JPH0818994B2 - Topical skin - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a novel external preparation for skin. More specifically, the present invention relates to a cosmetic characterized by normalizing keratinization of the epidermis of the skin by incorporating the Rokujou extract and the Ougon extract into liposomes and containing them as active ingredients.

[Conventional technology]

There are some examples in which Rokujo extract and Astragalus membranaceus extract are individually added to cosmetics. Loquat extract contains recovery of heart function, promotion of renal function, promotion of digestive system function,
Although many effects such as recovery from muscle fatigue are known, no studies have been found on the effect on keratinization of the skin epidermis.

In addition, although the anti-inflammatory effect and the antipyretic effect are known for the Scutellariae Radix extract, no study has been found on the effect on the keratinization of the skin epidermis. Further, it has not been found until now that liposomes encapsulating Rokujou extract and liposomes encapsulating Ougon extract are incorporated into cosmetics to normalize keratinization of the skin epidermis.

[Problems to be solved by the invention]

Most of the cells that make up the epidermis of the skin are called keratinocytes, which are produced by dividing the basal layer at the bottom of the epidermis, gradually flattening, and presenting a stratum corneum and a granule layer. It is pushed up to and it takes 14 days to reach the stratum corneum and become corneocytes (cell layer turnover). The cells take an additional 14 days to be pushed up, eventually becoming horny pieces and shedding from the surface of the skin. The exchange of cells in the stratum corneum is called turnover of the stratum corneum, and the number of days required for this is called the number of turnover days of the stratum corneum. In addition, the shape of keratinocytes changes while moving from the organic layer to the stratum corneum, and the nucleus disappears in the stratum corneum. The comprehensive differentiation phenomenon of keratinocytes is called keratinization. The change of epidermal cells due to this keratinization is called epidermal turnover, and in the normal case, it is 28 days (the number of epidermal turnover days), which is the sum of turnover of the cell layer and turnover of the stratum corneum. Since the stratum corneum is part of the display, the epidermis turnover is naturally closely related to the stratum corneum turnover. Therefore, the keratinization rate of the epidermis can be observed by measuring the turnover days of the stratum corneum. The faster the keratinization rate of the epidermis, the shorter the number of turnover days in the stratum corneum.

There are two types of abnormal keratinization of the skin epidermis. One is the one that occurs with aging, and the rate of keratinization of the epidermis is slowed by the slow rate of cell division (the turnover days of the stratum corneum are prolonged). As a result, the cell layer of the epidermis becomes thinner and the stratum corneum becomes thicker. As a result of this, the water content on the skin surface is reduced and the elastic, soft skin is lost. To make the aged skin look fresh, it is necessary to apply a lotion or cream to keep the skin moist, but this is not a fundamental solution.

Another abnormality is keratinization, which is caused by changes in epidermal cells on the cheeks and forehead due to external ultraviolet rays, dryness, temperature changes, etc. May be faster (shorter turnover time of stratum corneum). As a result, the epidermal cells are pushed up to the stratum corneum before the keratinization is completed, and a phenomenon occurs in which nuclei remain in the keratinocytes that should be essentially anucleate. If normal keratinization is not performed, NMF and ceramide will not be sufficiently produced, and the water retention capacity of the skin will decrease, resulting in a decrease in the amount of water on the skin surface.

Until now, no cosmetics have been found that normalize such abnormally fast or slow keratinization.

[Means for solving problems]

The present inventors have found that when a topical skin preparation containing a liposome encapsulating Loxochus extract is used on skin with slow keratinization rate of the epidermis (longer than 14 days, which is the normal turnover time of the stratum corneum), the keratinization rate is increased. It was found to be faster and to normalize (approaching 14 days of normal stratum corneum turnover). In addition, keratinization occurs when a skin external preparation containing liposomes containing Scutellaria baicalensis extract is used for skin with a high keratinization rate of the epidermis (shorter than 14 days of normal turnover of the stratum corneum, and nuclei remain in keratinocytes). It slows down and normalizes (approaches 14 days, which is the normal turnover time of the stratum corneum,
The nucleus of keratinocytes disappears). Furthermore, when these liposomes were used in combination with an external preparation for skin, it was found that the part of the epidermis with a slow keratinization rate was fast and the part with a fast keratinization rate was slowed to normalize, and the present invention was completed. .

The Rokujo extract used in the present invention is obtained by extracting unkeratinized antler (deer antler) of Manshu sika deer (idiot) or Manshu deer (plum flower deer) with ethanol or a mixture of ethanol and water. Further, a solvent of an aqueous solution other than ethanol, for example, 1,3-butylene glycol,
It is also possible to extract using propylene glycol or the like.

The Astragalus membranaceus extract used in the present invention is obtained by extracting roots (Agonaceae) of Scutellaria baicalensis (golden flower) of the Lamiaceae plant with ethanol or a mixture of ethanol and water. It is also possible to extract using a water-soluble solvent other than ethanol, such as 1,3-butylene glycol or propylene glycol.

The liposome of the present invention can be obtained by applying ultrasonic waves to three components of Rokujou extract and / or Ougon extract, phospholipid and water. This liposome is a spherical endoplasmic reticulum composed of a monolayer or multilayer of a phospholipid bilayer, and is a state (encapsulation) in which Rokujo extract or Astragalus membranaceus extract is taken up in the phospholipid membrane or in the endoplasmic reticulum. .

Cholesterol, glucose, amino acids, higher alcohols, nonionic surfactants, ionic surfactants and the like can be added for the purpose of stabilizing liposomes. In addition to this, there are a homomixer method, a thin film method, an injection method, a surfactant removal method and the like for forming liposomes, and the liposome of the present invention can be prepared by any method.

The phospholipid used for liposome formation is soybean phospholipid,
Egg yolk phospholipids, hydrogenated soybean phospholipids, hydrogenated egg yolk phospholipids,
Synthetic phospholipids and the like can be used alone or in combination of two or more.

In the present invention, the Rokujou extract used for the liposome compounded in the external preparation for skin is 0.0001 to 0.2% by weight as a dried product of Rokujou extract. No effect is seen at a compounding amount of 0.0001% by weight or less. Further, when the content is 0.2% by weight or more, the effect is not significantly increased, which is not economical.

In the present invention, the Astragalus membranaceus extract used in the liposome compounded in the external preparation for skin is 0.0001 to 0.1% by weight as a dried product of the Aumeuron extract. No effect is seen at a compounding amount of 0.0001% by weight or less. Further, when the content is 0.2% by weight or more, the effect is not significantly increased, which is not economical.

Even when two types of liposomes containing Rokujou extract and liposomes containing Ougon extract are used in combination with a skin external preparation, the Rokujou extract used for the liposome is 0.0001 ~ as a dried product of Rokujou extract.
0.2% by weight, and the amount of the Scutellaria extract used for the liposome is 0.0001 to 0.1% by weight as a dried product of the Scutellariae extract.

Almost no effect is observed when the Rokujo extract and the Astragalus membranaceus extract are not made into liposomes and directly blended with cosmetics. It is considered that this is because the active ingredient of the extract exerts its effect only after reaching the basal cells, and it is considered that the transdermal absorbability is remarkably enhanced by forming the liposome. Further, the effect can be obtained by mixing the Rokujou extract and the Astragalus membranaceus extract, and then making them into liposomes and blending them into the skin external preparation.

〔Example〕

Next, the present invention will be further described with reference to examples, but the present invention is not limited thereto. The numbers in the formulations indicate weight%.

Example-1 Cream 1 Squalane 10.0 Cetyl alcohol 2.0 Polyoxyethylene (20) sorbitan monostearate 1.5 Polyoxyethylene (20) cetyl ether 2.0 Vaseline 5.0 Octyldodecyl myristate 10.0 Purified water 49.3 1,3-Butylene glycol 10.0 Paraoxybenzoic acid Methyl acid 0.2 Hydrogenated soybean phospholipid 0.2 Rokujou extract A 2.0 Purified water 7.8 Rokujou extract A is 100 g of shredded Manshu sika deer mushrooms, dipped in 900 g of 70% by weight ethanol aqueous solution.
After standing for 5 days, it is filtered to obtain an extract. Rokujo extract A
The dry matter is 1.7% by weight. Liposomes are components ~
Sonicate at 75 ° C and cool to 30 ° C to prepare.

After the components ~ were heated and dissolved at 80 ° C, the components ~ which had been previously heated and dissolved at 80 ° C were added to emulsify, and the mixture was cooled to 30 ° C, and the liposomes (0.034% by weight as a dried product of Rokujo extract) prepared by the components ~ were added. Add and stir mix to obtain Cream 1.

Example-2 Cream 2 Squalane 10.0 Cetyl alcohol 2.0 Polyoxyethylene (20) sorbitan monostearate 1.5 Polyoxyethylene (20) cetyl ether 2.0 Vaseline 5.0 Octyldodecyl myristate 10.0 Purified water 49.3 1,3-Butylene glycol 10.0 Paraoxybenzoic acid Methyl acid 0.2 Hydrogenated soybean phospholipid 0.2 Ogon extract A 2.0 Purified water 7.8 Ogon extract A is 100g Ogon and 600g purified water
After heating to 60 ° C., 1 kg of ethanol was added, and the mixture was left standing for 3 days and filtered to obtain an extract. The dried product of Scutellaria extract A
It is 2.1% by weight. The liposomes are prepared by sonicating the components (1) to (3) at 75 ° C and cooling to 30 ° C.

After the ingredients ~ were heated and dissolved at 80 ° C, the ingredients ~ which had been previously heated and dissolved at 80 ° C were added to emulsify, and the mixture was cooled to 30 ° C, and the liposomes (0.042% by weight as a dried product of Scutellariae Radix extract) prepared by the ingredients ~ were added. Add and stir mix to obtain Cream 2.

Example-3 Emulsion 1 Squalane 5.0 Cetyl alcohol 1.0 Polyoxyethylene (20) sorbitan monostearate 2.5 Glyceryl monostearate 1.0 Stearic acid 1.0 Cetyl isooctanoate 5.0 Purified water 65.3 Propylene glycol 8.0 Methyl paraoxybenzoate 0.2 Egg yolk phospholipid 1.0 Ougon Extract B 5.0 Purified Water 5.0 Ougon Extract B is 100 g Ougon and 1 kg ethanol.
Is added, and the mixture is left for 7 days and filtered to obtain an extract. The dried product of Scutellaria extract B is 2.3% by weight. Liposomes are prepared by heating the components ~ at 50 ° C with a homomixer and cooling to 30 ° C.

After the components ~ were heated and dissolved at 80 ° C, the components ~ which had been previously heated and dissolved at 80 ° C were added to emulsify, and the mixture was cooled to 30 ° C, and the liposomes (0.115% by weight as a dried product of Scutellariae Radix extract) prepared by the components ~ were added. Emulsion 1 is obtained by adding and stirring. .

Example-4 Lotion 1 Ethanol 10.0 1,3-Butylene glycol 2.0 Glycerin 3.0 Methyl paraoxybenzoate 0.2 Purified water 74.8 Synthetic phospholipids 0.5 Cholesterol 0.1 Locus japonica extract B 0.5 Purified water 8.9 Locus japonica extract B is shredded Manshu deer 100 g of antler mushroom is immersed in 900 g of 50% by weight ethanol aqueous solution, left for 5 days and filtered to obtain an extract. The dried product of Loquat extract B is 1.6% by weight. Liposomes are composed of 55
Prepare by sonicating at ℃ and cooling to 30 ℃.

After stirring and dissolving component (1), the component and the liposomes prepared in component (1) are added (0.008% by weight as a dried product of Rokujo extract) and mixed with stirring to obtain a lotion 1.

Example-5 Cream 3 Squalane 10.0 Cetyl alcohol 2.0 Polyoxyethylene (20) sorbitan monostearate 1.5 Polyoxyethylene (20) cetyl ether 2.0 Vaseline 5.0 Octyldodecyl myristate 10.0 Purified water 39.3 1,3-Butylene glycol 10.0 Paraoxybenzoic acid Methyl acid 0.2 Hydrogenated soybean phospholipid 0.2 Rokujo extract A 2.0 Purified water 7.8 Hydrogenated soybean phospholipid 0.2 Ougon extract A 2.0 Purified water 7.8 Ingredients were heated and dissolved at 80 ℃, and then heated to 80 ℃ And emulsified, cooled to 30 ° C., and added with the Rokujo extract-blended liposomes prepared in components (1) to (3) and the Auregon extract-blended liposomes prepared in (1) to components (3), and the mixture is stirred to obtain cream 3.

Example-6 Emulsion 2 Squalane 5.0 Cetyl alcohol 1.0 Polyoxyethylene (20) sorbitan monostearate 2.5 Glyceryl monostearate 1.0 Stearic acid 1.0 Cetyl isooctanoate 5.0 Purified water 55.3 Propylene glycol 8.0 Methyl paraoxybenzoate 0.2 Egg yolk phospholipid 1.0 Ogon extract B 5.0 Purified water 5.0 Soybean phospholipids 0.5 Rhizoma extract A 0.1 Polyoxyethylene (60) hydrogenated castor oil 0.2 Purified water 9.2 Liposomes containing Ogon extract have a component of ~ 50 ℃
So, the liposomes with the Rokujo extract are
Prepare by cooling with a homomixer at 60 ℃ and then cooling to 30 ℃.

After the ingredients ~ were dissolved by heating at 80 ° C, the ingredients ~ that had been heated and dissolved at 80 ° C were added to emulsify, and the mixture was cooled to 30 ° C, and the liposomes containing the ogon extract prepared in the ~ were prepared (as a dried product of the ogon extract). 0.115% by weight) and the ingredient-containing liposomes prepared by the above method (0.0017% by weight as a dried product of L. japonicus extract)
Is added and mixed with stirring to obtain Emulsion 2. .

〔The invention's effect〕

The cosmetic of the present invention is a cosmetic excellent in normalizing the keratinization of the epidermis by blending the liposome-encapsulated Rokujou extract and the liposome-encapsulated Ougon extract alone or in combination.

Next, regarding the effect of the present invention, the results of the epidermal keratinization rate normalization test and the keratinocyte normalization test are shown.

(Epidermal keratinization rate normalization test) 1) Test on liposome-encapsulated loquat extract A female monitor over 40 years of age with slow epidermal keratinization rate 60
15 people each as a test subject in each group Example-1
And Example-4, and the following Comparative Example-1 and Comparative Example-
2 creams were used daily for 2 months.

The degree of improvement of the turnover of the stratum corneum after two months was measured by the Dansyl chloride method.

(Dansyl chloride fluorescence method) 5% of dansyl chloride of fluorescence test to white petrolatum
Disperse and occlude the skin with a fin chamber with a diameter of 10 mm for 24 hours, and fluorescently stain the stratum corneum. Next, the maximum wavelength
UV light of 338 nm is irradiated, and the fluorescence intensity of the stratum corneum that has been fluorescently stained with dansyl chloride is measured daily with a measuring instrument.

The fluorescence intensity of dansyl chloride applied to the skin is
If the number of days when the fluorescence intensity of the uncoated area is reduced is defined as the number of days of turnover of the stratum corneum, it is 14 days in the normal case.

Comparative Example-1 Cream Except for the hydrogenated soybean phospholipid of Example-1, Lokujo extract A was blended without forming liposomes, and the others were prepared in the same manner.

Comparative example-2 cream Except for the hydrogenated soybean phospholipid and the loquat extract A of Example-1, other preparations were made in the same manner.

Test results Table 1 shows the results of a test for normalizing the keratinization rate of the epidermis with the liposome-encapsulated extract. As is clear from Table 1, the lococutaneous external preparation for external use of the present invention is a novel skin external preparation excellent in normalizing the keratinization rate of the epidermis.

2) Test on Liposome-Grilled Ogon Extract Using 60 female monitors whose epidermal keratinization rate was abnormally high due to ultraviolet rays and external factors as subjects, 15 females per group were used for Example-2 and Example-3, respectively. Then, the creams of Comparative Examples 3 and 4 below were used daily for 2 months.

Two months later, the degree of improvement in turnover of the stratum corneum was measured by the dansyl chloride method.

Comparative Example-3 Cream Except for the hydrogenated soybean phospholipid of Example-2, Scutellariae Radix Extract A was blended without forming liposomes, and the others were prepared in the same manner.

Comparative Example-4 Cream Except for the water-added soybean phospholipid and Scutellariae Extract A of Example-2, the same preparation was carried out in the same manner.

Test results Table 2 shows the results of a test for normalizing the keratinization rate of the epidermis with the liposome-enriched sorghum extract. As is clear from Table.2,
The skin external preparation containing the Scutellaria extract of the present invention is a new skin external preparation excellent in normalizing the keratinization rate.

3) A test using a combination of liposome-encapsulated occlusion extract and liposome-encapsulated Ougon extract A monitor with nucleated cells in the cheek region and a region with a rapid keratinization rate among women with a slow keratinization rate over the age of 40 years 60 people were the subjects. The creams of Example-5 and Example-6, and the creams of Comparative Example-5 and Comparative Example-6 were used daily for two months, each containing 15 persons per group.

Two months later, the degree of improvement in turnover of the stratum corneum was measured by the dansyl chloride method.

Comparative Example-5 Cream Except for the hydrogenated soybean phospholipids of the cream of Example-5, Rokujo extract A and Agon extract A were blended as they were.

Comparative example-6 cream The hydrogenated soybean phospholipid of the cream of Example-5, the Rokujo extract A, and the Aurgon extract A were prepared in the same manner except for the above.

Test results Table 3 shows the results of the epidermal keratinization rate normalization test using a combination of the liposome-encapsulated sardine extract and the liposome-encapsulated loquat extract. As is apparent from Table.3, the lococutaneous extract and the sardine extract external preparation for external use of the present invention have a high rate of slow keratinization rate and a slow rate of fast keratinization rate, which is excellent in normalization of keratinization rate. It is a new skin external preparation.

(Corneocyte normalization test) Test method When the keratinization rate increases due to external factors such as ultraviolet rays, humidity, and temperature, nucleated cells that are not originally found in the stratum corneum are recognized. Therefore, the degree of improvement in keratinization rate was measured using the nucleated cells as an index.

As a measuring method, a double-sided adhesive tape with a size of 1 x 1 cm was applied, and the adhesive surface was pressed onto the face of the monitor for 10 minutes after washing the face for about 2 seconds and collected when peeled off. The first stratum corneum that could be formed was sampled. The keratinocytes collected on the slide glass were subjected to hematoxylin / eosin staining (HE staining) according to the information. Using an optical microscope, the presence or absence of nucleated cells that stained blue with hematoxylin was confirmed at a magnification of 15 × 20. For the measurement, the number was counted for 5 consecutive visual fields in one direction. Since nucleated cells are usually exfoliated in clusters, they were counted according to the following criteria, a score was given, and the sum of products with each number was scored.

As for the monitor, 40 women with nucleated cells were used in groups of 10 each, and the emulsions of Examples 3 and 6 and the emulsions of Comparative Example 5 and Comparative Example 6 were used every day for 3 months. .

Test results The test results are shown in Table 4. As is clear from Table.4, the skin external preparations of Example-3 and Example-6 are novel skin external preparations that reduce the number of nucleated cells and normalize the keratinization rate (turnover time). .

In addition, also with respect to the skin external preparations of Example-2 and Example-5, an excellent keratinization rate normalizing action was similarly recognized.

Comparative Example-5 Emulsion Aurgon Extract A except for the egg yolk phospholipid of Example-3
Was formulated without forming liposomes, and the other components were prepared in the same manner.

Comparative Example-6 Emulsion An egg yolk phospholipid of Example-3 and the Agon extract A were prepared in the same manner except for the above.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical indication location A61K 35/78 Q 8217-4C (72) Inventor Jiro Kitahara 2-chome Torimicho, Nishi-ku, Aichi No. 130 Japan Menard Cosmetics Co., Ltd. Central Research Institute Examiner Shoei Hoshino (56) Reference JP-A-59-73509 (JP, A) JP-A-55-127309 (JP, A) JP-A-48-99347 ( JP, A)

Claims (3)

[Claims] 1. An external preparation for skin, which comprises a liposome encapsulating a loach extract to normalize keratinization of skin epidermis. 2. An external preparation for skin, comprising a liposome encapsulating an extract of Scutellaria baicalensis to normalize keratinization of skin epidermis. 3. An external preparation for skin, which comprises a liposome encapsulating Rokujou extract and a liposome encapsulating Ougon extract to normalize keratinization of skin epidermis.