JPS63227514A - Dermatic drug for external application - Google Patents
Dermatic drug for external applicationInfo
- Publication number
- JPS63227514A JPS63227514A JP6071987A JP6071987A JPS63227514A JP S63227514 A JPS63227514 A JP S63227514A JP 6071987 A JP6071987 A JP 6071987A JP 6071987 A JP6071987 A JP 6071987A JP S63227514 A JPS63227514 A JP S63227514A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- skin
- formula
- drug
- branched
- 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.)
- Granted
Links
- 239000003814 drug Substances 0.000 title abstract 4
- 229940079593 drug Drugs 0.000 title abstract 4
- 150000001408 amides Chemical class 0.000 claims abstract description 13
- 239000004094 surface-active agent Substances 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims description 17
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 11
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 abstract description 9
- 235000014113 dietary fatty acids Nutrition 0.000 abstract description 8
- 239000000194 fatty acid Substances 0.000 abstract description 8
- 229930195729 fatty acid Natural products 0.000 abstract description 8
- 150000004665 fatty acids Chemical class 0.000 abstract description 4
- 150000002430 hydrocarbons Chemical group 0.000 abstract description 4
- 239000002736 nonionic surfactant Substances 0.000 abstract description 4
- 239000003795 chemical substances by application Substances 0.000 abstract description 2
- 125000004185 ester group Chemical group 0.000 abstract description 2
- 230000003301 hydrolyzing effect Effects 0.000 abstract description 2
- 239000004711 α-olefin Substances 0.000 abstract description 2
- 239000004215 Carbon black (E152) Substances 0.000 abstract 1
- 239000004593 Epoxy Substances 0.000 abstract 1
- 206010040849 Skin fissures Diseases 0.000 abstract 1
- 229930195733 hydrocarbon Natural products 0.000 abstract 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 1
- 210000003491 skin Anatomy 0.000 description 30
- -1 ethanolamine compound Chemical class 0.000 description 9
- 239000002537 cosmetic Substances 0.000 description 8
- 210000000434 stratum corneum Anatomy 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 206010040880 Skin irritation Diseases 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000003020 moisturizing effect Effects 0.000 description 3
- 230000036556 skin irritation Effects 0.000 description 3
- 231100000475 skin irritation Toxicity 0.000 description 3
- 206010013786 Dry skin Diseases 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- GPLRAVKSCUXZTP-UHFFFAOYSA-N diglycerol Chemical compound OCC(O)COCC(O)CO GPLRAVKSCUXZTP-UHFFFAOYSA-N 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- RZJRJXONCZWCBN-UHFFFAOYSA-N octadecane Chemical compound CCCCCCCCCCCCCCCCCC RZJRJXONCZWCBN-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 235000015961 tonic Nutrition 0.000 description 2
- 230000001256 tonic effect Effects 0.000 description 2
- 229960000716 tonics Drugs 0.000 description 2
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 2
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- JRLTTZUODKEYDH-UHFFFAOYSA-N 8-methylquinoline Chemical group C1=CN=C2C(C)=CC=CC2=C1 JRLTTZUODKEYDH-UHFFFAOYSA-N 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 206010039792 Seborrhoea Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000002280 amphoteric surfactant Substances 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000003908 antipruritic agent Substances 0.000 description 1
- 239000003212 astringent agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 210000000736 corneocyte Anatomy 0.000 description 1
- 239000008271 cosmetic emulsion Substances 0.000 description 1
- 239000008406 cosmetic ingredient Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 230000003779 hair growth Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229940125697 hormonal agent Drugs 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 229910001410 inorganic ion Inorganic materials 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 229940038384 octadecane Drugs 0.000 description 1
- HPEUJPJOZXNMSJ-UHFFFAOYSA-N octadecanoic acid methyl ester Natural products CCCCCCCCCCCCCCCCCC(=O)OC HPEUJPJOZXNMSJ-UHFFFAOYSA-N 0.000 description 1
- 230000037312 oily skin Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/02—Acyclic radicals, not substituted by cyclic structures
- C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/68—Sphingolipids, e.g. ceramides, cerebrosides, gangliosides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/007—Preparations for dry skin
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明はアミド誘導体を含有する皮膚外用剤、更に詳し
くは、角層の水分保持力を高め、肌あれを改善すること
ができる皮膚外用剤に関する。[Detailed Description of the Invention] [Industrial Application Field] The present invention provides an external skin preparation containing an amide derivative, more specifically, a skin external preparation that can improve the moisture retention of the stratum corneum and improve skin roughness. Regarding.
従来、肌にうるおいを与え、肌を柔軟にするには、角質
層の水分が重要であることが知られている。そして、当
該水、分の保持は、角質層に含まれている水溶性成分、
すなわち遊離アミノ酸、有機酸、尿素又は無機イオンに
よるものであるとされ、これらの物質は単独でるるいは
組合せて薬用皮膚外用剤おるいは化粧料に配合して、肌
あれの改善又は予防の目的で使用されている。It has been known that moisture in the stratum corneum is important for moisturizing the skin and making it soft. The retention of water is caused by water-soluble components contained in the stratum corneum,
In other words, it is said to be caused by free amino acids, organic acids, urea, or inorganic ions, and these substances can be used alone or in combination in medicated skin preparations or cosmetics for the purpose of improving or preventing rough skin. used in
また、これとは別に水と親和性が高い多くの保湿性物質
が開発され、同様の目的で使用されている。In addition, many other moisturizing substances that have a high affinity for water have been developed and are used for similar purposes.
しかしながら、これらの保湿性物質は、皮膚に適用した
場合、その作用は、皮膚角質層上にあって水分を角質に
供給するというもので、しかもその効果は一時的であり
、根本的に角質層の水分保持能力を改善し、肌あれを本
質的に予防わるいは治癒させるというものではなかった
。However, when these moisturizing substances are applied to the skin, their action is to supply moisture to the stratum corneum on the skin, but their effect is temporary and fundamentally affects the stratum corneum. It did not essentially prevent or cure rough skin by improving the water retention ability of the skin.
斯かる実情において、本発明者らは上記問題点を解決す
べく鋭意研究を行なったところ、今回本発明者らによっ
て初めて合成された次の一般式（Ｉ）％式％
（式中、Ｒ１は炭素数８〜２４の直鎖若しくは分岐鎖の
飽和若しくは不飽和の炭化水素基、Ｒ２は炭素数９〜２
５の直鎖若しくは分岐鎖の飽和若しくは不飽和の炭化水
素基金示す）
で表わされるアミド誘導体が角質層の水分保持能力を根
本的に改善する効果を奏すること、そしてこのアミド誘
導体に界面活性剤を併用するとその効果を更に増大でき
ることを見出し、本発明を完成した。Under such circumstances, the present inventors conducted intensive research to solve the above problems, and found that the following general formula (I)% formula% (wherein R1 is synthesized for the first time by the present inventors) A straight chain or branched chain saturated or unsaturated hydrocarbon group having 8 to 24 carbon atoms, R2 is a carbon number 9 to 2
The amide derivative represented by the linear or branched saturated or unsaturated hydrocarbon group (5) has the effect of fundamentally improving the water retention ability of the stratum corneum; The present invention was completed based on the discovery that the effect can be further enhanced when used in combination.
すなわち本発明は、前記式（Ｉ）で表わされるアミド誘
導体を含有する皮膚外用剤、並びに前記式（Ｉ）で表わ
されるアミド誘導体及び界面活性剤を含有する皮膚外用
剤を提供するものでるる。That is, the present invention provides an external skin preparation containing the amide derivative represented by the formula (I), and an external skin preparation containing the amide derivative represented by the formula (I) and a surfactant.
本発明で使用される式（Ｉ）で表わされるアミド誘導体
は、例えば次の反応式に従って、α−オレフインエ？キ
シ化合物とエタノールアミントノ反応によって得られる
化合物（Ｉｆ） （Ｂｕｌｌｅｔｉｎ ｏｆ ｔｈｅＪ
ａｐａｎ Ｐｅｔｒｏｌｅｕｍ Ｉｎ５ｔｉｔｕｔｅ
、 ７ ＊ ２５ （Ｉ９６５） ）、を脂肪酸クロラ
イドでアシル化して化合物（ＩＩ［）となし、次いでこ
れのエステル基を選択的に加水分解することによって製
造することができる。The amide derivative represented by formula (I) used in the present invention can be prepared, for example, from α-olefin ether according to the following reaction formula. Compound (If) obtained by reaction of an ethanolamine compound and an ethanolamine compound (Bulletin of theJ
apan Petroleum In5 position
, 7*25 (I965)) with a fatty acid chloride to form compound (II[), and then selectively hydrolyzing the ester group thereof.
Ｔ？１
ＣＨ２ＣＨ２０Ｈ
（ｎ）
ＣＨ，ＣＨ，０ＣＯＲ”
（ＩＩＩ）
（式中、Ｒ′及びＲ２は前記と同じ）
更にまた、上記（ＩＩ）式の化合物に脂肪酸エステルを
、塩基性触媒の存在下、副生ずるアルコールを留去しな
がら反応させることによシ、−挙にアミド誘導体（Ｉ）
を得ることもできる。T? 1 CH2CH20H (n) CH,CH,0COR'' (III) (In the formula, R' and R2 are the same as above) Furthermore, a fatty acid ester is added to the compound of formula (II) above in the presence of a basic catalyst. By reacting while distilling off the resulting alcohol, the amide derivative (I) can be obtained.
You can also get
アミド誘導体（Ｉ）の本発明皮膚外用剤への配合量は、
特に制限されないが、通常乳化型の皮膚外用剤の場合に
は全組成の０．００１〜５０重量％（以下単に％で示す
）、特に０．１〜２０％が好ましく、またスクワレン等
の液状炭化水素を基剤とする油性の皮膚外用剤の場合に
は１〜５０％、特に５〜２５％が好ましい。The amount of amide derivative (I) to be incorporated into the skin external preparation of the present invention is as follows:
Although not particularly limited, in the case of emulsion-type skin preparations for external use, it is preferably 0.001 to 50% by weight (hereinafter simply expressed as %), particularly 0.1 to 20%, of the total composition; In the case of hydrogen-based oily skin preparations for external use, the content is preferably 1 to 50%, particularly 5 to 25%.
界面活性剤としては、非イオン界面活性剤、陰イオン界
面活性剤、両性界面活性剤の何れをも使用できるが、就
中特に非イオン界面活性剤が好適でおる。As the surfactant, any of nonionic surfactants, anionic surfactants, and amphoteric surfactants can be used, but nonionic surfactants are particularly preferred.
非イオン界面活性剤としては、例えば？リオキシエチレ
ンアルキルエーテル、択すオキシエチレンアルキルフェ
ニルエーテル Ｚ ＩＪオキシエチレン脂肪酸エステル
、ソルビタン脂肪酸エステル、？リオキシエチレンソル
ビタン脂肪酸エステル、脂肪酸モノグリセライド、グリ
セリルエーテル等が挙げられる。その中でも、次の一般
式（ＩＶ）Ｒ０ＣＨｔ ＣＨ−ＣＨｚＯＨ（Ｒ’）【
Ｈ
（式中、Ｒは炭素数８〜２４のアルキル基を示す）で表
わされるグリセリルエーテル、就中Ｒが次式％式％（）
（式中、ｐは４〜１０の整数、ｑは５〜１１の整数を示
し、ｐ＋ｑ＝１１〜１７でｐ＝７、ｑ＝＝８を頂点とす
る分布を有する）
で表わされるものが特に好ましい。What are some examples of nonionic surfactants? Lyoxyethylene alkyl ether, selected oxyethylene alkyl phenyl ether Z IJ oxyethylene fatty acid ester, sorbitan fatty acid ester, ? Examples include lyoxyethylene sorbitan fatty acid ester, fatty acid monoglyceride, and glyceryl ether. Among them, glyceryl ether represented by the following general formula (IV) R0CHt CH-CHzOH (R') [H (wherein, R represents an alkyl group having 8 to 24 carbon atoms), especially when R is represented by the following formula % Represented by the formula %() (in the formula, p is an integer of 4 to 10, q is an integer of 5 to 11, and has a distribution with p+q=11 to 17, with p=7 and q==8 as the apex) Particularly preferred are those in which
界面活性剤の配合量は、全組成の０．０１〜２０％、特
に０．１〜５％が好ましい。The blending amount of the surfactant is preferably 0.01 to 20%, particularly 0.1 to 5% of the total composition.
本発明の皮膚外用剤は、その使用形態において、薬用皮
膚外用剤と化粧料に大別される。The skin external preparations of the present invention are broadly classified into medicated skin external preparations and cosmetics in terms of their usage forms.
薬用皮膚外用剤としては、例えば薬効成分を含有する各
種軟膏剤を挙げることができる。軟膏剤としでは、油性
基剤をベースとするもの、油／水、水／油型の乳化系基
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。Examples of medicated skin external preparations include various ointments containing medicinal ingredients. The ointment may be one based on an oily base, or one based on an oil/water or water/oil type emulsion base. There are no particular restrictions on the oily base, such as vegetable oil, animal oil,
Examples include synthetic oils, fatty acids, natural or synthetic glycerides, and the like.
また薬効成分としては、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
モン剤等を必要に応じて適宜使用することができる。There are no particular limitations on the medicinal ingredients, and for example, analgesic and antiinflammatory agents, antipruritic agents, sterilizing disinfectants, astringents, emollients, hormonal agents, and the like can be used as appropriate.
また、化粧料として使用する場合は、必須成分の他に化
粧料成分として一般に使用されている油分、保湿剤、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、香料等を任意に組合せて配合
することができる。When used as a cosmetic, in addition to the essential ingredients, oils, humectants, ultraviolet rays, absorbers, alcohols, chelating agents, pH adjusters, preservatives, and thickeners that are commonly used as cosmetic ingredients should be added. , pigments, fragrances, etc. can be blended in any combination.
化粧料としては、種々の形態、例えば水／油、油／水壓
乳化化粧料、クリーム、化粧乳液、化粧水、油性化粧料
、口紅、ファウンデーション、皮膚洗浄剤、ヘアートニ
ック、整髪剤、養毛剤、育毛剤等の皮膚化粧料とするこ
とができる。Cosmetics can be used in various forms, such as water/oil, oil/water emulsion cosmetics, creams, cosmetic emulsions, lotions, oil-based cosmetics, lipsticks, foundations, skin cleansers, hair tonics, hair styling products, hair tonics, etc. It can be used as a skin cosmetic such as a hair growth agent.
本発明皮膚外用剤における式（Ｉ）で示されるアミド誘
導体の作用機構の詳細は完全には解明されていないが、
これが角質細胞間に脂質膜を再構築して角質層の水分保
持機能を発揮するものと考えられる。Although the details of the mechanism of action of the amide derivative represented by formula (I) in the skin external preparation of the present invention have not been completely elucidated,
It is thought that this rebuilds the lipid membrane between corneocytes and exerts the water retention function of the stratum corneum.
本発明皮膚外用剤は、このような作用を有するアミド誘
導体（Ｉ） ’に含有するものであるため、肌おれに対
して優れた改善及び予防効果を発揮することができる。Since the skin external preparation of the present invention contains the amide derivative (I)' having such an effect, it can exhibit excellent improvement and preventive effects against skin irritation.
次に参考例及び実施例を挙げて説明する。 Next, reference examples and examples will be given and explained.
参考例Ｉ
Ｎ−（２−ヒドロキシヘキサデシル）−Ｎ−２−ヒドロ
キシエチルオクタデカナミド（Ｉａ） の合成：
攪拌装置、滴下漏斗、温度計、還流冷却器および窒素ガ
ス導入管を備えた５００ＷＬ１４ツロフラスコに、モノ
エタノールアミン１１７ｇ（Ｉ，９１モル）及びエタノ
ール１１７ｇを入れ、窒素雰囲気下で８０℃に加熱攪拌
しつつ、これに、１．２−エ？キシオクタデカン２６．
８ｇ（０，１０モル）をエタノール５３．６．９に溶か
した溶液を、９０分かけて滴下した。滴下終了後、更に
同条件下で１時間加熱攪拌したのち、蒸留装置をとりつ
けエタノール及び未反応のエタノールアミンを減圧下で
留去し、残渣をメタノール２５０１Ｒ１？用いて再結晶
することにより、長鎖エタノールアミン中間体として淡
黄色の固形物（Ｉｌａ）２４．０９？得た。Reference Example I Synthesis of N-(2-hydroxyhexadecyl)-N-2-hydroxyethyl octadecanamide (Ia): 500WL14 equipped with stirrer, dropping funnel, thermometer, reflux condenser and nitrogen gas inlet tube 117 g (I, 91 mol) of monoethanolamine and 117 g of ethanol were placed in a Tulo flask, and while stirring and heating to 80° C. under a nitrogen atmosphere, 1.2-E? xyoctadecane26.
A solution of 8 g (0.10 mol) dissolved in ethanol 53.6.9 was added dropwise over 90 minutes. After the dropwise addition was completed, the mixture was further heated and stirred for 1 hour under the same conditions, and then a distillation apparatus was attached to remove ethanol and unreacted ethanolamine under reduced pressure, and the residue was converted into methanol 2501R1? A pale yellow solid (Ila) was obtained as a long chain ethanolamine intermediate by recrystallization using 24.09? Obtained.
得られた粗生成物のうち２０．０９ （０，０６（Ｉモ
ル）を分取し、水酸化カリウム０．２２５９ｆ加え、８
０℃／２０ Ｔｏｒｒで加熱攪拌しながら、と九にオク
タデカン酸メチル１８、Ｏｇ（０，０６０モル）全１時
間かけて滴下した。滴下終了後、更に同条件下１時間加
熱攪拌することにより、淡黄色の粗生成物を得た。これ
をシリカゲルフラッシュカラムクロマトグラフィーにて
精製することにより、目的化合物（Ｉａ） １８．５９
（０，０３１モル）を無色結晶として得た。Of the obtained crude product, 20.09 (0.06 (I mol)) was collected, 0.2259 f of potassium hydroxide was added, and 8
Methyl octadecanoate 18, Og (0,060 mol) was added dropwise to the mixture over a total of 1 hour while stirring at 0° C./20 Torr. After completion of the dropwise addition, the mixture was further heated and stirred for 1 hour under the same conditions to obtain a pale yellow crude product. By purifying this using silica gel flash column chromatography, the target compound (Ia) 18.59
(0,031 mol) was obtained as colorless crystals.
全収率 ６２．０％（ただし、１．２−工？キシｍ、ｐ
。Total yield 62.0% (However, 1.2-engine?xy m, p
.
Ｉ、Ｒ。I,R.
’Ｈ−ＮＭＲ
元素分析
オクタデカン基準として）
７２、３−７３．８℃
３４３６．２９２０．２８５４，１６０２，１４７３゜
０．８７（ｔ、６Ｈ） １．１−１．７（ｍ、６０Ｈ
）２．３７（ｔ、２Ｈ） ３．１−４．１（ｍ、 ９
Ｈ）Ｃニア６．７８（７６，５８）
Ｈ： １３．０５（Ｉ３，０２）
Ｎ： ２．２８（２，３５）
参考例２
参考例１と同様にして次の第１表に示すアミド誘導体を
製造した。'H-NMR elemental analysis octadecane standard) 72, 3-73.8℃ 3436.2920.2854,1602,1473゜0.87 (t, 6H) 1.1-1.7 (m, 60H
) 2.37 (t, 2H) 3.1-4.1 (m, 9
H) C near 6.78 (76,58) H: 13.05 (I3,02) N: 2.28 (2,35) Reference Example 2 Amides shown in the following Table 1 were prepared in the same manner as Reference Example 1. A derivative was produced.
実施例１
参考例１及び２で得たアミド誘導体とワセリンの混合物
（Ｉ／３）ｔ’用い、下記方法にニジ皮膚コンダクタン
ス及び肌めれについて評価した。結果を第２表に示す。Example 1 Using the mixture (I/3)t' of the amide derivatives and petrolatum obtained in Reference Examples 1 and 2, rainbow skin conductance and skin irritation were evaluated using the following method. The results are shown in Table 2.
（試験方法）
冬期に頬部に肌あれを起こしている２０〜５０才の女性
１０名を被験者とし、左右の頬に異なる皮膚外用剤を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。(Test method) Ten women between the ages of 20 and 50 who suffer from rough skin on their cheeks during the winter were used as subjects, and two different topical skin preparations were applied to their left and right cheeks.
Apply weekly. The next day after the two-week application was completed, the following tests were conducted.
（Ｉ） 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あれし、５以
下ではひどい肌あれでろる。一方この値が２０以上であ
れば肌おれはほとんど認められない。(I) Skin conductance After washing the face with warm water at 37°C, the subjects were allowed to rest for 20 minutes in a room with a temperature of 20°C and a humidity of 40%, and the water content of the stratum corneum was measured using a skin conductance meter (manufactured by IBS). . The smaller the conductance value, the rougher the skin, and if it is less than 5, the skin becomes severely rough. On the other hand, if this value is 20 or more, skin irritation is hardly observed.
（２）肌あれスコア 肌６Ａｅ肉眼で観測し、下記基準により判定した。(2) Skin roughness score Skin 6Ae was observed with the naked eye and judged according to the following criteria.
スコアは平均値で示した。Scores are shown as average values.
実施例２
参考例１及び２で得た本発明化合物（Ｉａ−ｅ）を用い
て下記第３表に示す組成の皮膚外用剤（乳化化粧料）を
製造し、その肌あれ改善効果全実施例１と同様の方法に
よシ評価した。結果全第４表に示す。Example 2 Using the compounds of the present invention (Ia-e) obtained in Reference Examples 1 and 2, an external skin preparation (emulsified cosmetic) having the composition shown in Table 3 below was produced, and all examples of its effect on improving rough skin were produced. Evaluation was made in the same manner as in 1. All results are shown in Table 4.
第 ４ 表 注）被験者数１２Å 以上 弁理士 小 野 信 夫（Ｉ′。Table 4 Note) Number of subjects: 12Å that's all Patent attorney Nobuo Kono (I'.
；′。;′.
；ｊ、 １．ｌ −一−，，Ｊ;j, 1. l -1-,,J
Claims (1)
の飽和若しくは不飽和の炭化水素基、Ｒ＾２は炭素数９
〜２５の直鎖若しくは分岐鎖の飽和若しくは不飽和の炭
化水素基を示す） で表わされるアミド誘導体を含有することを特徴とする
皮膚外用剤。 ２、更に界面活性剤を含有する特許請求の範囲第１項記
載の皮膚外用剤。[Claims] 1. General formula (I) ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (I) (In the formula, R^1 is a linear or branched saturated or unsaturated linear or branched chain having 8 to 24 carbon atoms. hydrocarbon group, R^2 has 9 carbon atoms
An external preparation for skin, characterized by containing an amide derivative represented by: 2. The skin external preparation according to claim 1, further comprising a surfactant.
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6071987A JPH0692297B2 (en) | 1987-03-16 | 1987-03-16 | External skin preparation |
| ES92115766T ES2077948T3 (en) | 1987-03-06 | 1988-03-02 | PREPARATION FOR EXTERNAL SKIN CARE. |
| EP88103177A EP0282816B1 (en) | 1987-03-06 | 1988-03-02 | External skin care preparation |
| DE3854275T DE3854275T2 (en) | 1987-03-06 | 1988-03-02 | External skin care preparation. |
| DE88103177T DE3884021T2 (en) | 1987-03-06 | 1988-03-02 | External skin care preparation. |
| EP92115766A EP0534286B1 (en) | 1987-03-06 | 1988-03-02 | External skin care preparation |
| US07/163,835 US4985547A (en) | 1987-03-06 | 1988-03-03 | External skin care preparation |
| US07/546,276 US5028416A (en) | 1987-03-06 | 1990-06-29 | External skin care preparation |
| US07/584,739 US5071971A (en) | 1987-03-06 | 1990-09-19 | External skin care preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6071987A JPH0692297B2 (en) | 1987-03-16 | 1987-03-16 | External skin preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63227514A true JPS63227514A (en) | 1988-09-21 |
| JPH0692297B2 JPH0692297B2 (en) | 1994-11-16 |
Family
ID=13150371
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6071987A Expired - Lifetime JPH0692297B2 (en) | 1987-03-06 | 1987-03-16 | External skin preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0692297B2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6431752A (en) * | 1987-07-27 | 1989-02-02 | Kao Corp | Amide derivative and skin external preparation containing said derivative |
| JPH04217610A (en) * | 1990-12-18 | 1992-08-07 | Kao Corp | Skin external preparation |
-
1987
- 1987-03-16 JP JP6071987A patent/JPH0692297B2/en not_active Expired - Lifetime
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6431752A (en) * | 1987-07-27 | 1989-02-02 | Kao Corp | Amide derivative and skin external preparation containing said derivative |
| JPH04217610A (en) * | 1990-12-18 | 1992-08-07 | Kao Corp | Skin external preparation |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0692297B2 (en) | 1994-11-16 |
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