JPWO2012042970A1 - Preventive or therapeutic agent for atopic dermatitis, and external preparation - Google Patents
Preventive or therapeutic agent for atopic dermatitis, and external preparation Download PDFInfo
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- JPWO2012042970A1 JPWO2012042970A1 JP2012536248A JP2012536248A JPWO2012042970A1 JP WO2012042970 A1 JPWO2012042970 A1 JP WO2012042970A1 JP 2012536248 A JP2012536248 A JP 2012536248A JP 2012536248 A JP2012536248 A JP 2012536248A JP WO2012042970 A1 JPWO2012042970 A1 JP WO2012042970A1
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Abstract
ステロイド剤と同等またはそれ以上の抗掻痒作用および抗炎症作用を有しており、アトピー性皮膚炎の予防剤または治療剤として有用な技術を提供する。本発明に係るアトピー性皮膚炎の予防剤または治療剤は、Ｖｅｒｎｏｎｉａ Ａｍｙｇｄａｌｉｎａ葉のアルコールおよび／または水の抽出物を有効成分として含有している。It has an anti-pruritic action and an anti-inflammatory action equivalent to or higher than those of steroids, and provides a technique useful as a preventive or therapeutic agent for atopic dermatitis. The preventive or therapeutic agent for atopic dermatitis according to the present invention contains an extract of alcohol and / or water of Vernonia Amygdalina leaves as an active ingredient.
Description
本発明は、Ｖｅｒｎｏｎｉａ Ａｍｙｇｄａｌｉｎａ（ＶＡＭ）葉のアルコールおよび／または水の抽出物を有効成分として含有するアトピー性皮膚炎の予防剤または治療剤；ＶＡＭ葉および／またはその上記抽出物を有効成分として含有する化粧料などの外用剤；並びに、ＶＡＭ葉および／またはその上記抽出物を含有する外用剤素材に関するものである。 The present invention relates to a prophylactic or therapeutic agent for atopic dermatitis containing an alcohol and / or water extract of Vernonia Amygdalina (VAM) as an active ingredient; VAM leaf and / or the extract thereof as an active ingredient And an external preparation material containing VAM leaves and / or the extract thereof.
アトピー性皮膚炎は強い痒みを伴う皮膚疾患であり、そのためアトピー性皮膚炎の患者は引っ掻き行動を頻繁に行なって炎症部位の慢性化を招いている。アトピー性皮膚炎では血清中のＩｇＥ濃度が上昇するほか、炎症の初期には好中球、中期にはマクロファージ、後期には好酸球の増加が見られるなど、炎症細胞の特徴的な推移が見られる。現在、アトピー性皮膚炎の治療剤として、副腎皮質ホルモンを主体とするステロイド剤が汎用されているが、抗かゆみ作用（抗掻痒作用）は不十分であるという問題を抱えている。 Atopic dermatitis is a skin disease accompanied by strong itching, and therefore, patients with atopic dermatitis frequently perform scratching behavior to cause chronic inflammation. In the case of atopic dermatitis, serum IgE concentration increases, neutrophils in the early stage of inflammation, macrophages in the middle stage, and eosinophils in the late stage. It can be seen. Currently, steroids mainly composed of corticosteroids are widely used as therapeutic agents for atopic dermatitis, but have a problem that anti-itch action (anti-pruritus action) is insufficient.
一方、Ｖｅｒｎｏｎｉａ Ａｍｙｇｄａｌｉｎａ（ベルノニア アミグダリナ）は、熱帯アフリカに広く自生するキク科潅木であり、この水溶性葉抽出物はヒト乳癌に対して抗癌活性を有することが知られている。また、特許文献１および２には、Ｖｅｒｎｏｎｉａ Ａｍｙｇｄａｌｉｎａ乾燥葉をクロロホルム抽出、ｎ−ヘキサン−メタノール抽出、シリカゲルクロマトグラフィー、ＨＰＬＣ等により精製して得られた水不溶性のベルノダリンまたはそのジヒドロ体が、マウス白血病細胞に対する抗腫瘍効果や、マウスＴ細胞依存性／非依存性の抗体産生能を有することが報告されている。また特許文献３には、極性溶媒またはその混合物により抽出されたＶｅｒｎｏｎｉａ Ａｍｙｇｄａｌｉｎａの抽出物が体毛喪失予防および／または体毛成長促進の作用を有することが報告されている。
On the other hand, Vernonia Amygdalina is a asteraceae shrub that grows naturally in tropical Africa, and this water-soluble leaf extract is known to have anticancer activity against human breast cancer. In
しかしながら、上記特許文献を含め、これまでにＶｅｒｎｏｎｉａ Ａｍｙｇｄａｌｉｎａ葉のアルコールおよび／または水の抽出物とアトピー性皮膚炎との関係について具体的に開示されたものはない。 However, there is nothing specifically disclosed about the relationship between the alcohol and / or water extract of Vernonia Amygdalina leaves and atopic dermatitis, including the above patent documents.
また、Ｖｅｒｎｏｎｉａ Ａｍｙｇｄａｌｉｎａ葉やその上記抽出物を化粧料や入浴剤に用いたものものこれまで開示されていない。 Moreover, the thing using Vernonia Amygdalina leaf and the said extract for cosmetics and a bath agent is not disclosed until now.
本発明は上記事情に鑑みてなされたものであって、その目的は、ステロイド剤と同等またはそれ以上の抗掻痒作用および抗炎症作用を有しており、アトピー性皮膚炎の予防剤または治療剤として極めて有用な技術を提供することにある。 The present invention has been made in view of the above circumstances, and its object is to have an anti-pruritic action and an anti-inflammatory action equivalent to or higher than that of a steroid agent, and a preventive or therapeutic agent for atopic dermatitis. It is to provide a very useful technique.
更に本発明の他の目的は、例えば、抗掻痒作用や抗炎症作用などを発揮し得る新規な外用剤およびその原料となる外用剤素材を提供することにある。 Still another object of the present invention is to provide a novel external preparation capable of exhibiting, for example, an anti-pruritic action or an anti-inflammatory action, and an external preparation material as a raw material thereof.
上記課題を解決し得た本発明に係るアトピー性皮膚炎の予防剤または治療剤は、Ｖｅｒｎｏｎｉａ Ａｍｙｇｄａｌｉｎａ葉のアルコールおよび／または水の抽出物を有効成分として含有するところに要旨を有するものである。 The prophylactic or therapeutic agent for atopic dermatitis according to the present invention, which has solved the above problems, has a gist in that it contains an alcohol and / or water extract of Vernonia Amygdalina leaf as an active ingredient.
また、上記課題を解決し得た本発明の外用剤は、Ｖｅｒｎｏｎｉａ Ａｍｙｇｄａｌｉｎａ葉、および／またはそのアルコールおよび／または水の抽出物を有効成分として含有するところに要旨を有するものである。 Moreover, the external preparation of this invention which could solve the said subject has a summary in the place which contains the extract of Vernonia Amygdalina, and / or its alcohol and / or water extract as an active ingredient.
本発明の好ましい実施形態において、上記外溶剤は、化粧料として用いられるものである。 In a preferred embodiment of the present invention, the outer solvent is used as a cosmetic.
本発明の好ましい実施形態において、上記化粧料は、入浴剤として用いられるものである。 In a preferred embodiment of the present invention, the cosmetic is used as a bath agent.
本発明には、Ｖｅｒｎｏｎｉａ Ａｍｙｇｄａｌｉｎａ葉、および／またはそのアルコールおよび／または水の抽出物を含有する化粧料用または入浴剤用素材も包含される。 The present invention also includes a cosmetic or bath additive material containing Vernonia Amygdalina leaves and / or an alcohol and / or water extract thereof.
本発明の予防剤または治療剤は、Ｖｅｒｎｏｎｉａ Ａｍｙｇｄａｌｉｎａ葉のアルコールおよび／または水の抽出物を有効成分として含有するため、汎用のステロイド剤と同等またはそれ以上に高い抗掻痒作用および抗炎症作用が発揮される。 Since the prophylactic or therapeutic agent of the present invention contains an extract of alcohol and / or water of Vernonia Amygdalina as an active ingredient, it exhibits an anti-pruritic action and an anti-inflammatory action equivalent to or higher than general-purpose steroids. Is done.
また、Ｖｅｒｎｏｎｉａ Ａｍｙｇｄａｌｉｎａ葉自体、および／またはその上記抽出物は、外用剤素材として有用であり、これらを含む外用剤は、例えばローション、乳液、石鹸、入浴剤などの化粧料として好適に用いられる。 Further, the Vernonia Amygdalina leaf itself and / or the extract thereof are useful as external preparation materials, and external preparations containing them are suitably used as cosmetics such as lotions, milky lotions, soaps, bathing agents and the like.
本発明者らは、Ｖｅｒｎｏｎｉａ Ａｍｙｇｄａｌｉｎａ（ベルノニア アミグダリナ）葉のアルコールおよび／または水の抽出物について種々検討をしてきた。その結果、上記抽出物はアトピー性皮膚炎の予防剤または治療剤のいずれにおいても適用可能であり、驚くべきことに、汎用のステロイド剤と同等またはそれ以上に優れた抗掻痒作用および抗炎症作用を両方有することを見出し、本発明を完成した。上述したようにステロイド剤は、抗掻痒作用が弱く、激しい痒みのために炎症部位が慢性化するといった問題があるのに対し、本発明の抽出物は抗掻痒作用にも優れているため、このような問題を解消することができる。 The present inventors have conducted various studies on alcohol and / or water extracts of Vernonia Amygdalina leaves. As a result, the above extract can be applied to any prophylactic or therapeutic agent for atopic dermatitis. Surprisingly, it has an anti-pruritic action and an anti-inflammatory action equivalent to or better than general-purpose steroids. The present invention was completed. As described above, the steroid agent has a weak anti-pruritic action and there is a problem that the inflammatory site becomes chronic due to intense itching, whereas the extract of the present invention has an excellent anti-pruritic action. Such problems can be solved.
また、Ｖｅｒｎｏｎｉａ Ａｍｙｇｄａｌｉｎａ葉自体、および／またはその上記抽出物は、外用剤素材として有用であり、これらを含む外用剤は、例えば化粧水、乳液、石鹸、入浴剤などの化粧料として好適に用いられる。例えば入浴剤などは、Ｖｅｒｎｏｎｉａ Ａｍｙｇｄａｌｉｎａの抽出物のみならずＶｅｒｎｏｎｉａ Ａｍｙｇｄａｌｉｎａ葉もそのまま、湯中に浸漬するなどして使用することができる。上記外用剤の使用により、例えば、抗掻痒作用や抗炎症作用などの効能が期待される。 In addition, the Vernonia Amygdalina leaf itself and / or the extract thereof are useful as external preparation materials, and external preparations containing these are suitably used as cosmetics such as skin lotions, emulsions, soaps, bathing agents, and the like. . For example, bathing agents and the like can be used by immersing Vernonia Amygdalina leaves as well as Vernonia Amygdalina leaves as they are in hot water. By using the above external preparation, for example, effects such as anti-pruritic action and anti-inflammatory action are expected.
以下、本発明について詳細に説明する。本明細書では、Ｖｅｒｎｏｎｉａ ＡｍｙｇｄａｌｉｎａをＶＡＭと略記する場合がある。また、Ｖｅｒｎｏｎｉａ Ａｍｙｇｄａｌｉｎａ葉のアルコールおよび／または水の抽出物を、単にＶＡＭ葉の抽出物と呼ぶ場合がある。 Hereinafter, the present invention will be described in detail. In this specification, Vernonia Amygdalina may be abbreviated as VAM. In addition, the alcohol and / or water extract of Vernonia Amygdalina leaves may be referred to simply as the VAM leaf extract.
（１）アトピー性皮膚炎の予防剤または治療剤
まず、本発明に係るアトピー性皮膚炎の予防剤または治療剤について説明する。上記予防剤または治療剤は、ＶＡＭ葉のアルコールおよび／または水の抽出物を有効成分として含有する。(1) Preventive or therapeutic agent for atopic dermatitis First, the preventive or therapeutic agent for atopic dermatitis according to the present invention will be described. The prophylactic or therapeutic agent contains an alcohol and / or water extract of VAM leaves as an active ingredient.
本発明に用いられる抽出物は、ＶＡＭ葉を用い、アルコールおよび／または水の溶媒で抽出した後の抽出液（ろ過後の溶出部分）である。ただし、これに限定されず、保存安定性などを考慮して、必要に応じて、その後に上記抽出液を濃縮したり上記溶媒に再溶解したり、あるいは乾燥したりするなど通常用いられる精製手段を行っても良く、このような処理を行なったものも、本発明に用いられる抽出物の範囲に包含される。 The extract used in the present invention is an extract (elution part after filtration) after extraction with a solvent of alcohol and / or water using VAM leaves. However, it is not limited to this, and in consideration of storage stability, etc., a purification means usually used, such as concentrating the extract, re-dissolving in the solvent, or drying afterwards, if necessary Those subjected to such treatment are also included in the scope of the extract used in the present invention.
以下、上記抽出物を得るための好ましい抽出方法を説明する。 Hereinafter, the preferable extraction method for obtaining the said extract is demonstrated.
まず、原料としてＶｅｒｎｏｎｉａ Ａｍｙｇｄａｌｉｎａ（ＶＡＭ）の葉を用意する。本発明に用いられるＶＡＭの産地や採取時期などは特に限定されないが、アトピー性皮膚炎に対する優れた予防作用または治療作用を得るためには、ＶＡＭの新葉などが好ましく用いられる。 First, a leaf of Vernonia Amygdalina (VAM) is prepared as a raw material. There are no particular limitations on the VAM production area and collection time used in the present invention, but in order to obtain an excellent preventive or therapeutic action against atopic dermatitis, new leaves of VAM are preferably used.
本発明では、ＶＡＭのうち葉を抽出材料として用いる。葉のなかにアトピー性皮膚炎の予防または治療に有用な成分が含まれていると考えられるからである。本発明では、葉のみを用いても良いが、本発明の作用を損なわない範囲で、葉以外の部分（茎や根など）が含まれていても良い。 In the present invention, leaves of VAM are used as the extraction material. This is because the leaves are considered to contain components useful for the prevention or treatment of atopic dermatitis. In the present invention, only leaves may be used, but portions other than the leaves (such as stems and roots) may be included as long as the effects of the present invention are not impaired.
以下の抽出を行なう前に、必要に応じて、ＶＡＭの葉を洗浄したり乾燥しても良い。乾燥の条件は特に限定されないが、有効成分の細胞内水分による変性や腐敗を考慮すると、収穫後、風通しを良くするために竿に吊るして天日で乾燥を行なうことが好ましい。 Before performing the following extraction, the leaves of VAM may be washed or dried as necessary. The conditions for drying are not particularly limited, but considering denaturation and spoilage of the active ingredient due to intracellular moisture, it is preferable to hang it on a straw after harvesting and dry it in the sun for better ventilation.
また、抽出効率を高めるため、抽出の前にＶＡＭの葉を粉砕することが好ましい。粉砕方法は特に限定されず、例えば、ボールミル、ハンマーミル、ローラーミル、ロッドミル、サンプルミル、スタンプミル、エヒスインテグレーター、冷却装置付きブレンダーなどを用い、おおむね１ｍｍ〜１０ｍｍのサイズに粉砕することが好ましい。 Moreover, in order to improve extraction efficiency, it is preferable to grind the leaf of VAM before extraction. The pulverization method is not particularly limited. For example, it is preferable to pulverize to a size of about 1 mm to 10 mm using, for example, a ball mill, a hammer mill, a roller mill, a rod mill, a sample mill, a stamp mill, an echs integrator, or a blender with a cooling device. .
次に、粉砕した材料にアルコールおよび／または水の溶媒を加えて浸漬させ、有効成分を抽出する。本発明では、抽出溶媒として、メタノール、エタノール、アセトン、イソプロピルアルコール等のアルコール：または水を単独で用いても良いし、これらの混合溶媒を用いても良い。上記混合溶媒としては、例えばメタノールと水、エタノールと水などが挙げられ、具体的には、例えばメタノール：水＝５０：５０〜８０：２０のものが例示される。後記する実施例に示すように、水よりもアルコール（特にメタノール）抽出物の方が、高い活性が得られる。 Next, a solvent of alcohol and / or water is added to the pulverized material and immersed to extract the active ingredient. In the present invention, as an extraction solvent, alcohols such as methanol, ethanol, acetone, and isopropyl alcohol: or water may be used alone, or a mixed solvent thereof may be used. Examples of the mixed solvent include methanol and water, ethanol and water, and specific examples include methanol: water = 50: 50 to 80:20. As shown in the examples described later, an alcohol (particularly methanol) extract is more active than water.
上記の浸漬条件は、抽出溶媒の種類や抽出材料の量などに応じ、適宜調節することができる。例えば用いられる抽出溶媒の量は、抽出材料であるＶＡＭ葉が、少なくとも万遍なく浸漬する程度とし、有効成分の抽出量や濃縮する際の効率などを考慮して適宜調節すればよいが、おおむね、乾燥状態の抽出材料１００質量部に対し、抽出溶媒を約１００〜１０００の割合で用いることが好ましい。 Said immersion conditions can be suitably adjusted according to the kind of extraction solvent, the quantity of extraction material, etc. For example, the amount of the extraction solvent to be used should be adjusted so that the VAM leaf as the extraction material is at least uniformly immersed, taking into consideration the extraction amount of the active ingredient and the efficiency at the time of concentration. The extraction solvent is preferably used at a ratio of about 100 to 1000 with respect to 100 parts by mass of the extraction material in a dry state.
抽出温度も特に制限されず、抽出効率を高めるために３０〜５０℃程度に加温してもよいが、有効成分が分解される恐れがあるので、室温で抽出することが好ましい。抽出時間も適宜調節すればよいが、おおむね、室温で５〜１０日間程度であることが好ましい。 The extraction temperature is not particularly limited and may be heated to about 30 to 50 ° C. in order to increase the extraction efficiency. However, since the active ingredient may be decomposed, it is preferable to extract at room temperature. The extraction time may be adjusted as appropriate, but it is preferably about 5 to 10 days at room temperature.
抽出効率を更に高めるために、抽出材料に抽出溶媒を加えた後、攪拌することが好ましい。あるいは、抽出材料に抽出溶媒を加えた後、上記の粉砕機などを用いて磨り潰すことも好ましい態様である。 In order to further increase the extraction efficiency, it is preferable to stir after adding the extraction solvent to the extraction material. Or after adding an extraction solvent to extraction material, it is also a preferable aspect to grind | pulverize using said pulverizer etc.
本発明では、上記の抽出処理を行なった後、濾過等によって抽出残渣を除去し、得られた抽出液を、そのままアトピー性皮膚炎の予防剤または治療剤として用いることができる。 In this invention, after performing said extraction process, an extraction residue is removed by filtration etc., and the obtained extract can be used as a preventive agent or a therapeutic agent of atopic dermatitis as it is.
あるいは本発明では、上記のようにして得られた抽出液を濃縮したものや、さらに前述したアルコールおよび／または水の抽出溶媒に再溶解したものを、アトピー性皮膚炎の予防剤または治療剤として用いることもできる。これにより、保存安全性などが向上する。濃縮処理では、濃縮温度の抑制や作業効率の観点からエバポレーターを用いて蒸留することが好ましい。具体的な蒸留条件は、有効成分の抽出量や濃縮する際の効率などを考慮して適宜調節すればよいが、おおむね、温度：約２０〜５５℃、圧力：約４００〜６００ｈＰａにて蒸留を行なうことが好ましい。 Alternatively, in the present invention, a concentrate obtained by the above-described method or a solution obtained by re-dissolving in the above-described alcohol and / or water extraction solvent is used as a prophylactic or therapeutic agent for atopic dermatitis. It can also be used. Thereby, storage safety etc. improve. In the concentration treatment, it is preferable to perform distillation using an evaporator from the viewpoint of suppressing the concentration temperature and working efficiency. Specific distillation conditions may be appropriately adjusted in consideration of the extraction amount of the active ingredient and the efficiency at the time of concentration, but generally the distillation is performed at a temperature of about 20 to 55 ° C. and a pressure of about 400 to 600 hPa. It is preferable to do so.
本発明では、上記のように濃縮や再溶解を行なったものを、そのままアトピー性皮膚炎の予防剤または治療剤として用いても良いが、一旦乾燥し、使用直前に抽出溶媒に適宜溶かして用いることもできる。 In the present invention, the concentrated or re-dissolved product as described above may be used as it is as a prophylactic or therapeutic agent for atopic dermatitis, but once dried, it is used after being appropriately dissolved in an extraction solvent immediately before use. You can also.
本発明に係るアトピー性皮膚炎の予防剤または治療剤は、上記のようにして得られた抽出物を有効成分として含むものである。上記の抽出物には、医薬的に通常用いられる公知の製剤成分を添加し、様々な製剤とすることができる。例えば、基材、賦形剤、着色剤、滑沢剤、矯味剤、乳化剤、増粘剤、湿潤剤、安定剤、保存剤、溶剤、溶解補助剤、懸濁化剤、抗酸化剤、佐薬、緩衝剤、ｐＨ調整剤、甘味料、香料などを添加することができる。また、これら添加剤の配合量は、本発明の作用効果を妨げない様な量である限り、必要に応じて適宜設定することができる。 The preventive or therapeutic agent for atopic dermatitis according to the present invention contains the extract obtained as described above as an active ingredient. To the above extract, known pharmaceutical ingredients that are ordinarily used in medicine can be added to obtain various preparations. For example, base materials, excipients, colorants, lubricants, flavoring agents, emulsifiers, thickeners, wetting agents, stabilizers, preservatives, solvents, solubilizers, suspending agents, antioxidants, Drugs, buffers, pH adjusters, sweeteners, fragrances and the like can be added. Moreover, the compounding quantity of these additives can be suitably set as needed as long as it is the quantity which does not prevent the effect of this invention.
上記予防剤又は治療剤の適用方法は特に限定されず、外用剤（軟膏剤、貼付剤、リニメント剤、ローション剤、パップ剤など）、粘膜適用剤（トローチ剤、坐剤など)、注射剤、経口投与剤（散剤、顆粒剤、カプセル剤、丸剤、錠剤、エキス剤、流エキス剤、エリキシル剤、懸濁剤・乳剤、チンキ剤、シロップ剤など）などの形態で適用することができる。 The application method of the prophylactic or therapeutic agent is not particularly limited, and external preparations (ointments, patches, liniments, lotions, poultices, etc.), mucosal agents (troches, suppositories, etc.), injections, It can be applied in the form of orally administered agents (powder, granule, capsule, pill, tablet, extract, flow extract, elixir, suspension / emulsion, tincture, syrup, etc.).
例えば上記ＶＡＭ葉抽出物を用いる場合、いったん濃縮して粉末とした抽出物を、水等の溶媒に再溶解または再分散する。このときの抽出物の濃度は特に制限されず、被験者の状態等により適宜調節すればよいが、例えば、乾燥状態の抽出物の濃度に換算して、約５０〜２００ｇ／Ｌ程度とすることが好ましい。 For example, when the above VAM leaf extract is used, the extract once concentrated to a powder is redissolved or redispersed in a solvent such as water. The concentration of the extract at this time is not particularly limited, and may be appropriately adjusted depending on the condition of the subject. For example, it may be about 50 to 200 g / L in terms of the concentration of the extract in the dry state. preferable.
上記抽出物の溶媒としては、ヒトや動物が飲用するに適した水が好ましい。例えば、蒸留水、精製水、純水、水道水などを用いればよい。また、微量のエタノールなどを添加してもよい。 The solvent for the extract is preferably water suitable for drinking by humans and animals. For example, distilled water, purified water, pure water, tap water, or the like may be used. A trace amount of ethanol or the like may be added.
本発明に係るアトピー性皮膚炎の予防剤または治療剤の投与量は、投与すべき被験者の症状や年齢や性別；抽出物の構成などに応じ、所望の作用効果が得られるように適宜適切に調製すれば良い。例えばラットには、おおむね、２００ｍｇ／ｋｇ／日程度投与することが好ましいが、ヒトに対しては、より少ない量であることが好ましい。何れにせよ、被験者の状態等を充分考慮し、投与量は適宜調節すればよい。 The dose of the preventive or therapeutic agent for atopic dermatitis according to the present invention is appropriately determined appropriately so as to obtain a desired effect according to the symptoms, age and sex of the subject to be administered; What is necessary is just to prepare. For example, it is preferable to administer about 200 mg / kg / day to rats, but a smaller amount is preferable for humans. In any case, the dose may be adjusted as appropriate in consideration of the condition of the subject.
（２）外用剤
上記ＶＡＭ葉および／またはその抽出物（アルコールおよび／または水の抽出物）は、外用剤の原料として用いることができる。外用剤は、更に皮膚外用剤と化粧料に大別される。上記皮膚外溶剤としては、例えば軟膏剤、貼付剤、リニメント剤、ローション剤、パップ剤などが挙げられる。(2) External preparation The said VAM leaf and / or its extract (alcohol and / or water extract) can be used as a raw material of an external preparation. External preparations are further broadly classified into skin external preparations and cosmetics. Examples of the external skin solvent include ointments, patches, liniments, lotions, and poultices.
上記化粧料の種類は特に限定されず、例えば乳液、化粧水（ローション）、クリーム、洗顔料、ジェル、エッセンス（美容液）、パック・マスク、ひげそり用化粧料などの基礎化粧品；ファンデーション類、口紅類。白粉・打粉類、頬紅類、眉目類、美爪類などのメーキャップ化粧品；洗髪用化粧品（シャンプーやリンスなど）、育毛剤、毛髪仕上げ用化粧品（ヘアスタイリング剤、ヘアトリートメント剤など）；パーマネントウェーブ用剤、染毛剤、ヘアブリーチなどの毛髪化粧品；香水やコロンなどの芳香化粧品；石鹸、液体ボディ洗浄料、サンケア製品、ハンドケア製品、防臭化粧品、脱色剤・除毛剤、入浴剤（浴用剤）などのボディ化粧品；歯磨類、口中清涼剤などの口腔用化粧品などが挙げられる。 The types of the above cosmetics are not particularly limited. For example, basic cosmetics such as milky lotion, lotion, cream, facial cleanser, gel, essence (beauty serum), pack / mask, shaving cosmetics, foundations, lipsticks, etc. Kind. Makeup cosmetics such as white powder, dusting powder, blusher, eyebrows, and beautiful nails; cosmetics for hair washing (shampoos, rinses, etc.), hair restoration agents, cosmetics for hair finishing (hair styling agents, hair treatment agents, etc.); for permanent waves Hair cosmetics such as hair, hair dye, hair bleach; aromatic cosmetics such as perfumes and colons; soap, liquid body cleansers, sun care products, hand care products, deodorant cosmetics, decolorizers / hair removers, bath preparations (bath preparations) Body cosmetics such as: toothpastes, oral cosmetics such as mouth fresheners.
上記化粧料として用いる場合、ＶＡＭ葉抽出物などの有効成分のほかに、化粧料原料として通常用いられる成分を適宜配合することができる。上記成分としては、例えば、油脂、ロウ類、炭化水素、高級脂肪酸、高級アルコール、エステル類、シリコーン油などの油性原料；アニオン界面活性剤、カチオン界面活性剤、両性界面活性剤、非イオン界面活性剤などの界面活性剤；グリセリン、プロピレングリコールなどの保湿剤；増粘剤高分子（キサンタンガム、カルボキシメチルセルロースナトリウムなど）、皮膜剤高分子（ポリビニルアルコール、ポリビニルピロリドンなど）などの高分子化合物；紫外線吸収剤；酸化防止剤；金属イオン封鎖剤などが挙げられる。 When used as the cosmetic, in addition to active ingredients such as VAM leaf extract, components that are usually used as cosmetic raw materials can be appropriately blended. Examples of the components include oily raw materials such as fats and oils, waxes, hydrocarbons, higher fatty acids, higher alcohols, esters, silicone oils; anionic surfactants, cationic surfactants, amphoteric surfactants, nonionic surfactants Surfactants such as agents; moisturizers such as glycerin and propylene glycol; polymer compounds such as thickener polymers (such as xanthan gum and sodium carboxymethylcellulose) and film-forming polymers (such as polyvinyl alcohol and polyvinylpyrrolidone); UV absorption Agents; antioxidants; sequestering agents and the like.
以下、本発明に用いられるが外用剤の代表例として、入浴剤および化粧料を代表的に取り上げて、より詳細に説明する。 Hereinafter, bathing agents and cosmetics will be taken up as representative examples of external preparations, which will be described in more detail.
（入浴剤）
入浴剤として用いる場合、前述したＶＡＭ葉の抽出物を用いても良いし、ＶＡＭ葉そのものを用いても良い。ＶＡＭ葉そのものを用いる場合、ＶＡＭ葉の乾燥品を用いても良いし、ＶＡＭ葉の粉砕物（粉末）を用いても良い。なお、入浴剤以外の化粧料として用いるときは、ＶＡＭ葉の抽出物を用いることが好ましい。(Bath additive)
When used as a bath agent, the aforementioned VAM leaf extract may be used, or the VAM leaf itself may be used. In the case of using the VAM leaf itself, a dried product of the VAM leaf may be used, or a pulverized product (powder) of the VAM leaf may be used. In addition, when using as cosmetics other than a bath agent, it is preferable to use the extract of VAM leaf.
上記ＶＡＭ葉（粉末などを含む）および／またはその抽出物は、そのまま湯中に入れて使用しても良いし、或いは、これらを不織布などの多孔質袋体に入れて湯中に浸漬して揉み出しながら使用することもできる。あるいは、スプレードライ処理などにより乾燥したＶＡＭ葉などを、血行促進効果のある無機塩類（例えば塩化ナトリウム、塩化カリウム、硫酸ナトリウムなど）、皮膚を清浄にする無機塩類（例えば炭酸水素ナトリウム、セスキ炭酸ナトリウム、炭酸ナトリウム、炭酸カリウムなど）に加えて使用しても良い。 The VAM leaves (including powders) and / or their extracts may be used as they are in hot water, or they may be immersed in hot water in porous bags such as nonwoven fabrics. It can also be used while squeezing out. Alternatively, VAM leaves dried by spray-drying treatment, etc., inorganic salts (for example, sodium chloride, potassium chloride, sodium sulfate, etc.) having blood circulation promoting effects, and inorganic salts (for example, sodium bicarbonate, sodium sesquicarbonate) for cleaning the skin , Sodium carbonate, potassium carbonate, etc.).
（化粧水）
化粧水の種類は、柔軟化粧水、収れん化粧水、洗浄用化粧水などに大別され、化粧水の種類に応じて通常用いられる方法によって製造することができる。例えば、例えば透明化粧水（弱酸性）を構成する基材の一般的な処方例は、以下のとおりであり、有効成分としてＶＡＭ葉の抽出物を適宜添加すれば良い。ただし、本発明は下記処方例に限定する趣旨ではない。(Lotion)
The types of lotions are broadly classified into soft lotions, astringent lotions, cleaning lotions, and the like, and can be produced by a method that is usually used according to the type of lotion. For example, a general formulation example of a base material constituting, for example, transparent lotion (weakly acidic) is as follows, and an extract of VAM leaves may be added as an active ingredient as appropriate. However, the present invention is not intended to be limited to the following prescription examples.
保湿剤（１，３−ブチレングリコールグリセリン）６．０質量部
（グリセリン）４．０質量部
エモリエント剤（オレイルアルコール）０．１質量部
界面活性剤（ＰＯＥ（２０）ソルビタンモノラウリン酸エステル)
０．５質量部
（ＰＯＥ（１５）ラウリルアルコールエーテル)０．５質量部
アルコール（エタノール）１０．０質量部
香料、色剤、防腐剤、褪色防止剤、緩衝剤 夫々、適量
精製水 ７８．９質量部Moisturizer (1,3-butylene glycol glycerin) 6.0 parts by mass
(Glycerin) 4.0 parts by mass Emollient (oleyl alcohol) 0.1 parts by mass Surfactant (POE (20) sorbitan monolaurate)
0.5 parts by mass
(POE (15) lauryl alcohol ether) 0.5 parts by mass Alcohol (ethanol) 10.0 parts by mass Perfume, coloring agent, preservative, anti-fading agent, buffer, each appropriate amount 78.9 parts by mass of purified water
精製水に保湿剤、緩衝剤、褪色防止剤を室温にて溶解して水相を得る。エタノールに防腐剤、香料、エモリエント剤、可溶化剤（界面活性剤）を入れて溶解した後、上記の水相に加えて混合し、可溶化する。その後、色剤を加えて調色後、濾過し、充填を行なう。 A water phase is obtained by dissolving a humectant, a buffer, and an anti-fading agent in purified water at room temperature. A preservative, a fragrance, an emollient, and a solubilizer (surfactant) are added to ethanol and dissolved, and then added to the aqueous phase and mixed to solubilize. Thereafter, a colorant is added to adjust the color, followed by filtration and filling.
（乳液）
乳液の種類としては、例えば、Ｏ／Ｗ型、Ｗ／Ｏ型、多層エマルションが挙げられ、乳液の種類に応じて通常用いられる方法によって製造することができる。例えば保湿・柔軟乳液を構成する基材の一般的な処方例は、以下のとおりであり、有効成分としてＶＡＭ葉の抽出物を適宜添加すれば良い。ただし、本発明は下記処方例に限定する趣旨ではない。(Milky lotion)
Examples of the type of emulsion include O / W type, W / O type and multilayer emulsion, and can be produced by a method usually used depending on the type of emulsion. For example, a general formulation example of a base material constituting a moisturizing / softening emulsion is as follows, and an extract of VAM leaves may be added as an active ingredient as appropriate. However, the present invention is not intended to be limited to the following prescription examples.
油分（ステアリン酸）２．０質量部
（セチルアルコール）１．５質量部
（ワセリン）４．０質量部
（スクワラン）５．０質量部
（グリセロールトリ−２−エチルヘキサン酸エステル）
２．０質量部
界面活性剤（ソルビタンモノオレイン酸エステル) ２．０質量部
保湿剤（ジプロピレングリコール) ５．０質量部
（ＰＥＧ１５００) ３．０質量部
アルカリ（トリエタノールアミン） １．０質量部
防腐剤、香料 夫々、適量
精製水 ７４．５質量部Oil (stearic acid) 2.0 parts by weight (cetyl alcohol) 1.5 parts by weight (Vaseline) 4.0 parts by weight (Squalane) 5.0 parts by weight (glycerol tri-2-ethylhexanoate)
2.0 parts by mass Surfactant (sorbitan monooleate) 2.0 parts by mass Moisturizer (dipropylene glycol) 5.0 parts by mass
(PEG 1500) 3.0 parts by mass Alkali (triethanolamine) 1.0 part by weight Preservatives, perfumes, appropriate amounts Purified water 74.5 parts by weight
以下、実施例を挙げて本発明をより具体的に説明するが、本発明は下記実施例によって制限されず、前・後記の趣旨に適合し得る範囲で変更を加えて実施することも可能であり、それらはいずれも本発明の技術的範囲に包含される。 Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited by the following examples, and can be implemented with modifications within a range that can meet the purpose described above and below. They are all included in the technical scope of the present invention.
実施例１
本実施例では、以下のようにして調製したＶＡＭ葉の抽出物を用い、マウスを用いたアトピー性皮膚炎に対する予防効果を調べた。Example 1
In the present Example, the preventive effect with respect to atopic dermatitis using a mouse | mouth was investigated using the extract of the VAM leaf prepared as follows.
（抽出物の調製）
コンゴ産のＶＡＭの葉を日干しにより十分に乾燥し、乾燥した葉０．１ｋｇを乳鉢・乳棒を用いて約２ｍｍのサイズに粉砕した。得られた粉砕物１ｇを抽出溶媒（水５ｍＬまたはメタノール５ｍＬ）に浸漬し、液体窒素を用いて充分すり潰した。ろ過後、得られた抽出液４ｍＬに水１５ｍＬまたはメタノール１５ｍＬを加え、エバポレーターにより、温度：４５℃、圧力：５００ｈＰａの条件で蒸留した後、３７℃で２時間乾燥させることにより、ＶＡＭの水抽出物またはＶＡＭのメタノール抽出物を得た。以下の実験では、各抽出物０．５ｇを５ｍＬの蒸留水に溶解したものを実験に供した（濃度は２００ｇ／Ｌ）。(Preparation of extract)
VAM leaves from Congo were thoroughly dried by sun-drying, and 0.1 kg of dried leaves was pulverized to a size of about 2 mm using a mortar and pestle. 1 g of the obtained pulverized product was immersed in an extraction solvent (5 mL of water or 5 mL of methanol) and sufficiently ground using liquid nitrogen. After filtration, 15 mL of water or 15 mL of methanol was added to 4 mL of the resulting extract, and after distillation using an evaporator under conditions of temperature: 45 ° C. and pressure: 500 hPa, drying at 37 ° C. for 2 hours allowed water extraction of VAM. Or a methanol extract of VAM was obtained. In the following experiment, 0.5 g of each extract dissolved in 5 mL of distilled water was used for the experiment (concentration was 200 g / L).
（供試動物）
７週齢の雄性ＮＣ／Ｎｇａマウス１６匹を日本エスエルシーより購入し、飼料および飲料水を自由に摂取させて７日間馴化させたものを実験に用いた。マウス１６匹を、４匹ずつ以下の４群に分けた。試験の前日には、小動物用バリカンを用いてマウスの腹部を剃毛した（Ｄａｙ０）。
・第１群（本発明例投与群）：
ＶＡＭの水抽出物（以下、「ＷＡＴ−ＶＡＭ」と略記する）投与群
・第２群（本発明例投与群）：
ＶＡＭのメタノール抽出物（以下、「ＭＥＴ−ＶＡＭ」と略記する）投与群
・第３群（溶媒対照群）：メタノール（以下、「ＶＥＨ」と略記する）投与群
・第４群（溶媒対照群）：水（以下、「ＮＯＲＭ」と略記する）投与群(Test animal)
16 7-week-old male NC / Nga mice were purchased from Japan SLC, and were allowed to acclimatize for 7 days with free intake of feed and drinking water. Sixteen mice were divided into the following four groups of 4 mice. On the day before the test, the abdomen of the mouse was shaved using a small animal clipper (Day 0).
First group (invention group):
VAM water extract (hereinafter abbreviated as “WAT-VAM”) administration group • Second group (invention example administration group):
VAM methanol extract (hereinafter abbreviated as “MET-VAM”) administration group • Group 3 (solvent control group): Methanol (hereinafter abbreviated as “VEH”) administration group • Group 4 (solvent control group) ): Water (hereinafter abbreviated as “NORM”) administration group
（試験方法）
第１群および第２群（いずれも本発明例投与群）について、以下の処置を行なった。(Test method)
The following treatments were performed for the first group and the second group (both of the groups administered with the present invention).
まず、剃毛した各群のマウスの腹部に、感作源として５％塩化ピクリルのアセトン溶液を５００μＬ塗布して感作を行なった（Ｄａｙ１）。感作後７日目（Ｄａｙ８）に、上記の各抽出物（「ＷＡＴ−ＶＡＭ」または「ＭＥＴ−ＶＡＭ」）７ｍｇ／ｍＬをマウスの右耳に５０μＬ塗布（予防処置）し、その３０分後に、０．５％塩化ピクリルのアセトン・オリーブオイル溶液を５０μＬ、マウスの両耳に塗布して追加感作を行なった（Ｄａｙ８）。上記Ｄａｙ８と同様の操作を、Ｄａｙ１４、Ｄａｙ１６、Ｄａｙ１８、およびＤａｙ２０に行い、アトピー性皮膚炎を惹起（チャレンジ）させた。
First, 500 μL of an acetone solution of 5% picryl chloride was applied to the abdomen of each group of shaved mice as a sensitizing source (Day 1). On day 7 after sensitization (Day 8), 50 μL of each extract (“WAT-VAM” or “MET-VAM”) 7 mg / mL was applied to the right ear of the mouse (preventive treatment), and 30 minutes later. Additional sensitization was performed by applying 50 μL of 0.5% picryl chloride in acetone / olive oil to both ears of mice (Day 8). The same operation as
比較のため、第３群（「ＶＥＨ」投与群）については、上記の抽出物を塗布する代わりにメタノールを塗布したこと以外は、前述した第１群と同様にして感作および惹起を行なった。 For comparison, the third group ("VEH" administration group) was sensitized and elicited in the same manner as the first group described above except that methanol was applied instead of the extract. .
一方、第４群（「ＮＯＲＭ」投与群）については、５％塩化ピクリルの感作を行なわないこと、および上記の抽出物を塗布する代わりに水を塗布したこと以外は、前述した第１群と同様にして処置した。 On the other hand, for the fourth group ("NORM" administration group), the first group described above, except that 5% picryl chloride was not sensitized and water was applied instead of the extract. Treated as described above.
（評価）
（１）引っ掻き行動の経時的変化
Ｄａｙ８、Ｄａｙ１４、Ｄａｙ２０のそれぞれにおいて、各群のマウスについて、３０秒以内に観察される引っ掻き行動の回数を測定し、各群（４匹）の平均値および標準偏差を算出した。この回数が少ない程、抗掻痒効果に優れることを示している。これらの結果を図１に示す。図１には、各実験群について、左から順にＤａｙ８、Ｄａｙ１４、Ｄａｙ２０の結果を示している。(Evaluation)
(1) Change with time of scratching behavior In each of Day8, Day14, and Day20, the number of scratching behaviors observed within 30 seconds was measured for each group of mice, and the average value and standard of each group (4 animals) Deviation was calculated. It shows that it is excellent in the anti-itching effect, so that this frequency | count is small. These results are shown in FIG. FIG. 1 shows the results of
（２）耳介厚さ（腫脹）の経時的変化
Ｄａｙ８、Ｄａｙ１４、Ｄａｙ２０のそれぞれにおいて、各群のマウスの右耳の厚さ（μｍ）をデジタルノギスを用いて測定し、Ｄａｙ０のマウスの右耳の厚さとの差（μｍ）を算出し、各群（４匹）の平均値を算出した。厚さの差が少ない程、耳腫脹抑制効果に優れることを示している。これらの結果を図２に示す。図２には、各実験群について、左から順にＤａｙ８、Ｄａｙ１４、Ｄａｙ２０の結果を示している。(2) Time course change of pinna thickness (swelling) In each of
（３）臨床症状の経時的変化
Ｄａｙ８、Ｄａｙ１４、Ｄａｙ２０のそれぞれにおいて、各群のマウスの背部に生じた炎症の程度を肉眼で観察し、スコアリングした。詳細には、（ａ）表皮剥脱／腐食の程度、（ｂ）紅班／出血の程度、（ｃ）purpuras（血管より漏れ出た血液により紫色の斑点状の内出血）および毛細血管拡張症の程度を肉眼で観察し、下記基準でスコアリングして各群（４匹）の平均値を算出した。スコアリング値が低い程、炎症抑制効果に優れることを示している。(3) Changes in clinical symptoms over time In each of
（ａ）表皮剥脱／腐食の評価
０以上、１以下：ほとんど変化なし
１超、２以下 ：軽度の症状
２超、３以下 ：高度の症状(A) Evaluation of skin exfoliation /
（ｂ）紅班／出血の評価
０以上、１０以下：ほとんど変化なし
１０超、２０以下：軽度の症状
２０超、３０以下：高度の症状(B) Evaluation of erythema / bleeding 0 or more and 10 or less: Almost no change More than 10 or 20 or less: Mild symptoms More than 20 or 30 or less: High symptoms
（ｃ）purpurasおよび毛細血管拡張症の評価
０以上、１以下：ほとんど変化なし
１超、２以下 ：軽度の症状
２超、３以下 ：高度の症状(C) Evaluation of purpuras and
これらの結果をそれぞれ、図３Ａ〜図３Ｃに示す。 These results are shown in FIGS. 3A to 3C, respectively.
（４）炎症細胞の浸潤
Ｄａｙ１４に、第１群〜第３群のそれぞれにつき１例ずつ無作為に抽出したマウス左耳の一部を生検し、ヘマトキシリン・エオジン(ＨＥ)染色による炎症細胞の同定（好中球、好酸球）を行なって病理組織標本を作製した。参考のため、上記第１群において、本発明抽出物を投与する前（Ｄａｙ２１）のマウス（アトピー性皮膚炎マウス）左耳の一部を生検し、上記と同様にして病理組織標本を作製した。図４Ａ〜図４Ｃに、アトピー性皮膚炎マウス（図４Ａ）、第１群の「ＶＡＭ−ＷＡＴ」投与群（図４Ｂ）、第２群の「ＶＡＭ−ＭＥＴ」投与群（図４Ｃ）におけるマウスの写真（上段）、病理組織標本の１０倍拡大写真（中段）、４０倍拡大写真（下段）の結果をそれぞれ示す。(4) Infiltration of inflammatory cells On Day 14, a part of the left ear of the mouse randomly extracted from each of the first to third groups was biopsied, and inflammatory cells were stained by hematoxylin and eosin (HE). Identification (neutrophils, eosinophils) was performed to prepare pathological tissue specimens. For reference, in the first group, a part of the left ear of a mouse (atopic dermatitis mouse) before administration of the extract of the present invention (Day 21) is biopsied, and a histopathological specimen is prepared in the same manner as described above. did. 4A to 4C, mice in an atopic dermatitis mouse (FIG. 4A), a first group “VAM-WAT” administration group (FIG. 4B), and a second group “VAM-MET” administration group (FIG. 4C). The results of a photograph (upper), a 10-fold magnified photograph (middle), and a 40-fold magnified photograph (lower) of the pathological tissue specimen are shown.
（５）血清中ＩｇＥの測定
Ｄａｙ１４に、第１群〜第４群のそれぞれにおいて、各群のマウスの血清中ＩｇＥを測定した。詳細には、キットに添付されている、段階希釈したＩｇＥ標準物質のシグナルから作製した検量線とサンプルのシグナルを比較して血清中ＩｇＥ濃度を決定し、各群（４匹）の平均値および標準偏差を算出した。これらの結果を図５に示す。(5) Measurement of serum IgE On day 14, the serum IgE of the mice of each group was measured in each of the first group to the fourth group. Specifically, a standard curve prepared from the serially diluted IgE standard signal attached to the kit was compared with the sample signal to determine the serum IgE concentration, and the average value of each group (4 animals) and Standard deviation was calculated. These results are shown in FIG.
図１〜図５より以下のように考察することができる。 1 to 5 can be considered as follows.
まず、抗掻痒作用について考察する。図１より、本発明抽出物を含まずメタノールのみを投与した「ＶＥＨ」（溶媒対照群）では引っ掻き回数が多く、感作回数が進むにつれ（Ｄａｙ８→Ｄａｙ１４→Ｄａｙ２０）、その回数が顕著に増加したのに対し、本発明に係るＶＡＭの水抽出物を投与した「ＷＡＴ−ＶＡＭ」（本発明例）およびＶＡＭのメタノール抽出物を投与した「ＭＥＴ−ＶＡＭ」（本発明例）は、引っ掻き回数の顕著な抑制効果が認められ、水投与群（「ＮＯＲＭ」）とほぼ同程度にまで抑えることができた。本発明例のなかでも特に、ＶＡＭのメタノール抽出物を投与した「ＭＥＴ−ＶＡＭ」では非常に著しい抑制効果が認められ、感作回数が増えても引っ掻き回数の上昇は殆ど見られなかった。よって、本発明抽出物は、極めて優れた抗掻痒作用を有していることが確認された。
First, the antipruritic action is considered. From FIG. 1, “VEH” (solvent control group) administered with methanol alone without the extract of the present invention has a high number of scratches, and the number of sensitization increases (
なお、図１には示していないが、本発明抽出物ではなく市販のステロイド剤（和光純薬製ハイドロコルチゾン）を用いて同様の実験を行なった場合は、メタノールのみを投与した「ＶＥＨ」（溶媒対照群）の結果と殆ど変わらなかったことを確認している。 Although not shown in FIG. 1, when a similar experiment was performed using a commercially available steroid (hydrocortisone manufactured by Wako Pure Chemical Industries) instead of the extract of the present invention, “VEH” administered with methanol alone ( It was confirmed that there was almost no difference from the result of the solvent control group.
次に図２〜図５に基づき、抗炎症作用について考察する。抗炎症作用についても前述した抗掻痒作用と同様の傾向が見られ、本発明抽出物を投与した「ＷＡＴ−ＶＡＭ」および「ＭＥＴ−ＶＡＭ」は、溶媒投与群の「ＶＥＨ」に比べ、耳介腫脹抑制効果（図２）、臨床症状の緩和（図３）、炎症細胞（好酸球および好中球）の減少（図４）、血清中ＩｇＥの減少（図５）が見られ、特にＶＡＭのメタノール抽出物を投与した「ＭＥＴ−ＶＡＭ」では非常に著しい抗炎症効果が確認された。 Next, the anti-inflammatory effect will be discussed based on FIGS. Similar anti-pruritic activity was observed with respect to anti-inflammatory activity, and “WAT-VAM” and “MET-VAM” to which the extract of the present invention was administered were compared to “VEH” in the solvent administration group, compared to “VEH” in the solvent administration group. Suppression effect (Fig. 2), alleviation of clinical symptoms (Fig. 3), reduction of inflammatory cells (eosinophils and neutrophils) (Fig. 4), reduction of serum IgE (Fig. 5), especially VAM In the “MET-VAM” administered with the methanol extract, a very remarkable anti-inflammatory effect was confirmed.
このうち図４を参照すると、アトピー性皮膚炎マウスでは症状が進行して皮膚のバリア層が破壊し（図４Ａの中段の写真をご参照）、好酸球および好中球の浸潤が多く見られた（図４Ａの下段の写真をご参照）のに対し、本発明抽出物を投与したものは図４Ｂおよび図４Ｃに示すように、バリア層の破壊も殆ど見られず（図４Ｂおよび図４Ｃの中段の写真をご参照）、好酸球および好中球の数も減少した（図４Ｂおよび図４Ｃの下段の写真をご参照）。よって、本発明抽出物は、極めて優れた抗炎症作用を有していることが確認された。 Among these, referring to FIG. 4, in atopic dermatitis mice, the symptoms progressed and the skin barrier layer was destroyed (see the middle photo in FIG. 4A), and infiltration of eosinophils and neutrophils was often observed. As shown in FIGS. 4B and 4C, the barrier layer was hardly destroyed as shown in FIGS. 4B and 4C (see FIGS. 4B and 4C). The number of eosinophils and neutrophils was also reduced (see the bottom pictures in FIGS. 4B and 4C). Therefore, it was confirmed that the extract of the present invention has an extremely excellent anti-inflammatory action.
なお、図２〜図５には示していないが、本発明抽出物ではなく市販のステロイド剤（和光純薬製ハイドロコルチゾン）を用いて同様の実験を行なった場合は、メタノールのみを投与した「ＶＥＨ」（溶媒対照群）の結果と殆ど変わらなかったことを確認している。 Although not shown in FIGS. 2 to 5, when a similar experiment was performed using a commercially available steroid (hydrocortisone manufactured by Wako Pure Chemical Industries) instead of the extract of the present invention, only methanol was administered. It was confirmed that there was almost no difference from the result of “VEH” (solvent control group).
以上の実験結果より、本発明抽出物は、アトピー性皮膚炎の予防剤として極めて有用であることが確認された。 From the above experimental results, it was confirmed that the extract of the present invention is extremely useful as a preventive agent for atopic dermatitis.
実施例２
本実施例では、実施例１と同様にして調製したＶＡＭ葉の抽出物を用い、マウスを用いたアトピー性皮膚炎に対する治療効果を調べた。Example 2
In this example, the therapeutic effect on atopic dermatitis using mice was examined using the VAM leaf extract prepared in the same manner as in Example 1.
（供試動物）
７週齢の雄性ＮＣ／Ｎｇａマウス３０匹を日本エスエルシーより購入し、飼料および飲料水を自由に摂取させて７日間馴化させたものを実験に用いた。マウス３０匹を、６匹ずつ以下の５群に分けた。試験の前日には、小動物用バリカンを用いてマウスの腹部を剃毛した（Ｄａｙ０）。
・第１群（本発明例投与群）：ＶＡＭの水抽出物（「ＷＡＴ−ＶＡＭ」）投与群
・第２群（本発明例投与群）：ＶＡＭのメタノール抽出物（「ＭＥＴ−ＶＡＭ」）投与群
・第３群（溶媒対照群）：メタノール（「ＶＥＨ」）投与群
・第４群（溶媒対照群）：水（「ＮＯＲＭ」）投与群
・第５群（比較群）：ステロイド（「ＨＣＴ」）投与群(Test animal)
Thirty male male NC / Nga mice aged 7 weeks were purchased from Japan SLC, and were allowed to freely feed and drink for 7 days and used for the experiment. Thirty mice were divided into the following 5 groups of 6 mice each. On the day before the test, the abdomen of the mouse was shaved using a small animal clipper (Day 0).
-Group 1 (Invention Example Administration Group): VAM water extract ("WAT-VAM") administration group-Group 2 (Invention Example Administration Group): VAM methanol extract ("MET-VAM") Administration group • Group 3 (solvent control group): Methanol (“VEH”) administration group • Group 4 (solvent control group): Water (“NORM”) administration group • Group 5 (comparison group): Steroid (“ HCT ") administration group
（試験方法）
第１群および第２群（いずれも本発明例投与群）について、以下の処置を行なった。(Test method)
The following treatments were performed for the first group and the second group (both of the groups administered with the present invention).
まず、剃毛した各群のマウスの腹部に、感作源として５％塩化ピクリルのアセトン溶液を５００μＬ塗布して感作を行なった（Ｄａｙ１）。感作後７日目（Ｄａｙ８）、９日目（Ｄａｙ１０）、１１日目（Ｄａｙ１２）、１３日目（Ｄａｙ１４）に、０．５％塩化ピクリルのアセトン・オリーブオイル溶液を５０μＬ、マウスの両耳に塗布してアトピー性皮膚炎を惹起（チャレンジ）させた。その後、Ｄａｙ２１、Ｄａｙ２３、Ｄａｙ２５、Ｄａｙ２７、Ｄａｙ２９にそれぞれ、上記の各抽出物（「ＷＡＴ−ＶＡＭ」または「ＭＥＴ−ＶＡＭ」）７ｍｇ／ｍＬをマウスの右耳に５０μＬ塗布（治療処置）した。
First, 500 μL of an acetone solution of 5% picryl chloride was applied to the abdomen of each group of shaved mice as a sensitizing source (Day 1). On the 7th day (Day8), 9th day (Day10), 11th day (Day12), 13th day (Day14) after sensitization, 50 μL of acetone / olive oil solution of 0.5% picryl chloride was added to both mice. It was applied to the ear to induce (challenge) atopic dermatitis. Thereafter, 7 mg / mL of each of the above extracts (“WAT-VAM” or “MET-VAM”) was applied to
比較のため、第３群（「ＶＥＨ」投与群）については、上記の抽出物を塗布する代わりにメタノールを塗布したこと以外は、前述した第１群と同様にして感作および惹起を行なった。 For comparison, the third group ("VEH" administration group) was sensitized and elicited in the same manner as the first group described above except that methanol was applied instead of the extract. .
一方、第４群（「ＮＯＲＭ」投与群）については、５％塩化ピクリルの感作を行なわないこと、および上記の抽出物を塗布する代わりに水を塗布したこと以外は、前述した第１群と同様にして処置した。 On the other hand, for the fourth group ("NORM" administration group), the first group described above, except that 5% picryl chloride was not sensitized and water was applied instead of the extract. Treated as described above.
更にステロイド剤との対比を行なうため、第５群（「ＨＣＴ」投与群）については、上記の抽出物を塗布する代わりに１０ｍｇ／ｍＬのハイドロコルチゾンを塗布したこと以外は、前述した第１群と同様にして処置した。 Further, for comparison with the steroid agent, for the fifth group ("HCT" administration group), the first group described above was applied except that 10 mg / mL hydrocortisone was applied instead of applying the above extract. Treated as described above.
（評価）
（１）耳介厚さ（腫脹）の経時的変化
Ｄａｙ２１、Ｄａｙ２３、Ｄａｙ２５、Ｄａｙ２７、Ｄａｙ２９における各群の耳介厚さ（Ｄａｙ０との差）の平均値を、前述した実施例１の（２）と同様にして算出した。これらの結果を図６に示す。図６には、各実験群について、左から順にＤａｙ２１、Ｄａｙ２３、Ｄａｙ２５、Ｄａｙ２７、Ｄａｙ２９の結果を示している。(Evaluation)
(1) Change with time of auricle thickness (swelling) The average value of the auricle thickness (difference from Day 0) of each group in
（２）耳介重量の変化
Ｄａｙ３０の解剖時にマウスから摘出した耳の重量を、デジタル天秤にて秤量した（０．１μｇまで）。実験群ごとに重量の平均値±標準誤差を算出し、群間の重量有意差を計算した。これらの結果を図７に示す。(2) Change in pinna weight The weight of the ear removed from the mouse during Day30 dissection was weighed with a digital balance (up to 0.1 μg). The mean value ± standard error of the weight was calculated for each experimental group, and the weight significant difference between the groups was calculated. These results are shown in FIG.
（３）臨床症状の経時的変化
Ｄａｙ２１、Ｄａｙ２３、Ｄａｙ２５、Ｄａｙ２７、Ｄａｙ２９のそれぞれにおいて、各群のマウスの背部に生じた扁平皮膚領域の分布を肉眼で観察し、下記基準でスコアリングして各群（６匹）の平均値を算出した。これらの結果を図８に示す。
０以上、１以下：ほとんど変化なし
１超、２以下 ：軽度の症状
２超、３以下 ：高度の症状(3) Changes in clinical symptoms over time In each of
0 or more, 1 or less: Almost no
（４）炎症細胞の浸潤
Ｄａｙ３０に、第１群、第２群（以上、本発明例）、第５群（ステロイド投与群）のそれぞれにつき１例ずつ無作為に抽出したマウス左耳の一部（７ｍｍ）を生検し、ヘマトキシリン・エオジン(ＨＥ)染色による炎症細胞の同定（好中球、好酸球）を行なって病理組織標本を作製した。参考のため、上記第１群において、本発明抽出物を投与する前（Ｄａｙ３０）のマウス（アトピー性皮膚炎マウス）左耳の一部を生検し、上記と同様にして病理組織標本を作製した。図９Ａ〜図９Ｄに、アトピー性皮膚炎マウス（図９Ａ）、第１群の「ＶＡＭ−ＷＡＴ」投与群（図９Ｂ）、第２群の「ＶＡＭ−ＭＥＴ」投与群（図９Ｃ）、第５群の「ＨＣＴ」投与群（図９Ｄ）におけるマウスの写真（上段）と病理組織標本の２０倍拡大写真（下段）の結果をそれぞれ示す。(4) Inflammatory cell infiltration A part of the left ear of the mouse randomly extracted in Day30, one for each of the first group, the second group (the present invention example), and the fifth group (steroid administration group) A biopsy of (7 mm) was performed, and identification of inflammatory cells (neutrophils, eosinophils) by hematoxylin and eosin (HE) staining was performed to prepare pathological tissue specimens. For reference, in the first group, a part of the left ear of a mouse (atopic dermatitis mouse) before administration of the extract of the present invention (Day 30) is biopsied, and a histopathological specimen is prepared in the same manner as described above. did. 9A to 9D, an atopic dermatitis mouse (FIG. 9A), a first group “VAM-WAT” administration group (FIG. 9B), a second group “VAM-MET” administration group (FIG. 9C), The results of a photograph of the mouse (upper row) and a 20-fold enlarged photograph (lower row) of the pathological tissue specimen are shown in each of the five “HCT” administration groups (FIG. 9D).
図６〜図９より以下のように考察することができる。 6 to 9 can be considered as follows.
図６より、本発明抽出物を投与した「ＷＡＴ−ＶＡＭ」および「ＭＥＴ−ＶＡＭ」は、溶媒投与群の「ＶＥＨ」およびステロイド投与群の「ＨＣＴ」に比べ、耳介腫脹抑制効果が有意差をもって顕著に見られ（ｐ＜０．０５またはｐ＜０．０１）、特にＶＡＭのメタノール抽出物を投与した「ＭＥＴ−ＶＡＭ」では非常に著しい抑制効果が確認された。図６とほぼ同様の傾向は図７でも見られ、本発明抽出物を投与した群はいずれも、溶媒投与群およびステロイド投与群に比べ、有意差はないが耳重量の減少が大きく見られた。このことは、本発明抽出物を投与したマウスには、浮腫や炎症の症状が減少していることを意味する。 From FIG. 6, “WAT-VAM” and “MET-VAM” administered with the extract of the present invention have a significant difference in ear swelling suppression effect compared to “VEH” in the solvent administration group and “HCT” in the steroid administration group. In particular, “MET-VAM” to which a methanol extract of VAM was administered was confirmed to have a very remarkable inhibitory effect (p <0.05 or p <0.01). A tendency similar to that in FIG. 6 was also observed in FIG. 7. In the group to which the extract of the present invention was administered, there was no significant difference compared to the solvent administration group and the steroid administration group, but the ear weight was greatly reduced. . This means that the edema and inflammation symptoms are reduced in the mice administered with the extract of the present invention.
また図８より、本発明抽出物を用いれば、溶媒投与群に比べて炎症症状を有意に改善でき、ステロイド投与群とほぼ同程度の改善効果が確認された。 Further, from FIG. 8, when the extract of the present invention was used, the inflammatory symptoms could be significantly improved as compared with the solvent administration group, and an improvement effect almost the same as that of the steroid administration group was confirmed.
更に図９より、アトピー性皮膚炎マウスでは症状が進行して皮膚のバリア層が破壊し、好酸球および好中球の著しい浸潤が見られた（図９の下段の写真をご参照）のに対し、本発明抽出物を投与すると図９Ｂおよび図９Ｃに示すように、バリア層の破壊も殆ど見られず、好酸球および好中球の数も減少した。本発明抽出物による改善作用は、ステロイド投与群（図９Ｄ）とほぼ同程度であった。 Furthermore, from FIG. 9, the symptoms progressed in the atopic dermatitis mouse, the skin barrier layer was destroyed, and significant infiltration of eosinophils and neutrophils was observed (see the lower photograph in FIG. 9). On the other hand, when the extract of the present invention was administered, as shown in FIGS. 9B and 9C, almost no destruction of the barrier layer was observed, and the number of eosinophils and neutrophils also decreased. The improvement effect of the extract of the present invention was almost the same as that of the steroid administration group (FIG. 9D).
以上の実験結果より、本発明抽出物は、極めて優れた抗炎症作用を有していることが確認された。 From the above experimental results, it was confirmed that the extract of the present invention has an extremely excellent anti-inflammatory action.
なお、上記図には示していないが、本発明抽出物を投与すると、顕著な抗掻痒効果が見られたことを実験により確認している。 In addition, although not shown in the said figure, it has confirmed by experiment that the remarkable anti-pruritic effect was seen when the extract of this invention was administered.
以上の実験結果より、本発明抽出物は、アトピー性皮膚炎の治療剤としても極めて有用であることが確認された。 From the above experimental results, it was confirmed that the extract of the present invention is extremely useful as a therapeutic agent for atopic dermatitis.
Claims (5)
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| PCT/JP2011/061910 WO2012042970A1 (en) | 2010-09-28 | 2011-05-24 | Prophylactic or therapeutic agent for atopic dermatitis, and preparation for external application |
| JP2012536248A JP5765744B2 (en) | 2010-09-28 | 2011-05-24 | Preventive or therapeutic agent for atopic dermatitis, and external preparation |
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| JP2015057377A (en) * | 2013-08-14 | 2015-03-26 | 国立大学法人高知大学 | Atopic dermatitis depressant |
| CN106038650A (en) * | 2016-08-02 | 2016-10-26 | 河北林益堂药业有限公司 | Anti-inflammatory application of Vernonia amygdalina Del. ethanol extract and preparation method thereof as well as preparation |
| CN108419864A (en) * | 2018-05-30 | 2018-08-21 | 大连民族大学 | A kind of preparation method of South Africa leaf tea beverage |
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| WO2005105126A1 (en) * | 2004-04-30 | 2005-11-10 | National University Corporation NARA Institute of Science and Technology | Active oxygen eliminator and moisturizer containing wild watermelon extract |
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