JPH06104620B2 - Skin cosmetics - Google Patents

Description

TECHNICAL FIELD The present invention relates to a skin cosmetic having excellent anti-aging effects (rough skin improving effect, keratin improving effect, moisturizing effect, etc.) and beautiful skin effect.

(Prior Art) Conventionally, in order to improve dry and aged skin, it has been known to blend a hydrophilic skin moisturizer and an oily emollient which give appropriate moisture and oil content to the skin cosmetics. ing. However, skin moisturizers such as glycerin and propylene glycol may absorb water in the stratum corneum, which is the outermost layer of the skin, and may cause water loss on the contrary. In addition, liquid softeners such as liquid paraffin and petrolatum inhibit the normal metabolism of the skin when it is contained in the skin cosmetics to the extent that water evaporation from the epidermis is sufficiently prevented, and give a feeling of strangeness such as stickiness. It was not always satisfactory.

That is, the reinforcement of water in the epidermis or the prevention of water transpiration from the epidermis by the physical action of these compounding agents has not been able to enhance the water retention function of the skin.

In recent years, JP-A-61-260008 and JP-A-61-271205
As described in Japanese Patent Publication, application of ceramides, which are known to exist in living tissues such as skin, to cosmetics has been proposed, but these ingredients are blended alone. Even if a skin cosmetic is applied to the skin, it is still insufficient to enhance the water retention function of the skin.

Further, acidic mucopolysaccharides such as hyaluronic acid are disclosed in JP-B-33-500, JP-B-51-11178, and JP-A-54-54.
Although it has been applied as a moisturizing agent as a component of skin cosmetics as seen in Japanese Patent Publication No. 52733/1993, acidic mucopolysaccharides alone only regulate the amount of water on the surface of the skin, and have a function of retaining water inside the skin. It did not reach the level where it was promoted and a beautiful skin effect was exhibited.

(Disclosure of the Invention) Therefore, the present inventors, in view of the above-mentioned current situation, as a result of intensive studies, at least one selected from the group of ceramide, glucosylceramide, and galactosylceramide, and a low-molecular-weight acidic mucopolysaccharide. And a skin cosmetic containing at least one selected from the group of salts thereof remarkably exhibits the antiaging effect (rough skin improving effect, keratin improving effect, moisturizing effect, etc.) and beautiful skin effect which are the objects of the present invention. The present invention has been completed and the present invention has been completed.

Skin water constantly moves from the inside of the skin to the outer layer along the gradient of the water content that decreases from the dermis to the basal cell layer of the epidermis and further to the stratum corneum toward the outer layer, and transpires to the outside through the stratum corneum. However, this water transpiration is controlled mainly by the defense function (barrier function) composed of dense cell tissues from the lamina granules at the top of the granule layer to the stratum corneum. (Abbreviated as value) is, for example, 0.2 to 0.3 mg for the forearm skin surface in the normal state of healthy skin.
It is in the range of / cm ² / hr, and is usually maintained at about 0.25 mg / cm ² / hr or less. On the other hand, in normal dry skin (dry skin) or dry skin found in aged skin, the TWL value shows the upper limit of the above range or a higher value depending on the degree, and It is recognized that the retention function is deteriorated. This is because, in the case of those dry skins, the normal control limit by the defense function of the stratum corneum has been exceeded, or the defense function has deteriorated.

Therefore, if the tissues of the stratum corneum and lamellar granules are densified and their defense function can be activated, the water retention function of the skin is enhanced by this, and the skin is maintained in a healthy state, and further dry skin It can be improved or repaired.

Therefore, the present inventors, as a result of intensive studies on the action effects of ceramide, glucosylceramide, galactosylceramide and low molecular weight acidic mucopolysaccharides and salts thereof on human skin, as a result of these specific ceramides and low molecular weight acidic When mucopolysaccharides and / or salts thereof are simultaneously mixed in a cosmetic base and applied to the skin, they show a strong affinity for the surface of the skin and the stratum corneum, which is the outermost layer of the skin,
It was found that they have the effect of densifying their structure and improving aged skin. In addition, low-molecular-weight acidic mucopolysaccharides and salts thereof have a strong affinity for the surface of the skin and the stratum corneum, which is the outermost layer of the skin, and because they are low-molecular substances, they penetrate into the stratum corneum and the moisture inside the skin It exerts the function of regulating the function and enhancing the moisturizing function of the skin. The skin cosmetic of the present invention improves dry skin by enhancing the water-retaining function of the skin itself, or keeps the skin in a healthy state to prevent its aging and moisturizes the skin (moist feeling). The present invention has been completed by finding out that it has a beautiful skin effect of imparting flexibility (smoothness), elasticity and luster. In the case of the skin cosmetic of the present invention, it is not necessary to add a large amount of the above-mentioned skin moisturizer and skin softener unlike the conventional skin cosmetics, and there is no fear that the normal physiological function of the skin will be disturbed.

(Object of invention) That is, the object of the present invention is to improve rough skin, improve keratin,
It is intended to provide a skin cosmetic having excellent skin aging prevention effects such as a moisturizing effect and a beautiful skin effect.

(Structure of the Invention) The present invention relates to a skin cosmetic composition containing at least one selected from the group consisting of ceramide, glucosylceramide, and galactosylceramide, and at least one selected from the group consisting of low molecular weight acidic mucopolysaccharides and salts thereof. It is a thing.

(Specific Description of Configuration) Ceramide, glucosylceramide, and galactosylceramide used in the present invention are compounds that are present in trace amounts in the epidermis of mammals such as humans, pigs, cows, horses, and sheep (Biochemistry, And, Physiology, Of, The, Skin, No.
Pages 363-381, Biochemistry and Physiology of the
Skin, Oxford University Press, Inc. 1983 New York, Journal, Ov, Lipid, Research Vol. 24, 1983, etc.), and can be obtained from these animal epidermis by a conventional extraction method. In the present invention, JP-A-61-27
Obtained by the production method described in No. 1205 bulletin and biochemistry experiment manual (lipid biochemistry, biochemistry experiment course, Volume 3, pages 20 to 21, 1974, edited by the Biochemical Society of Japan, Tokyo Kagaku Dojin). Ceramide, glucosylceramide and galactosylceramide can be used. Here, the ceramide is a mixture of N-acyl sphingosine, N- (α-hydroxyacyl) -phytosphingosine, N-acyl phytosphingosine and the like. Further, glucosylceramide is mainly N-acylglucosylsphingosine, N- (α-hydroxyacyl) -glucosylphytosphingosine, N-
(Α-hydroxyacyl) -glucolsphingosine,
A mixture of N- (acyl-ω-hydroxyacyl) glucosylphytosphingosine and the like. Galactosylceramide is mainly N-acylgalactosylsphingosine,
It is a mixture of N- (α-hydroxyacyl) -galactosylphytosfungosin, N- (α-hydroxyacyl) -galatosylsphingosine and the like.

As the acidic mucopolysaccharide used in the present invention, hyaluronic acid, dermatan sulfate, chondroitin 4 sulfate, chondroitin 6 sulfate, heparin, heparan sulfate and the like can be used, and they are all known substances, cartilage,
It becomes a matrix component in joints, eyes, skin, and other connective tissues, binds to proteins, and is widely distributed in the animal body.

The molecular weight of the acidic mucopolysaccharide used in the present invention is 1,000 to 9,000 for hyaluronic acid, 1,000 to 9,000 for dematan sulfate, chondroitin 4-sulfate, and chondroitin 6-sulfate, heparin,
Heparan sulfate having 1,000 to 6,000 is preferable.

Examples of the salt of the acidic mucopolysaccharide used in the present invention include lithium metal salts of the mucopolysaccharide, sodium salts, alkali metal salts such as potassium salts, alkaline earth metal salts such as magnesium salts and calcium salts, ammonium salts, triethanol. Preferred are alkanolamine salts such as amine salts and diisopropanolamine salts, and basic amino acid salts such as lysine salts, arginine salts and histidine salts.
Further, these acidic mucopolysaccharides can also be used as a free acid.

The low molecular weight acidic mucopolysaccharides and salts thereof used in the present invention can be obtained as follows.

(1) Low molecular weight hyaluronic acid and its salt 5 g of commercially available hyaluronic acid having an average molecular weight of 1 million
Is dispersed and dissolved in 100 ml of 0.02N hydrochloric acid aqueous solution, and the pH is 2 to 2.
It was adjusted to 3 and heated to 65 ° C. in a warm bath with sufficient stirring. By changing the heating treatment time from 120 minutes to 200 minutes, hyaluronic acid having an average molecular weight of 1,000 to 9,000 can be obtained.

Next, after neutralizing with N-caustic soda, the solution was cooled to room temperature, 3 times volume of ethanol was added, the precipitate obtained was washed with ethanol, and then dried to obtain a powder of low molecular weight hyaluronic acid sodium salt. It was Further, this low-molecular-weight hyaluronic acid sodium salt is treated with an acid to give free hyaluronic acid, which is then treated with another basic substance, for example, potassium salt, triethanolamino salt, L-arginine salt, etc. Was prepared.

(2) Low molecular weight chondroitin tetrasulfate and its salt, etc. 5 g of commercially available sodium chondroitin tetrasulfate having an average molecular weight of 30,000 was dissolved in 50 ml of water, and Amberlite IR was used.
The effluent obtained by passing through a −120 (H type) resin column was heated to 75 ° C. in a warm bath while being sufficiently stirred. By changing the heating treatment time from 120 minutes to 200 minutes,
Chondroitin tetrasulfate having an average molecular weight of 1,000 to 9,000 can be obtained. Next, it is neutralized with N-caustic soda.
After the solution was cooled to room temperature, 3 times volume of ethanol was added and the obtained precipitate was centrifuged and washed with ethanol.
After drying, powder of chondroitin tetrasulfate sodium salt was obtained. Next, this chondrontin tetrasulfate sodium salt is treated with an acid to give free chondroitin tetrasulfate, which is then treated with another basic substance such as potassium salt,
Salts such as triethanolamine salt and L-arginine salt were prepared.

Further, low-molecular-weight chondroitin 6-sulfate, low-molecular-weight dermatan sulfate, low-molecular-weight heparin, low-molecular-weight heparan sulfate, etc. were prepared in free form or their respective salts by the same treatment as in the above example of chondroitin 4-sulfate.

The method for measuring the average molecular weight of the acidic mucopolysaccharide obtained by each treatment time was Somogyi-Nelson (Somogyi-Nelson).
son) method was used.

The blending amount of ceramide, glucosylceramide, and galactosylceramide is 0 based on the total amount of the skin cosmetic (composition).
The range of 01 to 3.0% by weight (hereinafter abbreviated as Wt%) is preferable. The content of the low molecular weight acidic mucopolysaccharide and its salts is preferably 0.01 to 3.0 Wt% based on the total amount of the skin cosmetic. Here, the blending amount of both components is 0.
If less than 01Wt%, the effect is not fully achieved, while 3.0Wt%
Even if it exceeds, the improvement of the effect commensurate with the increase cannot be expected.

The skin cosmetics of the present invention include, for example, lotions, emulsions,
It can be applied to creams, packs and the like.

In addition to the above, a colorant, a fragrance, an antiseptic, a surfactant, a pigment, an antioxidant and the like can be appropriately added to the skin cosmetic of the present invention within the range where the object of the present invention is achieved.

Further, the rough skin improving effect test, which was used to evaluate the skin aging preventing effect of the skin cosmetics of the present invention, the keratin improving effect test,
The moisturizing effect test (TWL value reduction rate) and the skin beautifying effect test (sensory test) are as follows.

(1) Rough skin improving effect test The lower leg of 20 middle-aged and elderly subjects complaining of rough skin, dry skin, and senile dry skin symptoms was tested for the effect of continuous application for 4 weeks. About 1 g of the sample was applied to the left lower leg test site of the test subject once a day, and the condition of the skin before and after the start of the test was visually judged by the following criteria. The lower right leg was not coated with the sample and served as a control.

If the skin dryness is improved by two or more levels by comparing the judgment results of the test site before and after the test and the control site (for example, + →
−, ++ → ±) is valid, 1 is slightly improved when it is improved, and is invalid when there is no change. The test results were shown by the number of subjects who were valid or slightly valid.

(2) Stratum corneum improvement effect test Scotch tape (Nichiban Mending Tape) was adhered to the subject's skin before and after the rough skin improvement effect test described above, and when this was peeled off, the state of the corneocytes adhering to the tape was confirmed. It was examined in detail by a scanning electron microscope, the skin keratinocyte anti-peeling property was analyzed according to the following criteria, and the effect of improving the stratum corneum (horny cell anti-peeling property increasing effect) was determined.

In the evaluation, when the difference between the evaluation point of the test site and that of the control site after continuous application for 4 weeks was 2 points or more, the case of 1 point was evaluated as valid, and the case of 0 point was evaluated as invalid. The test results are shown by the number of valid and moderately effective subjects out of 20 persons.

(3) Moisturizing effect test (TWL value reduction rate) TWL value and T before and after continuous application for 4 weeks on the subject's skin before and after the rough skin improving effect test
The moisturizing effect was investigated by calculating the reduction rate of the WL value (water retaining function enhancing effect) as follows.

TWL value The method of measuring the humidity change of the air on the sealed epidermis within a fixed time by electric resistance was used.

That is, the skin surface of the test subject is sealed with a measurement cell, and after forcedly drying air through the cell to sufficiently replace the inside of the cell with dry air, the ventilation of the dry air is stopped and the cell at that time is stopped. Calculate the relative humidity RHs (%) in the cell, then leave it for 10 minutes and measure the relative humidity RH ₁₀ (%) in the cell again. From the change in humidity at this time, the TWL value (mg / cm ² / hr) was calculated.

However, Dt: density of saturated steam in air at measurement temperature (t ° C) (mg /) V: cell volume () S: measurement area (cm ² ) TWL value reduction rate TWL value reduction rate is , TWL value before and after sample application, TWLT _A and TWL
It was calculated by substituting _B into the following formula.

TWL value reduction rate = (1-TWL _B / TWL _A ) × 100 (%) TWL _A : TWL value before sample application TWL _B : TWL value after sample application When the TWL value reduction rate is 20% or more, Effective ”, reduction rate is 2
The case of less than 0% was defined as "invalid". The test results were displayed by the number of subjects who were “effective” in 20 persons.

(4) Skin beautification test (practical test) Twenty middle-aged female subjects complaining rough skin, dry skin, and senile psoriasis, etc. evaluated the effect after using the sample twice a day (morning and evening) for three consecutive months. did. The test results are the wettability of the skin,
For each item of smoothness and elasticity, the number of people who responded that the skin was moisturized, the skin was smooth, and the skin was taut.

Comparative Examples 1 to 9 and Examples 1 to 12 [Bilayer Skin Lotion] A bilayer skin lotion base having a ceramide (hereinafter abbreviated as Cer) and glucosyl ceramide (hereinafter abbreviated as GluC) as shown in the following compositions. ), Galactosylceramide (hereinafter abbreviated as GalC), hyaluronic acid having a molecular weight of 4800 and 55,000 (hereinafter abbreviated as HA), sodium hyaluronate having a molecular weight of 4,800 and 48,000 (hereinafter abbreviated as HAN), Dermatan sulfate (hereinafter referred to as DS
Abundant potassium dermatan sulfate (hereinafter abbreviated as DSK), molecular weight 4,600 chondroitin 4-sulfate (hereinafter abbreviated as C4S), molecular weight 5,000 chondroitin 6-sulfate (hereinafter abbreviated as C6S), Molecular weight 5,0
Acid mucopolysaccharides such as 00 chondroitin 4-sulfate L-lysine (hereinafter abbreviated as C4SL), heparin having a molecular weight of 4,300 (hereinafter abbreviated as Hep), heparan sulfate having a molecular weight of 5,400 (hereinafter abbreviated as HS), etc. Each sample was prepared by blending and as shown in Tables 1 and 2 and used in each test.

(1) Composition (2) Preparation method The ceramides as the component (C) are dissolved in the component (A) in advance, and the acidic mucopolysaccharides as the component (D) are dissolved in the component (B), and then the components (A) and (B) are added. Each of the components was dissolved by heating at 80 ° C. and mixed. Then, each lotion was prepared by cooling to 30 ° C. with stirring.

(3) Properties The results of various tests of each two-layer type skin lotion are shown in the right column of Table 1.

Compared with the cosmetics in which the ceramides or acidic mucopolysaccharides were individually blended in Comparative Examples 1 to 9, the skin cosmetics of the present invention in Examples 1 to 12 in which both components were blended at the same time covered all of the tests. Good results were observed.

Examples 13 to 25, Comparative Examples 10 to 20 [Skin Cream] Similar to Experimental Example 1, each skin cream was prepared with the following composition and various tests were carried out. The results are shown in Tables 3 and 4. .

(1) Composition (2) Preparation method The ceramides as the component (C) are dissolved in the component (A) in advance, and the acidic mucopolysaccharides as the component (D) are dissolved in the component (B), and then the components (A) and (B) are added. Each of the components was dissolved by heating at 80 ° C. and mixed. Then, each skin cream was prepared by cooling to 30 ° C. with stirring.

(3) Characteristics As shown in Tables 3 and 4, the skin creams of Examples 13 to 26, which are the skin cosmetics of the present invention, are excellent in all of the characteristics as compared with Comparative Examples 10 to 18. Is clear,
No abnormality was found in the compounding characteristics. As Comparative Example 19, 0.2 wt% ceramide, cream containing 0.3 wt% of high molecular weight sodium hyaluronate (average molecular weight 6 million), and as Comparative Example 20, rhamnolipid 0.2 wt%
%, Low molecular weight sodium hyaluronate (average molecular weight 480
0) About the cream containing 0.3 wt%, the sample was used for 20 consecutive middle and old aged female subjects who complained of rough skin, dry skin and senile dry skin symptoms, three times a day (morning, noon and evening) for 4 consecutive weeks. The elasticity was evaluated by a short-term continuous test. As a result, the number of people
There were 9 in 19 and 5 in Comparative Example 20. On the other hand, Example
As 25, a cream containing 0.2 wt% of ceramide and 0.3 wt% of low molecular weight sodium hyaluronate (average molecular weight 4800) was similarly evaluated for elasticity,
The number of people who responded that the skin had become ten was 14 people.

(Effects of the Invention) As described above, it is apparent that the present invention provides an excellent and useful skin cosmetic that enhances skin function and exerts a remarkable effect in preventing skin aging.

Claims (1)

[Claims] 1. At least one of ceramide, glucosylceramide, and galactosylceramide, and an average molecular weight of 1,000 to
9,000 hyaluronic acid, average molecular weight 1,000 to 9,000 chondroitin sulfate, dermatan sulfate, average molecular weight 1,000 to
A skin cosmetic comprising 6,000 heparin and at least one selected from the group of low molecular weight acidic mucopolysaccharides of heparan sulfate and its salts.