JP2001064185A - Stimulation depressant, composition and detergent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a stimulation depressant which does not drop out easily by washing with water, and to provide composition and detergent for kitchen containing the stimulation depressant. SOLUTION: This stimulation depressant is composed of a hydrophobic group- containing polysaccharide derivative. In more detail, the stimulation depressant is composed of the hydrophobic group-containing polysaccharide derivative where 0.1-10 hydrophobic groups based on 100 monosaccharides in the polysaccharide are introduced. This stimulation depressant-containing composition and detergent for kitchens each contain 0.001-20 wt.% of the stimulation depressant.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a stimulus inhibitor, a composition containing the stimulus inhibitor, and a kitchen cleaner.

[0002]

2. Description of the Related Art Humans are constantly exposed to various stimulants due to changes in the living environment. For this reason, an increasing number of patients with atopic dermatitis and hay fever, and diseases that did not exist in the past have become major social problems. Especially in the field of dermatology, the skin becomes sensitive due to exposure to various irritants, and it reacts sensitively to substances that did not cause irritation until now. The inflammation caused by such substances has increased, which is a problem. Conventionally, measures against these inflammations have been taken to reduce the inflammation by applying a drug containing an anti-inflammatory agent after the inflammation has occurred, or to enhance the skin function by protecting the epidermis with various moisturizing agents. .

On the other hand, apart from coping with skin irritation, a substance that prevents skin irritation is used in advance,
Attempts have been made in recent years to protect sensitive skin. As such an attempt, for example, suppression of irritation has been carried out by using a polymer comprising a phosphorylcholine-like group-containing monomer as an irritation inhibitor (JP-A-9-315949).
No.). However, a polymer composed of a monomer having a phosphorylcholine-like group has a high degree of hydrophilicity, and is easily removed by subsequent washing with water.For example, at the time of sea bathing or daily work such as washing dishes in a kitchen. However, it was difficult to maintain the effect for a long time. Therefore, there has been a demand for the development of a stimulus inhibitor which does not easily fall off by washing with water after application but continues to exert its effect. In particular, the development of a kitchen cleaner that reduces or does not cause symptoms such as housewife eczema caused by repeated exposure to the drying and surfactants in winter has been urgently desired.

On the other hand, as emulsions of oils and fats, hydrophobic group-containing polysaccharide derivatives have hitherto been known in the pharmaceutical field (JP-A-63-319046, JP-A-3-292).
No. 301), however, it has never been known that this is particularly effective as an anti-irritant.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to provide a stimulus inhibitor which does not easily fall off by washing with water or the like, and a stimulus inhibitor-containing composition containing the same.

[0006]

Means for Solving the Problems The present inventors have conducted intensive studies in view of the above-mentioned problems, and as a result, have found that a hydrophobic group synthesized with a hydrophobic group having a high affinity for a hydrophobic surface and a polysaccharide as constituent units. The inventors have found that a polysaccharide derivative having a functional group is water-resistant and has a long-lasting effect of suppressing irritation, thereby completing the present invention. That is, the present invention provides the following (1) to
(4). (1) A stimulus inhibitor comprising a hydrophobic group-containing polysaccharide derivative. (2) A stimulation inhibitor comprising a hydrophobic group-containing polysaccharide derivative obtained by introducing 0.1 to 10 hydrophobic groups per 100 polysaccharide monosaccharides. (3) A stimulant-containing composition comprising 0.001 to 20% by weight of the stimulant according to (1) or (2). (4) A kitchen detergent containing 0.001 to 20% by weight of the stimulus inhibitor according to (1) or (2).

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention is a stimulus inhibitor comprising a polysaccharide derivative having a hydrophobic group. The hydrophobic group-containing polysaccharide derivative according to the present invention is generally regarded as a hydrophobic group-containing polysaccharide derivative, and refers to a hydrophobic group-containing polysaccharide derivative obtained by introducing a hydrophobic group into a polysaccharide. . Preferred as the hydrophobic group-containing polysaccharide derivative used in the present invention is a derivative obtained by using a polysaccharide as a raw material and reacting a part of the polysaccharide with a hydrophobic group. Examples of such a hydrophobic group-containing polysaccharide derivative include pullulan, amylose, xyloglucan, amylopectin, dextran, dextrin, cyclodextrin, mannan, hydroxyethyldextran, levan, inulin, chitin, chitosan, and water-soluble cellulose. There are hydrophobic group-containing polysaccharide derivatives obtained by chemically bonding a hydrophobic group to a saccharide via an appropriate molecule, and these can be preferably used in the present invention from the viewpoint of availability.

[0008] For example, siliconized polysaccharides used in JP-A-10-29910 and JP-A-10-18
Pullulan fatty acid ester used in JP-A-2341 and JP-A-53-142540;
Dextran fatty acid ester used in JP-A No. 107-107, JP-A-2-144140 and JP-A-6-144140.
Polysaccharide-sterol derivatives disclosed in JP-A-3-319046 and JP-A-3-292301 can be preferably used as a kind of the hydrophobic group-containing polysaccharide derivative according to the present invention. Among these, the polysaccharide-sterol derivative is a hydrophobic group-containing polysaccharide derivative having good performance such as water resistance, and further, the pullulan-sterol derivative in which the polysaccharide portion is pullulan has the best performance. Among these, polysaccharide 100
A hydrophobic group-containing polysaccharide derivative obtained by introducing 0.1 to 10 hydrophobic groups per monosaccharide is more preferably used as a stimulation inhibitor. At this time, if the number of introduced hydrophobic groups is less than 0.1 per 100 monosaccharides of the polysaccharide, it is easy to peel off from the skin surface, and the duration of the stimulus suppressing effect is shortened. The amount of the hydrophobic group to be introduced is adjusted in an appropriate range of about 0.1 to 10 per 100 monosaccharides of the polysaccharide, because the stimulus-inhibiting effect of the polysaccharide may be reduced by the group and the stimulus-suppressing effect may be reduced. Is preferred.

As a method for producing the hydrophobic group-containing polysaccharide derivative used in the present invention, synthesis may be made by appropriately devising based on known chemical knowledge in order to obtain the desired hydrophobic group-containing polysaccharide derivative. Alternatively, it may be synthesized by referring to known publications that disclose a method for producing a hydrophobic group-containing polysaccharide derivative. For example, as a hydrophobic group-containing polysaccharide derivative, polysaccharide-
When a sterol derivative or the like is used, see JP-A-3-292.
Production by the method described in Japanese Patent Publication No. 301,
It is preferably performed. More preferably, from the viewpoint of the effect as a stimulant inhibitor, 0.1 to 10 hydroxyl groups per 100 sugar units constituting the polysaccharide are represented by the following general formula (1)

[0010]

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Since the hydrophobic group-containing polysaccharide derivative substituted with the group represented by the formula (1) has high environmental degradability and high biosafety, it suppresses irritation such as irritation from chemical fibers and irritation from a detergent. It is suitably used as an agent. At this time, R ¹
Is a hydrocarbon group having 1 to 50 carbon atoms, and if it is a divalent hydrocarbon group, it may be linear, branched, or cyclic, and may be either saturated or unsaturated. May be
Preferably, a straight-chain saturated hydrocarbon group having 3 to 8 carbon atoms is most preferable. R ² is a hydrocarbon group having 12 to 50 carbon atoms or a sterol group, and is preferably a sterol residue. For example, a cholesterol residue, a stigmasterol residue, a β-sitosterol residue, a lanosterol residue, and an ergosterol residue are preferable. From the viewpoint of availability, a cholesterol residue is most preferred. Such a hydrophobic group-containing polysaccharide derivative can be synthesized by using a compound having a hydrophobic group at one end of a molecule and an isocyanate group at the other end, and reacting with a hydroxyl group of the polysaccharide.
A compound having a hydrophobic group at one end of a molecule and an isocyanate group at the other end can be obtained, for example, by the following reaction formula (2)

[0012]

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As shown in the above, the isocyanate group at one end of the diisocyanate compound is reacted with, for example, a hydroxyl group-containing hydrocarbon or a sterol-containing hydroxyl group having 12 to 50 carbon atoms, which is a hydroxyl group-containing hydrophobic molecule, to form a urethane bond. Obtained by combining. At this time, as the hydroxyl group-containing hydrocarbon molecule having 12 to 50 carbon atoms used in the reaction with the diisocyanate compound, any known hydrocarbon having 12 to 50 carbon atoms having at least one hydroxyl group may be used. For example, lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol,
Hydroxy group-containing hydrocarbons derived from alcohols such as araquinyl alcohol, docosanol, pentacosanol, hexacosanol, and octacosanol are preferred. As the sterol, for example, cholesterol, stigmasterol, β-sitosterol, lanosterol, ergosterol and the like are used, and cholesterol is preferred from the viewpoint of availability. The diisocyanate compound to be reacted with sterol is OCN-R ^1-
A compound represented by NCO and in which R ¹ is a hydrocarbon group having 1 to 50 carbon atoms is preferable, for example, ethylene diisocyanate in which R ¹ is an ethylene group, butylene diisocyanate in a butylene group, hexamethylene diisocyanate in a hexamethylene group, And diphenylmethane diisocyanate which is a diphenylmethane group. Of these, butylene diisocyanate and hexamethylene diisocyanate are particularly preferably used. The polysaccharide-sterol derivative preferably used in the present invention can be obtained by reacting the above-described compound having a hydrophobic group at one end of a molecule and an isocyanate group at the other end with a polysaccharide. The reaction of a compound having a hydrophobic group at one end of a molecule and an isocyanate group at the other end with a polysaccharide is performed by, for example, the following reaction formula (3)

[0014]

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As shown in the above, the reaction is carried out by a one-step addition reaction of the hydroxyl group of the monosaccharide constituting the polysaccharide with the isocyanate group of a compound having a hydrophobic group at one end of the molecule and an isocyanate group at the other end. be able to. In the reaction formula (3),
Although a reaction between one hexasaccharide unit and a compound having an isocyanate group is shown as a model, in the synthesis of the hydrophobic group-containing polysaccharide derivative used in the present invention, the sugar unit constituting the polysaccharide is used. 0.1 ~ per 100
It is preferable to cause a reaction as shown in the reaction formula (3) for 10 hydroxyl groups from the viewpoint of enhancing the effect as a stimulus inhibitor. As the raw material polysaccharide used in the above reaction, any polysaccharide can be used, and in particular, pullulan, amylose, xyloglucan, amylopectin, dextran, dextrin, cyclodextrin, mannan, hydroxyethyldextran , Levan, inulin, chitin, chitosan,
Polysaccharides selected from water-soluble cellulose and the like are preferably used. These polysaccharides may be of natural or synthetic origin, and may be of any molecular weight as long as they are available, but more effective when used as a stimulant inhibitor. In order to exert the effect, those having an average molecular weight of about 1,000 to 1,000,000 are preferred. Also,
As the kind of polysaccharide, any kind of polysaccharide can be usually used, but pullulan is particularly preferably used in view of the effect when it is blended as a stimulant inhibitor.

The solvent used in the reaction between the polysaccharide and the isocyanate group of the compound having a hydrophobic group at one end of the molecule and an isocyanate group at the other end includes a hydrophobic group at one end of the molecule. A solvent in which both the compound having an isocyanate group at the other end and the polysaccharide are dissolved, and a solvent in which the hydrophobic group-containing polysaccharide derivative as a reaction product is dissolved is preferable.Typically, dimethylformamide, dimethylsulfoxide, formamide, dioxane, An aprotic solvent such as tetrahydrofuran is preferably used. The reaction temperature and time at this time are appropriately selected according to the progress of the reaction, depending on the polysaccharide and the solvent used, but the reaction is preferably performed at 0 to 200 ° C. for about 1 to 48 hours.

The charge ratio of the polysaccharide to the compound having a hydrophobic group at one end of the molecule and a compound having an isocyanate group at the other end may be any ratio, and by changing this charge ratio, the hydrophobic group to the polysaccharide is changed. Can be appropriately controlled, but 0.1 per 100 saccharide units constituting the polysaccharide.
When 10 to 10 hydrophobic groups are introduced, 10
It is desirable that the amount be in the range of 0.1 to 500 mol equivalent relative to 0 monosaccharide unit. As a method for purifying the hydrophobic group-containing polysaccharide derivative thus obtained, a reprecipitation purification method, a separation / purification method by various types of chromatography, a dialysis method, and the like can be used. As a drying method, a freeze drying method or a vacuum drying method is desirable.

As described above, among the hydrophobic group-containing polysaccharide derivatives thus produced, from the viewpoints of safety, ease of production, performance, etc., the average molecular weight is 1,000 to 1,000,000.
To the degree of pullulan, 0.1 ~ per 100 pullulan monosaccharides
A pullulan-cholesterol derivative obtained by reacting a compound having a sterol group at one end of a molecule and an isocyanate group at the other end so that sterol groups are introduced at a ratio of 10 is the most excellent, and the irritation is suppressed. It is suitably used as an agent.

The stimulus inhibitor composition of the present invention is characterized in that the stimulus inhibitor is contained in a generally known stimulus inhibitor composition. The preferred content of the irritation inhibitor in the irritation inhibitor composition of the present invention is 0.001 to 20% by weight.
And more preferably 0.1 to 5% by weight. If the content of the irritation inhibitor is less than 0.001% by weight, it is difficult to exhibit the irritation inhibitory effect, and even if added in excess of 20% by weight, a remarkable increase in the effect corresponding thereto cannot be expected.

The kitchen cleaner of the present invention is characterized in that the above-mentioned irritation inhibitor is contained in a generally known kitchen cleaner. The preferred content of the stimulant in the kitchen detergent of the present invention is 0.001 to 20% by weight, more preferably 0.1 to 5% by weight. If the content of the irritation inhibitor is less than 0.001% by weight, it is difficult to exhibit the irritation inhibitory effect, and even if added in excess of 20% by weight, a remarkable increase in the effect corresponding thereto cannot be expected.

The irritation inhibitor composition of the present invention can be used as an external preparation for skin applied to the outer skin such as cosmetics, pharmaceuticals, and quasi-drugs. Accordingly, the dosage form can take a wide range of forms such as an aqueous solution type, a solubilizing type, an emulsifying type, a powder type, an oil liquid type, a gel type, an ointment type, a water-oil two-layer system, a water-oil-powder three-layer system.

The stimulant suppressant composition of the present invention can be used in addition to the hydrophobic group-containing polysaccharide derivative, in addition to aqueous components, powders, surfactants, oils, humectants, alcohols, and pH adjusting agents commonly used in cosmetics and pharmaceuticals. It is prepared by appropriately mixing agents, enzymes, preservatives, fungicides, antioxidants, thickeners, pigments, fragrances, and the like as necessary.

Further, the stimulant inhibitor composition of the present invention may further contain a known drug, if necessary. Examples of these drugs include drugs having a whitening effect, such as ascorbic acid derivatives, placenta extract, and glutathione;
Drugs having a moisturizing effect such as glycerin and sorbitol; anti-inflammatory agents such as glycyrrhetinic acid derivatives and indomethacin; extracts such as aloe, loofah and lily; activators such as biotin and pantothenic acid; vitamin E derivatives and nicotinic acid derivatives Blood circulation promoters and the like.

The kitchen detergent of the present invention can be used as various detergents (for tableware, food, kitchen surroundings) used in the kitchen every day. Accordingly, the dosage form can take a wide range of forms such as an aqueous solution type, a solubilizing type, an emulsifying type, a powder type, and a gel type.

The kitchen detergent of the present invention is characterized by containing a hydrophobic group-containing polysaccharide derivative. The hydrophobic group-containing polysaccharide derivative itself has a surfactant activity, but is separately washed. It is all right to mix other types of surfactants together as a component. As the surfactant used, any type of surfactant may be used as long as it is a surfactant usually used in kitchen detergents, and in particular, nonionic surfactants, cationic surfactants, and anionic surfactants may be used. Various surfactants suitably used for kitchen detergents such as amphoteric surfactants and amphoteric surfactants can be preferably used. Examples of the nonionic surfactant include fatty acid amide, polyoxyethylene alkyl ether, sugar ester type, sugar ether type, sugar amide type and the like, and polyoxyethylene alkyl ether, polyoxyethylene alkylphenol ether, polyoxyethylene. Monoacylate, sorbitan monoacylate, polyoxyethylene sorbitan monoacylate, glycerol monoacylate, polyoxyethylene alkylamine, polyoxyethylene
Polyoxypropylene random copolymer, polyoxyethylene-block copolymer and the like can be preferably used. Examples of commercially available nonionic surfactants include, for example, Nonion (trade name, manufactured by NOF CORPORATION), Monogly (trade name), NOF Corporation, Unigri, trade name, Nippon Oil and Fat Co., Ltd. Manufactured by Nippon Oil and Fat Co., Ltd., manufactured by Nippon Oil and Fat Co., Ltd., manufactured by Nippon Oil and Fat Co., Ltd. A trade name, 油 manufactured by NOF Corporation, etc. can be preferably used.

As the cationic surfactant, a long-chain alkylamine acetate, a long-chain alkyltrimethylammonium chloride and the like can be preferably used. As a commercially available cationic surfactant, a cation (trade name, manufactured by NOF Corporation) can be preferably used.

Examples of the anionic surfactant include a carboxylic acid type anionic surfactant, a sulfate type anionic surfactant, and a sulfonic acid type anionic surfactant. As the carboxylic acid-based anionic surfactant,
Examples include higher fatty acid salts, N-acyl sarcosine salts, alkyl ether acetates, and polyoxyethylene alkyl ether acetates. Among them, as higher fatty acid salts,
For example, a base salt of a fatty acid having 8 to 22 carbon atoms may be mentioned.
Specific examples include base salts of single fatty acids such as lauric acid, myristic acid, palmitic acid, isostearic acid, and oleic acid, as well as mixed fatty acids such as coconut oil fatty acids and tallow fatty acids. Here, examples of the salt include inorganic basic salts such as sodium and potassium; ammonium salts, monoethanolamine salts, diethanolamine salts, triethanolamine salts, 2-amino-2-methylpropanol, 2-amino-2-methylpropanediol. Alkanolamine salts; basic amino acid salts such as lysine and arginine; Examples of commercially available anionic surfactants include, for example, Nonsalle (trade name), Nippon Oil & Fats Co., Ltd.
Brand name, Nilube brand name, Nippon Yushi Co., Ltd., Suncall® brand name, Nippon Yushi Co., Ltd. brand, Sun Alpha ™ brand name, Nippon Yushi Co., Ltd. brand, Marcel II Brand name, Nippon Yushi Co., Ltd., Lapisol®, brand name, Nippon Yushi Co., Ltd., Parsoft®, brand name, Nippon Yushi Co., Ltd., Sintrexus, brand name, Nippon Yushi ( Co., Ltd., Diapon Co., Ltd., Nippon Yushi Co., Ltd., Newrex Co., Ltd., Nippon Yushi Co., Ltd., Succinide, Co., Ltd., Nippon Yushi Co., Ltd.,
Trucks ｛brand name, manufactured by NOF Corporation, Polystar ｛brand name, manufactured by NOF Corporation, Sanamide ｛brand name, manufactured by NOF Corporation, fillet ｛brand name, NOF And Sunbase (trade name, manufactured by NOF Corporation) and the like can be preferably used.

Examples of the sulfonic acid type or sulfuric acid type anionic surfactant include sulfosuccinic acid type, isethionate type, taurate type, alkylbenzenesulfonic acid type, olefinsulfonic acid type, alkanesulfonic acid type, alkyl or alkenyl sulfate type and the like. Anionic surfactants are included. Here, examples of the sulfosuccinic anionic surfactant include sulfosuccinates of higher alcohols or ethoxylates thereof, sulfosuccinates derived from higher fatty acid amides, and salts thereof. Examples of the alkylbenzenesulfonic acid-based anionic surfactant include a linear or branched alkylbenzenesulfonic acid salt having an alkyl group having an average of 10 to 16 carbon atoms; Olefin sulfonates having 10 to 20 carbon atoms in one molecule; alkane sulfonates having an average of 10 to 20 carbon atoms in one molecule as alkanesulfonic acid-based anionic surfactants; An alkyl or alkenyl sulfate-based anionic surfactant having a linear or branched alkyl or alkenyl group having an average of 10 to 20 carbon atoms, and having an average of 0.1 or less per molecule.
5-8 moles of ethylene oxide, propylene oxide,
Butylene oxide, ethylene oxide and propylene oxide in a ratio of 0.1 / 9.9 to 9.9 / 0.1, or ethylene oxide and butylene oxide in a ratio of 0.1 / 9.
Examples thereof include an alkyl or alkenyl ether sulfate added at a ratio of 9 to 9.9 / 0.1 and an alkyl or alkenyl sulfate having an alkyl or alkenyl group having an average of 10 to 20 carbon atoms.

Examples of the amphoteric surfactant include imidazoline-based and betaine-based surfactants, and dimethylalkyl betaine is preferably used. As commercially available amphoteric surfactants, for example, Nissan Anone (trade name, manufactured by NOF Corporation) can be preferably used. These surfactants may be added alone or as a mixture.
The amount of the surfactant may be appropriately selected, but is preferably 1 to 50% by weight, particularly preferably 5 to 30% by weight in the kitchen detergent.

The kitchen detergent of the present invention may contain other optional components as long as the stability and the cleaning performance of the detergent are not impaired. For example, viscosity modifiers such as viscosity minerals and water-soluble polymers; water-insoluble abrasives such as calcite, silica, calcium phosphate, zeolite, polyethylene, nylon and polystyrene; humectants such as glycerin and sorbitol; other animal and plant extracts, metals Chelates, alcohols, pH regulators, organic acids, enzymes, fragrances, dyes, preservatives,
A fungicide, water, an aqueous solvent and the like can be added and blended.

[0031]

The irritation inhibitor of the present invention comprises a polysaccharide derivative having a hydrophobic group, and remains on the skin even after washing, and exerts a remarkable irritation inhibitory effect. In addition, the stimulus inhibitor-containing composition containing the stimulus inhibitor has an excellent stimulus protection effect because it contains a hydrophobic group-containing polysaccharide derivative, and further exhibits a long-term protection effect without being easily dropped off by washing with water or the like. . The kitchen detergent containing the stimulus suppressant of the present invention suppresses stimulus such as a surfactant and exhibits an excellent effect of preventing rough skin.

[0032]

The present invention will be described in detail with reference to the following examples. Next, test methods and the like will be described. Reference Example 1 <Synthesis of N- (6-isocyanatohexyl) cholesteryl carbamate> In a 1-L eggplant-shaped flask, 25 g (0.065 mol) of cholesterol and 300 m of toluene were placed.
L and dissolve, then add 17 mL of triethylamine.
(0.12 mol) was added. There, toluene 300
Hexamethylene diisocyanate 161 dissolved in mL
g (0.96 mol), and reacted at 80 ° C. for about 6 hours under a nitrogen atmosphere. After the reaction was completed, toluene and excess hexamethylene diisocyanate were removed under reduced pressure. The resulting yellow oily residue was allowed to stand at room temperature overnight to produce pale yellow crystals. The crystals were taken out, about 1 liter of hexane was added, the mixture was shaken vigorously, and the supernatant was removed by decantation. After performing this washing operation four times in total, the solid was dried under reduced pressure at room temperature for 3 hours to obtain a white solid. The yield is 18.25 g and the yield is 50.
9%. The results of IR measurement of the obtained product are shown. IR (KBr, cm ^-1 ): 3260, 2320, ¹
680, 1130. From the above, it was confirmed that N- (6-isocyanatohexyl) cholesteryl carbamate was obtained.

Synthesis Example 1 <Pullulan-cholesterol derivative (hereinafter CH) having 0.9 cholesteryl groups introduced per 100 pullulan monosaccharides
Synthesis of P0.9) 40 g of pullulan (average molecular weight, 108000) and 420 mL of dimethyl sulfoxide were added to an eggplant-shaped flask of> 1 L, and stirred and dissolved at 80 ° C. under a nitrogen atmosphere. There, N-synthesized in Reference Example 1
1.78 g (3.21 mmol) of (6-isocyanatohexyl) cholesteryl carbamate was added to pyridine.
The solution dissolved in 4 ml (0.40 mol) was added, and 90
The reaction was carried out at 1.5 ° C. for 1.5 hours. After completion of the reaction, dimethyl sulfoxide was removed under reduced pressure, and the obtained oily residue was dropped into 6 L of acetone to form a precipitate. After removing the supernatant, 4 L of acetone was added to the obtained precipitate, and the mixture was left overnight at room temperature. The precipitate was collected by filtration and dried under reduced pressure. The obtained solid was dissolved in dimethyl sulfoxide, and this was filled in a dialysis membrane (Spectropore, Spectra / Por3, molecular weight cut off: 3500), and dialyzed against distilled water for one week. A white solid was obtained by freeze-drying 1.5 L of the obtained polymer solution by an ordinary method. Yield 3
1.7 g (76.2% yield). Next, the product ¹ H-NM
The measurement results of R and IR are shown. ¹ H-NMR ((δpp
m), DMSO-d6 / D2O = 20/1, vol, TM
S): 0.68-2.40, 2.60-4.60, 4.
60-5.05. IR (KBr, cm ^-1 ): 1680,
1180-900. From the ¹ H-NMR spectrum, the peak area derived from a cholesterol group (δ = 0.6 to 2.
3) and the peak area derived from pullulan (δ = 4.7-5.
From 1), the degree of substitution of cholesterol groups per 100 monosaccharides was calculated. As a result, the degree of substitution of cholesterol groups per 100 monosaccharides was 0.9. From the above data, it was confirmed that the obtained compound was CHP0.9.

Synthesis Example 2 <Pullulan-cholesterol derivative (hereinafter CH) having 0.1 cholesteryl group introduced per 100 pullulan monosaccharides
Synthesis of P0.1) By the same reaction procedure as in Synthesis Example 1, only the charged amount of N- (6-isocyanatohexyl) cholesterylcarbamate was 0.198 g (0.357 g).
mmol), CHP0.1 was synthesized. ¹ H-N
From the MR spectrum, the degree of substitution of the cholesterol group per 100 monosaccharides was calculated from the peak area derived from the cholesterol group and the peak area derived from the pullulan.
As a result, the degree of substitution of cholesterol groups per 100 monosaccharides was 0.1.

Synthesis Example 3 <Pullulan-cholesterol derivative having 0.05 cholesteryl groups introduced per 100 pullulan monosaccharides (hereinafter referred to as C
Synthesis of HP0.05) By the same reaction procedure as in Synthesis Example 1, only the charged amount of N- (6-isocyanatohexyl) cholesterylcarbamate was reduced to 0.099 g (0.17 g).
8 mmol) to synthesize CHP0.05. ¹ H
From the NMR spectrum, the degree of substitution of the cholesterol group per 100 monosaccharides was calculated from the peak area derived from the cholesterol group and the peak area derived from the pullulan. As a result, the degree of substitution of cholesterol groups per 100 monosaccharides was 0.05.

Synthesis Example 4 <Pullulan-cholesterol derivative (hereinafter CHP) having 10 cholesteryl groups introduced per 100 pullulan monosaccharides
10) by the same reaction procedure as in Synthesis Example 1.
Only 29.7 g (53.6 mmol) of-(6-isocyanatohexyl) cholesteryl carbamate was charged.
Instead, CHP10 was synthesized. ^{From the 1} H-NMR spectrum, the degree of substitution of the cholesterol group per 100 monosaccharides was calculated from the peak area derived from the cholesterol group and the peak area derived from the pullulan. As a result, 1
The degree of substitution of cholesterol groups per 100 monosaccharides was 10.

Synthesis Example 5 <Pullulan-cholesterol derivative (hereinafter referred to as CHP) having 15 cholesteryl groups introduced per 100 pullulan monosaccharides
15) by the same reaction procedure as in Synthesis Example 1.
Only the charged amount of-(6-isocyanatohexyl) cholesteryl carbamate was 49.5 g (89.3 mmol).
Instead, CHP15 was synthesized. ^{From the 1} H-NMR spectrum, the degree of substitution of the cholesterol group per 100 monosaccharides was calculated from the peak area derived from the cholesterol group and the peak area derived from the pullulan. As a result, 1
The degree of substitution of cholesterol groups per 00 monosaccharide was 15.

Synthesis Example 6 <Mannan-cholesterol derivative having 0.9 cholesteryl groups introduced per 100 mannan monosaccharides (hereinafter referred to as C
Synthesis of HM> Pullulan was converted to mannan (average molecular weight, 85000) 26.2 by the same reaction procedure as in Synthesis Example 1.
g, and the charged amount of N- (6-isocyanatohexyl) cholesteryl carbamate was changed to 1.08 g (1.95 m
mol), the charge amount of pyridine was changed to 19.6 mL, and the charge amount of dimethyl sulfoxide was changed to 320 mL.
1.5 g of mannan-cholesterol derivative was synthesized. From ¹ H-NMR and IR measurements of the product, it was confirmed that the obtained compound was mannan-cholesterol (CHM). ^{From the 1} H-NMR spectrum, the degree of substitution of the cholesterol group per 100 monosaccharides was calculated from the peak area derived from the cholesterol group and the peak area derived from the mannan. As a result, the degree of substitution of cholesterol groups per 100 monosaccharides was 0.9.

Synthesis Example 7 <Synthesis of Tristrimethylsiloxysilylpropylcarbamate Pullulan (hereinafter abbreviated as TSP) having 1.7 tristrimethylsiloxysilylpropyl groups introduced per 100 pullulan monosaccharides> Pullulan (average molecular weight, 10
(8000) was dissolved in 300 mL of N-methylpyrrolidone, 0.01 g of triethylamine was added as a catalyst, 0.7 g of tristrimethylsiloxysilylpropyl isocyanate was added dropwise, and the mixture was reacted at 100 ° C. for 2 hours. The reaction solution was poured into acetone, and the resulting precipitate was washed with methanol and dried to obtain 50 g of pullulan tristrimethylsiloxysilylpropylcarbamate. In addition,
The degree of substitution of the tristrimethylsiloxysilylpropyl group per 100 monosaccharides of pullulan in this product was calculated based on the elemental analysis value, and was 1.7.

Example 1 <SDS Stimulation Inhibition Test Using CHP 0.9 as Stimulant> CHP 0.9 synthesized in Synthesis Example 1 and 1 g
Dissolve in 0 ml of 30% ethanol aqueous solution and add 1% CHP
A 0.9% 30% aqueous ethanol solution was prepared. Then 5
Approximately 0.2 ml of a 50% aqueous ethanol solution containing 5% dodecyl sulfate sodium salt (SDS) was applied to the back of five week-old male hairless mice with a brush, and the applied surface was dried and overlapped with the applied surface. , Containing 1% CHP0.93
About 0.2 ml of a 0% ethanol aqueous solution was applied with a brush. This operation is repeated twice a day, and after five consecutive days,
The rough skin condition of the hairless mouse was scored based on the rough skin criterion shown in Table 1. Those with a low score are considered to have a stimulus-suppressing effect. The results are shown in Table 2.

[0041]

[Table 1]

[0042]

[Table 2]

Example 2 <SDS Stimulation Inhibition Test Using CHP0.1 as Stimulation Inhibitor> Instead of CHP0.9 synthesized in Synthesis Example 1,
1% CHP using CHP0.1 synthesized in Synthesis Example 2
1% C instead of 0.9% 30% ethanol aqueous solution
All procedures were performed in the same manner as in Example 1 except that a 30% ethanol aqueous solution containing HP0.1 was prepared and used. The results are shown in Table 2.

Example 3 <SDS Stimulation Inhibition Test Using CHP0.05 as Stimulus Inhibitor> Instead of CHP0.9 synthesized in Synthesis Example 1, CHP0.05 synthesized in Synthesis Example 3 was used and 1% C
Instead of 30% ethanol aqueous solution containing HP0.9, 1
All procedures were performed in the same manner as in Example 1, except that a 30% ethanol aqueous solution containing 0.05% of CHP was prepared and used. The results are shown in Table 2.

Example 4 <SDS Stimulation Inhibition Test Using CHP10 as Stimulant Inhibitor> Instead of CHP0.9 synthesized in Synthesis Example 1, CHP10 synthesized in Synthesis Example 4 was used and 1% CHP0.9
Instead of containing 30% ethanol aqueous solution, 1% CHP1
All procedures were the same as in Example 1, except that a 0% aqueous 30% ethanol solution was prepared and used. The results are shown in Table 2.

Example 5 <SDS Stimulation Inhibition Test Using CHP15 as Stimulant Inhibitor> Instead of CHP0.9 synthesized in Synthesis Example 1, CHP15 synthesized in Synthesis Example 5 was used and 1% CHP0.9
Instead of containing 30% ethanol aqueous solution, 1% CHP1
All of the procedures were performed in the same manner as in Example 1, except that a 5% aqueous 30% ethanol solution was prepared and used. The results are shown in Table 2.

Example 6 <SDS Stimulation Inhibition Test Using CHM as Stimulation Inhibitor> Instead of CHP0.9 synthesized in Synthesis Example 1, the CHM synthesized in Synthesis Example 6 was used, and 1% CHP0.9 was contained.
30% containing 1% CHM instead of 1% ethanol aqueous solution
All procedures were performed in the same manner as in Example 1 except that an aqueous ethanol solution was prepared and used. The results are shown in Table 2.

Example 7 <SDS Stimulation Inhibition Test Using TSP as Stimulant Inhibitor> Instead of CHP 0.9 synthesized in Synthesis Example 1, the TSP synthesized in Synthesis Example 7 was used and containing 1% CHP 0.9.
30% containing 1% TSP instead of 1% ethanol aqueous solution
All procedures were performed in the same manner as in Example 1 except that an aqueous ethanol solution was prepared and used. The results are shown in Table 2.

Comparative Example 1 <SDS Stimulation Inhibition Test Using Sodium Hyaluronate (Humectant)> Instead of CHP 0.9 synthesized in Synthesis Example 1, commercially available sodium hyaluronate was used and 1% CHP was used.
The same procedure was performed as in Example 1 except that a 30% ethanol aqueous solution containing 1% sodium hyaluronate was prepared and used instead of the 0.9% 30% ethanol aqueous solution. The results are shown in Table 2.

Comparative Example 2 <SDS Stimulation Inhibition Test without Using Stimulant (Control Test)> A 30% aqueous ethanol solution containing 1% CHP0.9 was used instead of a 30% aqueous ethanol solution containing 1% CHP0.9. Was carried out in the same manner as in Example 1 except that a 30% aqueous ethanol solution was used as it was. The results are shown in Table 2.

From Table 2, Comparative Example 1 having a moisturizing effect was obtained.
In contrast, the sodium hyaluronate group also tends to worsen the rough skin, whereas Examples 1 to 7 containing the hydrophobic group-containing polysaccharide derivative suppressed the appearance of rough skin, and a remarkable irritation suppressing effect was observed. .

Example 8 <Roughness test using diluted solution of kitchen detergent containing 1% CHP0.9> Commercial kitchen detergent (manufactured by P & G, diluted with a 50% aqueous ethanol solution to 7.5%) Name, Joy) was dissolved in 1% of CHP0.9 powder synthesized in Synthesis Example 1 to prepare a 1% CHP0.9-containing diluted solution for kitchen detergent. Next, about 0.2 ml of a 1% CHP0.9-containing kitchen detergent dilution was applied to the back of five 5-week-old male hairless mice with a brush. This operation was repeated twice a day, and after 5 consecutive days, the rough skin condition of the hairless mouse was scored using the rough skin determination criteria shown in Table 1 above. The results are shown in Table 3.

[0053]

[Table 3]

Comparative Example 3 <Skin roughness test using diluted solution for kitchen detergent> A commercially available kitchen detergent (manufactured by P & G, trade name, Joy) was diluted with a 50% aqueous ethanol solution to 7.5%. A kitchen cleaning solution was prepared. Next, approximately 0.2 ml of a kitchen detergent dilution was applied to the back of five 5-week-old male hairless mice with a brush. Repeat this operation twice a day,
After 5 consecutive days, the rough skin condition of the hairless mouse was scored using the criteria for rough skin shown in Table 1 above. The results are shown in Table 3. From Table 3, in Comparative Example 3 using the kitchen detergent diluent solution not containing the stimulus inhibitor of the present invention, the kitchen detergent diluent solution containing 1% CHP0.9 containing the stimulus inhibitor of the present invention was used. As compared with the test result of Example 8 which was found, marked skin roughness was recognized. From these results, it was confirmed that the stimulus inhibitor of the present invention suppressed stimulus caused by the kitchen cleaner.

Example 9 <Test for measuring the water retention effect of each layer of CHP0.9> Synthesis Example 1
0.9 g of CHP synthesized in the above was dissolved in 100 ml of a 50% aqueous solution of butylene glycol to prepare a 50% aqueous solution of butylene glycol containing 1% CHP0.9. Then 1%
0.1 ml of a 50% aqueous solution of butylene glycol containing CHP0.9 was applied to the inside of the forearm of a test subject (male, 25 to 50 years old, number of persons: 10), and washed with water after one hour. The water content of the stratum corneum of the applied skin was measured using SKICON-200 (manufactured by IBS) immediately after and 5 minutes after the water load. The measurement results were evaluated with the water content of the stratum corneum immediately after water load as 100. The results are shown in Table 4.

[0056]

[Table 4]

Comparative Example 4 <Test for measuring the water retention effect of each layer of pullulan> 1 g of commercially available pullulan (trade name: Pullulan PF20, manufactured by Hayashibara Shoji Co., Ltd., molecular weight: 200,000) was dissolved in 100 ml of a 50% aqueous solution of butylene glycol, and 1% A 50% aqueous solution of butylene glycol containing pullulan was prepared. Next, 50% with 1% pullulan
% Aqueous solution of butylene glycol
0.1 ml was applied to the inner side of the forearm of a 50-year-old man (10 persons), and washed one hour later. The water content of the stratum corneum of the skin to be applied was measured immediately after the water load, and 5 minutes after that, by SKICON-200.
(Manufactured by IBS). The measurement results were evaluated with the water content of the stratum corneum immediately after water load as 100. The results are shown in Table 4.

As is clear from Table 4 showing the water content of each layer, in the case of Example 9 using CHP0.9 which is a hydrophobic group-containing polysaccharide derivative, the water content of the stratum corneum was high even after washing. In contrast, in Comparative Example 4 using pullulan, which is a polysaccharide, the water content of the stratum corneum after 5 minutes of washing was low, and it was found that water retention was difficult. It is presumed that polysaccharides impart moisturizing properties to the skin when present on the skin surface. However, there was a great difference between Example 9 and Comparative Example 4 in the water retention of the stratum corneum. This is because the hydrophobic group-containing polysaccharide derivative, which is a stimulus inhibitor of the present invention, has a hydrophobic group and thus remains on the skin even after washing with water to contribute to the retention of moisture in each layer, whereas the large hydrophobic group This was thought to be due to the fact that the pullulan, a polysaccharide into which no was introduced, fell off the skin by washing with water and could not contribute to the retention of moisture in each layer.

Example 10 <Skin irritation test with lactic acid containing 1% CHP0.9> 1%
Thus, CHP0.9 synthesized in Synthesis Example 1 was dissolved in lactic acid so that lactic acid containing 1% CHP0.9 was prepared. next,
1% C on the ventral side of 6 previously shaved female guinea pigs
0.05 ml of HP0.9-containing lactic acid was applied. Observed 24 hours later, the inflammatory status was scored according to the criteria in Table 5. The results are shown in Table 6.

[0060]

[Table 5]

[0061]

[Table 6]

Comparative Example 5 <Skin irritation test with lactic acid> 0.05 ml of lactic acid was applied to the abdomen of six female guinea pigs shaved in advance. 2
Observed 4 hours later, inflammatory status was scored according to the criteria in Table 5. The results are shown in Table 6. From Table 6, in the guinea pig of Comparative Example 5 to which lactic acid containing no stimulus inhibitor of the present invention was applied, inflammation due to lactic acid stimulation was observed, but 1% CHP0.9-containing lactic acid containing the stimulus inhibitor of the present invention was observed. The inflammation was suppressed in the guinea pig of Example 10 to which was applied. From Table 6, it was confirmed that the irritation inhibitor of the present invention suppressed irritation of lactic acid which is a kind of skin irritant.
From the results of Examples 1 to 10 and Comparative Examples 1 to 5,
It has been found that the stimulus inhibitor comprising a hydrophobic group-containing polysaccharide derivative has an excellent function of protecting the living body from various stimulants, forms a coating, and does not easily fall off by washing with water. Therefore, it has been found that when added to a kitchen detergent or the like, it becomes an ideal stimulus inhibitor for suppressing skin roughness during washing with water.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 31/722 A61K 31/722 31/724 31/724 A61P 17/00 A61P 17/00 C11D 3/22 C11D 3/22

Claims (4)

[Claims] 1. A stimulus inhibitor comprising a hydrophobic group-containing polysaccharide derivative. 2. A stimulus inhibitor comprising a hydrophobic group-containing polysaccharide derivative obtained by introducing 0.1 to 10 hydrophobic groups per 100 polysaccharide monosaccharides. 3. A stimulant-containing composition comprising the stimulant of claim 1 or 2 in an amount of 0.001 to 20% by weight. 4. A kitchen cleaner comprising 0.001 to 20% by weight of the stimulant inhibitor according to claim 1.