JP2022183357A - external composition - Google Patents
external composition Download PDFInfo
- Publication number
- JP2022183357A JP2022183357A JP2022169091A JP2022169091A JP2022183357A JP 2022183357 A JP2022183357 A JP 2022183357A JP 2022169091 A JP2022169091 A JP 2022169091A JP 2022169091 A JP2022169091 A JP 2022169091A JP 2022183357 A JP2022183357 A JP 2022183357A
- Authority
- JP
- Japan
- Prior art keywords
- composition
- mass
- acid
- kprp
- ufenamate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
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- 229950010121 ufenamate Drugs 0.000 claims abstract description 27
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Landscapes
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Abstract
Description
本発明は、外用組成物に関する。 The present invention relates to topical compositions.
近代社会においては、人間は常に太陽光、大気汚染、活性酸素、化学物質、温度、乾燥、喫煙、皮膚過洗浄、ストレス等によって、各種刺激物質に曝されている。そのため、皮膚の状態が過敏になり、また今まで刺激を起こさなかった物質などにも過敏に反応してしまう症状が報告されている。 In modern society, humans are constantly exposed to various irritants such as sunlight, air pollution, active oxygen, chemical substances, temperature, dryness, smoking, skin overwashing, and stress. As a result, it has been reported that the skin becomes hypersensitive, and that it reacts hypersensitively to substances that have not previously been irritating.
上記のような刺激物質は、正常な皮膚の状態であれば影響は少ないが、特に表皮のバリア機能が損なわれている場合に過敏に反応しやすい。このため、表皮バリア機能を維持、修復できる技術の開発が求められている。 Irritants such as those mentioned above have little effect on the skin under normal conditions, but tend to cause hypersensitivity reactions particularly when the barrier function of the epidermis is impaired. Therefore, there is a demand for the development of techniques capable of maintaining and restoring the epidermal barrier function.
hKPRP(human keratinocyte proline-rich protein)遺伝子は、ヒト染色体の1q21に位置することが知られている公知の遺伝子である。hKPRP遺伝子は、表皮分化複合体(EDC)を構成する1つの遺伝子であり、hKPRPタンパク質をコードする。hKPRPタンパク質は、プロリンタンパク質を約18%程度含むタンパク質であり、正常表皮の顆粒層上部で断続的に発現することが知られ、表皮バリア機能形成に関与することが示唆されている(非特許文献1、2)。 The hKPRP (human keratinocyte proline-rich protein) gene is a known gene known to be located at 1q21 of human chromosome. The hKPRP gene is one of the genes that constitute the epidermal differentiation complex (EDC) and encodes the hKPRP protein. The hKPRP protein is a protein containing about 18% proline protein, is known to be intermittently expressed in the upper part of the granular layer of normal epidermis, and has been suggested to be involved in the formation of the epidermal barrier function (non-patent literature). 1, 2).
しかしながら、種々の刺激に対し過敏になっている皮膚の状態を改善し、肌表面に近い角層から、正常な状態に近づけることが可能となる薬剤は報告されていない状況である。 However, no drug has been reported that can improve the condition of the skin, which is hypersensitive to various stimuli, and bring the stratum corneum close to the skin surface to a normal condition.
特に、KPRPタンパク質の発現を亢進させることにより、KPRP遺伝子が介在する角層正常化をもたらす成分については、十分に検証された報告はない。 In particular, there are no reports that have been sufficiently verified for components that promote KPRP gene-mediated normalization of the stratum corneum by enhancing the expression of the KPRP protein.
本発明は、上記に鑑みてなされたものであり、KPRPタンパク質の発現を顕著に亢進させる成分を見出し、KPRP遺伝子が介在する角層正常化をもたらす外用組成物を提供することを目的とする。 The present invention has been made in view of the above, and aims to find a component that remarkably enhances the expression of the KPRP protein, and to provide an external composition that brings about the normalization of the stratum corneum mediated by the KPRP gene.
前記課題に鑑み、鋭意検討を行った結果、ウフェナマート及びその塩、並びにイソプロピルメチルフェノールからなる群より選択される少なくとも1種が、表皮角化細胞(ケラチノサイト)でのKPRPタンパク質発現に影響を与え、そのタンパク質産生を促進することが見出された。すなわち、ウフェナマート及びその塩、並びにイソプロピルメチルフェノールからなる群より選択される少なくとも1種が、KPRP遺伝子が介在する角層正常化をもたらし得ることを見出し、本発明を完成させるに至った。 In view of the above problems, as a result of intensive studies, at least one selected from the group consisting of ufenamate and its salts, and isopropylmethylphenol affects KPRP protein expression in epidermal keratinocytes (keratinocytes), It was found to promote its protein production. That is, the inventors have found that at least one selected from the group consisting of ufenamate and its salts and isopropylmethylphenol can bring about KPRP gene-mediated stratum corneum normalization, and have completed the present invention.
すなわち、本発明は、下記に掲げる組成物を提供する。
項1.
(A)ウフェナマート及びその塩、並びにイソプロピルメチルフェノールからなる群より選択される少なくとも1種を、KPRPタンパク質発現亢進作用を示す有効量を含む、KPRP遺伝子が介在する角層正常化機能亢進のための外用組成物。
項2.
(A)ウフェナマート及びその塩、並びにイソプロピルメチルフェノールからなる群より選択される少なくとも1種を有効成分として含有する、過敏肌の予防及び/又は改善用外用組成物。
項3.
(A)ウフェナマート及びその塩、並びにイソプロピルメチルフェノールからなる群より選択される少なくとも1種を有効成分として含有する、接触性皮膚炎の予防、治療及び/又は改善用外用組成物。
項4.
(A)ウフェナマート及びその塩、並びにイソプロピルメチルフェノールからなる群より選択される少なくとも1種を有効成分として含有する、角層正常化用組成物。
項5.
(A)ウフェナマート及びその塩、並びにイソプロピルメチルフェノールからなる群より選択される少なくとも1種を有効成分として含有する、KPRP発現亢進用組成物。
項6.
前記(A)成分の含有量が、組成物全量に対して、0.0001~10質量%である、項1~5のいずれか1項に記載の組成物。
項7.
さらに、(B)ジフェンヒドラミン、グリチルリチン酸、グリチルレチン酸、グリチルレチン酸ステアリル、リドカイン及びそれらの塩からなる群より選択される少なくとも1種を含有する、項1~6のいずれか1項に記載の組成物。
項8.
外陰部、臀部及び/又は肛門部に対して適用される、項1~7のいずれか1項に記載の組成物。
項9.
接触性皮膚炎の起因物質が、尿、汗、便及び/又は尿ケア製品である、項3に記載の組成物。
項10.
中高年齢者に対して適用される、項1~9のいずれか1項に記載の組成物。
That is, the present invention provides compositions listed below.
Section 1.
(A) for KPRP gene-mediated stratum corneum normalization enhancement, containing at least one selected from the group consisting of ufenamate and its salts, and isopropylmethylphenol in an effective amount exhibiting a KPRP protein expression-enhancing action; External composition.
Section 2.
(A) An external composition for preventing and/or improving hypersensitive skin, containing as an active ingredient at least one selected from the group consisting of ufenamate and its salts and isopropylmethylphenol.
Item 3.
(A) An external composition for preventing, treating and/or improving contact dermatitis, containing as an active ingredient at least one selected from the group consisting of ufenamate and its salts and isopropylmethylphenol.
Section 4.
(A) A composition for normalizing the stratum corneum containing, as an active ingredient, at least one selected from the group consisting of ufenamate, salts thereof, and isopropylmethylphenol.
Item 5.
(A) A composition for enhancing KPRP expression, containing as an active ingredient at least one selected from the group consisting of ufenamate, salts thereof, and isopropylmethylphenol.
Item 6.
Item 6. The composition according to any one of Items 1 to 5, wherein the content of component (A) is 0.0001 to 10% by mass relative to the total amount of the composition.
Item 7.
Item 7. The composition according to any one of Items 1 to 6, further comprising (B) at least one selected from the group consisting of diphenhydramine, glycyrrhizic acid, glycyrrhetinic acid, stearyl glycyrrhetinate, lidocaine, and salts thereof. .
Item 8.
8. The composition according to any one of Items 1 to 7, which is applied to the vulva, buttocks and/or anus.
Item 9.
4. A composition according to Item 3, wherein the causative agent of contact dermatitis is urine, perspiration, faeces and/or urinary care products.
Item 10.
Item 10. The composition according to any one of Items 1 to 9, which is applied to middle-aged and elderly people.
(A)ウフェナマート及びその塩、並びにイソプロピルメチルフェノールからなる群より選択される少なくとも1種を含有する組成物を皮膚等に適用することにより、表皮バリア機能形成に関与することが示唆されているKPRPタンパク質をコードする、KPRP遺伝子の発現を促進させ、KPRPタンパク質の産生量を増加させることが出来る。よって、本発明により、表皮バリアの機能形成が促進され、種々の刺激に対し過敏になっている皮膚の状態を改善し、肌表面に近い角層から、正常な状態に近づけることが可能となる。 (A) KPRP, which is suggested to be involved in the formation of epidermal barrier function by applying a composition containing at least one selected from the group consisting of ufenamate and its salts and isopropylmethylphenol to the skin or the like. The expression of the KPRP gene, which encodes the protein, can be promoted to increase the amount of KPRP protein produced. Therefore, according to the present invention, the functional formation of the epidermal barrier is promoted, the condition of the skin, which is hypersensitive to various stimuli, is improved, and the stratum corneum close to the surface of the skin can be restored to a normal condition. .
本発明の外用組成物は、(A)ウフェナマート及びその塩、並びにイソプロピルメチルフェノールからなる群より選択される少なくとも1種を含有するものである。 The composition for external use of the present invention contains (A) at least one selected from the group consisting of ufenamate and its salts, and isopropylmethylphenol.
[(A)成分]
(A)成分のうち、ウフェナマート(フルフェナム酸ブチルとも言う)は、非ステロイド系抗炎症剤(NSAIDs)の1種として公知の成分である。ウフェナマートは、ステロイド系抗炎症剤と比較して、安全性が高いことが知られており、過敏に反応しやすい皮膚やデリケートな部位へも長期的に連用しやすい。
[(A) component]
Among the components (A), ufenamate (also referred to as butyl flufenamate) is a component known as one type of non-steroidal anti-inflammatory drugs (NSAIDs). Ufenamate is known to be safer than steroidal anti-inflammatory drugs, and can be used continuously for a long time on sensitive skin and delicate areas.
(A)成分のうち、イソプロピルメチルフェノールは、フェノール系抗菌剤の一つであり、高い安定性や安全性を有し、さらにカビや細菌に広く効果を発揮するものである。イソプロピルメチルフェノールは、その安全性の高さから、過敏に反応しやすい皮膚やデリケートな部位へも長期的に連用しやすい。 Among the components (A), isopropylmethylphenol is one of the phenolic antibacterial agents, has high stability and safety, and is widely effective against mold and bacteria. Due to its high safety, isopropylmethylphenol is easy to use for a long period of time, even on sensitive skin and delicate areas.
これらの(A)成分は、合成して用いてもよく、市販品を用いてもよい。また、これらの(A)成分は、1種単独で用いてもよく、2種以上を任意に組み合わせて用いてもよい。 These (A) components may be synthesized and used, or commercially available products may be used. Moreover, these (A) components may be used individually by 1 type, and may be used in combination of 2 or more types arbitrarily.
本発明の組成物において、(A)成分の含有量は、(A)成分の種類、他の配合成分の種類及び含有量、製剤形態、使用方法等に応じて適宜設定される。限定はされないが、例えば、(A)成分の総含有量は、組成物全量に対して、好ましくは0.0001質量%以上であり、より好ましくは0.001質量%以上、さらに好ましくは0.005質量%以上、特に好ましくは0.01質量%以上、さらに特に好ましくは0.05質量%以上、最も好ましくは0.1質量%以上である。また、(A)成分の総含有量は、組成物全量に対して、好ましくは10質量%以下であり、より好ましくは8質量%以下、特に好ましくは、6重量%以下、最も好ましくは5質量%以下である。(A)成分の総含有量は、組成物全量に対して、好ましくは0.0001質量%~10質量%であり、より好ましくは0.001質量%~8質量%、更に好ましくは0.01質量%~6質量%、特に好ましくは0.1質量%~5質量%である。 In the composition of the present invention, the content of component (A) is appropriately set according to the type of component (A), the type and content of other ingredients, the formulation form, the method of use, and the like. Although not limited, for example, the total content of component (A) is preferably 0.0001% by mass or more, more preferably 0.001% by mass or more, and still more preferably 0.001% by mass or more, based on the total amount of the composition. 005% by mass or more, particularly preferably 0.01% by mass or more, even more preferably 0.05% by mass or more, and most preferably 0.1% by mass or more. In addition, the total content of component (A) is preferably 10% by mass or less, more preferably 8% by mass or less, particularly preferably 6% by mass or less, and most preferably 5% by mass, relative to the total amount of the composition. % or less. The total content of component (A) is preferably 0.0001% by mass to 10% by mass, more preferably 0.001% by mass to 8% by mass, and still more preferably 0.01% by mass, relative to the total amount of the composition. % to 6% by weight, particularly preferably 0.1% to 5% by weight.
限定はされないが、好ましい態様では、例えば、ウフェナマート及び/又はその塩を(A)成分として含有する場合に、ウフェナマート及び/又はその塩の単独の含有量は、組成物全量に対して、好ましくは0.1質量%~10質量%であり、より好ましくは1質量%~8質量%、更に好ましくは3質量%~6質量%、特に好ましくは4質量%~5.5質量%、最も好ましくは5質量%である。 Although not limited, in a preferred embodiment, for example, when ufenamate and/or a salt thereof is contained as the component (A), the content of ufenamate and/or a salt thereof alone is preferably 0.1% by mass to 10% by mass, more preferably 1% by mass to 8% by mass, still more preferably 3% by mass to 6% by mass, particularly preferably 4% by mass to 5.5% by mass, most preferably 5% by mass.
限定はされないが、好ましい態様では、例えば、イソプロピルメチルフェノールを(A)成分として含有する場合に、イソプロピルメチルフェノールの単独の含有量は、組成物全量に対して、好ましくは0.005質量%~5質量%であり、より好ましくは0.01質量%~2質量%、更に好ましくは0.05質量%~1質量%である。 Although not limited, in a preferred embodiment, for example, when isopropylmethylphenol is contained as the component (A), the content of isopropylmethylphenol alone is preferably from 0.005% by mass to the total amount of the composition. 5 mass %, more preferably 0.01 mass % to 2 mass %, and still more preferably 0.05 mass % to 1 mass %.
[(B)成分]
本発明の組成物は、さらに、(B)ジフェンヒドラミン、グリチルリチン酸、グリチルレチン酸、グリチルレチン酸ステアリル、リドカイン及びそれらの塩からなる群より選択される少なくとも1種を含有することが好ましい。これらの(B)成分は、角層の正常化が求められる部位へ適用されることにより、皮膚状態の改善に作用し得る。
[(B) component]
The composition of the present invention preferably further contains (B) at least one selected from the group consisting of diphenhydramine, glycyrrhizic acid, glycyrrhetinic acid, stearyl glycyrrhetinate, lidocaine and salts thereof. These (B) components can act to improve the skin condition by being applied to a site where normalization of the stratum corneum is desired.
(B)成分の塩としては、生理学的に許容され得る塩であれば特に制限されず、例えば、無機塩基との塩[例えば、アンモニウム塩;アルカリ金属(ナトリウム、カリウム等)、アルカリ土類金属(カルシウム、マグネシウム等)、アルミニウム等の金属との塩等];有機塩基との塩(例えば、メチルアミン、トリエチルアミン、トリエタノールアミン、モルホリン、ピペラジン、ピロリジン、トリピリジン、ピコリン等の有機アミンとの塩等);無機酸塩(例えば、塩酸塩、硫酸塩、硝酸塩、臭化水素酸塩、リン酸塩等);有機酸塩[例えば、モノカルボン酸塩(酢酸塩、トリフルオロ酢酸塩、酪酸塩、パルミチン酸塩、ステアリン酸塩等)、多価カルボン酸塩(フマル酸塩、マレイン酸塩、コハク酸塩、マロン酸塩等)、オキシカルボン酸塩(乳酸塩、酒石酸塩、クエン酸塩等)、有機スルホン酸塩(メタンスルホン酸塩、トルエンスルホン酸塩、トシル酸塩等)等]等が挙げられる。これらの塩の中でも、好ましくは無機塩基との塩及び/又は有機塩基との塩、より好ましくは無機塩基との塩、更に好ましくは塩酸塩、アルカリ金属塩及び/又はアンモニウム塩、特に好ましくはカリウム塩、ナトリウム塩及び/又はアンモニウム塩が挙げられる。 The salt of component (B) is not particularly limited as long as it is a physiologically acceptable salt, and examples thereof include salts with inorganic bases [e.g., ammonium salts; (calcium, magnesium, etc.), salts with metals such as aluminum]; salts with organic bases (e.g., salts with organic amines such as methylamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, picoline, etc.) etc.); inorganic acid salts (e.g., hydrochlorides, sulfates, nitrates, hydrobromides, phosphates, etc.); organic acid salts [e.g., monocarboxylates (acetates, trifluoroacetates, butyrates, , palmitate, stearate, etc.), polyvalent carboxylates (fumarate, maleate, succinate, malonate, etc.), oxycarboxylates (lactate, tartrate, citrate, etc.) ), organic sulfonates (methanesulfonate, toluenesulfonate, tosylate, etc.)] and the like. Among these salts, preferably a salt with an inorganic base and/or a salt with an organic base, more preferably a salt with an inorganic base, still more preferably a hydrochloride, an alkali metal salt and/or an ammonium salt, particularly preferably potassium salts, sodium and/or ammonium salts.
(B)成分の塩としては、限定はされないが、ジフェンヒドラミン塩酸塩、グリチルリチン酸二カリウム、グリチルリチン酸モノアンモニウム、リドカイン塩酸塩が好適に用いられる。 The salt of component (B) is not limited, but diphenhydramine hydrochloride, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, and lidocaine hydrochloride are preferably used.
これらの(B)成分は、合成して用いてもよく、市販品を用いてもよい。また、これらの(B)成分は、1種単独で用いてもよく、2種以上を任意に組み合わせて用いてもよい。 These (B) components may be synthesized and used, or commercially available products may be used. Moreover, these (B) components may be used individually by 1 type, and may be used in combination of 2 or more types arbitrarily.
本発明の組成物において、(B)成分の含有量は、(B)成分の種類、他の配合成分の種類及び含有量、製剤形態、使用方法等に応じて適宜設定される。限定はされないが、例えば、(B)成分の総含有量は、組成物全量に対して、好ましくは0.005質量%以上であり、より好ましくは0.01質量%以上、さらに好ましくは0.05質量%以上、特に好ましくは0.1質量%以上である。また、(B)成分の総含有量は、組成物全量に対して、好ましくは20質量%以下であり、より好ましくは10質量%以下、さらに好ましくは5質量%以下、特に好ましくは2質量%以下、最も好ましくは1質量%以下である。
(B)成分の総含有量は、組成物全量に対して、好ましくは0.005質量%~20質量%であり、より好ましくは0.01質量%~10質量%、更に好ましくは0.05質量%~5質量%、特に好ましくは0.1質量%~4質量%である。
In the composition of the present invention, the content of component (B) is appropriately set according to the type of component (B), the type and content of other ingredients, the formulation form, the method of use, and the like. Although not limited, for example, the total content of component (B) is preferably 0.005% by mass or more, more preferably 0.01% by mass or more, and still more preferably 0.01% by mass or more, based on the total amount of the composition. 05% by mass or more, particularly preferably 0.1% by mass or more. In addition, the total content of component (B) is preferably 20% by mass or less, more preferably 10% by mass or less, still more preferably 5% by mass or less, and particularly preferably 2% by mass, relative to the total amount of the composition. Below, it is most preferably 1% by mass or less.
The total content of component (B) is preferably 0.005% by mass to 20% by mass, more preferably 0.01% by mass to 10% by mass, and still more preferably 0.05% by mass, relative to the total amount of the composition. % to 5% by weight, particularly preferably 0.1% to 4% by weight.
限定はされないが、好ましい態様では、例えば、ジフェンヒドラミン及び/又はその塩を(B)成分として含有する場合に、ジフェンヒドラミン及び/又はその塩の単独の含有量は、組成物全量に対して、好ましくは0.05質量%~10質量%であり、より好ましくは0.1質量%~5質量%、更に好ましくは0.5質量%~3質量%、特に好ましくは1質量%~2質量%である。 Although not limited, in a preferred embodiment, for example, when diphenhydramine and/or a salt thereof is contained as the component (B), the content of diphenhydramine and/or a salt thereof alone is preferably 0.05% by mass to 10% by mass, more preferably 0.1% by mass to 5% by mass, still more preferably 0.5% by mass to 3% by mass, particularly preferably 1% by mass to 2% by mass .
限定はされないが、好ましい態様では、例えば、グリチルリチン酸及び/又はその塩を(B)成分として含有する場合に、グリチルリチン酸及び/又はその塩の単独の含有量は、組成物全量に対して、好ましくは0.005質量%~10質量%であり、より好ましくは0.01質量%~5質量%、更に好ましくは0.05質量%~2質量%、特に好ましくは0.1質量%~1質量%である。 Although not limited, in a preferred embodiment, for example, when glycyrrhizic acid and/or its salt is contained as the component (B), the content of glycyrrhizic acid and/or its salt alone is, relative to the total amount of the composition, It is preferably 0.005% by mass to 10% by mass, more preferably 0.01% by mass to 5% by mass, still more preferably 0.05% by mass to 2% by mass, and particularly preferably 0.1% by mass to 1% by mass. % by mass.
限定はされないが、好ましい態様では、例えば、グリチルレチン酸及び/又はその塩を(B)成分として含有する場合に、グリチルレチン酸及び/又はその塩の単独の含有量は、組成物全量に対して、好ましくは0.005質量%~10質量%であり、より好ましくは0.01質量%~5質量%、更に好ましくは0.05質量%~1質量%、特に好ましくは0.1質量%~0.5質量%である。 Although not limited, in a preferred embodiment, for example, when glycyrrhetinic acid and/or its salt is contained as the component (B), the content of glycyrrhetinic acid and/or its salt alone is, relative to the total amount of the composition, It is preferably 0.005% by mass to 10% by mass, more preferably 0.01% by mass to 5% by mass, still more preferably 0.05% by mass to 1% by mass, and particularly preferably 0.1% by mass to 0% by mass. 0.5 mass %.
限定はされないが、好ましい態様では、例えば、リドカイン及び/又はその塩を(B)成分として含有する場合に、リドカイン及び/又はその塩の単独の含有量は、組成物全量に対して、好ましくは0.005質量%~10質量%であり、より好ましくは0.01質量%~5質量%、更に好ましくは0.05質量%~3質量%、特に好ましくは0.1質量%~2質量%である。 Although not limited, in a preferred embodiment, for example, when lidocaine and/or a salt thereof is contained as the component (B), the content of lidocaine and/or a salt thereof alone is preferably 0.005% by mass to 10% by mass, more preferably 0.01% by mass to 5% by mass, still more preferably 0.05% by mass to 3% by mass, particularly preferably 0.1% by mass to 2% by mass is.
本発明の組成物において、本発明による効果をより顕著に奏する観点から、(A)成分に対する(B)成分の配合比率は、例えば、(A)成分の総含有量1質量部に対して、(B)成分の総含有量が0.001~500質量部とすることができ、0.005~300質量部、0.01~100質量部、0.02~50質量部とすることも可能である。 In the composition of the present invention, from the viewpoint of exhibiting the effects of the present invention more remarkably, the blending ratio of component (B) to component (A) is, for example, based on 1 part by mass of the total content of component (A), The total content of component (B) can be 0.001 to 500 parts by mass, and can also be 0.005 to 300 parts by mass, 0.01 to 100 parts by mass, and 0.02 to 50 parts by mass. is.
[用途]
一つの実施態様において、本発明の組成物は、KPRP遺伝子が介在する角層正常化機能亢進のために用いられる。本発明の組成物は、KPRPタンパク質発現亢進作用が新たに見出された(A)ウフェナマート及びその塩、並びにイソプロピルメチルフェノールからなる群より選択される少なくとも1種を含有するため、適用部位の表皮顆粒層上部でKPRPタンパク質の産生量を増加させ、角層の正常化機能を亢進することが可能となる。
[Use]
In one embodiment, the composition of the present invention is used for KPRP gene-mediated hypercorneal normalization. Since the composition of the present invention contains at least one selected from the group consisting of (A) ufenamate and its salts, and isopropylmethylphenol, which has been newly found to have a KPRP protein expression-enhancing effect, the epidermis of the application site It is possible to increase the production of KPRP protein in the upper part of the granular layer and enhance the normalizing function of the stratum corneum.
本明細書において、皮膚の角層(角質細胞層ともいう)とは、皮膚の最外層に位置して、表皮角化細胞が角化し、扁平な角化細胞が重なった層をいう。表皮は、最深部から順に基底層、有棘層、顆粒層、及び最上部の角層に至るまでの4層に分類される。基底層を構成する基底細胞が分裂し、成熟するに従って上方の層に移って行く。基底細胞が分裂を起こして、角層まで移行し、脱落するまでのターンオーバーにかかる期間は約45日と考えられている。 As used herein, the stratum corneum of the skin (also referred to as stratum corneum) is the outermost layer of the skin, and refers to a layer in which epidermal keratinocytes are keratinized and flattened keratinocytes are superimposed. The epidermis is classified into four layers, from the deepest to the stratum basale, the stratum spinosum, the stratum granulosum, and the stratum corneum at the top. The basal cells that make up the stratum basale divide and move to the upper layers as they mature. It is believed that it takes about 45 days for basal cells to divide, migrate to the stratum corneum, and turn over until they are exfoliated.
顆粒層には、球形のオドランド小体が分布しており、その内容物であるセラミドなどの脂質を放出することにより、細胞間脂質を形成し、角層の角化及び/又は保湿の点から重要な層である。一つの実施態様において、本発明の組成物は、主に顆粒層の上部に働きかけ、KPRPタンパク質の発現を亢進させることができ、角層の角化を正常に促すことが可能となる。よって、本発明の組成物は、角層正常化用途に好適に用いられる。 In the granular layer, spherical Odland's bodies are distributed, and by releasing lipids such as ceramide, which are the contents thereof, intercellular lipids are formed, and from the viewpoint of keratinization and / or moisturizing of the stratum corneum. It is an important layer. In one embodiment, the composition of the present invention can act mainly on the upper part of the stratum granulosum, enhance the expression of KPRP protein, and promote normal keratinization of the stratum corneum. Therefore, the composition of the present invention is suitably used for normalizing the stratum corneum.
正常な角層は、周辺帯と呼ばれる構造が存在し、太陽光、大気汚染、活性酸素、化学物質、温度、乾燥、喫煙、皮膚過洗浄、ストレス等の外界からの物理的及び/又は化学的刺激に対して安定である。しかし、角層に異常を来し、その構造に乱れが生じると、上記の物理的及び/又は化学的刺激に対して過敏に反応してしまうようになる。一つの実施態様において、本発明の組成物は、KPRPタンパク質発現亢進作用が新たに見出された(A)ウフェナマート及びその塩、並びにイソプロピルメチルフェノールからなる群より選択される少なくとも1種を含有するため、皮膚を内側から正常化し、上記の物理的及び/又は化学的刺激に対して過敏に反応してしまう肌状態(過敏肌ともいう)を予防及び/又は改善することが可能となる。 A normal stratum corneum has a structure called a marginal zone, which is exposed to physical and/or chemical influences from the outside world such as sunlight, air pollution, active oxygen, chemical substances, temperature, dryness, smoking, over-cleansing of the skin, and stress. Stable to stimulation. However, when the stratum corneum becomes abnormal and its structure is disturbed, it becomes hypersensitive to the above physical and/or chemical stimuli. In one embodiment, the composition of the present invention contains at least one selected from the group consisting of (A) ufenamate, a salt thereof, and isopropylmethylphenol, which have been newly found to enhance KPRP protein expression. Therefore, it is possible to normalize the skin from the inside and prevent and/or improve the skin condition (also referred to as hypersensitive skin) in which the skin reacts hypersensitively to the above physical and/or chemical stimuli.
また、上記の作用から、例えば、尿(尿中のアンモニア)、汗、便、経血、尿パッド、生理用ナプキン、おむつ等、なかでも特には、尿、尿パッド、汗、便等が刺激になって発生する、デリケート部位における接触性皮膚炎等においても、角層の角化及び又は保湿機能を高めて角層を正常化することによって、接触性皮膚炎による痛痒さや、しみるような痒さなどの症状を改善することが出来る。よって、一つの実施態様において、本発明の組成物は、KPRPタンパク質発現亢進作用が新たに見出された(A)ウフェナマート及びその塩、並びにイソプロピルメチルフェノールからなる群より選択される少なくとも1種を含有するため、接触性皮膚炎の予防、治療及び/又は改善用途に好適に用いられる。特に高齢者においては、元々の皮膚の状態において角層の構造に乱れが生じていることが多く、上記の症状(尿、汗、便及び/又は尿パッド等の尿ケア製品に起因する刺激)が特に顕著に発生する可能性があるが、そのような状態の皮膚においても、症状を速やかに改善することが可能となる。本明細書において、尿ケア製品には、尿パッド、尿ケアライナー、尿ケアパンツ、おむつ等の公知の製品が含まれ、男性用であってもよく、女性用であってもよい。 In addition, from the above action, for example, urine (ammonia in urine), sweat, feces, menstrual blood, urine pads, sanitary napkins, diapers, etc., especially urine, urine pads, sweat, feces, etc. are stimulated. Even in contact dermatitis, etc. in delicate areas that occur after a Symptoms such as itching can be improved. Therefore, in one embodiment, the composition of the present invention contains at least one selected from the group consisting of (A) ufenamate and its salts, and isopropylmethylphenol, which have been newly found to have an effect of enhancing KPRP protein expression. Since it contains, it is suitably used for prevention, treatment and/or improvement of contact dermatitis. Especially in the elderly, the original skin condition often causes disturbance in the structure of the stratum corneum, and the above symptoms (irritation caused by urine, sweat, feces and/or urinary care products such as urine pads) can occur particularly remarkably, but it is possible to quickly improve the symptoms even in such a state of the skin. As used herein, urinary care products include known products such as urine pads, urinary care liners, urinary care pants, diapers, etc., and may be for men or women.
他の実施態様において、本発明の組成物は、角層の構造に乱れを生じる状態、症状及び/又は疾患に対して好適に用いられる。 In another embodiment, the composition of the present invention is preferably used for conditions, symptoms and/or diseases that cause disturbance in the structure of the stratum corneum.
白癬菌(トリコフィトン属真菌)が関与する状態、症状及び/又は疾患(水虫やたむし等)では、角層において白癬菌が増殖し、角層に異常を来す。典型的には、足裏の皮膚(角層)に白癬菌が感染し、角層が増殖・肥厚して、皮膚が厚く、固くなることがある。よって、一つの実施態様において、本発明の組成物は、白癬菌が関与する状態、症状及び/又は疾患の予防、治療及び/又は改善用途に好適に用いられる。限定はされないが、角質増殖型白癬に対しては、本発明の組成物は、主に顆粒層の上部に働きかけ、KPRPタンパク質の発現を亢進させることができ、角層の角化を正常に促すことが可能となる。 In conditions, symptoms and/or diseases (athlete's foot, ringworm, etc.) associated with trichophyton fungi (fungi of the genus Trichophyton), trichophyton proliferates in the stratum corneum and causes abnormalities in the stratum corneum. Typically, the skin of the sole (stratum corneum) is infected with trichophyton fungus, the stratum corneum proliferates and thickens, and the skin becomes thick and hard. Therefore, in one embodiment, the composition of the present invention is suitably used for prevention, treatment and/or amelioration of conditions, symptoms and/or diseases associated with trichophyton. Although not limited, for hyperkeratotic tinea, the composition of the present invention can act mainly on the upper part of the granular layer, can enhance the expression of KPRP protein, and promotes normal keratinization of the stratum corneum. becomes possible.
アクネ菌(プロピオバクテリウム・アクネス)、黄色ブドウ球菌、マラセチア属真菌が関与する状態、症状及び/又は疾患(ニキビ、癜風、マラセチア毛包炎、脂漏性湿疹(脂漏性皮膚炎とも言う)、脂漏性角化症、アトピー性皮膚炎、外耳炎等)では、アクネ菌やマラセチア属真菌が増殖し、角層に異常を来す。よって、一つの実施態様において、本発明の組成物は、アクネ菌(プロピオバクテリウム・アクネス)及び/又はマラセチア属真菌が関与する状態、症状及び/又は疾患の予防、治療及び/又は改善用途に好適に用いられる。ニキビでは、炎症を生じて所謂赤ニキビを生じる前の初期の段階から角質の肥厚が生じることがある。限定はされないが、本発明の組成物は、角層が肥厚し、毛穴が塞がった初期ニキビ(白ニキビ)の予防、治療及び/又は改善用途に好適に用いられる。また、限定はされないが、ニキビに炎症を生じた場合、角層の構造の乱れは一層悪化することとなるため、本発明の組成物は、炎症を生じたニキビ(赤ニキビ)の予防、治療及び/又は改善用途に好適に用いられる。 Conditions, symptoms and/or diseases involving Propiobacterium acnes, Staphylococcus aureus, Malassezia spp. (acne, tinea versicolor, Malassezia folliculitis, seborrheic eczema ), seborrheic keratosis, atopic dermatitis, otitis externa, etc.), P. acnes and Malassezia fungi proliferate, causing abnormalities in the stratum corneum. Therefore, in one embodiment, the composition of the present invention is used for the prevention, treatment and/or amelioration of conditions, symptoms and/or diseases involving Propiobacterium acnes and/or fungi of the genus Malassezia. It is preferably used for In acne, thickening of keratin may occur from an early stage before inflammation occurs and so-called red acne occurs. Although not limited, the composition of the present invention is suitably used for the prevention, treatment and/or improvement of initial acne (white acne) in which the stratum corneum is thickened and the pores are clogged. In addition, although not limited thereto, when inflammation occurs in acne, the disorder of the structure of the stratum corneum is further exacerbated. and/or preferably used for improvement purposes.
他の実施態様において、本発明の組成物は、角層に炎症を生じる状態、症状及び/又は疾患に対して好適に用いられる。 In another embodiment, the composition of the present invention is preferably used for conditions, symptoms and/or diseases that cause inflammation in the stratum corneum.
[適用部位]
本発明の組成物が適用される部位は、皮膚等の角層の異常が問題となる部位であれば特に制限されず、例えば、顔、首元、胸元、背中、腕、肘、手、腋窩部、腹部、外陰部、臀部、肛門部、脚、指、足先及び足裏からなる群より選択される少なくとも1種であり得る。角層の異常が問題となりやすい部位としては、衣服着用時に開放部が無く、高温、多湿(蒸れ)になりやすい観点から、背中、上腕、腋窩部、腹部、外陰部、臀部、肛門部、脚、足の指及び足裏からなる群より選択される少なくとも1種が好ましく、背中、上腕、肘、外陰部、臀部、肛門部、足の指及び足裏からなる群より選択される少なくとも1種がより好ましい。また、角層の異常が問題となりやすい部位としては、衣服、尿、汗、便、尿ケア製品等への接触による物理的及び/又は化学的刺激を受けやすいとの別の観点から、首元、胸元、背中、腕、肘、腹部、外陰部、臀部、肛門部、脚、足先及び足裏からなる群より選択される少なくとも1種が好ましく、デリケートな部位である、外陰部、臀部及び肛門部からなる群より選択される少なくとも1種がより好ましい。また、本発明の組成物に含有される(A)成分は安全性が高いため、デリケートな子どもや赤ちゃんの薄い皮膚に対しても用いられ得る。
[Applicable part]
The site to which the composition of the present invention is applied is not particularly limited as long as it is a site where abnormalities in the stratum corneum such as skin are a problem. It may be at least one selected from the group consisting of the buttocks, abdomen, vulva, buttocks, anus, legs, fingers, toes and soles. Areas where abnormalities in the stratum corneum are likely to be a problem include the back, upper arms, armpits, abdomen, vulva, buttocks, anus, and legs because there are no open areas when wearing clothes and they are prone to high temperatures and humidity (stuff). , toes and soles, preferably at least one selected from the group consisting of back, upper arms, elbows, vulva, buttocks, anus, toes and soles. is more preferred. In addition, as a part where abnormalities of the stratum corneum are likely to be a problem, the neck is prone to physical and/or chemical irritation due to contact with clothing, urine, sweat, feces, urine care products, etc. , Chest, back, arms, elbows, abdomen, vulva, buttocks, anus, legs, toes and soles of the feet, which are delicate parts, vulva, buttocks and At least one selected from the group consisting of the anal region is more preferred. In addition, since the component (A) contained in the composition of the present invention is highly safe, it can be used even for sensitive children and babies with thin skin.
[適用対象者]
本発明の組成物が適用される対象者は、角層の異常が問題となる可能性があれば、特に制限されないが、角層の乱れを生じやすい年齢層であることが好ましく、おむつによるお尻かぶれが生じやすい新生児(生後28日まで)、乳児(生後28日以降、1歳未満)、幼児(1歳から就学前まで)であってもよく、ニキビを生じやすい思春期(10歳頃から18歳頃)、大人ニキビを生じやすい青年期(15歳頃から30歳頃)であってもよく、尿等によるかぶれを生じやすい中年齢者(45歳頃以上55歳未満)や高年齢者(55歳以上)であってもよい。衣服、尿、汗、便、尿ケア製品等への接触による物理的及び/又は化学的刺激を受けやすい観点から、本発明の組成物は、中高年齢者(45歳頃以上)に対して適用されることが好ましい。
[Applicable people]
Subjects to whom the composition of the present invention is applied are not particularly limited as long as there is a possibility that abnormalities in the stratum corneum may become a problem. Newborns (up to 28 days after birth), infants (after 28 days of age, less than 1 year old), infants (from 1 year old to preschool age) prone to rashes on the buttocks, and adolescents prone to acne (around 10 years old) to around 18 years old), adolescents (around 15 to around 30 years old) who are prone to adult acne, middle-aged people (around 45 to 55 years old) and elderly people who are prone to urinary rashes person (55 years old or older). The composition of the present invention is applicable to middle-aged and elderly people (around 45 years old and over) from the viewpoint of being susceptible to physical and/or chemical irritation due to contact with clothes, urine, sweat, feces, urine care products, etc. preferably.
[pH]
本発明の組成物のpHは、(A)成分の種類、他の配合成分の種類及び含有量、製剤形態、使用方法等に応じて適宜設定され、生理学的又は薬学的に許容できる範囲であれば制限されないが、例えば、pH2~9とすることができる。本発明の効果を安定的に発揮する観点から、本発明の組成物のpHは、好ましくは2~9.5、より好ましくは3~9、更により好ましくは4~8.5、更により好ましくは4.5~8、更により好ましくは5.5~7.5とすることができる。
[pH]
The pH of the composition of the present invention is appropriately set depending on the type of component (A), the type and content of other ingredients, formulation form, method of use, etc., and is within a physiologically or pharmaceutically acceptable range. For example, it can be pH 2-9. From the viewpoint of stably exhibiting the effect of the present invention, the pH of the composition of the present invention is preferably 2 to 9.5, more preferably 3 to 9, still more preferably 4 to 8.5, and even more preferably can be between 4.5 and 8, even more preferably between 5.5 and 7.5.
[剤形]
本発明の組成物は、医薬品、医薬部外品又は化粧品として公知の形態であれば、特に限定されないが、例えば、液剤、懸濁剤、乳剤、クリーム剤、軟膏剤、ゲル剤、リニメント剤、ローション剤、エアゾール剤、パウダー剤、不織布等のシートに本発明の組成物を含浸させたシート剤等の形態により、公知の方法で製剤化することができる。
[Dosage form]
The composition of the present invention is not particularly limited as long as it is in a form known as pharmaceuticals, quasi-drugs or cosmetics. It can be formulated by a known method in the form of lotions, aerosols, powders, sheets of non-woven fabric or the like impregnated with the composition of the present invention.
液剤、懸濁剤、乳剤、クリーム剤、軟膏剤、ゲル剤、ローション剤等の形態で本発明の組成物を液状又は半固形状に製剤化した場合、限定はされないが、例えば、ノズル付き容器に収容することにより、本発明の組成物を、患部に直接的に塗布することができる。ノズルの先端にロール又はボール等の回転体を用いることにより、本発明の組成物を患部に均一に塗布するよう設計することも可能である。患部に本発明の組成物を塗布した後に、不織布や指等により、塗り拡げて用いることも可能である。 Liquids, suspensions, emulsions, creams, ointments, gels, lotions, etc. When the composition of the present invention is formulated in a liquid or semi-solid form, for example, a container with a nozzle is not limited. The composition of the present invention can be applied directly to the affected area by housing it in the . By using a rotating body such as a roll or a ball at the tip of the nozzle, it is possible to design so that the composition of the present invention is evenly applied to the affected area. After applying the composition of the present invention to the affected area, it is also possible to use it by spreading it with a non-woven fabric, fingers or the like.
本発明の組成物を適用する際には、手の届きにくい患部にも適用しやすいように、スプレー型容器を用いることも可能である。スプレー型容器は、逆さまにしても噴霧が可能なミストタイプのスプレー型容器を用いることも可能である。スプレー型容器の形状は特に制限されないが、例えば、ポンプ式スプレーやトリガー式スプレー、エアゾール式スプレー等の公知の形状を用いることが可能である。ポンプ式スプレーでは、例えば、ポンプ式ノズルを容器に装着した形状とすることができ、汎用性や携帯性に優れる。トリガー式スプレーでは、例えば、ピストル型のノズル付噴霧器を容器に装着した形状とすることができ、小さな力で噴霧力を得られる。エアゾール式スプレーでは、例えば、炭酸ガス、窒素ガス、酸素ガス、フロンガス、液化石油ガス(LPG)ジメチルエーテル(DME)等の噴射剤を充填した容器形状とすることができ、より細かな液滴を噴霧することができるようになる。スプレー型容器の材質は特に制限されないが、例えば、ポリプロピレンやポリエチレン等の公知のプラスチック素材を用いることが可能である。 When applying the composition of the present invention, it is also possible to use a spray-type container to facilitate application to affected areas that are difficult to reach. As the spray type container, it is also possible to use a mist type spray type container that can spray even if it is turned upside down. The shape of the spray-type container is not particularly limited, but known shapes such as pump-type spray, trigger-type spray, and aerosol-type spray can be used. A pump-type spray, for example, can have a shape in which a pump-type nozzle is attached to a container, and is excellent in versatility and portability. In the trigger-type spray, for example, a pistol-type sprayer with a nozzle can be attached to a container, and spray force can be obtained with a small force. In the aerosol spray, for example, a container filled with a propellant such as carbon dioxide gas, nitrogen gas, oxygen gas, Freon gas, liquefied petroleum gas (LPG), dimethyl ether (DME), etc., can be used to spray finer droplets. be able to Although the material of the spray type container is not particularly limited, it is possible to use, for example, known plastic materials such as polypropylene and polyethylene.
本発明の組成物の別の態様として、泡状に吐出されるフォーム剤(泡状製剤ともいう)として適用することも可能である。フォーム剤は、例えば、過敏肌の状態によっては、塗布に伴う物理的刺激を低減させることが可能となり、また介護等で使用する際にも介護する側のハンドリングが容易となることから、好ましい。フォーム剤は、エアゾール式容器や、ポンプフォーマーなど、公知の形状を用いて提供することが出来る。 As another aspect of the composition of the present invention, it can be applied as a foaming agent (also referred to as a foaming formulation) that is discharged in the form of foam. Foam agents are preferable because, for example, depending on the condition of hypersensitive skin, it is possible to reduce the physical irritation associated with application, and when used for nursing care, etc., the caregiver can easily handle it. Foams can be provided using known forms such as aerosol containers and pump foamers.
[使用方法]
本発明の組成物の使用方法は、適用する対象者の状態、適用部位の状態、年齢などによって適宜変更され得るが、例えば、1日数回(例えば、約1回~5回、好ましくは2回~3回)、適量を適用部位の皮膚に塗布することで使用することができる。塗布期間は、適用する対象者の状態、適用部位の状態、年齢などによって適宜変更され得るが、例えば、約1~14日間、好ましくは約3~14日間とすることができる。
[how to use]
The method of using the composition of the present invention may be appropriately changed depending on the condition of the subject to be applied, the condition of the application site, age, etc. For example, several times a day (for example, about 1 to 5 times, preferably 2 times ~ 3 times), it can be used by applying an appropriate amount to the skin of the application site. The application period can be appropriately changed depending on the condition of the subject to be applied, the condition of the application site, age, etc., and can be, for example, about 1 to 14 days, preferably about 3 to 14 days.
本発明の組成物は、公知の方法により製造することができる。必要に応じて、滅菌工程を含めることができる。 The composition of the present invention can be produced by known methods. A sterilization step can be included, if desired.
本発明の組成物は、本発明の効果を損なわない範囲で、医薬品、医薬部外品、化粧品等として用いられ得る、公知の基剤又は担体と共に混合して製剤化することができる。その他に、本発明の組成物には、例えば、界面活性剤、油分、アルコール類、増粘剤、防腐剤、抗酸化剤、酸化防止剤、保存剤、キレート剤、pH調整剤、安定化剤、溶解補助剤、懸濁化剤、等張化剤、緩衝剤、無痛化剤、分散剤、香料、着色剤、色素、水等の添加剤を配合することができる。これらの添加剤は、1種を単独で又は2種以上を組み合わせて使用できる。 The composition of the present invention can be formulated by mixing with a known base or carrier that can be used as pharmaceuticals, quasi-drugs, cosmetics, etc., as long as the effects of the present invention are not impaired. In addition, the composition of the present invention may contain, for example, surfactants, oils, alcohols, thickeners, preservatives, antioxidants, antioxidants, preservatives, chelating agents, pH adjusters and stabilizers. , a solubilizing agent, a suspending agent, a tonicity agent, a buffering agent, an analgesic agent, a dispersing agent, a flavoring agent, a coloring agent, a pigment, and water. These additives can be used individually by 1 type or in combination of 2 or more types.
基剤又は担体としては、流動パラフィン、スクワラン、ゲル化炭化水素(プラスチベースなど)、オゾケライト、α-オレフィンオリゴマー、軽質流動パラフィンのような炭化水素;メチルポリシロキサン、架橋型メチルポリシロキサン、高重合メチルポリシロキサン、環状シリコーン、アルキル変性シリコーン、架橋型アルキル変性シリコーン、アミノ変性シリコーン、ポリエーテル変性シリコーン、ポリグリセリン変性シリコーン、架橋型ポリエーテル変性シリコーン、架橋型アルキルポリエーテル変性シリコーン、シリコーン・アルキル鎖共変性ポリエーテル変性シリコーン、シリコーン・アルキル鎖共変性ポリグリセリン変性シリコーン、ポリエーテル変性分岐シリコーン、ポリグリセリン変性分岐シリコーン、アクリルシリコン、フェニル変性シリコーン、シリコーンレジンのようなシリコーン油;ポリエチレングリコール;ジオキサン;ミリスチン酸イソプロピル、ミリスチン酸オクチルドデシル、パルミチン酸イソプロピル、パルミチン酸セチル、イソノナン酸イソノニル、テトラ2-エチルヘキサン酸ペンタエリスリットのようなエステル類;エタノール、イソプロパノールのような低級アルコール;ジエチレングリコールモノメチルエーテル、ジエチレングリコールモノエチルエーテルのようなグリコールエーテル;ポリエチレングリコール、プロピレングリコール、1,3-ブチレングリコール、グリセリン、イソプレングリコールなどの多価アルコール;水などの水系基剤などが挙げられる。本発明の効果を安定的に発揮する観点から、基剤又は担体は、1,3-ブチレングリコール及び/又はグリセリンが好ましい。 As bases or carriers, hydrocarbons such as liquid paraffin, squalane, gelling hydrocarbons (plastibase, etc.), ozokerite, α-olefin oligomers, light liquid paraffin; methylpolysiloxane, crosslinked methylpolysiloxane, highly polymerized methyl Polysiloxane, cyclic silicone, alkyl-modified silicone, cross-linked alkyl-modified silicone, amino-modified silicone, polyether-modified silicone, polyglycerin-modified silicone, cross-linked polyether-modified silicone, cross-linked alkyl polyether-modified silicone, both silicone and alkyl chain Modified polyether-modified silicone, silicone/alkyl chain co-modified polyglycerin-modified silicone, polyether-modified branched silicone, polyglycerin-modified branched silicone, acrylic silicone, phenyl-modified silicone, silicone oil such as silicone resin; polyethylene glycol; dioxane; myristine Esters such as isopropyl acid, octyldodecyl myristate, isopropyl palmitate, cetyl palmitate, isononyl isononanoate, pentaerythrityl tetra-2-ethylhexanoate; lower alcohols such as ethanol and isopropanol; diethylene glycol monomethyl ether, diethylene glycol monomethyl ether; glycol ethers such as ethyl ether; polyhydric alcohols such as polyethylene glycol, propylene glycol, 1,3-butylene glycol, glycerin and isoprene glycol; water-based bases such as water; From the viewpoint of stably exhibiting the effects of the present invention, the base or carrier is preferably 1,3-butylene glycol and/or glycerin.
基剤又は担体は、1種を単独で又は2種以上を組み合わせて使用できる。 The base or carrier can be used singly or in combination of two or more.
界面活性剤としては、例えば、ソルビタンモノイソステアレート、ソルビタンモノラウレート、ソルビタンモノパルミテート、ソルビタンモノステアレート、ペンタ-2-エチルヘキシル酸ジグリセロールソルビタン、テトラ-2-エチルヘキシル酸ジグリセロールソルビタンのようなソルビタン脂肪酸エステル類;モノステアリン酸プロピレングリコールのようなプロピレングリコール脂肪酸エステル類;ポリオキシエチレン硬化ヒマシ油40(HCO-40)、ポリオキシエチレン硬化ヒマシ油50(HCO-50)、ポリオキシエチレン硬化ヒマシ油60(HCO-60)、ポリオキシエチレン硬化ヒマシ油80などの硬化ヒマシ油誘導体;モノラウリル酸ポリオキシエチレン(20)ソルビタン(ポリソルベート20)、モノステアリン酸ポリオキシエチレン(20)ソルビタン(ポリソルベート60)、モノオレイン酸ポリオキシエチレン(20)ソルビタン(ポリソルベート80)、イソステアリン酸ポリオキシエチレン(20)ソルビタンのようなポリオキシエチレンソルビタン脂肪酸エステル類;ポリオキシエチレンモノヤシ油脂肪酸グリセリル;モノステアリン酸グリセリル、モノステアリン酸グリセリンリンゴ酸のようなグリセリン脂肪酸類;グリセリンアルキルエーテル;アルキルグルコシド;ポリオキシエチレン(20)オレイルエーテル、ポリオキシエチレンセチルエーテル、ポリオキシエチレン(9)ラウリルエーテルのようなポリオキシアルキレンアルキルエーテル;ステアリルアミン、オレイルアミンのようなアミン類;ポリオキシエチレン・メチルポリシロキサン共重合体、ラウリルPEG-9ポリジメチルシロキシエチルジメチコン、PEG-9ポリジメチルシロキシエチルジメチコンのようなシリコーン系界面活性剤;ラウリン酸塩、パルミチン酸塩、ココイルグルタミン酸塩、ヤシ油メチルアラニン塩、アシルメチルタウリン塩、ポリオキシエチレンラウリル硫酸塩のようなアニオン性界面活性剤、ラウリルジアミノエチルグリシン塩、ヤシ油脂肪酸ベタイン塩などの両性界面活性剤、ポリオキシエチレンラウリルアルコールエーテルなどの非イオン性界面活性剤などが挙げられる。なお、本明細書において、ポリオキシエチレンは「POE」とも記載され、括弧内の数値はエチレンオキシドの付加モル数を示す。 Examples of surfactants include sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, diglycerol sorbitan penta-2-ethylhexylate, and diglycerol sorbitan tetra-2-ethylhexylate. sorbitan fatty acid esters; propylene glycol fatty acid esters such as propylene glycol monostearate; polyoxyethylene hydrogenated castor oil 40 (HCO-40), polyoxyethylene hydrogenated castor oil 50 (HCO-50), polyoxyethylene hydrogenated Hydrogenated castor oil derivatives such as castor oil 60 (HCO-60), polyoxyethylene hydrogenated castor oil 80; polyoxyethylene (20) sorbitan monolaurate (polysorbate 20), polyoxyethylene (20) sorbitan monostearate (polysorbate 60), polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene (20) sorbitan monooleate (polysorbate 80), polyoxyethylene (20) sorbitan isostearate; polyoxyethylene monococonut fatty acid glyceryl; monostearic acid Glyceryl fatty acids such as glyceryl, glycerol monostearate malic acid; glycerol alkyl ether; alkyl glucoside; polyoxyethylene (20) oleyl ether, polyoxyethylene cetyl ether, polyoxyethylene (9) lauryl ether Alkylene alkyl ethers; amines such as stearylamine and oleylamine; silicone surfactants such as polyoxyethylene/methylpolysiloxane copolymer, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, and PEG-9 polydimethylsiloxyethyl dimethicone Anionic surfactants such as laurate, palmitate, cocoyl glutamate, coconut oil methylalanine, acylmethyltaurate, polyoxyethylene lauryl sulfate, lauryldiaminoethylglycinate, coconut fatty acid betaine Examples include amphoteric surfactants such as salts and nonionic surfactants such as polyoxyethylene lauryl alcohol ether. In this specification, polyoxyethylene is also described as "POE", and the numbers in parentheses indicate the number of added moles of ethylene oxide.
油分としては、天然動植物油脂類、炭化水素油、エステル油、シリコーン油、高級アルコール、高級脂肪酸、動植物や合成の精油などが挙げられる。 Examples of oils include natural animal and vegetable oils, hydrocarbon oils, ester oils, silicone oils, higher alcohols, higher fatty acids, animal and plant and synthetic essential oils, and the like.
天然動植物油脂類としては、例えば、アボガド油、アマニ油、アーモンド油、オリーブ油、カカオ油、牛脂、キリ油、小麦胚芽油、ゴマ油、米胚芽油、米糠油、サフラワー油、大豆油、月見草油、ツバキ油、トウモロコシ油、ナタネ油、馬脂、パーシック油、パーム油、パーム核油、ヒマシ油、ヒマワリ油、豚脂、ブドウ油、ホホバ油、マカデミアナッツ油、ミンク油、綿実油、モクロウ、ヤシ油、硬化ヤシ油、落花生油、ラノリン、卵黄油、ローズヒップ油等が挙げられる。 Natural animal and plant oils and fats include, for example, avocado oil, linseed oil, almond oil, olive oil, cacao oil, beef tallow, paulownia oil, wheat germ oil, sesame oil, rice germ oil, rice bran oil, safflower oil, soybean oil, and evening primrose oil. , camellia oil, corn oil, rapeseed oil, horse fat, persic oil, palm oil, palm kernel oil, castor oil, sunflower oil, lard, grape oil, jojoba oil, macadamia nut oil, mink oil, cottonseed oil, Japanese wax, coconut oil , hardened coconut oil, peanut oil, lanolin, egg yolk oil, rosehip oil and the like.
炭化水素油としては、パラフィン系炭化水素、オレフィン系炭化水素が用いられ、例えば、スクワラン、スクワレン、セレシン、パラフィン、プリスタン、マイクロクリスタリンワックス、流動パラフィン、ワセリン等が挙げられる。 As the hydrocarbon oil, paraffinic hydrocarbons and olefinic hydrocarbons are used, and examples thereof include squalane, squalene, ceresin, paraffin, pristane, microcrystalline wax, liquid paraffin, and vaseline.
エステル油としては、合成エステル類、高級アルコールと高級脂肪酸とのエステル類が用いられ、例えば、アジピン酸ジイソブチル、アジピン酸2-ヘキシルデシル、アジピン酸ジ-2-ヘプチルウンデシル、イソステアリン酸イソステアリル、トリイソステアリン酸トリメチロールプロパン、2-エチルヘキサン酸セチル、ジ-2-エチルヘキサン酸ネオペンチルグリコール、トリ-2-エチルヘキサン酸トリメチロールプロパン、テトラ-2-エチルヘキサン酸ペンタエリスリトール、オクタン酸セチル、オレイン酸オレイル、オレイン酸オクチルドデシル、オレイン酸デシル、ジカプリン酸ネオペンチルグリコール、コハク酸2-エチルヘキシル、ステアリン酸イソセチル、ステアリン酸ブチル、セバシン酸ジイソプロピル、乳酸セチル、乳酸テトラデシル、ミリスチン酸イソプリピル、ミリスチン酸オクチルドデシル、ミリスチン酸セチル、ミリスチン酸ミリスチル、パルミチン酸オクチル、パルミチン酸2-エチルヘキシル、パルミチン酸2-ヘキシルデシル、パルミチン酸2-ヘプチルウンデシル、12-ヒドロキシステアリン酸コレステリル、オレイン酸フィトステリル、リンゴ酸ジイソステアリル、パラメトキシケイ皮酸エステル、テトラロジン酸ペンタエリスリット、中鎖脂肪酸トリグリセリド等が挙げられる。 As ester oils, synthetic esters and esters of higher alcohols and higher fatty acids are used, such as diisobutyl adipate, 2-hexyldecyl adipate, di-2-heptylundecyl adipate, isostearyl isostearate, trimethylolpropane triisostearate, cetyl 2-ethylhexanoate, neopentyl glycol di-2-ethylhexanoate, trimethylolpropane tri-2-ethylhexanoate, pentaerythritol tetra-2-ethylhexanoate, cetyl octanoate, Oleyl oleate, octyldodecyl oleate, decyl oleate, neopentyl glycol dicaprate, 2-ethylhexyl succinate, isocetyl stearate, butyl stearate, diisopropyl sebacate, cetyl lactate, tetradecyl lactate, isopropyl myristate, octyl myristate Dodecyl, cetyl myristate, myristyl myristate, octyl palmitate, 2-ethylhexyl palmitate, 2-hexyldecyl palmitate, 2-heptylundecyl palmitate, cholesteryl 12-hydroxystearate, phytosteryl oleate, diisomalate Examples include stearyl, p-methoxycinnamate, pentaerythrityl tetrarosinate, medium-chain fatty acid triglyceride, and the like.
シリコーン油としては、例えば、ジメチルポリシロキサン、高重合メチルポリシロキサン、メチルフェニルポリシロキサン、メチルハイドロジェンポリシロキサン、オクタメチルシクロテトラシロキサン、オクタメチルシクロペンタシロキサン、デカメチルシクロヘキサシロキサン、ステアロキシシリコーン等の高級アルコキシ変性シリコーン、アルキル変性シリコーン、高級脂肪酸エステル変性シリコーン等が挙げられる。 Examples of silicone oils include dimethylpolysiloxane, highly polymerized methylpolysiloxane, methylphenylpolysiloxane, methylhydrogenpolysiloxane, octamethylcyclotetrasiloxane, octamethylcyclopentasiloxane, decamethylcyclohexasiloxane, and stearoxysilicone. higher alkoxy-modified silicones, alkyl-modified silicones, and higher fatty acid ester-modified silicones.
高級アルコールとしては、例えば、オクチルドデカノール、イソステアリルアルコール、オレイルアルコール、ステアリルアルコール、セタノール、ベヘニルアルコール等が挙げられる。 Examples of higher alcohols include octyldodecanol, isostearyl alcohol, oleyl alcohol, stearyl alcohol, cetanol, and behenyl alcohol.
高級脂肪酸としては、飽和又は不飽和の直鎖もしくは分岐鎖の炭素数12~22の脂肪酸を用いることができ、例えば、イソステアリン酸、オキシステアリン酸、オレイン酸、ステアリン酸、パルミチン酸、ベヘニン酸、ミリスチン酸、ラウリン酸、ラノリン酸、リノール酸、リノレン酸等が挙げられる。 As the higher fatty acid, a saturated or unsaturated linear or branched fatty acid having 12 to 22 carbon atoms can be used. Examples thereof include isostearic acid, oxystearic acid, oleic acid, stearic acid, palmitic acid, behenic acid, Examples include myristic acid, lauric acid, lanolinic acid, linoleic acid, and linolenic acid.
増粘剤としては、例えば、グアーガム、ローカストビーンガム、カラギーナン、キサンタンガム、カルボキシメチルセルロース、ヒドロキシメチルセルロース、ヒドロキシエチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、疎水化ヒドロキシプロピルメチルセルロース、ポリビニルアルコール、ポリビニルピロリドン、カルボキシビニルポリマー、アクリル酸メタクリル酸アルキル共重合体、ポリエチレングリコール、ベントナイト、(アクリル酸ヒドロキシエチル/アクリロイルジメチルタウリンNa)コポリマー、(アクリロイルジメチルタウリンアンモニウム/ビニルピロリドン)コポリマーなどが挙げられる。 Thickeners include, for example, guar gum, locust bean gum, carrageenan, xanthan gum, carboxymethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydrophobized hydroxypropylmethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer. , alkyl acrylate methacrylate copolymer, polyethylene glycol, bentonite, (hydroxyethyl acrylate/acryloyldimethyltaurate Na) copolymer, (acryloyldimethyltaurate ammonium/vinylpyrrolidone) copolymer, and the like.
防腐剤の好適な例としては、例えばパラオキシ安息香酸エステル類、クロロブタノール、ベンジルアルコール、フェネチルアルコール、デヒドロ酢酸、ソルビン酸などが挙げられる。 Preferable examples of preservatives include paraoxybenzoic acid esters, chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid, sorbic acid and the like.
抗酸化剤の好適な例としては、例えば亜硫酸塩、アスコルビン酸などが挙げられる。 Suitable examples of antioxidants include sulfites, ascorbic acid, and the like.
酸化防止剤としては、ジブチルヒドロキシトルエン(BHT)、ブチルヒドロキシアニソール、ソルビン酸、亜硫酸ナトリウム、アスコルビン酸、エリソルビン酸、L-システイン塩酸塩などが挙げられる。 Antioxidants include dibutylhydroxytoluene (BHT), butylhydroxyanisole, sorbic acid, sodium sulfite, ascorbic acid, erythorbic acid, L-cysteine hydrochloride and the like.
保存剤としては、安息香酸、安息香酸ナトリウム、デヒドロ酢酸、デヒドロ酢酸ナトリウム、パラオキシ安息香酸イソブチル、パラオキシ安息香酸イソプロピル、パラオキシ安息香酸ブチル、パラオキシ安息香酸エチル、パラオキシ安息香酸プロピル、パラオキシ安息香酸ベンジル、パラオキシ安息香酸メチル、フェノキシエタノールなどが挙げられる。 Preservatives include benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, isobutyl parahydroxybenzoate, isopropyl parahydroxybenzoate, butyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, benzyl parahydroxybenzoate, paraoxy Examples include methyl benzoate and phenoxyethanol.
キレート剤としては、EDTA・2ナトリウム塩、EDTA・カルシウム・2ナトリウム塩などが挙げられる。本発明の効果を顕著に奏する観点から、本発明の背中用にきび予防及び/又は治療薬は、EDTA・2ナトリウム塩をさらに含むことが好ましい。 The chelating agent includes EDTA.disodium salt, EDTA.calcium.disodium salt, and the like. From the viewpoint of exhibiting the effects of the present invention remarkably, the acne preventive and/or therapeutic agent for the back of the present invention preferably further contains EDTA.disodium salt.
pH調整剤としては、無機酸(塩酸、硫酸など)、有機酸(乳酸、乳酸ナトリウム、クエン酸、クエン酸ナトリウム、コハク酸、コハク酸ナトリウムなど)、無機塩基(水酸化カリウム、水酸化ナトリウムなど)、有機塩基(トリエタノールアミン、ジイソプロパノールアミン、トリイソプロパノールアミンなど)などが挙げられる。 Examples of pH adjusters include inorganic acids (hydrochloric acid, sulfuric acid, etc.), organic acids (lactic acid, sodium lactate, citric acid, sodium citrate, succinic acid, sodium succinate, etc.), inorganic bases (potassium hydroxide, sodium hydroxide, etc.). ), organic bases (triethanolamine, diisopropanolamine, triisopropanolamine, etc.), and the like.
安定化剤としては、ポリアクリル酸ナトリウム、ジブチルヒドロキシトルエン、ブチルヒドロキシアニソールなどが挙げられる。 Stabilizers include sodium polyacrylate, dibutylhydroxytoluene, butylhydroxyanisole and the like.
溶解補助剤の好適な例としては、例えばポリエチレングリコール、プロピレングリコール、D-マンニトール、安息香酸ベンジル、エタノール、トリスアミノメタン、コレステロール、トリエタノールアミン、炭酸ナトリウム、クエン酸ナトリウムなどが挙げられる。 Preferable examples of solubilizing agents include polyethylene glycol, propylene glycol, D-mannitol, benzyl benzoate, ethanol, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate and the like.
懸濁化剤の好適な例としては、例えばステアリルトリエタノールアミン、ラウリル硫酸ナトリウム、ラウリルアミノプロピオン酸、レシチン、塩化ベンザルコニウム、塩化ベンゼトニウム、モノステアリン酸グリセリンなどの界面活性剤;例えばポリビニルアルコール、ポリビニルピロリドン、カルボキシメチルセルロースナトリウム、メチルセルロース、ヒドロキシメチルセルロース、ヒドロキシエチルセルロース、ヒドロキシプロピルセルロースなどの親水性高分子などが挙げられる。 Suitable examples of suspending agents include surfactants such as stearyltriethanolamine, sodium lauryl sulfate, laurylaminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, glyceryl monostearate; Hydrophilic polymers such as polyvinylpyrrolidone, sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, and hydroxypropylcellulose.
等張化剤の好適な例としては、例えば塩化ナトリウム、グリセリン、D-マンニトールなどが挙げられる。 Preferable examples of tonicity agents include sodium chloride, glycerin, D-mannitol and the like.
緩衝剤の好適な例としては、例えばリン酸塩、酢酸塩、炭酸塩、クエン酸塩などの緩衝液などが挙げられる。 Preferable examples of buffers include phosphate, acetate, carbonate, citrate buffers, and the like.
無痛化剤の好適な例としては、例えばベンジルアルコールなどが挙げられる。 Preferable examples of soothing agents include benzyl alcohol and the like.
分散剤としては、例えば、ピロリン酸ナトリウム、ヘキサメタリン酸ナトリウム、ポリビニルアルコール、ポリビニルピロリドン、メチルビニルエーテル/無水マレイン酸架橋コポリマー、有機酸等が挙げられる。 Dispersants include, for example, sodium pyrophosphate, sodium hexametaphosphate, polyvinyl alcohol, polyvinylpyrrolidone, methyl vinyl ether/maleic anhydride crosslinked copolymer, organic acids and the like.
着色剤としては、無機顔料、天然色素などが挙げられる。 Examples of coloring agents include inorganic pigments and natural pigments.
本発明の組成物は、本発明の効果を損なわない範囲で、その他の有効成分を含むことができる。有効成分の具体例としては、例えば、保湿成分、パール光沢付与剤、コンディショニング剤、スクラブ剤、血行促進成分、収斂成分、紫外線吸収成分、紫外線散乱成分、洗浄成分、抗菌成分、抗炎症剤、ビタミン類、ペプチド又はその誘導体、アミノ酸又はその誘導体、細胞賦活化成分などが挙げられる。 The composition of the present invention can contain other active ingredients as long as the effects of the present invention are not impaired. Specific examples of active ingredients include moisturizing ingredients, pearl luster imparting agents, conditioning agents, scrubbing agents, blood circulation promoting ingredients, astringent ingredients, ultraviolet absorbing ingredients, ultraviolet scattering ingredients, cleaning ingredients, antibacterial ingredients, anti-inflammatory agents, and vitamins. , peptides or derivatives thereof, amino acids or derivatives thereof, cell activation components and the like.
保湿成分としては、グリセリン、1,3-ブチレングリコール、プロピレングリコール、ポリエチレングリコール、ジグリセリンのような多価アルコール;トレハロース、キシリトール、オリゴ糖のような糖類;ヒアルロン酸ナトリウム、ヘパリン類似物質、コンドロイチン硫酸ナトリウム、コラーゲン、エラスチン、ケラチン、キチン、キトサンのような高分子化合物;グリシン、アスパラギン酸、アルギニンのようなアミノ酸;乳酸ナトリウム、尿素、ピロリドンカルボン酸ナトリウムのような天然保湿因子;セラミド、コレステロール、リン脂質のような脂質;カミツレエキス、ハマメリスエキス、チャエキス、シソエキスのような植物抽出エキスなどが挙げられる。本発明の効果を安定的に発揮する観点から、保湿成分は、グリセリン及び/又は1,3-ブチレングリコールが好ましい。 Moisturizing ingredients include polyhydric alcohols such as glycerin, 1,3-butylene glycol, propylene glycol, polyethylene glycol, and diglycerin; sugars such as trehalose, xylitol, and oligosaccharides; sodium hyaluronate, heparin analogues, and chondroitin sulfate. Polymer compounds such as sodium, collagen, elastin, keratin, chitin, chitosan; amino acids such as glycine, aspartic acid, arginine; natural moisturizing factors such as sodium lactate, urea, sodium pyrrolidone carboxylate; ceramide, cholesterol, phosphorus lipids such as lipids; plant extracts such as chamomile extract, hamamelis extract, tea extract, perilla extract, and the like. From the viewpoint of stably exhibiting the effect of the present invention, the moisturizing component is preferably glycerin and/or 1,3-butylene glycol.
パール光沢付与剤としては、例えば、ジステアリン酸エチレングリコール、モノステアリン酸エチレングリコール、ジステアリン酸トリエチレングリコールなどが挙げられる。 Examples of pearl luster imparting agents include ethylene glycol distearate, ethylene glycol monostearate, and triethylene glycol distearate.
コンディショニング剤としては、例えば、カチオン化セルロース、カチオン化澱粉、カチオン化フェヌグリークガム、カチオン化グアーガム、カチオン化タラガム、カチオン化ローカストビーンガム、カチオン化キサンタンガム、ジアリル四級アンモニウム塩/アクリルアミド共重合物、ポリクオタニウム、ビニルイミダゾリウムトリクロライド/ビニルピロリドン共重合体、ヒドロキシエチルセルロース/ジメチルジアリルアンモニウムクロライド共重合体、ビニルピロリドン/四級化ジメチルアミノエチルメタクリレート共重合体、ポリビニルピロリドン/アルキルアミノアクリレート共重合体、ポリビニルピロリドン/アルキルアミノアクリレート/ビニルカプロラクタム共重合体、ビニルピロリドン/メタクリルアミドプロピル塩化トリメチルアンモニウム共重合体、アルキルアクリルアミド/アクリレート/アルキルアミノアルキルアクリルアミド/ポリエチレングリコールメタクリレート共重合体、アジピン酸/ジメチルアミノヒドロキシプロピルエチレントリアミン共重合体等が挙げられる。 Conditioning agents include, for example, cationized cellulose, cationized starch, cationized fenugreek gum, cationized guar gum, cationized tara gum, cationized locust bean gum, cationized xanthan gum, diallyl quaternary ammonium salt/acrylamide copolymer, polyquaternium. , vinylimidazolium trichloride/vinylpyrrolidone copolymer, hydroxyethylcellulose/dimethyldiallylammonium chloride copolymer, vinylpyrrolidone/quaternized dimethylaminoethyl methacrylate copolymer, polyvinylpyrrolidone/alkylaminoacrylate copolymer, polyvinylpyrrolidone /alkylamino acrylate/vinylcaprolactam copolymer, vinylpyrrolidone/methacrylamidopropyl trimethylammonium chloride copolymer, alkylacrylamide/acrylate/alkylaminoalkylacrylamide/polyethylene glycol methacrylate copolymer, adipic acid/dimethylaminohydroxypropylethylenetriamine A copolymer etc. are mentioned.
スクラブ剤としては、例えば、アプリコット核粉末、アーモンド殻粉末、アンズ核粉末、塩化ナトリウム粒、オリーブ核粉末、海水乾燥物粒、キャンデリラワックス、くるみ殻粉末、さくらんぼ核粉末、サンゴ粉末、炭粉末、はしばみ殻粉末、ポリエチレン末、無水ケイ酸等が挙げられる。 Examples of scrub agents include apricot kernel powder, almond shell powder, apricot kernel powder, sodium chloride grains, olive kernel powder, dried seawater grains, candelilla wax, walnut shell powder, cherry kernel powder, coral powder, charcoal powder, Hazel husk powder, polyethylene powder, silicic anhydride and the like can be used.
血行促進剤としては、例えば、アセチルコリン、イクタモール、カフェイン、カプサイシン、カンタリスチンキ、ガンマーオリザノール、ショオウキョウチンキ、ジンゲロン、セファランチン、センブリエキス、タンニン酸、トウガラシチンキ、トラゾリン、ニコチン酸トコフェロール、ニコチン酸ベンジルエステル等が挙げられる。 Blood circulation promoters include, for example, acetylcholine, ictamol, caffeine, capsaicin, cantharis tincture, gamma oryzanol, ginger tincture, gingerone, cepharanthine, jersey extract, tannic acid, capsicum tincture, tolazoline, tocopherol nicotinate, and benzyl nicotinate. Ester etc. are mentioned.
収斂成分としては、硫酸亜鉛、ヒドロキシアルミニウム、塩化アルミニウム、スルホ石炭酸亜鉛及びタンニン酸等が挙げられる。 Astringents include zinc sulfate, aluminum hydroxy, aluminum chloride, zinc sulfonate and tannic acid.
紫外線吸収成分としては、オクチルトリアゾン、ジエチルアミノヒドロキシベンゾイル安息香酸ヘキシル、ジメトキシベンジリデンジオキソイミダゾリジンプロピオン酸オクチル、パラメトキシケイ皮酸2-エチルヘキシル、t-ブチルメトキシジベンゾイルメタン、フェニルベンズイミダゾールスルホン酸、メトキシケイヒ酸オクチル、メトキシケイヒ酸エチルヘキシルなどが挙げられる。 Examples of ultraviolet absorbing components include octyl triazone, diethylaminohydroxybenzoylhexylbenzoate, dimethoxybenzylidenedioxoimidazolidine octylpropionate, 2-ethylhexyl paramethoxycinnamate, t-butylmethoxydibenzoylmethane, phenylbenzimidazolesulfonic acid, octyl methoxycinnamate, ethylhexyl methoxycinnamate, and the like.
紫外線散乱成分としては、含水ケイ酸、ケイ酸亜鉛、ケイ酸セリウム、ケイ酸チタン、酸化亜鉛、酸化ジルコニウム、酸化セリウム、酸化チタン、酸化鉄、無水ケイ酸等の無機化合物、それらの無機化合物を含水ケイ酸、水酸化アルミニウム、マイカやタルク等の無機粉体で被覆したり、ポリアミド、ポリエチレン、ポリエステル、ポリスチレン、ナイロン等の樹脂粉体に複合化したもの、さらにシリコン油や脂肪酸アルミニウム塩等で処理したものなどが挙げられる。 As the ultraviolet scattering component, inorganic compounds such as hydrous silicic acid, zinc silicate, cerium silicate, titanium silicate, zinc oxide, zirconium oxide, cerium oxide, titanium oxide, iron oxide, and silicic anhydride, and those inorganic compounds. Coated with inorganic powder such as hydrated silicic acid, aluminum hydroxide, mica and talc, compounded with resin powder such as polyamide, polyethylene, polyester, polystyrene, nylon, etc., and further with silicon oil, fatty acid aluminum salt, etc. processed, etc.
洗浄成分としては、ラウリン酸カリウム、ミリスチン酸カリウム、パルミチン酸カリウム又はステアリン酸カリウムなどのアルカリ金属塩、アルカノールアミド塩又はアミノ酸塩などの石けん類、ココイルグルタミン酸ナトリウム、ココイルメチルタウリンナトリウムなどのアミノ酸系界面活性剤、ラウレス硫酸ナトリウムなどのエーテル硫酸エステル塩、ラウリルエーテル酢酸ナトリウムなどのエーテルカルボン酸塩、アルキススルホコハク酸エステルナトリウムなどのスルホコハク酸エステル塩、ヤシ油脂肪酸モノエタノールアミド、ヤシ油脂肪酸時エタノールアミドなどの脂肪酸アルカノールアミド、ラウリルリン酸ナトリウム、ポリオキシエチレンラウリルエーテルリン酸ナトリウムなどのモノアルキルリン酸エステル塩、ヤシ油脂肪酸アミドプロピルジメチルアミノ酢酸ベタイン、ラウリルジメチルアミノ酢酸ベタイン、2-アルキル-N-カルボキシメチル-N-ヒドロキシエチルイミダゾリニウムベタイン、ラウリルヒドロキシスルホベタイン及びラウロイルアミドエチルヒドロキシエチルカルボキシメチルベタインヒドロキシプロピルリン酸ナトリウムなどのベタイン型両性界面活性剤、ラウリルアミノプロピオン酸ナトリウムなどのアミノ酸型両性界面活性剤などが挙げられる。 Detergents include alkali metal salts such as potassium laurate, potassium myristate, potassium palmitate and potassium stearate; soaps such as alkanolamide salts and amino acid salts; Active agents, ether sulfate salts such as sodium laureth sulfate, ether carboxylates such as sodium lauryl ether acetate, sulfosuccinate salts such as sodium alkis sulfosuccinate, coconut oil fatty acid monoethanolamide, coconut oil fatty acid ethanolamide Fatty acid alkanolamides such as sodium lauryl phosphate, monoalkyl phosphate ester salts such as sodium polyoxyethylene lauryl ether phosphate, coconut oil fatty acid amidopropyl dimethylamino acetate betaine, lauryl dimethylamino acetate betaine, 2-alkyl-N- Betaine-type amphoteric surfactants such as carboxymethyl-N-hydroxyethylimidazolinium betaine, lauryl hydroxysulfobetaine and lauroylamidoethyl hydroxyethyl carboxymethyl betaine sodium hydroxypropyl phosphate, amino acid-type amphoteric surfactants such as sodium laurylaminopropionate activator and the like.
抗菌成分としては、クロルヘキシジン、塩化ベンザルコニウム、アクリノール、エタノール、塩化ベンゼトニウム、クレゾール、グルコン酸及びその誘導体、ポピドンヨード、ヨウ化カリウム、ヨウ素、トリクロカルバン、トリクロサン、感光素101号、感光素201号、パラベン、フェノキシエタノール、1,2-ペンタンジオール、塩酸アルキルジアミノグリシン、ピロクトオラミン、ミコナゾールなどが挙げられる。 Antibacterial components include chlorhexidine, benzalkonium chloride, acrinol, ethanol, benzethonium chloride, cresol, gluconic acid and its derivatives, povidone iodine, potassium iodide, iodine, triclocarban, triclosan, photosensitizer No. 101, photosensitizer No. 201, Paraben, phenoxyethanol, 1,2-pentanediol, alkyldiaminoglycine hydrochloride, pyroctoolamine, miconazole and the like.
抗炎症剤としては、他の非ステロイド系抗炎症剤を更に配合することも可能であり、アラントイン又はその誘導体;インドメタシン;イブプロフェン;イブプロフェンピコノール;ブフェキサマク;フルフェナム酸ブチル;ベンダザック;ピロキシカム;ケトプロフェン;フェルビナク;サリチル酸メチルおよびサリチル酸グリコール等のサリチル酸誘導体;メントール;カンフルなどが挙げられる。 As anti-inflammatory agents, other non-steroidal anti-inflammatory agents can be further compounded, such as allantoin or its derivatives; indomethacin; ibuprofen; ibuprofenpiconol; bufexamac; butyl flufenamate; felbinac; salicylic acid derivatives such as methyl salicylate and glycol salicylate; menthol; camphor;
ビタミン類としては、トコフェロール酢酸エステル、dl-α-トコフェロール、コハク酸dl-α-トコフェロール、コハク酸dl-α-トコフェロールカルシウム等のビタミンE類;リボフラビン、フラビンモノヌクレオチド、フラビンアデニンジヌクレオチド、リボフラビン酪酸エステル、リボフラビンテトラ酪酸エステル、リボフラビン5’-リン酸エステルナトリウム、リボフラビンテトラニコチン酸エステル等のビタミンB2類;ニコチン酸dl-α-トコフェロール、ニコチン酸ベンジル、ニコチン酸メチル、ニコチン酸β-ブトキシエチル、ニコチン酸1-(4-メチルフェニル)エチル等のニコチン酸類;アスコルビゲン-A、アスコルビン酸ステアリン酸エステル、アスコルビン酸パルミチン酸エステル、ジパルミチン酸L-アスコルビルなどのビタミンC類;メチルヘスペリジン、エルゴカルシフェロール、コレカルシフェロールなどのビタミンD類;フィロキノン、ファルノキノン等のビタミンK類、γ-オリザノール、ジベンゾイルチアミン、ジベンゾイルチアミン塩酸塩;チアミン塩酸塩、チアミンセチル塩酸塩、チアミンチオシアン酸塩、チアミンラウリル塩酸塩、チアミン硝酸塩、チアミンモノリン酸塩、チアミンリジン塩、チアミントリリン酸塩、チアミンモノリン酸エステルリン酸塩、チアミンモノリン酸エステル、チアミンジリン酸エステル、チアミンジリン酸エステル塩酸塩、チアミントリリン酸エステル、チアミントリリン酸エステルモノリン酸塩等のビタミンB1類;塩酸ピリドキシン、酢酸ピリドキシン、塩酸ピリドキサール、5’-リン酸ピリドキサール、塩酸ピリドキサミン等のビタミンB6類;シアノコバラミン、ヒドロキソコバラミン、デオキシアデノシルコバラミン等のビタミンB12類;葉酸、プテロイルグルタミン酸等の葉酸類;ニコチン酸、ニコチン酸アミドなどのニコチン酸類;パントテン酸、パントテン酸カルシウム、パントテニルアルコール(パンテノール)、D-パンテサイン、D-パンテチン、補酵素A、パントテニルエチルエーテル等のパントテン酸類;ビオチン、ビオチシン等のビオチン類;アスコルビン酸、アスコルビン酸ナトリウム、デヒドロアスコルビン酸、アスコルビン酸リン酸エステルナトリウム、アスコルビン酸リン酸エステルマグネシウム等のアスコルビン酸誘導体であるビタミンC類;カルニチン、フェルラ酸、α-リポ酸、オロット酸等のビタミン様作用因子などが挙げられる。 Vitamins include vitamin E such as tocopherol acetate, dl-α-tocopherol, dl-α-tocopherol succinate, dl-α-tocopherol calcium succinate; riboflavin, flavin mononucleotide, flavin adenine dinucleotide, riboflavin butyric acid Vitamin B2s such as esters, riboflavin tetrabutyrate, riboflavin 5′-phosphate sodium, riboflavin tetranicotinate; dl-α-tocopherol nicotinate, benzyl nicotinate, methyl nicotinate, β-butoxyethyl nicotinate, Nicotinic acids such as 1-(4-methylphenyl)ethyl nicotinate; Vitamin Cs such as ascorbigen-A, ascorbyl stearate, ascorbyl palmitate, and L-ascorbyl dipalmitate; methylhesperidin, ergocalciferol , Vitamin D such as cholecalciferol; Vitamin K such as phylloquinone and farnoquinone, γ-oryzanol, dibenzoylthiamine, dibenzoylthiamine hydrochloride; thiamine hydrochloride, thiamine cetyl hydrochloride, thiamine thiocyanate, thiamine lauryl hydrochloride Salt, thiamine nitrate, thiamine monophosphate, thiamine lysine salt, thiamine triphosphate, thiamine monophosphate phosphate, thiamine monophosphate, thiamine diphosphate, thiamine diphosphate hydrochloride, thiamine triphosphate, thiamine Vitamin B1s such as triphosphate ester monophosphate; Vitamin B6s such as pyridoxine hydrochloride, pyridoxine acetate, pyridoxal hydrochloride, 5'-pyridoxal phosphate, pyridoxamine hydrochloride; Vitamin B12s such as cyanocobalamin, hydroxocobalamin, deoxyadenosylcobalamin folic acids such as folic acid and pteroylglutamic acid; nicotinic acids such as nicotinic acid and nicotinamide; pantothenic acid, calcium pantothenate, pantothenyl alcohol (panthenol), D-panthesaine, D-pantethine, coenzyme A, Pantothenic acids such as pantothenyl ethyl ether; Biotins such as biotin and biotisin; Vitamin C which is an ascorbic acid derivative such as ascorbic acid, sodium ascorbate, dehydroascorbic acid, sodium ascorbyl phosphate, and magnesium ascorbyl phosphate. Class; carnitine, ferulic acid, α-lipo Acids, vitamin-like acting factors such as orotic acid and the like can be mentioned.
ペプチド又はその誘導体としては、ケラチン分解ペプチド、加水分解ケラチン、コラーゲン、魚由来コラーゲン、アテロコラーゲン、ゼラチン、エラスチン、エラスチン分解ペプチド、コラーゲン分解ペプチド、加水分解コラーゲン、塩化ヒドロキシプロピルアンモニウム加水分解コラーゲン、エラスチン分解ペプチド、コンキオリン分解ペプチド、加水分解コンキオリン、シルク蛋白分解ペプチド、加水分解シルク、ラウロイル加水分解シルクナトリウム、大豆蛋白分解ペプチド、加水分解大豆蛋白、小麦蛋白、小麦蛋白分解ペプチド、加水分解小麦蛋白、カゼイン分解ペプチド、アシル化ペプチド(パルミトイルオリゴペプチド、パルミトイルペンタペプチド、パルミトイルテトラペプチド等)などが挙げられる。 Peptides or derivatives thereof include keratin-degrading peptides, hydrolyzed keratin, collagen, fish-derived collagen, atelocollagen, gelatin, elastin, elastin-degrading peptides, collagen-degrading peptides, hydrolyzed collagen, hydroxypropylammonium chloride hydrolyzed collagen, and elastin-degrading peptides. , conchiolin hydrolyzed peptide, hydrolyzed conchiolin, silk proteolytic peptide, hydrolyzed silk, lauroyl hydrolyzed silk sodium, soybean proteolytic peptide, hydrolyzed soy protein, wheat protein, wheat proteolytic peptide, hydrolyzed wheat protein, casein hydrolyzed peptide , acylated peptides (palmitoyl oligopeptide, palmitoyl pentapeptide, palmitoyl tetrapeptide, etc.).
アミノ酸又はその誘導体としては、ベタイン(トリメチルグリシン)、プロリン、ヒドロキシプロリン、アルギニン、リジン、セリン、グリシン、アラニン、フェニルアラニン、β-アラニン、スレオニン、グルタミン酸、グルタミン、アスパラギン、アスパラギン酸、システイン、シスチン、メチオニン、ロイシン、イソロイシン、バリン、ヒスチジン、タウリン、γ-アミノ酪酸、γ-アミノ-β-ヒドロキシ酪酸、カルニチン、カルノシン、クレアチン等が挙げられる。 Amino acids or their derivatives include betaine (trimethylglycine), proline, hydroxyproline, arginine, lysine, serine, glycine, alanine, phenylalanine, β-alanine, threonine, glutamic acid, glutamine, asparagine, aspartic acid, cysteine, cystine, methionine. , leucine, isoleucine, valine, histidine, taurine, γ-aminobutyric acid, γ-amino-β-hydroxybutyric acid, carnitine, carnosine, creatine and the like.
細胞賦活化成分としては、γ-アミノ酪酸、ε-アミノカプロン酸などのアミノ酸類、レチノール、チアミン、リボフラビン、塩酸ピリドキシン、パントテン酸類などのビタミン類、グリコール酸、乳酸などのα-ヒドロキシ酸類、タンニン、フラボノイド、サポニン、感光素301号などが挙げられる。 Cell activation components include amino acids such as γ-aminobutyric acid and ε-aminocaproic acid, vitamins such as retinol, thiamine, riboflavin, pyridoxine hydrochloride and pantothenic acids, α-hydroxy acids such as glycolic acid and lactic acid, tannins, flavonoids, saponins, photosensitizer No. 301 and the like.
次に、実施例や試験例により本発明を具体的に説明するが、本発明は以下の実施例や試験例に限定されるものではない。 Next, the present invention will be described in detail with reference to examples and test examples, but the present invention is not limited to the following examples and test examples.
(試験例1.ケラチノサイトでのKPRP遺伝子の発現に影響を与える物質のスクリーニング)
[試験方法]
以下の手順に従い、表皮角化細胞によって産生されたKPRPタンパク質を測定した。
ヒト正常表皮角化細胞(NHEK)(倉敷紡績株式会社製)を9×104cells/wellになるように96ウェルプレート(BDファルコン社製、No.353219)に播種し、37℃で2日間培養した。細胞の生育に問題がないことを顕微鏡観察により確認した後、塩化カルシウムを終濃度1mM、及び、表1に記載の各種薬剤を、終濃度が表1の所定濃度となるよう培地に添加し、37℃で5日間培養した。細胞間KPRPタンパク質を、抗KPRP抗体(アブカム社製)を用いた免疫染色により染色し、細胞核をHoechst33342(同仁化学研究所社製)にて染色した後、ImageXpress
(モレキュラーデバイス社製)にて染色面積、強度並びに核数を計測し、KPRPタンパク質産生量を評価した。
(Test Example 1. Screening for Substances Affecting KPRP Gene Expression in Keratinocytes)
[Test method]
KPRP protein produced by epidermal keratinocytes was measured according to the following procedure.
Human normal epidermal keratinocytes (NHEK) (manufactured by Kurashiki Boseki Co., Ltd.) were seeded at 9×10 4 cells/well in a 96-well plate (manufactured by BD Falcon, No. 353219) and incubated at 37° C. for 2 days. cultured. After confirming by microscopic observation that there is no problem with cell growth, calcium chloride at a final concentration of 1 mM and various agents listed in Table 1 were added to the medium so that the final concentrations were the predetermined concentrations in Table 1, Cultured at 37° C. for 5 days. Intercellular KPRP protein was stained by immunostaining using an anti-KPRP antibody (manufactured by Abcam), cell nuclei were stained with Hoechst33342 (manufactured by Dojindo Laboratories), and then subjected to ImageXpress.
(manufactured by Molecular Devices), the stained area, intensity and number of nuclei were measured to evaluate the amount of KPRP protein produced.
評価対象となる薬剤を添加しないこと以外は、上記と同様に処理したサンプルをブランクとし、ブランクにおけるKPRPタンパク質の産生量を100%とした場合の、各サンプルのKPRPの産生量(%)を表1に併せて示す。 The amount of KPRP produced in each sample (%) is shown when the amount of KPRP protein produced in the blank is 100%, and the sample treated in the same manner as described above is used as a blank, except that the drug to be evaluated is not added. 1 together.
表1に示されるとおり、ウフェナマート及び、イソプロピルメチルフェノールは表皮角化細胞におけるKPRPタンパク質の産生を促進することが明らかとなった。 As shown in Table 1, ufenamate and isopropylmethylphenol were found to promote the production of KPRP protein in epidermal keratinocytes.
これらの結果は、ウフェナマート及びイソプロピルメチルフェノールが、KPRPタンパク質の産生を促進することにより、皮膚バリア機能を促進し、過敏状態となった皮膚を正常化することを示唆するものである。 These results suggest that ufenamate and isopropylmethylphenol promote the production of KPRP protein, thereby promoting skin barrier function and normalizing hypersensitive skin.
[製剤処方例]
以下、本発明の製剤処方例を示す。表2に記載の処方で、乳液(製剤例1、5)、クリーム剤(製剤例2)、ゲル剤(製剤例3)、液剤(製剤例4)を常法により調製した。これらの製剤は、KPRPタンパク質発現亢進作用が新たに見出された(A)ウフェナマート及びその塩、並びにイソプロピルメチルフェノールからなる群より選択される少なくとも1種を含有するため、KPRP遺伝子が介在する角層正常化機能亢進によりもたらされる各種用途のために有効に用いられる。
[Formulation example]
Hereinafter, formulation examples of the present invention are shown. Using the formulations shown in Table 2, emulsions (formulation examples 1 and 5), creams (formulation example 2), gels (formulation example 3), and liquid formulations (formulation example 4) were prepared by conventional methods. Since these formulations contain at least one selected from the group consisting of (A) ufenamate and its salts, and isopropylmethylphenol, which have been newly found to have a KPRP protein expression-enhancing effect, the KPRP gene-mediated horn It is effectively used for a variety of applications provided by layer normalization hyperfunction.
Claims (10)
The composition according to any one of claims 1 to 9, which is applied to middle-aged and elderly people.
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