JP3702393B2 - Topical preparation - Google Patents
Topical preparation Download PDFInfo
- Publication number
- JP3702393B2 JP3702393B2 JP2004099024A JP2004099024A JP3702393B2 JP 3702393 B2 JP3702393 B2 JP 3702393B2 JP 2004099024 A JP2004099024 A JP 2004099024A JP 2004099024 A JP2004099024 A JP 2004099024A JP 3702393 B2 JP3702393 B2 JP 3702393B2
- Authority
- JP
- Japan
- Prior art keywords
- external
- skin
- blood circulation
- vanillyl nonanoate
- lipolysis
- 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.)
- Expired - Lifetime
Links
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Landscapes
- Cosmetics (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
本発明は、外用の血行促進剤及び外用の脂肪分解促進剤に関する。より詳細には、本発明は皮膚刺激の少ない外用の血行促進剤及び外用の脂肪分解促進剤に関する。さらには外用組成物に関する。 The present invention relates to an external blood circulation promoter and an external lipolysis promoter. More specifically, the present invention relates to an external blood circulation promoter and an external lipolysis promoter with less skin irritation. Furthermore, it is related with the composition for external use.
従来より、カプサイシン、ジンゲロール、及びショウガロール等の化合物にはその末梢血管拡張作用に基づいて優れた血行促進作用があることが知られており、これらの化合物並びに当該化合物を含む、例えば唐辛子末、唐辛子チンキ、唐辛子エキス、及び生姜エキス等の植物の加工物は、血行促進剤として広く応用されている（例えば、特許文献１等参照のこと）。 Conventionally, it is known that compounds such as capsaicin, gingerol, and gingerol have an excellent blood circulation promoting action based on their peripheral vasodilatory action, and these compounds and the compounds containing such compounds, for example, pepper powder, Processed plants such as pepper tincture, pepper extract, and ginger extract are widely applied as blood circulation promoters (see, for example, Patent Document 1).
しかしながら、これらカプサイシンなどの化合物は強い皮膚刺激性を有しており、この刺激性を低減するために使用量を減少すると血行促進効果が低下するという問題を有している。このため、従来より皮膚刺激性を低減しながらも優れた血行促進作用を有する薬剤の開発が求められており、例えば、特定のフェニルシクロアルキルエーテル誘導体、メトキシフェニルアルキルエーテル誘導体、並びにメトキシ基置換フェニルアルコキシアルキルエーテル誘導体がこうした目的を達成し得る血行促進剤として提案されている（例えば、特許文献２〜４等参照のこと）。
本発明の目的は、良好な血行促進作用を有しながらも皮膚への刺激性が少ない新規の外用血行促進剤、及び良好な脂肪分解促進作用を有しながらも皮膚への刺激性が少ない新規の外用脂肪分解促進剤を提供することである。さらに、本発明は皮膚刺激性が少なく良好な血行促進作用及び脂肪分解促進作用を有する外用組成物を提供することを目的とする。 An object of the present invention is to provide a novel topical blood circulation promoter that has a good blood circulation promoting action but has little skin irritation, and a novel skin circulation stimulating novel that has a good lipolysis promoting action. It is to provide a lipolysis promoter for external use. Furthermore, an object of the present invention is to provide an external composition having a good blood circulation promoting action and a lipolysis promoting action with little skin irritation.
本発明者らは、上記目的を達成すべく、日夜鋭意研究を重ねていたところ、カプサイシノイド様化合物であるノナン酸バニリルが外用で優れた血行促進効果及び優れた脂肪分解促進効果を発揮し、しかも皮膚に対する刺激性が少ないことを見いだした。そして当該ノナン酸バニリルは、その免疫賦活作用、エネルギー代謝活性作用、肥満抑制作用、体脂肪蓄積抑制作用、アドレナリン分泌促進作用、並びに血中グルコース増加作用等に基づいて、従来より食品や経口薬剤等の経口摂取される用途が提案されているものの（例えば、特許文献５〜７等参照のこと）、皮膚に対する低刺激性並びに外用剤としての用途は知られていないことを確認し、本発明を完成するに至った。 In order to achieve the above object, the present inventors have conducted extensive research on a day and night, and the capsaicinoid-like compound vanillyl nonanoate exhibits an excellent blood circulation promoting effect and an excellent lipolysis promoting effect for external use, Found less irritating to the skin. The vanillyl nonanoate has been conventionally used for foods, oral drugs, etc. based on its immunostimulatory effect, energy metabolic activity effect, obesity inhibiting effect, body fat accumulation inhibiting effect, adrenaline secretion promoting effect, blood glucose increasing effect, etc. Although it has been proposed to be orally ingested (see, for example, Patent Documents 5 to 7), it has been confirmed that its hypoallergenicity to skin and its use as an external preparation are not known. It came to be completed.
すなわち、本発明は下記に掲げるものである：
項１．ノナン酸バニリルを有効成分とする外用血行促進剤。
項２．ノナン酸バニリルを有効成分とする外用脂肪分解促進剤。
項３．項1記載の外用血行促進剤を含有する外用組成物。
項４．項2記載の外用脂肪分解促進剤を含有する外用組成物。
項５．皮膚化粧料、頭皮化粧料、入浴剤、医薬外用剤または点眼剤である項３又は項４に記載する外用組成物。
That is, the present invention is as follows:
Item 1. An external blood circulation promoter containing vanillyl nonanoate as an active ingredient.
Item 2. A topical lipolysis promoter comprising vanillyl nonanoate as an active ingredient.
Item 3. An external composition containing the external blood circulation promoter according to Item 1.
Item 4. Item 3. A composition for external use comprising the topical lipolysis promoter according to Item 2.
Item 5. Item 5. The topical composition according to Item 3 or 4, which is a skin cosmetic, a scalp cosmetic, a bath agent, a pharmaceutical external preparation, or an eye drop.
（１）外用血行促進剤
本発明の外用血行促進剤は、下式：
(1) External blood circulation promoter The external blood circulation promoter of the present invention has the following formula:
で示されるノナン酸バニリルを有効成分として含有することを特徴とする。 It contains the vanillyl nonanoate shown by this as an active ingredient.
当該ノナン酸バニリルは公知の化合物であり、常法に従って調製することができる。具体的には、例えばノナン酸クロライドとバニリルアルコール（4-ヒドロキシ-3-メトキシベンジルアルコール）を出発原料として用いて、慣用の方法に従ってエステル化反応させることによって容易に調製することができる。具体的には、後述する参考例に記載する方法に従って製造することができる。但し、かかる方法に制限されるものではない。 The vanillyl nonanoate is a known compound and can be prepared according to a conventional method. Specifically, for example, nonanoic acid chloride and vanillyl alcohol (4-hydroxy-3-methoxybenzyl alcohol) are used as starting materials, and can be easily prepared by an esterification reaction according to a conventional method. Specifically, it can be produced according to the method described in Reference Examples described later. However, it is not limited to such a method.
斯くして得られるノナン酸バニリルは、皮膚や粘膜等に経皮適用ないし経粘膜適用した場合に良好な血行促進効果を発揮し、しかも皮膚等に対して刺激性が抑制されて、刺激性を感じないか若しくは低減されてなるという外用血行促進剤として適した特性を備えている。 Vanillyl nonanoate thus obtained exerts a good blood circulation promoting effect when applied transdermally or transmucosally to the skin, mucous membranes, etc., and the irritation is suppressed to the skin etc. It has characteristics suitable as an external blood circulation promoter that is not felt or reduced.
このようなノナン酸バニリルは、外用血行促進剤の有効成分として有効に利用することができる。なお、本発明の外用血行促進剤はノナン酸バニリルを有効成分とするものであればよく、本発明の効果を損なわない限り、他の成分を含有することを妨げるものではない。 Such vanillyl nonanoate can be effectively used as an active ingredient of an external blood circulation promoter. In addition, the external blood circulation promoter of this invention should just contain vanillyl nonanoate as an active ingredient, and unless the effect of this invention is impaired, it does not prevent containing another component.
例えばかかる他の成分としては、本発明の有効成分と同様に皮膚への刺激性がなく血行促進効果を有する各種の植物エキスを挙げることができる（特開平９−２６８１１８号公報、特開平１０−２２６６２１号公報等参照）。具体的な植物エキスとしては、ユズ、シナノキ、ボダイジュ、イチョウ、マロニエ、ブッチャーブルーム等を挙げることができる。また、添加剤や希釈剤として、多価アルコール等のアルコール類、油性成分、無機粉体、界面活性剤、ｐＨ調整剤、防腐剤、香料、色素などを例示することができる。 Examples of such other components include various plant extracts that have no blood irritation effect and have a blood circulation promoting effect as in the case of the active ingredient of the present invention (JP 9-268118 A, JP 10-10 A). 226621). Specific examples of plant extracts include citrus, linden, bodaige, ginkgo, maroonier, butcher bloom, and the like. Examples of additives and diluents include alcohols such as polyhydric alcohols, oil components, inorganic powders, surfactants, pH adjusters, preservatives, fragrances, and pigments.
本発明の外用血行促進剤に含まれるノナン酸バニリルの割合は、本発明の効果を奏することを限度として特に制限されないが、例えば０.１重量％以上、好ましくは１重量％以上を例示することができる。なお、本発明の外用血行促進剤はノナン酸バニリルだけからなるものであってもよく、ゆえにノナン酸バニリルの割合の上限は１００重量％である。 The ratio of vanillyl nonanoate contained in the external blood circulation promoter of the present invention is not particularly limited as long as the effect of the present invention is exhibited, but for example, 0.1% by weight or more, preferably 1% by weight or more is exemplified. Can do. The external blood circulation promoter of the present invention may be composed only of vanillyl nonanoate, and therefore the upper limit of the proportion of vanillyl nonanoate is 100% by weight.
（２）外用脂肪分解促進剤
上記ノナン酸バニリルはまた、皮膚や粘膜等に経皮適用ないし経粘膜適用した場合に良好な脂肪分解促進効果を発揮し、しかも皮膚等に対して刺激性が抑制されて、刺激性を感じないか若しくは微弱な外用脂肪分解促進剤として適した特性を備えている。
(2) Lipolysis accelerator for external use The above vanillyl nonanoate also exerts a good lipolysis promoting effect when applied transdermally or transmucosally to the skin, mucous membrane, etc., and suppresses irritation to the skin, etc. Thus, it has characteristics suitable as an external lipolysis promoter that does not feel irritation or is weak.
本発明の脂肪分解促進剤は、ノナン酸バニリルを有効成分とするものであればよく、本発明の効果を損なわない限り、他の成分を含有することができる。例えば、かかる成分としては、ノナン酸バニリルと同様に脂肪分解促進作用を有する又は増強するものを使用してもよい。このような成分として、キサンチン誘導体、βアドレナリン作用興奮薬、α2アドレナリン作用抑制薬等を挙げることができる。また、添加剤や希釈剤としては、（１）で述べたものと同様のものを使用することができる。 The lipolysis promoter of the present invention may be any one that contains vanillyl nonanoate as an active ingredient, and can contain other components as long as the effects of the present invention are not impaired. For example, as such a component, a component that has or enhances lipolysis may be used in the same manner as vanillyl nonanoate. Examples of such components include xanthine derivatives, β-adrenergic stimulants, α 2 adrenergic inhibitors and the like. Moreover, as an additive and a diluent, the thing similar to what was described in (1) can be used.
ノナン酸バニリルを本発明の脂肪分解促進剤に使用する場合には、脂肪分解促進剤中に含まれるノナン酸バニリルの割合は、脂肪分解促進効果を奏することを限度として特に制限されないが、例えば０.１重量％以上、好ましくは１重量％以上を例示することができる。なお、本発明の外用脂肪分解促進剤はノナン酸バニリルだけからなるものであってもよく、ゆえにノナン酸バニリルの割合の上限は１００重量％である。 When vanillyl nonanoate is used in the lipolysis accelerator of the present invention, the ratio of vanillyl nonanoate contained in the lipolysis accelerator is not particularly limited as long as it exhibits the effect of promoting lipolysis. An example is 0.1% by weight or more, preferably 1% by weight or more. The external lipolysis accelerator of the present invention may be composed only of vanillyl nonanoate, and therefore the upper limit of the proportion of vanillyl nonanoate is 100% by weight.
（３）外用組成物（血行促進）
上記ノナン酸バニリルは、血行促進を目的もしくは作用とする外用組成物の成分として使用することもできる。ここでいう外用組成物の例としては、例えば末梢血行障害に起因する例えばしもやけ、冷え性、手足のしびれ、むくみ、レイノー症、肩や首のこり、及び抜け毛（頭髪）等の各種疾患や病態（症状）に対する予防及び治療用の皮膚外用剤、血行を促進することで病態の改善を促進するための皮膚外用剤〔例えば、筋肉痛等のように血行不全が少なからず病態の改善の妨げになっているような疾患や病態（症状）の改善のための皮膚外用剤〕、または血行を促進して有効成分の経皮吸収性や薬効を促す作用を有する皮膚外用剤などの外用医薬組成物；眼の充血や疲れ目の抑制または改善作用を有する点眼剤、または眼の血行を促進して有効成分の経皮吸収性や薬効促進を促す作用を有する点眼剤；頭皮の血行を促進する作用を有する頭皮化粧料、または頭皮の血行を促進して有効成分の頭皮吸収性を促す作用を有する頭皮化粧料；血行を促進して温感作用または代謝を促す作用を有する皮膚化粧料、血行を促進して有効成分の経皮吸収性を促す作用を有する皮膚化粧料等を例示することができる。
(3) External composition (blood circulation promotion)
The vanillyl nonanoate can also be used as a component of an external composition intended to promote blood circulation or act. Examples of the composition for external use herein include various diseases and pathological conditions (symptoms) such as, for example, moistness, coldness, numbness of limbs, swelling, Raynosis, shoulder and neck stiffness, and hair loss (head hair) caused by peripheral blood circulation disorders. ) External skin preparations for prevention and treatment, and skin external preparations for promoting improvement of the disease state by promoting blood circulation [for example, there is not a little blood circulation failure such as muscle pain, which hinders the improvement of the disease state Skin external preparations for improving diseases and pathological conditions (symptoms), or external pharmaceutical compositions such as skin external preparations that promote blood circulation and promote the transdermal absorbability and medicinal properties of active ingredients; eye Ophthalmic solution that suppresses or ameliorates hyperemia and fatigue, or ophthalmic solution that promotes blood circulation of the eye and promotes percutaneous absorption and efficacy of active ingredients; has the effect of promoting blood circulation of the scalp Scalp cosmetics Or a scalp cosmetic having an action of promoting scalp resorption by promoting scalp blood circulation; a skin cosmetic having an action of promoting blood circulation to promote warm feeling or metabolism; and promoting blood circulation of active ingredients Examples thereof include skin cosmetics having an effect of promoting transdermal absorbability.
ゆえに、本発明はノナン酸バニリルを含有する外用組成物を提供するものである。本発明の外用組成物は、ノナン酸バニリルを有効成分として別個単独に配合して調製してもよいし、またノナン酸バニリルを含む上記本発明の血行促進剤を外用組成物の有効成分として配合して調製することもできる。 Therefore, the present invention provides an external composition containing vanillyl nonanoate. The composition for external use of the present invention may be prepared by separately blending vanillyl nonanoate as an active ingredient separately, or the blood circulation promoter of the present invention containing vanillyl nonanoate is blended as an active ingredient of the composition for external use. It can also be prepared.
外用組成物としては、具体的には上記の皮膚化粧料、頭皮化粧料、入浴剤（浴用剤）、外用医薬品、点眼剤等を挙げることができる。外用医薬品としては、例えば、本発明の目的及び効果を妨げないことを限度に、ノナン酸バニリル以外に他の薬効成分を含有してもよい各種軟膏、クリーム、ゲル、ローション、エアゾール剤、またはパップ剤等を挙げることができる。なお、軟膏剤とする場合には、油性基剤をベースとするもの、水中油型又は油中水型の乳化系基剤をベースとするもののいずれであっても良く、油性基剤としては、例えば、植物油、動物油、合成油、脂肪酸、エステル類、高級アルコール及び天然又は合成のグリセライド等が挙げられる。これらは製剤の形態に応じて常法に従って調製することができ、また常法に従って使用することができる。 Specific examples of the composition for external use include the skin cosmetics, scalp cosmetics, bath preparations (bath preparations), external medicines, eye drops and the like. As an external medicine, for example, various ointments, creams, gels, lotions, aerosols, or paps that may contain other medicinal ingredients in addition to vanillyl nonanoate as long as the purpose and effect of the present invention are not hindered. An agent etc. can be mentioned. In the case of an ointment, it may be one based on an oily base or one based on an oil-in-water or water-in-oil emulsified base. Examples include vegetable oils, animal oils, synthetic oils, fatty acids, esters, higher alcohols, and natural or synthetic glycerides. These can be prepared according to conventional methods according to the form of the preparation, and can be used according to conventional methods.
ここで薬効成分としては、特に制限はなく、例えば、鎮痛消炎剤、鎮痒剤、殺菌消毒剤、収斂剤、皮膚軟化剤、ホルモン剤、温感付与剤、冷感付与剤、保湿剤等を必要に応じて適宜使用することができる。 The medicinal component is not particularly limited, and for example, an analgesic / anti-inflammatory agent, anti-pruritic agent, bactericidal disinfectant, astringent, emollient, hormone agent, warming agent, cooling agent, moisturizing agent, etc. are necessary. Can be used as appropriate.
また皮膚化粧料または頭皮化粧料は、種々の形態、例えば油中水型又は水中油型の乳化型（クリーム、乳液）、ペースト状、ジェル状、エアゾール状、固形等の油性又は水性の化粧料とすることができる。皮膚化粧料として具体的には、クリーム、乳液、化粧水、美容液、口紅、ファンデーション、ローション、マッサージ剤、皮膚洗浄剤（液体石鹸、固形石鹸）等を挙げることができる。また頭皮化粧料としては、頭皮に適用されるものであれば特に制限はなく、例えば、ヘアトニック、整髪料、ヘアスタイリング剤、シャンプー、ヘアトリートメント、ヘアコンディショナー、ヘアリンス、ヘアマッサージ剤、養毛剤、育毛剤等を挙げることができる。 Skin cosmetics or scalp cosmetics can be used in various forms, for example, oil-in-water or oil-in-water emulsions (creams, emulsions), pastes, gels, aerosols, solids, etc. It can be. Specific examples of skin cosmetics include creams, emulsions, lotions, cosmetics, lipsticks, foundations, lotions, massage agents, skin cleansers (liquid soaps, solid soaps) and the like. The scalp cosmetic is not particularly limited as long as it is applied to the scalp. For example, hair tonic, hair styling agent, hair styling agent, shampoo, hair treatment, hair conditioner, hair rinse, hair massage agent, hair nourishing agent, hair restoration An agent etc. can be mentioned.
入浴剤としては、水又は湯に添加することにより適用されるものであれば特に制限はなく、例えば、粉末状、細粒状の入浴剤を使用することもできるし、液状（水溶液、油中水型又は水中油型の乳化型）の入浴剤を使用することもできる。 The bathing agent is not particularly limited as long as it is applied by adding it to water or hot water. For example, a powdery or fine-grained bathing agent can be used, or a liquid (aqueous solution, water-in-oil) can be used. Type or oil-in-water emulsified bath).
さらに点眼剤は溶液の状態であっても、また眼軟膏のようにクリームやゲル等のようにペースト状態を有するものであってもよい。なお、これらの皮膚化粧料、頭皮化粧料並びに点眼剤は製品形態に応じて常法に従って調製することができ、また常法に従って使用することができる。 Further, the eye drops may be in a solution state or may have a paste state such as a cream or gel like an eye ointment. In addition, these skin cosmetics, scalp cosmetics, and eye drops can be prepared according to conventional methods according to product forms, and can be used according to conventional methods.
本発明の外用組成物における外用血行促進剤、具体的には、その有効成分であるノナン酸バニリルの含有量は、本発明の効果を奏することを限度として特に制限されない。下限として通常０.１重量％、好ましくは１重量％、より好ましくは１０重量％を挙げることができる。上限も特に制限されず外用組成物の種類や目的、並びに形状に応じて適宜選択することができる。通常８０重量％以下、好ましくは５０重量％以下の割合を挙げることができる。 The content of the external blood circulation promoter in the external composition of the present invention, specifically, vanillyl nonanoate, which is an active ingredient thereof, is not particularly limited as long as the effect of the present invention is exhibited. The lower limit is usually 0.1% by weight, preferably 1% by weight, more preferably 10% by weight. The upper limit is not particularly limited, and can be appropriately selected according to the type, purpose, and shape of the composition for external use. The ratio is usually 80% by weight or less, preferably 50% by weight or less.
なお、本発明の外用組成物に配合する担体は、ノナン酸バニリルとの相溶性並びに安定性の点から、疎水性（無極性）の基剤または溶媒であることが望ましい。かかる基剤または溶媒としては、具体的にはワセリン（黄色ワセリン、白色ワセリン）、パラフィン、流動パラフィン、形質流動パラフィン、ミツロウ、サラシミツロウ、鯨ロウ、豚脂、牛脂、ラノリン（加水ラノリン、精製ラノリン）、オリーブ油、ゴマ油、ダイズ油、ツバキ油、トウモロコシ油、ナタネ油、ラッカセイ油、ヒマシ油、スクワラン、ラウリン酸、ミリスチン酸、パルミチン酸、ステアリン酸、オレイン酸、ウンデシレン酸、イソステアリン酸、ラウリルアルコール、セタノール、ステアリルアルコール、オレイルアルコール、ラノリンアルコール、ヘキシルデカノール、オクチルドデカノール、オレイン酸エステル、リノール酸エステル、及びリノレン酸エステルを例示することができる。 The carrier to be blended in the composition for external use of the present invention is preferably a hydrophobic (nonpolar) base or solvent from the viewpoint of compatibility with vanillyl nonanoate and stability. Specific examples of such a base or solvent include petrolatum (yellow petrolatum, white petrolatum), paraffin, liquid paraffin, plasma liquid paraffin, beeswax, white beeswax, whale wax, lard, beef tallow, lanolin (hydrolanolin, purified lanolin). ), Olive oil, sesame oil, soybean oil, camellia oil, corn oil, rapeseed oil, peanut oil, castor oil, squalane, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, undecylenic acid, isostearic acid, lauryl alcohol, Cetanol, stearyl alcohol, oleyl alcohol, lanolin alcohol, hexyl decanol, octyldodecanol, oleic acid ester, linoleic acid ester, and linolenic acid ester can be exemplified.
（４）外用組成物（脂肪分解促進）
また、ノナン酸バニリルは、脂肪分解促進を目的もしくは作用とする外用組成物の成分として使用することもできる。ここでいう外用組成物としては、新陳代謝を促進し、肥満の改善、高脂血症の予防又は改善、体の全体又は部分を細くする、セルライトを除去するための外用医薬組成物、皮膚化粧料、入浴剤等を例示することができる。
(4) External composition (facilitation of lipolysis)
Vanillyl nonanoate can also be used as a component of an external composition intended to promote or promote lipolysis. As used herein, the composition for external use includes the promotion of metabolism, improvement of obesity, prevention or improvement of hyperlipidemia, slimming of the whole or part of the body, removal of cellulite, and skin cosmetics. And bathing agents.
皮膚化粧料としては、種々の形態、例えば油中水型又は水中油型の乳化型（クリーム、乳液）、ペースト状、ジェル状、エアゾール状、固形等の油性又は水性の化粧料とすることができる。より具体的には、クリーム、乳液、化粧水、美容液、口紅、ファンデーション、ローション、マッサージ剤、皮膚洗浄剤（液体石鹸、固形石鹸）等を挙げることができる。また、入浴剤としては、水又は湯に添加することにより適用されるものであれば特に制限はなく、例えば、粉末状、細粒状の入浴剤を使用することもできるし、液状（水溶液、油中水型又は水中油型の乳化型）の入浴剤を使用することもできる。 As skin cosmetics, various forms, for example, oil-in-water or oil-in-water emulsified types (creams, emulsions), pastes, gels, aerosols, solids, and other oily or aqueous cosmetics may be used. it can. More specifically, creams, emulsions, lotions, cosmetics, lipsticks, foundations, lotions, massage agents, skin cleansers (liquid soaps, solid soaps) and the like can be mentioned. The bathing agent is not particularly limited as long as it is applied by adding it to water or hot water. For example, a powdery or fine-grained bathing agent can be used, or a liquid (aqueous solution, oil) can be used. A water-in-oil type or an oil-in-water type emulsion type bathing agent can also be used.
より詳細には、例えば、当該外用組成物を、痩せたい部分又は全身に、塗布、噴霧、貼付等することにより、脂肪の分解を促進することができる。 More specifically, for example, by applying, spraying, sticking, or the like to the part or the whole body of the external composition, fat breakdown can be promoted.
塗布する場合には、肌に擦り込むようにして塗布することにより、噴霧する場合には、噴霧した後に当該外用組成物を肌に擦り込むことにより、より高い脂肪分解促進効果を得ることができる。また、皮膚洗浄剤として使用する場合、体を洗浄しながら脂肪の分解を促進することができる。さらに、入浴剤として使用する場合には、お湯につかることで痩せることができる。お湯につかりながらマッサージを施すことにより、より高い脂肪分解促進効果を得ることができる。 In the case of application, it is applied by rubbing on the skin. In the case of spraying, a higher lipolysis promoting effect can be obtained by rubbing the externally applied composition on the skin after spraying. In addition, when used as a skin cleanser, it is possible to promote fat degradation while washing the body. Furthermore, when used as a bath agent, it can be thinned by soaking in hot water. By applying massage while bathing in hot water, a higher effect of promoting lipolysis can be obtained.
本発明の外用組成物におけるノナン酸バニリルの含有量は、本発明の効果を奏することを限度として特に制限されない。下限として通常０.１重量％、好ましくは１重量％、より好ましくは１０重量％を挙げることができる。上限も特に制限されず外用組成物の種類や目的、並びに形状に応じて適宜選択することができる。通常８０重量％以下、好ましくは５０重量％以下の割合を挙げることができる。なお、本発明の外用組成物に配合する担体は、上記（３）で示したものと同様のものが使用できる。 The content of vanillyl nonanoate in the external composition of the present invention is not particularly limited as long as the effect of the present invention is exhibited. The lower limit is usually 0.1% by weight, preferably 1% by weight, more preferably 10% by weight. The upper limit is not particularly limited, and can be appropriately selected according to the type, purpose, and shape of the composition for external use. The ratio is usually 80% by weight or less, preferably 50% by weight or less. In addition, as a carrier mix | blended with the composition for external use of this invention, the thing similar to what was shown by said (3) can be used.
ノナン酸バニリルを有効成分とする本発明の外用血行促進剤、並びにノナン酸バニリルをその血行促進作用が発揮される態様で含有する本発明の外用組成物は、皮膚または眼に適用した場合に良好な血行促進効果を発揮する。また、ノナン酸バニリルを有効成分とする本発明の外用脂肪分解促進剤、並びにノナン酸バニリルをその脂肪分解促進作用が発揮される態様で含有する本発明の外用組成物は、皮膚に適用した場合に良好な脂肪分解促進効果を発揮する。さらに、皮膚などに対して刺激性が少ないという優れた特徴を備えている。 The external blood circulation promoter of the present invention containing vanillyl nonanoate as an active ingredient, and the external composition of the present invention containing vanillyl nonanoate in an embodiment that exerts its blood circulation promoting action are good when applied to the skin or eyes. Exerts a significant blood circulation promoting effect. In addition, when the externally applied lipolysis promoter of the present invention containing vanillyl nonanoate as an active ingredient and the externally applied composition of the present invention containing vanillyl nonanoate in a mode in which the lipolysis promoting action is exerted are applied to the skin It has a good effect of promoting lipolysis. Furthermore, it has an excellent feature that it is less irritating to the skin.
以下、本発明を実験例ならびに実施例によって更に詳細に説明するが、本発明はこれらの実験例などによって何ら制限されるものではない。 Hereinafter, the present invention will be described in more detail with reference to experimental examples and examples, but the present invention is not limited to these experimental examples.
参考例１ ノナン酸バニリルの製造
文献Journal of Medicinal Chemistry 1993, Vol. 36, No. 16 p.2337の記載に従って、下記の方法によりノナン酸バニリルを製造した。
Reference Example 1 Production of Vanillyl Nonanoate Vanillyl nonanoate was produced by the following method according to the description in the literature Journal of Medicinal Chemistry 1993, Vol. 36, No. 16 p.2337.
4-ヒドロキシ-3-メトキシベンジルアルコール（化合物(1)）2g(14.5mmol) と酢酸エチル10mlを仕込み、トリエチルアミン2.9g(29mmol)を加えて氷冷した。そこにノナン酸クロライド5.1g(29mmol)の酢酸エチル20ml溶液を滴下し、撹拌して反応させた。得られた反応液をろ過後、ろ液を、洗浄液として2N-塩酸50ml、水、飽和塩化ナトリウムのそれぞれを用いて順次洗浄し、硫酸ナトリウムを用いて脱水乾燥した。黄色い油状物質として3-メトキシ-4-ノナノイルオキシベンジルノナン酸エステル（化合物(2)） 2.3g(収率40.5%)を得た。 4-hydroxy-3-methoxybenzyl alcohol (compound (1)) (2 g, 14.5 mmol) and ethyl acetate (10 ml) were charged, triethylamine (2.9 g, 29 mmol) was added, and the mixture was ice-cooled. Thereto was added dropwise a solution of 5.1 g (29 mmol) nonanoic acid chloride in 20 ml of ethyl acetate, and the mixture was stirred and reacted. After filtration of the resulting reaction solution, the filtrate was washed successively with 50 ml of 2N hydrochloric acid, water, and saturated sodium chloride as a washing solution, and dehydrated and dried using sodium sulfate. As a yellow oily substance, 2.3 g (yield: 40.5%) of 3-methoxy-4-nonanoyloxybenzylnonanoic acid ester (compound (2)) was obtained.
ついで、ピロリジンのエチレン溶液で処理して保護基（ノナノイル基）をはずし、粗生成物をカラムクロマトグラフィー(シリカゲル 展開溶媒：シクロヘキサン／酢酸エチル= 1／1)により精製し、ノナン酸バニリル（化合物(3)） 0.84g（収率19.8%）を得た。得られたノナン酸バニリルの1H-NMRデータを下記に示す。
1H NMR(300MHz CDCl3)：δ0.9(3H, t, alkyl CH3), 1.25(12H, env, alkyl CH2), 2.35(2H, t, CH2CO), 3.85(3H, s, ArOCH3), 5.02(2H, s, ArCH2OCO), 5.9(1H, brs, ArOH), 6.85(3H, m, ArH)
上記で調製したノナン酸バニリル（99%以上）を用いて下記の試験（試験例１）を行った。
Subsequently, the protecting group (nonanoyl group) was removed by treatment with an ethylene solution of pyrrolidine, and the crude product was purified by column chromatography (silica gel developing solvent: cyclohexane / ethyl acetate = 1/1), and vanillyl nonanoate (compound ( 3)) 0.84 g (yield 19.8%) was obtained. 1 H-NMR data of the obtained vanillyl nonanoate are shown below.
1 H NMR (300 MHz CDCl 3 ): δ0.9 (3H, t, alkyl CH 3 ), 1.25 (12H, env, alkyl CH 2 ), 2.35 (2H, t, CH 2 CO), 3.85 (3H, s, ArOCH 3 ), 5.02 (2H, s, ArCH 2 OCO), 5.9 (1H, brs, ArOH), 6.85 (3H, m, ArH)
The following test (Test Example 1) was performed using vanillyl nonanoate (99% or more) prepared above.
試験例１（血行促進効果）
ノナン酸バニリルを皮膚に適用した場合の血行促進効果を、下記に記載するようにラットを用いて評価した。なお、被験サンプルは実施例として参考例１で調製したノナン酸バニリル（実施例１）を用い、比較例としてノニル酸ワニリルアミド（東洋ファルマー社製・99％以上）の０.１重量％溶液（比較例１）、コントロールとしてエタノール／水混合溶液（1:1(w/w)の等量混合液）（コントロール１）を用いた。ここでノニル酸ワニリルアミドは、皮膚に対する血行促進作用が知られた化合物であり、陽性コントロールとして用いた。上記においてノニル酸ワニリルアミドの０.１重量％溶液はエタノール／水の等量混合液（1:1(w/w)）で調製した溶液である。
Test example 1 (blood circulation promotion effect)
The blood circulation promoting effect when vanillyl nonanoate was applied to the skin was evaluated using rats as described below. As a test sample, vanillyl nonanoate (Example 1) prepared in Reference Example 1 was used as an example, and 0.1% by weight solution of nonyl acid vanillylamide (manufactured by Toyo Falmer, 99% or more) as a comparative example (Comparison) Example 1) An ethanol / water mixed solution (equal mixture of 1: 1 (w / w)) (control 1) was used as a control. Here, nonylic acid vanillylamide is a compound known to have a blood circulation promoting action on the skin, and was used as a positive control. In the above, a 0.1% by weight solution of nonylic acid vanillylamide is a solution prepared with an equal volume of ethanol / water (1: 1 (w / w)).
ラット（雄性、９週齢）は、試験前日に予め電気シェーバー及び除毛クリームを用いて背部の毛を除いておいた。試験当日、上記ラットをエーテル麻酔して、レーザードップラー血流計を背部に装着し、被験サンプル塗布前の定常血流量を測定した。次に血流プローブを一旦はずし、背部に被験サンプルをそれぞれ１０μL/cm2の割合で塗布した（各被験サンプルについて、５匹を対象として実施）。塗布後、背部塗布領域に再び血流プローブを貼り付け血流量を連続的に測定した。塗布１５〜２０分後の血流量から平均血流量を求め、先に測定しておいた定常血流量（100％）に対する相対値（％）を求めた。その結果を表１に示す。 Rats (male, 9 weeks old) had their back hair removed beforehand using an electric shaver and hair removal cream on the day before the test. On the day of the test, the rats were anesthetized with ether, a laser Doppler blood flow meter was attached to the back, and the steady blood flow before application of the test sample was measured. Next, the blood flow probe was once removed, and the test sample was applied to the back at a rate of 10 μL / cm 2 (performed for five test samples). After application, a blood flow probe was attached again to the back application area, and blood flow was continuously measured. The average blood flow was determined from the blood flow 15 to 20 minutes after application, and the relative value (%) to the steady blood flow (100%) measured previously was determined. The results are shown in Table 1.
表1の結果からわかるように、ノナン酸バニリルを塗布した場合、陽性コントロールであるノニル酸ワニリルアミドと同様に塗布背部の血流量は有意に上昇していた。このことから、ノナン酸バニリルには、皮膚に適用することによって血流を上昇させ、血行を促進する効果があることが確認された。 As can be seen from the results in Table 1, when vanillyl nonanoate was applied, the blood flow rate at the back of the application was significantly increased as in the case of nonyl acid vanillylamide as a positive control. From this, it was confirmed that vanillyl nonanoate has the effect of increasing blood flow and promoting blood circulation when applied to the skin.
試験例２（脂肪分解促進効果）
ノナン酸バニリルを皮膚に適用した場合の脂肪分解促進効果を、下記に記載するようにラットを用いて評価した。なお、被験サンプルは実施例として参考例１で調製したノナン酸バニリル（実施例1）を用い、比較例としてアミノフィリン（ICN社製 Cat. No. 190144）の2重量%溶液（比較例2）、コントロールとしてエタノール／水混合溶液（1:1(W/W)の等量混合液）（コントロール１）を用いた。ここでアミノフィリンは、皮膚適用で脂肪分解作用が知られた化合物であり、陽性コントロールとして用いた。上記においてアミノフィリンの2重量%溶液はエタノール／水の等量混合液（1:1(W/W)）で調製した溶液である。
Test Example 2 (Lipolysis promotion effect)
The effect of promoting lipolysis when vanillyl nonanoate was applied to the skin was evaluated using rats as described below. The test sample used was vanillyl nonanoate (Example 1) prepared in Reference Example 1 as an example, and a 2% by weight solution (Comparative Example 2) of aminophylline (Cat. No. 190144, manufactured by ICN) as a comparative example, As a control, an ethanol / water mixed solution (equal mixed solution of 1: 1 (W / W)) (control 1) was used. Here, aminophylline is a compound known to have a lipolytic action when applied to the skin, and was used as a positive control. In the above, a 2% by weight solution of aminophylline is a solution prepared with an equal volume of ethanol / water (1: 1 (W / W)).
ラット（雄性、11週齢）は、試験前日に予め電気シェーバー及び除毛クリームを用いて腹部の毛を除いておいた。試験当日、上記ラットの腹部に被験サンプルを250μl、できるだけ広範囲に塗布し、塗布２０分後にエーテル麻酔下で開腹の後、腹大静脈より採血を行った（各被験サンプルについて、５匹を対象として実施）。採取血から血清を分離し、血清中の遊離脂肪酸量をNEFA C-テストワコー（和光純薬）にて測定した。エタノール/水混合溶液（1:1(W/W)の等量混合液）（コントロール）に対するその相対値(%)を求めた。その結果を表２に示す。 Rats (male, 11 weeks old) had their abdominal hair removed using an electric shaver and depilation cream the day before the test. On the day of the test, 250 μl of the test sample was applied as widely as possible to the abdomen of the rat, and after 20 minutes of application, blood was collected from the abdominal vena cava after laparotomy under ether anesthesia (for each test sample, 5 animals were used as subjects) Implementation). Serum was separated from the collected blood, and the amount of free fatty acid in the serum was measured with NEFA C-Test Wako (Wako Pure Chemical Industries). The relative value (%) to the ethanol / water mixed solution (equal mixed solution of 1: 1 (W / W)) (control) was determined. The results are shown in Table 2.
表2の結果からわかるように、ノナン酸バニリルを塗布した場合、陽性コントロールであるアミノフィリンと同様に血中の遊離脂肪酸量はエタノール／水混合溶液（1:1(W/W)の等量混合液）を塗布した場合に比べて有意に上昇していた。脂肪は分解されると遊離脂肪酸とグリセロールを生成するため、ノナン酸バニリルには、皮膚に適用することによって血中遊離脂肪酸濃度を上昇させ、脂肪を分解する効果があることが確認された。 As can be seen from the results in Table 2, when vanillyl nonanoate was applied, the amount of free fatty acid in the blood was mixed with an equal volume of ethanol / water mixture (1: 1 (W / W), as with the positive control aminophylline. (Liquid) was significantly increased as compared with the case of application. When fat is broken down, it produces free fatty acid and glycerol, so it was confirmed that vanillyl nonanoate has the effect of breaking down fat by increasing the blood free fatty acid concentration by applying it to the skin.
試験例３（皮膚刺激性）
ノナン酸バニリルの皮膚に対する刺激性を、下記に記載するようにラットを用いて評価した。なお、被験サンプルは実施例として参考例１で調製したノナン酸バニリル（実施例１）を用い、比較例としてノニル酸ワニリルアミド（東洋ファルマー社製・99％以上）の０.１重量％溶液（比較例１）、コントロールとしてエタノール／水混合溶液（1:1(w/w)の等量混合液）（コントロール１）を用いた。
Test Example 3 (Skin irritation)
The irritation to the skin of vanillyl nonanoate was evaluated using rats as described below. As a test sample, vanillyl nonanoate (Example 1) prepared in Reference Example 1 was used as an example, and 0.1% by weight solution of nonyl acid vanillylamide (manufactured by Toyo Falmer, 99% or more) as a comparative example (Comparison) Example 1) An ethanol / water mixed solution (equal mixture of 1: 1 (w / w)) (control 1) was used as a control.
ラット（雄性、１０週齢）は、試験前日に予め電気シェーバー及び除毛クリームを用いて両腋部の毛を除いておいた。試験当日、上記ラットについて、一方の腋部に対して上記各被験サンプルを２０μｌずつ塗布し、他一方の腋部は何も処置しなかった（各被験サンプルについて、３匹を対象として実施）。塗布直後から塗布１時間までの間で、塗布した腋部側と無処理の腋部側への振り向き回数をそれぞれ計測し、塗布側振り向き回数から無処理側振り向き回数を差し引いた数値を求め、これを塗布による皮膚刺激性を判定する指標とした。その結果を表3に示す。 Rats (male, 10 weeks of age) had their hair removed from both hips using an electric shaver and hair removal cream in advance on the day before the test. On the day of the test, 20 μl of each test sample was applied to one of the buttocks of the rat, and no treatment was performed on the other buttocks (implemented for three test samples for each test sample). From the time immediately after application to 1 hour of application, the number of swinging directions to the applied buttocks side and the untreated buttocks side is measured, and the value obtained by subtracting the number of untreated side swinging times from the number of application side swinging times is obtained. Was used as an index for judging skin irritation by application. The results are shown in Table 3.
その結果、表3に示すように、参考例１で調製したノナン酸バニリルはノニル酸ワニリルアミド（東洋ファルマー社製・99％以上）0.1％とほぼ同等の血行促進作用があるのに対し、皮膚に対する刺激性は約1/3に低減されており、皮膚に対する刺激性が極めて少ないことが判明した。 As a result, as shown in Table 3, the vanillyl nonanoate prepared in Reference Example 1 has a blood circulation promoting effect almost equal to 0.1% nonyl acid vanillylamide (Toyo Farmer, 99% or more), while The irritation was reduced to about 1/3, and the skin irritation was found to be extremely low.
以上試験例１、試験例２及び試験例３の結果から、ノナン酸バニリルは皮膚への刺激性が少ない血行促進剤及び脂肪分解促進剤として有用であることがわかる。 From the results of Test Example 1, Test Example 2 and Test Example 3, it can be seen that vanillyl nonanoate is useful as a blood circulation promoter and a lipolysis promoter with little skin irritation.
実施例２
下記の処方に従って、軟膏状の皮膚外用医薬組成物（軟膏剤）を調製した。この軟膏剤は、皮膚に塗布することにより、血行促進剤としても脂肪分解促進剤としても使用することができる。
Example 2
An ointment-form external pharmaceutical composition (ointment) was prepared according to the following formulation. This ointment can be used as a blood circulation promoter or a lipolysis promoter by applying to the skin.
白色ワセリン ２５０.００ｇ
ステアリルアルコール ２２０.００ｇ
プロピレングリコール １２０.００ｇ
ラウリル硫酸ナトリウム １５.００ｇ
パラオキシ安息香酸メチル ０.２５ｇ
パラオキシ安息香酸プロピル ０.１５ｇ
ノナン酸バニリル １０.００ｇ
精製水 残 部
合 計 １０００.００ｇ。
White petrolatum 250.00g
Stearyl alcohol 220.00g
Propylene glycol 120.00g
Sodium lauryl sulfate 15.00g
0.25 g of methyl paraoxybenzoate
0.15 g of propyl paraoxybenzoate
Vanillyl nonanoate 10.00 g
Purified water balance
Total 1000.00g.
実施例３
下記の処方に従って、クリーム状の皮膚化粧料を調製した。この皮膚化粧料は、皮膚に塗布することにより、血行促進剤としても脂肪分解促進剤としても使用することができる。
Example 3
A creamy skin cosmetic was prepared according to the following formulation. This skin cosmetic can be used as a blood circulation promoter or a lipolysis promoter by applying to the skin.
ステアリン酸 ２０ｇ
ステアリルアルコール ７０ｇ
還元ラノリン ２０ｇ
スクワラン ５０ｇ
オクチルドデカノール ６０ｇ
ポリオキシエチレンセチルエーテル(25E.O.) ３０ｇ
親油型モノステアリン酸グリセリン ２０ｇ
ノナン酸バニリル １０ｇ
香料 ３ｇ
防腐剤 適 量
酸化防止剤 適 量
プロピレングリコール ５０ｇ
精製水 残 部
合 計 １０００ｇ。
Stearic acid 20g
Stearyl alcohol 70g
Reduced lanolin 20g
Squalane 50g
Octyldodecanol 60g
Polyoxyethylene cetyl ether (25E.O.) 30g
Lipophilic glyceryl monostearate 20g
Vanillyl nonanoate 10g
Fragrance 3g
Antiseptic appropriate amount Antioxidant appropriate amount Propylene glycol 50g
Purified water balance
Total 1000g.
実施例４
下記の処方に従って、液状の消炎鎮痛剤（皮膚外用組成物：液剤）を調製した。この液剤は、皮膚に塗布することにより、より効果の高い消炎鎮痛剤として、また、脂肪分解促進作用を有する消炎鎮痛剤として使用することができる。
Example 4
A liquid anti-inflammatory analgesic (skin external composition: liquid) was prepared according to the following formulation. By applying this solution to the skin, it can be used as a more effective anti-inflammatory analgesic or as an anti-inflammatory analgesic having a lipolysis promoting action.
Ｌ−メントール ３０ｇ
アジピン酸ジイソプロピル ５０ｇ
プロピレングリコール １００ｇ
ラウロマクロゴール ３０ｇ
精製水 ２７０ｇ
ノナン酸バニリル １０ｇ
イソプロパノール 残 部
合 計 １０００ｇ。
L-menthol 30g
50g diisopropyl adipate
Propylene glycol 100g
Lauro Macrogol 30g
270 g of purified water
Vanillyl nonanoate 10g
Isopropanol balance
Total 1000g.
Claims (4)
The composition for external use according to claim 3, which is a skin cosmetic, a scalp cosmetic, a bath agent, a pharmaceutical external preparation or an eye drop.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2004099024A JP3702393B2 (en) | 2003-03-31 | 2004-03-30 | Topical preparation |
| PCT/JP2004/013315 WO2005099682A1 (en) | 2004-03-30 | 2004-09-13 | Preparations for external use |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2003096451 | 2003-03-31 | ||
| JP2004099024A JP3702393B2 (en) | 2003-03-31 | 2004-03-30 | Topical preparation |
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| Publication Number | Publication Date |
|---|---|
| JP2004331651A JP2004331651A (en) | 2004-11-25 |
| JP3702393B2 true JP3702393B2 (en) | 2005-10-05 |
Family
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| JP2004099024A Expired - Lifetime JP3702393B2 (en) | 2003-03-31 | 2004-03-30 | Topical preparation |
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Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9399030B2 (en) | 2005-02-01 | 2016-07-26 | Ajinomoto Co., Inc. | Topically applied circulation enhancing agent and skin and hair cosmetic and bath agent containing the same |
| JP4978015B2 (en) * | 2005-02-01 | 2012-07-18 | 味の素株式会社 | External agent for promoting blood circulation, cosmetic for skin and hair and bathing agent containing the same |
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| Publication number | Publication date |
|---|---|
| JP2004331651A (en) | 2004-11-25 |
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