JP7299682B2 - Skin topical composition - Google Patents

Description

The present invention relates to an external skin composition containing ufenamate and zinc oxide.

Ufenamate is used as a non-steroidal anti-inflammatory agent by being blended in pharmaceuticals or quasi-drugs for external use on the skin. For example, Patent Literature 1 discloses that an emulsified composition for external use on the skin in which heparin is blended with ufenamate exhibits an excellent anti-inflammatory action.

Zinc oxide has various uses such as an anti-inflammatory agent, an antibacterial agent (bactericidal agent), an ultraviolet scattering agent, or an astringent agent, and is used by blending it in pharmaceuticals, quasi-drugs, or skin preparations for external use in cosmetics. For example, Patent Document 2 discloses a composition for external use on the skin that may contain zinc oxide as an anti-inflammatory ingredient, and Patent Document 3 discloses that zinc oxide may be contained as an antibacterial agent for the treatment of acne and the like. Suitable compositions are disclosed, Patent Document 4 discloses a sunscreen external composition that may be formulated with zinc oxide as an ultraviolet scattering agent, and Patent Document 5 discloses zinc oxide as an astringent. A skin cosmetic that may contain zinc is disclosed.

On the other hand, itching of the skin associated with skin diseases such as eczema and rashes is not only uncomfortable for patients, but also causes symptoms such as eczema and rashes to aggravate due to additional irritation caused by itching, leading to a vicious cycle of more intense itching. often do. For this reason, for skin itching, topical therapeutic agents containing antihistamines (diphenhydramine, etc.), antipruritic agents (crotamiton, etc.), local anesthetics (dibucaine, lidocaine, etc.), steroids (dexamethasone, hydrocortisone, etc.), etc. as active ingredients and internal medicines are applied.

However, topical therapeutic agents for treating itchy skin may not be able to effectively suppress itching, or may even aggravate itching. For example, antihistamines have a slow onset of antipruritic effects due to their mechanism of action, and may not be able to effectively suppress itching. Antipruritics and local anesthetics have side effects of rashes, and steroids have side effects due to excessive immunosuppression, both of which can exacerbate itching.

JP 2015-199709 A JP 2015-086224 A Japanese translation of PCT publication No. 2014-501776 Japanese Patent Application Laid-Open No. 2001-220338 JP-A-10-182347

Ufenamate and zinc oxide are known to be used in pharmaceuticals, quasi-drugs, or cosmetics, respectively. It is also unknown about the action and effect on the skin due to the combination of

An object of the present invention is to provide a novel formulation useful as an external composition.

The present inventors conducted intensive studies and found that although neither ufenamate nor zinc oxide is an active ingredient against skin itching, when they are combined into an external composition, they have an effect against skin itching (hereinafter simply referred to as " It is also described as "antipruritic effect", and the property of producing an antipruritic effect is also described as "antipruritic"). The present invention was completed by further studies based on this finding.

That is, the present invention provides inventions in the following aspects.
Section 1. An external skin composition containing ufenamate and zinc oxide.
Section 2. Item 1. The external composition for skin according to Item 1, which is used for antipruritic purposes.

By containing ufenamate and zinc oxide, the external composition for skin of the present invention can exhibit an antipruritic effect.

4 shows the results of the pruritus test in Test Example 1. FIG.

The composition for external use on skin of the present invention is characterized by containing ufenamate and zinc oxide. The composition for external use on skin of the present invention will be described in detail below.

Ufenamate The external composition for skin of the present invention contains ufenamate. Ufenamate, also called butyl flufenamate, is an ingredient known as a fat-soluble non-steroidal anti-inflammatory drug. Ufenamate by itself does not exert an effective antipruritic effect, and even acts to worsen the antipruritic effect in the initial stage after application. It becomes possible to express effective antipruritic properties by.

In the external composition for skin of the present invention, the content of ufenamate is appropriately set according to the efficacy to be imparted, and is, for example, 1 to 20% by weight. From the viewpoint of effective performance, it is preferably 2 to 10% by weight, more preferably 3 to 7% by weight.

Zinc Oxide The external composition for skin of the present invention contains zinc oxide. Zinc oxide is an ingredient known as an anti-inflammatory agent, UV scattering agent, or astringent. Zinc oxide by itself does not exhibit effective antipruritic properties, but when combined with ufenamate, it becomes possible to exhibit effective antipruritic properties.

In the composition for external use on the skin of the present invention, the content of zinc oxide is appropriately set according to the efficacy to be imparted, and is, for example, 1 to 40% by weight. From the viewpoint of effective performance, it is preferably 3 to 35% by weight, more preferably 5 to 35% by weight.

In the composition for external use on skin of the present invention, the ratio of zinc oxide to ufenamate is determined according to the respective contents of ufenamate and zinc oxide. parts by weight. From the viewpoint of exhibiting antipruritic properties more effectively, the amount is preferably 0.5 to 20 parts by weight, more preferably 0.8 to 10 parts by weight, per 1 part by weight of ufenamate.

Other Ingredients The composition for external use on skin of the present invention may contain other pharmacological ingredients in addition to the ingredients described above, if necessary. Examples of such pharmacological ingredients include antihistamines (diphenhydramine, chlorpheniramine maleate, etc.), local anesthetics (lidocaine, dibucaine, procaine, tetracaine, bupipacine, mepipacaine, chloroprocaine, proparacaine, meprilcaine, or salts thereof, Benzoic acid alkyl ester (e.g. ethyl aminobenzoate, diethylaminoethyl parabutylaminobenzoate hydrochloride), orthocaine, oxethazain, oxypolyentoxydecane, rot extract, percamimpase, tecitdecitin, etc.), anti-inflammatory agents (glycyrrhetinic acid, glycyrrhetinate, Allantoin, salicylic acid, glycol salicylate, methyl salicylate, indomethacin, felbinac, diclofenac sodium, loxoprofen sodium, etc.), fungicides (benzalkonium chloride, decalinium chloride, benzethonium chloride, cetylpyridinium chloride, isopropylmethylphenol, chlorhexidine hydrochloride, chlorhexidine gluconate) , ammonia water, sulfadiazine, lactic acid, phenol, etc.), antipruritic agents (crotamiton, thianthol, etc.), skin protective agents (collodion, castor oil, etc.), blood circulation-promoting ingredients (nonylic acid vanillylamide, benzyl nicotinate, capsaicin, red pepper extract, etc.) ), cooling agents (menthol, camphor, etc.), vitamins (vitamins A, B, C, D, etc.), mucopolysaccharides (sodium chondroitin sulfate, hyaluronic acid, etc.) and the like.

In addition to the components described above, other bases and additives commonly used for external preparations for skin may be included, if necessary. Such base materials and additives are not particularly limited as long as they are pharmaceutically acceptable. , 1,3-butylene glycol, etc.); Oils (olive oil, safflower oil, soybean oil, camellia oil, corn oil, rapeseed oil, sunflower oil, cottonseed oil, peanut oil, lard, squalane, fish oil, etc.) , Mineral oil (liquid paraffin, paraffin, gelatinized hydrocarbon, vaseline, etc.), waxes/waxes (beeswax, carnauba wax, candelilla wax, ceresin, rice wax, microcrystalline wax, etc.), ester oil (isopropyl myristate, Isopropyl adipate, diethyl sebacate, isopropyl sebacate, isopropyl palmitate, cetyl palmitate, ethyl oleate, etc.), fatty acid alkyl esters, fatty acids (stearic acid, oleic acid, palmitic acid, behenic acid, linoleic acid, lanolin, etc.) , fatty acid esters (cetyl palmitate, isopropyl palmitate, ethyl linoleate, etc.), higher alcohols (stearyl alcohol, cetanol, behenyl alcohol, myristyl alcohol, oleyl alcohol, hexadecyl alcohol, lanolin alcohol, etc.), cholesterol, tri-2-ethylhexane Oily bases such as glyceryl acid, cetyl 2-ethylhexanoate, silicone oil (dimethylpolysiloxane, cyclic silicone, etc.); POE (10 to 50 mol) phytosterol ether, POE (10 to 50 mol) dihydrocholesterol ether, POE ( 10-50 mol) 2-octyldodecyl ether, POE (10-50 mol) decyltetradecyl ether, POE (10-50 mol) oleyl ether, POE (2-50 mol) cetyl ether, POE (5-50 mol) Polyoxyethylene alkyl such as behenyl ether, POE (5-30 mol) polyoxypropylene (5-30 mol) 2-decyltetradecyl ether, POE (10-50 mol) polyoxypropylene (2-30 mol) cetyl ether Ethers, phosphoric acids and phosphates thereof (POE cetyl ether sodium phosphate, etc.), POE (20-60 mol) sorbitan monooleate, POE (10-60 mol) sorbitan monoisostearate, POE (10-80 mol ) glyceryl monoisostearate, POE (10 to 30 mol) glyceryl monostearate, POE (20 to 100 mol)/polyoxypropylene-modified silicone, POE/alkyl-modified silicone, polyethylene glycol monolaurate, polyethylene glycol monopalmitate, Polyethylene glycol monostearate, polyethylene glycol dilaurate, polyethylene glycol dipalmitate, polyethylene glycol distearate, polyethylene glycol dioleate, polyethylene glycol diricinoleate, polyoxyethylene hydrogenated castor oil (5-100), polysorbate (20-85) ), surfactants such as glycerin fatty acid esters (glyceryl monostearate, etc.), hydrogenated soybean phospholipids, hydrogenated lanolin alcohol; cooling agents (menthol, camphor, borneol, peppermint water, peppermint oil, etc.), preservatives ( methylparaben, propylparaben, benzoic acid, sodium benzoate, sorbic acid, etc.), flavoring agents (citral, 1,8-cionell, citronellal, farnesol, etc.), coloring agents (tar pigments (brown No. 201, blue No. 201, yellow No. 4, Yellow No. 403, etc.), cacao pigment, chlorophyll, aluminum oxide, etc.), thickeners (carboxyvinyl polymer, hypromellose, polyvinylpyrrolidone, sodium alginate, ethyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, xanthan gum, carrageenan, etc.), pH adjuster (phosphoric acid, hydrochloric acid, citric acid, sodium citrate, succinic acid, tartaric acid, sodium hydroxide, potassium hydroxide, triethanolamine, triisopropanolamine, etc.), wetting agent (dl-sodium pyrrolidonecarboxylate solution, D-sorbitol solution, macrogol, etc.), stabilizers (dibutylhydroxytoluene, butylhydroxyanisole, sodium edetate, sodium metaphosphate, L-arginine, L-aspartic acid, DL-alanine, glycine, sodium erythorbate, gallic acid propyl acid, sodium sulfite, sulfur dioxide, chlorogenic acid, catechin, rosemary extract, etc.), antioxidants, UV absorbers, chelating agents, adhesives, buffers, solubilizers, solubilizers, preservatives, etc. Additives are included.

Properties, Formulations, etc. The properties of the composition for external use on the skin of the present invention are not particularly limited, and include aqueous liquid compositions, aqueous gel compositions, oily gel compositions, emulsion compositions, and the like. Among these, from the viewpoint of formulation stability, preferred are aqueous gel compositions, oily gel compositions, and emulsion compositions, and more preferred are emulsion compositions. The emulsified state of the emulsified composition may be either an oil-in-water type or a water-in-oil type, but the oil-in-water type is preferred from the viewpoint of feeling during use such as suppression of stickiness.

The formulation form of the external composition for skin of the present invention is not particularly limited, and examples thereof include lotions, emulsions, ointments, creams and the like. Among these, emulsions and creams are preferred from the viewpoint of formulation stability.

Specific examples of the composition for external use on the skin of the present invention include pharmaceuticals, quasi-drugs, cosmetics and the like. Among these dosage forms, pharmaceuticals and quasi-drugs are preferred.

Method of use The external composition for skin of the present invention can be used for antipruritic purposes, and is used by applying it to the part of the skin where itching is felt or the part of the skin where itching is to be prevented. There are no particular limitations on the skin symptoms at the skin site to which the composition for external use of the present invention is applied, as long as it causes itching, but it is preferably applied to redness and eczema. Such redness and eczema are preferably skin symptoms caused by dampness, friction/irritation, weight bearing, and the like.

The site of the skin to which the composition for external use of the present invention is applied is not particularly limited as long as it is a site accompanied by itching, preferably the site where the aforementioned redness or eczema is likely to occur. Specific examples include the buttocks and thighs, more preferably the vicinity of the boundary between the buttocks and thighs, which are likely to be repeatedly subjected to stuffiness, friction/irritation, weight bearing, and the like.

The composition for external use on the skin of the present invention can be applied by applying, for example, 0.1 to 0.5 g per 100 cm ² of skin once or twice a day.

On the skin site to which the composition for external use of the present invention was applied, the skin was itchy due to the rapid antipruritic effect, prevention of itching, and the anti-inflammatory and antibacterial effects originally possessed by ufenamate and zinc oxide. Symptoms can also improve.

EXAMPLES The present invention will be described in more detail with reference to examples below, but the present invention is not limited to these.

Test example 1
An external skin composition having the composition shown in Table 1 was prepared and applied to a pruritus model mouse prepared by administering a pruritus-inducing substance to conduct a pruritus test. In the scratch test, the antipruritic effect was evaluated by counting the number of scratching movements of the mice. The details of the pruritus model mouse, the method of application, and the method of counting the number of scratching movements are as follows.

・Pruritus model mouse Animal used Species Mouse strain Slc: ICR
Age: 5 weeks Source: Japan SLC Co., Ltd.
Administration of prurigenic substance Prurigenic substance Compound 48/80
Available from Sigma-Aldrich Co.;
Route of administration Intradermal administration Dose 50 μg/site
Administration method A glass syringe (Top Co., Ltd.) and a 30G needle (Dentronics Co., Ltd.) were used to administer to the back immediately after shaving and applying the composition for external use to the skin.
Dosing frequency 1 time

- Application of topical skin composition Route of administration Application Dose 100 mg/mouse Administration method Immediately before administration of the pruritus, the composition was spread over the entire shaved back with a rubber-gloved finger.
Dosing frequency 1 time

・Count of scraping motions
The behavior of the mouse was observed during video images using Windows Media Player (version: 12.0.7601.23517), and the scratching behavior of the mouse's hind limbs on the back of the mouse was observed from immediately after administration of the pruritus to 5 minutes after administration of the pruritus. , from immediately after administration of the pruritus to 15 minutes after the administration of the pruritus, the number of times was counted. The number of scratching motions was set to 1 when the mouse completed a series of motions in which the hind leg was raised to scratch, the scratching behavior was performed, and the hind leg was lowered again. A multi-tally counter (DS-404: Takano Keiki Co., Ltd.) was used for counting, and it was confirmed by the timer display in the video that the video was not interrupted. Table 1 and FIG. 1 show the results of counting the scratching motions.

As shown in Table 1 and FIG. 1, in the control to which petrolatum was applied (Comparative Example 3), many scratching movements were observed from an early stage after the induction (5 minutes after the induction), and 5 minutes after the induction and 15 minutes after the induction. As can be seen from the number of scraping operations per minute, the number of scraping operations increased with the passage of time. On the other hand, when ufenamate was applied alone (Comparative Example 1) and when zinc oxide was applied alone (Comparative Example 2), for example, the number of scratching movements decreased compared to the control (Comparative Example 3) within 15 minutes after the induction. However, the degree of reduction did not significantly reduce the scratching motion. In particular, when ufenamate was applied alone (Comparative Example 1), the number of scratching movements exceeded that of the control (Comparative Example 3) within 5 minutes after the induction, and ufenamate rather exacerbated the pruritus.

In contrast, when ufenamate and zinc oxide were used in combination (Example 1), a significant reduction in the number of scratching movements was observed within 15 minutes after the induction. The extent of this reduction far exceeds the sum of the extent of reduction in the number of scraping motions of ufenamate alone (Comparative Example 1) and zinc oxide alone (Comparative Example 2) relative to the control (Comparative Example 3). In view of this, it can be seen that this is particularly conspicuous. In addition, when ufenamate and zinc oxide were applied in combination (Example 1), a significant reduction in the number of scratching movements was observed even in just 5 minutes after the induction. The extent of this reduction is that when ufenamate is used alone (Comparative Example 1), the number of scraping operations is rather increased compared to the control (Comparative Example 3), and when zinc oxide is used alone (Comparative Example 2), the number is greater than that of the control (Comparative Example 3). In view of the fact that the number of scraping operations was only slightly reduced, it can be seen that this is particularly remarkable. In view of the fact that the antipruritic effect was obtained in just 5 minutes after the induction, it was found that the anti-inflammatory effect and antibacterial effect originally possessed by ufenamate and zinc oxide improved the skin symptoms in the applied area. As a secondary result, it can also be seen that it was not antipruritic. In other words, it is expected that the external composition for skin of the present invention, which contains ufenamate and zinc oxide in combination, can exhibit a particularly marked antipruritic effect at an early stage, although these components alone do not have an effective antipruritic effect. It was found to have an outside effect.

Test example 2
A skin care composition having the composition shown in Table 2 was prepared as an oil-in-water emulsified composition. The prepared composition for external use on the skin was applied to a subject complaining of skin symptoms such as redness and eczema in the vicinity of the boundary between the buttocks and the thighs, and itching at the site. The amount applied was about 0.2 g per 100 cm ² and the frequency of application was twice a day. As a result, a reduction in itchiness was felt from about 10 minutes after application. Furthermore, about 2 hours after application, a tendency toward improvement in skin symptoms such as redness and eczema was also observed.

Claims (2)

A composition for external use on the skin containing 5 to 20% by weight of ufenamate and zinc oxide (provided that [i] when it contains uwaurushi; and polyethylene hydrogenated castor oil; [iii] polyglycerin fatty acid ester, glycerin fatty acid ester, fatty acid that constitutes a fatty acid soap that is neutralized by a base and functions as an anionic surfactant , the base, water-soluble polymer, oil and water; [iv ] polyoxyethylene sorbitan monofatty acid ester, anionic surfactant, glycerin fatty acid ester and water; and [v] except when used for UV protection). The external composition for skin according to claim 1, which is used for antipruritic purposes.

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