JP3720067B2 - Novel pantoic acid derivatives and hair nourishing agents containing these as active ingredients - Google Patents
Novel pantoic acid derivatives and hair nourishing agents containing these as active ingredients Download PDFInfo
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- JP3720067B2 JP3720067B2 JP21327494A JP21327494A JP3720067B2 JP 3720067 B2 JP3720067 B2 JP 3720067B2 JP 21327494 A JP21327494 A JP 21327494A JP 21327494 A JP21327494 A JP 21327494A JP 3720067 B2 JP3720067 B2 JP 3720067B2
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- pentadecanoyl
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Description
【０００１】
【産業上の利用分野】
本発明は新規なパントイン酸誘導体及びそれらを含有する養毛料に関し、更に詳細にはパントイン酸のペンタデカン酸誘導体及び／又はそれらの塩と、これら化合物の１もしくは２以上を有効成分として含有させたことを特徴とする養毛料に関する。
【０００２】
【従来の技術】
一般的に脱毛症の詳細な発症メカニズムは未解明であるが、休止期毛の増加、毛包サイズの縮小、毛髪直径の減少等が指摘されている。又、頭皮の血管網の萎縮化や頭皮結合組織の変化も指摘されている。
従って現在使用されている養毛料には、血行促進剤、細胞賦活剤、皮脂腺抑制剤、殺菌抗炎症剤、保湿剤、栄養補給剤などが複数配合されている程度である。そして、単独で強力な養毛効果を示し、しかも安全性に優れた物質はいまだ存在しないというのが現状である。
【０００３】
【発明が解決しようとする課題】
本発明は単独の投与によっても育毛・脱毛予防効果に優れ、しかも安全性の高い養毛料を提供することを目的とするものである。
【０００４】
【課題を解決するための手段】
本発明者らは、鋭意研究を重ねた結果、パントイン酸誘導体に優れた毛母細胞成長促進効果のあることを見い出し、同時にこのパントイン酸化合物をペンタデカン酸誘導体にすることにより、頭皮のエネルギー代謝を活発化させるという効果を付加させ、今迄に例を見ない強力な育毛効果及び脱毛予防効果が又それらの塩には優れた界面活性作用のあることを確認し、更には安全性についても確認し、本発明の完成に至った。
【０００５】
本発明は、次の一般式（１）
【０００６】
【化２】
で表わされるパントイン酸誘導体もしくはこれらの塩に関し、かつ、これら化合物の１もしくは２以上を含有することを特徴とする養毛料に関するものである。
【０００８】
本発明の物質はまったくの新規の物質であるが、一般的には下記の合成法により、容易に合成することができる。
パントラクトン環を有する本発明化合物については塩基性物質の存在下、有機溶媒中でパントラクトンとペンタデカン酸ハライドを反応させ、濾過あるいは水洗により、副生する無機塩を除去した後、アルコールにより再結晶すると精製品が容易に得られる。
【０００９】
塩基性物質としては、トリアルキルアミン、ピリジンなどが一般的に使用され、好ましくはトリエチルアミンが使用される。反応溶媒としては、無極性溶媒が使用され、一般的にはトルエン、ベンゼン、キシレン、クロロホルム等が使用されるが、好ましくはトルエンが使用される。パントラクトンはＤ体、Ｌ体、ＤＬ体のいずれもが使用できる。ペンタデカン酸ハライドとしては塩化物、臭化物が使用でき、好ましくは塩化物である。
【００１０】
パントラクトン環が開いたパントイン酸を含む本発明化合物は、パントイン酸の塩に塩基性物質の存在下、ペンタデカン酸ハライドを反応させることによって得られる。
【００１１】
モノペンタデカノイルあるいはジペンタデカノイル誘導体に関しては、水溶媒中、水酸化アルカリの存在下、反応を行い、反応物を減圧乾固した後、有機溶媒で抽出、抽出物を減圧乾固後、アルコールで再結晶すると精製品が得られる。
酸無水物誘導体に関しては、無極性溶媒中塩基性物質の存在下ペンタデカン酸ハライドと反応させることによって得られる。塩基としてはピリジンが好ましい。反応液を水洗後、乾燥、減圧乾固、再結晶すると目的物である酸無水物が得られる。
パントイン酸アミド誘導体、パントイン酸エステル誘導体に関しても、上述の合成法と類似の既知の方法により合成することができる。
【００１２】
上記方法により合成した本発明化合物の代表的なものについて以下に例示するが、本発明の請求範囲がこれらによって限定されるものではない。
１． ｎ−ペンタデカノイル−ＤＬ−パントラクトン
２． ｎ−ペンタデカノイル−Ｄ−パントラクトン
３． ｎ−ペンタデカノイル−Ｌ−パントラクトン
４． γ−ｎ−ペンタデカノイル−ＤＬ−パントイン酸ナトリウム
５． γ−ｎ−ペンタデカノイル−Ｄ−パントイン酸ナトリウム
６． γ−ｎ−ペンタデカノイル−Ｌ−パントイン酸ナトリウム
７． ジ−ｎ−ペンタデカノイル−ＤＬ−パントイン酸ナトリウム
８． ジ−ｎ−ペンタデカノイル−Ｄ−パントイン酸ナトリウム
９． ジ−ｎ−ペンタデカノイル−Ｌ−パントイン酸ナトリウム
10． ジ−ｎ−ペンタデカノイル−ＤＬ−パントイン酸ペンタデカン酸無水物
11． ジ−ｎ−ペンタデカノイル−Ｄ−パントイン酸ペンタデカン酸無水物
12． ジ−ｎ−ペンタデカノイル−Ｌ−パントイン酸ペンタデカン酸無水物
13． Ｎ−ブチル−ジ−ｎ−ペンタデカノイル−ＤＬ−パントイン酸アミド
14． Ｎ−ブチル−ジ−ｎ−ペンタデカノイル−Ｄ−パントイン酸アミド
15． Ｎ−ブチル−ジ−ｎ−ペンタデカノイル−Ｌ−パントイン酸アミド
16． ジ−ｎ−ペンタデカノイル−ＤＬ−パントイン酸エチル
17． ジ−ｎ−ペンタデカノイル−Ｄ−パントイン酸エチル
18． ジ−ｎ−ペンタデカノイル−Ｌ−パントイン酸エチル
19． ジ−ｎ−ペンタデカノイル−ＤＬ−パントイン酸メチル
20． ジ−ｎ−ペンタデカノイル−Ｄ−パントイン酸メチル
21． ジ−ｎ−ペンタデカノイル−Ｌ−パントイン酸メチル
22． ジ−ｎ−ペンタデカノイル−ＤＬ−パントイン酸カリウム
23． ジ−ｎ−ペンタデカノイル−Ｄ−パントイン酸カリウム
24． ジ−ｎ−ペンタデカノイル−Ｌ−パントイン酸カリウム
25． ジ−ｎ−ペンタデカノイル−ＤＬ−パントイン酸２−エチルヘキシル
26． ジ−ｎ−ペンタデカノイル−Ｄ−パントイン酸２−エチルヘキシル
27． ジ−ｎ−ペンタデカノイル−Ｌ−パントイン酸２−エチルヘキシル
【００１３】
本発明のパントイン酸誘導体の養毛料中への配合量は総量を基準として０．００１〜１０．０ｗｔ％であれば良く、より好ましくは０．１〜５．０ｗｔ％である。本発明の養毛料で使用される他の原料成分としては、通常、化粧料に適用される炭化水素類、ロウ類、油脂類、エステル類、高級脂肪酸類、高級アルコール類、界面活性剤、保湿剤、香料、色素、防腐剤、抗酸化剤、紫外線防禦剤、ｐＨ調整剤および本発明の目的に合った薬効成分などが適宜選択され、調整される。更に公知公用の育毛、養毛成分と併用することもできる。また本発明の養毛料は種々の剤型で使用でき、それには例えばヘアトニック、ヘアローション、ヘアクリーム、ポマード、ヘアコンディショナー、シャンプー、リンス、ヘアジェル、ヘアミスト、ヘアフォーム等が挙げられるが、特にパントイン酸誘導体の塩に関してはその優れた界面活性作用によりシャンプーが好ましい。
次に本発明に係る化合物について実施された雄性ラットを用いた急性毒性試験の結果を表１に示す。
【００１４】
【表１】
表１からも明らかな様に、本発明に係る化合物はいずれもＬＤ50値が２ｇ以上と非常に安全性が高い化合物であることが判明した。
次に本発明に係る化合物についての実施例を挙げる。
【００１６】
【実施例】
【００１７】
〔実施例１〕 ｎ−ペンタデカノイル−ＤＬ−パントラクトン
ＤＬ−パントラクトン６．５０ｇにトルエン６５ｍｌ、トリエチルアミン６．１０ｇを加え、室温にて溶解し、−５℃迄冷却し、ｎ−ペンタデカノイルクロライド１５．６０ｇをトルエン６５ｍｌに溶解したものを冷却下滴下した。１晩放置後、不溶物を濾過し、濾液を濃縮乾固した。
トルエンを加え、濃縮乾固するという操作を何度か繰り返した後、メタノールより再結晶し、白色結晶１６．３０ｇを得た。収率７１．７％。
下記データにより、上記目的化合物であることを確認した。
〔実施例２〕 ｎ−ペンタデカノイル−Ｄ−パントラクトン
Ｄ−パントラクトン１０．３２ｇにトルエン１００ｍｌ、トリエチルアミン９．６４ｇを加え、室温にて溶解し、−５℃迄冷却し、ｎ−ペンタデカノイルクロライド２４．８０ｇをトルエン８０ｍｌに溶解したものを冷却下滴下した。１晩放置後、不溶物を濾過し、濾液を濃縮乾固した。トルエンを加え、濃縮乾固するという操作を何度か繰り返した後、メタノールより再結し、白色結晶２５．２０ｇを得た。収率６５．２％。
下記データにより、上記目的化合物であることを確認した。
〔実施例３〕 ジ−ｎ−ペンタデカノイル−ＤＬ−パントイン酸ナトリウム
ＤＬ−パントイン酸ナトリウム８．４５ｇを２Ｎ ＮａＯＨ ５０ｍｌに溶解した後、−１０℃迄冷却し、ｎ−ペンタデカノイルクロライド２８．６０ｇをエーテル１００ｍｌに溶解したものを冷却下滴下した。１晩放置後、濃縮乾固し、トルエン５００ｍｌを加え４０℃に加温して不溶物を濾過し濾液を濃縮乾固した。更にエタノール５００ｍｌを加え不溶物を除去した濾液を冷却晶出後、濾過した。その結晶をメタノールより再結し、白色結晶１２．２０ｇを得た。収率３９．５％。
下記データにより、上記目的化合物であることを確認した。
〔実施例４〕 ジ−ｎ−ペンタデカノイル−Ｄ−パントイン酸ナトリウム
Ｄ−パントイン酸ナトリウム４．６０ｇを２Ｎ ＮａＯＨ ２７．２ｍｌに溶解後、−１０℃迄冷却し、ｎ−ペンタデカノイルクロライド１５．６０ｇをエーテル６０ｍｌに溶解したものを冷却下滴下した。１晩放置後、濃縮乾固し、トルエン２５０ｍｌを加え４０℃に加温して不溶物を濾過し、濾液を濃縮乾固した。更にエタノール２５０ｍｌを加え不溶物を除去した濾液を冷却晶出後、濾過した。その結晶をメタノールより再結し、白色結晶４．５０ｇを得た。収率２６．８％。
下記データにより上記目的化合物であることを確認した。
〔実施例５〕 ジ−ｎ−ペンタデカノイル−ＤＬ−パントイン酸ペンタデカン酸無水物
ＤＬ−パントイン酸ナトリウム３．４０ｇをトルエン１００ｍｌに分散、氷冷下、０〜５℃でｎ−ペンタデカン酸クロライド１５．７０ｇ、ピリジン４．７０ｇを滴下した。同温度で１時間反応させた後、５０〜６０℃で５時間反応した。水洗後、希塩酸３０ｍｌで洗浄、飽和食塩水で水洗し、ＭｇＳＯ4で乾燥した後、減圧乾固し、微黄色の結晶１４．９６ｇを得た。収率９０．０％。
下記データにより、上記目的化合物であることを確認した。
〔実施例６〕 Ｎ−ブチル−ジ−ｎ−ペンタデカノイル−ＤＬ−パントイン酸アミド
Ｎ−ブチル−ＤＬ−パントイン酸アミド１０．２０ｇにトルエン１００ｍｌ、トリエチルアミン１０．３０ｇを加え、室温にて溶解し、０℃迄氷冷し、ｎ−ペンタデカノイルクロライド２６．６０ｇをトルエン８０ｍｌに溶解したものを０〜５℃で滴下した。１晩放置後、不溶物を濾過し、濾液を濃縮乾固し、メタノールより２度再結し、白色結晶２７．７０ｇを得た。収率８５．０％。
下記データにより上記目的化合物であることを確認した。
次に本発明に係る化合物の効果を確認した試験例について述べる。
【００２４】
〔試験例１〕 モルモットによる毛成長促進作用
モルモットの背部全体の毛を剃毛し、左右３分画の片側に被検物質を３０日間連続塗布（２ｍｌ／日）し、他側を無処理部とした。３０日間被検物質塗布後、各動物の処置部及び無処置部より各々５０本を抜毛し、その長さをノギスを用いて測定し、長いものから順に１０本を選んで測定値とした。動物は１群３匹を使用した。
表２に結果を示す。
【００２５】
【表２】
表２に示す様に本発明に係る化合物はすべて成長期状態の毛を更に活性化させる作用が認められた。
【００２７】
〔試験例２〕 ウザギによる休止期毛活性化作用
ウサギの毛周期は約２ヶ月ごとに背部全体が成長期と休止期を繰り返す。毛周期が成長期から休止期へ移行した直後のウサギを使用し、背部全体を剪毛し剪毛部を等間隔に８分画した。各分画中央に被検物質０．２ｍｌ／日を繰り返し塗布し、毛周期が休止期から成長期に変換するまでの期間を尺度として育毛効果を評価した。結果を表３に示す。
【００２８】
【表３】
以上の様に本発明に係る化合物には休止期毛を活性化させる作用の有ることが判明した。
【００３０】
次に本発明に係る養毛料の処方例を示す。
【００３１】
【発明の効果】
本発明では新規なパントイン酸誘導体もしくはこれらの塩を用いることによって安全性に優れ、育毛効果、脱毛予防効果に優れた養毛料を提供することができた。[0001]
[Industrial application fields]
The present invention relates to a novel pantoic acid derivative and a hair nourishing agent containing them, and more specifically, contains a pentadecanoic acid derivative of pantoic acid and / or a salt thereof and one or more of these compounds as active ingredients. It is related with the hair nourishing agent characterized by.
[0002]
[Prior art]
In general, the detailed onset mechanism of alopecia has not been elucidated, but it has been pointed out that an increase in resting hair, a reduction in hair follicle size, a decrease in hair diameter, and the like. In addition, atrophy of the vascular network of the scalp and changes in the scalp connective tissue have been pointed out.
Therefore, the currently used hair nourishing agent is only to the extent that a plurality of blood circulation promoters, cell activators, sebaceous gland inhibitors, bactericidal anti-inflammatory agents, moisturizers, nutritional supplements and the like are blended. And the present condition is that the substance which shows a strong hair-restoration effect independently and was excellent in safety does not exist yet.
[0003]
[Problems to be solved by the invention]
It is an object of the present invention to provide a hair restoration that is excellent in hair growth and hair removal prevention effects and that is highly safe even when administered alone.
[0004]
[Means for Solving the Problems]
As a result of extensive research, the present inventors have found that a pantoic acid derivative has an excellent hair matrix cell growth promoting effect, and at the same time, by making this pantoic acid compound a pentadecanoic acid derivative, the energy metabolism of the scalp is reduced. Add the effect of activating, confirming the strong hair-growth effect and hair loss prevention effect that has never been seen before, and that their salts have excellent surface-active action, and also confirm safety Thus, the present invention has been completed.
[0005]
The present invention relates to the following general formula (1)
[0006]
[Chemical formula 2]
And to a hair nourishing agent characterized by containing one or more of these compounds.
[0008]
Although the substance of the present invention is a completely new substance, it can generally be easily synthesized by the following synthesis method.
The compound of the present invention having a pantolactone ring is reacted with pantolactone and pentadecanoic acid halide in an organic solvent in the presence of a basic substance, removed by-product inorganic salts by filtration or water washing, and then recrystallized with alcohol. Then, the purified product can be easily obtained.
[0009]
As the basic substance, trialkylamine, pyridine and the like are generally used, and triethylamine is preferably used. As the reaction solvent, a nonpolar solvent is used, and generally toluene, benzene, xylene, chloroform or the like is used, but preferably toluene is used. Any of D-form, L-form and DL-form can be used for pantolactone. As the pentadecanoic acid halide, chloride and bromide can be used, and chloride is preferred.
[0010]
The compound of the present invention containing pantoic acid having an open pantolactone ring can be obtained by reacting a salt of pantoic acid with a pentadecanoic acid halide in the presence of a basic substance.
[0011]
For monopentadecanoyl or dipentadecanoyl derivatives, the reaction was performed in an aqueous solvent in the presence of alkali hydroxide, the reaction product was dried under reduced pressure, extracted with an organic solvent, the extract was dried under reduced pressure, Recrystallized with alcohol to obtain a purified product.
The acid anhydride derivative can be obtained by reacting with a pentadecanoic acid halide in the presence of a basic substance in a nonpolar solvent. Pyridine is preferred as the base. The reaction solution is washed with water, dried, dried under reduced pressure, and recrystallized to obtain the target acid anhydride.
The pantoic acid amide derivative and the pantoic acid ester derivative can also be synthesized by a known method similar to the above synthetic method.
[0012]
Although the typical thing of this invention compound synthesize | combined by the said method is illustrated below, the claim of this invention is not limited by these.
1. n-pentadecanoyl-DL-pantolactone2. 2. n-pentadecanoyl-D-pantolactone n-pentadecanoyl-L-pantolactone4. 4. γ-n-pentadecanoyl-DL-sodium pantoate 5. γ-n-pentadecanoyl-D-pantoic acid sodium salt6. γ-n-pentadecanoyl-L-pantoic acid sodium salt7. Di-n-pentadecanoyl-DL-sodium pantoate 8 Di-n-pentadecanoyl-D-pantoic acid sodium salt9. Di-n-pentadecanoyl-L-pantoic acid sodium salt
Ten. Di-n-pentadecanoyl-DL-pantoic acid pentadecanoic anhydride
11． Di-n-pentadecanoyl-D-pantoic acid pentadecanoic anhydride
12． Di-n-pentadecanoyl-L-pantoic acid pentadecanoic anhydride
13. N-butyl-di-n-pentadecanoyl-DL-pantoic acid amide
14. N-butyl-di-n-pentadecanoyl-D-pantoic acid amide
15． N-butyl-di-n-pentadecanoyl-L-pantoic acid amide
16． Di-n-pentadecanoyl-DL-ethyl pantoate
17． Di-n-pentadecanoyl-D-ethyl pantoate
18． Di-n-pentadecanoyl-L-ethyl pantoate
19. Di-n-pentadecanoyl-DL-methyl pantoynate
20． Di-n-pentadecanoyl-D-methyl pantoate
twenty one. Di-n-pentadecanoyl-L-pantoic acid methyl ester
twenty two. Di-n-pentadecanoyl-DL-potassium pantoate
twenty three. Di-n-pentadecanoyl-D-potanoic acid potassium salt
twenty four. Di-n-pentadecanoyl-L-pantoic acid potassium salt
twenty five. Di-n-pentadecanoyl-DL-pantoic acid 2-ethylhexyl
26. Di-n-pentadecanoyl-D-pantoic acid 2-ethylhexyl
27. Di-n-pentadecanoyl-L-pantoic acid 2-ethylhexyl
The blending amount of the pantoic acid derivative of the present invention in the hair nourishing agent may be 0.001 to 10.0 wt%, more preferably 0.1 to 5.0 wt%, based on the total amount. Other raw material components used in the hair nourishing agent of the present invention are usually hydrocarbons, waxes, fats and oils, esters, higher fatty acids, higher alcohols, surfactants, moisturizing agents applied to cosmetics. Agents, fragrances, pigments, preservatives, antioxidants, ultraviolet antifungal agents, pH adjusters and medicinal components that meet the purpose of the present invention are appropriately selected and adjusted. Furthermore, it can also be used in combination with publicly known and used hair growth and hair nourishing ingredients. The hair nourishing agent of the present invention can be used in various dosage forms, and examples thereof include hair tonics, hair lotions, hair creams, pomades, hair conditioners, shampoos, rinses, hair gels, hair mists, hair foams, etc. With regard to the salt of the acid derivative, shampoo is preferred due to its excellent surface activity.
Next, Table 1 shows the results of an acute toxicity test using male rats carried out on the compounds according to the present invention.
[0014]
[Table 1]
As is clear from Table 1, it was found that all the compounds according to the present invention are very safe compounds having an LD 50 value of 2 g or more.
Next, the Example about the compound based on this invention is given.
[0016]
【Example】
[0017]
Example 1 n-pentadecanoyl-DL-pantolactone To 6.50 g of DL-pantolactone, 65 ml of toluene and 6.10 g of triethylamine were added, dissolved at room temperature, cooled to −5 ° C., and n-pentadecane. A solution prepared by dissolving 15.60 g of noyl chloride in 65 ml of toluene was added dropwise under cooling. After standing overnight, the insoluble material was filtered off, and the filtrate was concentrated to dryness.
The operation of adding toluene and concentrating to dryness was repeated several times, and then recrystallized from methanol to obtain 16.30 g of white crystals. Yield 71.7%.
Based on the following data, it was confirmed to be the target compound.
[Example 2] 100 ml of toluene and 9.64 g of triethylamine were added to 10.32 g of n-pentadecanoyl-D-pantolactone D-pantolactone, dissolved at room temperature, cooled to -5 ° C, and n-pentadecane. What melt | dissolved 24.80g of noyl chloride in 80 ml of toluene was dripped under cooling. After standing overnight, the insoluble material was filtered off, and the filtrate was concentrated to dryness. The operation of adding toluene and concentrating to dryness was repeated several times, and then recrystallized from methanol to obtain 25.20 g of white crystals. Yield 65.2%.
Based on the following data, it was confirmed to be the target compound.
[Example 3] Di-n-pentadecanoyl-DL-sodium pantoic acid 8.45 g of DL-sodium pantoic acid was dissolved in 50 ml of 2N NaOH, cooled to -10 ° C, and n-pentadecanoyl chloride 28. A solution obtained by dissolving 60 g in 100 ml of ether was added dropwise under cooling. After standing overnight, the mixture was concentrated to dryness, 500 ml of toluene was added, and the mixture was heated to 40 ° C., insoluble matters were filtered, and the filtrate was concentrated to dryness. Further, 500 ml of ethanol was added to remove insoluble matters, and the filtrate was cooled and crystallized and then filtered. The crystals were recrystallized from methanol to obtain 12.20 g of white crystals. Yield 39.5%.
Based on the following data, it was confirmed to be the target compound.
Example 4 Di-n-pentadecanoyl-D-sodium pantoate 4.60 g of sodium D-pantoate was dissolved in 27.2 ml of 2N NaOH, cooled to −10 ° C., and n-pentadecanoyl chloride 15 A solution obtained by dissolving 60 g in 60 ml of ether was added dropwise under cooling. After standing overnight, the mixture was concentrated to dryness, 250 ml of toluene was added, the mixture was heated to 40 ° C., insoluble matters were filtered, and the filtrate was concentrated to dryness. Further, 250 ml of ethanol was added to remove insoluble matters, and the filtrate was cooled and crystallized and then filtered. The crystals were recrystallized from methanol to obtain 4.50 g of white crystals. Yield 26.8%.
It was confirmed by the following data that the compound was the target compound.
[Example 5] Di-n-pentadecanoyl-DL-pantoic acid pentadecanoic acid anhydride 3.40 g of DL-pantoic acid sodium salt was dispersed in 100 ml of toluene and n-pentadecanoic acid chloride 15 at 0 to 5 ° C under ice cooling. .70 g and 4.70 g of pyridine were added dropwise. After making it react at the same temperature for 1 hour, it reacted at 50-60 degreeC for 5 hours. After washing with water, washing with 30 ml of diluted hydrochloric acid, washing with saturated brine, drying over MgSO 4 , and drying under reduced pressure gave 14.96 g of pale yellow crystals. Yield 90.0%.
Based on the following data, it was confirmed to be the target compound.
Example 6 N-butyl-di-n-pentadecanoyl-DL-pantoic acid amide 10.20 g of N-butyl-DL-pantoic acid amide was added 100 ml of toluene and 10.30 g of triethylamine and dissolved at room temperature. The mixture was ice-cooled to 0 ° C., and 26.60 g of n-pentadecanoyl chloride dissolved in 80 ml of toluene was added dropwise at 0 to 5 ° C. After standing overnight, the insoluble matter was filtered off, and the filtrate was concentrated to dryness and recrystallized twice from methanol to obtain 27.70 g of white crystals. Yield 85.0%.
It was confirmed by the following data that the compound was the target compound.
Next, test examples for confirming the effect of the compound according to the present invention will be described.
[0024]
[Test Example 1] Promotion of hair growth by guinea pigs The entire back of the guinea pig was shaved, and the test substance was continuously applied to one side of the left and right three fractions (2 ml / day) for 30 days, while the other side was untreated. It was. After application of the test substance for 30 days, 50 hairs were removed from the treated and untreated parts of each animal, the length was measured using calipers, and 10 were selected in order from the longest to obtain measured values. Three animals were used per group.
Table 2 shows the results.
[0025]
[Table 2]
As shown in Table 2, all the compounds according to the present invention were found to have the effect of further activating the hair in the growth phase.
[0027]
[Test Example 2] Resting hair activation effect by rabbits The rabbit's hair cycle repeats the growing and resting periods for the entire back every approximately two months. A rabbit immediately after the hair cycle shifted from the growth phase to the resting phase was used, and the entire back portion was shaved and the shaved portions were divided into 8 equal intervals. The test substance 0.2 ml / day was repeatedly applied to the center of each fraction, and the hair growth effect was evaluated using the period from the hair cycle to the transition to the growth phase as a scale. The results are shown in Table 3.
[0028]
[Table 3]
As described above, it was found that the compound according to the present invention has an action of activating telogen hair.
[0030]
Next, a prescription example of the hair nourishing agent according to the present invention will be shown.
[0031]
【The invention's effect】
In the present invention, by using a novel pantoic acid derivative or a salt thereof, it is possible to provide a hair nourishing agent that is excellent in safety, excellent in hair-growth effect and hair-loss preventing effect.
Claims (2)
Ｒ2、Ｒ3は水素又はペンタデカノイル基を示すが、共に水素を示すことはなく；Ｒ0、Ｒ3が共に水素である場合は、分子内エステルを形成することがある。）
で表わされるｎ−ペンタデカノイル基を１又は２個有するパントイン酸誘導体もしくはこれらの塩。The following general formula (1)
R 2 and R 3 each represent hydrogen or a pentadecanoyl group, but both do not represent hydrogen; when both R 0 and R 3 are hydrogen, an intramolecular ester may be formed. )
A pantoic acid derivative having one or two n-pentadecanoyl groups represented by the formula:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21327494A JP3720067B2 (en) | 1994-08-16 | 1994-08-16 | Novel pantoic acid derivatives and hair nourishing agents containing these as active ingredients |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21327494A JP3720067B2 (en) | 1994-08-16 | 1994-08-16 | Novel pantoic acid derivatives and hair nourishing agents containing these as active ingredients |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0859544A JPH0859544A (en) | 1996-03-05 |
| JP3720067B2 true JP3720067B2 (en) | 2005-11-24 |
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| JP21327494A Expired - Fee Related JP3720067B2 (en) | 1994-08-16 | 1994-08-16 | Novel pantoic acid derivatives and hair nourishing agents containing these as active ingredients |
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| JP (1) | JP3720067B2 (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH11292753A (en) * | 1998-04-14 | 1999-10-26 | Dowa Yakushou Kk | Agent for external use for head skin |
| JP5457699B2 (en) * | 2009-03-26 | 2014-04-02 | ミヨシ油脂株式会社 | Nonionic surfactant |
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