JP2009280511A - Antipruritic agent for external use - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an antipruritic agent for external use that has excellent effects on dry skins, gives a good feeling of use and is very excellently effective particularly against itch. <P>SOLUTION: The antipruritic agent for external use includes a solvent containing a lower alcohol and water, and, dissolved or dispersed therein, urea, an antihistamine agent and a local anesthetic, where the weight ratio of the lower alcohol to water is 1:(0.6 to 1.3) and the total amount of the lower alcohol and water is 60-90 w/v% based on the whole antipruritic agent. <P>COPYRIGHT: (C)2010,JPO&amp;INPIT

Description

  The present invention relates to an external anti-itch agent for skin.

  The dry skin disease is a disease that is always accompanied by pruritus as well as dry and keratinized skin, as represented by atopic dermatitis, senile xeroderma. Especially in senile xeroderma, the elderly's skin becomes dry and keratinized due to a decrease in sebum secretion and skin blood flow with atrophy of the skin with age, and a decrease in stratum corneum moisture. Accompanying them, eczema, itching, etc. may occur, and scratching may result in dermatitis throughout the body. Especially for elderly people who are bedridden, itching is said to cause secondary disorders such as insomnia, irritability, and loss of appetite.Today, the above problems are no longer for some people. Yes.

  In recent years, the number of allergic patients is increasing due to rapid changes in the environment and the style of clothing, food, and shelter, and the number of patients with atopic dermatitis caused by allergies is increasing rapidly. These patients suffer from external problems due to dryness and roughness of the skin, discomfort due to severe itching, and mental anxiety and distress.

  Dry skin diseases are difficult to cure due to the above-mentioned etiology, and worse, there is a tendency to cause scratch marks and blood clots due to itching, resulting in worsening of the disease state. Therefore, the treatment requires a drug capable of suppressing not only dry skin but also itching.

  However, many of the commercially available external preparations for skin currently used for dry skin diseases do not have satisfactory performance for the treatment of the above-mentioned dry skin diseases. Only one of them has an effect, and there is almost no one that can treat both. Therefore, when using a commercial item for the treatment of dry skin disease, two agents must be used in combination, which is extremely inconvenient for the patient. Moreover, in most cases, commercially available external preparations for skin are ointments or creams, which are uncomfortable, such as stickiness, and have a problem that foreign substances such as dust are likely to adhere to the used part. It is not preferred for skin diseases.

  On the other hand, as prescriptions in hospitals, crotamine preparations and corticosteroid preparations containing an effective amount of urea are known, but these are merely a mixture of the above-mentioned commercial products, and the dosage form is also inevitable However, it is limited to ointments or creams and cannot solve the problems of discomfort and foreign matter adhesion.

  As described above, the conventional external preparation for skin has a problem in applying it to dry skin diseases, and is effective for both dry skin and pruritus and has a good feeling of use and the problem of foreign matter adhesion. There is a need for new external preparations.

  The present inventors have succeeded in providing an external skin preparation comprising a predetermined amount of urea, an antihistamine, a local anesthetic, a lower alcohol, and a moisturizer as an external liquid that meets the above requirements (see Patent Document 1). . Although this skin external solution showed a significant improvement in feeling of use and the like as compared with this conventional seed solution, it was effective for both intended dry skin and pruritus. , There was room for improvement in terms of stickiness due to its application.

  Furthermore, the present inventors further formulated a diester composed of alcohol having 4 or less carbon atoms and adipic acid and / or sebacic acid in a liquid for external use containing urea, an antihistamine, a local anesthetic, a lower alcohol and a humectant. By doing so, it was found that an improvement was recognized in terms of stickiness (see Patent Document 2).

However, even if it is a skin external preparation by which these various characteristics were improved, the effect with respect to a pruritus is still not satisfactory, and the further improvement is desired.
JP-A-3-291221 JP-A-10-139687

  The present invention has been made in view of the problems of the prior art as described above, and its main purpose is to have an excellent effect on dry skin and a good feeling of use. It is an object of the present invention to provide an external anti-itching agent for skin which has a very excellent effect on wrinkles.

  The present inventor has intensively studied to achieve the above-described object. As a result, in a skin external preparation containing urea, an antihistamine and a local anesthetic, using a mixture of lower alcohol and water as a solvent, and increasing the proportion of water relative to the lower alcohol as compared with conventional skin external preparations, By keeping the total content of lower alcohol and water in a specific range, while maintaining excellent effects on dry skin, the itching suppression effect is remarkably improved, and the moisture retention, feeling of use, etc. are also good. The present invention was completed here.

  That is, the present invention provides the following skin anti-itch agent for external use.

1. An anti-itching agent for external skin use, wherein urea, antihistamine and local anesthetic are dissolved or dispersed in a solvent containing lower alcohol and water, wherein lower alcohol: water (weight ratio) = 1: 0.6-1. 3. An anti-itching agent for external skin, characterized in that the total amount of lower alcohol and water is 60 to 90 w / v% based on the whole of the anti-itch agent.
2. 5-20 w / v% urea, 0.5-5 w / v% antihistamine. Item 2. The anti-itch agent for external use according to Item 1, which contains 0.5 to 5 w / v% of a local anesthetic.
3. Item 3. The skin anti-itch agent for external use according to Item 1 or 2, comprising each component in the following composition range.
Urea 5-20w / v%
Antihistamine 0.5 ~ 5w / v%
Local anesthetic 0.5 ~ 5w / v%
Lower alcohol 30-50w / v%
Purified water 25-40w / v%
Moisturizer 1-10 w / v%
4). Item 4. The topical skin anti-itch agent according to any one of Items 1 to 3, wherein the antihistamine is diphenhydramine or a pharmacologically acceptable salt thereof, the local anesthetic is lidocaine, and the lower alcohol is ethanol.

  The external anti-itch agent for skin according to the present invention contains urea, an antihistamine and a local anesthetic, and is characterized by using, as a solvent, a lower alcohol and water having a specific blending ratio. Specifically, the lower alcohol and water are mixed at a ratio of lower alcohol: water (weight ratio) = 1: 0.6 to 1.3, and the total amount of the anti-itch agent for external use of the present invention is used as a reference. The total amount of the lower alcohol and water needs to be about 60 to 90 w / v%.

  The amount of the above-mentioned solvent used is characterized in that the proportion of water used relative to the lower alcohol is considerably higher than that of conventional skin external liquids, and the total amount of the lower alcohol and water is also large. By using a solution in which urea, antihistamine, and local anesthetics are dispersed or dissolved in a solvent with such a specific blending amount, good efficacy, moisturizing properties, and feeling of use are required as a therapeutic agent for dry skin diseases. In addition to the above, in particular, the effect of suppressing itching is remarkably exhibited.

  In the anti-itch agent of the present invention, the mixing ratio of lower alcohol and water is particularly preferably lower alcohol: water (weight ratio) = 1: 0.6 to 1.1, and 1: 0.6 to More preferably, it is about 0.9. The total amount of lower alcohol and water is preferably about 60 to 80 w / v%, more preferably about 60 to 75 w / v%.

  In the anti-itch agent of the present invention, as the lower alcohol, an alcohol having 4 or less carbon atoms such as ethanol and isopropanol is preferable, and ethanol is particularly preferable. Ethanol is excellent in the dissolving power of each component essential for the present invention described above, and is well mixed with water, so that it has an action of facilitating absorption of drugs and moisture from the skin, and also has a bactericidal disinfection action, Since it evaporates quickly from the skin after use, it does not give a sticky feeling like an ointment or cream, and has the advantage of bringing a refreshing feeling to the skin by removing heat of evaporation. However, if the amount of lower alcohol used is increased, the effect of suppressing itchiness is reduced.In the anti-itch agent of the present invention, the amount of water used is increased to relatively reduce the amount of lower alcohol used, Succeeded in improving the effect of suppressing itching.

  In the external anti-itch agent for skin of the present invention, urea is mainly used as a medicinal component for dry skin treatment. The blending amount is preferably an amount sufficient to show the above-mentioned medicinal effect, that is, about 5 to 20% (w / v%, the same shall apply hereinafter) of the total composition, more preferably about 8 to 20%. . When used in an amount outside this range, in particular below the above range, the above effects may not be sufficiently obtained.

  Both the antihistamine and the local anesthetic act as antipruritic components, and as the antihistamine, pharmacologically acceptable salts such as diphenhydramine, its hydrochloride, tannate, and the like can be typically used. As the local anesthetic, for example, lidocaine can be used. About the compounding quantity of these components, when using diphenhydramine or its salt as an antihistamine, it is preferable to set it as about 0.5 to 5%, and it is more preferable to set it as about 0.5 to 2%. Moreover, when using lidocaine as a local anesthetic, it is preferable to set it as about 0.5-5%, and it is more preferable to set it as about 1-3%.

  In addition to the above-mentioned components, other similar medicinal components can be additionally added and blended with the external anti-itch agent for skin of the present invention in order to supplement the medicinal properties of these components. Examples of other medicinal components include salicylic acid as a dry skin treatment component, and crotamiton and chlorpheniramine maleate as antipruritic components. About the compounding quantity of these components, it is necessary to set it as the quantity which the anti-itch agent of this invention hold | maintains a liquid agent form.

  The itch inhibitor of the present invention may further contain a humectant as a component that promotes the moisturizing and drying skin treatment action of urea. As the humectant, any of various conventionally known ones may be used. Specific examples thereof include, for example, polyhydric alcohols such as glycerin, propylene glycol, and 1,3-butylene glycol, and high water solubility such as polyethylene glycol and hydroxypropyl cellulose. Examples include molecular substances, other lactic acid, sodium lactate and the like. The blending ratio of the humectant in the anti-itch agent of the present invention is slightly different depending on the kind of the humectant, but usually it may be appropriately selected from the range of about 1 to 10% and does not hinder the action of the medicinal ingredients and the preparation. It goes without saying that it is a quantity.

  If necessary, the anti-itch agent of the present invention can further contain a diester of adipic acid and / or sebacic acid and an alcohol having 4 or less carbon atoms. Examples of the alcohol component constituting the diester include those having 4 or less carbon atoms, such as methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, t-butyl alcohol and the like. By blending the above-mentioned diester, it is possible to improve the sticky feeling caused mainly by urea having a stratum corneum moisture retention effect. The amount of the diester is preferably about 0.5 to 10 w / v%, more preferably about 1 to 5 w / v%.

  In addition to the above-mentioned components, other medicinal ingredients can be added to the itching inhibitor of the present invention as necessary. Examples of such components include anti-inflammatory agents such as glycyrrhetinic acid and methyl salicylate, refreshing agents such as menthol and mint oil, fragrances such as eucalyptus oil, deodorants, and stabilizers.

  However, in the anti-itch agent of the present invention, the use of poorly water-soluble components such as camphor, tocopherol, and salts thereof should be avoided. By not using such a poorly water-soluble component, even a composition with a large proportion of water used as described above can be made into a uniform liquid form, suppressing irritation to the skin, and excellent usability It can be set as the liquid agent which has an itching suppression effect.

  An example of a typical composition of the external anti-itch agent for skin according to the present invention is as follows.

Urea 5-20w / v%
Antihistamine 0.5 ~ 5w / v%
Local anesthetic 0.5 ~ 5w / v%
Lower alcohol 30-50w / v%
Purified water 25-40w / v%
Moisturizer 1-10 w / v%

  As long as the anti-itch agent for external use of the present invention contains each of the above-mentioned components, its production method is not particularly limited, but in general, the components are mixed and dissolved in a lower alcohol and a part of water, It can be prepared by adding a humectant to the solution and adding the remaining water to the solution to form a uniform liquid form.

  The external anti-itch agent for skin of the present invention can be made into a product by filling it in a suitable container. The anti-itch agent can be applied at once by applying an appropriate amount to the affected area by dropping or applying it to the affected area. Moreover, it is also possible to make the product form applicable to the spray container by filling the spray container.

  The external anti-itch agent for skin according to the present invention is excellent in the effect of suppressing itching, and has a good absorbability of drug and anti-component and has an excellent effect on dry skin. Furthermore, there is little stickiness, the feeling of use is very good, the moisture retention is excellent, and it has a lubricating action, and there is an advantage that problems such as adhesion of foreign matters hardly occur at the time of application.

  Therefore, the external anti-itch agent for skin of the present invention is very useful as a liquid agent that can achieve dry skin treatment and pruritus treatment effect with a single agent.

  Hereinafter, in order to explain the present invention in more detail, production examples of the external anti-itch agent for skin of the present invention are given as examples, and then test examples for clarifying the effectiveness of the anti-itch agent of the present invention are given.

Example 1
An itching agent having a composition (w / v%) shown in Table 1 was prepared by the following method.

  Among the components shown in Table 1, a part of ethanol and purified water was added to a mixture of urea, diphenhydramine hydrochloride and lidocaine and dissolved by stirring.

  Then, after adding other components to the obtained solution, the remaining purified water was added and mixed to make the total amount 100 mL, thereby preparing the present itch inhibitor.

Comparative Example 1
As a known external preparation for skin, a liquid preparation having the composition (w / v%) shown in Table 2 below was prepared by a method according to Example 1. This is designated as Comparative Sample 1.

Test example 1 (itch control test)
(1) Test sample Using the anti-itch agent of the present invention obtained in Example 1 and the anti-itch agent (Comparative Sample 1) obtained in Comparative Example 1, the effect of suppressing the itching by mice was tested by the following method. Furthermore, a solution obtained by removing diphenhydramine hydrochloride from the itching inhibitor of the present invention obtained in Example 1 (Comparative Sample 2), a solution obtained by removing lidocaine from the itching agent of the present invention obtained in Example 1 (Comparative Sample 3), The same applies to the case of using each liquid agent (comparative sample 4) obtained by removing urea, diphenhydramine hydrochloride, and lidocaine from the itching inhibitor of the present invention obtained in Example 1, and the case of not applying the anti-itch agent. A test was conducted.

(2) Test method Each test sample was applied to NAO mice, and histamine releaser (Compound 48/80), which is an itching agent, was subcutaneously administered 30 minutes later, and the mice in 30 minutes from 5 minutes to 35 minutes after administration. The itch scratching behavior was observed and the time was measured (N = 5). The results are shown in FIG.

(3) Results As is clear from FIG. 1, according to the anti-itch agent of the present invention, a high anti-itch effect was recognized as compared with Comparative Sample 1 which is a known external preparation for skin.

  In addition, when compared with Comparative Samples 2 and 3, the itching inhibitor of the present invention was found to have a very good itching inhibiting effect, so that it contains both diphenhydramine hydrochloride and lidocaine. A synergistic effect was confirmed.

  In Comparative Sample 4 consisting only of the base material, the results were the same as in the case of no application, and no itching suppression effect was observed.

Test example 2 (absorbency test)
Using the Franz diffusion cell schematically shown in FIG. 2, an absorption test of lidocaine with a silicon film was performed on the anti-itch agent of the present invention and comparative sample 1 which is a known skin external solution by the following method.

  First, a silicon film was attached to the Franz diffusion cell, and 0.5 mL of each sample was applied on the silicon film. Thereafter, the change in the amount of lidocaine permeated through the silicon film was determined by high performance liquid chromatography. The results are shown in FIG.

  From FIG. 3, according to the anti-itch agent of the present invention, the transmissivity of lidocaine, which is a medicinal component, was about 6 times as high as that of a known skin external solution. From this result, it was confirmed that the anti-itch agent of the present invention was excellent in absorbability of medicinal ingredients.

Test Example 3 (Moisturizing test)
A test of the moisturizing effect was performed on the itch prevention agent of the present invention and Comparative Sample 1 which is a known external preparation for skin by the following method.

  First, about 100 μL of each sample was continuously applied to the human forearm flexion side immediately after bathing for 2 weeks, and the change in the amount of horny water before and after application was measured (N = 4). The results are shown in FIG.

  From FIG. 4, when the itching inhibitor of the present invention and the comparative sample 1 were continuously applied, the amount of keratin moisture increased as compared with the case of no application. From this result, it was confirmed that the anti-itch agent of the present invention has a moisturizing effect comparable to that of a known skin external solution.

The graph which shows the result of the itching suppression test in Test Example 1. Schematic of the Franz diffusion cell used in Test Example 2. FIG. The graph which shows the result of the absorptivity test in Test Example 2. The graph which shows the result of the moisture retention test in Test Example 3.

Claims (4)

An anti-itching agent for external skin use, wherein urea, antihistamine and local anesthetic are dissolved or dispersed in a solvent containing lower alcohol and water, wherein lower alcohol: water (weight ratio) = 1: 0.6-1. 3. An anti-itching agent for external skin, characterized in that the total amount of lower alcohol and water is 60 to 90 w / v% based on the whole of the anti-itch agent. 5-20 w / v% urea, 0.5-5 w / v% antihistamine. The external anti-itch agent for skin according to claim 1, comprising 0.5 to 5 w / v% of a local anesthetic. It contains each component of the following composition range, The skin anti-itch agent for external use of Claim 1 or 2 characterized by the above-mentioned.
Urea 5-20w / v%
Antihistamine 0.5 ~ 5w / v%
Local anesthetic 0.5 ~ 5w / v%
Lower alcohol 30-50w / v%
Purified water 25-40w / v%
Moisturizer 1-10 w / v% The anti-itch agent for external skin use according to any one of claims 1 to 3, wherein the antihistamine is diphenhydramine or a pharmacologically acceptable salt thereof, the local anesthetic is lidocaine, and the lower alcohol is ethanol.

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