JP3272891B2 - Bath additive - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a bath preparation which has an effect of improving the rate of turnover of collagen due to aging, has an excellent skin effect, and has no commercial cohesiveness. The present invention relates to a bath preparation characterized by containing a silicic acid alkyl ester which promotes procollagenase production or ascorbic acid or a derivative thereof which promotes collagen synthesis.

[0002]

2. Description of the Related Art Collagen is 70% by dry weight in the skin.
It has physical properties to the skin as well as physiological effects such as cell proliferation, differentiation and migration. It is known that the turnover rate of this collagen is physiologically lowered with aging (see Hyundai Kagaku, December, p. 36, 1990).

[0003] When the rate of collagen turnover decreases with aging, the life span of collagen molecules increases, the rate of intermolecular cross-linking increases, and the collagen molecules become resistant to collagenase degradation (Aging of the Skin, page 121). , 1989,
Raven Press, New York). As a result, the amount of collagenase required to degrade a certain amount of collagen increases, causing a vicious cycle of increasingly slowing turnover.

[0004] It has been suggested that as a result of this vicious cycle, skin softness and elasticity are reduced and wrinkles are increased.

[0005] Collagenase is a rate-limiting enzyme in decomposing interstitial collagen (type I, type II, and type III collagen) in connective tissue, and plays an important role in collagen metabolism. Collagenase is secreted from cells as a precursor, procollagenase, and then activated in vivo by collagenase by proteolytic enzymes such as plasmin and stromlysin (Bioch.
emical Journal, 166, 21 pages, 1977 and Proceedi
ngs of the National Academy of Sciences of the U.
SA, 86, 2632, 1989).

[0006] From the above, it is considered that a procollagenase production promoting substance is effective for improving the decrease in collagen turnover rate due to aging.

Further, in order to improve the decrease in the turnover rate of collagen, it is more effective not only to promote the degradation by collagenase but also to promote the synthesis of collagen at the same time, and to use the collagen synthesis promoting substance together with the procollagenase production promoting substance. Is considered effective.

[0008] Interleukin 1, tumor necrosis factor (TNF), epidermal growth factor (EG) have been known as substances capable of enhancing the procollagenase-producing ability of cells.
F), cytokines such as platelet-derived growth factor (PDGF) and phorbol esters are known. However, these cytokines are expensive and the production cost is high. In addition, phorbol ester is a tumor promoter and its use is hard to say safe.

[0009] On the other hand, various bathing agents have been conventionally developed, but when the above-mentioned physiologically active substances are to be blended, when they are mixed with a bathing agent component which is generally used, the components coagulate. There are drawbacks, such as the appearance and bad appearance, and it is difficult to disperse in bath water.
In some cases, the product value is significantly reduced.

[0010]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide a bath which has an effect of improving a decrease in the turnover rate of collagen due to aging, is excellent in beautiful skin effect, and has no commercial cohesiveness. To provide an agent.

[0011]

SUMMARY OF THE INVENTION An object of the present invention is to provide an organoalkoxy compound that promotes the production of procollagenase in cells.
Silicic acid alkyl ester excluding orchid or organoa
This is achieved by a bath additive characterized by containing an alkyl silicate ester excluding lucoxysilane and ascorbic acid or a derivative thereof that promotes collagen synthesis.

[0012] As silicic acid alkyl ester as procollagenase production promoting substance for use in the present invention, O
Silicic acid alkyl esters excluding luganoalkoxysilane
Specifically , for example, silicic acid methyl ester,
Examples include ethyl silicate, methyl meta-silicate, ethyl meta-silicate, propyl meta-silicate, methyl ortho-silicate, and ethyl ortho-silicate.

The content of the alkyl silicate used in the present invention is 0.1 to 20 based on the total amount of the bath agent.
% By weight, more preferably 1 to 15% by weight.

Ascorbic acid or a derivative thereof as a collagen synthesis promoter used in the present invention includes:
Ascorbic acid and its salts ( such as sodium salts and magnesium salts), ascorbic acid phosphates and sulfates and their salts ( such as magnesium salts), stearates, dipalmitates and monopalmitates.

The content of ascorbic acid or a derivative thereof used in the present invention is 0.1% based on the total amount of the bathing agent as 100.
It is preferably from 001 to 10% by weight, more preferably from 0.1 to 10% by weight.
01 to 3% by weight.

The other bathing agent components to be blended with the active ingredient alkyl silicate in the present invention include:
Any of the commonly used substances can be used, but can be appropriately selected from the following substances according to the efficacy and effect.

1) Inorganic salts: sodium chloride, sodium hydrogen carbonate, sodium carbonate, boric acid, borax, sodium sulfate, sodium sulfide, potassium sulfide, sodium nitrate, calcium nitrate,
Ammonium sulfate, sodium thiosulfate, calcium hydrogen phosphate, potassium chloride, ammonium chloride, sodium phosphate, sodium hyposulfite, calcium thiosulfate,
Sulfur, urea, sodium sesquicarbonate, magnesium sulfate, etc.

2) Organic acids Benzoic acid, citric acid, fumaric acid, tartaric acid, malic acid, salicylic acid and the like.

3) Oils and fats Olive oil, soybean oil, almond oil, castor oil, coconut oil, palm oil, turtle oil, nuka oil, jojoba oil, mink oil, egg yolk oil, squalane, avocado oil, lanolin, liquid paraffin, white Vaseline, DHA, EPA and the like.

4) Binders Sodium carboxymethylcellulose, methylcellulose, sodium salt, casein, pectin, starch,
Sodium alginate, polyvinyl alcohol, polyvinylpyrrolidone, locust bean gum, carrageenan,
Agar, carbopol, etc.

5) Polyhydric alcohols, humectants glycerin, propylene glycol, sorbitol, polyethylene glycol, 1,3-butylene glycol,
Vitamin C and its derivatives, hydrolyzed silk, collagen, chondroitin and its protein complexes, glycyrrhizin and its derivatives, and the like.

6) Surfactant Sodium lauryl sulfate, sodium polyoxyethylene lauryl ether sulfate, diethanolamide laurate, glycerin monostearate, polyethylene glycol monostearate, polyoxyethylene glyceryl monostearate, sorbitan monolaurate, poly Oxyethylene sorbitan monooleate, polyoxyethylene cetyl ether, polyoxyethylene hydrogenated castor oil, fatty acid soap, N-acyl glutamate and the like.

7) Flavors Lavender oil, jasmine oil, rose oil, lemon oil, orange oil, peppermint oil, thyme oil, shobu oil, fennel oil, cedar oil, hiba oil, hinoki oil, rose oil, eucalyptus oil, camphor And natural and synthetic flavors such as peppermint oil, spearmint oil, geraniol, mandarin oil, spruce and citronellol.

Further, the bath composition of the present invention may optionally contain, as necessary, other ingredients other than the above, such as crude drugs, bactericides, vitamins, and tar dyes for cosmetics. .

When the bath preparation of the present invention is used, the skin whose collagen turnover has been reduced due to aging is 1 to
It is appropriate to bathe at a concentration of 200 mg / l for 10 to 30 minutes per day.

[0026]

The present invention will be described below in detail with reference to Test Examples, Examples and Comparative Examples. However, the present invention is not limited to the raw materials and compounding ratios described in the examples. In addition, the definition of the phrase used in the test example is described.

MEM medium : Minimum essential medium 10-101
(Dai Nippon Pharmaceutical Co., Ltd.) Add 1 liter of purified water to one bag, each with a final concentration of 0.1% by weight lactalbumin enzyme hydrolyzate (Sigma), 1% by volume non-essential amino acid, 1 mM sodium pyruvate (all above are large) It is prepared by adding 0.12% by weight of sodium hydrogen carbonate and 50 mg / l of streptomycin.

FBS : fetal calf serum

Measurement buffer : 0.2 M NaCl, 5 mM CaCl ₂ , 0.05
A buffer in which a 50 mM aqueous solution of Tris (hydroxymethyl) aminomethane (hereinafter simply referred to as Tris) containing volume% Brij-35 is adjusted to pH 7.5 with hydrochloric acid at room temperature.

Procollagenase production : In this experiment, procollagenase production was quantified as collagenase activity obtained by activation with trypsin.

Test Example 1 In the cells used in the present experiment, the produced collagenase is recovered as a procollagenase having no activity as it is, and thus the amount of procollagenase produced is determined by the collagenase activity obtained by activating with trypsin. As quantified.

A normal human fibroblast cell line [Detroit-551 (ATCC CCL110) collected from the skin of a Caucasian woman] was cultured at 1 × 10 ⁵ cells / ml in a MEM medium containing 10% by volume of fetal bovine serum (hereinafter abbreviated as FBS). And 2 ml of each was seeded on a 6-well plate, and cultured at 37 ° C. under 5% carbon dioxide gas and saturated steam.

The MEM medium is the minimum essential medium 10-
101 (manufactured by Dainippon Pharmaceutical Co., Ltd.), a final concentration of 0.1% by weight lactalbumin enzyme hydrolyzate (manufactured by Sigma), 1% by volume non-essential amino acid, 1 mM sodium pyruvate (all are manufactured by Dainippon Pharmaceutical Co., Ltd.) , 0.12% by weight sodium bicarbonate and 50 mg / l streptomycin.

The 10 mM ethyl metasilicate solution of Example 1 described later was diluted with MEM medium supplemented with 0.6% by volume of FBS to obtain additive solutions of various concentrations.

After 24 hours, the culture medium was removed by suction, and the cells were washed twice with MEM medium supplemented with a final concentration of 0.6% by volume of FBS. I got

To 250 μl of the obtained culture supernatant, 1.75 ml of 10 mM Tris-HCl buffer (adjusted to pH 7.8 at 4 ° C. and containing 1 mM calcium chloride and 0.05% by volume Brij-35) was added, and the same buffer was added. CM-Sepharose CL-6B equilibrated with
^TM (Pharmacia, bed capacity 0.5 ml).

Next, the same buffer solution containing 125 mM saline was added.
Inhibitor was removed with 5 ml (total 4 times, total volume 2 ml),
Procollagenase was recovered with 0.5 ml of the same buffer containing 500 mM salt (total 4 times, 2 ml in total) to prepare a test solution.

Further, 50 μl of the test solution was mixed with a trypsin solution (Type 12 manufactured by Sigma) at a concentration of 1 mg / m 2 in a measuring buffer.
20 μl) and incubated at 35 ° C. for 5 minutes, and then add 30 μl of soybean trypsin inhibitor solution (Merck's No. 24020 to a concentration of 3 mg / ml in a measurement buffer). Trypsin was inactivated to obtain a collagenase solution.

Using type I collagen labeled with fluorescein isothiocyanate (FITC-collagen acetate solution at a concentration of 1 mg / ml, manufactured by Cosmo Bio Inc.) as a substrate solution, the method of Nagai et al. (Inflammation, Vol. 4, No. 2, 123 pages, 1984
Activity of the above collagenase (unit / ml)
Was measured. The amount of collagenase generated from procollagenase by the above-described trypsin treatment to decompose 1 μg of type I collagen (FITC-collagen) per minute at 35 ° C. is defined as one unit of procollagenase. / Ml of culture solution) (this value is defined as X).

On the other hand, as a control test, purified water was added in place of metasilicate ethyl ester, and the amount of procollagenase production (unit / ml of culture solution) without addition of metasilicate ethyl ester was determined in the same manner as described above. This value is Y).

Next, the procollagenase production promotion rate was calculated from these values according to the following equation.

Procollagenase production promotion rate = (X / Y)

The results of quantifying the amount of procollagenase in the obtained culture supernatant are shown in Table 1.

[0044]

[Table 1]

As shown in Table 1, in the control (no addition), 5
6.5 ± 3.6 units / ml (mean ± standard error, n = 3)
In contrast, the addition of ethyl metasilicate significantly promoted the production of procollagenase in a dose-dependent manner.

Test Example 2 Similarly to Test Example 1, the silicate alkyl ester solutions of Examples 2, 3, and 4 described below were added to normal human fibroblasts, and the production of procollagenase was examined.

Table 2 shows the results obtained by quantifying the amount of procollagenase in the obtained culture supernatant.

[0048]

[Table 2]

As described in Table 2, in the control (no addition), 56.5 ± 6.2 units / ml (mean ± standard error, n =
In contrast to 3), ethyl silicate, propyl metasilicate and ethyl orthosilicate significantly promoted the production of procollagenase.

Test Example 3 The bathing effect of a bathing agent containing ethyl metasilicate was actually examined as follows.

50 g of the bath agent of Example 5 described later and 50 g of the bath agent of Comparative Example 1 or 50 g of the bath agent of Example 6 described later.
And 50.0 g of the bath preparation of Comparative Example 2 at 41 ° C.
Into 180 liters of hot water. Ten test subjects were partially bathed with the right foot in the hot water of Example 5 or 6 and the left foot in the hot water of Comparative Example 2 or 3 three times a day (morning, noon, night) for 5 minutes and 10 days, respectively. Ten days later, the state of the skin sulcus on the skin surface of the forefoot was observed with a magnifying video camera, and scored based on the following criteria. In addition, the evaluation based on the questionnaire was performed according to the following criteria.

Table 3 shows the evaluation criteria for the state of the skin groove on the skin surface.

[0053]

[Table 3]

Table 4 shows the questionnaire evaluation method.

[0055]

[Table 4]

Table 5 shows the results of examining the bathing effect.

[0057]

[Table 5]

As described in Table 5, ethyl metasilicate (and ascorbic acid phosphate, hereinafter A)
In the case where a bath preparation containing sc-P) was used, the state of the crevices on the skin surface was clear and the moist feeling of the skin was high in the questionnaire evaluation as compared with the comparative example.

Example 1 14.4 mg of ethyl metasilicate was suspended in 9 ml of a 0.1% aqueous solution of sodium polyoxyethylene (20) lauryl ether sulfate, and the solution was made up to 10 ml with purified water. It was sterilized by filtration through a nitrocellulose membrane having a pore size of 0.2 μm (manufactured by Advantech Toyo, DISMIC-25) to obtain a metasilicate ethyl ester solution.

Example 2 A silicate methyl ester solution was prepared in the same manner as in Example 1 except that 20.8 mg of silicate methyl ester was used.

Example 3 A propyl metasilicate solution was prepared in the same manner as in Example 1 except that 15.8 mg of propyl metasilicate and 9 ml of a 0.1% sodium polyoxyethylene (20) lauryl ether sulfate solution were used. .

Example 4 14.4 mg of ethyl orthosilicate was dissolved in 9 ml of 0.1% sodium polyoxyethylene (20) lauryl ether sulfate solution, the pH was neutralized with 1N sodium hydroxide, and 10 mg of Asc-P was further added. In addition, the volume was adjusted to 10 ml with purified water. It was sterilized by filtration in the same manner as in Example 1 to prepare an orthosilicate ethyl ester solution.

Example 5 A bath preparation composition having the following formulation was prepared by a usual method of mixing powder, and 100 g of a bath preparation containing 10.00 g of ethyl metasilicate was prepared. No cohesiveness occurred during preparation. No aggregation occurred even after storage at 45 ° C. for 3 months.

Ethyl metasilicate 10.00 g Sodium sulfate 45.00 g Sodium bicarbonate 32.65 g Sodium chloride 5.00 g Polyoxyethylene (20) 5.00 g Sodium lauryl ether sulfate Peach leaf extract 30 g Fragrance 1.00 g Organic dye 0.05 g １０ 100.00 g

Example 6 A bath preparation composition having the following formulation was prepared by a usual method of mixing powder, and 100 g of a bath preparation containing 15.00 g of ethyl metasilicate and 10.0 g of Asc-P were prepared. No cohesiveness occurred during preparation. 45 ° C, 3
There was no aggregation after storage for months.

Ethyl metasilicate 15.00 g 22.95 g sodium sulfate 46.00 g sodium bicarbonate 10.0 g Asc-P 5.0 g Polyoxyethylene (20) 5.0 g Sodium lauryl ether sulfate 1.0 g Organic dye 0.05 g １０ 100.00 g

Comparative Example 1 A bath preparation composition having the following formulation was prepared by a usual method of mixing powder, and 100 g of a bath preparation for comparison was prepared.

Sodium sulfate 45.00 g Sodium bicarbonate 42.65 g Sodium chloride 5.00 g Polyoxyethylene (20) 5.00 g Sodium lauryl ether sulfate Peach leaf extract 1.30 g Flavor 1.00 g Organic Dye 0.05 g １０ 100.00 g

Comparative Example 2 A bath preparation composition having the following formulation was prepared by an ordinary method of mixing powder, and 100 g of a bath preparation for comparison was prepared.

Sodium sulfate 22.95 g Sodium bicarbonate 61.00 g Asc-P 10.0 g Polyoxyethylene (20) 5.0 g Sodium lauryl ether sulfate Perfume 1.0 g Organic dye 0.05 g ───────────────────────────────── 100.00 g

[0071]

As described above, the bath preparation of the present invention has an effect of improving a decrease in collagen turnover rate due to aging,
In a practical human test, it is clear that a bath agent excellent in beautiful skin effect and commercially non-cohesive can be provided.

────────────────────────────────────────────────── ─── Continued on the front page (58) Field surveyed (Int. Cl. ⁷ , DB name) A61K ^7/ 00-7/50 CA (STN) REGISTRY (STN)

Claims (2)

(57) [Claims] 1. A bath additive comprising an alkyl silicate other than an organoalkoxysilane . 2. A bath agent comprising an alkyl silicate other than an organoalkoxysilane and ascorbic acid or a derivative thereof.