JPH09110680A - Dermatitis-curing strap - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a dermatitis-curing strap exhibiting sufficient penetration of an antipruritic component, a sterilizing component and a humectant component and durability of their effects, and capable of protecting a patient part from scratching off and other stimulus from outside by blending the antipruritic component, the sterilizing component and the humectant component in a base agent. SOLUTION: This dermatitis-curing strap is obtained by blending a base agent with an antipruritic component (preferably at least one kind of diphenhydramine, chlorpheniramine maleate and crotamiton), a sterilizing component (preferably at least one kind of chlorhexidine gluconate, isopropylmethylphenol and povidone-iodine) and a humectant component (preferably at least one kind of triglyceride, a phospholipid, sodium hyaluronate, chondroitin sodium sulfate, glycerol, a lactate, dl-pyrrolidone carboxylate and urea).

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a new external patch for skin intended for the treatment of dry skin diseases such as senile xerosis, keratoderma and atopic dermatitis.

[0002]

2. Description of the Related Art In recent years, an extremely large number of cases of dry skin diseases such as senile xerosis and atopic dermatitis have been seen, and a large ripple is cast.

Dry skin disorders such as senile xerosis are
It is a skin disease in which the buttocks and lower limbs of middle-aged people are the most common site, and the secretion of sebum is reduced and the skin becomes dry and keratinized. Accompany. It is known that, especially in winter, when sweating and sebum secretion are reduced, the skin is dried, and skin symptoms and itching are exacerbated. It may be difficult to sleep at night due to severe itching, and it is a painful disease.Scratching the affected area with nails damages the surface of the skin and causes an eczema reaction.
In many cases, skin symptoms and itching are exacerbated. Also,
Due to recent changes in environment and lifestyle, the number of allergic patients is rapidly increasing, and the number of patients with atopic dermatitis due to the allergies is also increasing. These patients suffer great pain not only due to dryness and rough skin but also severe itching.

By the way, even in a normally healthy human body, bacterial groups called normal bacterial flora exist on the skin surface. A representative bacterium is S. Epidermidi.
s), Staphylococcus aureus (S. Aureus), which usually do not affect the human body. However, in the case where the skin condition is deteriorated as described above, this bacterium is one of the causes of deterioration of the affected area. In particular, a lot of Staphylococcus aureus is present in the skin of patients with atopic dermatitis, and it has been reported that removing this is also effective for the treatment (Masako Hirata et al .: Nisshikai 104 (11), 1994, Y. Kozuka: Allergy Clinic 14 (14), 1994, Kaori Isobe et al .: 199
5th Japan Cosmetic Science Society).

Due to such etiologies, dry skin diseases are difficult to cure, and effective treatments for these are first to treat dryness and keratinization of the skin, as well as to cause insomnia and irritability. It is effective to suppress itching as soon as possible and to suppress bacteria that cause deterioration of the affected area.

Many external preparations for the skin are marketed as therapeutic agents for such dry skin diseases, but none are effective against each symptom (itch, skin symptom) of these diseases. , But the effect was weak and lacking in sustainability. For example, Japanese Examined Patent Publication 7-74152
Since the external preparation for skin contains a large amount of lower alcohol, skin irritation such as tingling sensation to scratches, which is often observed at pruritus sites, has been a problem. In addition, it cannot be said that it is a drug that is easy to use when applied to the affected area for the elderly with limited limbs. In addition, since the effects of the contained antihistamines and local anesthetics are weak, the affected areas were often unconsciously scratched at bedtime and exacerbated. Further, since such an affected area is sensitive, even if it is not scratched, it may be stimulated by clothes or the like.

[0007]

DISCLOSURE OF THE INVENTION The present invention provides a new external preparation which is useful for treating dry skin symptoms, particularly dry skin accompanied by itch, and which has solved the problems found in conventional external preparations. To aim.

[0008]

In order to solve the above problems, the present inventor has paid attention to a dosage form of a patch as a device, and as a result of intensive studies, as a result, sufficient penetration of medicinal components such as an antipruritic component was confirmed. We have found a composition capable of exhibiting its durability and protecting the affected area from scratches and other antigens. That is, all of the above objects have been successfully solved by incorporating an antipruritic component, a bactericidal component and a moisturizing component in the base.

It should be further noted that water, which is the base component of this device, not only exerts the effect of moisturizing dry skin, but the cooling effect of this water further promotes the antipruritic effect. The optimal dosage form is for the treatment of dermatological skin diseases.

More specifically, the present invention is a patch prepared by spreading a plaster containing an antipruritic component, a bactericidal component and a moisturizing component in a base material on a support such as a non-woven fabric.

The patch of the present invention generally means a so-called water-based poultice. That is, a typical example is a type in which an adhesive such as gelatin, an excipient such as kaolin, and a gel paste containing water are coated on a support such as a non-woven fabric and covered with a liner such as a plastic film. is there. In the hydrous gel-like plaster, polyhydric alcohols such as glycerin, propylene glycol, 1,3-butylene glycol, polyethylene glycol and sorbitol can be used in addition to water. Some of these may also function as humectants.

The pressure-sensitive adhesive is preferably one which exhibits viscosity in a water-polyhydric alcohol mixture, and examples thereof include gelatin, casein, carrageenan, gum arabic, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl alcohol, polyacrylic. It is possible to use conventional ones such as sodium acid salt, sodium carboxymethyl cellulose, sodium alginate, propylene glycol alginate, xanthan gum, carboxyvinyl polymer, and methyl vinyl ether / maleic anhydride copolymer.

As the excipient, those conventionally used such as kaolin, bentonite, zinc oxide, titanium oxide, and aluminum silicate can be used.

As the surfactant, glycerin fatty acid ester, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, sorbitan fatty acid ester,
Examples thereof include propylene glycol fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyethylene glycol fatty acid ester and the like.

As the antipruritic component which can be used in the present invention, an antihistamine such as diphenhydramine, chlorpheniramine maleate, or crotamiton is preferable.

The bactericidal components that can be used in the present invention include chlorhexidine gluconate, chlorhexidine hydrochloride, isopropylmethylphenol, benzalkonium chloride,
Examples thereof include benzethonium chloride and povidone iodine. Chlorhexidine gluconate, isopropylmethylphenol, and povidone iodine are preferable.

The moisturizing ingredients which can be used in the present invention include triglyceride, phospholipids, sodium hyaluronate,
Sodium chondroitin sulfate, glycerin, lactate,
Examples thereof include dl-pyrrolidonecarboxylic acid and urea, with sodium hyaluronate, sodium chondroitin sulfate, glycerin and urea being preferred.

Furthermore, a local anesthetic component can be added to the patch of the present invention. This local anesthetic component acts on sensory nerves around the application site to block the conduction of excitement, paralyze the sensory nerves, and relieve pruritus in the affected area. Specific examples include lidocaine, dibucaine, and ethyl aminobenzoate.

The pH of the preparation is the skin pH of 4.2 to
Since the range of 6.4 is desirable, the pH can be adjusted using citric acid, malic acid, tartaric acid, gluconic acid, lactic acid or the like.

The support that can be used in the present invention is not particularly limited as long as it is flexible and does not give a feeling of strangeness when attached to the skin. Specific examples include films or sheets of polyolefin, polyvinyl chloride, polyester, polypropylene, polyurethane, polyvinyl alcohol, polyvinylidene chloride, polyamide and the like, non-woven fabrics, cotton fabrics, and laminated films and sheets thereof.

In addition to the above components, the patch of the present invention may optionally contain other medicinal components such as anti-inflammatory agents such as glycyrrhetinic acid and methyl salicylate, perfumes such as peppermint oil and eucalyptus oil, and tocopherol. It is also possible to appropriately add vitamins, stabilizers and the like.

[0022]

The patch for dermatitis of the present invention is applied to the affected area of dry skin to continuously improve skin symptoms and suppress itch, and the affected area is protected by the patch. Therefore, scratching or other external irritation can be avoided, and the symptom is not worsened by it. In addition, the combination of bactericidal components is effective in treating the deterioration of the affected area due to infection.

[0023]

[Examples] Examples of the patch for skin inflammation of the present invention will be shown below, which will be described more specifically. Needless to say, various applications can be made without departing from the technical idea of the present invention.

Examples 1 to 7 In the formulations shown in Table 1, a water-soluble base, an antipruritic component, a bactericidal component, a moisturizing component and purified water were dissolved and mixed and spread on a support to prepare the poultices of Examples 1 to 7. I got an agent.

[0025]

[Table 1]

A manufacturing method will be briefly described by taking Example 1 as an example.
Crotamiton, diphenhydramine, isopropylmethylphenol, sodium chondroitin sulfate, sodium hyaluronate, urea, lidocaine, sodium polyacrylate, carboxymethylcellulose, titanium oxide, glycerin, polysorbate 80, sorbitan sesquioleate, synthetic aluminum silicate and dihydroxyaluminum aminoacetate. Knead a predetermined amount of. Separately, D-sorbitol solution, polyvinyl alcohol,
Water is added to gelatin, methyl paraoxybenzoate and tartaric acid and dissolved by heating. Both solutions are kneaded to obtain a hydrogel. The obtained hydrous gel is applied to a non-woven fabric, and a polypropylene film is attached to the surface to obtain a patch.

Comparative Examples 1 to 6 In the formulations shown in Table 2, Comparative Examples 1 and 2 (prescription without antipruritic components), Comparative Examples 3 and 4 (prescription without sterilizing components), Comparative Examples 5 and 6 ( A formulation excluding moisturizing ingredients) was prepared.

[0028]

[Table 2]

Comparative Example 7 Liquid Agent Crotamiton 5g Diphenhydramine 1g Isopropylmethylphenol 0.1g Sodium chondroitin sulfate 0.1g Sodium hyaluronate 0.01g Urea 5g Lidocaine 2g Ethanol 45g 1,3-Butylene glycol 20g Purified water Appropriate amount of crotamiton, diphenhydramine, isopropyl Ethanol was added to a mixture of methylphenol, sodium chondroitin sulfate, sodium hyaluronate, urea and lidocaine, and dissolved by stirring. Further, the above-mentioned amount of 1,3-butylene glycol was added to the obtained solution, and purified water was added to adjust the total amount to 100 ml to prepare a liquid preparation of Comparative Example 7.

Comparative Example 8 Ointment (gel) crotamiton 5g diphenhydramine 1g isopropylmethylphenol 0.1g sodium chondroitin sulfate 0.1g sodium hyaluronate 0.01g urea 5g lidocaine 2g macrogol 4000 5g polyvinylpyrrolidone 5g carboxyvinyl polymer 5g triethanolamine 3g ethanol 43g Purified water Appropriate amount Dissolve the above amounts of crotamiton, diphenhydramine, isopropylmethylphenol, sodium chondroitin sulfate, sodium hyaluronate, urea, lidocaine and ethanol with stirring. Separately, a solution in which Macrogol 4000 and a carboxyvinyl polymer are dispersed and swollen in purified water and a solution in which polyvinylpyrrolidone is dispersed and swollen in ethanol are stirred and dissolved. This was combined with the above solution and stirred, and a solution prepared by mixing triethanolamine with purified water was added and well stirred to prepare an ointment of Comparative Example 8.

Comparative Example 9 Plaster agent crotamiton 5g diphenhydramine 1g isopropylmethylphenol 0.1g sodium chondroitin sulfate 0.1g sodium hyaluronate 0.01g urea 5g lidocaine 2g styrene-isophenyl-styrene block copolymer 13g alicyclic saturated hydrocarbon resin 39.5g Liquid paraffin 34.3 g Components other than the drug were blended in the proportions shown above, and heated and stirred at a temperature of 120 to 150 ° under nitrogen substitution to melt. After melting, this was cooled to 100 to 120 °, the chemicals were added and uniformly mixed to obtain a pressure-sensitive adhesive solution. Next, the adhesive layer solution melted using a hot melt coater is spread on a release paper made of polyethylene-coated high-quality paper so that the thickness after drying is about 100 μm, and a soft vinyl chloride film as a support is laminated. By doing so, the plaster-type patch of Comparative Example 9 was obtained.

Test Example 1 (Antipruritic effect) Using adults and aged patients with xerosis and atopic skin diseases with itch as subjects, Examples 1, 3, 5 and Comparative Examples 1, 3, 5, 7, 8 Regarding 9 and 9, the effect of improving itch was examined by the following method.

Targeting adults and elderly people with dry skin and atopic dermatitis between the ages of 20 to 80, each formulation was applied to 5 persons, before application of each formulation, 2 hours after application and 8 hours after application. The degree of itch was evaluated. The patch of the test example was applied until the evaluation was completed. Drugs that may affect the test during the test period (steroids, antiallergic agents, etc.)
As a general rule, the combination of external use and internal use is prohibited.

The degree of itchiness is based on the severity standard (Table 3) modified by quoting the Shiratori original table, 4: advanced, 3: moderate,
The evaluation was carried out on a scale of 5: 2: mild, 1: slight, 0: none.

[0035]

[Table 3]

Table 4 shows the effect of antipruritus in Examples and Comparative Examples of the present invention.

[0037]

[Table 4]

As shown in the above table, the antipruritic effect of the Examples is
It was confirmed that the efficacy and durability were superior to those of the comparative examples. Moreover, according to this, it is clear that the durability of the liquid preparation and the ointment preparation is inferior.

Test Example 2 (Amelioration Effect of Skin Symptoms) In addition to Test Example 1, 5 subjects of each prescription were applied to test subjects under the same conditions, and the effect of improving skin symptoms was evaluated. Each formulation was applied for 2 weeks during bedtime. The skin symptoms were evaluated before applying each preparation. During the study period, as a rule, external use of drugs that affect the study (steroids, anti-allergic agents, etc.) and internal use are prohibited.

The skin symptoms were evaluated by classifying the degree into the following 5 grades. 4: Altitude, 3: Moderate, 2: Mild, 1: Minor, 0: None

The degree of symptoms at the start of use and the degree of symptoms after 2 weeks and 4 weeks of use were observed and evaluated according to the following criteria. Excellent response: markedly improved, effective: significantly improved, moderately effective: somewhat improved, ineffective: symptom unchanged, exacerbated: symptom deteriorated. Table 5 shows the results.

[0042]

[Table 5]

As shown in the above table, the skin symptom-improving effect of the Examples was superior to that of Comparative Examples, especially to the formulations containing no antipruritic or moisturizing ingredients. Even with the same patch, the effect of Comparative Example 9 containing no water was weak. In addition, with respect to liquid preparations and ointments, there were cases in which the symptoms progressed gradually due to physical irritation such as partial scratching.

Test Example 3 (Effect of Bactericidal Component) Skin of a test subject group to which Examples 1 and 3 and Comparative Example 3 (prescription from which a bactericidal component was removed from Example 3) were applied during the execution of Test Example 2. Simultaneously with the observation of symptoms, the number of bacteria (colony count) on the skin surface of the affected area was measured by the stamp method (a method in which a small medium is pressed against the skin surface to collect and culture the bacteria and measure the bacteria), and the transition was traced. . Table 6 shows the results.

[0045]

[Table 6]

As shown in the above table, Example 1 containing a sterilizing component,
No. 3 had a greater decrease in the number of bacteria in the affected area than Comparative Example 3. Then, the skin condition of the test subject in which the number of bacteria was significantly reduced tended to be higher.

As described above, the liquid preparation and the ointment are inferior in the itch and the skin condition, which are characteristic symptoms of dry skin disease, and are vulnerable to external physical irritation. In addition, a plaster-type patch containing no water cannot sufficiently exert the effect of the medicinal component. In contrast to these techniques, the patch of the present invention solves all of the above drawbacks.

[0048]

The preparation of the present invention comprises an antipruritic ingredient, a bactericidal ingredient,
By incorporating a moisturizing component and using a dosage form called an adhesive patch, sufficient penetration of the above components and sustainability of the effect can be exhibited, and the affected area can be protected from scratches and other external stimuli.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display area A61K 31/05 ADB A61K 31/05 ADB 31/135 ADA 31/135 ADA 31/155 31/155 31 / 165 31/165 31/44 31/44 33/18 33/18

Claims (4)

[Claims] 1. An adhesive patch comprising an antipruritic component, a bactericidal component and a moisturizing component in a base. 2. The patch according to claim 1, wherein the antipruritic component is at least one selected from diphenhydramine, chlorpheniramine maleate and crotamiton. 3. The patch according to claim 1, wherein the bactericidal component is at least one selected from chlorhexidine gluconate, isopropylmethylphenol, and povidone iodine. 4. The moisturizing component is at least one selected from triglyceride, phospholipids, sodium hyaluronate, sodium chondroitin sulfate, glycerin, lactate, dl-pyrrolidone carboxylic acid, and urea.
Patch.