JP5704809B2 - External preparation for skin and pruritus - Google Patents

Description

  The present invention relates to an external preparation for skin and an agent for reducing pruritus.

At present, it is said that there are about 270,000 patients undergoing artificial dialysis in Japan. In the skin of dialysis patients who tend to be deficient in water, the barrier function of the stratum corneum is lowered and sensitive to external stimuli, and skin dryness such as xeroderma and sebum deficiency is a heavy burden on dialysis patients. It has become.
In patients requiring artificial dialysis, the function of excreting water as urine is reduced, so about 3 to 5 liters of water is discharged from the body in one artificial dialysis. For this reason, there is a strong itching feeling even during the treatment of artificial dialysis, and “skin itching” is a common problem for dialysis patients.
In addition, not only patients with dialysis, but also patients with atopic dermatitis and senile xeroderma, a strong itching sensation in the skin occurs. If itching is strong, scratching the skin can cause inflammation throughout the body, which can interfere with life itself.

In order to relieve such itching and skin irritation, for example, moisturizers such as petrolatum preparations, urea preparations and heparin-like ointments, steroidal and non-steroidal anti-inflammatory agents, herbal medicines and plant ingredients And the like (see, for example, Patent Documents 1 and 2 and Non-Patent Document 1).
Particularly in the case of dialysis patients, dialysis usually takes a long time of about 2 to 4 hours, so a moisturizing cream is applied over a wide area to suppress dryness and pruritus during dialysis.

  However, in order to perform dialysis, it is necessary to puncture the skin with a needle, and fixing tape is used to fix the needle over a long period of time. When moisturizing cream containing petrolatum is used, there is a problem that the fixing tape is peeled off. In particular, when a moisturizing cream containing petrolatum was used, peeling of the fixing tape was remarkable.

  Similarly, tapes may be used to protect wounds even for patients with atopic dermatitis and senile xerosis, but they are easily peeled off after applying a moisturizer containing glycerin or petrolatum. There was a need to change the tape frequently. Thus, in general, when using a highly moisturizing cream or the like for the purpose of moisturizing or suppressing the itching sensation caused by drying, a sheet for bioadhesive use such as a tape for preventing keratinous damage and repairing the wound is sufficient. I could not use it.

  On the other hand, cosmetics using a temperature sensitive polymer compound having LCST (Lower Critical Solutino Temperature) are known (for example, Patent Document 3). Such a temperature-sensitive polymer compound becomes a hydrogel that dissolves in water at a low temperature and retains a large amount of water at a high temperature. Therefore, by using this temperature-dependent sol-gel transition, a cosmetic pack, a foundation, etc. Have been proposed for use in various applications (see, for example, Patent Documents 4 to 6). All of these techniques focus on the feeling of use that changes depending on the temperature, and do not take into account the use of a fixed tape on the coated surface.

JP 2003-89658 A JP 2004-224745 A Japanese Patent No. 3121660 Japanese Patent No. 3585309 Japanese Patent No. 3403491 JP 2007-269713 A

“Allergy Clinical”, 1998, Vol. 34, No. 12, pp. 1469-1477

Accordingly, an object of the present invention is to provide a skin external preparation and an itching sensation relieving agent that provide a good moisturizing effect and relief of pruritus without peeling off the bioadhesive tape.
Another object of the present invention is to provide a method of using a tape for bioadhesive for long-term use while simultaneously realizing a moisturizing effect on the skin and alleviating itching.

The present invention is as follows.
[1] A block copolymer or graft copolymer having a molecular weight of 100,000 or more in which a polymer part (a) having an LCST higher than 0 ° C. and lower than 37 ° C. and a hydrophilic polymer part (b) are combined. Temperature sensitive polymer compound (A), polyhydric alcohol (B1) of 50% by mass to 85% by mass with respect to the non-volatile component, and oil of 2% by mass to 8% by mass with respect to the non-volatile component And a component for external use on the skin containing 15% by mass or less of the non-volatile component.
[2] The temperature-sensitive polymer compound (A) is a structural unit derived from at least one structural unit of a poly N-alkyl-substituted acrylamide derivative and a poly N-alkyl-substituted methacrylamide derivative and a hydrophilic monomer. And an external preparation for skin according to [1], which is a copolymer comprising a structural unit derived from a hydrophobic monomer.
[3] The skin external preparation according to [1] or [2], wherein the content of the temperature sensitive polymer compound (A) with respect to the nonvolatile component is 2.5% by mass or more and 6.5% by mass or less.
[4] Any of [1] to [3], wherein the oily component (B2) includes one or more selected from the group consisting of fats and oils, waxes, mineral oils, higher fatty acids, higher fatty acid esters, and silicone oils. The skin external preparation of Claim 1.
[5] The polyhydric alcohol (B1) includes one or more selected from the group consisting of glycerin, polyethylene glycol, propylene glycol, dipropylene glycol, butylene glycol, pentanediol, hexanediol, and octanediol [1] The external preparation for skin according to any one of to [4].
[6] The skin external preparation according to any one of [1] to [5], wherein the content ratio of the oily component (B2) to the polyhydric alcohol (B1) is 15% by mass or less.
[7] The skin external preparation according to any one of [1] to [6], further comprising a thickener, wherein the thickener contains at least one water-soluble polymer compound.
[8] The external preparation for skin according to any one of [1] to [7], further comprising astaxanthin.
[9] The external preparation for skin according to any one of [1] to [8], further comprising a crude drug component, wherein the crude drug component comprises an agate extract.
[10] The skin according to any one of [1] to [9], wherein the external preparation for skin is applied to a glass surface, and the peel strength of the fixing tape for skin application with the applied surface as a target surface is 5 g or more. Topical agent.

[11] An itching sensation relieving agent comprising the external preparation for skin according to any one of [1] to [10].
[12] A method for using the bioadhesive sheet, wherein the bioadhesive sheet is affixed to the application surface of the external preparation for skin according to any one of [1] to [10].

According to the external preparation for skin and the itching sensation relieving agent of the present invention, it is possible to bring about a good moisturizing effect and alleviation of the pruritic sensation without peeling off the bioadhesive tape.
Moreover, according to the method for using the biomedical adhesive sheet of the present invention, it can be used for a long period of time while simultaneously realizing the moisturizing effect on the skin and the relief of itching.

  Hereinafter, the external preparation for skin and the itching sensation relieving agent of the present invention, and further, the method of using the bioadhesive sheet using the same will be described in detail.

<External preparation for skin>
The skin external preparation of the present invention is a block copolymer or graft having a molecular weight of 100,000 or more in which a polymer part (a) having an LCST higher than 0 ° C. and lower than 37 ° C. and a hydrophilic polymer part (b) are combined. A temperature-sensitive polymer compound (A) comprising a copolymer, a polyhydric alcohol (B1) of 50 to 85% by mass with respect to the nonvolatile component, and 2 to 8% by mass with respect to the nonvolatile component 8 And an oily component (B2) in an amount of not more than mass%, and a skin external preparation in which the nonvolatile component is not more than 15 mass%.

According to the present invention, the specific temperature-sensitive polymer compound (A), the polyhydric alcohol (B1), and the oily component (B2) are included, and the amount of the non-volatile component and the non-volatile component By setting the amounts of the polyhydric alcohol (B1) and the oily component (B2) in the above ranges, the bioadhesive sheet can be easily peeled off even when the bioadhesive sheet is used on the application surface of the skin external preparation. In addition, it has a good moisturizing effect and can relieve itching.
Here, the “nonvolatile component” in the present invention means a component that remains when a volatile component is evaporated by heating at 120 ° C. for 16 hours at normal pressure using a heating furnace. Compounds used in general skin external preparations include powders, polymers, surfactants, fats and oils (boiling point of 120 ° C. or higher), polyhydric alcohols (boiling point of 120 ° C. or higher), and the like. include.
In the case of a skin external preparation of unknown composition, this is heated at a normal pressure at 120 ° C. for 16 hours using a heating furnace, and the amount of non-volatile components is determined by measuring the amount of the remaining components. can do.

Although not limited to a specific theory, when the external preparation for skin of the present invention is applied to the skin, the temperature-sensitive polymer compound in the composition is gelled by the temperature on the skin (generally said to be 32 to 34 ° C.). Thus, it is presumed that a film is formed, thereby preventing moisture from evaporating from the skin and moisturizing, thereby reducing the itching sensation. In addition, surprisingly, the formed film does not impair the sticking property of the bioadhesive sheet affixed to the application surface of the external preparation for skin, and as a result, it is presumed that the bioadhesive sheet is not easily peeled off. .
The present invention will be described below.

[Temperature sensitive polymer (A)]
The temperature-sensitive polymer compound used in the present invention has a molecular weight of 100,000 or more in which a temperature-sensitive polymer part (block) having an LCST higher than 0 ° C. and lower than 37 ° C. and a hydrophilic polymer part are combined. A block copolymer or a graft copolymer. This temperature-sensitive polymer compound becomes a gel (hydrogel) having poor fluidity when the aqueous solution or aqueous dispersion is at a temperature higher than the LCST, and becomes a sol (or liquid) at a temperature lower than the LCST. Has characteristics.

  The “temperature-sensitive polymer having LCST” used in the present invention is a polymer compound having a negative temperature coefficient of solubility in water, and is used for hydrogen bonding between a polymer compound generated at low temperature and water molecules. The dependent hydrate (oxonium hydroxide) is decomposed at a high temperature, and polymer compounds are aggregated and precipitated by dehydration. Accordingly, the LCST is shown in an aqueous solution of a temperature sensitive polymer compound.

In the present invention, LCST (Lower Critical Solution Temperature) refers to a transition temperature between hydration and dehydration of a polymer compound (for example, J. Macromol. Sci.-Chem., A2 of M. Heskins et al. (8), 1441 (1968)). The temperature sensitive polymer moiety is hydrophilic and soluble in water at temperatures below LCST, but becomes hydrophobic and insoluble and precipitates in water at temperatures above LCST, and this change is reversible. In the present invention, the LCST of the above temperature-sensitive polymer portion is from the point that the above-mentioned polymer compound gives a reversible change of soluble-insoluble that quickly corresponds to the temperature of the living body surface and a "lower temperature". It is preferably higher than 0 ° C. and lower than 37 ° C., more preferably 15 ° C. or higher and lower than 37 ° C.).
In the present invention, according to the difference in the skin surface temperature based on individual differences in the use environment or body temperature of the external preparation for skin, in order to make a design that can be used appropriately by anyone at any time, a “temperature-sensitive polymer having LCST”. The polymer is preferably a polymer compound in which a plurality of “parts” are present in one molecule.

As long as it has the LCST, it can be used as the temperature-sensitive polymer in the present invention without any particular limitation. Examples of the polymer compound that can be suitably used in the present invention include poly N-substituted acrylamide derivatives, poly N-substituted methacrylamide derivatives, copolymers thereof; polypropylene oxide, copolymers of propylene oxide and other alkylene oxides. Polymers: Polyvinyl methyl ether, polyvinyl alcohol partially acetylated product, polyalkylene oxide, methyl cellulose and derivatives thereof, polyethers and the like. Of these, the use of poly-N-substituted acrylamide derivatives, particularly poly-N-isopropylacrylamide, which is being studied in general, provides a great deal of information and can be used safely. In addition, the polymer compound may be a homopolymer or a copolymer of a monomer constituting the polymer and another monomer. As the other monomer constituting such a copolymer, either a hydrophilic monomer or a hydrophobic monomer can be used.
Among these, from the viewpoint of easy application to cream or gel dosage forms and easy availability on the market, as the temperature-sensitive polymer compound, poly N-alkyl-substituted acrylamide derivatives and poly N -A copolymer containing at least one structural unit of an alkyl-substituted methacrylamide derivative, a structural unit derived from a hydrophilic monomer, and a structural unit derived from a hydrophobic monomer is preferable.
The concept of selecting a temperature-sensitive polymer, a hydrophilic monomer, and a hydrophobic monomer when using a copolymer is described below.

  The compound of the temperature-sensitive polymer portion suitable for the temperature-sensitive polymer compound in the present invention includes poly-N-acryloylpiperidine; poly-Nn-propylmethacrylamide; poly-N-isopropylacrylamide; poly-N. , N-diethylacrylamide; poly-N-isopropylmethacrylamide; poly-N-cyclopropylacrylamide; poly-N-acryloylpyrrolidine; poly-N, N-ethylmethylacrylamide; poly-N-cyclopropylmethacrylamide; Mention may be made of N-ethylacrylamide. The use of poly-N-isopropylacrylamide as a basic compound has been extensively studied and is common, but is not limited thereto.

  Examples of the hydrophilic monomer include N-vinylpyrrolidone, vinylpyridine, acrylamide, methacrylamide, N-methylacrylamide, hydroxyethyl methacrylate, hydroxyethyl acrylate, hydroxymethyl methacrylate, hydroxymethyl acrylate, and an acidic group. Acrylic acid, methacrylic acid and their salts, ethylene glycol dimethacrylate, triethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, 1,3-butylene glycol dimethacrylate, polyethylene glycol dimethacrylate, vinyl sulfonic acid , Styrene sulfonic acid, etc., as well as N, N-dimethylaminoethyl methacrylate, N, N-diethylaminoethyl methacrylate, N, N-dimethyl having basic groups Aminopropyl acrylamide, and salts thereof, but not limited thereto.

  On the other hand, examples of the hydrophobic monomer include acrylate derivatives and methacrylate derivatives such as methyl acrylate, ethyl acrylate, butyl acrylate, methyl methacrylate, ethyl methacrylate, butyl methacrylate, and glycidyl methacrylate, and N-type such as Nn-butylmethacrylamide. Examples thereof include, but are not limited to, substituted alkylmethacrylamide derivatives, vinyl chloride, acrylonitrile, styrene, and vinyl acetate.

  In general, it is possible to increase LCST by copolymerizing a hydrophilic monomer with the above polymer compound, while decreasing LCST by copolymerizing a hydrophobic monomer. It becomes possible. Therefore, a polymer compound having a desired LCST can also be obtained by selecting these copolymerization components (hydrophilic monomer and / or hydrophobic monomer).

  On the other hand, the hydrophilic polymer compound corresponding to the hydrophilic polymer portion (b) to be bonded to the temperature-sensitive polymer compound in the present invention is not particularly limited as long as it is a water-soluble polymer compound. , Dextran, polyethylene oxide, polyvinyl alcohol, poly N-vinyl pyrrolidone, polyvinyl pyridine, polyacrylamide, polymethacrylamide, poly N-methylacrylamide, polyhydroxymethyl acrylate, polyacrylic acid, polymethacrylic acid, polyvinyl sulfonic acid, polystyrene sulfone Examples thereof include acids and salts thereof, poly N, N-dimethylaminoethyl methacrylate, poly N, N-diethylaminoethyl methacrylate, poly N, N-dimethylaminopropyl acrylamide and salts thereof.

Examples of the temperature-sensitive polymer compound of the present invention having such a structure include N-isopropylacrylamide, Nn-propylacrylamide, N-cyclopropylacrylamide, N, N-diethylacrylamide, N-methyl-N-. There are compounds based on acrylamide polymers such as isopropyl acrylamide and acroyl morpholine. Among them, isopropyl acrylamide is preferable, (ethyl acrylate / isopropyl acrylamide), (acrylic) (Propyl acrylate / isopropyl acrylamide) (butyl acrylate / isopropyl acrylamide), (ethyl acrylate / isopropyl acrylamide / ethylene glycol dimethacrylate), (butyl acrylate / isopropyl Preferable examples include chloramide / ethylene glycol dimethacrylate), (ethyl acrylate / isopropyl acrylamide / dimethacrylic acid PEG-18) crosspolymer, (butyl acrylate / isopropylacrylamide / dimethacrylic acid PEG-18) crosspolymer, and the like. Can do.
In addition, as the temperature-sensitive polymer compound in the present invention, a commercially available product can be used. Specific examples of the commercially available product include “Mebigel-20” and “Mebigel-20 (WD) manufactured by Ichimaru Falcos Co., Ltd. And "Mebigel-32".

  The bonding mode of the copolymer in which the polymer part (a) and the hydrophilic polymer part (b) are combined in the temperature-sensitive polymer compound used in the present invention is not particularly limited. For example, a block of a and b A mode such as a copolymer, a graft copolymer in which the side chain b is bonded to the main chain a, or a graft copolymer in which the side chain a is bonded to the main chain b can be suitably used.

  For example, a block copolymer of a polymer part having LCST and a hydrophilic polymer part may be prepared by, for example, introducing a plurality of reactive functional groups (hydroxyl group, carboxyl group, amino group, isocyanate group, etc.) into both in advance. It can be obtained by bonding by chemical reaction.

  In general, the graft copolymer can be synthesized by 1) using a chain transfer reaction of the polymer, 2) introducing a functional group that can be split into free radicals into the trunk polymer, and polymerizing from the functional group. A method of starting, 3) a method of starting ionic polymerization from a trunk polymer, and the like are known. Although the graft copolymer to be used in the present invention can be obtained by these methods, from the viewpoint of controlling the polymerization degree of the side chain, one polymerizable functional group is added to the polymer portion having LCST. Introduced and copolymerized with a monomer that gives a hydrophilic polymer part; or a monomer that introduces one polymerizable functional group into the hydrophilic polymer part and gives a polymer part having LCST; It is advantageous to obtain it by copolymerization.

  The molecular weight of the temperature-sensitive polymer compound used in the external preparation for skin of the present invention is not particularly limited, but from the viewpoint of dispersion stability when used in a dispersion system (emulsion, dispersion, etc.), the larger the molecular weight. It is advantageous. More specifically, a temperature-sensitive polymer compound containing at least one having a molecular weight of 100,000 or more is preferably used. Here, the “polymer compound having a molecular weight of 50,000 or more” means an ultrafiltration membrane having a molecular weight cut off of 50,000 (made by Amicon) at a temperature lower than the sol-gel transition temperature. When ultrafiltration is performed using, it is not substantially filtered. Here, “substantially not filtered” means that when the volume of the stock solution is ultrafiltered to 1/3, the concentration of the polymer compound detected in the filtrate is higher than that in the stock solution (before concentration). It means 1/10 or less of the concentration of the molecular compound. This “substantially not filtered” can be confirmed, for example, by measuring the concentration ratio of the polymer compound in the stock solution and the filtrate by UV measurement or the like.

  By adjusting the composition of the temperature-sensitive polymer part having LCST and the hydrophilic polymer part, the hydrophobicity, the hydrophilicity, and / or the molecular weight of both polymer parts, The gel transition temperature, that is, the sol-gel transition temperature of the external preparation for skin of the present invention can be controlled to be higher than 0 ° C. and lower than 37 ° C. Further, even if “other components” (for example, urea, guanidine, thioglycolate, pH adjuster, etc.) added to the aqueous polymer compound solution are contained, the sol-gel transition temperature is higher than 0 ° C. , And can be controlled to be lower than 37 ° C.

  The content of the temperature-sensitive polymer compound in the external preparation for skin of the present invention is preferably 0.1% by mass or more and 15% by mass or less from the viewpoint of moisture content, osmotic pressure action or film formation degree, More preferably, it is 1 mass% or more and 10 mass% or less. If it is 0.1% by mass or more, it is possible to obtain a sufficient effect for extending the use time of the bioadhesive sheet, as well as to relieve pruritus and moisturize, and to suppress tape rash. On the other hand, if it is 15 mass% or less, it can be set as the viscosity for maintaining the cream-like and gel-like shape as a skin external preparation, and each is preferable.

  The content of the temperature-sensitive polymer compound in the non-volatile component in the external preparation for skin of the present invention is 2.5 masses from the viewpoint of applicability that can be applied so as to extend thinly on the skin in addition to reducing the itching sensation and moisturizing effect. % To 6.5% by mass, more preferably 3.5% to 5.0% by mass.

[Polyhydric alcohol (B1) and oily component (B2)]
In the external preparation for skin of the present invention, 50% by mass or more and 85% by mass or less of polyhydric alcohol (B1) with respect to the nonvolatile component, and 2% by mass or more and 8% by mass or less of the oily component (B2 with respect to the nonvolatile component). ) And.
The content of the polyhydric alcohol (B1) with respect to the nonvolatile component is more preferably 60% by mass to 85% by mass, and further preferably 70% by mass to 80% by mass. When the content of the polyhydric alcohol (B1) is in the above range, the skin can be moisturized and the adhesiveness of the bioadhesive sheet (fixing tape) affixed to the application surface of the external skin preparation can be improved. Can be maintained.
On the other hand, the content of the oily component (B2) with respect to the nonvolatile component is more preferably 6% by mass or less, and still more preferably 4% by mass or less. Moreover, as a lower limit of content of the oily component (B2) with respect to a non-volatile component, 2.5 mass% is preferable and 3 mass% is more preferable. If the content of the oily component (B2) is in the above range, the skin can be moisturized and the adhesiveness of the bioadhesive sheet (fixing tape) affixed to the application surface of the skin external preparation is maintained. can do.
That is, by using the polyhydric alcohol (B1) and the oily component (B2) in the above range, the water retention effect of the temperature-sensitive polymer compound that becomes hydrophobic at a temperature equal to or higher than the body temperature can be supplemented. On the other hand, the effect of extending the use time according to the present invention can be obtained without peeling off the living body sticking sheet.

Furthermore, the total amount of the polyhydric alcohol (B1) and the oily component (B2) is preferably 65% by mass or more and 85% by mass with respect to the non-volatile component, and 70% by mass or more from the viewpoint of moisturizing and reducing the itching sensation. It is preferable that it is 85 mass% or less.
When the content of the polyhydric alcohol (B1) and the oily component (B2) with respect to the nonvolatile components exceeds 85% by mass, the bioadhesive sheet affixed to the application surface of the external skin preparation may be peeled off, and the present invention. May reduce the effect of extending the usage time. Further, if the content of the total amount of the polyhydric alcohol (B1) and the oily component (B2) with respect to the non-volatile component is less than 65% by mass, there is a possibility that the moisturizing performance is problematic and the feeling of use may be lowered.

  The content ratio of the oily component (B2) to the polyhydric alcohol (B1) is preferably 15% by mass or less, and the mass ratio of the oily component (B2) to the polyhydric alcohol (B1) is The ratio is more preferably 2.5: 100 to 10: 100, and further preferably 2.5: 100 to 8: 100. If the content ratio of the oily component (B2) and the polyhydric alcohol (B1) is in the above range, the skin can be moisturized and the adhesiveness of the bioadhesive sheet (fixing tape) can be maintained. be able to.

[Polyhydric alcohol (B1)]
The following are used as the polyhydric alcohol (B1) in the external preparation for skin of the present invention.
That is, for example, glycerin, ethanediol, diethylene glycol, triethylene glycol, polyethylene glycol (molecular weight 2 to 1,000,000), propylene glycol, dipropylene glycol, 2-amino-2-methyl-1,3-propanediol, 1, 2 -Propanediol, 1,3-propanediol, polypropylene glycol, 1,3-butylene glycol, 1,2-butanediol, 1,3-butanediol, 1,4-butanediol, isopentanediol, pentylene glycol, Xylene glycol, 1,2-pentanediol, 1,3-pentanediol, 1,4-pentanediol, 1,5-pentanediol, 1,2,3-pentanetriol, 2,3,4-pentanetriol, 1 , 3,4-Pentane Liol, 1,3,5-pentanetriol, 1,2-hexanediol, 1,3-hexanediol, 1,4-hexanediol, 1,5-hexanediol, 1,6-hexanediol, 1,2, hexane 3-hexanetriol, 1,3,4-hexanetriol, 1,3,5-hexanetriol, 1,4,6-hexanetriol, 2-ethyl-1,3-hexanediol, etc .; erythritol, pentaerythritol, di Pentaerythritol, threitol, arabitol, xylitol, ribitol, galactitol, sorbitol, mannitol, lactitol, maltitol, inositol, panthenol, laminitol, valienamine, validamine, validatol; ethylene oxide, ethylene glycol, ethylene glycol Bruno ethyl ether, ethylene glycol monobutyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, propylene oxide, and can include a combination of two or more of these. Among these compounds, glycerin, polyethylene glycol, propylene glycol, dipropylene glycol, 1,3-butylene glycol, 1,2-pentanediol, 1,2 in particular, from the viewpoint of moisture retention and prevention of peeling of the biomedical sheet. -Hexanediol and 2-ethyl-1,3-hexanediol (octanediol) are preferable, and glycerin and other polyhydric alcohols are particularly preferably used in combination.

Glycerin, one of the polyhydric alcohols, is preferably used as a moisturizing component at a non-volatile component mass of 0.5% by mass to 10% by mass, and preferably 0.5% by mass to 5% by mass. Is more preferable.
Further, the total amount of the polyhydric alcohol (B1) is preferably 0.5% by mass or more and 15% by mass or less, and preferably 4% by mass or more and 8% by mass or less of the total mass of the composition from the viewpoint of moisture retention. It is more preferable.

[Oil component (B2)]
Examples of the oil component (B2) in the external preparation for skin of the present invention include oils and fats, waxes, mineral oils, higher fatty acids, higher fatty acid esters, and silicone oils described later.
The total amount of the oily component (B2) is preferably 2% by mass or more and 8% by mass or less, and more preferably 3% by mass or more and 5% by mass or less based on the mass of the nonvolatile component from the viewpoint of moisture retention. preferable.

The external preparation for skin of the present invention is preferably in the form of a cream or gel from the viewpoint of moisture retention. In order to obtain a cream or gel dosage form, the external preparation for skin of the present invention can preferably contain a thickener. The thickener varies depending on the form of the intended skin external preparation, but it has a suitable viscosity as a cream or gel, for example, 1000 mPa · s to 20000 mPa · s, preferably 5000 mPa · s to 10,000 mPa · s. Therefore, for example, the content may be 5% by mass or less of the total mass of the composition, and more preferably 0.001% by mass to 2% by mass.
In the present invention, the viscosity of the external preparation for skin can be measured at room temperature using a model LVDV-E manufactured by Brookfield.

The thickening agent is preferably a hydrophilic thickening agent from the viewpoint of moisture retention, pruritus sensation, and prevention of peeling of the bioadhesive sheet. Typical thickeners include hydroxyalkyl acrylate-based, hydroxyalkyl methacrylate-based, hydroxyalkyl cellulose-based and hydroxyalkyl starch-based polymer compounds. More preferred are alkyl acrylate-based, hydroxyalkyl methacrylate-based polymer compounds, and copolymer compounds containing such polymers.
Such hydroxyalkyl acrylate and hydroxyalkyl methacrylate polymer compounds are represented by hydroxymethyl acrylate, hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxymethyl methacrylate, hydroxyethyl methacrylate, hydroxypropyl methacrylate, and the like. There is no particular limitation as long as the molecular weight has a thickening effect, and examples thereof generally include those having an average molecular weight of 10,000 to 500,000. Above all, from the viewpoint of selecting a material with low irritation to the skin and high water solubility, hydroxyethyl acrylate, hydroxypropyl acrylate, (hydroxyethyl acrylate / acryloyldimethyltaurine Na) copolymer, (hydroxypropyl acrylate / Examples include acryloyldimethyltaurine Na) copolymer, (hydroxyethyl acrylate / acrylamide) copolymer, acrylic resin alkanolamine, etc. Furthermore, from the viewpoint of preventing peeling of the biomedical sheet, it is suitable without increasing the amount of oily substance. It is more preferable to use (hydroxyethyl acrylate / acryloyldimethyltaurine Na) copolymer or (hydroxypropyl acrylate / acryloyldimethyltaurine Na) copolymer which can be adjusted to a high viscosity.

  Examples of other hydrophilic thickeners include saccharides such as other water-soluble polymer thickeners, gums, neutral polysaccharides, anionic polysaccharides, and cationic polysaccharides. For example, xanthan gum, gum arabic, benzoin gum, danmar gum, guaiac gum, Irish moss, Karaya gum, tragacanth gum, carob gum, quinseed, agar, casein, lactose, fructose, sucrose or esters thereof, trehalose or derivatives thereof, dextrin, gelatin, Pectin, starch, carrageenan, carboxymethyl chitin or chitosan, hydroxyalkyl (C2-C4) chitin or chitosan to which alkylene (C2-C4) oxide such as ethylene oxide is added, low molecular chitin or chitosan, chitosan salt, sulfated chitin Or chitosan, phosphorylated chitin or chitosan, alginic acid or its salt, hyaluronic acid or its salt, chondroitin sulfate or its salt, heparin, ethylcellulose, methylcellulose, carbo Polymethyl cellulose, carboxyethyl cellulose, sodium carboxyethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, nitrocellulose, crystalline cellulose, polyvinyl alcohol, polyvinyl methyl ether, polyvinyl pyrrolidone, polyvinyl methacrylate, polyacrylate, polyethylene oxide, polypropylene oxide, etc. Examples include alkylene oxide or a crosslinked polymer thereof, carboxyvinyl polymer, polyethyleneimine, (acrylates / alkyl acrylate (C10-30)) crosspolymer, and the like. Among these, from the viewpoint of keeping the skin weakly acidic, a cross polymer having an acidic liquid property (acrylates / alkyl acrylate (C10-30)) is preferred.

In addition to the above, the external preparation for skin of the present invention may contain other components that can be used in normal external preparations for skin according to desired properties. In the case of containing other components, from the viewpoint of preventing peeling of the biomedical sheet, the content of the oily component (B2) is generally lower, although it varies depending on the properties of the oily component that can be used in the external preparation for skin. More specifically, the oil component (B2) is preferably used in the above-described range in the content of the nonvolatile component.
Hereinafter, other components will be described.

  The present invention can contain other emollient components in addition to the moisturizing component. As such an emollient component, it is preferable that it is 5 mass% or less of the whole composition from a viewpoint of moisture retention and prevention of peeling of the sheet | seat for biological sticking, and it is 0.01 mass% or more and 3 mass% or less. More preferred. Examples of such emollient components include squalane, macadamia nut oil, jojoba oil, and lauroyl glutamate di (phytosteryl / octyldodecyl).

  The external preparation for skin according to the present invention may contain a crude drug component from the viewpoint of alleviating pruritus. The herbal medicine component used for this purpose can be used in a range that is usually used as long as it is within the allowable content range of the oily component. For example, the herbal medicine has a unique odor of 10% by weight or less of the total weight of the composition. From the viewpoint that the effect may be exerted even if the amount of the crude drug is small, it can be preferably compounded at 0.01% by mass or more and 5% by mass or less.

  Any herbal ingredient that can be used for the purpose of reducing pruritus can be used as long as it has an effect of reducing pruritus, and among them, toki extract, peony extract, senkyu extract, diou extract, auren extract, and oak. The extract is preferably an extract, a gourd extract, a gardenia extract, or a combination of two or more of these, more preferably containing at least an agaric extract, and more preferably containing all of these 8 types.

In addition, as other components that can be contained in the external preparation for skin of the present invention, other components that are usually blended in cosmetics, pharmaceuticals, foods, etc., such as alkyl sulfates, polyoxyethylene alkyl sulfates, α-olefins, etc. Fatty acids such as alkyl sulfates, sulfosuccinic acid half alkyl esters, acylated glutamic acids, monoalkyl phosphoric acids, silicon derivatives, ester oils and higher alcohols; antibacterial agents such as anti-dandruff agents, bactericides, and vitamins; parabens, Preservatives such as urea; UV absorbers such as oxybenzone; Antioxidants such as dibutylhydroxytoluene and tocopherol acetate; Coloring agents such as dyes and pigments; Conditioning agents such as cationic polymers; Lecithin, nonionic surfactants, etc. Emulsifiers; various blended fragrances; other, sequestering agents, pH Seizai, cooling agents, stabilizing agents, wound healing agents, and the like enzymes. By including the following components, an additive or synergistic improvement of other cosmetic effects can be expected.
Any of these other components can be included in the skin external preparation in the present invention at a commonly used content as long as it is within the allowable content range of the oily component for various components.
An example of such other components is as follows.

(1) Various fats and oils Avocado oil, almond oil, fennel oil, sesame oil, olive oil, orange oil, orange rafa oil, sesame oil, cacao oil, chamomile oil, carrot oil, cucumber oil, beef fat fatty acid, cucumber nut oil, safflower oil, Shea fat, liquid shea fat, soybean oil, camellia oil, corn oil, rapeseed oil, persic oil, castor oil, cottonseed oil, peanut oil, turtle oil, mink oil, egg yolk oil, palm oil, palm kernel oil, molasses, palm oil , Beef tallow, pork tallow, squalene, squalane, pristane or hydrogenated products of these oils (hardened oil, etc.).

(2) wax beeswax, carnauba wax, whale wax, lanolin, liquid lanolin, reduced lanolin, hard lanolin, candelilla wax, montan wax, shellac wax, rice wax and the like.

(3) Mineral oils Liquid paraffin, paraffin, petrolatum, ozokelide, ceresin, microcrystalline wax and the like.

(4) Fatty acids Lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, linolenic acid, docosahexaenoic acid, eicosapentaenoic acid, 12-hydroxystearic acid, undecylenic acid, tall oil, lanolin fatty acid Natural fatty acids such as isononanoic acid, caproic acid, 2-ethylbutanoic acid, isopentanoic acid, 2-methylpentanoic acid, 2-ethylhexanoic acid and isopentanoic acid.

(5) Alcohols Natural alcohols such as ethanol, isopyropanol, lauryl alcohol, cetanol, stearyl alcohol, oleyl alcohol, lanolin alcohol, cholesterol, phytosterol, phenoxyethanol, synthetic alcohols such as 2-hexyldecanol, isostearyl alcohol, 2-octyldodecanol .

(6) Esters Isopropyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, oleyl oleate, decyl oleate, octyldodecyl myristate, hexyl decyl dimethyloctanoate, cetyl lactate, myristyl lactate, Diethyl phthalate, dibutyl phthalate, lanolin acetate, ethylene glycol monostearate, propylene glycol monostearate, propylene glycol dioleate, and the like.

(7) Metal soaps Aluminum stearate, magnesium stearate, zinc stearate, calcium stearate, zinc palmitate, magnesium myristate, zinc laurate, zinc undecylenate and the like.

(8) Various vitamins Vitamin A group: retinol, retinal (vitamin A1), dehydroretinal (vitamin A2), carotene, lycopene (provitamin A), vitamin B group: thiamine hydrochloride, thiamine sulfate (vitamin B1), Riboflavin (vitamin B2), pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), folic acid, nicotinic acids, pantothenic acids, biotins, choline, inositols, vitamin C group: vitamin C acid or derivatives thereof, vitamin D group: Ergocalciferol (vitamin D2), cholecalciferol (vitamin D3), dihydrotaxosterol, vitamin E group: vitamin E or derivatives thereof, ubiquinones, vitamin K group: phytonadione (vitamin K1), menaquinone (vitamin K2), Menadione (vitamin K3), menadiol (vitamin K4), other essential fatty acids (vitamin F), carnitine, ferulic acid, γ-oryzanol, orotic acid, vitamin Ps (rutin, eriocitrin, hesperidin), vitamin U and the like.

(9) Various amino acids Valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine, glycine, alanine, asparagine, glutamine, serine, cysteine, cystine, tyrosine, proline, hydroxyproline, aspartic acid, glutamic acid, hydroxylysine , Arginine, ornithine, histidine and the like, and their amino acid derivatives such as sulfate, phosphate, nitrate, citrate or pyrrolidone carboxylic acid.

(10) Various additives derived from plant or animal raw materials These are processed in a conventional manner according to the product type and form to be added (for example, pulverization, milling, washing, hydrolysis, fermentation, purification) , Compression, extraction, fractionation, filtration, drying, pulverization, granulation, dissolution, sterilization, pH adjustment, deodorization, decolorization, etc., arbitrarily selected and combined), arbitrarily selected from various materials You can use it.
As such plant or animal-based raw materials, plants known to be usable for external preparations for skin (fruit, leaves, stems, bark, roots, seeds, etc.); green algae such as chlorella, brown algae such as giant kelp , Red algae such as Tengusa, cyanobacteria such as Spirulina, axle algae such as Spiraea spp., Algae such as yellow algae such as Hikarimo; chicken crown extract, placenta extract, elastin or elastin hydrolysate, protein or its degradation Products, hemoglobin degradation products, milk, casein and degradation products thereof, lactoferrin, chicken egg components, fish meat degradation products, animal-derived materials such as nucleic acid-related materials, and the like. These may be derived from a gene recombinant or a cell fusion, or may be obtained by cell culture or the like.

(11) Microbial culture metabolite Yeast metabolite, yeast extract, bacterial metabolite, bacterial extract, mold or actinomycete metabolite, mold or actinomyces extract, natto metabolite, natto extract, rice fermentation extract , Fermented rice bran (red rice bran, white birch) extract, Euglena extract or decomposition product thereof or water-soluble derivative thereof, trehalose or derivative thereof, lactic acid fermentation product of raw milk or skim milk powder, fermented lactic acid bacteria of legumes, coconut plant Lactic acid bacteria fermented products.

(12) Marine components Seawater such as deep seawater, for example, sea salt, dried seawater, inorganic sea salt (sodium chloride, magnesium chloride, potassium chloride, etc.), sea mud or mud Fango), for example, Italian mud, German fungo, Eifelfango, Freiburg fungo, etc. Sea mud or mud from various locations (containing components: silicon dioxide, titanium dioxide, aluminum oxide, iron oxide, manganese oxide, sodium oxide, potassium oxide, Magnesium oxide, calcium oxide, strontium oxide, sodium, potassium, magnesium, calcium, chromium, iron, copper, nickel, zinc, lead, manganese, arsenic, water), saintoku stone, black meteorite, etc.

(13) α-hydroxy acids Glycolic acid, citric acid, malic acid, tartaric acid, lactic acid and the like.

(14) Inorganic pigments Silicic anhydride, magnesium silicate, talc, kaolin, bentonite, mica, titanium mica, bismuth oxychloride, zirconium oxide, magnesium oxide, zinc oxide, titanium oxide, calcium carbonate, magnesium carbonate, yellow iron oxide, Bengala, black iron oxide, gunjo, chromium oxide, chromium hydroxide, carbon black, calamine, etc.

(15) UV absorber / blocker benzophenone derivatives (2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid sodium salt, dihydroxy Dimethoxybenzophenone, dihydroxydimethoxybenzophenone-sodium sulfonate, 2,4-dihydroxybenzophenone, tetrahydroxybenzophenone, etc.), paraaminobenzoic acid derivatives (paraaminobenzoic acid, ethyl paraaminobenzoate, glyceryl paraaminobenzoate, amyl paradimethylaminobenzoate, Octyl paradimethylaminobenzoate), methoxycinnamate derivatives (ethyl paramethoxycinnamate, isopropyl paramethoxycinnamate, paramethoxycinnamate) Octyl, 2-ethoxyethyl paramethoxycinnamate, sodium paramethoxycinnamate, potassium paramethoxycinnamate, diparamethoxycinnamate mono-2-ethylhexanoate glyceryl, etc.), salicylic acid derivatives (octyl salicylate, phenyl salicylate, homomenthyl salicylate, dipropylene glycol salicylate) , Ethylene glycol salicylate, myristyl salicylate, methyl salicylate, etc.), anthranilic acid derivatives (such as methyl anthranilate), urocanic acid derivatives (urocanic acid, ethyl urocanate etc.), coumarin derivatives, amino acid compounds, benzotriazole derivatives, tetrazole derivatives, Imidazoline derivatives, pyrimidine derivatives, dioxane derivatives, camphor derivatives, furan derivatives, pyrone derivatives, nucleic acid derivatives, allanto Derivatives, nicotinic acid derivatives, vitamin B6 derivatives, umbelliferone, esculin, benzyl cinnamate, cinoxalate, oxybenzone, dioxybenzone, octabenzone, soribenzone, benzoresorcinol, arbutin, guaiazulene, shikonin, baicalin, baicalein, berberine, neoheliopan, Escalol, zinc oxide, talc, kaolin, etc.

(16) Whitening agent Paraaminobenzoic acid derivative, salicylic acid derivative, anthranilic acid derivative, coumarin derivative, amino acid compound, benzotriazole derivative, tetrazole derivative, imidazoline derivative, pyrimidine derivative, dioxane derivative, camphor derivative, furan derivative, pyrone derivative, Nucleic acid derivatives, allantoin derivatives, nicotinic acid derivatives, vitamin C or derivatives thereof (vitamin C phosphate magnesium salt, vitamin C glucoside, etc.), vitamin E or derivatives thereof, kojic acid or derivatives thereof, oxybenzone, benzophenone, arbutin, guaiazulene, Shikonin, baicalin, baicalein, berberine, placenta extract, ellagic acid, lucinol, etc.

(17) Tyrosinase activity inhibitor Vitamin C or a derivative thereof (vitamin C phosphate magnesium salt, vitamin C glucoside, etc.), hydroquinone or a derivative thereof (hydroquinone benzyl ether, etc.), kojic acid or a derivative thereof, vitamin E or a derivative thereof, N-acetyltyrosine or derivatives thereof, glutathione, hydrogen peroxide, zinc peroxide, placenta extract, ellagic acid, arbutin, lucinol, silk extract, plant extract (camille, mulberry, gardenia, pearl oyster, clam, clam, mugwort, honeysuckle) , Kihada, dokudami, matsuhod, pearl barley, mussel, hops, hawthorn, eucalyptus, yarrow, altea, keihi, mankaishi, hamamelis, karaguwa or yamagwa, life-prolonging grass, bellflower, toshishi, goblin, gyoza, mao, Senkyu, Dokatsu, Psycho, Bowfu, Hamaboufu, Ogon, Peony skin, Peonies, Gennoshouko, Kakkon, Licorice, Pyrup, Aloe, Shouma, Safflower, Green tea, Black tea, Assen).

(18) Melanin pigment reduction / decomposition substance Phenylmercury hexachlorophene, mercuric oxide, mercuric chloride, hydrogen peroxide, zinc peroxide, hydroquinone or its derivative (hydroquinone benzyl ether).

(19) Turnover promoting action / cell activator hydroquinone, lactic acid bacteria extract, placenta extract, ganoderma extract, vitamin A, vitamin E, allantoin, spleen extract, thymus extract, yeast extract, fermented milk extract, plant extract (aloe, Ogon, Japanese horsetail, Gentian, Burdock, Shikon, Carrot, Camelis, Hop, Yokuinin, Odori, Semburi, Japanese cypress, Japanese red snapper, Achacha, Hypericum, Cucumber, Necklace, Mannenrou, Parsley).

(20) Astringents Succinic acid, allantoin, zinc chloride, zinc sulfate, zinc oxide, calamine, zinc paraphenolsulfonate, potassium aluminum sulfate, resorcin, ferric chloride, tannic acid (including catechin compounds) and the like.

(22) Active oxygen scavenger SOD, catalase, glutathione peroxidase and the like.

(24) Antioxidant Vitamin C or a salt thereof, stearic acid ester, vitamin E or a derivative thereof, nordihydrogua ceretenoic acid, butylhydroxytoluene (BHT), butylhydroxyanisole (BHA), hydroxytyrosol, parahydroxyanisole Propyl gallate, sesamol, sesamorin, gossypol, propolis, coenzyme Q10, astaxanthin (derived from hematococcus algae such as hematococcus prubiaris oil, and krill). As these antioxidants, among them, astaxanthin having good antioxidant power is preferable.

(23) Lipid peroxide production inhibitor β-carotene, plant extract (sesame culture cell, hamcha, hypericum, hamamelis, clove, melissa, enamel, birch, salvia, mannenro, Nanten, Eiji, Ginkgo, green tea) and the like.

(24) Anti-inflammatory agent Itamol, indomethacin, kaolin, salicylic acid, sodium salicylate, methyl salicylate, acetylsalicylic acid, diphenhydramine hydrochloride, d-camphor, dl-camphor, hydrocortisone, guaiazulene, camazulene, chlorpheniramine maleate, glycyrrhizic acid or the like Salt, glycyrrhetinic acid or a salt thereof, licorice extract, sicon extract, age extract, propolis, etc.

(25) Antibacterial / bactericidal / disinfectant Acrinol, sulfur, calcium gluconate, chlorhexidine gluconate, sulfamine, mercurochrome, lactoferrin or hydrolyzate thereof, alkyldiaminoethylglycine chloride solution, triclosan, sodium hypochlorite, chloramine T, Sarashi flour, iodine compound, iodoform, sorbic acid or salt thereof, propionic acid or salt thereof, salicylic acid, dehydroacetic acid, parahydroxybenzoic acid esters, undecylenic acid, thiamine lauryl sulfate, thiamine lauryl nitrate, phenol, cresol, p -Chlorophenol, p-chloro-m-xylenol, p-chloro-m-cresol, thymol, phenethyl alcohol, O-phenylphenol, Irgasan CH3565, halocarban, hexac Lorophene, chlorohexidine, ethanol, methanol, isopropyl alcohol, benzyl alcohol, ethylene glycol, propylene glycol, 2-phenoxyethanol, 1,2-pentanediol, zinc pyridione, chlorobutanol, isopropylmethylphenol, nonionic surfactant (polyoxy Ethylene lauryl ether, polyoxyethylene nonyl phenyl ether, polyoxyethylene octyl phenyl ether, etc.), cationic surfactant (cetyltrimethylammonium bromide, benzalkonium chloride, benzethonium chloride, methylrosaniline chloride), formaldehyde, hexamine, brilliant green, Malachite Green, Crystal Violet, Jamal, Photosensitive Element 101, Photosensitive Element 201, Sensation No. 401-containing, N- long chain acyl basic amino acid derivative and its acid shark salts, zinc oxide, hinokitiol, Sophora root, propolis, etc., a silver ion.

(26) Moisturizer Propylene glycol, 1,3-butylene glycol, polyethylene glycol, glycerin tricaprycapric acid, glycolic acid (α-hydroxy acid), hyaluronic acid or a salt thereof, chondroitin sulfate or a salt thereof, water-soluble chitin or a derivative thereof Or chitosan derivative, pyrrolidone carboxylic acid or salt thereof, sodium lactate, urea, sorbitol, amino acid or derivative thereof (valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine, glycine, alanine, asparagine, glutamine, serine, cysteine Cystine, tyrosine, proline, hydroxyproline, aspartic acid, glutamic acid, hydroxylysine, arginine, ornithine, histidine and their sulfates, Phosphate, nitrate, citrate, or pyrrolidone carboxylic acid), oils and fats, mineral oil, natto metabolite, natto extract, silk fiber extract, plant extract (Akamatsu sap, aloe, kudzu, chamomile, Licorice, cucumber, licorice, rice or rice bran, purple root, white birch or white birch sap, assembly, mulberry white peel, birch leaf, loofah, peony skin, straw) etc.

(27) Elastase activity inhibitor Diisopropyl fluorophosphate, plant extract (Ogon, Hypericum, Clara, Mulberry leaf, Keihi, Genso pepper, Comfrey, Salvia, Elderberry, Bodaige, Buttonpi), seaweed extract and the like.
(28) Peripheral vascular blood flow promoter Vitamin E or derivatives thereof, assembly extract, garlic extract, ginseng extract, aloe extract, gentian extract, toki extract, cephalanthin, carpronium chloride, minoxidil and the like.
(29) Keratolytic agent Resorcin, salicylic acid, lactic acid, urea and the like.

(30) Fragrance Natural animal fragrances such as musk, civet, castorium, ambergris, anise essential oil, angelica essential oil, ylang ylang essential oil, iris essential oil, fennel essential oil, orange essential oil, cananga essential oil, caraway essential oil, cardamom essential oil, guayakwood essential oil, Cumin essential oil, black letter essential oil, cinnamon essential oil, cinnamon essential oil, geranium essential oil, copaiba balsam essential oil, coriandel essential oil, perilla essential oil, cedarwood essential oil, citronella essential oil, jasmine essential oil, gingergrass essential oil, cedar essential oil, spearmint essential oil, western peppermint essential oil, Otsuka perfume essential oil, tuberose essential oil, clove essential oil, orange flower essential oil, winter green essential oil, trout balsam essential oil, buttery essential oil, rose essential oil, palmarosa essential oil, persimmon essential oil, hiba essential oil, sandalwood essential oil, petit gren essential oil, bay essential oil, vetiva essential oil, bergamoc Essential oil, peruvian balsam essential oil, boad rose essential oil, melamine essential oil, mandarin essential oil, eucalyptus essential oil, lime essential oil, lavender essential oil, linaloe essential oil, lemongrass essential oil, lemon essential oil, rosemary (mannenrou) essential oil, Japanese mint mint essential oil, etc. Sexual fragrances, other synthetic fragrances, etc.

(31) Dye / Colorant: Cyanocobalamin, Berberine, Red cabbage dye, Red rice dye, Akane dye, Anato dye, Ikumi dye, Turmeric dye, Enju dye, Krill dye, Amber dye, Caramel, Gold, Silver, Gardenia dye, Corn Dye, onion dye, tamarind dye, spirulina dye, buckwheat whole plant dye, cherry dye, laver dye, hibiscus dye, grape juice dye, marigold dye, purple potato dye, purple yam dye, lac dye, rutin, etc.

As described above, the external preparation for skin of the present invention is capable of suppressing peeling of the biomedical sheet together with moisturizing and suppressing itching. As a result, it is possible to prevent the use period of the bioadhesive sheet from being shortened.
Here, in the present invention, the expression “the sheet for bioadhesive is not easily peeled” or the expression “suppresses the peeling of the sheet for bioadhesive” means that the sheet for bioadhesive is applied to the application surface of the external preparation for skin. When affixed, it means that the affixing of the bioadhesive sheet is maintained over the expected period of use based on the adhesive strength of the bioadhesive sheet. For such a skin external preparation, for example, the skin external preparation is applied to a glass surface, and the peel strength of the fixing tape for bioadhesive with the applied surface as the target surface is 5 g or more, preferably 20 g or more, more preferably 40 g or more. Can be. The peel strength test at this time shall be performed according to the following.

Regarding the peel strength, a constant speed tensile tester “Force Gauge FGX” manufactured by Nidec Sympo Co., Ltd. was used in a laboratory where the air conditioning was set to 25 ° C. (actual measurement: 22 to 26 ° C., relative humidity 40 to 65% RH). -1 ”, and 0.5 to 1 g of the test article was evenly applied to a Matsunami glass slide glass (S-1112, size: 76 mm × 26 mm), and then acetate cloth surgical tape (“ Keep (registered trademark) silk made by Nichiban ”was used. “(12 mm × 9 m, tape coated with acrylic adhesive on acetate cloth), and the value measured under the condition of a pulling speed of 2 mm / second. You may use the manufacturer's.
Moreover, in order to actually evaluate the fixability of the bioadhesive sheet on the human skin, the peel strength on the human skin can be measured by fixing the upper arm of the human to the place where the slide glass is installed.

The biological sticking sheet that can be stuck on the application surface of the external preparation for skin of the present invention is not particularly limited as long as it is usually used by sticking on the surface of a living body such as skin. For example, a woven fabric, a nonwoven fabric, a knitted fabric or the like may be used as a single layer or a base material configured as a laminate thereof, and more specifically, nylon, polypropylene, polyester, polyethylene, polystyrene, polyurethane , Synthetic fibers such as polyolefin, woven fabrics such as natural fibers made of silk, cotton, hemp, rayon, collagen, cellulose, acetate, etc., or non-woven fabrics, or those based on paper . Further, a commonly used adhesive component such as an acrylic adhesive may be applied to the contact surface with the living body. Examples of such a tape include a surgical tape, a medical puncture needle fixing tape, a hemostatic tape, and the like. In some cases, the effect of the present invention can be obtained even when an office tape is used.
Moreover, it may be composed of a hydrogel that does not include a substrate.

  Examples of such a bio-adhesive sheet include fixing tapes that are usually used for medical purposes, and sheet-like cosmetics. Specifically, catheter puncture site fixation dressing “Karitape (registered trademark) IV” (adhesion 60 mm × 80 mm, observation unit 34 mm × 39 mm, manufactured by Nichiban), acetate cloth surgical tape “Keep (registered trademark) Silk” ( 12 mm × 9 m (manufactured by Nichiban), “Injection Pad” No. 36-A (beige color, diameter 36 mm, manufactured by Nichiban), circuit fixing tape “Chirofix (registered trademark)” No. 18M (18 mm × 76 mm, manufactured by Nichiban) and the like.

The method of using the bioadhesive sheet of the present invention relates to the method of using the bioadhesive sheet as described above, and includes affixing the bioadhesive sheet to the application surface of the skin external preparation of the present invention. It is a waste.
As described above, the external preparation for skin of the present invention has a good moisturizing effect and alleviation of pruritus without peeling off the bioadhesive sheet even if the bioadhesive sheet is applied after application (application) to the skin. Therefore, the sheet for living body application can be used effectively while reducing the moisturizing and itching feeling on the surface of the skin.

Moreover, since the external preparation for skin of this invention can bring about the favorable moisturizing effect and a relief of a pruritic feeling, without peeling the tape for biological sticking as mentioned above, it can be used as a pruritus feeling alleviator. Therefore, the pruritus sensation mitigating agent of the present invention comprises the above-mentioned external preparation for skin.
About each component and the compounding quantity which can be mix | blended in the pruritus feeling alleviator of this invention, the matter mentioned above as a skin external preparation about the specific exemplary compound and compounding quantity of each component can be applied as it is.

  EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to the following examples unless it exceeds the gist thereof. Unless otherwise specified, “part” and “%” are based on mass.

[Example 1]
<1> Prescription of gel for external use of skin Each component shown in Table 1 and Table 2 was blended according to a conventional method to produce gels A to F and comparative products 1 to 3. The viscosity of the gels A to F was 6900 mPa · s when measured at room temperature with a rotary viscometer (Brookfield model LVDV-E). In gels A and B, the types and amounts of herbal ingredients are mainly changed.
In gels A to F, “Mebigel-20” (manufactured by Ichimaru Falcos Co., Ltd.) containing a cross-polymer (butyl acrylate / isopropylacrylamide / PEG-dimethacrylate PEG-18) as the temperature sensitive polymer compound (A). WD) "(molecular weight 300,000 to 500,000).
In addition, the non-volatile components in Tables 1 and 2 are components according to the above-described definitions, and are solid compounds at room temperature, squalane and tocopherol as oily substances, glycerin, polybutylene glycol, and pentylene glycol as polyhydric alcohols. 1,2-hexanediol corresponds to this. In Tables 1 and 2, the content ratio was calculated assuming that these components are non-volatile components.

<2> Evaluation 1: Moisturizing test The gels A and B obtained in Example 1 were tested for moisture retention during skin application as follows.
For one healthy 40-year-old male, each gel A and B obtained in Example 1 was put into a pump-type cosmetic container and pushed once to give about 0.1 to 0.3 g. It was applied to the forearm skin and spread evenly and left for 30 minutes. The environment at this time was a room temperature of 26 to 27 ° C. and a relative humidity of 55 to 60%.
Moreover, three types of commercially available moisturizing creams containing petrolatum or glycerin that are outside the range of the external preparation for skin of the present invention were used as comparative products. Specifically, (Comparative product A) Curel medicinal cream F (quasi-drug) manufactured by Kao Co., Ltd. (Comparative product B) Atopology skin care cream E (whole body moisturizing cream) manufactured by Sunstar Co., Ltd. ( Comparative product C) Amorel J cream (cream) manufactured by Hino Pharmaceutical Co., Ltd. was used. Table 3 shows the components of the comparative products A to C. These comparative products A to C were also tested for moisture retention in the same manner as gels A and B.

(1) Surface moisture content A moisture measuring device “moisture checker” (manufactured by SCARA, Moisture Checker MY-808S) was applied to the coated surface to measure the surface moisture content, and an average value measured seven times was obtained. The results are shown in Table 4.
Table 4 also shows the amount of surface moisture in a state where nothing is applied.

(2) Moisturizing evaluation-1
For each of the gels A and B and the comparative products A to C (three types of commercially available products), the usability before and after coating was evaluated by a five-point method from 1 point “bulkyness” to 5 points “moist”. The results are shown in Table 5.

(3) Moisturizing evaluation-2
For one healthy male in his 60s, the same evaluation regarding the feeling of use as in (2) above was performed for each of Gels A to F and Comparative products 1 to 3 obtained in Example 1. The results are shown in Table 6.

From Table 3, comparative products A and B do not contain a thermosensitive polymer compound, and gels A and B have a total blending amount of petrolatum, glycerin, oils and fats and fatty acid esters as comparative products A and B. , C is considered to be less.
Further, as shown in Tables 4 and 5, gels A and B containing a temperature-sensitive polymer compound have good usability even though the surface moisture content is low, and comparative products A, B and C There was no difference.
Furthermore, as shown in Table 6, Gels A to F had a moist feeling after application and had good moisture retention. Moreover, since the comparative product 1 also contains a large amount of glycerin, the moisturizing effect was sufficient, whereas the comparative products 2 and 3 did not have a sufficient feeling of use. .

<3> Evaluation 2: Tape peeling test (1) Test using slide glass In a laboratory with air conditioning set to 25 ° C (actual measurement 22 ° C to 26 ° C, relative humidity 40% to 65% RH) Using a constant-speed tensile tester “Force Gauge FGX-1” manufactured by Co., Ltd., comparison with Gel A and Gel B on Matsunami Glass slide glass (S-1112, size: 76 mm × 26 mm, weight 5.7 g) After 0.05 to 0.1 g of each of the products A to C was applied evenly, the hot air from the dryer was blown for 1 minute to evaporate the moisture, and then the acetate cloth surgical tape (Nichiban “Keep (registered trademark) Silk” (12mm x 9m) or office tape (3M "Scotch (registered trademark) transparent beautiful color" 18mm width) cut to 15cm, and 30 seconds later Then, a peel test was conducted under the condition of a pulling speed of 2 mm / sec.

(2) Test-1 using skin
In the same manner as in <2> above, each of the gels A and B obtained in Example 1 and the comparative products A, B, and C were pump-type cosmetics for one healthy 40-year-old male. Put in a container and push once to get about 0.1-0.3g, spread it evenly on the left forearm skin, leave it for 30 minutes, then apply the surgical tape or office tape used in (1) above Then, a peel test was performed in the same manner as (1) above. The results are shown in Table 7.

(3) Test-2 using skin
For a healthy male in his 60s, the same peel test as in (2) above was performed on gels A to F and Comparative products 1 to 3 obtained in Example 1 using only surgical tape. . The results are shown in Table 8.
The determination results in Table 8 are “◯” when the tensile stress was 10 g or more, “Δ” when the tensile stress was 5 g or more and less than 10 g, and “X” when the tensile stress was less than 5 g. It was written as.

As shown in Table 7, it was shown that gels A and B were difficult to peel off after applying each tape to the coated surface, regardless of whether they were applied to slide glass or skin.
On the other hand, none of the comparative products could maintain the adhesive force of the tape at all, and even if the tape was applied, it was peeled off immediately.
As is clear from Evaluation 1 and Evaluation 2, it was shown that Gel A and Gel B according to the present invention both have good moisture retention and are effective in preventing tape peeling. On the other hand, although the comparative products A, B, and C all showed moisture retention, the adhesive strength of each tape could not be maintained, and it was clear that the comparative products A, B, and C were unsuitable for the use of the tape.
Moreover, as Table 8 shows, it is understood that the gels A to F are less likely to peel off after application, and the comparative products 1 to 3 are more easily peeled off than the gels A to F. When these results and the results shown in Table 6 are combined, Gels A to F can achieve both moisture retention and maintenance of the adhesive strength of the tape, while Comparative products 1 to 3 have moisture retention properties. It has been found that the maintenance of the adhesive strength of the tape is not compatible.

[Example 2]
Obtained in Example 1 for 19 dialysis patients over 20 years old (11 men: average age 52.3 ± 7.6 years, 8 women: average age 52.0 ± 10.5 years) Evaluation was made on the effectiveness of Gel A and Gel B. Prior to the test, the subjects were thoroughly explained about the contents of the test, and the test was conducted after obtaining written consent for the test. In addition, the test subject group was composed of a person with an average itch score of 2 or more during sleep for 3 days immediately before the registration date, an outpatient, and a person who was deemed appropriate to participate. The study used the multicenter double-blind crossover method.

During sleep (after bathing), the application method is 1 push (about 0.5 mm) for each of the four areas of the shunt-fixed forearm, the forearm opposite to the shunt, the right shin, and the left shin. ˜1 g) It was applied, spread evenly and left as it was.
The average itch score was evaluated in five stages according to Shiratori's criteria (Clinical Medicine, Vol. 18, pp. 71-86 (2002)), and the itch VAS (Visual Analogue Scale) score is Visual Evaluation was made in 100 stages according to Dermatology, Vol.6, No.7, pp.716-719 (2007). The results are shown in Table 9.

  As shown in Table 9, the average itch score for both Gel A and Gel B is significantly improved compared to before application (Wiocoxon rank sum test), and the itch VAS score is also compared to before application. All were significantly improved (paired t-test). When the subjects were asked about the effectiveness of itching suppression, 80% or more answered “somewhat effective” and 60% or more answered “effective”. The answer of “invariant” was 20%.

  Moreover, regarding the adhesiveness of the shunt fixing tape during the dialysis period, the shunt was firmly fixed even when Gel A and Gel B were used, and the shunt fixing tape was not peeled off. When asked about the adhesiveness of the fixed tape, all subjects answered that they were satisfied.

In addition, when the usage period of the gel A and the gel B was changed every week, the same effect was obtained no matter which one was used first.
Moreover, when the change in skin moisture content during the dialysis period was measured in the same manner as in <2> (1) of Example 1, the dialysis start time and the dialysis end time were measured at any of the four target sites. There was no significant change.

  Thus, by using the gel A and the gel B according to the present invention, good moisturizing and itching sensation can be obtained. Moreover, even if it uses the sheet | seat for biological sticking like a shunt fixing tape with this, it does not peel and can use a fixing tape over a desired period.

[Example 3]
Other prescription examples are shown below. Each formulation example is manufactured by a conventional method in manufacturing each product.
In addition, the same thing as what was used in Example 1 and 2 was used for the temperature sensitive polymer in each prescription example.

(Formulation Example 1) Spray Mass%
Acrylic acid octylamide, acrylic hydroxypropyl
・ Butylaminoethyl methacrylate copolymer 3.0
Acrylic resin alkanolamine 0.5
Aminomethylpropanol 0.6
Chamomile extract 1.0
Temperature sensitive polymer compound 0.2
Maltitol 0.5
Inositol deoxy derivative 0.1
Grapefruit extract 0.5
Purified water 2.0
Perfume Appropriate amount Ethanol remaining Propellant (LPG) 6.0

(Formulation example 2) Skin care lotion
Polyoxyethylene hydrogenated castor oil (60EO) 0.5
Triethyl citrate 2.0
Dipropylene glycol 1.0
Diglycerin 1.0
Temperature sensitive polymer compound 0.2
γ-oryzanol 0.2
Aspartic acid 0.4
Asparagine 0.3
Mixed fruit extract (lemon, apple, peach, orange) 0.5
Mixed plant extract (Arnica, Hypericum, Chamomile, Linden, Horsetail,
Yarrow, sage, mallow, milkweed) 0.5
Panax ginseng extract 0.1
Purified water remaining

(Formulation example 3) Skin care foam
Alkyl-modified organopolysiloxane 2.0
Mixed plant extract (Arnica, Nettle, Cucumber, Atlantic Kizuta,
Mallow, elderberry) 1.0
Ogon Extract 0.1
Polyoxyethylene hydrogenated castor oil (60EO) 0.5
Polyoxyethylene cetyl ether (10EO) 0.3
Temperature sensitive polymer compound 0.5
Sodium pyrrolidonecarboxylate 0.5
Panthenol 0.1
Sodium chondroitin sulfate 1.0
Purified water remaining

(Formulation example 4) Mist mass%
Temperature sensitive polymer compound 0.2
Aminoguanidine 0.2
β-sitosterol 0.1
Stigmasterol 0.1
Licorice extract 0.001
Green tea extract 0.1
Mixed plant extract (Clara, Showa, Senkyu, Tokyo,
Peach, ginseng) 0.5
Glycerin 0.1
Ethanol 2.0
Hexylene glycol 2.0
Purified water remaining

(Formulation example 5) Water mass%
LOVEGE EXTRACT 0.5
Polyoxyethylene-modified silicone 0.5
Polyethylene glycol 1.0
1,3-butanediol 1.0
Temperature sensitive polymer compound 0.2
Tocotrienol nicotinate 0.1
Nordihydrogua cetelenic acid 0.1
Ethylene glycol 0.2
Stearyltrimethylammonium chloride 0.5
Polyoxyethylene lauryl ether 0.4
Lauryldimethylamine oxide 0.2
Sodium pyrrolidonecarboxylate 1.0
Methylparaben 0.3
Sodium citrate 0.1
Sodium hydroxymethoxybenzophenone sulfonate 0.1
Perfume appropriate amount ethanol 20.0
Purified water remaining

(Prescription Example 6) Lotion Mass%
1,3-butylene glycol 2.0
Glycerin 3.0
Oleyl alcohol 0.1
Monolauric acid polyoxyethylene (20) sorbitan 0.5
Polyoxyethylene (15) lauryl ether 0.5
Ethyl alcohol 10.0
Preservative 0.1
Fragrance 0.1
Temperature sensitive polymer compound 0.2
Purified water remaining

Claims (10)

  A temperature-sensitive polymer compound (A) composed of a cross-polymer having a molecular weight of 100,000 or more (butyl acrylate / isopropylacrylamide / PEG methacrylic acid PEG-18) and 50% by mass to 85% by mass with respect to the nonvolatile component. A skin external preparation comprising a polyhydric alcohol (B1) and an oily component (B2) of 2% by mass to 8% by mass with respect to the nonvolatile component, and the nonvolatile component is 15% by mass or less.   The skin external preparation according to claim 1, wherein the content of the temperature-sensitive polymer compound (A) with respect to the nonvolatile component is 2.5% by mass or more and 6.5% by mass or less.   The skin external preparation according to claim 1 or 2, wherein the oily component (B2) contains one or more selected from the group consisting of fats and oils, waxes, mineral oils, higher fatty acids, higher fatty acid esters, and silicone oils. .   The said polyhydric alcohol (B1) contains 1 or more types selected from the group which consists of glycerol, polyethyleneglycol, propylene glycol, dipropylene glycol, butylene glycol, pentanediol, hexanediol, and octanediol. 4. The external preparation for skin according to any one of 3 above.   The skin external preparation according to any one of claims 1 to 4, wherein a content ratio of the oily component (B2) to the polyhydric alcohol (B1) is 15% by mass or less.   The skin external preparation according to any one of claims 1 to 5, further comprising a thickener, wherein the thickener contains at least one water-soluble polymer compound.   The external skin preparation according to any one of claims 1 to 6, further comprising astaxanthin.   The skin external preparation according to any one of claims 1 to 7, further comprising a herbal medicine component, wherein the herbal medicine component contains a buckwheat extract.   The skin external preparation according to any one of claims 1 to 8, wherein the skin external preparation is applied on a glass surface, and the peel strength of the bioadhesive fixing tape having the applied surface as a target surface is 5 g or more.   An itching sensation relieving agent comprising the external preparation for skin according to any one of claims 1 to 9.