JP4777645B2 - Collagen synthesis promoter and collagen metabolism activator - Google Patents

Description

  The present invention relates to a collagen synthesis promoter and a collagen metabolism activator, and more particularly, a collagen synthesis promoter containing a specific plant extract, and collagen turnover by enhancing collagen degradation and stimulating collagen synthesis. The present invention relates to a collagen metabolism activator capable of increasing the pH.

  It is known that the turnover rate of collagen is much slower than that of a normal protein, and the turnover rate of collagen further decreases with aging even under physiological conditions. The turnover rate of collagen is determined by the degradation rate and synthesis rate of collagen, but such a decrease in turnover rate due to aging leads to an increase in collagen cross-linking structure (aging cross-linking), for example, hardening of skin and wrinkles Involved in formation. Increased hard collagen, which is difficult to decompose and extract, impairs the function of collagen involved in proliferation, differentiation and migration as a cell scaffold, resulting in decreased cellular activity and further reduced collagen turnover rate. It is thought to fall into a vicious circle of doing (see Hyundai Kagaku, December issue, page 36, 1990).

  As a means to stop the decrease in the rate of collagen turnover accompanying such aging, collagen formation, which is the rate-determining enzyme for collagen degradation, is enhanced to promote the degradation of collagen, thereby preventing the formation of aging bridges and at the same time the rate of collagen synthesis It is conceivable to promote the metabolism of collagen by increasing the amount.

By the way, collagenase is a rate-limiting enzyme for 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, and is then considered to be activated to collagenase in vivo by a proteolytic enzyme such as plasmin or stromalysin (Biochemical Journal, 166, 21). 1977 and Proceedings of the National
Academy of Sciences of the U.S. S. A. 86, 2632, 1989).

  As substances that can enhance the ability of cells to produce procollagenase, cytokines such as interleukin 1, tumor necrosis factor (TNF), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), Ball esters and the like are known. However, these cytokines are expensive and have limited production due to high production costs. Moreover, phorbol ester is a carcinogenic promoter substance, and its use is hardly safe.

  On the other hand, collagen, particularly type I collagen, which is the main collagen in connective tissue, has been synthesized or secreted by TGF-β, ascorbic acid and its derivatives, estrogen, testosterone, insulin and the like by experiments using fibroblasts. It is known that this can be achieved (see Bioscience and Biotechnology of Extracellular Matrix, page 165, IPC Corporation, 1990).

By the way, for example, TGF-β and estrogen are substances that promote collagen accumulation rather than collagen metabolism activation in order to promote collagen synthesis and suppress collagenase secretion. In addition, it is considered that italeukin-1 promotes collagenase secretion and suppresses collagen synthesis, and in this case, promotes unilateral decrease of collagen rather than activation of collagen metabolism. Glucocorticoids and retinoic acid are substances that suppress both the secretion of collagen and collagenase (see Bioscience and Biotechnology of Cell Matrix, page 165, IPC Inc., 1990).

  The present inventors have simultaneously promoted the conflicting actions of collagen synthesis and degradation, tried to more actively promote collagen metabolism, and have already been a collagenase production promoting substance, a silk partial hydrolyzate and a collagen synthesis promoting substance. A combination of ascorbic acid phosphates (see Patent Document 1), ethanolamine derivatives, pentoxifylline, serine derivatives, or sulfates as collagenase production promoters, and ascorbic acid derivatives as collagen synthesis promoters We have applied for a collagen metabolism activator characterized in that (see Patent Document 2).

However, combinations with other collagen production-promoting substances, which are not restricted by dosage forms and blending conditions, are safer and have a natural preference and are natural plant extracts, are desired in cosmetics and pharmaceutical applications.
JP-A-4-346936 JP-A-6-157232

  In view of such circumstances, the present inventors have intensively studied various substances with the intention of preventing skin hardening and wrinkles by activating collagen metabolism, and as a result, licorice, Sakuhakuhi, Sugina, aloe, kinginka, oak Silk, including sulfates, nitrates, ammonium salts, and sulfate hydrolysates of silk fibers having a molecular weight of 500 or less, wherein an extract of at least one plant selected from the group consisting of gaiyo and gentian promotes collagen synthesis. The present inventors have found that collagen turnover is increased when combined with partial hydrolyzate, serine derivatives, ethanolamine and derivatives thereof, and collagenase production promoters such as silicic acid related substances and salts thereof, and the present invention has been completed. The purpose is to promote collagen synthesis and collagen metabolism activator. It is to provide.

  The above-mentioned object is achieved by a collagen synthesis promoter characterized by containing an extract of at least one plant selected from the group consisting of licorice, Sakuhakuhi, Japanese horsetail, aloe, goldfish, grasshopper, bayberry and gentian. In addition, it is achieved by a collagen metabolism activator that combines the collagen synthesis promoter and collagenase production promoter.

  As described above, it is apparent that the present invention can provide a collagen synthesis promoter and a collagen metabolism activator.

  Hereinafter, embodiments of the present invention will be described in detail.

Collagen synthesis promoting substances used in the present invention include leguminous licorice or related plant roots, rhizomes or stems, mulberry family mulberry or related plant root bark, cassaceae sugina or related plants whole plant, lily family Leaves or leaf juice of aloe or related plants, flowers of honeysuckle kingweed (honeysuckle) or related plants, leaves or stems, bark of mandarin orange plantaceae or related plants, bark of asteraceae (mugwort, mugwort mugwort, wormwood) or similar Leaves of plants, roots or rhizomes of Gentianaceae gentians or related plants, water, lower alcohols such as ethanol, polyhydric alcohols such as propylene glycol and 1,3-butylene glycol, polyhydric alcohol alkyl ethers such as diethylene glycol ether, etc. Polar solvents or mixtures thereof It can be obtained by extraction with, but not limited thereto.

  The content of the collagen synthesis promoting substance according to the present invention is preferably in the range of 0.1 to 5.0% by mass based on the total amount of the prescription ingredients.

As a collagenase production promoting substance used in the present invention, a procollagenase producing substance (collagenase is secreted from a cell as a precursor procollagenase and then activated in the living body by collagenase. and are) as is generally known, for example, sulfate, nitrate or ammonium salts, silk partial hydrolyzate, serine and derivatives thereof, ethanolate Ruamin and its derivatives, there may be mentioned silicic acid-related substance and a salt it can.

  Examples of the sulfate used in the present invention include sodium sulfate, magnesium sulfate, ammonium sulfate, and potassium sulfate.

  Examples of the nitrate used in the present invention include sodium nitrate, magnesium nitrate, and ammonium nitrate. Examples of the ammonium salt include ammonium acetate, ammonium tartrate, and ammonium lactate.

  Partially hydrolyzed silk, in particular, water-soluble silk peptide, is a known substance used for skin cosmetics and the like. For example, as a production method thereof, Japanese Patent Publication Nos. 58-17773, 59-31520, 60-41043. No. publication etc. are known. Among the partially hydrolyzed silk, a sulfuric acid hydrolyzate of silk fibers having a molecular weight of 500 or less can be mentioned as a particularly preferable one.

Examples of serine and derivatives thereof include compounds represented by the following general formula (1), and more specifically, for example, serine, N-methyl-L-serine, N-methyl-DL-serine, N, N -Dimethyl-L-serine, N, N-dimethyl-DL-serine and the like can be mentioned.

In the above formula (1), R ¹ and R ² each represent a hydrogen atom or a methyl group, and may be the same or different.

Examples of ethanolamine and its derivatives include compounds represented by the following general formula (2), and more specifically, for example, monoethanolamine, N-methylethanolamine, N, N-dimethylethanolamine, 2- Amino-1-butanol, 2-amino-1-propanol, N-methyl-2-amino-1-butanol, N-methyl-2-amino-1-propanol and the like can be mentioned. Ethanolamine and its derivatives are used in the form of a free amine or amine salt. Examples of amine salts include salts of mineral acids such as hydrochloride, sulfate, nitrate and phosphate, acetate, lactate, citrate, malate, tartrate, fumarate, maleate, and lower fatty acids. And salts of organic acids such as salts and higher fatty acid salts.

(2) wherein R ³ and R ⁴ are each a hydrogen atom or represents a methylation group or may differ even for the same. R ⁵ represents a hydrogen atom, a methyl group or an ethyl group. However, if R ³ and R ⁴ are not hydrogen atoms at the same time, or at the same time methyl group, R ⁵ is hydrogen atom.

  Examples of the silicate-related substances and salts thereof include silicic acid, potassium silicate, sodium metasilicate, and sodium orthosilicate described in JP-A-7-188036.

  The content of the collagenase production promoting substance used in the present invention varies depending on the dosage form, but when using nitrate, ammonium salt, serine or derivative thereof, ethanolamine or derivative thereof, silicic acid related substance or salt thereof, Preferably content is 0.001-10 mass% on the basis of prescription component whole quantity. Moreover, when using the sulfuric acid hydrolyzate of silk fiber, it is preferable to contain 0.0001-5 mass% in conversion of silk fiber on the basis of the prescription component whole quantity. If the content is less than the lower limit, the effect is not sufficient, and even if the content exceeds the upper limit, an effect commensurate with the increased amount may not be expected.

In addition to the above, the collagen synthesis accelerator and collagen metabolism activator of the present invention include tar pigments, colored pigments such as iron oxide, preservatives such as paraben and phenoxyethanol, dimethylpolysiloxane, methylphenylpolysiloxane, and cyclic silicon. Hydrocarbons such as silicon oil, paraffin, petrolatum, etc., olive squalane, rice squalane, rice germ oil, jojoba oil, sunflower oil, safflower oil, olive oil, macadamia nut oil, sunflower oil and other vegetable oils, beeswax, owl, carnauba wax, etc. Waxes, octyldodecyl myristate, cetyl palmitate, isostearyl isostearate, isopropyl myristate, etc., lower alcohols such as ethanol, cetanol, behenyl alcohol, stearyl alcohol, long-chain branched aliphatic alcohols Higher alcohols, cholesterol, phytosterols, branched fatty acid cholesterol esters, sterols and derivatives such as macadamia nut fatty acid phytosteryl esters, processing oils such as hardened oils, stearic acid, myristic acid, isostearic acid, oleic acid, isoform long chain Fatty acids, higher fatty acids such as anteiso type long chain fatty acids, terpenes such as limonene, hydrogenated bisabolol, triglycerides such as tricapryl / glyceryl caprate, glyceryl 2-ethylhexanoate, triglyceryl long chain fatty acid glyceryl, glyceryl tripalmitate, Anionic surfactants such as sodium cetyl sulfate, N-stearoyl-L-glutamate, polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, polyoxyethylene polyvalent alkyl Fatty acid ester, polyoxyethylene hydrogenated castor oil, polyhydric alcohol fatty acid ester, polyglycerin fatty acid ester, modified silicone, sucrose ester and other nonionic surfactants, tetraalkylammonium salt and other cationic surfactants, betaine type , Amphoteric surfactants such as sulfobetaine type and sulfoamino acid type, natural surfactants such as lecithin, lysophosphatidylcholine, ceramide and cerebroside, pigments such as titanium oxide and zinc oxide, and antioxidants such as dibutylhydroxytoluene Agent, inorganic salts such as sodium chloride, magnesium chloride, sodium sulfate, potassium nitrate, sodium sulfate, sodium metasilicate, calcium chloride, sodium citrate, potassium acetate, sodium oxalate, sodium aspartate, sodium lactate, dichloroacetic acid Organic acids such as mevalonic acid and glycyrrhizic acid and salts thereof, ethanolamine hydrochloride, ammonium nitrate, arginine hydrochloride, diisopropylamine salts, urea, organic salts such as decarboxycarnosine and salts thereof, chelating agents such as edetic acid, xanthan gum, Carboxyvinyl polymer, carrageenan, pectin, alkyl-modified carboxyvinyl polymer, thickener such as agar, neutralizing agent such as potassium hydroxide, diisopropanolamine, triethanolamine, ultraviolet absorber such as hydroxymethoxybenzophenone sulfonate, Dipropylene glycol, 1,3-butylene glycol, glycerin, propylene glycol, sorbitol, malbitol, diglycerin, raffinose and other polyhydric alcohols, various amino acids, ascorbic acid, biotin Vitamins and ascorbic acid sulfuric acid ester salts of tocopherol, ascorbic acid phosphate ester salts, can be appropriately blended as vitamin derivative tocopherol nicotinate, etc. to the extent that achieving the object of the present invention.

  Hereinafter, the present invention will be described in more detail with reference to examples. In addition, the licorice, Sakuhakuhi, Sugina, Aloe, Goldfish, Ogaku, Guiyou, and Gentian used in the Examples were obtained by pulverizing each plant dried product and extracting it at room temperature all day and night using 10 times the amount of ethanol. What was dried under reduced pressure by a conventional method was used.

Test example 1
The concentration of normal human fibroblast cell line [Detroit-551 (ATCC CCL 110) collected from white female skin] in a MEM medium containing 10% by volume fetal calf serum (hereinafter abbreviated as FBS) is 1 × 10 ⁵ cells. The solution was adjusted to 1 mL / mL, seeded at a rate of 0.4 mL each in two 24-well plates (4 × 10 ⁴ cells / hole), and cultured at 37 ° C. under 5% carbon dioxide gas and saturated steam for 24 hours. In addition, MEM culture medium is Dainippon Pharmaceutical's minimum essential medium 10-101, final concentration 0.1 mass% lactalbumin enzyme hydrolyzate (manufactured by Sigma), 1% by volume non-essential amino acid, 1 mmol / L pyruvic acid, respectively. It was prepared by adding sodium (all of which were manufactured by Dainippon Pharmaceutical Co., Ltd.), 0.12% by mass sodium bicarbonate and 50 mg / L streptomycin. After 24 hours, the culture solution was removed by suction, and the cells were washed twice with a MEM medium supplemented with a final concentration of 0.6% by volume FBS, and then a nitrocellulose membrane having a pore size of 0.2 μm (manufactured by Advantech Toyo, DISMIC-25) The medium was replaced with the same medium supplemented with a collagen synthesis promoter or collagen metabolism activator sterilized by filtration. Two plates were prepared, and one was used for measuring the amount of collagen produced, and the other one was used for measuring the amount of procollagenase produced.

Quantification of collagen production: Collagen production is resistant to pepsin from a culture solution in which β-aminopropionitrile is added at a final concentration of 50 μg / mL and tritium-L-proline is added at a final concentration of 50 μCi / mL, and further cultured for 24 hours. And it measured by the radioactivity incorporated in the collagen fraction fractionated by the salt concentration dependent solubility. The method of fractionating collagen by pepsin treatment and salt concentration was in accordance with the method of Webster et al. (See Analytical Biochemistry, page 220, 1979).

  The collagen synthesis promoting activity is shown as a ratio obtained by dividing the sample added group radioactivity by the non-sample added group radioactivity.

  Prior to examining procollagenase production promoting activity, collagenase inhibitor (protein) produced simultaneously with procollagenase in the culture supernatant was removed.

Removal of collagenase inhibitors:
To 250 μL of the obtained culture supernatant, 10 mmol / L Tris-HCl buffer (adjusted to pH 7.8 at 4 ° C., 1 mmol / L calcium chloride, 0.05 vol% Brij-35 [polyoxyethylene (23) lauryl produced by ICI) 1.75 mL of [containing ether]] was added and subjected to CM-Sepharose CL-6B TM (Pharmacia, bed volume 0.5 mL) equilibrated with the same buffer.

  Next, the inhibitor was removed with 0.5 mL of the same buffer containing 125 mmol / L sodium chloride (total 4 times, total volume 2 mL), and procollagenase was recovered with 0.5 mL of the same buffer containing 500 mmol / L sodium chloride (total 4 times, total volume 2 mL).

Quantification of procollagenase production:
In the cells used in this experiment, the produced collagenase is recovered as a procollagenase having no activity as it is, so the amount of procollagenase produced was quantified as the collagenase activity obtained by activation with trypsin. The activation method using trypsin and the method for measuring collagenase activity using collagen I labeled with fluorescein isothiocyanate (manufactured by Cosmo Bio) as a substrate are the methods of Nagai et al. (Japan Journal of Inflammation, Vol. 4, 123). Page, 1984).

  In addition, 1 unit shows the enzyme amount which decomposes | disassembles 1 microgram type I collagen in 1 minute at 35 degreeC.

  The results of the collagen synthesis acceleration rate obtained are shown below.

Concentration Collagen synthesis acceleration rate
(Mg / L) (% ± SE)
------------------------------
Licorice 50 270 ± 8.8
12.5 135 ± 23
Sohakuhi 200 194 ± 23
50 124 ± 17
Horsetail 200 140 ± 4.8
50 84.7 ± 6.3
Aloe 200 137 ± 3.6
50 108 ± 8.0
Kinginka 200 135 ± 8.0
50 128 ± 13
Awaku 20 200 ± 20
10 127 ± 13
Guiyou 12.5 149 ± 37
10 125 ± 25
Gentian 200 153 ± 8.0
50 107 ± 9.3

  As described above, it has been clarified that licorice, grasshopper, horsetail, aloe, goldfish, grasshopper, gayyo and gentian have an effect of promoting collagen synthesis.

  The results of the collagenase production promoting activity obtained are shown below.

Concentration Collagenase production promoting activity
(Mmol / L) (unit / mL ± SE)
---------------------------------
No addition-22.5 ± 3.7
Sodium nitrate 80 46.5 ± 4.8
Ammonium nitrate 2 38.5 ± 6.6
Ammonium acetate 10 51.3 ± 3.8
Ammonium tartrate 5 49.6 ± 5.5
Ammonium lactate 5 78.7 ± 3.7
Silk fiber hydrolyzate 2.5 * 30.3 ± 6.8
N-methylserine 0.001 36.2 ± 4.2
N-methylethanolamine 1 111.0 ± 13
Sodium metasilicate 1 47.9 ± 6.4

*: The silk fiber hydrolyzate used herein was obtained by the method described in Examples of JP-A-4-346936.

  As described above, sodium nitrate, ammonium nitrate, ammonium acetate, ammonium tartrate, ammonium lactate, silk fiber hydrolyzate, N-methylserine, N-methylethanolamine and sodium metasilicate were confirmed to have collagenase production promoting activity. .

  Tables 1 and 2 show the results of examining the collagen synthesis promoting rate and the collagenase production promoting activity by simultaneously adding a collagen synthesis promoting substance and a collagenase production promoting substance.

  As shown in Tables 1 and 2, even when a collagen synthesis promoting substance and a collagenase production promoting substance are added simultaneously, both the synthesis and degradation of collagen can be promoted without offsetting each other's action.

  Hereinafter, application examples (skin cosmetics) of the collagen synthesis promoter and collagen metabolism activator of the present invention will be shown.

Formulation Examples 1-3 (skin cream)
A skin cream was prepared by blending the collagen synthesis promoting substance and collagenase production promoting substance of the present invention in the following composition (prescription examples 1 to 3). The concentrations are all shown in mass% below.

(1) Composition
Formulation Example 1 Formulation Example 2 Formulation Example 3
(A)
Stearic acid 1 1 0
Isostearic acid 0 0 1
Glyceryl monostearate 2 2 2
Behenyl alcohol 2 2 2
White beeswax 1 1 0
Cetyl myristate 1 1 1
Sorbitan sesquioleate 1 1 1
N-stearoyl phytosphingosine 0.1 0.1 0.1
Hydrogenated lecithin 0.1 0.1 0.1
Plant squalane 5 5 5
Octyldodecyl myristate 5 5 5
(B)
Oat 0.01 0.1 1.0
Silk fiber hydrolyzate 0.01 0.1 1.0
1,3-butylene glycol 5 10 5
Concentrated glycerin 5 5 5
Methyl paraoxybenzoate 0.2 0.2 0.2
Ascorbic acid phosphate Na salt 0.2 0.2 0.2
γ-aminobutyric acid 0.1 0.1 0.1
N-stearoyl glutamic acid Na salt 0.2 0.2 0.2
Alkyl-modified carboxyvinyl polymer 0.05 0.05 0.005
Nicotinamide 0.1 0.1 0.1
Sarcosine 0.1 0.1 0.1
Purified water remaining amount remaining amount remaining amount

(2) Preparation method Each of the components (A) and (B) was heated and dissolved at 80 ° C, mixed and then cooled to 30 ° C while stirring to prepare a skin cream.

Formulation Examples 4-6 (Lotion)
The collagen synthesis promoting substance and collagenase production promoting substance of the present invention were blended in the following composition to prepare lotions (Application Examples 4 to 6).

(1) Composition
Formulation Example 4 Formulation Example 5 Formulation Example 6
Licorice 0.1 0.3 1.0
N-methyl-L-serine 0.1 0.3 1.0
1,3-butylene glycol 5 0 5
Dipropylene glycol 0 5 5
Raffinose 1 1 1
Ethanol 0 0 1
Phenoxyethanol 0.2 0.2 0.2
Pectin 0 0 0.05
Xanthan gum 0 0 0.1
Sodium citrate 0.05 0.05 0.05
Horsetail extract (ethanol extraction) 0.1 0.1 0.1
Diisopropylamine dichloroacetic acid 0.2 0.2 0.2
γ-amino-β-hydroxybutyric acid 0.2 0.2 0.2
Sodium hyaluronate 0.001 0.001 0.001
Dipotassium glycyrrhizinate 0.2 0.2 0.2
Kurita extract (ethanol extraction) 0.05 0.05 0.05
Decarboxycarnosine hydrochloride 0.05 0.05 0.05
Perfume 0.02 0.02 0.02
Purified water remaining amount remaining amount remaining amount

(2) Preparation method Each component was mixed and dissolved and stirred to prepare a lotion.

Formulation Examples 7-9 (Gel)
The collagen synthesis promoting substance and collagenase production promoting substance of the present invention were blended in the following compositions to prepare gels (Prescription Examples 7 to 9).

(1) Composition
Formulation Example 7 Formulation Example 8 Formulation Example 9
(A)
Decamethylcyclopentasiloxane 10 10 10
Isostearyl isostearate 1 0 0
Olive oil 0 1 0
Macadamia nut oil 0 0 1
Eucalyptus oil 0.1 0 0.1
Hexyldecanol 1 0.1 0
POE hydrogenated castor oil (60 EO) 2 2 2
Spherical silicon powder (Note 1) 1 1 5
(B)
Horsetail 0.1 0.1 0.1
Sodium metasilicate 0.1 0.1 0.1
Glucosamine 0 0 0
Glucuronic acid 0 0 0.1
1,3-butylene glycol 5 10 5
Sorbitol solution 3 3 3
Polyethylene glycol 4000 1 1 1
Carboxyvinyl polymer 0.2 0.2 0.2
Sugar ceramide (Note 2) 0.1 0.1 0.1
Methyl paraoxybenzoate 0.2 0.2 0.2
Mevalonolactone 0.5 0.5 0.5
Edetate disodium 0.02 0.02 0.02
Potassium hydroxide 0.05 0.05 0.05
Purified water remaining amount remaining amount remaining amount

Note 1: Toshiba Silicone Tospearl 145A
Note 2: Bioceramide manufactured by Kibun Food Chemical Co., Ltd.

(2) Preparation method Each of the components (A) and (B) was heated and dissolved at 60 ° C, mixed and then cooled to 30 ° C while stirring to prepare a cream.

Formulation examples 10-12 (lipophilic cream)
The collagen synthesis promoting substance and collagenase production promoting substance of the present invention were blended in the following composition to prepare a lipophilic cream (Application Examples 10 to 12).

(1) Composition
Formulation Example 10 Formulation Example 11 Formulation Example 12
(A)
Co-modified silicon (Note 3) 2 2 2
POE-modified silicon dispersion (Note 4) 0 2 0
Squalane 0 0 10
Decamethylcyclopentasiloxane 15 20 10
Methyl polysiloxane 5 2 3
Long-chain branched fatty acid cholesteryl (Note 5) 0 0 3
Silicon elastomer dispersion (Note 6) 5 2 0
(B)
Sohakuhi 0.1 0.1 0.1
Ammonium nitrate 0.1 0.1 0.1
Niacin 0.1 0 0
Kurita extract (ethanol extraction) 0 0.1 0
Orange homofruit extract (Note 7) 0 0 0.1
Sodium chloride 1 1 1
Dipropylene glycol 5 5 5
Concentrated glycerin 5 5 5
Raffinose 1 1 1
Methyl paraoxybenzoate 0.3 0.3 0.3
Purified water remaining amount remaining amount remaining amount

Note 3: ABIL EM90 manufactured by Goldschmidt
Note 4: Silicon BY22-008 manufactured by Toray Dow Corning Silicone
Note 5: YOFCO CLE-NH manufactured by Nippon Seika Co., Ltd.
Note 6: Trefill E-500 manufactured by Toray Dow Corning Silicone
Note 7: Fruit juice concentrate manufactured by Koei Kogyo Co., Ltd.

(2) Preparation method Each of the components (A) and (B) was heated and dissolved at 60 ° C, mixed and then cooled to 30 ° C while stirring to prepare a lipophilic cream.

Claims (1)

  A collagen synthesis promoter comprising at least one selected from the group consisting of Sakuhakuhi, Guiyou and Gentian.