid monoglyceride which uses 1 type, or 2 or more types of a palmitic acid, a stearic acid, and myristic acid as a constituent fatty acid is preferable, and it is preferable to use these together especially. The temperature of the oil phase and the water phase is preferably 50 to 80 ° C., more preferably 52 to 78 ° C., and particularly preferably 57 to 63 ° C. as the temperature during mixing. Alternatively, an oil phase maintained at 50 to 90 ° C., preferably 70 to 80 ° C., and an aqueous phase maintained at 30 to 80 ° C., preferably 40 to 50 ° C., can be mixed and carried out. . According to this method, it is possible to obtain fine particle lamellar vesicles in which 50% or more of the obtained lamellar vesicles have a substantially uniform particle diameter of 0.5 μm or less.

In any preparation method, it is preferable to use, for example, an ultrasonic emulsification apparatus, a high-pressure uniform dispersion apparatus, a nanomizer, a homogenizer, a colloid mill, or a microfluidizer for physical dispersion. Furthermore, when it adjusts in the state in which Ca ^<2+> exists in a water phase, a multilayer film lamellar vesicle can be obtained.

  In addition, as the lamellar vesicle of the present invention, either a single layer film lamellar vesicle or a multilayer film lamellar vesicle may be used, and a single layer film and a multilayer film lamellar vesicle may be used in combination.

  The blending ratio of lamellar vesicles having different particle sizes in the composition of the present invention is not particularly limited, and may be appropriately selected depending on the activity of the lamellar vesicles used. For example, the blending ratio of lamella vesicles having an average particle diameter of 0.05 to 5 μm and lamella vesicles having an average particle diameter of 6 to 30 μm is 1: 100 to 100: 1, more preferably 1:50 to 50: 1, particularly 1: It is preferably 20 to 20: 1.

  In the case of a lamella vesicle having an average particle diameter of 0.05 to 5 μm, one kind may be used, but a 0.05 to 1 μm lamella vesicle and a 1 to 5 μm lamella vesicle may be used in combination.

  In the aqueous phase components of the two types of lamellar vesicles used in the present invention, various ascorbates, vitamin A esters, and derivatives thereof, lactic acid bacteria culture supernatants, preservatives, humectants, hyaluronic acid, and other water-soluble substances Water-soluble components such as water-soluble polymers may be included.

  As the external preparation composition of the present invention, a composition in which two or more types of lamella vesicles having different particle diameters are blended may be used as it is, but known external preparation components such as water, as long as the effects of the present invention are not hindered. Alcohols, oil components, surfactants, preservatives, fragrances, dyes, moisturizers, thickeners, water-soluble polymers, antioxidants, chelating agents, pH adjusters, foaming agents, pigments, UV absorbers / scattering agents Powders, vitamins, amino acids, antibacterial agents, plant extracts, animal-derived components, microorganism-derived components, microorganism culture supernatants, seaweed extracts, various drugs, additives and the like can be blended.

  The external preparation composition of the present invention can be produced by a conventional method, such as skin lotion, milky lotion, moisturizing cream, cleansing cream, facial cleansing cream, pack, cosmetic liquid and other basic cosmetics, hair products such as shampoo and rinse, Various forms such as bath cosmetics such as bath preparations, makeup cosmetics such as foundations, and special cosmetics such as sunscreens can be used, but skin cosmetics are preferred.

  The blending amount of the lamella vesicle in the external preparation composition is not particularly limited, but is preferably 0.01 to 100% by weight, more preferably 0.1 to 90% by weight in the external preparation composition. 3 to 80% by weight is preferred.

  EXAMPLES Next, although an Example is given and this invention is demonstrated in detail, this invention is not limited to these. Hereinafter, “%” represents “% by weight”.

Production Example 1
Each lipid was weighed in an amount of 1% monopalmitin, 0.3% batyl alcohol and 0.1% cholesterol with respect to 1 mL of distilled water to prepare a lipid mixture A. After lipid mixture A was dried in a container, 10 mM CaCl ₂ solution was added and sonication (Branson sonifer 250; Branson, 20 kHz, 55 W, 10 minutes) was performed in a 60 ° C. warm bath. The supernatant was replaced with distilled water by centrifuging the obtained mixture, and sample 1 was obtained.

Production Example 2
Lipid mixture A was prepared in the same manner as in Example 1, and after drying in a container, distilled water was added and sonication was performed in a 60 ° C. warm bath under the same conditions as in Production Example 1 to obtain Sample 2.

Production Example 3
Each lipid was weighed to an amount of 0.5% monomyristin, 0.5% monopalmitin, 0.3% batyl alcohol and 0.1% cholesterol with respect to 1 mL of distilled water to prepare a lipid mixture B. Distilled water was added after the lipid mixture B was dried in a container, and sonication was performed in a warm bath at 60 ° C. under the same conditions as in Production Example 1 to obtain Sample 3.

Production Example 4
Sample 1 and sample 2 obtained in Production Examples 1 and 2 were mixed in an equivalent amount to obtain Example Product 1.

Test example 1
The particle size distribution of the lamellar vesicles was measured by using the samples 1 to 3 obtained in Production Examples 1 to 3 and measuring the particle distribution of each lamellar vesicle according to a conventional method. That is, the sample was dispersed in a measuring cup in an amount of 0.1 to 1 mL and immediately measured at room temperature using a Shimadzu laser diffraction particle size distribution analyzer (SALD-2000; manufactured by Shimadzu Corporation). The results are shown in FIG.

  As shown in FIG. 1, the average particle size of Sample 1 was 10 μm, but it was revealed that the particle size distribution was in a wide range, with some being 20 to 30 μm. In contrast, sample 2 had an average particle size of 3 μm and a narrow particle size distribution. Sample 3 had a narrower particle size distribution and an average particle size of 0.2 μm.

Test example 2
Influence on skin thickening For the test, Samples 1 and 2 obtained in Production Examples 1 and 2 and 4 and Example 1 were used. Hairless mice (Hr-1: Hos, female, 7 weeks old) were irradiated with 40 mJ / cm ² / day of ultraviolet rays once a day for 4 days. Immediately after each irradiation, 200 μl each of Samples 1 and 2 and Example 1 were applied to the back skin every day (n = 4-6). Distilled water was used as a sample. The skin was peeled off on the experiment end date (irradiation day 4), and the skin thickness was measured using a Digimagic indicator 543 (manufactured by Mitoyo). The results are shown in FIG.

  As shown in FIG. 2, both lamella vesicles having an average particle diameter of 10 μm and an average particle diameter of 3 μm showed a tendency to suppress skin thickening due to ultraviolet rays, but did not show a significant inhibitory effect. On the other hand, it was found that the combined use of these particle sizes suppresses synergistically as compared with the case of using them alone.

Test example 3
Influence on skin elasticity The samples 1 and 2 obtained in Production Examples 1 and 2 and 4 and the product 1 were used for the test. In the same manner as in Test Example 2, ultraviolet irradiation and sample application were performed, and skin elasticity was measured at a suction pressure of 50 mbar using a Cutometer SM575 (manufactured by C + K) and a measuring sensor having a diameter of 2 mm. The results are shown in FIG.

  As shown in FIG. 3, none of the lamellar vesicles having an average particle diameter of 10 μm and an average particle diameter of 3 μm was able to suppress a decrease in skin elasticity due to ultraviolet rays. On the other hand, it was found that when these particle sizes were used in combination, the skin elasticity was not lowered at all and an extremely excellent suppression effect was obtained.

Test example 4
Effect of Lipid Amount on Particle Size of Lamella Vesicle Fatty acid monoglyceride (monostearin: monopalmitin = 7: 3), batyl alcohol, and cholesterol were mixed at a ratio shown in Table 1 to obtain a lipid mixture. The obtained lipid mixture was each administered into a container, melted at 75 ° C., and then stirred with a stirrer (polytron homogenizer PT3000 type; manufactured by KINEMATICA, 6000 rpm, 1 minute). Next, purified water heated to 45 ° C. was added to make the whole 100%, and then stirred using a stirrer at 6000 rpm for 2 minutes for homogenization. After homogenization, cooling was started with a water bath under stirring (1000 rpm) and cooled to 32 ° C. to obtain Samples 4 to 7. The state of the obtained sample was observed with the naked eye to confirm the state of the sample. The obtained lamella vesicle mixture was diluted 25 times with distilled water, and the lamella states were compared under a polarizing microscope (10 × 40 times).

As shown in Table 2, the lamella vesicles of Samples 6 and 7 had relatively uniform particles as compared with Samples 4 and 5, and Sample 6 particularly had a good composition. On the other hand, sample 7 had the smallest particle diameter of the resulting lamellar vesicle, but the composition was inferior to sample 6.
The particle distribution of the lamella vesicle of Sample 6 was measured. That is, the sample was measured using FPIA-2100 (manufactured by SYSMEX) under the condition where the sample was diluted 4000 times, and the average particle size was determined. As a result, the average particle size of Sample 6 was 0.45 μm. Therefore, it is understood that a good lamellar vesicle having an average particle size of 0.05 to 1 μm can be obtained by adding 60 to 80 parts by weight of an aqueous phase to 20 to 40 parts by weight of a high-concentration lipid and stirring. It was.

Test Example 5
Effect of stirring speed and temperature on particle diameter of lamellar vesicle Fatty acid monoglyceride (monostearin: monopalmitin = 7: 3), batyl alcohol, and cholesterol were mixed in the same ratio as in Production Example 1 to obtain a lipid mixture. The obtained lipid mixture was weighed to 28% of the total amount, administered into a container, and melted at the temperature described in Table 3. Next, purified water heated to the temperature shown in Table 3 was added to make the whole 100%, and the mixture was stirred and homogenized using a stirrer. After homogenization, cooling was started with a water bath under stirring (1000 rpm or 500 rpm), and cooled to 32 ° C. to obtain Samples 8 to 11. The state of the obtained sample was observed with the naked eye to confirm the state of the sample. The obtained lamella vesicle mixture was diluted 25 times with distilled water, and the lamella state and the particle distribution of the lamella vesicle were measured under the same conditions as in Test Example 4. The results are shown in Table 4.

  As shown in Table 4, all of the samples 8 to 10 are in a lamellar vesicle state and the particle size of the lamellar vesicle is almost the same as that of the sample 6, and the stirring speed at the start of the production of the lamellar vesicle is the particle size of the lamellar vesicle. The condition was not affected. Sample 11 is also in the state of lamellar vesicles and the particle size of lamellar vesicles is almost the same as sample 6, and the temperature of the oil phase during production is 40 ° C. or higher, or a mixture of oil phase components and water phase components during stirring. It was found that a lamellar vesicle having an average of 0.45 μm can be obtained when the temperature of is 50 ° C. or higher.

Production Example 5
Among the following components, 1 to 3 lipids were weighed and dissolved by heating at 60 to 85 ° C. to obtain a lipid mixture D. On the other hand, 4 and 5 were weighed and mixed, and dissolved by heating at 60 to 85 ° C. to obtain an aqueous phase component. A lipid mixture was added to the obtained aqueous phase component and stirred with a stirrer (Polytron homogenizer PT3000 type; manufactured by KINEMATICA, 6000 rpm, 1 minute) to obtain Sample 12.

1. Monopalmitin 5.0 (wt%)
2. Batyl alcohol 1.5
3. Cholesterol 0.5
4). Calcium chloride 0.1
5. Purified water 92.9

Production Example 6
Samples 1 and 12 obtained in Production Examples 1 and 5 were mixed in an equivalent amount to obtain Example Product 2.

Production Example 7
Sample 1, Sample 2, and Sample 12 obtained in Production Examples 1, 2, and 5 were mixed in an equivalent amount to obtain Example Product 3.

Test Example 6
The particle size distribution of lamella vesicles was measured in the same manner as in Test Example 1 using Sample 1, Sample 2 and Sample 12 obtained in Production Examples 1, 2, and 4. The results are shown in FIG.
As shown in FIG. 4, the average particle size of Sample 12 was 0.1 μm.

Test Example 7
Influence on skin thickening For the test, the thickness of the skin was measured in the same manner as in Test Example 2 using Sample 2 and Example 3 obtained in Production Examples 2 and 7. The results are shown in FIG.
As shown in FIG. 5, it was found that an excellent inhibitory effect on the thickening of the skin caused by ultraviolet rays can be obtained by using lamella vesicles having an average particle size of 10 μm, 3 μm and 0.1 μm in combination.

Test Example 8
Influence on Skin Elasticity For the test, skin elasticity was measured in the same manner as in Test Example 3, using Sample 1 and Example 3 obtained in Production Examples 1 and 7. The results are shown in FIG.
As shown in FIG. 6, it was found that by using lamella vesicles having an average particle size of 10 μm, 3 μm and 0.1 μm in combination, the skin elasticity did not decrease and an excellent suppression effect was obtained.

Formulation Example 1 Moisturizing cream Among the following components, the oil phase component (1-13) is dissolved by heating, and the water phase component (14-22) is also dissolved by heating. The oil phase is mixed with the heated aqueous phase, stirred with a homogenizer, and then cooled. During the cooling, the additive components (23 to 32) were added and mixed to obtain a moisturizing cream.

1. Squalane 4.30% (% by weight)
2.2 Cetyl 2-ethylhexanoate 4.50
3. Octyldodecyl myristate 4.50
4). Heavy liquid isoparaffin 4.00
5. White beeswax 2.40
6). Stearic acid 2.40
7. Batyle stearate 1.20
8). Behenyl alcohol 1.20
9. Polyethylene glycol monostearate (40) 0.50
10. Stearyl glycyrrhetinate 0.10
11. Dl-α-tocopherol acetate 0.10
12 Natural vitamin E 0.001
13. Methylpolysiloxane 0.20
14 Purified water 15.879
15. Acrylic acid / methacrylic acid copolymer 3.00
16. Whey (2) 19.90
17. Glycerin 10.00
18. Polyoxyethylene methyl glucoside 1.50
19.1.3-Butylene glycol 7.00
20. Licorice extract 0.12
21. Edetate disodium 0.10
22. P-Hydroxybenzoate 0.20
23. KOH 0.20
24. Hyaluronic acid Na solution (0.6%) 4.90
25.2-Methacryloyloxyethylphoscholine / butyl methacrylate copolymer 3.00
26. Bukuryu extract 0.10
27. Carrot extract 0.05
28. Yeast extract 0.05
29. Royal Jelly 0.05
30. Chlorhexidine gluconate 0.05
31. Lamella vesicle composition (sample 12, average particle size 10 μm)
8.00
32. Lamella vesicle composition (sample 6, average particle size 0.45 μm)
0.50

  The obtained moisturizing cream was excellent in feeling of use, moisturizing and the like.

It is a figure which shows the particle size distribution of a lamella vesicle. It is a figure which shows the effect | action which acts on the thickening of the skin of each sample. It is a figure which shows the effect | action which acts on the skin elasticity of each sample. It is a figure which shows the particle size distribution of a lamella vesicle. It is a figure which shows the effect | action which acts on the thickening of the skin of each sample. It is a figure which shows the effect | action which acts on the skin elasticity of each sample.

Claims (4)

  An external preparation composition comprising a lamellar vesicle mainly composed of a fatty acid monoglyceride and comprising a lamellar vesicle having an average particle size of 0.05 to 5 µm and an lamellar vesicle having an average particle size of 6 to 30 µm.   The external preparation composition according to claim 1, which is a skin cosmetic composition.   The external preparation composition according to claim 1 or 2, wherein the fatty acid monoglyceride is a saturated or unsaturated fatty acid monoglyceride having 8 to 20 carbon atoms.   A method for producing a lamellar vesicle having an average particle size of 0.05 to 1 µm, wherein 60 to 80 parts by weight of an aqueous phase component is added to 20 to 40 parts by weight of a lipid component mainly composed of a fatty acid monoglyceride and stirred.

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