JP3338877B2 - Spray for pruritic skin disease - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a spray for pruritic skin diseases. More specifically, the present invention relates to a spray for pruritic skin diseases, which contains a predetermined amount of an antipruritic, a local anesthetic, a bactericide, an astringent, and a hygroscopic agent as an active ingredient.

[0002] According to the spray of the present invention, it removes sweat and waste products from the skin, alleviates the symptoms of itching, redness and rash due to skin diseases such as hot flashes, eczema and rash, and treats the diseases. It is valid. Further, since the agent according to the present invention is a spray, it is useful in that it can uniformly apply a drug which has been conventionally difficult to apply. Furthermore, when the propellant of the present invention is an aerosol containing a propellant such as a liquefied gas, the affected part is instantaneously cooled by spraying the drug, thereby exhibiting a higher anesthetic effect, and thus having a rapid antipruritic effect and anti-inflammatory effect. And so on.

[0003]

2. Description of the Related Art Conventionally, for treatment of skin diseases, particularly eczema caused by sweat and waste products, use is mainly made of tobacco powder (zinc white talc powder), and treatment of these skin diseases accompanied by eczema, inflammation and itch. Antipruritic agents such as antihistamines and corticosteroids are used.

[0004] However, although starch is effective for drying the affected area, it does not have anti-inflammatory and antipruritic effects and cannot be expected to have any symptomatic effect. In addition, since the powder is splashed, it is difficult to use because the powder is scattered around when applied, and the skin and clothes are stained. Further, since some tools are required for the application, it takes time and effort to apply, and it is undeniable that the applicator may become a medium of infection, such as contamination of the affected part via the applicator.

[0005] In addition, antipruritic agents are not a fundamental remedy for skin diseases such as hot flashes, and commonly used antipruritic agents include:
Many of them have a creamy form, and thus have problems in use such as soiling of hands during application, soiling of clothes, poor drying properties, and the inability to wear clothes immediately.

[0006]

DISCLOSURE OF THE INVENTION The present invention has been made to solve the above problems, and an object of the present invention is to provide an external preparation for skin diseases which can be used in a sanitary manner without soiling hands and clothing during use. It is another object of the present invention to provide a spray for pruritic skin disease which is excellent in anti-inflammatory effect and antipruritic effect.

[0007]

Means for Solving the Problems In the development of an external preparation for skin effective for pruritic skin diseases accompanied by itching or inflammation such as heat rash, eczema and rash, the present inventors have studied a specific medicinal ingredient including an antipruritic agent and a hygroscopic agent. It has been found that the above-mentioned problems can be solved by combining the agents and further using them as sprays. The present invention is based on this finding.

[0008] That is, the present invention is a therapeutic agent for pruritic skin disease comprising any of the following embodiments.

[0009] (1) an antipruritic agent as an active ingredient, topical anesthetics, fungicides, corn star as astringents, and moisture absorbents
60 to 90 weight per 100 parts by weight of components other than propellant
Propane, normal as a propellant
At least one of butane and isobutane
Pruritic skin in the form of a spray, containing liquefied petroleum gas
Disease treatment agent.

(2) As described in (1), which further contains a lubricant.
The therapeutic agent for pruritic skin disease described above.

(3) Drug component containing active ingredient and propellant
Is a drug component: propellant (weight ratio) of 1:
The pruritic skin disease according to (1) or (2), which is 5 to 9.
Therapeutic agent.

(4) 100 parts by weight of components other than the propellant
0.5 to 5 parts by weight of antipruritic, 0.5 to 5 parts by weight of local anesthetic
10 parts by weight, 0.05-1 part by weight of fungicide and astringent
(1) to (3) containing 1 to 20 parts by weight of
The therapeutic agent for pruritic skin disease according to any one of the above.

(5) The pruritus according to any of (1) to (4), wherein the antipruritic comprises at least one selected from the group consisting of diphenhydramine or a salt thereof, chlorpheniramine maleate and isothipendyl hydrochloride.
For treating skin diseases .

(6) The method according to any one of (1) to (5), wherein the local anesthetic comprises at least one selected from the group consisting of lidocaine, procaine, ethyl aminobenzoate, dibucaine and a hydrochloride thereof. Pruritic skin
Agent for treating skin diseases .

(7) The fungicide contains at least one selected from the group consisting of benzalkonium chloride, benzethonium chloride , chlorhexidine gluconate, chlorhexidine hydrochloride, isopropylmethylphenol and cetylpyridinium chloride (1) to (6). ) The therapeutic agent for pruritic skin disease according to any one of the above.

(8) The pruritic skin disease according to any of (1) to (7), wherein the astringent comprises at least one selected from the group consisting of zinc oxide, aluminum sulfate, potassium aluminum sulfate and azulene. Cure
Remedies .

(9) Applicable to at least one kind of pruritic skin disease selected from the group consisting of rash, rash, diaper rash, syrup, rash, insect bite, pruritus and prurigo (1) to ( The scratch according to any of 8)
A therapeutic agent for pruritic skin disease . "

[0018]

BEST MODE FOR CARRYING OUT THE INVENTION The drug for pruritic skin diseases of the present invention is an external preparation for skin containing an antipruritic agent, a local anesthetic, a bactericide, an astringent and a hygroscopic agent as an active ingredient, and is a spray. Characterized by the following aspects.

The pruritic skin disease targeted by the present invention broadly refers to a skin disease accompanied by itch, such as allergic dermatitis, infectious dermatitis, contact dermatitis, parasitic dermatitis, and insect dermatitis. It widely covers eczema caused by sweat and skin waste. More specifically, heat rash, rash (including diaper rash), morbidity, rash, insect bite,
Examples include pruritus cutaneous, prurigo, athlete's foot, and the like, and preferably rash (including diaper rash).

The present invention is characterized in that it is in the form of a propellant as described above.

The form of the spray is not particularly limited as long as the drug component contained therein can be sprayed out and applied to the skin surface. Therefore, a propellant is added to a drug containing an antipruritic agent, a local anesthetic, a bactericide, an astringent, and a hygroscopic agent as an active ingredient, and the propellant is filled into a container having, for example, a push-type valve device. It can be a so-called aerosol which sprays the drug by pressure.

According to the aerosol, the affected area of the skin can be instantaneously cooled by the propellant ejected together with the drug, and the immediate effect of the propellant of the present invention can be further improved.

The antipruritic agent used in the present invention is not particularly limited as long as it has an action of relieving itch and is used as an external preparation, and any of them can be used.

More specifically, antihistamines such as diphenhydramine and salts thereof, chlorpheniramine maleate (including d-chlorpheniramine maleate) and isotipendyl hydrochloride; fluocinolone acetonide, fluocinonide, betamethasone valerate , Betamethasone dipropionate, betamethasone butyrate, hydrocortisone acetate, methylprednisolone acetate, dexamethasone, dexamethasone valerate, dexamethasone propionate, fludoxycortide, flumethasone pivalate,
Beclomethasone propionate, hydrocortisone butyrate,
Clobetasol propionate, diflucortron valerate, halcinide, prednisolone acetate valerate, amcinide, hydrocortisone butyrate propionate, clobetasone butyrate, diflorazone acetate, diflupredner, alclomethasone propionate, budesonide, deprodone propionate, mometasone furoate, etc. Corticosteroids; non-steroidal agents such as ibuprofen piconol, suprofen, bufexamac, bendazac, ufenamate; coal tar, carboxylate, naphthol, menthol, thymol, salicylic acid, chloral hydrate, aconitine, tannin and the like. But,
It is not limited to these examples.

Preferred are antihistamines such as diphenhydramine and salts thereof. Here, examples of the salt include an inorganic acid salt such as a hydrochloride and an organic acid salt such as a lauryl sulfate, and preferably a hydrochloride.

[0026] These antipruritic agents may be used alone or in combination of two or more.

The proportion of these antipruritic agents is not particularly limited and is appropriately selected from the types and amounts of other active ingredients and the type and degree of skin diseases. , 0.5 to 5 parts by weight, preferably 0.5 to 2 parts by weight. Here, 100 parts by weight of the propellant component means the total volume of the propellant of the present invention excluding the propellant described below (the same applies to the following description).

The hygroscopic agent used in the present invention is a chemical absorbent.
It is a pharmaceutically inert carrier and has a hygroscopic property. Such a hygroscopic agent has such an effect,
There is no particular limitation as long as it is used for external use, and any of them can be used.

Specifically, corn starch, talc, tragacanth, sodium alginate, kaolin, polyethylene powder, silicon dioxide, soft silicic anhydride, wheat starch, lactose, magnesium carbonate, starch acrylate, sodium alginate, agar powder, synthetic silica Examples thereof include aluminum oxide, titanium oxide, and gelatin. These are preferably in powder form. Preferred are powders of corn starch, silicon dioxide, talc, polyethylene powder and the like.

These may be used alone or in combination of two or more. The mixing ratio of these moisture absorbents is not particularly limited, and is appropriately selected from the types and amounts of other active ingredients and the types and degrees of skin diseases.
To 95 parts by weight, preferably 60 to 90 parts by weight.

The local anesthetic used in the present invention includes:
Without particular limitation, those suitable for surface anesthesia can be broadly listed. More specifically, aminobenzoic acid alkyl ester preparations such as ethyl aminobenzoate (benzocaine), orthocaine and salts thereof; aminobenzoic acid alkamine ester preparations such as procaine, tetracaine, proparacaine and salts thereof; dibucaine and And dixaine-based preparations such as lidocaine, mepivacaine, bupivacaine and salts thereof. However, it is not limited to these examples. Here, the salt is not particularly limited as long as it is a pharmaceutically acceptable salt, and examples thereof include salts of inorganic acids such as hydrochloride.

Suitable local anesthetics include lidocaine, lidocaine hydrochloride, dibucaine hydrochloride, ethyl aminobenzoate and procaine hydrochloride.

[0033] These local anesthetics may be used alone or in combination of two or more. The mixing ratio of these local anesthetics is not particularly limited, and is appropriately selected from the types and amounts of other active ingredients and the types and degrees of skin diseases.
0.5 to 10 parts by weight, preferably 0.1 to 10 parts by weight per 0 parts by weight.
5 to 2 parts by weight.

The bactericide used in the present invention is not particularly limited as long as it has a bactericidal action and is used externally, and any of them can be used.

More specifically, positive soaps such as benzalkonium chloride and benzethonium chloride; phenols such as isopropylmethylphenol and chlorophenol; phenolic acids such as cresol, hexachlorophene and bitionol; acrinol; methylrosaniline chloride; Furans; alcohols such as ethanol; iodine compounds such as iodoform, iodine tincture, and povidone-iodine; chloro compounds such as bleached meal and chloramine; hexidine preparations such as chlorhexidine, chlorhexidine gluconate, chlorhexidine hydrochloride; and cetylpyridinium chloride. Can be. However, it is not limited to these examples.

Preferred are positive soaps such as benzalkonium chloride and benzethonium chloride, cetylpyridinium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, and isopropylmethylphenol.

These fungicides may be used alone or in combination of two or more. The mixing ratio of these fungicides is not particularly limited, and is appropriately selected from the types and amounts of other active ingredients and the types and degrees of skin diseases. 05 to 2 parts by weight, preferably 0.1 to
1 part by weight can be mentioned.

The astringent used in the present invention is not particularly limited as long as it has an astringent action and is used externally, and any of them can be used.

Specifically, tannic acids such as tannic acid and gallic acid; zinc compounds such as zinc oxide (zinc white), zinc sulfate and zinc p-phenolsulfonate; lead compounds such as lead acetate and lead monoxide; Examples include aluminum compounds such as aluminum sulfate, potassium potassium (dry) aluminum sulfate, aluminum chloride, allantochlorohydroxyaluminum and chlorohydroxyaluminum, and metal compounds such as bismuth subgallate; azulene. Preferably, zinc oxide, aluminum sulfate,
Potassium aluminum sulfate and azulene.

These astringents may be used alone or in a combination of two or more. The mixing ratio of these astringents is not particularly limited and is appropriately selected from the type and amount of other active ingredients and the type and degree of skin disease.
1 to 20 parts by weight, preferably 5 to 10 parts by weight, per part by weight.

The spray of the present invention may contain optional components in addition to the above components as long as the effects of the present invention are not impaired.

The optional components include, for example, carriers, bases, solvents and various additives used in pharmaceuticals such as external preparations. Specific examples include lubricants such as magnesium stearate, ethanol and isopropyl Examples thereof include alcohols such as alcohols, solvents such as isopropyl myristate, and other additives such as adhesion improvers, stabilizers, preservatives, dissolution aids, emulsifiers, suspending agents, and pH adjusters.

The spray of the present invention is prepared by mixing the above-mentioned antipruritic, local anesthetic, bactericide, astringent and hygroscopic agent as active ingredients and, if necessary, further mixing the above-mentioned optional ingredients. The composition is prepared by filling the container with the drug component together with the propellant.

The mode of the composition containing the active ingredient is not particularly limited as long as it can be filled in a sprayer and can be ejected or ejected in the form of a mist, and examples thereof include a solution, a suspension, and an emulsion. Can be.

The propellant is not particularly limited as long as it does not affect the efficacy of the active ingredient of the present invention and is pharmaceutically acceptable. Any of those usually used in the art can be used. be able to.

Specifically, fluorinated hydrocarbons, fluorocarbons;
Liquefied gas such as liquefied petroleum gas, pentane gas, dimethyl ether or the like containing at least one of propane, normal butane and isobutane; carbon dioxide; nitrogen gas. A liquefied petroleum gas containing at least one of propane, normal butane and isobutane, and a liquefied gas such as dimethyl ether, more preferably a liquefied petroleum gas. The liquefied petroleum gas usually contains propane, normal butane or isobutane alone or in combination of two or more, and contains 90% by weight or more, preferably 95% or more, and contains pentane gas and the like as other components. Is also good.

In the propellant of the present invention, the mixing ratio of the drug component containing the above-mentioned active ingredient and the propellant is not particularly limited, but is usually 1: 1 as the drug component: propellant (weight ratio).
1 to 100, preferably 1 to 1 to 10, more preferably 1 to 5 to 9.

The spray agent for pruritic skin disease of the present invention is applied to a dermatological lesion accompanied by itch and can promptly alleviate and calm itching and inflammation, and also has a moisture absorbing and astringent action. The affected area infiltrated by the exudation of lymph fluid can be protected and dried by forming a film with the composition, thereby promoting early healing of the affected area. In addition, according to the spray of the present invention, there is no risk of soiling the hands because the hands are not used for applying the medicine, and the medicines can be contaminated even when used for various different persons because the application does not involve other tools. It can be used hygienically to the end.

The amount of the propellant of the present invention varies depending on the type of the disease, the degree of the symptom, and the size of the affected part, and cannot be specified unconditionally. However, it can be usually used in the range of about 0.01 to 10 g per day. This is applied to the affected area once a day or in an appropriate number of times.

[0050]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples and Experimental Examples, but the present invention is not limited to the Examples and the like. In addition,% described below means% by weight unless otherwise specified.

Example 1 <Formulation> Diphenhydramine 1.0% Lidocaine 2.0% Benzethonium chloride 0.1% Zinc oxide 10.0% Magnesium stearate 0.5% Corn starch 74.4% Isopropyl myristate 12.0% A total of 100.0% of a composition having the above formulation was prepared and powdered. The mixture was filled in a sprayer so as to have a ratio, thereby preparing a spray (aerosol) of the present invention.

Example 2 <Formulation> Diphenhydramine hydrochloride 1.5% Ethyl aminobenzoate 3.0% Chlorhexidine gluconate 0.1% Potassium aluminum sulfate 15.0% Magnesium stearate 1.0% Silicon dioxide 60.4% Isopropyl myristate 19.0% Total 100.0% A composition having the above formulation was prepared and made into a powder, and the composition was added to a liquefied petroleum gas (propellant: containing 95% or more of normal butane) in a proportion of 1%. : 9 (weight ratio) to prepare a spray (aerosol) according to the present invention.

Example 3 <Formulation> Chlorpheniramine maleate 1.0% Procaine 1.5% Cetylpyridinium chloride 0.2% Aluminum sulfate 15.0% Magnesium stearate 0.5% Talc 66.8% Myristic acid Isopropyl 15.0% Total 100.0% A composition having the above formulation was prepared and made into a powder, and the composition was 1: 9 with respect to liquefied petroleum gas (propellant: containing 95% or more of normal butane). (A weight ratio) was filled into a sprayer to prepare a spray (aerosol) of the present invention.

Example 4 <Formulation> Isotipendyl hydrochloride 3.0% Dibucaine 1.5% Isopropyl methylphenol 0.3% Azulene 10.0% Magnesium stearate 0.5% Polyethylene powder 74.7% Isopropyl myristate 0% Total 100.0% A composition comprising the above formulation was prepared and made into a powder, and the composition was 1: 9 (weight ratio) to liquefied petroleum gas (propellant: containing 95% or more of normal butane). ) To prepare a spray (aerosol) of the present invention.

Experimental Example 1 The spray agent of the present invention prepared in Example 1 was tested for its antipruritic effect on 60 volunteers suffering from sweat rash, atopic dermatitis, contact dermatitis or parasitic dermatitis. The immediate effect, the persistence of the antipruritic effect, the alleviation effect of the redness symptom and the alleviation effect of the papule symptom were evaluated. Specifically, 2 g of the propellant of the present invention was sprayed onto 200 cm ² of the affected area of the skin, and left as it was for 4 hours to examine each effect.

As a comparative experiment, propellants each containing the active ingredient of the present invention shown in Table 1 alone (Comparative Examples 1 to 5)
7: LPG containing 95% or more of normal butane as a propellant
Used), a commercially available antihistamine-containing cream (Comparative Example 8: containing 1% by weight of diphenhydramine as an antihistamine), a commercially available antihistamine-containing liquid (Comparative Example 9:
Each effect was similarly evaluated using diphenhydramine (containing 1% by weight as an antihistamine) and commercially available sky pollen (Comparative Example 10).

[0057]

[Table 1]

The evaluation criteria for each experiment are as follows: <Immediate effect of antipruritic effect> A: Immediately after use of the drug, an antipruritic effect was obtained. △: The antipruritic effect was obtained in 10 minutes after using the drug. ×: The antipruritic effect was not obtained until 60 minutes after using the drug. XX: No antipruritic effect was obtained after using the drug. .

<Persistence of antipruritic effect> A: The antipruritic effect was continuously obtained 8 hours after the use of the drug. ：: The antipruritic effect was continuously obtained 4 hours after the use of the drug. 1 hour after use of the drug, the antipruritic effect disappeared. X: 1 minute after the use of the drug, the antipruritic effect disappeared. XX: No antipruritic effect was obtained after using the drug.

<Easing Effect of Redness Symptoms> A: The redness of the affected area was remarkably improved. ：: The redness of the affected area was significantly improved. Δ: The redness of the affected area was improved. X: Redness of the affected area was observed. The symptoms were hardly improved. XX: The redness of the affected area was not improved at all or worsened.

<Easy effect of papule symptom> A: papule symptom of the affected area was significantly improved o: papule symptom of the affected area was significantly improved Δ: papule symptom of the affected area was improved x: papule of the affected area The symptoms were hardly improved. XX: The papule symptoms in the affected area were not improved at all or worsened.

Table 2 shows the results. The results were obtained by comprehensively judging the results of 60 volunteers.

[0063]

[Table 2]

From these results, it can be seen that the spray of the present invention has an immediate and sustained effect on itch caused by various skin diseases, and has an excellent therapeutic effect on itch due to sweat rash, redness and papules. You can see that it works.

In addition, the use of the spray of the present invention in advance in a portion prone to sweat rash prevented the appearance of sweat rash symptoms.

From the above, it was confirmed that the spray of the present invention is useful as an agent for preventing or treating various pruritic skin diseases.

EXPERIMENTAL EXAMPLE 2 With respect to the above-mentioned 60 volunteers, the spraying properties of the present invention of Example 1 were evaluated with respect to the dispersibility, ease of use during use and portability of Comparative Examples 8, 9 and 10. Questionnaires were taken in comparison with creams, solutions and powders.

Table 3 shows the results.

[0069]

[Table 3]

[0070]

[0071]

[0072]

Although the spray of the present invention has a slight scattering of the drug compared to the cream or the liquid, it does not require the trouble of once applying it to the hand and is easy to use. There is no risk of contamination by dust, garbage, or bacteria because it does not come into contact with the like. In view of the above, it was determined that the spray of the present invention is a therapeutic agent for pruritic skin disease that is easy for consumers to handle and excellent in portability.

Continuation of the front page (56) References JP-A-9-110677 (JP, A) JP-A-9-143079 (JP, A) JP-A-3-148212 (JP, A) JP-A-8-12964 (JP) , A) JP-A-62-148586 (JP, A) "Pharmaceutical Handbook 4th Edition", Pharmaceutical Times Co., Ltd., published in 1987, pp. 1118-1119 (58) Fields investigated (Int. Cl. ⁷ , DB Name) A61K 9/12

Claims (9)

(57) [Claims] Claims: 1. As an active ingredient, 100 parts by weight of an ingredient other than an antipruritic, a local anesthetic, a bactericide, an astringent, and a propellant.
60 to 90 parts by weight of cornstar as a moisture absorbent
And propane and normal butane as propellants
Or at least one of isobutane
Treatment of pruritic dermatosis in spray form containing liquefied petroleum gas
Agent. 2. The method according to claim 1, further comprising a lubricant.
A therapeutic agent for pruritic skin disease. 3. A combination of a drug component containing an active ingredient and a propellant.
The ratio is 1: 5 to 9 as drug component: propellant (weight ratio).
3. The treatment for pruritic skin disease according to claim 1 or 2.
Agent. 4. The composition of the present invention comprises 100 parts by weight of a component other than the propellant.
0.5 to 5 parts by weight of itching agent, 0.5 to 10 parts of local anesthetic
Parts, fungicide 0.05 to 1 part by weight and astringent 1 to 1
4. The composition according to claim 1, wherein the content is 20 parts by weight.
2. The therapeutic agent for pruritic skin disease according to item 1. 5. An antipruritic agent comprising diphenhydramine or diphenhydramine.
Its salts, chlorpheniramine maleate and isothiocyanate
At least one selected from the group consisting of
5. The pruritic skin disease according to any one of claims 1 to 4
Therapeutic agent. 6. The pruritus according to any one of claims 1 to 5, wherein the local anesthetic comprises at least one selected from the group consisting of lidocaine, procaine, ethyl aminobenzoate, dibucaine and a hydrochloride thereof . Skin disease cure
Remedies . 7. A fungicide, benzalkonium chloride, salt
The therapeutic agent for pruritic skin disease according to any one of claims 1 to 6, comprising at least one selected from the group consisting of benzethonium bromide , chlorhexidine gluconate, chlorhexidine hydrochloride, isopropylmethylphenol and cetylpyridinium chloride. 8. The therapeutic agent for pruritic skin disease according to claim 1, which comprises at least one selected from the group consisting of zinc oxide, aluminum sulfate, potassium aluminum sulfate and azulene as an astringent. 9. The method according to claim 1, which is applied to at least one kind of pruritic skin disease selected from the group consisting of rash, rash, diaper rash, syrup, rash, insect bite, pruritus and prurigo. Pruritic skin according to any of the above
Agent for treating skin diseases . "