JP5945566B2 - Itching agent, itching reducing composition using the same, and method for reducing itching caused by external stimulation - Google Patents

Description

  The present invention relates to an itching reducing agent, an itching reducing composition using the same, and a method for reducing itching caused by an external stimulus, and in particular, an itching reducing agent for reducing an itching caused by a temperature change or drug stimulation and the same. Itching relates to an itching reducing composition and a method for reducing itching.

  Itching is a special sensation that causes the sensation of the site where the sensation has occurred, and it is caused by chemical irritation such as food allergies, skin diseases that induce itching such as atopic dermatitis, There are various causes of itching, such as blood sucking by mosquitoes and mites, environmental exposure such as drying and frost burning, psychological factors, and itching caused by external stimuli typified by temperature changes.

  The cause of itching is not well understood, but suppression of itching due to skin diseases and environmental exposure is being investigated. For example, Patent Document 1 proposes a compound having chymase inhibitory action as an inhibitor against itching caused by chemical substances such as histamine. Further, Patent Document 2 proposes an improving agent for hypersensitive itch, and can quickly replace itch of hypersensitive skin with other sensations (cool feeling, burning sensation).

JP 2000-247908 A JP 2007-262031 A

However, in the conventional examination example, the purpose is to suppress itch caused by skin diseases and environmental exposure, and itch caused by external stimulation is not specifically mentioned. In addition, no means has been known for reducing the itch caused by the external stimulus.
Therefore, the present invention reduces itching caused by external stimuli due to various environmental factors such as temperature change, humidity change, friction with clothes, wind of an air conditioner, etc., drug stimulus, external stimulus by shaving, etc. An itching agent, an itching reducing composition using the same, and an itching reducing method are provided. Especially, itching that you may feel when using a heater or when you suddenly go from a cold place to a warm place, itching that you may feel when bathing, itching that you may feel when drinking alcohol, etc. An itching reducing agent, an itching reducing composition using the same, and an itching reducing method for reducing the itching caused by a change in body temperature and the itching caused by drug stimulation.

  As a result of intensive studies to solve the above problems, the present inventors have found that itching can be reduced by external stimulation by using cationized cellulose, and the present invention has been completed.

That is, the present invention is achieved by the following (1) to (4).
(1) An itching agent for reducing itching caused by external irritation, comprising cationized cellulose.
(2) The itching reducing agent according to (1), wherein the external stimulus is a temperature change or a drug stimulus.
(3) An itching reducing composition having an effect of reducing the itching of the skin caused by an external stimulus, comprising the itching reducing agent according to the above (1) or (2).
(4) A method for reducing the itching caused by external stimulation by applying the itching reducing composition according to the above (3) to the skin.

  The itching agent of the present invention comprises cationized cellulose, and the cationized cellulose has an effect of reducing skin itch caused by external irritation. In particular, itching can be reduced due to temperature changes in body temperature that can be felt when using heaters, suddenly going from a cold place to a warm place, bathing, drinking, etc. Further, the present invention can reduce itching caused by drug stimulation.

FIG. 1 is a graph showing the initial state and change with time of the degree of human itching in Examples and Comparative Examples. FIG. 2 is a graph showing changes over time in the degree of human itching when the sample of Example 3 is used continuously. FIG. 3 is a graph showing the number of scratches in a mouse when the sample of Example 3 was applied and not applied after the drug was applied to the shaved mouse skin to induce itching.

<Itching agent>
The present invention provides an itching agent for reducing the itching of the skin caused by an external stimulus, which comprises a cationized cellulose.

  Examples of external stimuli targeted by the present invention include temperature changes and drug stimuli. Among external stimuli, itch caused by temperature change is considered to be caused by temperature information (temperature change) sensed by the epidermis being transmitted to sensory nerves. Moreover, itching is considered to be caused by degreasing and removal of water-soluble components due to drug stimulation.

  Itching that occurs due to temperature changes, as described above, for example, itching that you may feel when using a heater or when you suddenly go from a cold place to a warm place, itching that you may feel when bathing, drinking alcohol The itching that you may feel when you go. The temperature difference that causes itching is characterized by large differences depending on environmental factors such as humidity and individuals.

  As described above, itching caused by drug stimulation is caused by, for example, applying a drug to the skin, and degreasing oil-soluble components (such as sebum) of the skin by components contained in the drug, The itching etc. which arise by being removed are mentioned.

The cationized cellulose which is an itching reducing agent of the present invention is a cellulose derivative having a cationic property as a whole by introducing a cationic group composed of quaternary ammonium. Specifically, O- [2-hydroxy-3- (trimethylammonio) propyl] hydroxyethylcellulose (also called “polyquaternium-10”), O- [2-hydroxy-3- (lauryldimethylammonio) propyl chloride. ] Hydroxyethyl cellulose etc. are mentioned. Among these, O- [2-hydroxy-3- (trimethylammonio) propyl] hydroxyethylcellulose chloride is excellent in the effect of reducing itch caused by external stimulation, and therefore can be suitably used in the present invention.
The above cationized cellulose of the present invention may be used alone or in combination.

  Among these, there are those having different molecular weights and cationization degrees, but they can be appropriately selected and used as long as the effects of the present invention are exhibited. The molecular weight is, for example, in the range of 10,000 to 3,000,000. Is more preferable, and the range of 50,000 to 2,000,000 is more preferable. The degree of cationization is preferably in the range of, for example, 0.1 to 5% by mass as the nitrogen atom content (% by mass).

<Itching reduction composition>
The itching reducing composition of the present invention contains the above itching reducing agent. Examples of the itching reducing composition include an external preparation for skin which contains the itching reducing agent of the present invention in a bath preparation, lotion, emulsion, paste, cream, cosmetic liquid, cosmetics, ointment and the like. The itching reducing composition of the present invention can improve the effect of reducing skin itching caused by external irritation as a skin external preparation or the like by containing the above itching reducing agent.

  The dosage form of these external preparations for skin may be, for example, powder, solid, liquid, gel, paste, etc., but when applied to the skin, the liquid state is preferred, that is, the skin as a liquid composition. It is preferable to apply to. In particular, as an example of itching caused by temperature changes, when taking a bath, by using it as a bath agent, it is possible to reduce the itching caused by temperature changes that occur during bathing, and at the same time to apply ingredients to the whole body. Itching can be reduced at the same time, and it is preferable.

  0.01 mass% or more is preferable and, as for content of the itching reducing agent of this invention in the whole itch reduction composition, 0.1 mass%-5 mass% are more preferable.

  The itching reducing composition is preferably a bath agent from the viewpoint of the itching reducing effect, the good feeling of use, and the application to the whole body. In the case of a bath agent, for example, when bathing, the content (concentration in use) of the itch reducing agent of the present invention in the bath water is preferably 0.1 ppm to 50 ppm, and more preferably 1 ppm to 10 ppm.

  Moreover, it is also preferable that it is an aspect applied directly to the skin as a skin external preparation, such as lotion, milky lotion, paste, cream, cosmetic liquid, cosmetics, ointment and the like. By applying directly to the skin, it can also be applied locally, such as where itching occurs due to external stimuli.

Examples of the direct application to the skin as an external preparation for skin include liquids such as lotions and emulsions, viscous (semi-solid) liquids such as creams and pastes, solids such as gels and waxes, and the like. . When directly applied to the skin as these skin external preparations, the content of the cationized cellulose in the skin external preparation as a product is preferably 0.01% by mass or more, and more preferably 0.1% by mass to 5% by mass. .
Furthermore, the method according to the present invention can be expected to have a sustained effect by improving the effect of reducing itching by continuous use (applied continuously for a certain period of time).

  The itching reducing composition of the present invention may contain other components together with the itching reducing agent of the present invention as long as the effects of the present invention are not impaired. Examples of other components include solvents, fragrances, surfactants, pigments, herbal medicines, enzymes, polymer compounds, inorganic salts, moisturizing ingredients, oils and fats, preservatives, animal / plant extracts, and refreshing agents. .

  Specifically, solvents such as water, methanol, ethanol, propanol, butanol; flavors such as lavender oil, jasmine oil, lemon oil, cedar oil, cypress oil, geraniol, citronellal, eugenol, limonene, phenethyl alcohol; glycerin fatty acid ester Block polymer such as sorbitan fatty acid ester, polyoxyethylene castor oil, polyglycerin fatty acid ester, polyoxyethylene polyoxypropylene glycol, polyoxyethylene alkyl ether, polyethylene glycol fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene cured Nonionic surfactants such as castor oil; sodium α-olefin sulfonate, sodium lauryl sulfate, polyoxyethylene sodium lauryl sulfate Anionic surfactants such as sodium palm fatty acid methyl taurine; amphoteric surfactants such as alkyl betaines, alkylamidopropyl betaines, 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaines; alkylamines Cationic surfactants such as salts and quaternary ammonium salts; Blue No. 1, Blue No. 2, Red No. 102, Red No. 106, Red No. 227, Red No. 230, Yellow No. 4, Yellow No. 5, Yellow 202 No., Green No. 3, pigments such as chlorophyll, riboflavin, safflower; Herbal medicines: trypsin, papain, protease, li Enzymes such as zoozyme and pepsin; polymer compounds such as gum arabic, xanthan gum, tragacanth gum, guar gum, locust bean gum, gelatin, shellac, rosin, casein, sodium carboxymethylcellulose, hydroxyethylcellulose, sodium alginate, crystalline cellulose; sodium chloride, chloride Potassium, sodium carbonate, magnesium carbonate, sodium bicarbonate, sodium sesquicarbonate, sodium sulfate, aluminum sulfate, sodium nitrate, potassium nitrate, sodium phosphate, sodium polyphosphate, calcium hydrogen phosphate, sulfur, anhydrous silicic acid, talc, hydroxylation Sodium, borax, calcium oxide and the like can be mentioned.

Furthermore, styrene polymer emulsions such as styrene polymer emulsions, styrene-α, β ethylenically unsaturated carboxylic acid copolymer emulsions, α-β-ethylenically unsaturated carboxylic acid polymer emulsions; polyethylene glycol, glycerin, Polyhydric alcohols such as propylene glycol; Moisturizing ingredients such as fatty acid esters such as cetyl octoate, myristyl lactate, isopropyl myristate, isopropyl palmitate, isopropyl adipate, butyl stearate; ceramides such as ceramides, ceramide derivatives, and ceramide-like substances Moisturizing components such as collagen; proteins such as collagen, elastin, keratin, mucin and derivatives and hydrolysates thereof and salts thereof; mucopolysaccharides such as hyaluronic acid and chondroitin sulfate; vitamin A; Vitamins such as Tamine Group B, vitamin D, vitamin E, tocopherol acetate, sodium ascorbate, magnesium ascorbate and derivatives thereof; amino acids such as glycine, alanine, arginine, cysteine, glutamic acid, sarcosine; jojoba oil, Avocado oil, shea fat, almond oil, nutka oil, olive oil, cacao butter, sesame oil, coconut oil, mink oil, beef tallow, pork fat, soybean oil, etc .; wax such as carnauba wax, whale wax, beeswax, lanolin; Hydrocarbons such as paraffin, white petrolatum, ceresin, squalane, squalene; fatty acids such as myristic acid, lauric acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, lanolinic acid; lauryl alcohol, cetyl alcohol, stearyl alcohol , Alcohols such as oleyl alcohol; fats and oils such as monoglycerides and triglycerides; benzoic acid and salts thereof, salicylic acid and salts thereof, sorbic acid and salts thereof, paraoxybenzoic acid alkyl esters (ethyl paraben, butyl paraben, etc.), dehydroacetic acid And its salts, parachlorometacresol, hexachlorophene, boric acid, resorcin, orthophenylphenol, chlorhexidine gluconate, thiram, photosensitizer 201, phenoxyethanol, cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride, halocarban, chloride Chlorhexidine, trichlorocarbanide, tocopherol acetate, zinc pyrithione, hinokitiol, phenol, isopropylmethylphenol, 2,4,4-trichloro Preservatives such as 2-hydroxyphenol and hexachlorophene; aloe extract, green tea extract, hamamelis water, loofah water, chamomile extract, licorice extract, comfrey extract, silk extract, Izayoi rose extract, yarrow extract, eucalyptus extract, Animal / plant extract components such as royal jelly extract and merirot extract; menthol, menthol derivatives, mint oil, camphor, thymol and other refreshing agents.
These may be used alone or in combination.

<Application method>
The present invention also provides a method for reducing the itching caused by an external stimulus by applying the above-mentioned itching reducing composition to the skin.

  When the itching reducing composition of the present invention is applied to the skin, it is preferably applied to the skin in a state containing moisture. The state containing moisture refers to a state in which the cationized cellulose, which is an itching reducing agent, is dissolved or emulsified in water or water and other media to become a solid state, a gel state, a liquid state, or the like. In particular, in the liquid state, fluidity can be imparted, and thus it is possible to apply the itching reducing agent to the skin more widely or effectively, which is preferable. The medium may be aqueous or oily as long as it contains moisture. Among the media, examples of the liquid state media include water, alcohols, polyhydric alcohols, fatty acids and esters thereof, and the like, which may be combined.

  Hereinafter, the present invention will be described specifically by way of examples. However, the present invention is not limited to only these examples.

(Test Example 1)
The sample of Examples 1-2 and the comparative example 1 was prepared by the prescription shown in Table 1 using polyquaternium-10 (trade name: Katchinal LC-100, manufactured by Toho Chemical Industry Co., Ltd.) as the cationized cellulose. Each sample was added at a rate of 80 g to 200 L of hot water at 40 ° C. Table 1 shows the concentration of polyquaternium-10 in each hot water.

Dip the subject's feet for 5 minutes in 3 types of hot water including the samples (Examples 1 and 2 and Comparative Example 1), and score the degree of itching with the VAS (Visual Analogue Scale) method in 10 levels (itch score). It was evaluated with.
The test subject was tested using five test subjects on the condition that he / she had itch symptoms and felt itching during daily bathing.

  The degree of itchiness before putting foot on hot water (initial itch score) is 100%, and the degree of itchiness (itch score over time) immediately after being applied and after 30 minutes as a relative value for each subject as a percentage Calculated and arithmetically averaged. Table 2 and FIG. 1 show the initial state and change with time of the average degree of itching (the average value of the evaluation values (itch score) of each subject).

From Table 2 and FIG. 1, in Comparative Example 1, the degree of itching immediately after the temperature change caused by adding foot to hot water of 40 ° C. increased, whereas Example 1 and Example containing polyquaternium-10 In No. 2 itching itself did not occur, and the degree of itching was lower than before the foot.
From the above, it is possible to reduce itch caused by temperature change by using Polyquaternium-10 in hot water.

(Test Example 2)
A specimen of Example 3 was prepared according to the formulation shown in Table 3 including polyquaternium-10 (trade name: Katchinal LC-100, manufactured by Toho Chemical Industry Co., Ltd.). This was added so that it might become a ratio of 80g with respect to 200L of hot water of 40 degreeC.

The whole body was immersed in the hot water to which Example 3 was added for 10 minutes. This was carried out once a day for 2 consecutive weeks (a total of 14 times), and the degree of itching was evaluated with a 10-point score (itching score) by VAS (Visual Analogue Scale) method.
The test subject was tested using 6 subjects, provided that the subject had subjective symptoms of itching and felt itching during daily bathing.

  The state of itch before the sample of Example 3 is used continuously (initial itch score) is 100%, and the degree of itch after 3 days from the start of continuous use, 7 days after the start of continuous use, and 14 days after the start of continuous use (temporal itch score). Was calculated as a relative value for each subject as a percentage and arithmetically averaged. Table 4 and FIG. 2 show the initial state and change with time of the average degree of itchiness (average value of evaluation values (itch score) of each subject).

  From Table 4 and FIG. 2, it was found that itching by hot water added with polyquaternium-10, that is, continuously applying the skin to polyquaternium-10, alleviates itch caused by temperature change.

(Reference Example 1)
In Test Example 2, the following test was conducted to confirm that the component that reduces itch caused by temperature change among the components of Example 3 was polyquaternium-10. A sample of Reference Example 1 was prepared with the same formulation as Example 3 except that it did not contain polyquaternium-10 (Table 5).

  Similar to Test Example 1, the test subject's foot was immersed for 5 minutes in hot water containing the sample of Reference Example 1, and the degree of itching was evaluated with a VAS (Visual Analogue Scale) method with a score of 10 (itch score). . The test subjects were tested using 8 test subjects on condition that they had subjective symptoms of itching and felt itching during daily bathing.

  The degree of itchiness before putting foot on hot water (initial itch score) is 100%, and the degree of itchiness (itch score over time) immediately after being applied and after 30 minutes as a relative value for each subject as a percentage Calculated and arithmetically averaged. As a result, the average degree of itching (average value of the evaluation value (itch score) of each subject) was 103% immediately after and 81% after 30 minutes, and the effect of reducing the itching was not seen. That is, in Test Example 2, it was confirmed that the component that reduces itch caused by temperature change among the components of Example 3 was polyquaternium-10. In addition, the degree of itching was the average value of the evaluation values (itch score) of each subject.

(Test Example 3)
This test was conducted with reference to a test system (Miyamoto T. et. Al., Jpn. J. Pharmacol. 88, 2002) published as a method for evaluating itching in animals.
Five-week-old ICR mice (18 mice) were individually caged and acclimated for 1 week, and the rostral back was shaved 3 days before the start of the test (treatment method A). Each of the 18 shaved mice was divided into 3 groups of 6 specimen treatment groups, a comparison group, and a control group.
<Sample treatment group>
In the sample treatment group, the mouse subjected to shaving treatment (Treatment Method A) was anesthetized with ether, and a 2 × 2 cm cotton dipped in a mixed solution of acetone (A): diethyl ether (E) (1: 1) on the rostral back. It was applied for 15 seconds, and then cotton soaked with ion-exchanged water (W) was applied for 30 seconds [hereinafter, a series of treatments are abbreviated as AEW treatment (treatment method B)]. AEW treatment was performed twice a day for 5 days at 7-hour intervals for a total of 10 times. Each time after the AEW treatment, 100 μL of the sample of Example 3 was applied (treatment method C).
<Comparison group>
In the comparative group, the AEW treatment (treatment method B) was performed on the mice that had been shaved (treatment method A).
<Control group>
In the control group, only shaving treatment (treatment method A) was performed.
Table 6 summarizes the treatments performed on the sample treatment group, the comparison group, and the control group. In Table 6, A indicates shaving treatment (processing method A), B indicates AEW processing (processing method B), and C indicates AEW processing + specimen processing (processing method C).

<Evaluation of scratching behavior>
On the day following the 10th AEW treatment for the sample treatment group and the comparison group, the mice were allowed to act for 1.5 hours in the unmanned environment with a video camera for all three groups of the sample treatment group, the comparison group, and the control group. A video was taken and the scratching behavior was observed and recorded. Scratching behavior refers to behavior in which a mouse scratches its rostral back with its hind legs. For the evaluation of scratching behavior, the number of scratches per unit time was counted with the number of scratches taken as 1 until the mouse left the hind paw off the floor, touched the rostral back, and again touched the hind paw to the floor. The method used was used.
In this test, out of 1.5 hours of the captured video, the first 30 minutes was used as the acclimatization time, and the hour after 30 minutes from the start of video recording was counted as the number of scratches, and the number of scratches during the hour was counted. . The results are shown in Table 7 and FIG. The number of scratches was the average of the number of scratches / time of mice in each group.

  From Table 7 and FIG. 3, the number of scratches in the sample-treated group to which the sample of Example 3 was applied after the AEW treatment was smaller than that in the control group subjected to the AEW treatment, which was the same as that of the control group mouse subjected to only shaving treatment. It was about. From the above results, it was found that itching after drug external stimulation (AEW treatment) can be reduced by applying a preparation containing polyquaternium-10.

Claims (4)

  An itching agent for reducing itching caused by an external stimulus, comprising cationized cellulose.   The itching reducing agent according to claim 1, wherein the external stimulus is a temperature change or a drug stimulus.   An itching reducing composition having an effect of reducing skin itching caused by an external stimulus, the composition comprising the itching reducing agent according to claim 1 or 2. A method for reducing the itching caused by an external stimulus by applying the itching reducing composition according to claim 3 to the skin (excluding a method for treating human itching) .

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