JP3333428B2 - External preparation for skin - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to the ability to activate lipid synthesis and metabolism in the epidermis of aging skin, improve the skin internal barrier by enhancing the epidermal penetration barrier function, and maintain homeostasis against skin irritation. The present invention relates to an external preparation for skin having an excellent effect of strengthening skin.

[0002]

2. Description of the Related Art Generally, skin aging is roughly classified into two types: natural aging, which shows a large biological change due to aging, and light aging due to the influence of sunlight. (Kligman, AM Aging and Skin, Skin and Light Aging, pp. 33-36, published by Seiji Shoin, 1986.
Year). In places where there is almost no body hair, such as the human face,
In particular, changes due to light aging tend to appear strongly.

[0003] Aging skin is skin in which keratinocyte exfoliation due to drying of the skin surface, phenomena such as wrinkles, tallness, and spots are observed. This aging skin is thought to be caused by the continued exposure of the skin to various stimuli from the environment, resulting in a decrease in the metabolic activity of the cells that make up the skin and the degeneration of epidermal cells, dermal fibroblasts, and fibrous components. (Haratake and Mimura, New Perspectives on Aging Control Cosmetics, Fragrance Journal, Vol. 22, pp. 38-46, 1994). From this point of view, various studies have been made to improve aging skin, and substances that improve wrinkles and tarmi such as vitamin A acid (retinoic acid) and α-hydroxy acid (Haratake,
Mimura, New Perspectives on Aging Control Cosmetic, Fragrance Journal, Vol. 22, pp. 38-46 (1994), Diisopropylamine dichloroacetate
136528), γ-aminobutyric acid (JP-A-51-
Cell activators and the like have been proposed.

[0004] However, vitamin A acid and α-hydroxy acid are effective for wrinkles and tarmi when added to a skin external preparation at a relatively high concentration, but have a problem in safety. In addition, DADA and GABA require a certain period of time to exhibit their effects, and their effectiveness is not always sufficient. Therefore, an external preparation for skin having an excellent effect of improving aging skin is not sufficiently satisfied at present.

[0005] It is an object of the present invention to enhance the keratinocyte intercellular lipid of the epidermal permeation barrier, which plays a role in protecting the inside of the skin from various stimuli to the inside of the skin that cause them both in natural aging and light aging. Another object of the present invention is to provide a skin external preparation that improves the skin internal environment by enhancing the epidermal permeation barrier function and is excellent in improving aging skin.

[0006]

Means for Solving the Problems The present inventors have conducted intensive studies in view of the above-mentioned circumstances, and as a result, have confirmed that the following external preparation for skin is excellent in improving the effect on corridor skin, and have determined the present invention. It was completed. That is, claim 1 of the present invention is a skin external agent characterized by containing Na Iashin'amido and mevalonate lactone.

[0007]

Embodiments of the present invention will be described below in detail. Niacin, niacinamide, nicotinic alcohol or a salt thereof, nicamate citrate, vitamin E nicotine as niacin derivatives used in the present invention
And lactone mevalonate are both known substances.

The amount of the niacin derivative and lactone mevalonate of the present invention is 0.001 to 1% by weight based on the total amount in the external preparation for skin of the present invention.
(Hereinafter abbreviated as wt%), it is preferable to combine mevalonate lactone in the range of 0.001 to 0.5 wt%. If the amount is less than each of the lower limits, the intended effect of the present invention may not be sufficient. On the other hand, even if the value exceeds the upper limit, the effect corresponding to the increase may not be improved, which is not preferable.

[0009] The niacin derivative of the present invention has the effect of promoting ceramide synthesis in epidermal cells (Japanese Patent Application No. 8-108).
No. 120871), but the moisturizing effect of lactone mevalonate (JP-A-4-99707) has already been known. Is not a known finding.

The external preparation for skin of the present invention can be applied to skin cosmetics, quasi-drugs, bath preparations, etc., and in dosage form, for example, lotions, emulsions, creams, packs and the like. Can be applied. In addition, the skin external preparation of the present invention may appropriately contain a pigment, a fragrance, a preservative, a surfactant, a pigment, an antioxidant and the like within a range that achieves the object of the present invention.

Hereinafter, the present invention will be described in detail based on Examples and Comparative Examples. Example 1, Comparative Examples 1 to 3 The recovery effect of the epidermal penetration barrier when the external preparation for skin of the present invention was applied to aged skin was examined by the following test method.

1. Experimental Animals Used in the Examples and Comparative Examples Five groups of hairless mice 85 weeks old at the start of the test were used. The life of the hairless mouse is about one and a half to two years (about 70 to 100 weeks), and it can be said that the hairless mouse used this time is in a sufficiently aged state.

2. Measurement of TEWL 2-1. Measurement device and conditions TEWL is a continuous sweating device Hydrograph AMU-10
0 (manufactured by K & S) was measured as follows. A 1 square centimeter capsule was brought into close contact with the skin, and the capsule was ventilated by introducing dry nitrogen (300 ml / min), and the amount of water in the recovered nitrogen gas was measured. From this measured value, the amount of water (milligram) evaporating from one square centimeter of skin per minute was calculated,
TEWL. 2-2. Samples and Experimental Methods 0.5% niacinamide, 0.1% mevalonate lactone and niacinamide in a 0.5% nonionic surfactant (polyoxyethylene nonylphenyl ether (NP-15), Nikko Chemicals) aqueous solution Three samples containing 0.5% and 0.1% mevalonate lactone were prepared. First, 0.05 ml of each of these samples was previously placed on the back skin (within a circle having a diameter of about 2.5 cm) of the hairless mouse for 1 day.
5 times a week for 4 consecutive weeks (pre-application). Then, on the third day from the last application of the continuous application, the back skin of the hairless mouse was gently wiped 50 times with a cotton swab containing acetone. The TEWL at this time was measured, the value is equal to or larger than 0.15 mg / cm ² / min, where it terminates the processing in acetone, 0.15 mg / cm ² /
If less than a minute, measure the TEWL every five wipes,
The treatment was performed until the concentration reached 0.15 mg / cm ² / min or more. The number of treatments at this time was recorded and defined as the skin transmission barrier strength. If the number of treatments increases by applying the sample,
This value indicates that the strength of the epidermal penetration barrier was enhanced. Next, T immediately after the treatment with acetone and 24 hours after the treatment.
The EWL was measured, and the value immediately after the treatment was taken as 100% epidermal permeation barrier collapse, that is, without recovery, and the value at 24 hours after the treatment was determined as a barrier recovery rate indicating how much the epidermal permeation barrier recovered in 24 hours. Was. The closer the barrier recovery rate is to 100, the more the epidermal penetration barrier is recovered.

The effect of the application of each sample on the epidermal penetration barrier strength of hairless mice is shown in Table 1.

[0015]

[Table 1]

The value of the skin permeation barrier strength was represented by an average value ± standard error. Comparative Example 1 shows that the barrier strength was less than 50 times for all individuals. The epidermal penetration barrier strength of the hairless mouse to which the sample of Example 1 was applied was measured in Comparative Example 1.
It shows that the sample of the present invention enhances the epidermal permeation barrier strength as compared with the values of No. 3 to No. 3. Next, Table 2 shows the permeation barrier recovery rate of the hairless mouse by application of each sample.

[0017]

[Table 2] The epidermal barrier recovery rate of this result was determined by TE
WL was set to a recovery rate of 0%, and T was measured 24 hours after each sample treatment.
This is a relative value calculated from EWL. That is, 100%
It indicates that the recovery was promoted as approaching. Values are shown as mean ± standard error.

The results of Example 1 clearly show that the recovery of the epidermal penetration barrier is promoted as compared with Comparative Examples 1 to 3. The results of Comparative Examples 2 and 3 show a slight effect of promoting the recovery of the barrier when compared with Comparative Example 1, but the results of Example 1 show a clear effect of promoting the recovery when compared with Comparative Examples 2 and 3. Show. Therefore, by combining niacinamide and mevalonate lactone, it can be said that a synergistic effect that could not be found alone was confirmed.

Examples 2 to 5 and Comparative Example 4 In the present Example and Comparative Example, skin lotions having the compositions shown in Table 3 were prepared according to the following preparation method, and were used as samples to obtain 10 healthy persons by the following procedure. (Male 55-64
Aged) was applied to the skin on the inner side of the upper arm, and an epidermal penetration barrier strength test was performed by the following procedure. Each sample was applied to the test site (4 cm 2, 2 × 2 cm for each sample) in 0.1 ml portions, once a day after bathing, seven times a week, for two consecutive months. Next, on the third day from the end of the final coating, TEWL was 0.15 mg /
The number of treatments to wipe the skin surface until cm2 / min was recorded in units of five.

[0020]

[Table 3]

Preparation Method Niacinamide of component C and lactone mevalonate are blended with component B, components A and B are uniformly dissolved, and then components A and B are mixed, stirred and dispersed, and then filled into a container. . When used, the contents are shaken and dispersed uniformly.

Table 4 shows the test results of the effect on the human epidermal permeation barrier strength.

[0023]

[Table 4] (Values are shown as mean ± standard error)

From these results, it can be seen that the skin lotions of Examples 2 to 5 have clearly enhanced skin permeation barrier strength as compared with Comparative Example 4. Further, the skin low of the present invention
No skin abnormalities such as redness and dryness due to the application were observed.

Examples 6 to 9 and Comparative Example 5 In the same manner as in Examples 2 to 5, skin creams having the compositions shown in Table 5 were prepared according to the following preparation method, and the skin transmission barrier strength was examined in the same manner.

[0026]

[Table 5]

Preparation Method Niacinamide of component C and lactone mevalonate are mixed with component B, and components A and B are each heated and dissolved at 80 ° C., and then mixed and stirred, cooled to 30 ° C. A skin cream was prepared.

The permeation barrier strength of human epidermis was examined, and the results are shown in Table 6.

[0029]

[Table 6] Values are shown as mean ± standard error.

From these results, it was confirmed that the skin creams of Examples 6 to 9 of the present invention had a clear effect of enhancing the epidermal permeation barrier as compared with Comparative Example 5. In addition, almost the same effect was observed between the skin creams of Examples 6 to 9, and by combining Niacinamide 0.001 to 1 wt% and mevalonate lactone 0.001 to 0.5 wt%, It has been found that a clear effect can be obtained. In addition,
No adverse effects such as redness on the skin due to continuous application of each skin cream were observed.

Examples 10 to 14 and Comparative Example 6 In addition, niacin, nicotinic alcohol, nicometate citrate, and vitamin E nicotine are used in place of niacinamide of the skin cream having the composition of Examples 6 to 9. , Respectively, and the same epidermal transmission barrier strength test was carried out. Table 7 shows the results.

[0032]

[Table 7] Values are shown as mean ± standard error.

From these results, it was confirmed that the skin creams of Examples 10 to 14 had a clear effect of enhancing the skin permeation barrier as compared with Comparative Example 6. In addition, the skin creams of Examples 11 to 14 exhibited substantially the same effects as those of the skin cream of Example 10, and it was found that the same effects were obtained with niacin derivatives other than niacinamide. No adverse effects such as redness on the skin due to continuous application of each skin cream were observed.

[0034]

Industrial Applicability As described above, the present invention provides a skin external preparation having an excellent effect of improving aging skin by activating the biosynthesis and metabolism of epidermal keratinocyte intercellular lipids, thereby enhancing the epidermal penetration barrier. It is clear.

──────────────────────────────────────────────────続 き Continuation of front page (56) References JP-A-7-145033 (JP, A) JP-A-62-138410 (JP, A) JP-A-62-135405 (JP, A) JP-A-4- 99707 (JP, A) JP-A-9-315930 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) A61K ^7/ 00-7/50

Claims (1)

(57) [Claims] 1. An external preparation for skin comprising niacinamide and lactone mevalonate.