JPH10139687A - Skin preparation for external use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a skin preparation for external use showing effects on both drying skin and itch, capable of improving greasy feeling by application. SOLUTION: This skin preparation for external use comprises 8-23w/v% of urea, 0.3-4w/v% of an antihistaminic agent, 0.5-5w/v% local narcotic, 40-70w/v% of a lower alcohol, 0.1-30w/v% of a humectant, 0.5-20w/v% of a diester consisting of a <=4C alcohol and adipic acid and/or sebacic acid and purified water as essential components.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a skin external preparation having an improved tackiness, and more particularly to a new skin external preparation having a dry skin treatment and an antipruritic effect and having an improved stickiness.

[0002]

2. Description of the Related Art In recent years, the problem of dry skin disease has been widely raised in the field of medical and welfare. The dry skin disease is typified by atopic dermatitis, senile xerosis, etc. As it is, not only is the skin dry and keratinized, but also a condition that is always itchy. In particular, the senile xeroderma is described in detail.Skin of the elderly decreases in sebum secretion and cutaneous blood flow with the atrophy of the skin with aging. Eczema, itch, etc. occur along with them, and dermatitis may occur throughout the body due to scratching. It is said that the above problems will no longer apply to some people as they are moving toward an aging society.

In recent years, the number of allergic patients has been increasing due to rapid changes in the environment and the style of eating, eating, and living. Along with this, the number of patients with atopic dermatitis causing allergy has also increased rapidly. These patients are suffering from cosmetic problems due to dry and rough skin, discomfort due to severe itching, and mental anxiety and pain.

[0004] Dry skin diseases are difficult to cure due to the above-mentioned etiology, and even worse, itching tends to produce scratches and blood crusts, and the pathology tends to worsen. Therefore, for the treatment, an agent capable of suppressing not only itching but also itching of the skin is required.

[0005] However, none of the many commercially available skin external preparations currently used for dry skin diseases have satisfactory performance in the treatment of the above-mentioned dry skin diseases. That is, a commercially available skin external preparation only shows an effect on either dry skin or pruritus, and there is no one that can treat both with one agent. Therefore, when a commercial product is used for the treatment of dry skin disease, two agents must be used in combination, which is extremely inconvenient for patients. In addition, most of the commercially available skin external preparations are in the form of ointments or creams, which cause discomfort such as stickiness to the user, and foreign substances such as dust easily adhere to the used area. However, it is not preferable for dry skin diseases.

[0006] On the other hand, as a prescription in a hospital, a crotamine preparation or a corticosteroid preparation containing an effective amount of urea is known [see Skin Diseases and Topical Preparations (Nanzando)]. It is merely a mixture of products, and the dosage form is necessarily limited to ointments or creams, and the problems of discomfort and adhesion of foreign substances cannot be solved.

[0007] As described above, the conventional external preparation for skin has a problem in applying it to dry skin diseases. The external preparation which solved this problem, that is, has an effect on both dry skin and pruritus. There has been a need in the art for a new external preparation which exhibits good feeling in use and has no problem of adhesion of foreign substances.

The present inventors have previously succeeded in providing a skin external solution comprising a predetermined amount of urea, an antihistamine, a local anesthetic, a lower alcohol and a moisturizer as an external solution which meets the above-mentioned demands in the art [ JP-A-3-291221
Reference).

This external preparation for skin shows a considerable improvement in the feeling of use, etc., as compared with the conventional liquid preparation of this kind, and shows an effect on both the intended dry skin and pruritus. However, there is room for improvement in the sticky feeling (mainly due to the humectant and urea having a moisturizing effect) due to the application.

[0010]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to solve the problems found in conventional external preparations, and in particular, it is suitable for application to patients with dry skin diseases and has a sticky feeling due to the application. However, it is an object of the present invention to provide a new external preparation which can be satisfactorily improved.

[0011] The present inventors have found that, in particular, urea,
As a result of intensive studies on a topical solution containing an antihistamine, a local anesthetic, a lower alcohol and a humectant, the above-mentioned topical solution further contains a diester composed of an alcohol having 4 or less carbon atoms and adipic acid and / or sebacic acid. When the prescribed amount is blended, the diester has a particularly excellent effect of improving the sticky feeling, and thus has a dry skin treatment effect, an antipruritic effect, a moisturizing effect, etc., and the sticky feeling is remarkably improved. It has been found that an external preparation in a liquid form meeting the above object can be obtained, and the present invention has been completed.

[0012]

According to the present invention, there is provided a skin external preparation having an improved sticky feeling, characterized by containing each of the following composition ranges and purified water as essential components.

Urea 8-23 w / v% Antihistamine 0.3-4 w / v% Local anesthetic 0.5-5 w / v% Lower alcohol 40-70 w / v% Humectant 0.1-30 w / v% Carbon number Diester composed of 4 or less alcohol and adipic acid and / or sebacic acid
5-20% w / v.

Further, according to the present invention, the above-mentioned external skin preparation wherein the antihistamine is diphenhydramine, the local anesthetic is lidocaine and the lower alcohol is ethanol and / or isopropyl alcohol, and an alcohol having 4 or less carbon atoms and adipine There is provided a urea-containing external skin solution containing a diester composed of an acid and / or sebacic acid as a sticky feeling improving agent.

The external preparation for skin of the present invention, which is in the form of a liquid preparation having the above-mentioned specific composition, has both a dry skin treatment effect and an antipruritic effect, and also has an excellent feeling of use due to an improved sticky feeling. In addition, it has the advantage of not causing the problem of foreign matter adhesion.

The external preparation for skin of the present invention also has the advantage of being more stable in that the decomposition of urea and the amount of ammonia produced thereby are small.

[0017]

DESCRIPTION OF THE PREFERRED EMBODIMENTS In the liquid preparation of the present invention, urea is used as a medicinal ingredient for dry skin treatment, and its compounding amount is an amount sufficient to exhibit the above medicinal effect, that is, 8 to 23 of the total composition. % (W / v%, the same applies hereinafter), preferably 10
It is important to select from the range of 20%, and when used in an amount outside this range, particularly in an amount below the above range, the intended effect of the present invention cannot be achieved.

It is important that the liquid preparation of the present invention contains predetermined amounts of an antihistamine and a local anesthetic. These act as antipruritic components, and as the antihistamine, typically, pharmacologically acceptable salts such as diphenhydramine, its hydrochloride, tannate, etc., and as a local anesthetic, Typically, lidocaine can each be used to advantage. In the case of diphenhydramine as an antihistamine, the amount of these components is 0.1.
In the range of 3-4%, preferably 0.5-2%, and in the case of lidocaine as a local anesthetic, the range is 0.5-5%, preferably 1-3%. Within the amount range, the desired effect of the present invention can be achieved.

In addition to the above-mentioned essential medicinal components, other similar medicinal components may be additionally added to the liquid preparation for external use of the present invention in order to supplement the medicinal effects of these components. Examples of the other medicinal components include salicylic acid and the like as dry skin treatment components, and crotamiton and chlorpheniramine maleate as antipruritic components. However, the amount of these components must be such that the preparation of the present invention maintains the liquid form.

The liquid preparation of the present invention further contains a humectant as an essential component, which has the function of promoting the action of urea for moisturizing and treating dry skin. As the humectant, any of various conventionally known humectants may be used, and specific examples thereof include polyhydric alcohols such as glycerin, propylene glycol and 1,3-butylene glycol, and water-soluble polymers such as polyethylene glycol and hydroxypropyl cellulose. Examples thereof include polymeric substances, lactic acid, and sodium lactate. The mixing ratio of the humectant in the liquid preparation of the present invention is slightly different depending on the type of the humectant, but may be appropriately selected from the range of 0.1 to 30%. It is needless to say that the amount is not so large.

Further, the liquid preparation of the present invention is characterized in that a lower alcohol is used in an amount of 40 to 70% as a base. As the lower alcohol, ethanol and / or isopropanol are particularly preferable. The ethanol is excellent in the dissolving power of each of the essential components of the present invention and is well miscible with water, so that it has an action of facilitating the absorption of drugs and water from the skin, and also has a disinfecting action. Since it evaporates quickly from the skin after use, it does not give a sticky feeling like an ointment or cream, and has an advantage that it gives a refreshing feeling to the skin by removing heat of evaporation.

It is important that the liquid preparation of the present invention contains, as an essential component, a diester of adipic acid and / or sebacic acid in an amount of 0.5 to 20 w / v%, preferably 2 to 12 w / v%. With this composition, it is possible to improve the sticky feeling which is mainly caused by urea having a horny layer moisture retaining effect. 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, and t-butyl alcohol.

The method for preparing the external preparation for skin of the present invention is not particularly limited as long as it contains each of the above-mentioned components. Generally, the essential medicinal components are mixed to form a mixture of adipic acid and / or sebacic acid. After dissolving in a part of diester, lower alcohol and water, a humectant is added to the solution,
It is prepared by adding the remaining water to this to make a uniform liquid form.

In addition to the above-mentioned components, the liquid preparation of the present invention further comprises
If necessary, other medicinal ingredients and the like, for example, anti-inflammatory agents such as camphor, glycyrrhetinic acid, methyl salicylate, etc., cooling agents such as menthol, peppermint oil, fragrances such as eucalyptus oil, vitamins such as tocopherol, deodorants, stabilization It is also possible to appropriately add and mix agents and the like.

The thus-prepared solution for external use on the skin of the present invention is filled into a suitable container to obtain a product, which comprises:
It is applied by dropping or applying an appropriate amount to the affected area at a time by using an applicator or the like. Further, it is also possible to fill a spray container into a product form applicable by a spray method.

The liquid preparation for external use on the skin of the present invention can exert a dry skin treatment and a pruritus treatment effect by a single agent. In addition to being suitable for the treatment of dry skin diseases, it has almost no sticky feeling. It has the advantage that it has a very good feeling in use, has a lubricating effect, and hardly causes problems such as adhesion of foreign substances when applied.

[0027]

EXAMPLES Hereinafter, in order to explain the present invention in more detail, a production example of a liquid preparation for external use on the skin of the present invention will be described as an example, followed by a clinical test example and a performance test example for clarifying the effectiveness of the liquid preparation of the present invention.

[0028]

Example 1 Urea 10 g Diphenhydramine hydrochloride 1 g Lidocaine 2 g Ethanol 45 g 1,3-butylene glycol 20 g Diethyl sebacate 4 g Refined water qty 100 ml About 10 g of purified water was added and dissolved by stirring. Further, the above solution was added to the solution obtained in the above amount.
-After adding butylene glycol and diethyl sebacate, add the remaining purified water to make the total volume 100 ml,
A skin preparation for external use of the present invention was prepared.

[0029]

Example 2 Urea 10 g Diphenhydramine hydrochloride 1 g Lidocaine 2 g Camphor 1 g Tocopherol acetate 0.3 g Ethanol 48 g 1,3-butylene glycol 10 g Sodium lactate 5 g Diisopropyl adipate 5 g Refined water qs 100 ml And in the same manner as in Example 1,
A skin preparation for external use of the present invention was prepared.

[0030]

Examples 3 to 6 In the same manner as in Example 1 except that predetermined amounts of the respective components shown in Table 1 below were used, liquid preparations for external use on the skin of the present invention were prepared.

[0031]

[Table 1]

[0032]

Test Example 1 (1) Reagents Example 3 was applied except that the liquid for external use of the skin of the present invention (samples 1 to 3 of the present invention) obtained in Examples 3 to 5 and diethyl sebacate were not used for comparison. A liquid preparation (comparative sample) prepared in the same manner as described above was used.

(2) Subjects 7 males (20 to 40 years old) and 7 females (20 to 30 years old)
A total of 14 people were selected.

(3) Test method Using two test sites on both sides of each subject's forearm flexure, test reagents of the present invention samples 1 to 3 and a comparative sample were sequentially applied to each site, and their tackiness was applied. The sensory evaluation was made by comparing the feeling. The evaluation was made based on the numerical values of the samples A and B marked on the sticky degree judgment recording paper by drawing straight lines of pleasant (100), acceptable (0) and unpleasant (-100). From the above numerical values, the acceptability of the tackiness of each test sample was calculated according to the following equation.

Acceptability of stickiness (%) = [1− (number of subjects evaluated as less than allowable (−evaluation)) / 14] × 100 (4) Results The results obtained are shown in Table 2 below and FIG. Comparative data between the sample 2 of the present invention (shown as a line (1) in the figure) obtained in Example 4 and a comparative sample (shown as a line (2) in the figure)].

[0036]

[Table 2]

From FIG. 1 and Table 2, it can be seen that each of the skin external liquid samples 1 to 3 of the present invention containing each of adipic acid diester and sebacic acid diester had a sticky feeling as compared with the comparative sample not containing this. It was evaluated that it was remarkably reduced, and it is clear from this that the addition and blending of the diester has an effect of improving the tackiness after application of the liquid preparation.

[0038]

Test Example 2 (1) Reagents Samples 2 and 3 of the present invention and a comparative sample were used.

(2) Subjects 3 males (20-40 years old) and 2 females (20-30 years old)
5) in total.

(3) Test Method Two portions on the left forearm flexion side and one on the right arm flexion side of the subject were set as test sites (4 cm × 4 cm each), and 20 μl of each sample was uniformly applied to each test site. And the water content of the stratum corneum was measured over time. The measurement was carried out using a high-frequency conductivity measuring device (manufactured by Hamamatsu IBM Co., Ltd., with a high-sensitivity probe with an inner pole of 2 mm and an outer pole of 4 to 6 mm) before, immediately after, and
3 minutes after 0 minute, 60 minutes after application and 120 minutes after application
The measurement was performed each time, and the average value was used as the measured value.

The same test was repeated for the same subject, changing the measurement date, and data was obtained for a total of 10 subjects.

(4) Results The data obtained are shown in Table 3 below.

[0043]

[Table 3]

From Table 3, it can be seen that the sample of the present invention has substantially no adverse effect on the moisturizing effect of urea even by the addition and mixing of adipic acid diester and sebacic acid diester.

[0045]

Test Example 3 (1) Reagents The liquid sample for external use of the skin of the present invention obtained in Example 6 and the comparative sample 1
Was used.

(2) Test Method 0.1 ml of each preparation sample was applied on artificial leather, and a friction element (made of silicon) with a constant load was moved horizontally on the artificial leather to apply the artificial leather and the friction element. The resulting MIU (mean coefficient of friction) was measured at four points immediately after, 30 minutes, 60 minutes and 120 minutes after application.

(3) Measurement conditions The following conditions were adopted.

Force sensitivity [H (dynamometer 20 g / V)] Moving speed [1 mm / sec] Static friction load [25 g] Friction sensor [silicon sensor] (4) Measurement results The results are shown in Table 4 below.

[0049]

[Table 4]

The MIU value of the friction tester is correlated with the slipperiness and the difficulty of slipping when a person rubs the surface of an object. As the value of the MIU increases, it is evaluated that the MIU is less slippery in the sensory evaluation.

As shown in Table 3, in this test, the MIU value of the skin external preparation sample of the present invention to which sebacic acid diester was added was lower than that of the comparative sample to which sebacic acid diester was not added. From this, it was clarified that the addition of the diester had an excellent lubricating effect on the resulting liquid.

[Brief description of the drawings]

FIG. 1 is a graph showing the evaluation of the sticky feeling of the liquid preparation for external use on the skin of the present invention obtained in accordance with Pharmacological Test Example 1.

Claims (4)

[Claims] 1. A liquid preparation for external use with improved sticky feeling, comprising the following components in the following composition ranges and purified water as essential components: Urea 8-23 w / v% Antihistamine 0.3-4 w / v% Local anesthetic 0.5-5 w / v% Lower alcohol 40-70 w / v% Humectant 0.1-30 w / v% C4 or less 1. Diester composed of alcohol and adipic acid and / or sebacic acid
5-20 w / v% 2. A liquid preparation for external use on the skin having an improved sticky feeling, comprising the following components in the following composition ranges and purified water as essential components. Urea 10-20 w / v% Antihistamine 0.5-2 w / v% Local anesthetic 1-3 w / v% Lower alcohol 40-70 w / v% Humectant 0.1-30 w / v% Alcohol having 4 or less carbon atoms Diester composed of adipic acid and / or sebacic acid 2
~ 12w / v% 3. The liquid preparation according to claim 1, wherein the antihistamine is diphenhydramine, the local anesthetic is lidocaine, and the lower alcohol is ethanol and / or isopropyl alcohol. 4. A urea-containing external skin solution containing a diester composed of an alcohol having 4 or less carbon atoms and adipic acid and / or sebacic acid as a sticky feeling-improving agent.