JP4112741B2 - Moisturizer - Google Patents

Description

〔式中、Ｒは炭素数５〜２３の直鎖又は分岐鎖のアルキル又はアルケニル基を示す。〕で表されるアミド誘導体を有効成分とする保湿剤を提供するものである。
【０００９】
一般式（１）で表されるアミド誘導体は、洗浄剤としての使用が報告されているが（特開平６−２７１８９３号公報）、皮膚角質層の水分保持能力を改善する効果があることはこれまでに知られていない。
【００１０】
【発明の実施の形態】
本発明における一般式（１）で示されるアミド誘導体の式中、Ｒは炭素数５〜２３の直鎖又は分岐鎖のアルキル又はアルケニル基を示すが、好ましいＲとしては、例えばペンチル、ヘプチル、ノニル、ウンデシル、トリデシル、ペンタデシル、ヘプタデシル、ノナデシル、ヘンエイコシル、トリコシル、イソヘプタデシル、１−エチルヘプチル、１−ヘプチルデシル、イソヘプタデシル、メチル分岐イソヘプタデシル、２，４，４−トリメチルペンチル、８−ヘプタデセニル、８，１１−ヘプタデカジエニル基等が挙げられる。このうち、炭素数１１〜２３、特に炭素数１３〜１７の直鎖又は分岐鎖のアルキル基が特に好ましい。
【００１１】
本発明におけるアミド誘導体（１）は、公知のアミド合成法によって合成することができるが、例えば次の方法によれば安全で且つ効率的に製造することができる。
【００１２】
【化３】

【００１３】
〔式中、Ｒは前記と同様の意味を示す。〕
【００１４】
即ち、対応するカルボン酸（２）又はその反応性誘導体（酸ハライド、エステル、酸無水物等）とジグリコールアミン（３）を縮合させることにより、アミド誘導体（１）を効率的に得ることができる。この縮合の条件としては、ジシクロヘキシルカルボジイミド等の脱水剤又は水酸化カリウム、水酸化ナトリウム等のアルカリ金属水酸化物、水酸化カルシウム等のアルカリ土類金属水酸化物、炭酸カリウム等のアルカリ金属炭酸塩、炭酸カルシウム等のアルカリ土類金属炭酸塩、ナトリウムメトキシド、ナトリウムエトキシド、カリウム−ｔｅｒｔ−ブトキシド等のアルカリ金属アルコラート等の塩基性触媒の存在下、あるいは非存在下、常圧〜０．０１mmHgの減圧下に室温〜２５０℃で反応させることが好ましい。この際、ジグリコールアミン（３）をカルボン酸（２）又はその反応性誘導体に対して過剰に用いるのが好ましく、また反応により生じる水又はアルコールを系外に除去しながら行なうと、反応が速く進行するので好ましい。このようにして得られるアミド誘導体（１）は、水洗、カラムクロマトグラフィー、蒸留、結晶化、再結晶化や粉体処理等の公知の方法により精製することもできる。
【００１５】
かくして得られるアミド誘導体（１）は、皮膚に対しては、試験例１に示すように角質細胞間の脂質膜に浸透し角質層の水分保持能力を改善（維持・補強）することにより皮膚炎症や肌荒れ等の改善・予防効果を発揮する。また、毛髪に対しては、試験例２に示すように保護作用を有することにより毛髪の感触を向上させる効果を発揮する。
【００１６】
従って、本発明におけるアミド誘導体（１）は、保湿剤、肌荒れ改善用皮膚外用剤及び毛髪化粧料として有用である。尚、ここでいう毛髪化粧料とは、ヘアリンス、ヘアトリートメント、ヘアコンディショナー、ヘアスタイリング剤等のシャンプーを除く毛髪化粧料をいう。
【００１７】
斯かる保湿剤、肌荒れ改善用皮膚外用剤及び毛髪化粧料は、通常外用剤に用いられる基剤（担体）にアミド誘導体（１）を含有させて製造することができる。
【００１８】
アミド誘導体（１）を保湿剤及び肌荒れ改善用皮膚外用剤として配合する対象は、化粧料だけでなく外用医薬品も含まれ、斯かる外用医薬品、例えば薬効成分を含有する各種軟膏剤としては、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よい。油性基剤としては特に制限はなく、例えば植物油、動物油、合成油、脂肪酸及び天然又は合成のグリセライド等が挙げられる。また、薬効成分としては特に制限はないが、例えば鎮痛消炎剤、鎮痒剤、殺菌消毒剤、収斂剤、皮膚軟化剤、ホルモン剤等を必要に応じて適宜使用することができる。
【００１９】
皮膚化粧料として使用する場合は、アミド誘導体（１）の他に、化粧料成分として一般に使用されている油分、界面活性剤、紫外線吸収剤、美白剤、しわ改善剤、アルコール類、キレート剤、pH調整剤、防腐剤、増粘剤、色素類、香料等を任意に組合せて配合することができる。
【００２０】
毛髪化粧料として使用する場合には、アミド誘導体（１）の他に、例えば油分、カチオン界面活性剤、シリコーン類、カチオン性ポリマー、紫外線吸収剤、アルコール類、キレート剤、pH調整剤、防腐剤、増粘剤、色素類、香料等を任意に組合せて配合することができる。
【００２１】
皮膚化粧料は、例えば油中水型又は水中油型の乳化化粧料、クリーム、化粧乳液、化粧水、油性化粧料、口紅、ファンデーション、浴剤等とすることができ、毛髪化粧料は、例えばヘアトニック、整髪料、ヘアスタイリング剤、ヘアリンス、ヘアトリートメント、ヘアコンディショナー、養毛剤、育毛剤等とすることができる。
【００２２】
皮膚化粧料又は毛髪化粧料におけるアミド誘導体（１）の配合量は、特に制限されないが、通常、乳化型化粧料の場合には、全組成の０．００１〜５０重量％（以下、単に％で示す）が好ましく、スクワラン等の液状炭化水素を基剤とする油性化粧料の場合には、全組成の０．０１〜５０％が好ましく、いずれの場合も特に好ましくは０．１〜２０％である。
【００２３】
【実施例】
実施例１
Ｎ−［２−（２−ヒドロキシエトキシ）エチル］オクタデカナミド（Ｒがヘプタデシル基であるもの）（化合物１）の製造
攪拌装置、窒素導入管及び蒸留装置を備えた５００ミリリットル３口フラスコに、ステアリン酸メチル１０３ｇ、ジグリコールアミン７３ｇ及びナトリウムメトキシド３ｇを仕込み、減圧下（２０torr）１４０℃で３時間攪拌した。反応終了後、過剰なジグリコールアミンを減圧留去し、標記化合物１２８ｇ（収率１００％）を得た。
【００２４】
性状：白色結晶
融点：87℃
¹H-NMR(CDCl₃,δ)；
0.87(t,J=7.2Hz,3H), 1.17-1.41(m,28H), 1.51-1.78(m,2H),
2.18(t,J=7.2Hz,2H), 3.40-3.53(m,2H), 3.53-3.65(m,4H), 3.70-3.86(m,2H),
5.86-6.11(m,1H).
【００２５】
実施例２
Ｎ−［２−（２−ヒドロキシエトキシ）エチル］−メチル分岐イソステアロイルアミド（Ｒがメチル分岐イソヘプタデシル基であるもの）（化合物２）の製造実施例１において、ステアリン酸メチルの代わりにメチル分岐イソステアリン酸メチルを用いる以外は、実施例１と同様に製造を行ない、標記化合物を得た。
【００２６】
性状：無色ペースト
¹H-NMR(CDCl₃,δ)；
0.66-0.97(m,6H), 1.00-1.49(m,25H), 1.49-1.77(m,2H),
2.18(t,J=7.2Hz,2H), 2.70-2.94(m,1H), 3.35-3.52(m,2H), 3.52-3.66(m,4H),
3.66-3.81(m,2H), 6.18-6.35(m,1H).
【００２７】
実施例３
Ｎ−［２−（２−ヒドロキシエトキシ）エチル］−２−ヘプチルウンデカナミド（Ｒが１−ヘプチルデシル基であるもの）（化合物３）の製造
実施例１において、ステアリン酸メチルの代わりに２−ヘプチルウンデカン酸メチルを用いる以外は、実施例１と同様に製造を行ない、標記化合物を得た。
【００２８】
性状：無色ペースト
¹H-NMR(CDCl₃,δ)；
0.70-1.00(m,6H), 1.05-1.48(m,26H), 1.48-1.71(m,2H),
1.90-2.10(m,1H), 2.25-2.64(m,1H), 3.37-3.67(m,6H), 3.67-3.87(m,2H),
5.96-6.14(m,1H).
【００２９】
試験例１
実施例１〜３で製造した化合物１〜３の３３％とワセリン６７％からなる本発明の組成物を調製し、それぞれについて下記の方法により皮膚コンダクタンス及び肌荒れについて評価した。また、比較品としてワセリンのみからなるものを用い同様の試験評価を行なった。結果を表１に示す。
【００３０】
（試験方法）
冬期に頬部に肌荒れを起こしている２０〜５０才の女性１０名を被験者とし、左右の頬に異なる組成物を２週間塗布する。２週間の塗布が終了した翌日に次の項目につき試験を行なった。
【００３１】
（１）皮膚コンダクタンス
３７℃の温水にて洗顔後、温度２０℃、湿度４０％の部屋で２０分間安静にした後、角質層の水分含有量を皮膚コンダクタンスメータ（ＩＢＳ社製）にて測定した。コンダクタンス値は値が小さいほど皮膚は肌荒れしており、５以下ではひどい肌荒れである。一方この値が２０以上であれば肌荒れはほとんど認められない。
【００３２】
（２）肌荒れスコア
肌荒れを肉眼で観測し、下記基準により判定した。スコアは平均値で示した。
【００３３】
０：肌荒れを認めない
１：かすかな肌荒れを認める
２：肌荒れを認める
３：ややひどい肌荒れを認める
４：ひどい肌荒れを認める
【００３４】
【表１】

【００３５】
試験例２
下記表２に示す組成のヘアリンスを調製し、該ヘアリンスによる処理後の髪の感触を５名の専門パネラーにより下記基準で評価し、５名の平均値で示した。この結果を併せて表２に示す。
【００３６】
−２：悪い
−１：やや悪い
０：どちらともいえない
＋１：やや良い
＋２：良い
【００３７】
【表２】

【００３８】
上記表１及び表２に示す結果から明らかな通り、アミド誘導体（１）を含有する組成物は、何れも角質層の水分含有量を増加させる効果と肌荒れを改善する効果に優れ、毛髪の感触を向上する効果に優れるものである。
【００３９】
【発明の効果】
本発明の保湿剤は、効率的に且つ安価に製造することができ、安定性に優れ、角質層の水分保持能力を本質的に改善し皮膚炎症や肌荒れ等の改善・予防効果を発揮し、また毛髪に対する保護作用によって毛髪の感触を向上させる効果を有する。更に、基剤に対する溶解性がよく、配合性や配合安定性に優れる。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a moisturizing agent having a rough skin improving effect and a hair protecting effect.
[0002]
[Prior art]
Conventionally, for the purpose of improving or preventing rough skin, for the purpose of hydration of the stratum corneum, water-soluble components such as free amino acids, organic acids, urea and inorganic ions, and highly hydrophilic moisturizing substances have been used. Formulated cosmetics have been used.
However, such water-soluble components and moisturizing substances cannot be said to essentially prevent or treat rough skin, and their moisturizing effect is also temporary.
On the other hand, the application of natural ceramide, an intercellular lipid in the stratum corneum, to the skin for the purpose of improving water retention capacity has also been studied, but it is also expensive and has good compoundability and stability in external preparations. There was also a problem that it was not preferable.
[0003]
In view of such a situation, the present inventors have the effect of fundamentally improving the water retention capacity of the stratum corneum in some amide derivatives, and the effect of penetrating into the hair to enhance its protective effect. (Japanese Patent Publication No. 1-42934, Japanese Patent Application Laid-Open No. 64-29347, Japanese Patent Application Laid-Open No. 8-319263, Japanese Patent Application Laid-Open No. 64-9913, etc.).
[0004]
However, it has been difficult for such amide derivatives to maintain good blendability and blending stability when blended as an external preparation. Further, in terms of production, there is also a problem that a multi-step reaction is required, which is not preferable in terms of economy.
[0005]
[Problems to be solved by the invention]
Therefore, the object of the present invention is to improve the moisture retention ability of the stratum corneum and to enhance the protective effect by penetrating into the hair, and has good solubility in the base and compounding properties and An object of the present invention is to provide a humectant that has excellent blending stability and can be produced efficiently and inexpensively.
[0006]
[Means for Solving the Problems]
As a result of studying various amide derivatives, the present inventors have found that an amide derivative represented by the following general formula (1) achieves the above object.
[0007]
That is, the present invention provides the following general formula (1)
[0008]
[Chemical formula 2]

[Wherein, R represents a linear or branched alkyl or alkenyl group having 5 to 23 carbon atoms. A humectant containing an amide derivative represented by formula (I) as an active ingredient is provided.
[0009]
The amide derivative represented by the general formula (1) has been reported to be used as a cleaning agent (Japanese Patent Laid-Open No. Hei 6-271893), but this has the effect of improving the moisture retention ability of the skin stratum corneum. Not known until.
[0010]
DETAILED DESCRIPTION OF THE INVENTION
In the formula of the amide derivative represented by the general formula (1) in the present invention, R represents a linear or branched alkyl or alkenyl group having 5 to 23 carbon atoms. Preferred examples of R include pentyl, heptyl, and nonyl. , Undecyl, tridecyl, pentadecyl, heptadecyl, nonadecyl, heneicosyl, tricosyl, isoheptadecyl, 1-ethylheptyl, 1-heptyldecyl, isoheptadecyl, methyl branched isoheptadecyl, 2,4,4-trimethylpentyl, 8-heptadecenyl, 8,11-hepta A decadienyl group etc. are mentioned. Among these, a linear or branched alkyl group having 11 to 23 carbon atoms, particularly 13 to 17 carbon atoms is particularly preferable.
[0011]
The amide derivative (1) in the present invention can be synthesized by a known amide synthesis method. For example, it can be produced safely and efficiently by the following method.
[0012]
[Chemical 3]

[0013]
[Wherein, R represents the same meaning as described above. ]
[0014]
That is, the amide derivative (1) can be efficiently obtained by condensing the corresponding carboxylic acid (2) or a reactive derivative thereof (acid halide, ester, acid anhydride, etc.) and diglycolamine (3). it can. The conditions for this condensation include a dehydrating agent such as dicyclohexylcarbodiimide, an alkali metal hydroxide such as potassium hydroxide and sodium hydroxide, an alkaline earth metal hydroxide such as calcium hydroxide, and an alkali metal carbonate such as potassium carbonate. In the presence or absence of a basic catalyst such as alkaline earth metal carbonates such as calcium carbonate, alkali metal alcoholates such as sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc., normal pressure to 0.01 mmHg The reaction is preferably carried out at room temperature to 250 ° C. under reduced pressure. At this time, it is preferable to use diglycolamine (3) in excess relative to carboxylic acid (2) or a reactive derivative thereof, and when the reaction is carried out while removing water or alcohol generated by the reaction out of the system, the reaction is fast. Since it progresses, it is preferable. The amide derivative (1) thus obtained can also be purified by known methods such as washing with water, column chromatography, distillation, crystallization, recrystallization and powder treatment.
[0015]
As shown in Test Example 1, the amide derivative (1) thus obtained permeates into a lipid membrane between keratinocytes and improves (maintains / reinforces) the water retention ability of the stratum corneum. Demonstrate the effect of improving and preventing skin roughness. Moreover, with respect to hair, as shown in Test Example 2, it exhibits the effect of improving the feel of hair by having a protective action.
[0016]
Therefore, the amide derivative (1) in the present invention is useful as a moisturizer, a skin external preparation for improving rough skin, and a hair cosmetic. The term “hair cosmetic” as used herein refers to a hair cosmetic excluding shampoo such as hair rinse, hair treatment, hair conditioner, hair styling agent.
[0017]
Such a moisturizing agent, a skin external preparation for improving rough skin, and a hair cosmetic can be produced by containing the amide derivative (1) in a base (carrier) usually used for an external preparation.
[0018]
The target of blending the amide derivative (1) as a moisturizer and a skin external preparation for improving rough skin includes not only cosmetics but also external medicines. For such external medicines, for example, various ointments containing medicinal ingredients, oily Any of those based on a base and those based on an emulsified base of an oil-in-water type or a water-in-oil type may be used. There is no restriction | limiting in particular as an oil-based base, For example, vegetable oil, animal oil, synthetic oil, a fatty acid, natural or synthetic glyceride etc. are mentioned. Moreover, there is no restriction | limiting in particular as a medicinal component, For example, an analgesic / anti-inflammatory agent, an antipruritic agent, a bactericidal disinfectant, an astringent agent, an emollient, a hormone agent etc. can be used suitably as needed.
[0019]
When used as a skin cosmetic, in addition to the amide derivative (1), oils, surfactants, UV absorbers, whitening agents, wrinkle improvers, alcohols, chelating agents, which are commonly used as cosmetic ingredients, A pH adjuster, preservative, thickener, pigments, fragrance and the like can be combined in any combination.
[0020]
When used as a hair cosmetic, in addition to the amide derivative (1), for example, oils, cationic surfactants, silicones, cationic polymers, ultraviolet absorbers, alcohols, chelating agents, pH adjusters, preservatives , Thickeners, pigments, fragrances and the like can be combined in any combination.
[0021]
Skin cosmetics can be, for example, water-in-oil or oil-in-water emulsified cosmetics, creams, cosmetic emulsions, lotions, oily cosmetics, lipsticks, foundations, bath preparations, etc. It can be used as a hair tonic, hair styling agent, hair styling agent, hair rinse, hair treatment, hair conditioner, hair nourishing agent, hair restoring agent and the like.
[0022]
The blending amount of the amide derivative (1) in skin cosmetics or hair cosmetics is not particularly limited. Usually, in the case of emulsified cosmetics, 0.001 to 50% by weight (hereinafter simply referred to as%) of the total composition. In the case of oily cosmetics based on liquid hydrocarbons such as squalane, 0.01 to 50% of the total composition is preferable, and in any case, particularly preferably 0.1 to 20%. is there.
[0023]
【Example】
Example 1
Production of N- [2- (2-hydroxyethoxy) ethyl] octadecanamide (R is a heptadecyl group) (Compound 1) Stirric acid was added to a 500 ml three-necked flask equipped with a stirrer, a nitrogen inlet tube and a distillation apparatus. 103 g of methyl, 73 g of diglycolamine and 3 g of sodium methoxide were charged and stirred at 140 ° C. under reduced pressure (20 torr) for 3 hours. After completion of the reaction, excess diglycolamine was distilled off under reduced pressure to obtain 128 g (yield 100%) of the title compound.
[0024]
Property: White crystal Melting point: 87 ° C
¹ H-NMR (CDCl ₃ , δ);
0.87 (t, J = 7.2Hz, 3H), 1.17-1.41 (m, 28H), 1.51-1.78 (m, 2H),
2.18 (t, J = 7.2Hz, 2H), 3.40-3.53 (m, 2H), 3.53-3.65 (m, 4H), 3.70-3.86 (m, 2H),
5.86-6.11 (m, 1H).
[0025]
Example 2
Production of N- [2- (2-hydroxyethoxy) ethyl] -methyl-branched isostearoylamide (where R is a methyl-branched isoheptadecyl group) (Compound 2) In Example 1, methyl-branched isostearin instead of methyl stearate Production was carried out in the same manner as in Example 1 except that methyl acid was used, and the title compound was obtained.
[0026]
Properties: colorless paste
¹ H-NMR (CDCl ₃ , δ);
0.66-0.97 (m, 6H), 1.00-1.49 (m, 25H), 1.49-1.77 (m, 2H),
2.18 (t, J = 7.2Hz, 2H), 2.70-2.94 (m, 1H), 3.35-3.52 (m, 2H), 3.52-3.66 (m, 4H),
3.66-3.81 (m, 2H), 6.18-6.35 (m, 1H).
[0027]
Example 3
Production of N- [2- (2-hydroxyethoxy) ethyl] -2-heptylundecanamide (R is a 1-heptyldecyl group) (Compound 3) In Example 1, instead of methyl stearate, 2- Production was carried out in the same manner as in Example 1 except that methyl heptylundecanoate was used to obtain the title compound.
[0028]
Properties: colorless paste
¹ H-NMR (CDCl ₃ , δ);
0.70-1.00 (m, 6H), 1.05-1.48 (m, 26H), 1.48-1.71 (m, 2H),
1.90-2.10 (m, 1H), 2.25-2.64 (m, 1H), 3.37-3.67 (m, 6H), 3.67-3.87 (m, 2H),
5.96-6.14 (m, 1H).
[0029]
Test example 1
Compositions of the present invention consisting of 33% of compounds 1 to 3 prepared in Examples 1 to 3 and 67% of petrolatum were prepared and evaluated for skin conductance and rough skin by the following methods. Moreover, the same test evaluation was performed using the thing which consists only of petrolatum as a comparative product. The results are shown in Table 1.
[0030]
(Test method)
In the winter, 10 females aged 20 to 50 who have rough skin on the cheeks are subjects, and different compositions are applied to the left and right cheeks for 2 weeks. The next item was tested the next day after the application for 2 weeks was completed.
[0031]
(1) After washing the face with warm water having a skin conductance of 37 ° C. and then resting in a room at a temperature of 20 ° C. and a humidity of 40% for 20 minutes, the moisture content of the stratum corneum was measured with a skin conductance meter (manufactured by IBS). . The smaller the conductance value is, the rougher the skin is, and when the conductance value is 5 or less, the skin is severely rough. On the other hand, if this value is 20 or more, rough skin is hardly recognized.
[0032]
(2) Rough skin score Rough skin was observed with the naked eye and judged according to the following criteria. The score was shown as an average value.
[0033]
0: Does not recognize rough skin 1: Approves faint rough skin 2: Approves rough skin 3: Appears slightly rough skin 4: Accepts rough skin rough [0034]
[Table 1]

[0035]
Test example 2
The hair rinse of the composition shown in the following Table 2 was prepared, and the feel of the hair after the treatment with the hair rinse was evaluated by the following criteria by five professional panelists, and the average value of the five was shown. The results are also shown in Table 2.
[0036]
-2: Bad -1: Slightly bad 0: Neither +1: Slightly good +2: Good
[Table 2]

[0038]
As is clear from the results shown in Table 1 and Table 2, the composition containing the amide derivative (1) is excellent in the effect of increasing the moisture content of the stratum corneum and the effect of improving rough skin, and the feel of hair. It is excellent in improving the effect.
[0039]
【The invention's effect】
The moisturizing agent of the present invention can be produced efficiently and inexpensively, has excellent stability, essentially improves the water retention ability of the stratum corneum, and exhibits an improvement / prevention effect such as skin inflammation and rough skin, In addition, it has an effect of improving the feel of hair by protecting the hair. Furthermore, the solubility with respect to a base is good, and it is excellent in compounding property and mixing | blending stability.

Claims (2)

The following general formula (1)

[Wherein, R represents a linear or branched alkyl or alkenyl group having 5 to 23 carbon atoms. A humectant comprising an amide derivative represented by the formula: The humectant according to claim 1, which is used for external use on the skin.