JPH07188036A - Collagen metabolism improving agent, cosmetics and bathing medicine - Google Patents

Abstract

PURPOSE:To obtain a collagen metabolism improving agent which contains a silicic acid-relating substance or its salt and has effects such as skin smoothing, hair tonic, depilation prevention and improves the diseases caused by anomalous accumulation of collagen or reduction in collagen metabolism accompanied by senility. CONSTITUTION:This improving agent contains silicic acid-relating compounds such as silicic acid, metasilicic acid, orthosilicic acid and water glass, preferably calcium silicate, sodium metasilicate, sodium orthosilicate or their salt. The agent is added to skin cosmetics, hair tonic cosmetic, and bathing agents. It is preferred that the bathing agents further contain ascorbic acid or its derivative.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a collagen metabolism-improving agent containing a silicic acid-related substance (silicic acid, metasilicic acid, orthosilicic acid, water glass) or a salt thereof as an active ingredient, and a cosmetic composition for activating collagen metabolism. The present invention relates to a bath agent, and more particularly to a collagen metabolism-improving agent, a cosmetic agent, and a bath agent containing a silicic acid-related substance or a salt thereof that promotes procollagenase production in cells as an active ingredient.

[0002]

2. Description of the Related Art Diseases associated with abnormal accumulation of collagen (liver and lung fibrosis, keloids, hypertrophic scars and scleroderma)
Have suggested that the balance between collagen synthesis and degradation is lost. For example, hardening of the skin associated with scleroderma increases the amount of collagen (Ar-thritis Rheum., 22), 1
(See p. 30, 1979) and degradation of collagen degradability (The Jou
rnal of Clinical Investigation, 56, 1175, 197
5 years)).

Among them, the decrease in collagen degradability is considered to be due to the decrease in collagenase activity of various tissues and skin fibroblasts (Skin, Vol. 14, p. 217, 1972, Journal.
l of Clinical Investigation, 56, 1175, 1975 and Life Sciences, 30, 23, 1982), enhancement of collagenase activity is desired.

70% collagen by dry weight on the skin
It is included and gives physical properties to the skin as well as physiological effects such as cell proliferation, differentiation and migration.
It is known that this collagen not only causes the above-mentioned diseases but also has a physiological decrease in turnover rate with aging (see Hyundai Kagaku, December issue, p. 36, 1990).

A decrease in collagen turnover rate with aging prolongs the life of collagen molecules, increases the proportion of intermolecular crosslinks, and makes them resistant to collagenase degradation (Aging of the Skin, p. 121). , 1989,
Raven Press, New York). As a result, the amount of collagenase required to decompose a certain amount of collagen is increased, which causes a vicious cycle in which the turnover rate is further reduced.

As a result of this vicious circle, the flexibility and elasticity of the skin are reduced and wrinkles are increased, and in the case of hair, the scalp is tense, the blood flow is reduced, the activity of hair mother cells is reduced, and hair loss occurs. It has been suggested to cause illness.

Conventionally, various skin cosmetics and hair nourishing cosmetics have been developed, but few attempts have been made to positively solve the above problems by directly acting on the metabolism of collagen. .

[0008] By the way, collagenase is a rate-limiting enzyme in degrading 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,
In vivo, collagenase is then activated by proteolytic enzymes such as plasmin and stromlysin (B
iochemical Journal, 166, 21 pages, 1977 and Pro
ceedings of the National Academy of Sciences of the
USA, Vol. 86, page 2632, 1989)).

From the above, it is considered that a substance that promotes the production of procollagenase is effective for improving the decrease in collagen turnover rate associated with 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 collagen synthesis at the same time, and it promotes collagen synthesis together with a substance that promotes the production of procollagenase. It is considered effective to share the substance that is used.

Interleukin-1, tumor necrosis factor (TNF), and epidermal growth factor (EG) have been used as substances capable of enhancing the ability of cells to produce procollagenase.
F), cytokines such as platelet-derived growth factor (PDGF) and phorbol ester are known. However, these cytokines are expensive and the manufacturing cost is high. Further, phorbol ester is a carcinogenic promoter substance, and its use is not safe.

[0012]

Therefore, the object of the present invention is to provide a procollagenase production promoting action and an effect of improving the decrease in collagen turnover rate due to aging, which is inexpensive and excellent in safety. It is to provide a collagen metabolism improving agent. Furthermore, skin softness, elasticity, skin cosmetics excellent in improving effects on wrinkles, hair nourishing cosmetics excellent in hair growth effect and hair loss prevention effect, cosmetics such as bath agents improving systemic skin collagen metabolism are provided. To provide.

[0013]

[Means for Solving the Problems] The above-mentioned objects include a collagen metabolism-improving agent characterized by containing a silicic acid-related substance or a salt thereof, a silicic acid-related substance or a salt thereof and ascorbic acid or a derivative thereof. Collagen metabolism improving agent characterized by the above, cosmetics (skin cosmetics, hair nourishing cosmetics) characterized by containing any of the above collagen metabolism improving agents, silicic acid-related substances or salts thereof and ascorbic acid Alternatively, it is achieved by a bathing agent containing a derivative thereof.

The silicic acid-related substances used in the present invention include, for example, silicic acid, metasilicic acid, orthosilicic acid, metadisilicic acid, metatrisilicic acid, and the salts thereof, such as water glass and sodium. Examples thereof include salts, potassium salts, magnesium salts, aluminum salts and calcium salts.

Since silicic acid is insoluble in water, metasilicic acid, orthosilicic acid, metadisilicic acid and metatrisilicic acid exist only in the solution, and silicic acid, metasilicic acid, orthosilicic acid and metadisilicic acid are present. Magnesium salts of silicic acid and meta-trisilicic acid are also insoluble in water. Therefore, as the collagen metabolism-improving agent of the present invention, potassium silicate, sodium metasilicate,
Sodium orthosilicate is preferable because it is easy to use.

The content of the silicic acid-related substance or its salt in the collagen metabolism-improving agent or cosmetic of the present invention varies depending on its use, but is 0.1 to 99 based on the total amount of the collagen metabolism-improving agent or cosmetic. Weight% is preferable, and 5-60 weight% is especially preferable.

Ascorbic acid or a derivative thereof used in the present invention includes ascorbic acid and its salts (sodium salt, magnesium salt, sulfate, etc.), ascorbic acid phosphoric acid ester and sulfuric acid ester and its salts (magnesium salt, sulfate). Etc.), stearic acid ester, dipalmitic acid ester, monopalmitic acid ester and the like can be used.

The content of ascorbic acid or its derivative varies depending on its use, but the total amount of the composition to be applied is 1
0.00 is preferably 0.001 to 10% by weight, more preferably 0.01 to 3% by weight.

The collagen metabolism-improving agent of the present invention is the above-mentioned silicic acid-related substance or its salt, ascorbic acid or its derivative itself, or a product obtained by diluting these with water, neutralized water, acidic water, or the like. It is provided in the form of a product to which a preservative such as methylparaben is appropriately added.

The collagen metabolism-improving agent of the present invention can be used for increasing the production amount of medically or pharmaceutically important procollagenase by adding it to the medium during cell culture.

[0021] The collagen metabolism-improving agent of the present invention is prepared into a dosage form for oral administration or a parenteral dosage form such as injection or transdermal preparation by blending with a commonly used known component according to the purpose of use. It is possible to administer to humans orally or parenterally such as injection and transdermal.

The dosage forms for oral administration include tablets, granules,
In addition to solid preparations such as powders, fine granules and hard capsules, liquid preparations such as syrups, elixirs and soft capsules are included.

Such preparations are manufactured by a conventional method. Tablets, granules, powders and fine granules are prepared by using silicic acid-related substances or salts thereof and usual pharmaceutical additives such as lactose, starch, crystalline cellulose, magnesium stearate, It is produced by mixing with hydroxypropyl cellulose, talc and the like, and the hard capsule is produced by appropriately filling the above-mentioned fine granules and powders in capsules.

The syrup is produced by dissolving a silicic acid-related substance or a salt thereof in an aqueous solution containing sucrose, D-sorbitol, carboxymethylcellulose and the like together with a preservative such as methyl paraoxybenzoate and propyl paraoxybenzoate. The elixir is produced by dissolving a silicic acid-related substance or a salt thereof in ethanol and mixing the solution with glycerin, orange oil, lemon oil, coriander oil, anise oil, talc and the like.

Soft capsules are produced by dissolving a silicic acid-related substance or a salt thereof in a lipid excipient such as vegetable oil, oily emulsion, glycols, etc., and filling the capsules with a soft capsule.

The injectable preparation is produced by dissolving or emulsifying a silicic acid-related substance or a salt thereof in physiological saline or a lipid vehicle such as vegetable oil, oily emulsion, glycol or the like and aseptically enclosing it in an ampoule or vial. To be done.

The transdermal agents include ointments, lotions, poultices, gels, creams, liquids, sprays, bath agents and patches. Such preparations include silicic acid-related substances or salts thereof and usual pharmaceutical additives such as hydrocarbons such as petrolatum, squalane, liquid paraffin, higher alcohols such as stearyl alcohol and cetanol, higher fatty acids such as isopropyl myristate and isopropyl palmitate. Lower alkyl esters, animal oils and fats such as lanolin, polyhydric alcohols such as glycerin and propylene glycol, Macrogol 400, Macrogol 400
0, etc. polyethylene glycol, glycerin fatty acid ester such as glyceryl monostearate, sodium lauryl sulfate, polyethylene glycol monostearate, polyoxyethylene alkyl ether phosphoric acid (trade name, NIKKOL DDP-2, Nippon Surfactant Industry Co., Ltd.), Surfactants such as sorbitan sesquioleate, various ions such as lactic acid, sodium citrate, sodium carbonate, anhydrous sodium sulfate, ethanol, wax, resin, water and, if necessary, methyl paraoxybenzoate, ethyl paraoxybenzoate, paraoxybenzoic acid It can be produced by a conventional method by mixing it with a preservative such as propyl acid ester or butyl paraoxybenzoate.

The collagen metabolism-improving agent of the present invention is administered orally or parenterally. It is, for example, liver fibrosis,
Collagen metabolism improving agent of the present invention by oral or injection for diseases in which collagen is abnormally accumulated in organs such as pulmonary fibrosis, and by percutaneous or local injection in diseases in which collagen is abnormally accumulated in epithelium such as keloid and hypertrophic scar Is administered.
In the case of a decrease in collagen turnover associated with aging, the agent for improving collagen metabolism of the present invention is orally or percutaneously administered.

The dose varies depending on the age, weight, symptoms, administration method, etc. of the patient or the person with reduced collagen turnover, but when administered to an adult, it is generally 0.05 times as a silicic acid-related substance or its salt per administration. Dosage of ~ 100 mg 1-3 times daily. For example, for diseases in which collagen is abnormally accumulated in organs such as liver fibrosis and pulmonary fibrosis, a dose of 3 to 100 mg per administration by oral administration or injection is appropriate, and keloids, hypertrophic scars, etc. For the skin where the collagen turnover is decreased due to aging and diseases in which collagen is abnormally accumulated in the epithelium of
1 to 50 mg per dose or 1 for bath salts
Bathing at a concentration of ~ 500 mg / l for 10-30 minutes per day is appropriate.

The cosmetics of the present invention are skin cosmetics such as lotions, milky lotions, creams, ointments and packs, or hair arts, hair lotions and
It can be in the form of a hair nourishing cosmetic such as a hair cream, a hair conditioner, a shampoo, a rinse, a hair gel, a hair mist and a hair foam. Also,
The purpose of the present invention is to provide surfactants, humectants, pH adjusters, thickeners, bactericides, antiseptics, keratolytic agents, antioxidants, fragrances, dyes, UV absorbers, pigments, anti-androgen agents, etc. Can be appropriately blended within a range that does not impair the above.

The present invention will be described in detail below with reference to test examples, examples and comparative examples. However, the present invention is not limited to the raw materials and the compounding ratios described in the examples. In addition,
The definitions of the terms used in the test examples are described.

MEM medium : minimum essential medium 10-101
(Dainippon Pharmaceutical Co., Ltd.) 1 bag of purified water was added to each to give a final concentration of 0.1% by weight lactalbumin enzyme hydrolyzate (Sigma), 1% by volume non-essential amino acid, 1 mM sodium pyruvate (all of which are large. (Manufactured by Nippon Pharmaceutical Co., Ltd.), 0.12% by weight sodium hydrogen carbonate and 50 mg / l streptomycin are added.

FBS : fetal bovine serum

Measurement buffer : 0.2 M NaCl, 5 mM CaCl ₂ , 0.05
A buffer solution containing 50 mM tris (hydroxymethyl) aminomethane (hereinafter simply abbreviated as Tris) aqueous solution containing Brij-35 by volume at pH 7.5 with hydrochloric acid at room temperature.

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

Test Example-1 In the cells used in this experiment, the collagenase produced is recovered as a procollagenase which has no activity as it is. Therefore, the amount of procollagenase produced is the collagenase activity obtained by activation with trypsin. Was quantified as

A normal human fibroblast cell line [Detroit-551 (ATCC CCL110) collected from the skin of a Caucasian woman] was added to 1 × 10 ⁵ cells / ml in a MEM medium containing 10% by volume of fetal bovine serum (hereinafter abbreviated as FBS). Prepared in 2m in a 6-well plate
Seed each 1 liter, 5% carbon dioxide gas, saturated steam, 37 ℃
It was cultured in.

The MEM medium is the minimum essential medium 10-
101 (manufactured by Dainippon Pharmaceutical Co., Ltd.) with 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 (both manufactured by Dainippon Pharmaceutical Co., Ltd.) , 0.12 wt% sodium bicarbonate and 50 mg / l streptomycin were added.

Collagen metabolism improver (10 mM sodium metasilicate solution) was added with 0.6% by volume FBS.
It diluted with the EM culture medium and it was set as the addition solution of each concentration.

After 24 hours, the culture solution 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. Then, 2 ml of each addition solution was added, and the cells were cultured for 7 days to culture supernatant. Got

To 250 μl of the obtained culture supernatant was added 10 mM Tris-hydrochloric acid buffer solution [adjusted to pH 7.8 at 4 ° C. and containing 1 mM calcium chloride and 0.05 vol% Brij-35] 1.7.
CM-Sepharose CL-6 added with 5 ml and equilibrated with the same buffer
^BTM (manufactured by Pharmacia, bed volume 0.5 ml) was used.

Next, the same buffer solution containing 125 mM sodium chloride was added.
Remove inhibitors with 5 ml (total 4 times, total volume 2 ml)
Then, the procollagenase was recovered with 0.5 ml of the same buffer containing 500 mM sodium chloride (total 4 times, total amount 2 ml) to obtain a test solution.

Next, 20 μl of a trypsin solution (Type 12, manufactured by Sigma, adjusted to a concentration of 1 mg / ml with a measurement buffer) was added to 50 μl of the test solution, and the mixture was incubated at 35 ° C. for 5 minutes, and then soybean was added. Trypsin inhibitor solution (Merck No.24020 was prepared to a concentration of 3 mg / ml with measurement buffer)
Trypsin was inactivated by adding 30 μl to obtain a collagenase solution.

Using type I collagen labeled with fluorescein isothiocyanate (FITC-collagen acetic acid solution having 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, 1984
(Refer to the year) and the activity of the above collagenase (unit / ml)
Was measured. The amount of collagenase produced from procollagenase by the above trypsin treatment decomposes 1 μg of type I collagen (FITC-collagen) per minute at 35 ° C. as 1 unit of procollagenase. / Ml of culture solution) (this value is designated as X).

On the other hand, as a control test, purified water was added in place of sodium metasilicate, and the amount of procollagenase produced when the collagen metabolism improver (sodium metasilicate solution) was not added by the same operation as above (unit / culture solution)
ml) was determined (this value is Y).

Next, the procollagenase production promoting rate was calculated from these values by the following formula.

[0047]

The results of quantifying the amount of procollagenase in the obtained culture supernatant are shown in Table 1. 5 for control (no addition)
8.5 ± 7.6 units / ml (mean ± standard error, n =
In contrast to 3), the addition of sodium metasilicate significantly promoted procollagenase production in a dose-dependent manner.

[0049]

[Table 1]

Test Example-2 In the same manner as in Test Example-1, the collagen metabolism-improving agents of Examples 2, 3, 4, and 5 described below were added to normal human fibroblasts, and procollagenase production was examined.

The results of quantifying the amount of procollagenase in the obtained culture supernatant are shown in Table 2. 5 for control (no addition)
8.5 ± 7.6 units / ml (mean ± standard error, n =
In contrast to 3), the addition of the metasilicic acid-related substance significantly promoted the production of procollagenase.

[0052]

[Table 2]

Test Example-3 (Beautiful skin effect practical test) 1) Test sample The solutions of Examples 7, 8, 9, 10 and Comparative Example 2 were used.

2) Test method Female subjects (35 to 55) who complain of rough skin, fine wrinkles, dry skin, etc.
20 years old, the test sample was applied twice daily in the morning and evening twice daily for 3 consecutive months, and then evaluated for improvement of skin flexibility, elasticity and wrinkles. For each item, the number of respondents who answered "improved skin flexibility", "improved skin elasticity", and "improved skin wrinkles" was shown.

3) Test results The results are shown in Table 3. As is clear from the table, the effect was recognized in the practical test. When ascorbic acid phosphate magnesium salt (Asc-P) was allowed to coexist, a better effect was obtained.

[0056]

[Table 3]

Test Example-4 (Practical test for hair-growth effect) 1) Test sample Hair-growth cosmetics described in Examples 19, 20, 21, and 22 and oily hair art nick described in Comparative Example 3.

2) Test Method Male subject 2 in the thirties and forties with a decline in hair growth 2
The effect was evaluated after the sample was applied to the heads of 0 persons twice daily in the morning and evening twice a day for 6 consecutive months. The evaluation of the effect was shown by the number of respondents who answered that "hairy hair became bristly or hair was increased" and "hair loss decreased" for each item of hair growth effect and hair loss prevention effect.

3) Test results The results are shown in Table 4. In a human practical test, a hair-growth agent effect and a hair loss prevention effect were observed. A better effect was obtained when Asc-P coexisted.

[0060]

[Table 4]

Test Example 5 With respect to the bathing agent containing sodium metasilicate, the bathing effect was actually examined as follows.

30 g of the bath salt of Example 27 and its comparative example 4
Bath salt of 0.35 g or bath salt of Example 28 of 33 g
And 15.5 g of the bathing agent of Comparative Example 5 at 41 ° C.
It was poured into 180 liters of hot water. 10 subjects each, the right foot in the hot water of Example 27 or 28, the left foot in the hot water of Comparative Example 4 or 5, three times a day (morning, noon, night) for 5 minutes, 1 respectively
Partially bathed for 0 days. Ten days later, the skin groove condition on the skin surface of the front part of the forefoot was observed with a magnifying video camera and scored according to the following criteria. In addition, the evaluation by questionnaire was performed according to the following criteria.

Scores of the condition of the observed cuticles and furrows

[0064]

[Table 5]

Questionnaire evaluation method

[0066]

[Table 6]

The results of examining the bathing effect are shown in Table 7. When the bath agent containing sodium metasilicate (and Asc-P) was used, the skin groove state on the skin surface was clear compared to the comparative example, and the moist feeling of the skin was also high in the questionnaire evaluation.

[0068]

[Table 7]

Example 1 12.2 mg of sodium metasilicate was dissolved in 9 ml of 20 mM hydrochloric acid solution, the pH was neutralized with 1N sodium hydroxide, and the volume was adjusted to 10 ml with purified water. It was sterilized by filtration through a nitrocellulose membrane with a pore size of 0.2 μm (manufactured by Advantech Toyo, DISMIC-25) to obtain a collagen metabolism improving agent.

Example 2 Example 1 except that 15.4 mg of potassium silicate was used.
A collagen metabolism improving agent was prepared in the same manner as in.

Example 3 A collagen metabolism improver was prepared in the same manner as in Example 1 except that 18.4 mg of sodium orthosilicate and 9 ml of 40 mM hydrochloric acid solution were used.

Example 4 A collagen metabolism improving agent was prepared in the same manner as in Example 1 except that 16.9 mg of water glass was used.

Example 5 12.2 mg of sodium metasilicate was dissolved in 9 ml of a 20 mM hydrochloric acid solution, and the pH was neutralized with 1N sodium hydroxide.
Further, 10 mg of Asc-P was added and the volume was adjusted to 10 ml with purified water. It is filter sterilized as in Example 1,
A collagen metabolism improving agent was prepared.

Example 6 Example 5 except that 15.4 mg of potassium silicate is added.
A collagen metabolism improving agent was prepared in the same manner as in.

Examples 7 to 10 The collagen metabolism-improving agents of Examples 1, 2, 5, and 6 were diluted 10 times with 0.1% by weight methylparaben solution to prepare collagen of Examples 7, 8, 9, and 10. A metabolism improver was prepared.

Examples 11 to 14 (lotion) The collagen metabolism-improving agent of any one of Examples 1, 2, 5, and 6, sodium lauryl sulfate, and purified water were heated to 80 ° C. in a hot water bath and mixed, while salic Beeswax, cetanol, and concentrated glycerin were heated to 80 ° C and mixed, and the heated collagen metabolism-improving agent mixture was gradually added to this mixture with stirring, and the mixture was vigorously stirred (2500 rpm) for 2.5 minutes with a homogenizer (TOKUSHUKIKAKOGYO). . The mixture was gradually cooled to room temperature with stirring to obtain lotions of Examples 11, 12, 13, and 14 containing 6 mM of metasilicate in 100 g.

[0077]

[Table 8]

Examples 15 to 18 (Cream) The following ingredients were uniformly mixed and dissolved at about 80 ° C., and then about 80 ° C.
After emulsifying by adding to the components that have been uniformly mixed and dissolved in Example 1, the components that have been uniformly mixed and dissolved at about 50 ° C. are added, and the mixture is cooled to about 30 ° C. to obtain Examples 15, 16, and 17. ,
Eighteen creams were prepared.

[0079]

[Table 9]

Examples 19 to 22 (Oily Hearthonic) The collagen metabolism-improving agent of any of Examples 1, 2, 5, and 6 was diluted 10 times with a 0.1% by weight methylparaben solution to prepare a 1 mM collagen metabolism-improving agent. Got Using 37.2 g of this aqueous solution, according to the composition of Table 10, the hydrophilic component and the lipophilic component were mixed and stirred, and Examples 19, 20, 21 and
I got 22 oily art tonics.

[0081]

[Table 10]

Examples 23-26 (Hair Cream) The hydrophilic components shown in Table 11 below, including the collagen metabolism-improving agents of Examples 1, 2, 5, and 6, were uniformly mixed and dissolved at about 80 ° C. After emulsifying by adding to the lipophilic component which was uniformly mixed and dissolved at 80 ° C., the perfume component was added at about 50 ° C., and stirring was continued until it reached about 30 ° C.
4, 25, 26 hair creams were prepared.

[0083]

[Table 11]

Example 27 A bathing agent composition having the following formulation was prepared by a usual method of mixing powders to prepare 100 g of a bathing agent containing 48.95 g of sodium metasilicate.

Sodium metasilicate 48.95 g Citric acid monohydrate 50.00 g Perfume 1.00 g Organic dye 0.05 g ─────────────────── ─────────────── 100.00 g

Example 28 A bathing agent composition having the following formulation was prepared by a conventional method of mixing powders, and 48.95 g of sodium metasilicate and A were prepared.
111 g of a bathing agent containing 11.0 g of sc-P was prepared.

Sodium metasilicate 48.95 g Citric acid monohydrate 50.00 g Asc-P 11.0 g Perfume 1.0 g Organic pigment 0.05 g ───────────── ────────────────────── 111 g

Comparative Example 1 A 20 mM sodium chloride solution was prepared and sterilized by filtration through a nitrocellulose membrane having a pore size of 0.2 μm (manufactured by Advantech Toyo Co., Ltd., DISMIC-25) to give Comparative Example 1 for a collagen metabolism improving agent. .

Comparative Example 2 Comparative Example 1 was used in Example 7 with 0.1% by weight methylparaben solution.
Comparative Example 2 was prepared by diluting in the same manner as 10 to 10.

Comparative Example 3 (Oily Hearthonic) Comparative Example 3 was prepared in the same manner as in Examples 19 to 22 except that 10 g of Comparative Example 1 was used.

Comparative Example 4 (Bathing Agent) A bathing agent composition having the following formulation was prepared by a usual method of mixing powders to prepare 51.05 g of a bathing agent for comparison.

Sodium citrate 50.00 g Perfume 1.00 g Organic dye 0.05 g ──────────────────────────── 51 .05 g

Comparative Example 5 (Bathing Agent) A bathing agent composition having the following formulation was prepared by a usual method of mixing powders to prepare 62.05 g of a bathing agent for comparison.

Sodium citrate 50.00 g Asc-P 11.0 g Perfume 1.00 g Organic dye 0.05 g ────────────────────── ────── 62.05 g

Formulation Example 1 (Tablet) Hydroxypropyl cellulose was dissolved in 30 g of purified water and added to a mixture of 50 g of sodium metasilicate and lactose, corn starch, and crystalline cellulose shown below, and kneaded sufficiently.

This kneaded product was passed through a 20-mesh sieve to be granulated into granules and dried, and then the obtained granules were mixed with magnesium stearate and tabletted into 200 mg per tablet. A tablet containing 100 mg of sodium metasilicate as an active ingredient was obtained.

“Ingredients” Lactose 10 g Corn starch 30 g Crystalline cellulose 8 g Hydroxypropyl cellulose 1 g Magnesium stearate 1 g ──────────────────────────── ─────── 50g

Formulation Example 2 (Capsule) 100 g of sodium metasilicate and lactose, corn starch, crystalline cellulose and magnesium stearate shown below were thoroughly mixed, and 300 mg each of the mixture was filled in No. 2 capsule, and 1 A capsule containing 100 mg of sodium metasilicate as an active ingredient was obtained.

“Ingredients” Lactose 100 g Corn starch 50 g Crystalline cellulose 47 g Magnesium stearate 3 g ─────────────────────────────── ─── 200g

Formulation Example 3 (Granule) 100 g of sodium metasilicate, lactose and corn starch shown below were thoroughly mixed, and hydroxypropyl cellulose was dissolved in 1000 g of purified water and added, followed by thorough kneading.

This mixture was granulated through a 20-mesh sieve, dried and then granulated to obtain a granule containing 1 mg of sodium metasilicate 100 mg as an active ingredient.

“Ingredients” Lactose 470 g Corn starch 400 g Hydroxypropyl cellulose 30 g ─────────────────────────────────── 900 g

[0103]

INDUSTRIAL APPLICABILITY The collagen metabolism-improving agent of the present invention promotes the production amount of procollagenase when added to the culture system of human skin fibroblasts. In the human practical test, the cosmetic of the present invention was found to have a skin beautifying effect, a hair restorer effect, and a hair loss preventing effect. Further, the collagen metabolism-improving agent of the present invention is a low-molecular substance that is advantageous in penetrating into tissues, and is useful as a collagen metabolism-improving agent for a disease associated with abnormal accumulation of collagen, or a decrease in collagen turnover associated with aging. Is expected to be.

[Procedure amendment]

[Submission date] August 10, 1994

[Procedure Amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0047

[Correction method] Change

[Correction content]

[0047]

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Office reference number FI technical display location A61K 7/48 7/50 33/06 33/12 ADA // (A61K 33/00 31: 375) (A61K 33/06 31: 375) (A61K 33/12 31: 375) (72) Inventor Seiji Matsuda 5-3 28, Kotobuki-cho, Odawara-shi, Kanagawa Inside Kanebo Co., Ltd. Cosmetic Research Institute (72) Inventor Ishida Takao 5-3 28, Kotobuki-cho, Odawara-shi, Kanagawa Inside Kanebo Co., Ltd. Cosmetic Research Laboratory

Claims (7)

[Claims] 1. A collagen metabolism improving agent, which comprises a silicic acid-related substance or a salt thereof. 2. A collagen metabolism-improving agent comprising a silicic acid-related substance or a salt thereof and ascorbic acid or a derivative thereof. 3. A cosmetic comprising the collagen metabolism-improving agent according to claim 1 or 2. 4. The cosmetic according to claim 3, wherein the cosmetic is a skin cosmetic. 5. The cosmetic according to claim 3, wherein the cosmetic is a hair nourishing cosmetic. 6. A bath agent containing a silicic acid-related substance or a salt thereof. 7. A bath salt containing a silicic acid-related substance or a salt thereof and ascorbic acid or a derivative thereof.