JP5933907B2 - Composition for protecting stratum corneum peeling enzyme - Google Patents

Description

  The present invention relates to a composition for protecting the stratum corneum peeling enzyme of skin. Specifically, the present invention relates to a composition having an effect of recovering the activity of a reduced protease while protecting the protease involved in the regulation of skin turnover from the decrease in activity due to drying in the skin.

  The skin consists of the dermis, epidermis, and outermost stratum corneum (stratum corneum). In normal skin, turnover of epidermal cell division, keratinization, stratum corneum formation, and stratum corneum detachment is repeated, and metabolism is always performed. The stratum corneum constituting the stratum corneum is firmly bound via a glycoprotein called desmosome, etc., but this intercellular adhesion structure is decomposed with the turnover, and the stratum corneum is naturally separated. It is becoming clear that protease (proteolytic enzyme) is involved in the degradation of this intercellular adhesion structure. As proteases involved in the control of turnover, those of serine protease type and cysteine protease type are known, and trypsin-like and chymotrypsin-like serine proteases are considered to be important.

  It has been observed that in skin with dry skin roughness (dry skin), the degradation of the intercellular adhesion structure and the exfoliation of the stratum corneum are not performed normally. This suggests that dry skin does not function sufficiently because the activity of the protease involved in the degradation of the intercellular adhesion structure is reduced.

  For this reason, preventing the decrease in activity of the protease under dry conditions and restoring the reduced protease function to a normal state leads to normalization of skin turnover, thereby preventing and improving dry rough skin. It is considered effective.

  For example, Japanese Patent Application Laid-Open No. 2002-234845 (Patent Document 1) discloses a keratin exfoliation accelerator and skin makeup containing cobalamins having vitamin B12 activity as substances that enhance the exfoliation effect of skin trypsin and chymotrypsin-like protease. Fees are disclosed. In addition, Japanese Patent Laid-Open No. 10-175844 (Patent Document 2) referred to in this document only leads to a state in which the activity of trypsin and chymotrypsin-like enzyme is reduced only by a moisturizing agent. Shows that sufficient exfoliation cannot be achieved.

  Japanese Patent Application Laid-Open No. 2003-226613 (Patent Document 3) discloses a protease activity promoter and a cosmetic composition containing a plant extract.

  All of the techniques described in these documents attempt to improve rough skin by enhancing the protease activity of the skin and accelerating the exfoliation of the stratum corneum. However, with these techniques, it was thought that protease may be excessively activated to cause skin irritation, and application to skin that is sensitive to irritation such as dry skin may be encouraged.

  On the other hand, as a conventional technique aiming at prevention and improvement of rough skin, it is known that a peptide or a metal salt is added to a skin external preparation as a moisturizing agent or other functional ingredient. For example, JP 2007-277119 A (Patent Document 4) discloses a skin external preparation containing ascorbic acid and a hydrolyzed silk protein. Japanese Patent Application Laid-Open No. 11-5725 (Patent Document 5) discloses a skin external preparation containing erythritol and a mineral.

  All of these techniques attempt to improve dry skin roughness by maintaining the moisture content of the skin. However, it has not been studied in terms of preventing the decrease in the activity of proteases involved in the regulation of skin turnover or restoring the decreased activity of proteases, and there is room for further improvement in the prevention and improvement effect against dry skin roughness it was thought.

  Japanese Patent Application Laid-Open No. 2004-284962 (Patent Document 6) discloses a skin external preparation for improving skin roughness containing alum, calcium salt and magnesium salt. Japanese Patent Application Laid-Open No. 2004-300065 (Patent Document 7) selects from monovalent metal and / or divalent metal, oxyacid, chelate-forming substance, polysaccharide carboxylic acid, and methyl vinyl ether-maleic anhydride copolymer. A skin protective agent comprising at least one water-soluble substance is disclosed.

  However, these techniques have not been studied from the viewpoint of preventing the protease activity from being lowered or recovering the lowered protease activity, and it has been considered that there is still room for improvement in the effect of preventing and improving dry skin roughness.

  Thus, there is still a demand for a composition for protecting proteases, which has an effect of preventing a decrease in protease activity caused by dryness in the skin and is excellent in prevention and improvement of dry skin roughness.

JP 2002-234845 A JP-A-10-175844 JP 2003-226613 A JP 2007-277119 A Japanese Patent Laid-Open No. 11-5725 Japanese Patent Laid-Open No. 2004-284963 JP 2004-300065 A

  The present inventors have unexpectedly found that when divalent metal ions and hydrolyzed silk proteins are used in combination, the inactivation due to drying of proteases involved in the control of turnover is extremely effectively prevented. Successful. Furthermore, the present inventors have unexpectedly found that when this combination is used for the protease having a reduced activity, the original enzyme activity of the protease can be recovered. The present invention is based on these findings.

  Therefore, the present invention provides a composition for protecting the stratum corneum peeling enzyme that protects proteases involved in the control of turnover from a decrease in activity due to drying, and can recover the activity of proteases when the activity decreases. An object of the present invention is to provide a composition for protecting the stratum corneum peeling enzyme that is excellent in the effect of preventing and improving dry skin roughness.

  The composition for protecting stratum corneum peeling enzyme according to the present invention is characterized by comprising divalent metal ions and hydrolyzed silk protein as essential components.

  According to one preferred embodiment of the present invention, the hydrolyzed silk protein is hydrolyzed sericin. According to a further preferred embodiment of the present invention, the hydrolyzed sericin has a weight average molecular weight of 1,000 to 100,000.

  According to another preferred embodiment of the present invention, the divalent metal ion is a calcium ion.

  According to another preferred embodiment of the present invention, the divalent metal ion is derived from calcium pantothenate added in the form of a water-soluble metal salt.

  According to a preferred embodiment of the present invention, the content of the metal ions is 0.01 to 10,000 mg / kg with respect to the total amount of the composition, and the content of the hydrolyzed silk protein is the total amount of the composition In contrast, it is 200 to 200,000 mg / kg.

  According to a further preferred embodiment of the present invention, the composition according to the present invention prevents or restores the reduced activity of proteases involved in the regulation of skin turnover due to drying in the skin. Used to make

  According to an even more preferred embodiment of the present invention, the composition according to the present invention is a composition for external use for preventing and improving dry skin roughness.

  According to the composition for protecting the stratum corneum peeling enzyme of the present invention, dry skin roughness can be effectively prevented and improved. That is, the composition according to the present invention has an effect of protecting various proteases, particularly serine proteases, which are considered to be involved in the regulation of skin turnover, from deactivation due to drying (protease activity lowering prevention effect). . The composition according to the present invention also has an effect of recovering its original activity (protease activity recovery effect) for proteases with reduced activity, leading to skin turnover that causes rough skin to a normal state. be able to. In addition, the hydrolyzed silk protein used in the present invention has been known for a long time to be a material excellent in biocompatibility, has no irritation to the skin, and has high safety. Thus, the composition of the present invention has an advantage that it can be applied to skin sensitive to external stimuli, and is extremely effective in preventing and improving dry skin roughness.

Detailed description of the invention

Composition for protecting stratum corneum peeling enzyme The composition for protecting stratum corneum peeling enzyme according to the present invention comprises, as described above, divalent metal ions and hydrolyzed silk protein as essential components. .

  Here, “comprising as an essential component” means that the composition for protecting the stratum corneum peeling enzyme according to the present invention contains the above-mentioned components, divalent metal ions, and hydrolyzed silk protein in a desired stratum corneum peeling enzyme protecting effect. Means that it is inevitably contained in an amount sufficient to exhibit (ie, an effective amount), and to the extent that it means that other components may be included if necessary.

Divalent Metal Ion The divalent metal ion used in the present invention is not particularly limited as long as it is highly safe to living organisms. For example, the second periodic table of magnesium, calcium, strontium, etc. Mention may be made of metal ions of group elements. You may use these in combination of 2 or more types. Calcium ion (Ca ²⁺ ) is preferable as the divalent metal ion from the viewpoint that there is little skin irritation when applied to the skin and the effect of the present invention is excellent.

  The divalent metal ion used in the present invention is considered to prevent inactivation due to drying of the protease by electrically interacting with the protease. Moreover, it is thought that the effect improves synergistically by using hydrolyzed silk protein together. In addition, description regarding these action mechanisms is one theoretical consideration, Comprising: This invention is not limited.

  In the present invention, the divalent metal ion can be added to the composition as a water-soluble metal salt. The metal salt is not particularly limited. For example, a salt of an inorganic acid such as hydrochloride, sulfate, nitrate, or phosphate, a salt of an organic acid such as pantothenate, acetate, citrate, or lactate. These may be used alone or in combination of two or more. Among these, as the metal salt having excellent safety to the skin and the effect of the present invention, the water-soluble metal salt is preferably calcium lactate, calcium chloride or calcium pantothenate. Furthermore, from the viewpoints of safety, stability, solubility, and skin irritation, the water-soluble metal salt is particularly preferably calcium pantothenate.

Hydrolyzed silk protein The hydrolyzed silk protein used in the present invention is obtained by hydrolyzing silk protein produced by rabbits ( Bombyx mori ) and wild boars. The silk protein is a mixture of proteins mainly composed of fibroin and sericin. In the present invention, one obtained by hydrolyzing fibroin and sericin alone or in a mixed state can be used.

  That is, the hydrolyzed silk protein used in the present invention is obtained by hydrolyzing silkworms, raw silk, or scoured silk thread from which sericin has been removed by high-temperature and high-pressure treatment, acid or alkali treatment, or enzyme treatment method, and fibroin or sericin alone. Alternatively, it can be obtained as a mixed aqueous solution. The obtained hydrolyzed silk protein aqueous solution can be concentrated or purified using a technique such as isoelectric point precipitation, alcohol precipitation, membrane separation, or gel filtration, if necessary. Moreover, the aqueous solution of hydrolyzed silk protein can be dried to powder the hydrolyzed silk protein.

  The molecular weight of the hydrolyzed silk protein thus obtained is usually distributed in the range of 200 to 200,000. Any of them can be used in the present invention.

  When the hydrolyzed silk protein is a fibroin hydrolyzate (hydrolyzed fibroin), the weight average molecular weight is preferably 300 to 50,000, more preferably 500 to 30,000. If the weight average molecular weight is less than 300, the peptide chain of the hydrolyzate is short, so that the functionality of fibroin may not be sufficiently exhibited. When the weight average molecular weight exceeds 50,000, the solution stability of the hydrolyzed fibroin is lowered or the penetration into the skin is insufficient, so that the effects of the present invention may not be sufficiently exhibited.

  When the hydrolyzed silk protein is a sericin hydrolyzate (hydrolyzed sericin), the weight average molecular weight is preferably 1,000 to 100,000, and preferably 2,000 to 70,000. More preferably, it is more preferably 5,000 to 50,000. If the weight average molecular weight is less than 1,000, the hydrolyzate peptide chain is short, so that the functionality of sericin may not be sufficiently exhibited. If the weight average molecular weight exceeds 100,000, the solution stability of hydrolyzed sericin may decrease or the penetration into the skin may be insufficient, and thus the effects of the present invention may not be sufficiently exhibited.

  Since the hydrolyzed silk protein in the present invention contains abundant hydroxyl groups and carboxyl groups in the molecule, it is considered to have an effect of stabilizing the three-dimensional structure of the enzyme by interacting with protease through hydrogen bonds and ionic bonds. It is done. In addition, description regarding these action mechanisms is one theoretical consideration, Comprising: This invention is not limited.

  As the hydrolyzed silk protein used in the present invention, hydrolyzed sericin is preferably used from the viewpoint that water solubility is high and moisturizing action is particularly excellent.

  As described in The Journal of Biological Chemistry 257 15192-15199 (1982), sericin has a characteristic amino acid sequence rich in serine, and is considered to be easily cleaved by proteases such as lysine and arginine. There are few amino acids. Accordingly, sericin and hydrolyzed sericin itself are not easily degraded by skin proteases. For this reason, the composition for protecting the stratum corneum peeling enzyme of the present invention has an excellent advantage that it can continue to exhibit the effect of preventing the decrease in protease activity and the effect of recovering protease activity over a long period of time.

  The content of the metal ions in the present invention is preferably 0.01 to 10,000 mg / kg, more preferably 0.05 to 5,000 mg / kg, still more preferably 0.1 to 0.1% based on the total amount of the composition. 1,000 mg / kg. If the content is lower than 0.01 mg / kg, the effects of the present invention may not be sufficiently obtained. Moreover, when it is higher than 10,000 mg / kg, the stability of the composition may be lowered.

  The content of the hydrolyzed silk protein in the present invention is preferably 200 to 200,000 mg / kg, more preferably 300 to 100,000 mg / kg, still more preferably 500 to 30,000 mg / kg based on the total amount of the composition. is there. If the content is lower than 100 mg / kg, the effect of the present invention may not be sufficiently obtained. Even if the content is higher than 200,000 mg / kg, it is difficult to obtain further improvement of the effect of the present invention, which is not practical. .

  In the present invention, the compounding ratio of the metal ion to the hydrolyzed silk protein is preferably such that the concentration ratio of metal ion / hydrolyzed silk protein is 0.0001 / 1 to 10/1, more preferably 0. 0.001 to 5/1. This range is preferable because the effects of the present invention are synergistically enhanced. If the compounding ratio of the metal ions to the hydrolyzed silk protein is less than 0.0001, the effect of the present invention may not be sufficiently obtained, and even if it is greater than 10, it is difficult to further improve the effect of the present invention. .

  In the production of the composition for protecting the stratum corneum peeling enzyme according to the present invention, the method for allowing the metal ions and the hydrolyzed silk protein to coexist is not particularly limited. For example, a water-soluble metal salt can be added to or removed from the hydrolyzed silk protein prepared from koji, if necessary. The addition of the metal salt can be performed at any time, such as before the hydrolysis process of the silk protein, during the hydrolysis, after the hydrolysis process, or at the time of formulation preparation. In addition, metal ions may be removed from the hydrolyzed silk protein to adjust the metal ion concentration. In the case of removing metal ions, a conventionally known desalting method can be used. For example, methods such as adsorption with an ion exchange resin, gel filtration, dialysis, and membrane separation can be used. For measuring the metal ion concentration, a known method such as an atomic absorption photometer can be used.

  The composition of the present invention can be applied, for example, in the form of a lotion, milky lotion, ointment, cream, pack or the like, and can be applied as an external composition for skin such as cosmetics, pharmaceuticals, and quasi drugs.

  When the composition of the present invention is used as an external composition for skin, in addition to the above metal ions and hydrolyzed silk protein, it is usually used for an external composition for skin such as cosmetics and pharmaceuticals, as long as the effects of the present invention are not impaired. Other optional ingredients such as humectants, antioxidants, UV absorbers, emulsifiers, thickeners, surfactants, chelating agents, oily ingredients, alcohols, colorants, powder ingredients, vitamins, anti-inflammatory agents , PH adjusters, preservatives and the like can be appropriately blended as necessary.

  The present invention will be described in detail by the following examples, but the present invention is not limited thereto.

1. Production of Hydrolyzed Silk Protein As hydrolyzed silk protein, aqueous solutions containing hydrolyzed sericin and hydrolyzed fibroin were produced.

1a) Hydrolyzed sericin First, 50 g of cut potato derived from rabbits was washed with water, immersed in 1 L of water, and sodium hydroxide was added so that the pH of the solution was 9.5. Subsequently, the koji was boiled for 2 hours under alkaline conditions, and sericin was extracted and hydrolyzed. The obtained extract was neutralized with hydrochloric acid. Subsequently, the extract was filtered using a filter having an average pore size of 0.2 μm to remove insoluble matters. Furthermore, the extract was desalted using a desalting column (PD-10: manufactured by GE Healthcare Biosciences) to obtain a hydrolyzed sericin aqueous solution having a concentration of about 50,000 mg / kg.
The weight average molecular weight of hydrolyzed sericin in the aqueous solution was about 30,000.

1b) Hydrolyzed fibroin First, 50 g of the cut straw derived from rabbits was washed with water, then immersed in 1 L of water, and sodium hydroxide was added so that the pH of the solution was 9.5. Subsequently, the koji was boiled under alkaline conditions for 2 hours to remove sericin, and fibroin fiber was obtained. The obtained fibroin fiber was washed with water and then dissolved in 500 mL of a 9M lithium bromide aqueous solution to prepare a fibroin aqueous solution. Further, this fibroin aqueous solution was dialyzed to remove lithium bromide in the solution, hydrochloric acid was added so that the final concentration was 0.2 N, and the mixture was heated at 80 ° C. for 1 hour for hydrolysis. After hydrolysis, the solution was neutralized with sodium hydroxide. Subsequently, the obtained solution was filtered using a filter having an average pore diameter of 0.2 μm to remove insoluble matters. Further, desalting was performed using a desalting column (PD-10: manufactured by GE Healthcare Biosciences) to obtain a hydrolyzed fibroin aqueous solution having a concentration of about 50,000 mg / kg.
The weight average molecular weight of hydrolyzed fibroin in the aqueous solution was about 1,500.

2. Preparation of each composition of Examples 1 to 7, Reference Example 8, Example 9 and Comparative Examples 1 to 11 Using the aforementioned aqueous solution of hydrolyzed silk protein, each composition shown in Table 1 and Table 2 was prepared. Applied to each test. Among them, the compositions of Comparative Examples 8 and 9 relate to a known skin external preparation (Japanese Patent Application Laid-Open No. 2007-277119 (Patent Document 4)) containing ascorbic acid and hydrolyzed silk protein. Was used as sodium L-ascorbate.
In each composition, calcium chloride, calcium pantothenate and magnesium chloride were added in the form of a water-soluble metal salt, and metal ions derived from these were used. Moreover, in order to make pH conditions constant, each composition was prepared using a 100 mM Tris-HCl buffer solution (pH 7.0) in this example.

2a) Test a [Protease activity lowering prevention effect]
Trypsin (manufactured by Sigma) was added to each of the compositions of Examples 1 to 7, Reference Example 8, Example 9 and Comparative Examples 1 to 11 so that the final concentration was 100 μg / ml, and the enzyme solution was prepared. Prepared.
Each 10 μl of the obtained enzyme solution was dispensed onto a 96-well microplate and left to stand in a thermostat at 40 ° C. for 2 hours for drying treatment. Subsequently, 190 μl of 100 mM Tris-HCl buffer (pH 7.0) was added thereto to redissolve the enzyme. As a comparison control, trypsin at the above concentration was added to 100 mM Tris-HCl buffer, and a sample not subjected to drying treatment was prepared at the same time.

  Next, 10 μl of an enzyme reaction substrate (N-Succinyl-Arg-p-Nitroanilide (manufactured by Sigma) dissolved in DMSO to a concentration of 10 mM) was added, and the enzyme reaction was carried out at 37 ° C. for 2 hours. After completion of the reaction, the color development (absorption wavelength: 420 nm) of the released p-nitroanilide was measured using a microplate reader IWAKI ASAHI TECHNO GLASS EZS-ABS (manufactured by IWAKI). The activity value of the comparative control was set to 100, and the ratio of the activity value of the protease after the drying treatment (ratio of the activity value after the drying treatment to the activity value when the drying treatment was not performed) was calculated for each sample. It means that it is excellent in the activity fall prevention effect of protease, so that this value is high.

  The results were as shown in the column of “Effect of preventing decrease in activity” in Tables 1 and 2.

  As is clear from the results, in the examples, the effect of preventing the decrease in protease activity is greatly increased, and it is confirmed that the excellent effect of preventing the decrease in protease activity can be obtained by the synergistic action of metal ions and hydrolyzed silk protein. It was done.

2b) Test b [Protease activity recovery effect]
First, trypsin (manufactured by Sigma) was added to a 100 mM Tris-HCl buffer (pH 7.0) so that the final concentration was 100 μg / ml, and this was used as an enzyme solution.
Next, 10 μl of this enzyme solution was dispensed onto a 96-well microplate and left to stand in a thermostat at 40 ° C. for 2 hours for drying treatment. Subsequently, 190 μl of each of the compositions of Examples 3 and 6 and Comparative Examples 1, 3, 4, 5, 6, 10, and 11 was added to redissolve the enzyme. As a comparative control, 180 μl of 100 mM Tris-HCl buffer (pH 7.0) was added to 10 μl of the enzyme solution, and a sample not subjected to drying treatment was prepared at the same time.

  Next, 10 μl of enzyme reaction substrate (N-Succinyl-Arg-p-Nitroanilide (manufactured by Sigma) dissolved in DMSO so as to be 10 mM) was added, and the enzyme reaction was carried out at 37 ° C. for 2 hours. After completion of the reaction, the color development (absorption wavelength: 420 nm) of the released p-nitroanilide was measured using a microplate reader IWAKI ASAHI TECHNO GLASS EZS-ABS (manufactured by IWAKI). Taking the activity value of the comparative control as 100, the ratio of the activity value of the protease after the drying treatment (ratio of the activity value after the drying treatment to the activity value of the enzyme when the drying treatment is not performed) was calculated. The higher this value, the better the activity recovery effect of the protease.

  The results were as shown in the column of “activity recovery effect” in Tables 1 and 2.

  As is apparent from the results, in the examples, the activity recovery effect of the protease was significantly increased. That is, it was confirmed that the composition of the present invention has an excellent effect of recovering protease activity, and leads the enzyme whose activity is reduced by drying to a normal active state again.

3. Test for use on human skin The composition of Example 10 shown in Table 3 was prepared. In the table, the appropriate amount of citric acid is the amount necessary to bring the composition to pH 6.5, and phenoxyethanol was used as a preservative.

A use test was carried out on 20 independent panelists who were aware of dry skin and felt the skin.
The panelist applied an appropriate amount (about 2 ml) of the composition of Example 10 to the entire face twice daily in the morning and evening for 8 weeks. The surface state of the skin before application start and 8 weeks after application was taken as a replica, and the texture state was evaluated according to the usual method of the replica method.

Here, “Kime” means a fine groove (skin groove) running in a mesh pattern on the skin surface, and a portion (skin) that is surrounded by the skin groove and is raised in the shape of a triangle, rhombus, polygon, etc. Hill). Here, the volume i.e. texture volume ratio of texture present per unit area ^{(μm 3 / mm 2/100} ), were evaluated texture number (N / mm) in per unit area.
In general, it can be said that the larger the texture volume ratio is, the higher the skin is, and the more regular the texture is. Moreover, it can be said that the more textured, the finer the texture.

The results were as shown in Table 4.
As is clear from the results, an increase in the texture volume ratio and an increase in the number of textures were observed after coating. From this, the composition of the present invention normalizes the turnover of the stratum corneum in dry skin, has an excellent effect of adjusting texture, and is highly useful as a skin external preparation for preventing and improving dry skin roughness. It was confirmed.

4). Formulation example of composition for protecting stratum corneum peeling enzyme Another formulation example of the composition for protecting stratum corneum according to the present invention is shown below.
Formulation Example 1: Lotion (1) 1,3-butylene glycol 8 (% by weight)
(2) Concentrated glycerin 6
(3) Ethanol 3
(4) L-ascorbic acid-2-glucoside 2
(5) Hydrolyzed sericin 0.2
(6) Aloe extract 0.2
(7) Chlorella extract 0.2
(8) Cuckoo extract 0.01
(9) Yeast extract 0.2
(10) Calcium chloride 0.001
(11) Sodium hydroxide appropriate amount (12) Sodium citrate appropriate amount (13) Citric acid appropriate amount (14) Paraoxybenzoic acid ester 0.1
(15) Purified water Residual pH: 6.7
Manufacturing method: All components are added to purified water sequentially, and mixed and homogenized.

Formulation Example 2: Milk (1) Concentrated glycerin 10 (% by weight)
(2) Ethanol 8
(3) Glyceryl tri-2-ethylhexanoate 6
(4) 1,3-butylene glycol 5
(5) Polyglyceryl distearate 2
(6) Batyl alcohol 2
(7) L-ascorbic acid-2-glucoside 2
(8) Hydrolyzed sericin 0.2
(9) Hydrogenated soybean phospholipid 0.5
(10) Aloe extract 0.2
(11) Chlorella extract 0.2
(12) Cuckoo extract 0.01
(13) Yeast extract 0.2
(14) Daylily powder 0.1
(15) d-δ-tocopherol 0.1
(16) Calcium chloride 0.005
(17) Diethylenetriaminepentaacetic acid pentasodium appropriate amount (18) Carboxyvinyl polymer appropriate amount (19) Hydroxyethylcellulose appropriate amount (20) Sodium citrate appropriate amount (21) Sodium hydroxide appropriate amount (22) Paraoxybenzoic acid ester 0.1
(23) Purified water Residual pH: 7.0
Production method: The oil component and the aqueous component are mixed and homogenized and heated to 80 ° C. The oil component is added to the aqueous component to emulsify, and the mixture is cooled with stirring.

Formulation Example 3: Cream (1) Concentrated glycerin 15 (% by weight)
(2) 1,3-butylene glycol 10
(3) Squalane 10
(4) Hardened oil 5
(5) Batyl alcohol 5
(6) Ethanol 5
(7) Behenyl alcohol 2
(8) Cetyl palmitate 2
(9) Lipophilic glyceryl monostearate 2
(10) Polyoxyethylene glyceryl isostearate 1
(11) Methyl polysiloxane 1
(12) L-ascorbic acid-2-glucoside 2
(13) Hydrolyzed sericin 1
(14) Aloe extract 0.2
(15) Chlorella extract 0.2
(16) Calcium chloride 0.01
(17) Cuckoo extract 0.01
(18) Mulberry extract 0.1
(19) Marronie extract 0.1
(20) Walnut extract 0.1
(21) Yeast extract 0.2
(22) Centella extract 0.1
(23) Terminaria extract 0.01
(24) Licorice extract powder 0.1
(25) Batyl alcohol 0.1
(26) Diethylenetriaminepentaacetic acid pentasodium appropriate amount (27) Hydroxyethylcellulose appropriate amount (28) Sodium citrate appropriate amount (29) Sodium hydroxide appropriate amount (30) Paraoxybenzoic acid ester 0.1
(31) Purified water Residual pH: 6.5
Production method: The oil component and the aqueous component are mixed and homogenized and heated to 80 ° C. The oil component is added to the aqueous component to emulsify, and the mixture is cooled with stirring.

Formulation Example 4: Lotion (1) 1,3-butylene glycol 8 (% by weight)
(2) Concentrated glycerin 6
(3) Ethanol 3
(4) L-ascorbic acid-2-glucoside 2
(5) Hydrolyzed sericin 0.2
(6) Aloe extract 0.2
(7) Chlorella extract 0.2
(8) Cuckoo extract 0.01
(9) Yeast extract 0.2
(10) Calcium pantothenate 0.005
(11) Sodium hydroxide appropriate amount (12) Sodium citrate appropriate amount (13) Citric acid appropriate amount (14) Paraoxybenzoic acid ester 0.1
(15) Purified water Residual pH: 6.7
Manufacturing method: All components are added to purified water sequentially, and mixed and homogenized.

Formulation Example 5: Milk (1) Concentrated glycerin 10 (% by weight)
(2) Ethanol 8
(3) Glyceryl tri-2-ethylhexanoate 6
(4) 1,3-butylene glycol 5
(5) Polyglyceryl distearate 2
(6) Batyl alcohol 2
(7) L-ascorbic acid-2-glucoside 2
(8) Hydrolyzed sericin 0.2
(9) Hydrogenated soybean phospholipid 0.5
(10) Aloe extract 0.2
(11) Chlorella extract 0.2
(12) Cuckoo extract 0.01
(13) Yeast extract 0.2
(14) Daylily powder 0.1
(15) d-δ-tocopherol 0.1
(16) Calcium pantothenate 0.01
(17) Diethylenetriaminepentaacetic acid pentasodium appropriate amount (18) Carboxyvinyl polymer appropriate amount (19) Hydroxyethylcellulose appropriate amount (20) Sodium citrate appropriate amount (21) Sodium hydroxide appropriate amount (22) Paraoxybenzoic acid ester 0.1
(23) Purified water Residual pH: 7.0
Production method: The oil component and the aqueous component are mixed and homogenized and heated to 80 ° C. The oil component is added to the aqueous component to emulsify, and the mixture is cooled with stirring.

Formulation Example 6: Cream (1) Concentrated glycerin 15 (% by weight)
(2) 1,3-butylene glycol 10
(3) Squalane 10
(4) Hardened oil 5
(5) Batyl alcohol 5
(6) Ethanol 5
(7) Behenyl alcohol 2
(8) Cetyl palmitate 2
(9) Lipophilic glyceryl monostearate 2
(10) Polyoxyethylene glyceryl isostearate 1
(11) Methyl polysiloxane 1
(12) L-ascorbic acid-2-glucoside 2
(13) Hydrolyzed sericin 1
(14) Aloe extract 0.2
(15) Chlorella extract 0.2
(16) Calcium pantothenate 0.01
(17) Cuckoo extract 0.01
(18) Mulberry extract 0.1
(19) Marronie extract 0.1
(20) Walnut extract 0.1
(21) Yeast extract 0.2
(22) Centella extract 0.1
(23) Terminaria extract 0.01
(24) Licorice extract powder 0.1
(25) Batyl alcohol 0.1
(26) Diethylenetriaminepentaacetic acid pentasodium appropriate amount (27) Hydroxyethylcellulose appropriate amount (28) Sodium citrate appropriate amount (29) Sodium hydroxide appropriate amount (30) Paraoxybenzoic acid ester 0.1
(31) Purified water Residual pH: 6.5
Production method: The oil component and the aqueous component are mixed and homogenized and heated to 80 ° C. The oil component is added to the aqueous component to emulsify, and the mixture is cooled with stirring.

Claims (4)

Calcium ion, Ri name and a hydrolyzed silk protein as an essential component, and,
Wherein the calcium ions, I desquamating enzyme composition for protecting der you from calcium pantothenate made in the form of a water-soluble metal salt,
A composition for protecting stratum corneum peeling enzyme, which is used to prevent a decrease in activity of a protease involved in the regulation of skin turnover due to drying in the skin or to recover the decreased activity of the protease.   The composition of claim 1, wherein the hydrolyzed silk protein is hydrolyzed sericin.   The composition according to claim 2, wherein the hydrolyzed sericin has a weight average molecular weight of 1,000 to 100,000. The content of the calcium ions is 0.01 to 10,000 mg / kg with respect to the total amount of the composition, and the content of the hydrolyzed silk protein is 200 to 200,000 mg with respect to the total amount of the composition. The composition according to any one of claims 1 to 3 , which is / kg.