JP2002338450A - Skin care preparation and method for beautification using the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a skin care preparation having excellent and stable viscosity, providing comfortableness obtained by a new sense of use, a new value such as information of sign, etc., of completion of massage action obtained by following change in sense and having excellent amelioration and prevention effects on various diseases followed by keratinization abnormality, such as contact dermatitis, psoriasis, pemphigus vulgaris, congential chicken pox, etc., and chapped skin caused by drying, detergent, etc., and to provide a method for beautification using the skin care preparation. SOLUTION: This skin care preparation comprises one or more kinds of polymer thickeners and one or more kinds of splitting enzymes for the polymers with the condition that the enzymes stably exist in the formulation prescription and do not hydrolyze the polymer thickeners in the preparation prescription. The skin care preparation is characterized in that the external preparation comprises a first preparation containing one or more kinds of the polymer thickeners and a second preparation containing one or more kinds of the polymer splitting enzymes and the first preparation is formulated with the second preparation when used. This method for beautification comprises using the skin care preparation.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an external preparation for skin and a cosmetic method using the same, and more particularly to an external preparation for skin containing a polymer thickener and its decomposing enzyme as active ingredients and a cosmetic method using the same.

[0002]

2. Description of the Related Art Various aqueous thickeners have been widely used in the fields of cosmetics, pharmaceuticals, and quasi-drugs to maintain their dosage forms. For example, as organic compounds, polysaccharides, casein, natural polymers such as xanthan gum,
Synthetic polymers such as polyoxyethylene, acrylic acid polymer, carboxyvinyl polymer, etc., as the inorganic compound, various clay minerals such as montmorillonite and silica, etc., are appropriately selected as a thickener according to the intended effect. It is used.

When such thickeners are used in cosmetics, pharmaceuticals, and quasi-drugs, they naturally require high safety for use on the human body, and at the same time, have various temperature ranges. It is required to obtain a stable viscosity, such as maintaining the dosage form, and to be used on the skin for external use in many cases.

[0004] However, there has not been known any conventional thickener which sufficiently satisfies the three points of safety, good stable viscosity, and preferable usability. For example, a cosmetic composition containing a conventionally used clay mineral has a high thixotropy and has a refreshing feeling of use and is preferable in terms of usability, but on the other hand, syneresis tends to occur due to a temperature change. It was unstable. In addition, cosmetic compositions containing conventional polymer thickeners such as vinyl and cellulose are relatively high in safety and require only a small amount of thickeners to be added. A peculiar slimy feeling was generated, which was not preferable in terms of usability.

In order to overcome the slimy feeling peculiar to polymers,
It has been practiced to incorporate a decomposed product of a polymer compound into an external preparation for skin. For example, chitin oligosaccharide (registration No. 260875)
6), maltooligosaccharides (JP-A-4-360820), and algin oligosaccharides (JP-A-8-81378). These oligosaccharides are obtained by hydrolyzing polysaccharides using acids or enzymes, or obtained by chemical synthesis or microbial production.

[0006]

However, since the above-mentioned external preparation for skin contains a decomposed product of a high molecular compound, it has insufficient viscosity, and it is difficult to take out a certain amount when taking it out of a container. Was not preferred. The present invention has been made in view of the prior art,
A skin external preparation that is safe, has good stable viscosity, and provides new comfort such as comfort obtained by a new feeling of use, and information such as a signal of completion of a massage action obtained with a change in feeling, and the like. The purpose is to provide a beauty method using.

[0007]

Means for Solving the Problems In view of the above problems, the present inventors have conducted intensive studies and have found that an external preparation for skin containing a polymer thickener and its decomposing enzyme in a stable state in a pharmaceutical formulation;
An external preparation for skin that is prepared by mixing a preparation containing a polymer thickener and a preparation containing its degrading enzyme at the time of use exhibits excellent effects for the above-mentioned purpose, and at the same time, various diseases accompanied by abnormal keratinization, such as contact Unexpectedly found that it has an excellent improvement / prevention effect on skin irritation caused by drying, detergents, etc., in addition to atopic dermatitis, psoriasis, pemphigus vulgaris, congenital chickenpox, etc., and complete the present invention. Reached.

A first subject of the invention is that it comprises one or more polymeric thickeners and one or more polymeric degrading enzymes, so that the enzymes are stable in the formulation. An external preparation for the skin characterized in that it does not decompose the polymer thickener in the formulation. In the skin external preparation,
It is preferable that the formulation is a two-phase type having two phases that do not mix with each other in the container, one phase containing a polymer thickener and the other phase containing a polymer degrading enzyme. Further, the external preparation for skin contains a two-layer preparation comprising a phase containing a polymer thickener and an oil gel phase containing a polymer degrading enzyme, or a phase containing a polymer thickener and a polymer degrading enzyme encapsulated in a capsule. Suitably, it is a capsule formulation comprising a phase.

In the above external preparation for skin, it is preferable that the compounding amount of the polymer thickener is 0.001 to 50.0% by mass and the compounding amount of the polymer degrading enzyme is 0.000001 to 10.0% by mass. It is. The amount of the polymer degrading enzyme is preferably 0.0005 to 20% by mass based on the polymer thickener.

A second subject of the present invention is that a first formulation containing one or more polymer thickeners and a second formulation containing one or more polymer degrading enzymes. A skin external preparation comprising a preparation, wherein the first preparation and the second preparation are mixed at the time of use. In the skin external preparation, the polymer thickener is 0.001 to 0.001 of the total amount of the skin external preparation.
It is preferable that the first preparation and the second preparation are mixed at the time of use so that the concentration becomes 50.0% by mass. In the skin external preparation, the amount of the polymer degrading enzyme is 0.000 with respect to the total amount of the skin external preparation.
It is preferable to mix the first formulation and the second formulation at the time of use so that the amount becomes 001 to 10.0% by mass. In the above external preparation for skin, the polymer-degrading enzyme is added to the polymer thickener in an amount of 0.1%.
It is preferable to mix the first preparation and the second preparation at the time of use so that the amount becomes 0005 to 20% by mass.

In the above external preparation for skin, it is preferable that the polymer thickener is a polysaccharide thickener. Further, it is preferable that the polysaccharide thickener is one or more selected from the group consisting of glucomannan, galactomannan, alginic acid, inulin or a derivative thereof, and a salt. The third subject of the present invention is a cosmetic method using the skin external preparation.

[0012]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Preferred embodiments of the present invention will be described below. The polymer degrading enzyme used in this application is EC3 (hydrolase) according to the rules of the International Commission on Biochemistry Enzymes.
And any enzyme classified into the category of EC4. (Lyase or lyase), as long as it has an action of decomposing macromolecules. In this stage, more preferred polysaccharide-degrading enzymes will be described in detail. According to the rules of the International Commission for Enzymes of the Biochemistry Union, EC3.2
(Enzymes that act on glycosyl compounds) and EC4.2 (enzymes that act on carbon-hydrogen bonds), but the polysaccharide-degrading enzymes used in the present invention are not necessarily restricted to those classifications, Any enzyme may be used as long as it is an enzyme that classifies as an oligosaccharide or a monosaccharide.

The enzymes classified into EC3.2 include α-Amy
lase (EC3.2.1.1), β-Amylase (EC3.2.1.2), glucoamyl
ase (EC3.2.1.3), Cellulase (EC3.2.1.4), Inulinase (EC
3.2.1.7), Endo-1,4-β-D-xylanase (EC 3.2.1.8), Oligo
-1,6-glucosidase (EC3.2.1.10), Dextranase (EC3.2.1.1
1), Polygalacturonase (EC3.2.1.15), Lysoxyne (EC3.2.
1.17), Neuraminidase (EC 3.2.1.18), α-D-Glacoside
(EC3.2.1.20), β-D-Glucosidase (EC3.2.1.21), β
-D-Galactosidase (EC 3.2.1.23), α-D-Mannosidase
(EC3.2.1.24), β-D-Mannosidase (EC3.2.1.25), Inv
ertase (EC 3.2.1.26), α, α'-Trehalase (EC 3.2.1.2
8), β-N-Acetyl-D-glucosaminidase (EC 3.2.1.30),
β-D-Glucuronidase (EC3.2.1.31), Xylamase (EC3.2.
1.32), Amyno-1,6-glucosidase (EC 3.2.1.33), Hyaluron
oglucosamidase (EC3.2.1.35), Hyaluronoglucuronidase
(EC3.2.1.36), β-Xylosidase (EC3.2.1.37), β-D-
Fucosidase (EC3.2.1.38), α-L-Rhamnosidase (EC3.2.
1.40), Pullulanase (EC 3.2.1.41), GDP glucosidase (EC
3.2.1.42), β-L-Rhamnosidase (EC 3.2.1.43), Fucoida
nase (EC3.2.1.44), Glucosylceramidase (EC3.2.1.45),
Galactocerebrosidase (EC3.2.1.46), Ceramide (EC3.2.
1.47), α-N-Acetyl-D-galactosaminidase (EC3.2.1.
49), α-N-Acetyl-D-glucosaminidase (EC 3.2.1.5
0), α-L-Fucosidase (EC 3.2.1.51), β-N-Acetyl-D
-Hexosaminididase (EC3.2.1.52), β-N-Acetyl-D-g
alactosaminidase (EC3.2.1.53), Cyclomaltodextrinase
(EC3.2.1.54), α-L-Arabinofaranosidase (EC3.2.1.5
3), Isopullulanase (EC 3.2.1.57), Exo-1,3-β-D-gl
ucosidase (EC3.2.1.58), Exo-maltotetrahydrolase (EC
3.2.1.60), Mycodextranase (EC 3.2.1.61), Glycosylcer
amidase (EC3.2.1.62), 1,2-α-L-Fucosidase (EC3.2.1.
63), Levsanase (EC 3.2.1.65), Quercitrinase (EC 3.2.1.
66), Exopolygalacturonase (EC 3.2.1.67), Isoamilase
(EC3.2.1.68), Endo-1,2-β-D-glucanase (EC3.2.1.7
1), Exo-1,3-β-D-xylosidase (EC 3.2.1.72), Licben
ase (EC3.2.1.73), Exo-1,4-β-D-glucosidase (EC3.
2.1.74), Endo-1,6-β-D-glucanase (EC 3.2.1.75), L
-Idironidase (EC3.2.1.76), Exo-1,2-1,3-α-D-mann
osidase (EC 3.2.1.77), Endo-1,4-β-D-manuanase (EC
3.2.1.78), Exo-β-D-fructosidase (EC 3.2.1.80), E
xo-poly-α-D-galacturonosidase (EC 3.2.1.82), ε-
Carrageenanase (EC3.2.1.83), Exo-1,4-α-glucanase
(EC3.2.1.84), 6-Phospho-β-D-galactosidase (EC3.
2.1.85), 6-Phospho-β-D-glucosidase (EC 3.2.1.8
6), Polysaccharide depolymerase (EC 3.2.1.87), β-L
-Arabinosidase (EC 3.2.1.88), Endo-1,4-β-D-gala
ctanase (EC 3.2.1.89), Endo-1,3-β-D-galactanase
(EC3.2.1.90), Exo-β-N-acetylmuramidase (EC3.2.1.
92), α, α'-Phosphotrehalase (EC 3.2.1.93), Exo-is
omaltohydrolase (EC 3.2.1.94), Exo-isomaltotriohydro
lase (EC3.2.1.95), Endoβ-N-acetylglacosaminidase
(EC3.2.1.96), Endo-α-N-acetylgalactosaminidase
(EC3.2.1.97), Exo-maltohexaohydrolase (EC3.2.1.9
8), L, 2-α-D-Mannosidase (EC3.2.1.-), Inosine nuc
leosidase (EC3.2.2.2), Uridine nucleosidase (EC3.2.
2.3), and AMP nucleosidase (EC3.2.2.4), etc.
Any enzyme that acts on glycosyl compounds is effective regardless of whether or not it has been registered with the International Commission on Enzymes of the Biochemical Union.
These enzymes are effective regardless of their origin, whether animal, plant, or microbial. The effects of these enzymes differ depending on the combination with the substrate polysaccharide. Among them, the combination of glucomannan and / or galactomannan with β-D-Mannosidase, inulin and Inuli
A combination with nase, a combination of pectin and Polygalacturonase, and a combination of cellulose and / or a cellulose derivative and Cellulase have excellent effects.

The enzymes classified into EC 4.2.2 include Hyalu
ronate lyase (EC4.2.1.1), Pectatelyase (EC4.2.2.2),
Alginase lyase (EC 4.2.2.3), Chpndroitin ABC lyase (E
C4.2.2.4), Chondroitin lyase (EC4.2.2.5), Oligogala
cturonase lyase (EC4.2.2.6), Heparin lyase (EC4.2.2.
7), Heparitin lyase (EC4.2.2.8), Exopolygalacturona
se lyase (EC4.2.2.9) and Pectin lyase (EC4.2.2.10)
Etc., but if it is an enzyme acting on carbon-hydrogen bond,
It is effective with or without registration with the International Commission on Biochemistry Enzymes. These enzymes are effective regardless of their origin, whether animal, plant, or microbial. The effect of these enzymes depends on the combination with the substrate polysaccharide. Among them, alginic acid and / or a combination of alginate and Alginaselyase, hyaluronic acid and Hyalu
Combination with ronate lyase has excellent action.

[0015] The polymer thickeners used in the present invention include glucomannan, galactomannan, guar gum, locust bean gum, alginic acid, inulin, pectin, cellulose, hemicellulose, starch (corn, wheat, rice, potato, kuzu, etc.). Etc.), carrageen, agar, porphyran, gum arabic, xanthan gum, dextran, succinoglucan, pullulan, quince seed, algae colloid, xyloglucan, α-glucan, β-glucan, gellan gum, tragacanth gum, karaya gum, tamarind gum, arabino Galactan gum,
Glycogen, chitin, chitosan, methylcellulose,
Examples include carboxymethyl cellulose, hydroxyalkylmethyl cellulose, ethyl cellulose, hydroxyethyl cellulose, starch acetate, hydroxyethyl starch, hydroxypropyl starch, hyaluronic acid, heparin, chondroitic acid, dermatan sulfate, heparan sulfate, fucoidan, and salts thereof.

The polymer thickener is 0.001 in the total amount of the external preparation.
It is preferably from 5 to 50.0% by mass, and more preferably from 0.01 to 10.0% by mass. If the amount is less than 0.001% by mass, the effect of the present invention is not sufficiently exhibited, and if the amount is 50% by mass or more, preparation becomes difficult.

The polymer-degrading enzyme is used in an amount of 0.00
It is preferably from 0001 to 10.0% by mass, more preferably from 0.00001 to 1.0% by mass.
If the amount is less than 0.000001% by mass, the effect of the present invention is not sufficiently exhibited, and even if added in an amount of 1.0% by mass or more, the effect is not so greatly improved. Absent.

The amount of the polymer degrading enzyme is preferably 0.0005 to 20% by mass based on the polymer thickener. 0.
If the amount is less than 0005% by mass, the effect of the present invention is not sufficiently exhibited, and even if it is blended at 20% by mass or more, the effect is not so greatly improved, and it is not preferable from the viewpoint of the formulation of an external preparation.

The external preparation for skin of the present invention is usually used for external preparation of skin such as cosmetics and pharmaceuticals, in addition to the above-mentioned polymer thickener and polymer decomposing enzyme, as long as the effect of the present invention is not impaired. Ingredients, such as moisturizers, antioxidants, oily components, UV absorbers, emulsifiers, surfactants, thickeners, alcohols, powder components, coloring materials, aqueous components, water, various skin nutrients, etc. It can be appropriately compounded depending on the situation.

Further, sequestering agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, malic acid, caffeine, tannin, verapamil, tranexamic acid, and the like Derivatives, licorice extract, glabridine, hot water extract of karin fruit, various crude drugs, drugs such as tocophenol acetate, glycyrrhizinate, and derivatives or salts thereof, retinoic acid, retinol, retinol acetate, retinol pyroionate, palmitic acid Drugs such as retinol and its derivatives or salts thereof, vitamin C, whitening agents such as magnesium ascorbate phosphate, glucoside ascorbate, arbutin, kojic acid, fructose, mannose, erythritol, trehalose, xylitol, etc. Sugars, arginine, amino acids such as lysine, and can be blended as appropriate also amino acids such as derivatives or salts thereof, such as trimethyl glycine.

The external preparation for skin of the present invention can be widely applied to cosmetics, pharmaceuticals and quasi-drugs applied to the outer skin. In a one-part type external preparation containing a polymer thickener and a polymer-degrading enzyme in one part, the dosage form is such that the enzyme is stably present in the preparation, and the enzyme is contained in the preparation. It can be in any drug formulation form provided that the polymer thickener is not decomposed, and can be a solution system, a solubilizing system, an emulsifying system, a powder dispersion system, a water-oil 2
Although it can be provided in any form, such as a layer system, a water-oil-powder tri-layer system, a gel, an aerosol, and a capsule, the preferred formulation has two phases that do not mix with each other in the container, while Is a two-phase type containing a polymer thickener in the phase and a polymer degrading enzyme in the other phase.
Layer formulation (FIG. 1 (A)) and capsule formulation (FIG. 1
(B)).

The two-layer preparation is composed of a phase containing a polymer thickener and an oil gel phase containing a polymer-degrading enzyme and has a viscosity, so that it does not mix in a container. The capsule preparation is composed of a phase containing a polymer thickener and a phase containing a polymer degrading enzyme encapsulated in a capsule, and does not mix in a container. In a two-part type external preparation comprising a first preparation containing a polymer thickener and a second preparation containing a polymer-degrading enzyme, the dosage form is such that the enzyme is stably present in the second preparation. It is possible to take any form of drug formulation on the condition that both the first formulation and the second formulation are a solution system, a solubilizing system, an emulsifying system, a powder dispersing system, a water-oil two-layer system, a water-oil-
It can be provided in any form, such as a three-layer powder system, a gel, an aerosol, and a capsule.

The form of use is arbitrary, for example, lotion, cream, milky lotion, lotion, pack, ointment,
In addition to mousse and soap, any form can be used as long as it is conventionally used for skin external preparations, such as makeup cosmetics such as foundations and lipsticks, bath preparations and the like.

[0024]

Next, the present invention will be described in more detail with reference to examples.
However, the technical scope of the present invention is limited by these examples.
It is not something to be done. In addition, all blending amounts are mass%.
You. First, the high-molecular-weight degrading enzyme used in the present invention
The effect on the child thickener was tested. As a polymer thickener
Glucomannan (White Propol A^TM： Shimizu Chemical
Co., Ltd.) as β-D-Mannos
idase (cellulosin GM5 ^TM: Hankyu Bio-Industry
These are mixed and stirred for 30 seconds.
After a specific time, a single cylindrical rotational viscometer (Bismetron)
VS-A1^TM: Shibaura System Co., Ltd.)
It was measured. Measure the viscosity at room temperature (24 ± 2 ℃).
No. 2 to 4 rotors are used properly, at 12 revolutions per minute
went. In addition, β-D-Mannosidase is β-D-Mannosidase.
This enzyme decomposes the side from the non-reducing end. Figure 2 shows the results.
Shown in

As can be seen from FIG. 2, β-D-Mannosidas
When e was 0.005 to 0.5% by mass with respect to glucomannan, a remarkable change in physical properties was exhibited. Although not shown in this test, β-D-Mann for glucomannan
It has been confirmed by another experiment that when the amount of osidase is 20% by mass, a remarkable change in physical properties exceeding 0.5% by mass is exhibited. In addition, β-D-
It has been confirmed by another experiment that when the amount of mannosidase is 0.0005% by mass, the reaction time is prolonged, but a clear change in physical properties is exhibited. Therefore, the polymer-degrading enzyme is used in an amount of 0.0005 to 20 with respect to the polymer thickener.
It is preferable to mix by mass%.

Next, a description will be given of a test method relating to the feeling of use of the polymer thickener and the polymer degrading enzyme used in the present invention, and its evaluation criteria. As shown in Table 1, glucomannan (white propol A) was used as a polymer thickener.
^TM: Shimizu Chemical Co., Ltd.), alginic acid derivatives (Duck Algin NSPH ^{T M:} manufactured by Kamogawa Kasei Co., Ltd.), cellulose derivatives (Natrosol 250HR ^TM: Hercules Co., Ltd.), or pectin (Classic AF50
1 ^TM: Dainippon Pharmaceutical Co., Ltd.), β-D-Mannosidase as the polymer-degrading enzyme (sumizyme ^{ACH T M:} manufactured by Shin Nippon Chemical Industrial Co., Ltd.), Alginase lyase (alginate lyase ^{S TM:} Nagase Seikagaku Corporation Made), Cell
Formulation Examples 1 to 10 were blended using ulase (Cellulosin AC40 ^™ : manufactured by Hankyu Bio Industries Co., Ltd.) and Polygalacturonase (Sumiteam AP-2 ^™ : manufactured by Shin Nippon Chemical Industry Co., Ltd.).

[0027]

[Table 1]  Formulation example1 2 3 4 5 6 7 8 9 10  Polymer thickener 0.8---------Alkionic acid derivative-1.0--------Cellulose derivative--1.5-------Pectin − − − 1.0 − − − − − −  Polymerase β-D-Mannosidase − − − − 0.001 − − − − − 0.00004 Alginase lyase − − − − − − 1.00 − − − − Cellulase − − − − − − − 0.01 − − −Polygalacturonase − − − − − − − 0.1 − − Citric acid 0.02 0.02 0.02 0.02 0.02 0.02 0.02 0.02 0.02 0.02 Sodium citrate 0.08 0.08 0.08 0.08 0.08 0.08 0.08 0.08 0.08 0.08Purified water residue residue residue residue residue residue residue residue residue residue residue residue

(1) Evaluation Test for Feeling of Use Ten healthy women were used as subjects, and the evaluation was performed using the cheeks of the face. The samples are shown in Table 2. The application method was to apply 0.3 ml of the liquid first, and then apply 0.3 ml of the liquid. Five subjects applied the sample according to Table 3 and the remaining five subjects applied the sample according to Table 4. That is, in one evaluation, two products (or one product) were evaluated simultaneously using the left and right cheeks. The evaluation was started by applying the sample 10 minutes after face washing, and the change in the feel during use was observed while rubbing immediately after the application, and the evaluation was made according to criteria I to III. Table 5 shows the results of the average scores of the ten subjects.

<Criterion I: Degree of change in use feeling> Rating 3: Dramatic change is felt. Rating 2: Change is clearly felt. Rating 1: slight change is felt. Rating 0: No change is felt. <Criterion II: Degree of occurrence of skewing after coating> Score 3: No skewing is observed. Score 2: Slight distortion is observed. Score 1: Distortion is clearly observed. Score 0: Violent, with a twist. <Criterion III: Taste of use feeling> Rating 3: Very liking. Score 2: I like it. Rating 1: Rather like. Rating 0: Neither. Rating -1: I dislike rather. Score-2: Dislike. Rating-3: Very disliked.

[0030]

[Table 2]

[Table 3]

[Table 4]

[Table 5]

As is apparent from Table 5, in Sample 2, Sample 4, Sample 6, Sample 8, and Sample 9 containing none of the polymeric thickener, no change in the use feeling was observed. The palatability for use feeling was not always good due to problems such as generation of twist. On the other hand, Sample 1, Sample 3, which combined a polymer thickener and a polymer degrading enzyme,
In Samples 5 and 7, a clear change in use feeling was observed,
Problems such as twisting were also improved, and the palatability for use feeling was very good.

(2) Roughness Prevention Effect Judgment Test (Prevention Effect for Experimental Roughness Caused by SDS)
Absorbent cotton (2 × 2 cm) soaked with a 5% SDS aqueous solution was applied to four places on the inner side of the forearm of 10 male panels, and fixed for 15 minutes. After washing this off, samples 10 to 13 in Table 6 were applied. The application method is to first apply 0.5 ml,
Was applied by 0.5 ml. This was repeated for 7 days, and on the 8th day, the test site was thoroughly washed and left for 60 minutes. Then, the degree of rough skin was observed and evaluated based on the following criteria IV. Table 7 shows the results.

<Criteria IV> Evaluation 4: Clear erythema and / or desquamation is observed. Evaluation 3: Moderate erythema and / or slight desquamation is observed. Evaluation 2: Slight erythema and / or cracks in the stratum corneum are observed. Evaluation 1: The keratinous surface appears whitish or powdery. Evaluation 0: No symptoms.

[0034]

[Table 6] Sample 10 Sample 11 Sample 12 Sample 13  Formulation Example 2 Formulation Example 2 Formulation Example 9 Formulation Example 9Formulation Example 6 Formulation Example 9 Formulation Example 6 Formulation Example 9

[0035]

[Table 7]  Evaluation of rough skin Sample 10 Sample 11 Sample 12 Sample 13  40 1 1 5 6  30 people 4 people 4 people 3 people  2 1 person 4 people 1 person 1 person  1 4 1 0 0  0 5 people 0 people 0 people 0 people

As is clear from Table 7, the sample 11 containing only the polymer thickener (alginate derivative), the sample 12 containing only the polymer degrading enzyme (alginate lyase), and the sample 13 containing neither of them have the effect of preventing rough skin. While almost no was observed, it was confirmed that the sample 10 in which the polymer thickener (alginate derivative) and the polymer-degrading enzyme (alginate lyase) were combined had an excellent skin roughness preventing effect.

(3) Test of Relationship between Combination of Substrate and Enzyme and Roughness Prevention Effect A cotton wool (2 × 2 cm) soaked with a 5% SDS aqueous solution was applied to four places on the inner side of the forearm of six male panels and fixed for 15 minutes. After this was washed away, samples 14 to 17 in Table 8 were applied. The application method is to first apply 0.5 ml,
Was applied by 0.5 ml. This was repeated for 4 days, the test site was thoroughly washed on the 5th day, left for 60 minutes, then the degree of skin roughness was observed, and evaluated based on the above judgment criteria IV. The result is shown in FIG.

[0038]

[Table 8] Sample 14 Sample 15 Sample 16 Sample 17  Formulation Example 9 Formulation Example 1 Formulation Example 1 Formulation Example 1Formulation Example 9 Formulation Example 9 Formulation Example 5 Formulation Example 10

As is clear from FIG. 3, as compared with the sample 15 containing only glucomannan, the sample 16 obtained by combining the polymer thickener (glucomannan) and the polymer degrading enzyme (β-D-Mannosidase) was used. No. 17 was found to exhibit an excellent effect of preventing rough skin.

The following are prescription examples of skin preparations suitable for carrying out the present invention, but the technical scope of the present invention is not limited by these examples. Further, in order for the present invention to be carried out well, it is required that the enzyme is stably present in the pharmaceutical formulation and that the enzyme does not decompose the polysaccharide thickener in the pharmaceutical formulation. In order to satisfy these conditions, in Examples 1 to 8, the enzyme was encapsulated in a gelatin capsule and used, and in Examples 9 and 10, a two-layer preparation was used. The amount of the enzyme in the gelatin capsule is 5% by mass.

[0041]Example 1 Cream  (Formulation) Mass% Stearic acid 5.0 Stearyl alcohol 4.0 Isopropyl myristate 18.0 Glycerin monostearate 3.0 Propylene glycol 10.0 Locust bean gum 3.0 Gelatin capsule 2.0 (Cellulosin GM5^TM: Included by Hankyu Bio-Industry Co., Ltd.) Sodium bisulfite 0.01 Preservatives Appropriate amount Fragrance Appropriate amount Ion exchange water residue (Production method) Propylene glycol, loca
Dissolve by adding bean gum and gelatin capsule
And heat to maintain at 70 ° C. (aqueous phase). Mix the other ingredients
Heat and maintain at 70 ° C (oil phase). Gradually add oil phase to water phase
In addition, keep at that temperature for a while after the addition and react
Wake up. Then, homogenize uniformly with a homomixer,
Cool to 30 ° C with good stirring.

[0042]Example 2 Cream  (Formulation) Mass% Stearic acid 2.0 Stearyl alcohol 7.0 Hydrogenated lanolin 2.0 Squalane 5.0 2-Octyldodecyl alcohol 6.0 Polyoxyethylene (25 mol) Cetyl alcohol ether 3.0 Glycerin monostearate 2.0 Propylene glycol 5.0 Carboxymethyl cellulose 0.01 Gelatin capsule 0.001 ( Cellulosin AC40^TM: Included by Hankyu Bio-Industry Co., Ltd.) Tranexamic acid 1.0 Sodium bisulfite 0.03 Ethyl paraben 0.3 Perfume Appropriate amount Ion-exchanged water Residue
Add the latin capsules, dissolve and heat to 70 ° C
(Aqueous phase). Mix with other ingredients, heat and melt to keep at 70 ° C
(Oil phase). Preliminary emulsification is performed by adding the oil phase to the aqueous phase.
Emulsify evenly with a momixer, 30 ° C while stirring well
Cool down to

[0043]Example 3 Emulsion  (Formulation) Mass% Stearic acid 2.5 Cetyl alcohol 1.5 Vaseline 5.0 Liquid paraffin 10.0 Polyoxyethylene (10 mol) Monooleate 2.0 Polyethylene glycol 1500 3.0 Triethanolamine 1.0 Carboxyvinyl polymer 0.05 (Carbopol 941^TM: B.F. Goodrich Chemical company) Propylene glycol 5.0 Natrosol 250HR^TM(Manufactured by Hercules) 0.1 Gelatin capsule 0.01 (Cellulosin T2^TM: Included by Hankyu Bio-Industry Co., Ltd.) Arbutin 1.0 Sodium bisulfite 0.01 Ethyl paraben 0.3 Perfume Appropriate amount Ion-exchanged water Residue
Dissolve (Phase A). Polyethylene in the remaining ion-exchanged water
Len glycol 1500, triethanolamine, and
Add gelatin capsule, heat and melt to keep at 70 ° C
(Aqueous phase). Mix with other ingredients, heat and melt to keep at 70 ° C
(Oil phase). Preliminary emulsification is performed by adding the oil phase to the aqueous phase.
Add the phases, emulsify uniformly with a homomixer, and stir well
While cooling to 30 ° C.

[0044]Example 4 Emulsion  (Prescription) Mass% Microcrystalline wax 1.0 Beeswax 2.0 Lanolin 20.0 Liquid paraffin 10.0 Squalane 5.0 Sorbitan sesquioleate 4.0 Polyoxyethylene (20 mol) Sorbitan monooleate 1.0 Propylene glycol 7.0 Classic CM201^TM(Dainippon Pharmaceutical Co., Ltd.) 0.1 Gelatin capsule 0.01 (Sumiteam AP-2^TM: Includes Nippon Chemical Industries Co., Ltd.) Arbutin 1.0 Sodium bisulfite 0.01 Ethylparaben 0.3 Perfume Appropriate amount Ion-exchange water residue (Production method) Propylene glycol, trie
Tanolamine, classic CM201, and gelatin
Add capsules and heat to melt and keep at 70 ° C. (aqueous phase).
The other components are mixed, melted by heating and kept at 70 ° C. (oil phase).
While stirring the oil phase, gradually add the aqueous phase and use a homomixer
Emulsify uniformly and cool to 30 ° C with good stirring
You.

[0045]Example 5 Jelly  (Prescription) mass% 95% ethanol 10.0 dipropylene glycol 15.0 polyoxyethylene (50 mol) oleyl alcohol ether 2.0 carboxyvinyl polymer 0.05 (Carbopol 940^TM: B.F. Goodrich Chemical company) Caustic soda 0.15 L-arginine 0.1 Leorex RS^TM(Manufactured by Shimizu Chemical Co., Ltd.) 2.0 Gelatin capsule 1.0 (GODO-BAM^TM: Included by Godo Shusei Co., Ltd.) Sodium bisulfite 0.01 Ethyl paraben 0.3 Perfume Appropriate amount Ion-exchanged water Residue
Uniform dissolution of Orex RS and gelatin capsule
(Aqueous phase), while polyoxyethylene in 95% ethanol
(50 mol) Dissolve oleyl alcohol ether and water phase
To be added. Then, after adding other ingredients, caustic soda,
Neutralize with L-arginine to thicken.

[0046] (Phase B) Olive oil 5.0 Tocophenol acetate 0.2 Ethyl paraben 0.2 Fragrance 0.2 (Phase C) Sodium bisulfite 0.03 Polyvinyl alcohol 13.0 (Saponification degree 90, Degree of polymerization 2,000) Ethanol 7.0 Gelatin capsule 0.1 (Included hyaluronate lyase) Purified water Residue (Preparation method) Dissolve A phase and B phase uniformly, and add B
Add phases and solubilize. Next, after adding the phase C in which the gelatin capsule is dispersed, filling is performed.

[0047]Example 7 Cream  (Formulation) Mass% Solid paraffin 5.0 Beeswax 10.0 Vaseline 15.0 Liquid paraffin 41.0 Glycerin monostearate 2.0 Polyoxyethylene (20 mol) Sorbitan monolaurate 2.2 Soap powder 0.1 Borax 0.2 Inulin 0.001 Gelatin capsule 0.01 (Inulinase included) Bisulfite Sodium 0.03 Ethylparaben 0.3 Perfume Appropriate amount Ion-exchanged water residue (Preparation method) Ion-exchanged water in gelatin capsule, soap
Powder and borax, and heated to 70 ° C (water
phase). In addition, mix other components, heat and dissolve, and keep at 70 ° C.
(Oil phase). Slowly add oil phase to water phase while stirring
After adding all, keep the temperature for a while and react
Awakened. Then, homogenize uniformly with a homomixer,
Cool to 30 ° C while stirring well to obtain cream
Was.

[0048]Example 8 Cream  (Formulation) Mass% Solid paraffin 5.0 Beeswax 10.0 Vaseline 15.0 Liquid paraffin 41.0 Glycerin monostearate 2.0 Polyoxyethylene (20 mol) Sorbitan monolaurate 2.2 Soap powder 0.1 Borax 0.2 Corn starch 3.0 Gelatin capsule 0.1 (Amylase AD Amano "1^TM： Included by Amano Pharmaceutical Co., Ltd.) Sodium bisulfite 0.03 Ethylparaben 0.3 Perfume Appropriate amount Ion-exchange water Residue (Production method) Corn starch and gelatin in ion-exchange water
Add capsules, soap powder and borax and heat to 7
It was kept at 0 ° C. (aqueous phase). Also, mix other ingredients and heat
Disassembled and kept at 70 ° C. (oil phase). Do not stir the oil phase into the water phase
And then add it slowly
The temperature was maintained to initiate the reaction. Then use a homomixer
Emulsify uniformly, cool to 30 ° C while stirring well,
I got a cream.

[0049]Example 9 Two-layer formulation  [Oil gel phase] (Formulation) Mass% Methyl polysiloxane 45.0 Cyclomethicone (D5) 44.8 Hydrophobized silica powder 7.0 Dimethylpolysiloxane / methyl (polyoxyethylene) siloxane copolymer 0.5 Silicone rubber powder 2.5 Cellulosin GM5^TM 0.2 [Polymer gel phase] (Formulation) Mass% Rheox RS^TM 1.0 Preservatives Appropriate amount Fragrance Appropriate amount Ion-exchange water residue (Preparation method)
Heat to ℃ and stir and dissolve (polymer gel phase). Ma
The oil gel phase components are mixed and heated to 50 ° C for melting.
(Oil gel phase). After cooling each phase, both phases are mixed in the vessel
Fill in a two-layer container that does not have a structure. that time
The ratio of the two phases is the oil gel phase to the polymer gel phase 9.
Set to 1. Also, fill both phases in separate containers
Then, they can be mixed at the time of use.

[0050]Example 10 Two-layer formulation  [Oil gel phase] (prescription) mass% dextrin fatty acid ester 20.0 methylphenylpolysiloxane 79.5 inulinase 0.5 [polymer gel phase] (prescription) mass% inulin 5.0 preservatives proper amount perfume proper amount ion exchange water residue (production method) high to ion exchange water Add molecular gel phase components and add 70
Heat to ℃ and stir and dissolve (polymer gel phase). Ma
The oil gel phase components are mixed and heated to 50 ° C for melting.
(Oil gel phase). After cooling each phase, both phases are mixed in the vessel
Fill in a two-layer container that does not have a structure. that time
The ratio of the two phases is the oil gel to the polymer gel phase 19
Make it phase 1. Also, fill both phases in separate containers
Then, they can be mixed at the time of use.

[0051]

As described above, according to the polymer thickener and the decomposing enzyme thereof of the present invention, it is safe, has a good stable viscosity, and provides a new feeling of use and comfort. At the same time, new value such as information such as a signal of completion of massage action obtained with change in sensation can be obtained, and various diseases accompanied by abnormal keratinization, such as contact dermatitis, psoriasis, pemphigus vulgaris, congenital It is possible to obtain an external preparation for skin that has an excellent effect of improving and preventing skin roughness caused by drying, detergents, etc., in addition to pesticidal pox and the like.

[Brief description of the drawings]

FIG. 1 is an explanatory view of a preferred formulation of a skin external preparation in the present invention.

FIG. 2 shows a polymer degrading enzyme (β-D-Mannnosidase) for a polymer thickener (glucomannan) in the present invention.
Is a time change of the action of

FIG. 3 is a test result of a relationship between a combination of a polymer thickener and a polymer degrading enzyme in the present invention and an effect of preventing rough skin.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 47/36 A61K 47/36 A61P 17/16 A61P 17/16 (72) Inventor Takaya Tsuda Chuo-ku, Tokyo 7-5-5 Ginza Shiseido Co., Ltd. (72) Inventor Takeshi Kusakari 2-2-1 Hayabuchi, Tsuzuki-ku, Yokohama-shi, Kanagawa Prefecture Shiseido Research Center (Shin-Yokohama) Co., Ltd. (72) Inventor Fumiaki Matsuzaki 2-2-1 Hayabuchi, Tsuzuki-ku, Yokohama-shi, Kanagawa Prefecture Shiseido Research Center (Shin-Yokohama) F-term (reference) 4C076 AA06 BB31 CC18 EE30 EE41 4C083 AA082 AA122 AB032 AB152 AB172 AB352 AC022 AC072 AC102 AC132 AC182 AC242 AC422 AC482 AC542 AC582 AC622 AD042 AD092 AD152 AD162 AD192 AD211 AD242 AD272 AD301 AD332 AD352 AD471 AD472 AD512 AD662 CC02 CC05 CC07 DD 31 DD41 EE12

Claims (14)

[Claims] (1) one or more polymer thickeners;
An external preparation for skin, comprising one or more kinds of the above-mentioned polymer-degrading enzymes, wherein the enzyme is stably present in the formulation and does not decompose the polymer thickener in the formulation. 2. The external preparation for skin according to claim 1, wherein the prescription form has two phases which are not mixed with each other in the container, one of which contains a polymer thickener and the other of which contains a polymer degrading enzyme. An external preparation for skin, which is of a two-phase type. 3. The external preparation for skin according to claim 2, wherein the two phases that do not mix with each other in the container are a two-layer preparation comprising a phase containing a polymer thickener and an oil gel phase containing a polymer degrading enzyme. An external preparation for skin characterized by the following. 4. The external preparation for skin according to claim 2, wherein the two phases that do not mix with each other in the container are a capsule preparation comprising a phase containing a polymer thickener and a phase containing a polymer degrading enzyme encapsulated in a capsule. An external preparation for skin, which is characterized in that: 5. The external preparation for skin according to claim 1, wherein the compounding amount of the polymer thickener is 0.001 to 50.0% by mass. 6. The external preparation for skin according to claim 1, wherein the amount of the polymer degrading enzyme is 0.000001 to 10.0% by mass. 7. The external preparation for skin according to claim 1, wherein the amount of the polymer degrading enzyme is 0.000 to the polymer thickener.
An external preparation for skin, which is 5 to 20% by mass. 8. A first preparation comprising: a first preparation containing one or more polymer thickeners; and a second preparation containing one or more polymer degrading enzymes. And an external preparation for skin, wherein the composition is mixed with a second preparation at the time of use. 9. The external preparation for skin according to claim 8, wherein the first preparation and the second preparation are used so that the amount of the polymer thickener is 0.001 to 50.0% by mass relative to the total amount of the external preparation for skin. An external preparation for skin characterized by mixing at the same time. 10. The external preparation for skin according to claim 8, wherein the amount of the polymer degrading enzyme is 0.000001 relative to the total amount of the external preparation for skin.
An external preparation for skin, characterized in that the first preparation and the second preparation are mixed at the time of use so that the amount becomes 10.0 mass%. 11. The external preparation for skin according to claim 8, wherein
The polymer-degrading enzyme is 0.0005 to polymer thickener.
An external preparation for skin, wherein the first preparation and the second preparation are mixed at the time of use so as to be 20% by mass. 12. The external preparation for skin according to claim 1, wherein
An external preparation for skin, wherein the polymer thickener is a polysaccharide thickener. 13. The external preparation for skin according to claim 1, wherein
An external preparation for skin, wherein the polysaccharide thickener is one or more selected from the group consisting of glucomannan, galactomannan, alginic acid, inulin or a derivative or salt thereof. 14. A cosmetic method using the external preparation for skin according to claim 1.