JP6920031B2 - Chronic keratinized eczema improving agent - Google Patents
Chronic keratinized eczema improving agent Download PDFInfo
- Publication number
- JP6920031B2 JP6920031B2 JP2016131069A JP2016131069A JP6920031B2 JP 6920031 B2 JP6920031 B2 JP 6920031B2 JP 2016131069 A JP2016131069 A JP 2016131069A JP 2016131069 A JP2016131069 A JP 2016131069A JP 6920031 B2 JP6920031 B2 JP 6920031B2
- Authority
- JP
- Japan
- Prior art keywords
- chronic
- eczema
- keratinized
- retinol
- acid
- 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.)
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- 239000011590 β-tocopherol Substances 0.000 description 1
- 239000002478 γ-tocopherol Substances 0.000 description 1
- QUEDXNHFTDJVIY-DQCZWYHMSA-N γ-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-DQCZWYHMSA-N 0.000 description 1
- 239000002446 δ-tocopherol Substances 0.000 description 1
- GZIFEOYASATJEH-VHFRWLAGSA-N δ-tocopherol Chemical compound OC1=CC(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1 GZIFEOYASATJEH-VHFRWLAGSA-N 0.000 description 1
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Description
本発明は、慢性角化型湿疹に対して優れた改善効果を奏する慢性角化型湿疹改善剤に関する。 The present invention relates to a chronic keratinized eczema improving agent which has an excellent improving effect on chronic keratinized eczema.
健康な肌は、適切なターンオーバーにより肌表面が滑らかに保たれている。しかしながら、皮膚に、圧迫や摩擦等の機械的刺激が繰り返されると、当該皮膚部位に炎症が生じると共に、メラニン産生、角質層の肥厚化、乾燥が進み、黒ずみを生じることがある。このように角層の肥厚化及び乾燥を伴って黒ずみを生じている皮膚症状は、慢性角化型湿疹と呼ばれている。慢性角化型湿疹は、肘や膝等、日常生活において機械的刺激が繰り返される皮膚部位によく見られる症状である。慢性角化型湿疹において、肥厚化した角質は水分含有量が低下し、細菌感染の原因になり、更に黒ずんだ皮膚は見た目を悪化させ、生活者のQOLを低下させる要因にもなる。 For healthy skin, the skin surface is kept smooth by proper turnover. However, when the skin is repeatedly subjected to mechanical stimuli such as compression and friction, the skin site may become inflamed, and melanin production, thickening of the stratum corneum, and dryness may progress, resulting in darkening. Such a skin symptom that causes darkening accompanied by thickening and dryness of the stratum corneum is called chronic keratinized eczema. Chronic keratinized eczema is a common symptom of skin areas such as elbows and knees where mechanical irritation is repeated in daily life. In chronic keratinized eczema, thickened keratin reduces the water content and causes bacterial infection, and darkened skin also deteriorates the appearance and causes a decrease in the quality of life of consumers.
従来、肘や膝の角質硬化部位を柔軟化させるには、尿素及びトレハロースを含有する乳化化粧料が有効であることが知られている(特許文献1参照)。しかしながら、特許文献1に記載の乳化化粧料では、慢性角化型湿疹に対する改善効果は緩慢であり、慢性角化型湿疹に適用した場合では十分満足のいくものではなかった。また、従来、医療現場では角質硬化部位の除去のためにレーザー治療等が行われていたが、慢性角化型湿疹はターンオーバー機能が低下していることから、治療後に組織がうまく再生できず、却ってメラニン産生が促進されてしまうことが懸念されていた。 Conventionally, it is known that an emulsified cosmetic containing urea and trehalose is effective for softening the keratin hardened part of the elbow or knee (see Patent Document 1). However, the emulsified cosmetics described in Patent Document 1 have a slow improving effect on chronic keratinized eczema, and are not sufficiently satisfactory when applied to chronic keratinized eczema. In addition, in the past, laser treatment was performed to remove the hardened keratinous part in the medical field, but since the turnover function of chronic keratinized eczema is reduced, the tissue cannot be regenerated well after the treatment. On the contrary, there was concern that melanin production would be promoted.
このような従来技術を背景として、慢性角化型湿疹を効果的に改善できる新たな製剤の開発が望まれている。 Against the background of such prior art, it is desired to develop a new preparation capable of effectively improving chronic keratinized eczema.
本発明の目的は、慢性角化型湿疹に対して優れた改善効果を奏する慢性角化型湿疹改善剤を提供することである。 An object of the present invention is to provide a chronic keratinized eczema improving agent which has an excellent improving effect on chronic keratinized eczema.
本発明者は、前記課題を解決すべく鋭意検討を行ったところ、(A)尿素、(B)グリチルリチン酸、グリチルレチン酸、それらの誘導体、及びそれらの塩よりなる群から選択される少なくとも1種、並びに(C)γ−オリザノールを組み合わせて使用することによって、これらの成分の相乗的作用によって、慢性角化型湿疹の改善効果が格段に高まることを見出した。本発明は、かかる知見に基づいてさらに検討を重ねることにより完成したものである。 The present inventor has conducted diligent studies to solve the above problems, and found that at least one selected from the group consisting of (A) urea, (B) glycyrrhizinic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof. , And (C) γ-oryzanol in combination, it was found that the synergistic action of these components significantly enhances the ameliorating effect of chronic keratinized eczema. The present invention has been completed by further studies based on such findings.
即ち、本発明は、下記に掲げる態様の発明を提供する。
項1.(A)尿素、
(B)グリチルリチン酸、グリチルレチン酸、それらの誘導体、及びそれらの塩よりなる群から選択される少なくとも1種、並びに
(C)γ−オリザノール
を含有する慢性角化型湿疹改善剤。
項2. 更に、(D)トコフェロール及び/又はその誘導体、或は/並びに(E)レチノール及び/又はその誘導体を含有する、項1に記載の慢性角化型湿疹改善剤。
項3. (D)トコフェロール及び/又はその誘導体、並びに(E)レチノール及び/又はその誘導体を含有する、項2に記載の慢性角化型湿疹改善剤。
項4. 慢性角化型湿疹における角層の肥厚化及び黒ずみの双方の症状を改善するために使用される、項1〜3のいずれかに記載の慢性角化型湿疹改善剤。
That is, the present invention provides the inventions of the following aspects.
Item 1. (A) Urea,
(B) At least one selected from the group consisting of glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof, and
(C) Chronic keratinized eczema improving agent containing γ-oryzanol.
Item 2. Item 2. The chronic keratinized eczema improving agent according to Item 1, further comprising (D) tocopherol and / or a derivative thereof, or / and (E) retinol and / or a derivative thereof.
Item 3. Item 2. The chronic keratinized eczema improving agent according to Item 2, which contains (D) tocopherol and / or a derivative thereof, and (E) retinol and / or a derivative thereof.
Item 4. Item 3. The chronic keratinized eczema improving agent according to any one of Items 1 to 3, which is used to improve the symptoms of both thickening and darkening of the stratum corneum in chronic keratinized eczema.
本発明の慢性角化型湿疹改善剤は、慢性角化型湿疹における角質層の肥厚化、黒ずみ等の症状を効果的に改善し、健康な皮膚状態に導くことができる。更に、本発明の慢性角化型湿疹改善剤は、レーザー治療のように角化した組織を強制的に除去するのではないため、治療後にメラニンの産生が促進され難い点でも優れている。 The chronic keratinized eczema improving agent of the present invention can effectively improve symptoms such as thickening of the stratum corneum and darkening in chronic keratinized eczema, leading to a healthy skin condition. Furthermore, the chronic keratinized eczema improving agent of the present invention is also excellent in that it is difficult to promote the production of melanin after the treatment because it does not forcibly remove the keratinized tissue as in the laser treatment.
本発明の慢性角化型湿疹改善剤は、尿素(以下、(A)成分と表記することもある)、グリチルリチン酸、グリチルレチン酸、それらの誘導体、及びそれらの塩よりなる群から選択される少なくとも1種(以下、(B)成分と表記することもある)、並びにγ−オリザノール(以下、(C)成分と表記することもある)を含有することを特徴とする。以下、本発明の慢性角化型湿疹改善剤について詳述する。 The chronic keratinized eczema improving agent of the present invention is at least selected from the group consisting of urea (hereinafter, also referred to as component (A)), glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof. It is characterized by containing one type (hereinafter, sometimes referred to as component (B)) and γ-oryzanol (hereinafter, sometimes referred to as component (C)). Hereinafter, the chronic keratinized eczema improving agent of the present invention will be described in detail.
(A)成分
本発明の慢性角化型湿疹改善剤は、尿素を含有する。尿素は、水素結合による水分保持作用と共に、タンパク質変性により不要な角質を除去する効果を併せ持つため、古くから角化症治療薬として知られている成分である。
(A) Ingredient The chronic keratinized eczema improving agent of the present invention contains urea. Urea is a component that has long been known as a therapeutic agent for keratosis because it has the effect of removing unnecessary keratin by protein denaturation as well as the water retention effect by hydrogen bonding.
本発明で使用される尿素については、その原料、製造方法、精製方法等は特に制限されず、化学合成により自ら製造したものであってもよく、また市販品を用いてもよい。尿素の市販品としては、例えば、高杉製薬株式会社、昭和化学株式会社、関東化学株式会社等で製造又は販売されている商品が挙げられる。 The raw material, production method, purification method, etc. of the urea used in the present invention are not particularly limited, and the urea may be produced by itself by chemical synthesis, or a commercially available product may be used. Examples of commercially available urea products include products manufactured or sold by Takasugi Pharmaceutical Co., Ltd., Showa Chemical Co., Ltd., Kanto Chemical Co., Inc., and the like.
本発明の慢性角化型湿疹改善剤おける尿素の含有量については、特に制限されないが、例えば、5〜25重量%、好ましくは5〜22重量%、更に好ましくは10〜20重量%が挙げられる。 The content of urea in the chronic keratinizing eczema improving agent of the present invention is not particularly limited, and examples thereof include 5 to 25% by weight, preferably 5 to 22% by weight, and more preferably 10 to 20% by weight. ..
(B)成分
本発明の慢性角化型湿疹改善剤は、グリチルリチン酸、グリチルレチン酸、それらの誘導体、及び/又はそれらの塩を含有する。これらの成分は、その炭素骨格がステロイドに類似しており、免疫反応を鈍化させ、炎症反応を弱める作用を有することが知られている成分である。
(B) Ingredient The chronic keratinized eczema improving agent of the present invention contains glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and / or salts thereof. These components have a carbon skeleton similar to that of steroids, and are known to have an action of slowing the immune response and weakening the inflammatory response.
グリチルリチン酸は、抗炎症作用や抗アレルギー作用等を有することが知られている公知の薬剤である。 Glycyrrhizic acid is a known drug known to have anti-inflammatory action, anti-allergic action and the like.
グリチルリチン酸の誘導体の種類については、薬学的に許容できることを限度として特に制限されないが、具体的には、グリチルリチン酸メチル、グリチルリチン酸ステアリル等が挙げられる。これらのグリチルリチン酸の誘導体は、1種単独で使用してもよく、また2種以上を組み合わせて使用してもよい。 The type of the derivative of glycyrrhizic acid is not particularly limited as long as it is pharmaceutically acceptable, and specific examples thereof include methyl glycyrrhizinate and stearyl glycyrrhizinate. These derivatives of glycyrrhizic acid may be used alone or in combination of two or more.
グリチルリチン酸及びその誘導体の塩としては、薬理学上許容されるものである限り特に制限されないが、具体的には、ナトリウム塩、カリウム塩、二カリウム塩等のアルカリ金属塩;アンモニウム塩等が挙げられる。これらのグリチルリチン酸及びその誘導体の塩は、1種単独で使用してもよく、また2種以上を組み合わせて使用してもよい。 The salt of glycyrrhizinic acid and its derivative is not particularly limited as long as it is pharmacologically acceptable, and specific examples thereof include alkali metal salts such as sodium salt, potassium salt and dipotassium salt; ammonium salt and the like. Be done. These salts of glycyrrhizic acid and its derivatives may be used alone or in combination of two or more.
グリチルレチン酸は、抗炎症作用や抗アレルギー作用等を有することが知られている公知の薬剤である。 Glycyrrhetinic acid is a known drug known to have an anti-inflammatory action, an antiallergic action and the like.
グリチルレチン酸の誘導体の種類については、薬学的に許容できることを限度として特に制限されないが、具体的には、グリチルレチン酸ピリドキシン、グリチルレチン酸ステアリル、グリチルレチン酸グリセリル、グリチルレチン酸モノグルクロニド等が挙げられる。これらのグリチルレチン酸の誘導体は、1種単独で使用してもよく、また2種以上を組み合わせて使用してもよい。 The type of the derivative of glycyrrhetinic acid is not particularly limited as long as it is pharmaceutically acceptable, and specific examples thereof include pyridoxine glycyrrhetinate, stearyl glycyrrhetinate, glyceryl glycyrrhetinate, and monoglucuronide glycyrrhetinate. These derivatives of glycyrrhetinic acid may be used alone or in combination of two or more.
グリチルレチン酸及びその誘導体の塩としては、薬理学上許容されるものである限り特に制限されないが、具体的には、ナトリウム塩、カリウム塩等のアルカリ金属塩;アンモニウム塩等が挙げられる。これらのグリチルレチン酸及びその誘導体の塩は、1種単独で使用してもよく、また2種以上を組み合わせて使用してもよい。 The salt of glycyrrhetinic acid and its derivative is not particularly limited as long as it is pharmacologically acceptable, and specific examples thereof include alkali metal salts such as sodium salt and potassium salt; ammonium salts and the like. These salts of glycyrrhetinic acid and its derivatives may be used alone or in combination of two or more.
本発明の慢性角化型湿疹改善剤において、(B)成分として、グリチルリチン酸、グリチルリチン酸の塩、グリチルリチン酸の誘導体、グリチルリチン酸の誘導体の塩、グリチルレチン酸、グリチルレチン酸の塩、グリチルレチン酸の誘導体、及びグリチルレチン酸の誘導体の塩の中から、1種を選択して使用してもよく、2種以上を組み合わせて使用してもよい。 In the chronic keratinized eczema improving agent of the present invention, the component (B) includes glycyrrhizic acid, a salt of glycyrrhizic acid, a derivative of glycyrrhizic acid, a salt of a derivative of glycyrrhizic acid, a salt of glycyrrhetinic acid, a salt of glycyrrhetinic acid, and a derivative of glycyrrhetinic acid. , And one of the salts of the derivative of glycyrrhizinic acid may be selected and used, or two or more thereof may be used in combination.
これらの(B)成分の中でも、慢性角化型湿疹の改善効果をより一層向上させるという観点から、好ましくはグリチルリチン酸、その誘導体、及び/又はそれらの塩、更に好ましくはグリチルリチン酸及び/又はその塩、より一層好ましくはグリチルリチン酸二カリウム又はグリチルリチン酸モノアンモニウム、特に好ましくはグリチルリチン酸モノアンモニウムが挙げられる。 Among these components (B), glycyrrhizic acid, a derivative thereof, and / or a salt thereof, more preferably glycyrrhizic acid and / or a salt thereof, is preferable from the viewpoint of further improving the effect of improving chronic keratinized eczema. Salts, more preferably dipotassium glycyrrhizinate or monoammonium glycyrrhizinate, particularly preferably monoammonium glycyrrhizinate.
本発明の慢性角化型湿疹改善剤における(B)成分の含有量については、特に制限されないが、例えば、0.1〜3重量%であり、好ましくは0.2〜2重量%であり、より好ましくは0.3〜1重量%が挙げられる。 The content of the component (B) in the chronic keratinized eczema improving agent of the present invention is not particularly limited, but is, for example, 0.1 to 3% by weight, preferably 0.2 to 2% by weight. More preferably, it is 0.3 to 1% by weight.
本発明の慢性角化型湿疹改善剤において、(A)成分と(B)成分の比率については、特に制限されず、前述する(A)成分と(B)成分の含有量の範囲内で適宜設定すればよいが、慢性角化型湿疹の改善効果をより一層向上させるという観点から、(A)成分100重量部当たり、(B)成分が総量で0.5〜30重量部、好ましくは1〜20重量部、更に好ましくは1.5〜10重量部が挙げられる。 In the chronic keratinized eczema improving agent of the present invention, the ratio of the component (A) to the component (B) is not particularly limited, and is appropriately within the range of the contents of the component (A) and the component (B) described above. It may be set, but from the viewpoint of further improving the effect of improving chronic keratinized eczema, the total amount of the component (B) is 0.5 to 30 parts by weight, preferably 1 per 100 parts by weight of the component (A). -20 parts by weight, more preferably 1.5 to 10 parts by weight.
(C)成分
本発明の慢性角化型湿疹改善剤は、更にγ−オリザノールを含有する。γ−オリザノールとは、フェルラ酸とトリテルペンアルコールとのエステル、又はフェルラ酸とステロールとのエステルである。
(C) Ingredient The chronic keratinized eczema improving agent of the present invention further contains γ-oryzanol. γ-Oryzanol is an ester of ferulic acid and triterpene alcohol, or an ester of ferulic acid and sterol.
本発明の慢性角化型湿疹改善剤において、γ−オリザノールとして、フェルラ酸とトリテルペンアルコールとのエステル又はフェルラ酸とステロールとのエステルのいずれか一方を単独で使用してもよく、またこれらを組み合わせて使用してもよい。本発明で使用されるγ−オリザノールの好適な例として、フェルラ酸シクロアルテニル(C40H58O4)を含むもの、更に好ましくはフェルラ酸シクロアルテニルを95重量%以上含むもの、特に好ましくはフェルラ酸シクロアルテニル98重量%以上含むものが挙げられる。 In the chronic keratinized eczema improving agent of the present invention, either one of ferulic acid and triterpene alcohol ester or ferulic acid and sterol ester may be used alone or in combination as γ-oryzanol. May be used. As a preferable example of the γ-oryzanol used in the present invention, those containing cycloartenyl ferlate (C 40 H 58 O 4 ), more preferably those containing 95% by weight or more of cycloartenyl ferlate, particularly preferably. Examples include those containing 98% by weight or more of cycloartenyl ferulate.
γ−オリザノールのCAS登録番号は、「11042−64−1」で表される。本発明で使用されるγ−オリザノールには、オリザノールA(CAS登録番号[21238−33−5])及びオリザノールC(CAS登録番号[469−36−3])等が含まれ得る。 The CAS Registry Number for γ-oryzanol is represented by "11042-64-1". The γ-oryzanol used in the present invention may include oryzanol A (CAS Registry Number [21238-33-5]), oryzanol C (CAS Registry Number [469-36-3]) and the like.
本発明で使用されるγ−オリザノールについては、その原料、製造方法、精製方法等は特に限定されず、例えば、米糠等から自ら単離及び精製したもの等が挙げられる。 The raw material, production method, purification method, etc. of γ-oryzanol used in the present invention are not particularly limited, and examples thereof include those isolated and purified by themselves from rice bran and the like.
また、γ−オリザノールは、例えば、オリザ油化株式会社、築野食品工業株式会社、和光純薬工業株式会社、理研ビタミン株式会社、岡安商店株式会社等により製造又は販売されており、本発明の慢性角化型湿疹改善剤では、γ−オリザノールとして、これらの市販品を使用することもできる。 Further, γ-oryzanol is manufactured or sold by, for example, Oryzanol Oil Chemical Co., Ltd., Tsukino Food Industry Co., Ltd., Wako Pure Chemical Industries, Ltd., Riken Vitamin Co., Ltd., Okayasu Shoten Co., Ltd., etc. In the chronic keratinized eczema improving agent, these commercially available products can also be used as γ-oryzanol.
本発明の慢性角化型湿疹改善剤におけるγ−オリザノールの含有量については、特に制限されないが、例えば0.01〜10重量%、好ましくは0.1〜5重量%、更に好ましくは0.5〜2重量%、特に好ましくは0.75〜1.5重量%が挙げられる。 The content of γ-oryzanol in the chronic keratinizing eczema improving agent of the present invention is not particularly limited, but is, for example, 0.01 to 10% by weight, preferably 0.1 to 5% by weight, more preferably 0.5. ~ 2% by weight, particularly preferably 0.75 to 1.5% by weight.
本発明の慢性角化型湿疹改善剤において、(A)成分と(C)成分の比率については、特に制限されず、前述する(A)成分と(C)成分の含有量の範囲内で適宜設定すればよいが、慢性角化型湿疹の改善効果をより一層向上させるという観点から、(A)成分100重量部当たり、(C)成分が総量で0.5〜50重量部、好ましくは2.5〜20重量部、更に好ましくは3.5〜15重量部が挙げられる。 In the chronic keratinized eczema improving agent of the present invention, the ratio of the component (A) to the component (C) is not particularly limited, and is appropriately within the range of the contents of the component (A) and the component (C) described above. It may be set, but from the viewpoint of further improving the effect of improving chronic keratinized eczema, the total amount of the component (C) is 0.5 to 50 parts by weight, preferably 2 per 100 parts by weight of the component (A). .5 to 20 parts by weight, more preferably 3.5 to 15 parts by weight.
(D)成分
本発明の慢性角化型湿疹改善剤は、前記(A)〜(C)成分に加えて、必要に応じて、トコフェロール及び/又はその誘導体(以下、(D)成分と表記することもある)を含んでいてもよい。このように(D)成分を含有させることにより、より一層効果的に、慢性角化型湿疹の改善効果を向上させることが可能になる。
Component (D) The chronic keratinized eczema improving agent of the present invention is, if necessary, tocopherol and / or a derivative thereof (hereinafter referred to as component (D)) in addition to the components (A) to (C). May include). By containing the component (D) in this way, it becomes possible to more effectively improve the effect of improving chronic keratinized eczema.
トコフェロールは、ビタミンEとしても知られている公知の成分である。本発明で使用されるトコフェロールは、d体又はdl体のいずれであってもよく、またα、β、γ、δの構造のいずれであってもよい。本発明で使用されるトコフェロールとして、具体的には、d−α−トコフェロール、d−β−トコフェロール、d−γ−トコフェロール、d−δ−トコフェロール、l−α−トコフェロール、l−β−トコフェロール、l−γ−トコフェロール、l−δ−トコフェロール、それらの混合物であるdl−α−トコフェロール、dl−β−トコフェロール、dl−γ−トコフェロール、dl−δ−トコフェロール等が挙げられる。 Tocopherol is a known ingredient also known as Vitamin E. The tocopherol used in the present invention may be either d-form or dl-form, and may have any of α, β, γ, and δ structures. Specific examples of the tocopherols used in the present invention include d-α-tocopherol, d-β-tocopherol, d-γ-tocopherol, d-δ-tocopherol, l-α-tocopherol, and l-β-tocopherol. Examples thereof include l-γ-tocopherol, l-δ-tocopherol, and mixtures thereof, dl-α-tocopherol, dl-β-tocopherol, dl-γ-tocopherol, and dl-δ-tocopherol.
トコフェロールの誘導体とは、トコフェロールと同じ骨格を有し、トコフェロールに置換基を付加することによって得られる成分である。 A derivative of tocopherol is a component having the same skeleton as tocopherol and obtained by adding a substituent to tocopherol.
本発明で使用されるトコフェロールの誘導体は、トコフェロールと同様に、d体又はdl体のいずれであってもよく、またα、β、γ、δの構造のいずれであってもよい。 The derivative of tocopherol used in the present invention may be either d-form or dl-form, and may have any of α, β, γ, and δ structures, like tocopherol.
トコフェロールの誘導体の種類については、薬学的に許容されることを限度として、特に制限されないが、例えば、トコフェロールと有機酸とのエステル等が挙げられる。トコフェロールと有機酸とのエステルとして、具体的には、トコフェロール酢酸エステル、トコフェロールニコチン酸エステル、トコフェロールコハク酸エステル、トコフェロールリノレン酸エステル等が挙げられる。これらのトコフェロールの誘導体は、1種単独で使用してもよく、また2種以上を組み合わせて使用してもよい。 The type of the tocopherol derivative is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include an ester of tocopherol and an organic acid. Specific examples of the ester of tocopherol and an organic acid include tocopherol acetate, tocopherol nicotinic acid ester, tocopherol succinic acid ester, and tocopherol linolenic acid ester. These tocopherol derivatives may be used alone or in combination of two or more.
これらの(D)成分は、その原料、製造方法、精製方法等は特に制限されず、動物等から自ら単離及び精製したものを用いてもよく、或いは市販品を用いてもよい。(D)成分の市販品としては、例えば、理研ビタミン株式会社、エーザイ株式会社、エーザイフード・ケミカル株式会社、DSMニュートリションジャパン株式会社、タマ生化学株式会社、岡見化学株式会社等で製造又は販売されている商品が挙げられる。 The raw material, production method, purification method, and the like of these components (D) are not particularly limited, and those isolated and purified by themselves from animals and the like may be used, or commercially available products may be used. Commercially available products of the component (D) are manufactured or sold by, for example, RIKEN Vitamin Co., Ltd., Eisai Co., Ltd., Eisai Food Chemical Co., Ltd., DSM Nutrition Japan Co., Ltd., Tama Biochemical Co., Ltd., Okami Chemical Co., Ltd., etc. The products that are available are listed.
本発明の慢性角化型湿疹改善剤において、(D)成分として、トコフェロール及びトコフェロールの誘導体の中から、1種を選択して使用してもよく、2種以上を組み合わせて使用してもよい。 In the chronic keratinized eczema improving agent of the present invention, as the component (D), one of tocopherol and a derivative of tocopherol may be selected and used, or two or more of them may be used in combination. ..
これらの(D)成分の中でも、慢性角化型湿疹の改善効果をより一層向上させるという観点から、好ましくはトコフェロールの誘導体、更に好ましくはトコフェロール酢酸エステルが挙げられる。 Among these components (D), a derivative of tocopherol is preferable, and tocopherol acetate is more preferable, from the viewpoint of further improving the effect of improving chronic keratinized eczema.
本発明の慢性角化型湿疹改善剤に(D)成分を含有させる場合、その含有量については、特に制限されないが、例えば、0.001〜10重量%、好ましくは0.01〜5重量%、より好ましくは0.1〜3重量%、更に好ましくは0.5〜3重量%、特に好ましくは0.5〜2重量%が挙げられる。 When the component (D) is contained in the chronic keratinized eczema improving agent of the present invention, the content thereof is not particularly limited, but is, for example, 0.001 to 10% by weight, preferably 0.01 to 5% by weight. , More preferably 0.1 to 3% by weight, still more preferably 0.5 to 3% by weight, and particularly preferably 0.5 to 2% by weight.
また、本発明の慢性角化型湿疹改善剤に(D)成分を含有させる場合、(A)成分と(D)成分の比率については、特に制限されず、前述する(A)成分と(E)成分の含有量の範囲内で適宜設定すればよいが、慢性角化型湿疹の改善効果をより一層向上させるという観点から、(A)成分100重量部当たり、(D)成分が総量で0.5〜30重量部、好ましくは2.5〜30重量部、更に好ましくは2.5〜20重量部が挙げられる。 When the chronic keratinized eczema improving agent of the present invention contains the component (D), the ratio of the component (A) to the component (D) is not particularly limited, and the above-mentioned component (A) and (E) are not particularly limited. ) It may be set appropriately within the range of the content of the component, but from the viewpoint of further improving the effect of improving chronic keratinized eczema, the total amount of the component (D) is 0 per 100 parts by weight of the component (A). .5 to 30 parts by weight, preferably 2.5 to 30 parts by weight, more preferably 2.5 to 20 parts by weight.
(E)成分
本発明の慢性角化型湿疹改善剤は、前記(A)〜(C)成分に加えて、必要に応じて、レチノール及び/又はその誘導体(以下、(E)成分と表記することもある)を含んでいてもよい。このように(E)成分を含有させることにより、より一層効果的に、慢性角化型湿疹の改善効果を向上させることが可能になる。特に、前記(A)〜(C)成分に加えて、(D)及び(E)成分を組み合わせて使用することにより、慢性角化型湿疹の改善効果を格段顕著に向上させることが可能になる。
(E) component The chronic keratinized eczema improving agent of the present invention is, if necessary, retinol and / or a derivative thereof (hereinafter referred to as (E) component) in addition to the above (A) to (C) components. May include). By containing the component (E) in this way, it becomes possible to further effectively improve the effect of improving chronic keratinized eczema. In particular, by using the components (D) and (E) in combination in addition to the components (A) to (C), it is possible to remarkably improve the effect of improving chronic keratinized eczema. ..
レチノールは、ビタミンAの1種であり、ビタミンAアルコールとも称されることがある成分である。 Retinol is a type of vitamin A and is a component sometimes also referred to as vitamin A alcohol.
レチノールの誘導体とは、レチノールと同じ骨格を有し、レチノールに置換基を付加することによって得られる成分である。レチノール誘導体の種類については、薬学的に許容されることを限度として、特に制限されないが、例えば、レチノールと脂肪酸とのエステル、レチノールと酢酸とのエステル(即ち、レチノール酢酸エステル)、レチノールの酸化物、及び当該酸化物のエステル等が挙げられる。 A derivative of retinol is a component having the same skeleton as retinol and obtained by adding a substituent to retinol. The type of retinol derivative is not particularly limited as long as it is pharmaceutically acceptable, but for example, an ester of retinol and a fatty acid, an ester of retinol and acetic acid (that is, a retinol acetate ester), and an oxide of retinol. , And the ester of the oxide.
レチノールと脂肪酸とのエステルとしては、具体的には、レチノールと、炭素数1〜30、好ましくは2〜18の脂肪酸とのエステルが挙げられる。レチノールと脂肪酸とのエステルとして、より具体的には、レチノール酢酸エステル、レチノールプロピオン酸エステル、レチノール酪酸エステル、レチノールオクチル酸エステル、レチノールラウリル酸エステル、レチノールパルミチン酸エステル、レチノールステアリン酸エステル、レチノールミリスチン酸エステル、レチノールオレイン酸エステル、レチノールリノレン酸エステル、レチノールリノール酸エステル等が挙げられる。これらのレチノールと脂肪酸とのエステルは、1種単独で使用してもよく、2種以上を組み合わせて使用してもよい。 Specific examples of the ester of retinol and fatty acid include an ester of retinol and a fatty acid having 1 to 30 carbon atoms, preferably 2 to 18 carbon atoms. More specifically, as esters of retinol and fatty acids, retinol acetate, retinol propionate, retinol butyrate, retinol octylate, retinol lauric acid ester, retinol palmitate, retinol stearate, retinol myristic acid. Examples thereof include esters, retinol oleic acid esters, retinol linolenic acid esters, and retinol linoleic acid esters. These esters of retinol and fatty acid may be used alone or in combination of two or more.
レチノールの酸化物としては、具体的には、レチノイン酸(「トレチノイン」と称することもある)、レチナール等が挙げられる。これらのレチノールの酸化物は、1種単独で使用してもよく、2種以上を組み合わせて使用してもよい。 Specific examples of the oxide of retinol include retinoic acid (sometimes referred to as "tretinoin"), retinal and the like. These retinol oxides may be used alone or in combination of two or more.
レチノールの酸化物のエステルとしては、具体的には、レチノイン酸メチル、レチノイン酸エチル、レチノイン酸レチノール、レチノイン酸トコフェロール(トコフェロールは、α、β、γ、又はδのいずれであってもよい)等が挙げられる。これらのレチノールの酸化物のエステルは、1種単独で使用してもよく、2種以上を組み合わせて使用してもよい。 Specific examples of the ester of the oxide of retinol include methyl retinoate, ethyl retinoate, retinol retinoate, tocopherol retinoate (tocopherol may be α, β, γ, or δ) and the like. Can be mentioned. These retinol oxide esters may be used alone or in combination of two or more.
これらの(E)成分は、その原料、製造方法、精製方法等は特に制限されず、動物等から自ら単離及び精製したものを用いてもよく、或いは市販品を用いてもよい。(E)成分の市販品としては、例えば、理研ビタミン株式会社、DSMニュートリションジャパン株式会社、小華薬品株式会社、BASFジャパン株式会社等で製造又は販売されている商品が挙げられる。 The raw material, production method, purification method, and the like of these components (E) are not particularly limited, and those isolated and purified by themselves from animals and the like may be used, or commercially available products may be used. Examples of commercially available products of the component (E) include products manufactured or sold by Riken Vitamin Co., Ltd., DSM Nutrition Japan Co., Ltd., Xiaohua Pharmaceutical Co., Ltd., BASF Japan Co., Ltd., and the like.
本発明の慢性角化型湿疹改善剤において、(E)成分として、レチノール及びレチノールの誘導体の中から、1種を選択して使用してもよく、2種以上を組み合わせて使用してもよい。 In the chronic keratinized eczema improving agent of the present invention, as the component (E), one of retinol and a derivative of retinol may be selected and used, or two or more of them may be used in combination. ..
これらの(E)成分の中でも、慢性角化型湿疹の改善効果をより一層向上させるという観点から、好ましくはレチノールの誘導体、更に好ましくはレチノールと脂肪酸とのエステル、特に好ましくはレチノールパルミチン酸エステルが挙げられる。 Among these (E) components, a derivative of retinol is preferable, an ester of retinol and a fatty acid is more preferable, and a retinol palmitate ester is particularly preferable, from the viewpoint of further improving the effect of improving chronic keratinized eczema. Can be mentioned.
また、本発明において、レチノール及び/又はその誘導体は、植物油等の油中に溶解させた状態で使用してもよい。このようにレチノール及び/又はその誘導体を油中に溶解させたものは、「ビタミンA油」として知られている。ビタミンA油は、例えば日本薬局方に記載の方法に従って製造することができる。ビタミンA油としては、通常、レチノール及び/又はその誘導体の含有量が10万〜200万I.U./g、好ましくは50万〜170万I.U./g、更に好ましくは50万〜100万I.U./gのものを使用できる。なお、本明細書において、レチノール及び/又はその誘導体の含有量の単位「I.U.」は、国際単位を示す。 Further, in the present invention, retinol and / or a derivative thereof may be used in a state of being dissolved in an oil such as vegetable oil. Such a solution of retinol and / or a derivative thereof in oil is known as "vitamin A oil". Vitamin A oil can be produced, for example, according to the method described in the Japanese Pharmacopoeia. The vitamin A oil usually has a content of retinol and / or a derivative thereof of 100,000 to 2 million I.U./g, preferably 500,000 to 1.7 million I.U./g, and more preferably 500,000 to 500,000. One million I.U./g can be used. In addition, in this specification, the unit "I.U." of the content of retinol and / or a derivative thereof indicates an international unit.
本発明の慢性角化型湿疹改善剤に(E)成分を含有させる場合、その含有量については、特に制限されないが、例えば、本発明の慢性角化型湿疹改善剤100g当たり、(E)成分が、0.1万〜1000万I.U.、好ましくは1万〜500万I.U.、より好ましくは10万〜300万I.U.、更に好ましくは10万〜150万I.U.、特に好ましくは25万〜100万I.U.が挙げられる。 When the component (E) is contained in the chronic keratinized eczema improving agent of the present invention, the content thereof is not particularly limited, but for example, the component (E) per 100 g of the chronic keratinized eczema improving agent of the present invention. However, 10 to 10 million I. U.S. , Preferably 10,000-5 million I. U.S. , More preferably 100,000 to 3 million I. U.S. , More preferably 100,000 to 1,500,000 I. U.S. , Particularly preferably 250,000 to 1 million I. U.S. Can be mentioned.
また、(E)成分としてビタミンA油を使用する場合、本発明の慢性角化型湿疹改善剤におけるビタミンA油の含有量については、ビタミンA油中のレチノール及び/又はその誘導体の含有量に応じて、本発明の慢性角化型湿疹改善剤中でレチノール及び/又はその誘導体が前述する含有量を充足するように設定すればよい。具体的には、100万I.U./gのレチノール及び/又はその誘導体を含有するビタミンA油を用いる場合であれば、本発明の慢性角化型湿疹改善剤におけるビタミンA油の含有量については、0.001〜10重量%、好ましくは0.01〜5重量%、より好ましくは0.1〜3重量%、更に好ましくは0.1〜1.5重量%、特に好ましくは0.25〜1重量%に設定すればよい。 When vitamin A oil is used as the component (E), the content of vitamin A oil in the chronic keratinized eczema improving agent of the present invention is the content of retinol and / or a derivative thereof in the vitamin A oil. Accordingly, retinol and / or a derivative thereof may be set to satisfy the above-mentioned content in the chronic keratinized eczema improving agent of the present invention. Specifically, 1 million I. U.S. When using vitamin A oil containing / g of retinol and / or a derivative thereof, the content of vitamin A oil in the chronic keratinizing eczema improving agent of the present invention is 0.001 to 10% by weight. It may be preferably set to 0.01 to 5% by weight, more preferably 0.1 to 3% by weight, still more preferably 0.1 to 1.5% by weight, and particularly preferably 0.25 to 1% by weight.
本発明の慢性角化型湿疹改善剤に(E)成分を含有させる場合、(A)成分と(E)成分の比率については、特に制限されず、前述する(A)成分と(E)成分の含有量の範囲内で適宜設定すればよいが、慢性角化型湿疹の改善効果をより一層向上させるという観点から、(A)成分1g当たり、(E)成分が総量で0.5万〜30万I.U.、好ましくは0.5万〜15万I.U.、更に好ましくは1.25万〜10万I.U.が挙げられる。 When the chronic keratinized eczema improving agent of the present invention contains the component (E), the ratio of the component (A) to the component (E) is not particularly limited, and the components (A) and (E) described above are not particularly limited. It may be set appropriately within the range of the content of (A), but from the viewpoint of further improving the effect of improving chronic keratinized eczema, the total amount of (E) component is 5,000 to 1 g per 1 g of component (A). 300,000 I. U.S. , Preferably 5,000 to 150,000 I. U.S. , More preferably 12,500 to 100,000 I. U.S. Can be mentioned.
多価アルコール
本発明の慢性角化型湿疹改善剤には、保湿性の向上等のために、必要に応じて多価アルコールが含まれていてもよい。
Polyhydric alcohol The chronic keratinized eczema improving agent of the present invention may contain a polyhydric alcohol, if necessary, in order to improve the moisturizing property.
多価アルコールとしては、薬学的に許容されることを限度として特に制限されないが、例えば、エチレングリコール、1,3−ブチレングリコール、プロピレングリコール、イソプレングリコール、ジエチレングリコール、ジプロピレングリコール、ポリプロピレングリコール、グリセリン等が挙げられる。これらの多価アルコールは、1種単独で使用してもよく、また2種以上を組み合わせて使用してもよい。 The polyhydric alcohol is not particularly limited as long as it is pharmaceutically acceptable, and for example, ethylene glycol, 1,3-butylene glycol, propylene glycol, isoprene glycol, diethylene glycol, dipropylene glycol, polypropylene glycol, glycerin and the like. Can be mentioned. These polyhydric alcohols may be used alone or in combination of two or more.
本発明の慢性角化型湿疹改善剤に、多価アルコールを含有させる場合、その含有量については、製剤形態等に応じて適宜設定すればよいが、例えば、0.5〜50重量%、好ましくは1〜30重量%、更に好ましくは2〜20重量%が挙げられる。 When the chronic keratinizing eczema improving agent of the present invention contains a polyhydric alcohol, the content thereof may be appropriately set according to the formulation form and the like, and is preferably 0.5 to 50% by weight, for example. Is 1 to 30% by weight, more preferably 2 to 20% by weight.
界面活性剤
また、本発明の外用組成物は、(C)成分、並びに必要に応じて添加される(D)成分及び/又は(E)成分を可溶化又は乳化させて所望の製剤形態にするために、界面活性剤が含まれていてもよい。界面活性剤としては、薬学的に許容されることを限度として特に制限されず、ノニオン性界面活性剤、アニオン性界面活性剤、カチオン性界面活性剤、両性界面活性剤のいずれを使用してもよいが、好ましくはノニオン性界面活性剤が挙げられる。
Surfactant In addition, the external composition of the present invention solubilizes or emulsifies the component (C) and the component (D) and / or the component (E) added as needed to obtain a desired pharmaceutical form. Therefore, a surfactant may be contained. The surfactant is not particularly limited as long as it is pharmaceutically acceptable, and any of nonionic surfactant, anionic surfactant, cationic surfactant, and amphoteric surfactant may be used. It is good, but preferably a nonionic surfactant is mentioned.
界面活性剤としては、具体的には、POE(10〜50モル)フィトステロールエーテル、POE(10〜50モル)ジヒドロコレステロールエーテル、POE(10〜50モル)2−オクチルドデシルエーテル、POE(10〜50モル)デシルテトラデシルエーテル、POE(10〜50モル)オレイルエーテル、POE(2〜50モル)セチルエーテル、POE(5〜50モル)ベヘニルエーテル、POE(5〜30モル)ポリオキシプロピレン(5〜30モル)2−デシルテトラデシルエーテル、POE(10〜50モル)ポリオキシプロピレン(2〜30モル)セチルエーテル等のポリオキシエチレンアルキルエーテル、これらのリン酸・リン酸塩(POEセチルエーテルリン酸ナトリウムなど)、POE(20〜60モル)ソルビタンモノオレエート、POE(20〜60モル)ソルビタンモノステアレート、POE(10〜60モル)ソルビタンモノイソステアレート等のポリオキシエチレンソルビタン脂肪酸エステル、POE(10〜80モル)グリセリルモノイソステアレート、POE(10〜30モル)グリセリルモノステアレート、POE(20〜100モル)・ポリオキシプロピレン変性シリコーン、POE・アルキル変性シリコーン、モノラウリン酸ポリエチレングリコール、モノパルミチン酸ポリエチレングリコール、モノステアリン酸ポリエチレングリコール、ジラウリン酸ポリエチレングリコール、ジパルミチン酸ポリエチレングリコール、ジステアリン酸ポリエチレングリコール、ジオレイン酸ポリエチレングリコール、ジリシノレイン酸ポリエチレングリコール、ポリオキシエチレン硬化ヒマシ油(5〜100)、グリセリン脂肪酸エステル(モノステアリン酸グリセリン等)、水素添加大豆リン脂質、水素添加ラノリンアルコール等が挙げられる。これらの界面活性剤は、1種単独で使用してもよく、また2種以上を組み合わせて使用してもよい。 Specific examples of the surfactant include POE (10 to 50 mol) phytosterol ether, POE (10 to 50 mol) dihydrocholesterol ether, POE (10 to 50 mol) 2-octyldodecyl ether, and POE (10 to 50 mol). Mol) decyltetradecyl ether, POE (10-50 mol) oleyl ether, POE (2-50 mol) cetyl ether, POE (5-50 mol) behenyl ether, POE (5-30 mol) polyoxypropylene (5-mol) Polyoxyethylene alkyl ethers such as 30 mol) 2-decyltetradecyl ether, POE (10 to 50 mol) polyoxypropylene (2 to 30 mol) cetyl ether, and their phosphates and phosphates (POE cetyl ether phosphoric acid). Polyoxyethylene sorbitan fatty acid esters such as (sodium, etc.), POE (20-60 mol) sorbitan monooleate, POE (20-60 mol) sorbitan monostearate, POE (10-60 mol) sorbitan monoisostearate, POE (10 to 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, mono Polyethylene glycol palmitate, polyethylene glycol monostearate, polyethylene glycol dilaurate, polyethylene glycol dipalmitate, polyethylene glycol distearate, polyethylene glycol dioleate, polyethylene glycol diricinoleate, polyoxyethylene hydrogenated castor oil (5-100), Examples thereof include glycerin fatty acid ester (glycerin monostearate, etc.), hydrogenated soybean phospholipid, hydrogenated lanolin alcohol, and the like. These surfactants may be used alone or in combination of two or more.
本発明の慢性角化型湿疹改善剤に、界面活性剤を含有させる場合、その含有量については、製剤形態等に応じて適宜設定すればよいが、例えば、0.1〜30重量%、好ましくは0.5〜20重量%、更に好ましくは1〜15重量%が挙げられる。 When the chronic keratinized eczema improving agent of the present invention contains a surfactant, the content thereof may be appropriately set according to the form of the preparation and the like, and is preferably 0.1 to 30% by weight, for example. Is 0.5 to 20% by weight, more preferably 1 to 15% by weight.
その他の成分
本発明の慢性角化型湿疹改善剤は、前述する成分の他に、必要に応じて、他の薬理成分を含有していてもよい。このような薬理成分としては、例えば、抗ヒスタミン剤(ジフェンヒドラミン、塩酸ジフェンヒドラミン等)、局所麻酔剤(プロカイン、テトラカイン、ブピパカイン、メピパカイン、クロロプロカイン、プロパラカイン、メプリルカイン又はこれらの塩、オルソカイン、オキセサゼイン、オキシポリエントキシデカン、ロートエキス、ペルカミンパーゼ、テシットデシチン等)、抗炎症剤(インドメタシン、フェルビナク、ジクロフェナクナトリウム、ロキソプロフェンナトリウム等)、皮膚保護剤(コロジオン、ヒマシ油等)、血行促進成分(ノニル酸ワニリルアミド、ニコチン酸ベンジルエステル、カプサイシン、トウガラシエキス等)、清涼化剤(メントール、カンフル、ボルネオール、ハッカ水、ハッカ油等)、ムコ多糖類(コンドロイチン硫酸ナトリウム、グルコサミン等)等が挙げられる。
Other Ingredients The chronic keratinized eczema improving agent of the present invention may contain other pharmacological components in addition to the above-mentioned components, if necessary. Examples of such pharmacological components include antihistamines (difenhydramine, difenhydramine hydrochloride, etc.), local anesthetics (procaine, tetracaine, bupipacaine, mepipacaine, chloroprocaine, proparacaine, meprilcaine or salts thereof, orthokines, oxesazein, oxypolyentoxy). Decane, funnel extract, percamine pase, tesitdecitin, etc.), anti-inflammatory agents (indomethacin, fervinac, diclofenac sodium, loxoprofen sodium, etc.), skin protectants (colodione, castor oil, etc.), blood circulation promoting ingredients (nonylate vanillylamide, nicotinic acid benzyl ester, etc.) , Capsaicin, capsicum extract, etc.), refreshing agents (menthol, camphor, borneol, peppermint water, peppermint oil, etc.), mucopolysaccharides (sodium chondroitin sulfate, glucosamine, etc.) and the like.
また、本発明の慢性角化型湿疹改善剤は、所望の製剤形態にするために、必要に応じて、前述する成分の他に、基材や添加剤が含まれていてもよい。このような基剤や添加剤については、薬学的に許容されることを限度として特に制限されないが、例えば、水、低級アルコール(エタノール、イソプロパノール等)等の水性基剤;油類(オリーブ油、サフラワー油、大豆油、つばき油、とうもろこし油、なたね油、ひまわり油、綿実油、落花生油、ラード、スクワラン、魚油等)、鉱物油(流動パラフィン、パラフィン、ゲル化炭化水素、ワセリン等)、ワックス類・ロウ類(ミツロウ、カルナウバロウ、キャンデリラロウ、セレシン、ライスワックス、マイクロクリスタリンワックス等)、エステル油(ミリスチン酸イソプロピル、アジピン酸イソプロピル、セバシン酸ジエチル、セバシン酸イソプロピル、パルミチン酸イソプロピル、パルミチン酸セチル、オレイン酸エチル等)、脂肪酸アルキルエステル、脂肪酸(ステアリン酸、オレイン酸、パルミチン酸、ベヘン酸、リノール酸、ラノリン等)、脂肪酸エステル(パルミチン酸セチル、パルミチン酸イソプロピル、リノール酸エチル等)、高級アルコール(ステアリルアルコール、セタノール、ベヘニルアルコール、ミリスチルアルコール、オレイルアルコール、ヘキサデシルアルコール、ラノリンアルコール等)、コレステロール、トリ2−エチルヘキサン酸グリセリル、2−エチルヘキサン酸セチル、シリコーンオイル(ジメチルポリシロキサン、環状シリコーン等)等の油性基剤;防腐剤(メチルパラベン、プロピルパラベン、安息香酸、安息香酸ナトリウム、ソルビン酸等)、着香剤(シトラール、1,8−シオネール、シトロネラール、ファルネソール等)、着色剤(タール色素(褐色201号、青色201号、黄色4号、黄色403号等)、カカオ色素、クロロフィル、酸化アルミニウム等)、粘稠剤(カルボキシビニルポリマー、ヒプロメロース、ポリビニルピロリドン、アルギン酸ナトリウム、エチルセルロース、カルボキシメチルセルロースナトリウム、キサンタンガム、カラギーナン等)、pH調整剤(リン酸、塩酸、クエン酸、クエン酸ナトリウム、コハク酸、酒石酸、水酸化ナトリウム、水酸化カリウム、トリエタノールアミン、トリイソプロパノールアミン等)、湿潤剤(dl−ピロリドンカルボン酸ナトリウム液、D−ソルビトール液、マクロゴール等)、安定化剤(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、エデト酸ナトリウム、メタリン酸ナトリウム、L−アルギニン、L−アスパラギン酸、DL−アラニン、グリシン、エリソルビン酸ナトリウム、没食子酸プロピル、亜硫酸ナトリウム、二酸化硫黄、クロロゲン酸、カテキン、ローズマリー抽出物等)、酸化防止剤、紫外線吸収剤、キレート剤、粘着剤、緩衝剤、溶解補助剤、可溶化剤、保存剤等の添加剤が挙げられる。 In addition, the chronic keratinized eczema improving agent of the present invention may contain a base material and additives in addition to the above-mentioned components, if necessary, in order to obtain a desired pharmaceutical form. Such bases and additives are not particularly limited as long as they are pharmaceutically acceptable, but are, for example, aqueous bases such as water and lower alcohols (ethanol, isopropanol, etc.); oils (olive oil, sodium). Flower 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, gelled hydrocarbon, vaseline, etc.), waxes, etc. Rows (mitsurou, carnauba wax, candelilla wax, selecin, rice wax, microcrystallin wax, etc.), ester oils (isopropyl myristate, isopropyl adipate, diethyl sebacate, isopropyl sebacate, isopropyl palmitate, cetyl palmitate, olein Ethyl acid acid, etc.), fatty acid alkyl esters, fatty acids (stearic acid, oleic acid, palmitic acid, bechenic acid, linoleic acid, lanolin, etc.), fatty acid esters (cetyl palmitate, isopropyl palmitate, ethyl linoleate, etc.), higher alcohols (such as ethyl linoleate) Stearyl alcohol, cetanol, behenyl alcohol, myristyl alcohol, oleyl alcohol, hexadecyl alcohol, lanolin alcohol, etc.), cholesterol, glyceryl tri2-ethylhexanoate, cetyl 2-ethylhexanoate, silicone oil (dimethylpolysiloxane, cyclic silicone, etc.) Oil-based bases such as; preservatives (methylparaben, propylparaben, benzoic acid, sodium benzoate, sorbic acid, etc.), flavoring agents (citral, 1,8-cyoner, citroneral, farnesol, etc.), colorants (tar pigments (tar pigments (tar pigments)) Brown 201, Blue 201, Yellow 4, Yellow 403, etc.), cocoa pigment, chlorophyll, aluminum oxide, etc.), viscous agent (carboxyvinyl polymer, hypromellose, polyvinylpyrrolidone, sodium alginate, ethyl cellulose, sodium carboxymethyl cellulose, etc. Xanthan gum, carrageenan, etc.), pH adjusters (phosphate, hydrochloric acid, citric acid, sodium citrate, succinic acid, tartaric acid, sodium hydroxide, potassium hydroxide, triethanolamine, triisopropanolamine, etc.), wetting agents (dl- Sodium pyrrolidone carboxylate solution, D-sorbitol solution, macrogol, etc.), stabilizers (dibutylhydroxytoluene, butylhydroxyanisole, sodium edetate, sodium metaphosphate, L- Arginine, L-aspartic acid, DL-alanine, glycine, sodium erythorbinate, propyl gallate, sodium sulfite, sulfur dioxide, chlorogenic acid, catechin, rosemary extract, etc.), antioxidants, UV absorbers, chelating agents, Additives such as pressure-sensitive adhesives, buffers, solubilizers, solubilizers and preservatives can be mentioned.
慢性角化型湿疹改善剤の製造方法
本発明の慢性角化型湿疹改善剤は、(A)〜(C)成分、並びに必要に応じて(D)成分、(E)成分、及びその他の成分を、その製剤形態に応じた手法で、所望量混合することにより調製される。
Method for Producing Chronic Keratinized Eczema Improver The chronic keratinized eczema improving agent of the present invention comprises components (A) to (C), and if necessary, components (D), (E), and other components. Is prepared by mixing a desired amount by a method according to the formulation form.
製剤形態・用途
本発明の慢性角化型湿疹改善剤は、経皮適用できる剤型である限り、その製剤形態については、特に制限されず、液状、固形状、半固形状(ゲル状、軟膏状、ペースト状)等のいずれであってもよい。
Formulation Form / Use The chronic keratinized eczema improving agent of the present invention is not particularly limited as long as it is a dosage form that can be applied transdermally, and is liquid, solid, or semi-solid (gel, ointment). It may be in the form of a paste or a paste.
また、本発明の慢性角化型湿疹改善剤は、皮膚に適用されるものである限り、皮膚外用医薬品、化粧料、皮膚洗浄料等のいずれの製剤形態であってもよい。本発明の慢性角化型湿疹改善剤の製剤形態として、具体的には、クリーム剤、軟膏剤、乳液剤、ゲル剤、油剤、液剤、ローション剤、リニメント剤、エアゾール剤、貼付剤、パック剤等の皮膚外用医薬品;軟膏、クリーム、乳液、化粧水、ローション、パック、ゲル等の化粧料;ボディーシャンプー、ヘアシャンプー、リンス等の皮膚洗浄料等が挙げられる。これらの製剤形態の中でも、好ましくは皮膚外用医薬品、更に好ましくはクリーム剤、軟膏剤、乳液剤、ローション剤が挙げられる。 In addition, the chronic keratinized eczema improving agent of the present invention may be in any pharmaceutical form such as an external preparation for skin, a cosmetic, and a skin cleaning agent as long as it is applied to the skin. Specific examples of the formulation form of the chronic keratinizing eczema improving agent of the present invention include creams, ointments, emulsions, gels, oils, liquids, lotions, liniments, aerosols, patches, and packs. Examples of external medicines for skin such as ointments, creams, milky lotions, lotions, lotions, packs, gels and the like; skin cleaning agents such as body shampoos, hair shampoos and rinses. Among these pharmaceutical forms, a skin external medicine is preferable, and a cream, an ointment, a milky lotion, and a lotion are more preferable.
本発明の慢性角化型湿疹改善剤は、慢性角化型湿疹を呈している皮膚部位に適用し、慢性角化型湿疹を改善するために使用される。慢性角化型湿疹は、肘、膝等の身体部位において多く認められ、各層の肥厚化及び黒ずみを伴う皮膚症状である。本発明の慢性角化型湿疹改善剤は、慢性角化型湿疹における角層の肥厚化及び黒ずみの双方の症状を改善することができる。また、本発明の慢性角化型湿疹改善剤は、慢性角化型湿疹の予防を目的として、慢性角化型湿疹を呈していない肘、膝等の身体部位に適用することもできる。 The chronic keratinized eczema improving agent of the present invention is applied to a skin site presenting chronic keratinized eczema and is used to improve chronic keratinized eczema. Chronic keratinized eczema is often found in body parts such as elbows and knees, and is a skin symptom accompanied by thickening and darkening of each layer. The chronic keratinized eczema improving agent of the present invention can improve the symptoms of both thickening and darkening of the stratum corneum in chronic keratinized eczema. In addition, the chronic keratinized eczema improving agent of the present invention can also be applied to body parts such as elbows and knees that do not exhibit chronic keratinized eczema for the purpose of preventing chronic keratinized eczema.
また、本発明の慢性角化型湿疹改善剤の用量については、製剤形態、症状の程度等に応じて適宜設定すればよい。本発明の慢性角化型湿疹改善剤の用量の一例として、1回当たり、皮膚1cm2当たり、前記(A)成分の適用量換算で0.1〜3mg程度となる量で、1日1〜数回程度の頻度が挙げられるが、かかる範囲に限定されるものではない。 In addition, the dose of the chronic keratinizing eczema improving agent of the present invention may be appropriately set according to the form of the preparation, the degree of symptoms, and the like. As an example of the dose of the chronic keratinizing eczema improving agent of the present invention, the amount is about 0.1 to 3 mg per 1 cm 2 of the skin in terms of the applied amount of the component (A), 1 to 1 day. The frequency is several times, but it is not limited to this range.
以下に実施例を示して本発明をより具体的に説明するが、本発明はこれらに限定されるものではない。 Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto.
参考試験例1:チロシナーゼ活性阻害率の評価
1.評価方法
表1に示す条件に従い、50mM リン酸バッファー(pH6.5)に、5mM L−DOPA(dihydroxy−L−phenylalanine)水溶液を加えた。次いで、各成分(L−アスコルビン酸、グリチルリチン酸モノアンモニウム、γ−オリザノール(フェルラ酸シクロアルテニル(C40H58O4)含有量:99.4重量%)、ビタミンA油(レチノールパルミチン酸エステル100万I.U./g)又はトコフェロール酢酸エステル)のDMSO(dimethyl sulfoxide)溶液を加え撹拌した後、チロシナーゼ水溶液(チロシナーゼ含有量:3.91 unit)を加えることで酵素反応を開始した(反応温度:37℃)。酵素反応開始から15分後、マイクロプレートリーダーを用いて吸光度(475nm)を測定した。各成分について段階希釈により複数濃度のチロシナーゼ活性阻害率を測定し、50%阻害濃度(IC50、w/v%)を算出した。なお、チロシナーゼ活性阻害率(%)は、以下の式により算出した。
Reference Test Example 1: Evaluation of tyrosinase activity inhibition rate
1. 1. Evaluation Method According to the conditions shown in Table 1, a 5 mM L-DOPA (dihydroxy-L-phenylalanine) aqueous solution was added to 50 mM phosphate buffer (pH 6.5). Next, each component (L-ascorbic acid, monoammonium glycyrrhizinate, γ-oryzanol (cycloartenyl ferlate (C 40 H 58 O 4 ) content: 99.4% by weight), vitamin A oil (retinol palmitate ester) A DMSO (dimethyl sulfoxide) solution of 1 million I.U./g) or tocopherol acetate) was added and stirred, and then an aqueous tyrosinase solution (tyrosinase content: 3.91 unit) was added to initiate an enzymatic reaction (reaction). Temperature: 37 ° C.). Fifteen minutes after the start of the enzymatic reaction, the absorbance (475 nm) was measured using a microplate reader. Multiple concentrations of tyrosinase activity inhibition rate were measured by serial dilution of each component, and a 50% inhibition concentration (IC50, w / v%) was calculated. The tyrosinase activity inhibition rate (%) was calculated by the following formula.
2.評価結果
得られた結果を表2に示す。この結果、L−アスコルビン酸及びグリチルリチン酸モノアンモニウムはより低濃度でチロシナーゼ活性を阻害できることが確認された。また、γ−オリザノール、トコフェロール酢酸エステル及びビタミンA油については、一定のチロシナーゼ活性阻害効果を有していたが、L−アスコルビン酸及びグリチルリチン酸モノアンモニウムに比べると低い結果であった。
2. Evaluation Results Table 2 shows the results obtained. As a result, it was confirmed that L-ascorbic acid and monoammonium glycyrrhizinate can inhibit the tyrosinase activity at lower concentrations. In addition, γ-oryzanol, tocopherol acetate and vitamin A oil had a certain tyrosinase activity inhibitory effect, but the results were lower than those of L-ascorbic acid and monoammonium glycyrrhizinate.
試験例1:メラニン生成及び明度に及ぼす影響の評価
1.評価方法
<試験試料の作製>
表3に示す組成のクリーム剤(水中油型乳化状のクリーム剤)を調製した(実施例1〜4、比較例1〜3、及び参考例1〜2)。具体的には、水性成分と油性成分をそれぞれ混合し、必要に応じて加熱し、溶解させ、それらを撹拌した後に冷却を行うことでクリーム剤を得た。なお、ビタミンA油には1g当たりレチノールパルミチン酸エステルを100万I.U.含有するものを使用し、また、γ−オリザノールにはフェルラ酸シクロアルテニル(C40H58O4)を99.4重量%含有するものを使用した。得られた各クリーム剤を試験試料として使用して以下の試験を行った。
Test Example 1: Evaluation of the effect on melanin production and lightness
1. 1. Evaluation method <Preparation of test sample>
A cream having the composition shown in Table 3 (oil-in-water emulsified cream) was prepared (Examples 1 to 4, Comparative Examples 1 to 3, and Reference Examples 1 to 2). Specifically, an aqueous component and an oily component were mixed, and if necessary, they were heated to dissolve them, and the mixture was stirred and then cooled to obtain a cream. In addition, 1 million I.D. of retinol palmitate ester per 1 g of vitamin A oil. U.S. Those containing 99.4% by weight of cycloartenyl ferulate (C 40 H 58 O 4 ) were used as γ-oryzanol. The following tests were conducted using each of the obtained creams as a test sample.
<試験方法>
「保湿・美白・抗シワ・抗酸化評価・実験法マニュアル」(フレグランスジャーナル社、2012年2月発行)に収載の「再構築表皮モデルを用いたメラニン産生抑制剤評価法」の試験方法に従って試験を行った。
<Test method>
Tested according to the test method of "Melanin production inhibitor evaluation method using reconstructed epidermis model" listed in "Moisturizing / Whitening / Anti-wrinkle / Antioxidant Evaluation / Experimental Method Manual" (Fragrance Journal, published in February 2012) Was done.
メラニン細胞含有培養皮膚モデルとして、MEL−300キット(MEL−300−A、倉敷紡績株式会社)を用いた。試験期間中、CO2インキュベーター(37℃、5%CO2)にて、EPI−100LLMM長期維持培地(倉敷紡績株式会社)を用いて維持、培養を行った。 A MEL-300 kit (MEL-300-A, Kurabo Industries Ltd.) was used as a melanocyte-containing cultured skin model. During the test period, maintenance and culturing were carried out in a CO 2 incubator (37 ° C., 5% CO 2 ) using EPI-100LLMM long-term maintenance medium (Kurabo Industries Ltd.).
メラニン細胞を6穴プレートに移し予備培養を行った後、試験試料を適用した。試験試料の適用は角層側から行った。2週間継続培養後、メラニン細胞の吸光度及び色調に基づき、メラニン定量及び明度測定を行った。更に、試験試料の適用による細胞傷害性の有無を確認するため、アラマーブルー法を用いて細胞生存率を評価し、「メラニン産生量」と「明度」の補正を行った。 After transferring the melanocytes to a 6-well plate and performing preculture, a test sample was applied. The test sample was applied from the stratum corneum side. After continuous culturing for 2 weeks, melanin quantification and brightness measurement were performed based on the absorbance and color tone of the melanocytes. Furthermore, in order to confirm the presence or absence of cytotoxicity due to the application of the test sample, the cell viability was evaluated using the Alamar blue method, and "melanin production" and "brightness" were corrected.
・メラニン産生量の測定
メラニン細胞をチューブに移し、PBS(−)を用いて洗浄した。更に、5%トリクロロ酢酸、エタノール/ジエチルエーテル溶液、ジエチルエーテルの順で洗浄した後、1mol/L水酸化ナトリウム水溶液を添加して、メラニン細胞に含まれるメラニンを加温溶解(100℃、10分間)した。マイクロプレートリーダーを用いて405nmの吸光度を測定した。合成メラニン(シグマアルドリッチジャパン株式会社)を用いて作成した検量線に基づき、測定値から「メラニン産生量」を算出した。次いで、比較例1のメラニン産生量を「100」とした場合の相対値を「メラニン産生率」(%)として算出した(小数点第1位を四捨五入した)。
-Measurement of melanin production The melanocytes were transferred to a tube and washed with PBS (-). Further, after washing in the order of 5% trichloroacetic acid, ethanol / diethyl ether solution, and diethyl ether, a 1 mol / L sodium hydroxide aqueous solution is added to warmly dissolve the melanin contained in the melanocytes (100 ° C., 10 minutes). )bottom. The absorbance at 405 nm was measured using a microplate reader. The "melanin production amount" was calculated from the measured values based on the calibration curve prepared using synthetic melanin (Sigma-Aldrich Japan Co., Ltd.). Next, the relative value when the amount of melanin produced in Comparative Example 1 was set to "100" was calculated as the "melanin production rate" (%) (rounded to the first decimal place).
・明度の測定
メラニン細胞の明度(L値)を、底部側から分光測色計(CR−13(コニカミノルタホールディング株式会社)にて測定した。測定を5回行い、その平均値を求めた。次いで、比較例1の明度を「100」とした場合の相対値を「明度改善率」(%)として算出した(小数点第1位を四捨五入した)。
-Measurement of lightness The lightness (L value) of melanocytes was measured from the bottom side with a spectrophotometer (CR-13 (Konica Minolta Holding Co., Ltd.). The measurement was performed 5 times, and the average value was calculated. Next, the relative value when the brightness of Comparative Example 1 was set to "100" was calculated as the "brightness improvement rate" (%) (rounded off to the first digit).
・アラマーブルー法を用いた細胞生存率評価
10%アラマーブルー試薬を含むEPI−100LLMM長期維持培地を24穴プレートに分注した。MEL−300をこのプレートへ移し、2時間培養した。培養上清の蛍光強度(Ex./Em.=544nm/590nm)を測定した。細胞生存率は、比較例1の蛍光強度を「100」とした場合のIndex(%)として算出した。結果はいずれも99〜105%であった。この細胞生存率に基づいて、「メラニン産生量」と「明度」の値を補正した。
-Evaluation of cell viability using the Alamar Blue method EPI-100LLMM long-term maintenance medium containing 10% Alamar Blue reagent was dispensed into a 24-well plate. MEL-300 was transferred to this plate and cultured for 2 hours. The fluorescence intensity of the culture supernatant (Ex./Em.=544 nm/590 nm) was measured. The cell viability was calculated as Index (%) when the fluorescence intensity of Comparative Example 1 was set to "100". The results were 99-105%. Based on this cell viability, the values of "melanin production" and "brightness" were corrected.
2.評価結果
得られた結果を表3に示す。尿素のみを含む比較例2は、メラニン産生量及び明度において、コントロール(比較例3)と大きな差は見られなかった。また、チロシナーゼ活性阻害効果を有するグリチルリチン酸モノアンモニウムを尿素との組合せた比較例1については、メラニン産生量及び明度において十分な効果を奏さなかった。一方、尿素とグリチルリチン酸モノアンモニウムと共に、γ−オリザノールを含む実施例1では、メラニン産生量を抑制し、かつ明度を向上させることができていた。更に、これらの3つの成分と共にビタミンA油又はトコフェロール酢酸エステルを含有させた実施例2及び3では、メラニン産生量をより効果的に低下させることができ、且つ明度の点にも優れた結果となった。とりわけ、これらの3つの成分と共にビタミンA油及びトコフェロール酢酸エステルの双方を含有させた実施例4では、メラニン産生量の低下及び明度の向上が格別顕著に認められた。
2. Evaluation Results Table 3 shows the results obtained. Comparative Example 2 containing only urea did not show a large difference from the control (Comparative Example 3) in the amount of melanin produced and the brightness. In addition, Comparative Example 1 in which monoammonium glycyrrhizinate having an inhibitory effect on tyrosinase activity was combined with urea did not exert a sufficient effect on the amount of melanin produced and the brightness. On the other hand, in Example 1 containing γ-oryzanol together with urea and monoammonium glycyrrhizinate, the amount of melanin produced could be suppressed and the brightness could be improved. Furthermore, in Examples 2 and 3 in which vitamin A oil or tocopherol acetate was contained together with these three components, the amount of melanin produced could be reduced more effectively, and the result was also excellent in terms of brightness. became. In particular, in Example 4 in which both vitamin A oil and tocopherol acetate were contained together with these three components, a decrease in melanin production and an increase in brightness were remarkably observed.
試験例3:慢性角化型湿疹の改善効果の評価
1.評価方法
表4に示す組成のクリーム剤(水中油型乳化状のクリーム剤)を、前記試験例1と同様の方法で調製した(実施例1、3、4、比較例1、2、4〜7)。なお、ビタミンA油には1g当たりレチノールパルミチン酸エステルを100万I.U.含有するものを使用し、また、γ−オリザノールにはフェルラ酸シクロアルテニル(C40H58O4)を99.4重量%含有するものを使用した。
Test Example 3: Evaluation of improvement effect of chronic keratinized eczema
1. 1. Evaluation Method A cream having the composition shown in Table 4 (oil-in-water emulsified cream) was prepared in the same manner as in Test Example 1 (Examples 1, 3, 4 and Comparative Examples 1, 2, 4 to 1). 7). In addition, 1 million I.D. of retinol palmitate ester per 1 g of vitamin A oil. U.S. Those containing 99.4% by weight of cycloartenyl ferulate (C 40 H 58 O 4 ) were used as γ-oryzanol.
各クリーム剤を用いて、肘に慢性角化型湿疹が生じており、肘の角層の肥厚化及び黒ずみが気になる被験者9名に対して臨床評価を行った。被験者1名当たり1つのクリーム剤を1日1回、1回当たり、約1.5mg/皮膚1cm2で1ヵ月間、肘に塗布した。1ヵ月後に、慢性角化型湿疹の改善満足度について、「肘の角層の肥厚化及び黒ずみが改善した」を「10」、「肘の角層の肥厚化及び黒ずみが改善しなかった」を「1」とするVAS法(Visual Analogue Scale)によって評価した。また、比較例1のVAS法による評点を「100」とした場合の相対値を「改善率」(%)として算出した(小数点第1位を四捨五入した)。 Using each cream, clinical evaluation was performed on 9 subjects who had chronic keratinized eczema on the elbow and were worried about thickening and darkening of the stratum corneum of the elbow. One cream was applied to the elbow once a day at about 1.5 mg / skin 1 cm 2 per subject for 1 month. One month later, regarding the degree of satisfaction with the improvement of chronic keratinized eczema, "the thickening and darkening of the elbow stratum corneum improved" was "10", and "the thickening and darkening of the elbow stratum corneum did not improve". Was evaluated by the VAS method (Visual Analogue Scale) in which "1" was set. In addition, the relative value when the score by the VAS method of Comparative Example 1 was set to "100" was calculated as the "improvement rate" (%) (rounded to the first decimal place).
2.評価結果
得られた結果を表4に示す。また、実施例4の塗布前と塗布1カ月後の肘の状態を撮影した写真を図1に示す。尿素又はグリチルリチン酸モノアンモニウムのみを含有する比較例2及び4では、角層の肥厚化及び黒ずみを十分に改善できず、慢性角化型湿疹の改善効果は満足できるものではなかった。また、尿素とグリチルリチン酸モノアンモニウムを組み合わせた比較例1、尿素とγ−オリザノールを組み合わせた比較例5、及び尿素とビタミンA油を組み合わせた比較例6でも、尿素単独の比較例2と同程度の効果しか認められなかった。更に、グリチルリチン酸モノアンモニウムとγ−オリザノールを組み合わせた比較例7では、尿素単独の比較例2に比べて、慢性角化型湿疹の改善効果は劣っていた。これに対して、尿素、グリチルリチン酸モノアンモニウム、及びγ−オリザノールを含む実施例1では、優れた慢性角化型湿疹の改善効果が認められた。特に、これらの3成分にトコフェロール酢酸エステルを組み合わせた実施例3では、慢性角化型湿疹の改善効果が顕著に優れており、とりわけ、これらの3成分にトコフェロール酢酸エステルとビタミンA油を組み合わせた実施例4では、慢性角化型湿疹の改善効果が格段に高まっていた。
2. Evaluation Results Table 4 shows the results obtained. In addition, FIG. 1 shows photographs of the state of the elbow before and one month after the application of Example 4. In Comparative Examples 2 and 4 containing only urea or monoammonium glycyrrhizinate, the thickening and darkening of the stratum corneum could not be sufficiently improved, and the effect of improving chronic keratinized eczema was not satisfactory. Further, Comparative Example 1 in which urea and monoammonium glycyrrhizinate are combined, Comparative Example 5 in which urea and γ-oryzanol are combined, and Comparative Example 6 in which urea and vitamin A oil are combined are also comparable to Comparative Example 2 in which urea alone is used. Only the effect of was observed. Furthermore, in Comparative Example 7 in which monoammonium glycyrrhizinate and γ-oryzanol were combined, the effect of improving chronic keratinized eczema was inferior to that in Comparative Example 2 in which urea alone was used. On the other hand, in Example 1 containing urea, monoammonium glycyrrhizinate, and γ-oryzanol, an excellent effect of improving chronic keratinized eczema was observed. In particular, in Example 3 in which tocopherol acetate was combined with these three components, the effect of improving chronic keratinized eczema was remarkably excellent, and in particular, tocopherol acetate and vitamin A oil were combined with these three components. In Example 4, the effect of improving chronic keratinized eczema was significantly enhanced.
製剤例
表5〜7に示す慢性角化型湿疹改善剤を調製した。表5に示す慢性角化型湿疹改善剤はクリーム剤(水中油型乳液状クリーム剤)、表6に示す慢性角化型湿疹改善剤は液剤、表5に示す慢性角化型湿疹改善剤はゲル剤である。得られた各慢性角化型湿疹改善剤を前記試験例2と同様の方法で慢性角化型湿疹の改善効果を評価したところ、優れた慢性角化型湿疹の改善効果が認められた。
Preparation Examples The chronic keratinized eczema improving agents shown in Tables 5 to 7 were prepared. The chronic keratinized eczema improving agent shown in Table 5 is a cream agent (oil-in-water milky liquid cream agent), the chronic keratinized eczema improving agent shown in Table 6 is a liquid agent, and the chronic keratinized eczema improving agent shown in Table 5 is a liquid agent. It is a gel agent. When each of the obtained chronic keratinized eczema improving agents was evaluated for improving chronic keratinized eczema by the same method as in Test Example 2, an excellent improving effect for chronic keratinized eczema was observed.
Claims (3)
(B)グリチルリチン酸、グリチルレチン酸、それらの誘導体、及びそれらの塩よりなる群から選択される少なくとも1種、
(C)γ−オリザノール、並びに
(E)レチノール及び/又はその誘導体を含有し、
前記(B)成分の前記誘導体が、グリチルリチン酸メチル、グリチルリチン酸ステアリル、グリチルレチン酸ピリドキシン、グリチルレチン酸ステアリル、グリチルレチン酸グリセリル、及びグリチルレチン酸モノグルクロニドからなる群より選択され、前記(E)成分の前記誘導体が、レチノールと脂肪酸とのエステル、レチノールと酢酸とのエステル、レチノール酸化物、及びレチノール酸化物のエステルからなる群より選択される慢性角化型湿疹改善剤。 (A) Urea,
(B) At least one selected from the group consisting of glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof .
( C) γ-oryzanol , and
(E) Containing retinol and / or its derivatives,
The derivative of the component (B) is selected from the group consisting of methyl glycyrrhizinate, stearyl glycyrrhetinate, pyridoxin glycyrrhetinate, stearyl glycyrrhetinate, glyceryl glycyrrhetinate, and monoglucuronide glycyrrhetinate, and the derivative of the component (E). but ester of retinol and a fatty acid, retinol and esters of acetic acid, retinol oxides, and chronic angle of type eczema improving agent that will be selected from the group consisting of esters of retinol oxide.
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