JPS60188314A - Antipruritic plaster - Google Patents

Abstract

PURPOSE:An antipruritic plaster that contains crotamiton as an active ingredient, thus developing satisfactorily medicinal effect of long duration. CONSTITUTION:Crotamiton of the formula: N-ethyl-N-(2-methylphenyl)-2-butenamide, is used as an active ingredient in an amount of 2-15wt% based on the total ointment. When the compound of the formula is used alone, the content is preferably more than 5wt%, much preferably 5-15wt%, while in case of combination with other antiinflammatories and antipruritics (such as glycyrrhetic acid) and antihistamic with antipruritic action such as difenhydramine, the content is more than 2wt%, preferably in the range from 5-20wt% in total. As the base of the antipruritic plaster, rubber tackifiers, or an acrylic resin such as acrylate polyester are used.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Application of the Invention] The present invention relates to an antipruritic plaster containing crotamiton as an antipruritic active ingredient. More specifically, the present invention relates to an anti-pruritic plaster that exhibits an anti-pruritic effect by incorporating 2 to 15% by weight of crotamiton based on the total amount of the plaster.

[Background of the Invention] Crotamiton is a pharmaceutical widely used for the treatment of eczema such as Qianfu, R measles, neurodermatitis, pruritus cutaneous, and childhood strophulus, and has the following structural formula.

[N-ethyl-N-(2-methylphenyl)-2-butenoamide] Conventionally, external preparations for antipruritic purposes have been liquid preparations.

The reality is that it is only commercially available in the form of ointment and hydrophilic ointment, and no patch is commercially available at all.

The same is true for crotamiton, and the only crotamiton preparations available are ointments based on polyethylene glycol, etc., while anti-pruritic and anti-inflammatory agents and anti-white spot preparations, which are combination preparations with steroid hormones, tolnaftate, etc., are expected to have the effect of assisting in the dissolution of crotamiton. A liquid agent that is slightly dissolved in a volatile solvent such as a lower alcohol.

Only hydrophilic ointments based on carboxyvinyl polymers and ointments such as those mentioned above are known.

9- However, in the treatment of skin pain and itching such as skin diseases and insect bites, it is necessary to select a dosage form that is appropriate for the cause of the itching and various skin symptoms. It volatilizes, crystals precipitate, and oily substances remain, making it impossible to expect sufficient medicinal efficacy or long-lasting medicinal efficacy, and oily substances have the disadvantage of causing stickiness and staining on clothing.

In addition, in the case of ointments, etc., the release of oily substances is unavoidable due to poor compatibility with the ointment base, and it is not possible to expect sufficient expression of medicinal efficacy or long-lasting medicinal efficacy.

There were problems such as staining of clothes due to the stickiness of the ointment itself.

On the other hand, in the field of patches, the development of new materials for patch bases has recently progressed rapidly, and their use in the medical field has become popular. As well as inflammatory agents.

Drugs that have excellent transdermal absorption or are preferable to be absorbed transdermally 1 For example, relatively new synthetic analgesic and anti-inflammatory drugs such as indomethacin, flufenamic acid, and ibuprofen, coronary vasodilators such as nifedipine and nicardipine, and various antibiotics. Various inventions have been made to incorporate drugs for other indications that have not been used in the field of patches.

Furthermore, it has been conventionally known that antihistamines such as diphenhydramines are added to analgesic and anti-inflammatory patches in order to achieve a suitable analgesic and anti-inflammatory effect.

However, patches for antipruritic purposes.

Patent documents generally list analgesics other than crotamiton as various drugs that can be used in the invention of patch bases, and generally list crotamiton as a drug to which crotamiton can be added as a solubilizing agent. Although some things have been described here and there, the reality is that they have not been substantially developed or invented.

Given this state of the art, the inventors of the present invention conducted intensive research with the aim of developing an antipruritic plaster with excellent long-lasting medicinal efficacy. As a result, we found that a plaster containing crotamiton as at least one of the antipruritic active ingredients has a long-lasting medicinal efficacy. The present invention was completed based on the findings that the present invention is superior.

Crotamiton itself is a high-boiling oily liquid.

It was originally believed that it would be difficult to formulate such an oily substance in large quantities in a medicinal patch in a medicinally effective amount. ), at least 2
It was completely unexpected that it was possible to blend the amount of 1% by weight or more (usually 5M% or more).

[Object of the Invention] One of the objects of the present invention is to provide an anti-pruritic plaster containing crotamiton as an anti-pruritic active ingredient. More specifically, the present invention provides an antipruritic plaster containing 2 to 15% by weight of crotamiton based on the total amount of the plaster.

[Structure of the Invention] The structure of the present invention is an anti-pruritic plaster containing crotamiton as an anti-pruritic active ingredient.

Here, as an anti-pruritic active ingredient, the amount of crotamiton that can sufficiently exert its anti-pruritic effect is 5% by weight or more based on the total amount of the product in the case of a single preparation, and it is clear that if it is a combination with other active ingredients, Although no specific standards have been set, it is considered a rough guideline of /2 to 15 for a single preparation;
% by weight or more.

The plaster used in the present invention is a plaster-type plaster in which an adhesive plaster containing an active ingredient is applied to a support such as flannel, plastic film, or nonwoven fabric.
e plaster or 5elf-adhesiv
eplaster) and includes various forms such as sheet, film, tape, and patch.

The antipruritic plaster of the present invention may contain crotamiton as at least one of the antipruritic active ingredients, and does not exclude the addition of other antipruritic active ingredients or other medicinal ingredients. As such a drug, it has excellent compatibility with crotamiton and plaster bases. Yes (・ indicates drugs that do not inhibit compatibility even if they coexist 1)
For example, anti-inflammatory and anti-pruritic agents such as glycyrrhetinic acid, glycyrrhetinic acid esters, glycyrrhizin (acid), and glycyrrhizin salts; antihistamine agents such as diphenhydramino and its salts, chlorphenoramine and its salts, which have anti-pruritic effects; anti-inflammatory effects Cortisone, which mainly expresses i! l[7 Local anesthetics and antipruritic agents such as cortisone, hydrocortisone, hydrocortisone acetate, glednisone, and prednisone; (・ indicates that it is desirable to include chlorhexidine gluconate, chlorhexidine hydrochloride, depotium chloride.

Examples include antibacterial agents such as isopropylmethylphenol, benozarkonium chloride and benzethonium chloride, and flavoring agents such as menthol.

To produce the antipruritic plaster of the present invention, first crotamiton or crotamiton and other active ingredients are added to a base and kneaded uniformly to produce a plaster.

In the case of crotamiton alone, the blending amount of the medicinal ingredient is preferably 5% by weight or more, particularly 5 to 15% by weight, based on the total amount of the paste.
In the case of a mixture with other active ingredients, it contains at least 2% by weight of crotamiton.

and the total amount of active ingredients is 5% by weight or more, especially 5 to 20%
The range of weight % is preferable.

The base material for producing the antipruritic plaster of the present invention includes a rubber adhesive component, other tackifier components, softeners, and other bases.Specifically, the rubber adhesive component includes natural rubber (N
R), styrene-butadiene copolymer (SBR), styrene-isoprene-styrene copolymer elastomer (
SIS).

Synthetic rubber such as silicone rubber (SR), other tackifier ingredients include Finton 0 (trade name 1 manufactured by Nippon Zeon Co., Ltd.),
aliphatic), Alcon ■ (product name).

Petroleum resins such as Arayo Kagaku Co., Ltd. (alicyclic type), rosin, hydrogenated rosin, ester gum, and other resins.

Polybutene and liquid paraffin are used as softeners.

Higher fatty acid esters such as isopropyl myristate, silicone, vegetable oil, etc., and other bases include antioxidants such as butylhydroxyanisole, guaiacol esters, dibutylhydroxytoluene, nordihydroguaiaretinoic acid, and preservatives such as thymol. agents, etc.

Note that polybuteno itself has adhesive properties.

Although it also behaves as a tackifying component, it has the effect of softening the rubber component without adding other softeners, so it is listed as one of the softeners.

In addition, when using acrylic resins such as acrylic ester polymers such as Brimal N-580 and ASE60 (both products of Acrylic Chemical Co., Ltd.), the rubber adhesive component, other tackifier components, and softeners may be added. It is possible to produce a suitable plaster without using it, and it is uniformly kneaded with the medicinal ingredients and the other bases mentioned above to form a paste for plaster.

Currently, solvent methods are used to produce plaster.

The hot-melt method and the emulsion method are used, and both methods can also be applied to the production of plaster of the present invention. When the solvent method is applied, a solution in which the medicinal ingredient is uniformly dissolved in the solvent, and and a solution in which the base is uniformly dissolved and kneaded uniformly to form a paste.The solvent used is an organic solvent that is compatible with both the medicinal ingredient and the base. Examples of solvents include toluene, benzene, carbon tetrachloride, and chloroform.

Methylene chloride, n-hexane, etc. are suitable.

Also, when applying the Emulshore method.

A method was adopted in which the entire plaster was made into an emulsion.

It is prepared using a latex emulsion of natural comb or synthetic rubber. Latex emulsion has a rubber content of 40
~80% is preferably used.

The base is a rubber-based adhesive component with an amount of about 15% to 15% based on the total amount of the paste.
Within the range of 60% by weight, the tackifier component and softener are selected appropriately taking into account the amount of rubber adhesive component used, but the tackifier component is approximately 15 to 60% by weight, and the softener is approximately 5 to 30% by weight. It is preferable to mix it in a range of 80 to 95% by weight.

In addition, when using acrylic resin as a base, the acrylic resin should be 95% by weight or less based on the entire plaster image, especially K 70.
The active ingredient may be blended with the above-mentioned other bases within a range of 95% by weight.

In addition, when the base is used as an emulsion,
As long as the amount of solid content is within the range of the above mixing ratio (
・0 When producing a paste, whether using a solvent method or other method, the order of addition of the base and medicinal ingredients should be set appropriately, taking into consideration the characteristics of the paste obtained and ease of operation. Alternatively, heating or sonication may be applied to promote dissolution.

The paste thus obtained is spread on a support and a release film is attached thereon, or it is spread on a release film and a support is attached thereon. In addition, K, which manufactures plaster by applying the above-mentioned solvent method or emulsion method, either distills off the solvent after spreading or removes water by drying.

Supports commonly used in the mechanical field, such as plastic films, flannel, and nonwoven fabrics, are used.

The release film is usually a plastic film that has been treated to be easy to peel (and leak).

The obtained plaster is processed into an appropriate shape, taking into account the indication, the area to which it is applied, and its various symptoms.

For example, for skin pruritus such as insect bite 1, it is most preferable to use a circular patch bond, which is convenient to carry and easy to apply.
.

[Effects of the Invention] The antipruritic plaster of the present invention exhibits sufficient medicinal efficacy and is excellent in its persistence, and is advantageous for intensive treatment of two localized areas, and has no unpleasant odor and does not stain clothes due to stickiness. Not at all.

Furthermore, when the plaster is in the form of a circular patch, it is extremely convenient to carry and is extremely convenient for uses such as insect bites.

Example 1゜ Polybutylene 285g 1 petroleum resin (manufactured by Nippon Zeono Co., Ltd.)

Fin Tono TJ-185) 47.3g, SI
S (styrene isoprene-styreno-tereblock copolymer resin, manufactured by Shell Chemical Co., Ltd., CARIFLEX TT
R-1107) 287 was added to an appropriate amount of toluene and dissolved by heating, and after cooling, 0.0% of diphenohydramine salicylate was added.
Add 5g dissolved in crotamiton and mix evenly.

After coating this on a mold release liner, toluene is distilled off and spread on a vinyl chloride film.

Examples 2 to 4 The following plasters were manufactured according to Example 1.

Example 2゜Total amount 1. OO, Og Solvent Toluene Appropriate amount Example 3゜Crotamiton 5.0 g Diphenhydramine hydrochloride 0.5 g Propylene glycol 2.5 g Total amount 100.0 g Solvent Toluene Appropriate amount Example 4 Crotamiton 5. Og Chrylphenirami maleate:y 0.5g Benzyl alcohol 5.0g Total amount 100.0g Solvent Toluene Appropriate amount Example Made by Kagakusha, Primal ■N-580-S
Add 152.5 g (solid content: 545-555%) and mix uniformly.

This is applied onto a release liner, dried, and then spread onto a vinyl chloride film.

Examples 6-7 The following plasters were manufactured according to Example 5.

Example 6 Crotamiton 5.0 g Diphenhydramino 1.0 g Isopropylmethylphenol 0.5 g Antioxidant 0.1 g Example 7゜Crotamiton 10.0 g Diphenhydramine 0.5 g Antioxidant 0.1 g Example 8゜Polybuteno 15 .0g, petroleum resin (manufactured by Nippon Zeon Co., Ltd.).

Crotamiton (1,85) 4.0.0g and 4.9g of liquid paraffin are heated and dissolved at 100-120C, and after cooling to an internal temperature of 50-60CK, 0.1g of antioxidant is added to 10.0g of crotamiton. Add the dissolved material to g and mix uniformly,
, B, R, latex 29.8g (using 60% solid content), N, R, latex 202g (using 60% solid content)
is added and mixed uniformly, coated on a release liner, dried, and spread on a vinyl chloride film.

Examples 9-10 The following plastering agent was manufactured according to Example 8.

Example 9 Crotamiton 5.0g Diphenhydramino salicylate 0.5g Antioxidant
0.1 g Petroleum resin (Qui/Ton @ U-185) 37.5 g Polybuteno 20.0 g Liquid paraffin 4.9 g Example lO Crotamiton 2.5 g Diphenhydramino 2.0 g Isopropylmethylphenol 0.5 g Isopropyl myristate 2.0 g Antioxidant 0.1 g Petroleum resin (Qui/ton U-185) 41.8 g Polybutene 16.2 g Liquid paraffin 4.9 g

Claims (2)

[Claims] (1) Anti-pruritic plaster containing crotamite as an anti-pruritic active ingredient (2) The antipruritic plaster according to claim (1), which contains 2 to 15% by weight of crotamiton based on the total amount of the plaster.