JP2017518963A - 生体表面付着組成物 - Google Patents
生体表面付着組成物 Download PDFInfo
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- JP2017518963A JP2017518963A JP2016563082A JP2016563082A JP2017518963A JP 2017518963 A JP2017518963 A JP 2017518963A JP 2016563082 A JP2016563082 A JP 2016563082A JP 2016563082 A JP2016563082 A JP 2016563082A JP 2017518963 A JP2017518963 A JP 2017518963A
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- compound
- trpm8
- aryl
- concentration
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- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
- A61K2800/24—Thermal properties
- A61K2800/244—Endothermic; Cooling; Cooling sensation
Abstract
Description
Qは、H2、O、−OR1、−N(R1)2、−OPO(OR1)x、−PO(OR1)x、−P(OR1)xであり、ただしxは、1〜2であり、
Vは、NR1、O、−OPO(OR1)x、−PO(OR1)x、−P(OR1)xであり、ただしxは、1〜2であり、
Wは、H2、Oであり、
X、Yは、nが0である場合、H、アリール、ナフチルから独立して選択され、
X、Yは、nが1以上である場合、脂肪族CH2又は芳香族CHであり、Zは、脂肪族CH2、芳香族CH、又はヘテロ原子から選択され、
Aは、低級アルコキシ、低級アルキルチオ、アリール、置換アリール、又は溶融アリールであり、
立体化学は、*印のある位置で変異性である)
を含む化合物を提供する。
Qは、2、O、−OR1、−N(R1)2、−OPO(OR1)x、−PO(OR1)x、−P(OR1)xであり、ただしxは、1〜2であり、
Vは、NR1、O、−OPO(OR1)x、−PO(OR1)x、−P(OR1)xであり、ただしxは、1〜2であり、
Wは、H2、Oであり、
X、Yは、nが0である場合、H、アリール、ナフチルから独立して選択され、
X、Yは、nが1以上である場合、脂肪族CH2又は芳香族CHである、Zは、脂肪族CH2、芳香族CH、又はヘテロ原子から選択され、
Aは、低級アルコキシ、低級アルキルチオ、アリール、置換アリール、又は溶融アリールであり、
立体化学は、*印のある位置で変異性である)
を含む化合物を提供する。
Qは、H2、O、−OR1、−N(R1)2、−OPO(OR1)x、−PO(OR1)x、−P(OR1)xであり、ただしxは、1〜2であり、
Vは、NR1、O、−OPO(OR1)x、−PO(OR1)x、−P(OR1)xであり、ただしxは、1〜2であり、
Wは、H2、Oであり、
X、Yは、nが0である場合、H、アリール、ナフチルから独立して選択され、
X、Yは、nが1である場合、脂肪族CH2又は芳香族CHであり、Zは、脂肪族CH2、芳香族CH、又はヘテロ原子から選択され、
Aは、低級アルコキシ、低級アルキルチオ、アリール、置換アリール、又は溶融アリールであり、
立体化学は、*印のある位置で変異性である)
を含む化合物を提供する。
Qは、H2、O、−OR1、−N(R1)2、−OPO(OR1)x、−PO(OR1)x、−P(OR1)xであり、ただしxは、1〜2であり、
Vは、NR1、O、−OPO(OR1)x、−PO(OR1)x、−P(OR1)xであり、ただしxは、1〜2であり、
Wは、H2、Oであり、
X、Yは、nが0である場合、H、アリール、ナフチルから独立して選択され、
X、Yは、nが1である場合、脂肪族CH2又は芳香族CHであり、Zは、脂肪族CH2、芳香族CH、又はヘテロ原子から選択され、
Aは、低級アルコキシ、低級アルキルチオ、アリール、置換アリール、又は溶融アリールであり、
立体化学は*、印のある位置で変異性である)
を有する化合物を含むパーソナルケア組成物を提供し、
化合物が、TRPV1、TRPV1、又はTRPM8のうちの少なくとも1つを活性化する。
Qは、H2、O、−OR1、−N(R1)2、−OPO(OR1)x、−PO(OR1)xであり、−P(OR1)x、ただしxは、1〜2であり、
Vは、NR1、O、−OPO(OR1)x、−PO(OR1)x、−P(OR1)xであり、ただしx=1〜2であり、
Wは、H2、Oであり、
X、Yは、nが0である場合、H、アリール、ナフチルから独立して選択され、
X、Yは、nが1以上である場合、脂肪族CH2又は芳香族CHであり、Zは、脂肪族CH2、芳香族CH、又はヘテロ原子から選択され、
Aは、低級アルコキシ、低級アルキルチオ、アリール、置換アリール、又は溶融アリールであり、
立体化学は、*印のある位置で変異性である。
Qは、H2、O、−OR1、−N(R1)2、−OPO(OR1)x、−PO(OR1)x、−P(OR1)xであり、ただしxは、1〜2であり、
Vは、NR1、O、−OPO(OR1)x、−PO(OR1)x、−P(OR1)xであり、ただしxは、1〜2であり、
Wは、H2、Oであり、
X、Yは、nが0である場合、H、アリール、ナフチルから独立して選択され、
X、Yは、nが1である場合、脂肪族CH2又は芳香族CHであり、Zは、脂肪族CH2、芳香族CH、又はヘテロ原子から選択され、
Aは、低級アルコキシ、低級アルキルチオ、アリール、置換アリール、又は溶融アリールであり、
立体化学は、*印のある位置で変異性である。
TRPM8(配列番号:3)、TRPA1(配列番号:2)、及びTRPV1(配列番号:1)の活性化に試験化合物(表1に示す)が及ぼした効果がある場合に、それを判定するため、以下に記載したプロトコルを使用した。
TRPA8が活性化されているかどうかを判定するために、TRPA8受容体配列(配列番号:3)で形質移入した細胞から、細胞内のカルシウムイオン(Ca2+)レベルを測定した。ヒトのTRPM8で安定に形質移入したHEK−293(ヒト胚腎臓)細胞を、5%のCO2に設定された哺乳動物細胞培養インキュベーター内で75cm2フラスコ内の増殖培地15mL(10%のFBS(ウシ胎児血清)、100μg/mLのペニシリン/ストレプトマイシン、5μg/mLのブラスチシジン、及び100μg/mLのゼオシンを追加した高グルコースDMEM(ダルベッコ変法イーグル培地))中で3日間、37℃にて増殖させた。2mLのトリプシンEDTA緩衝液(GIBCO(登録商標)25200、Invitrogen、Grand Island,NY)を添加することによって、約2〜3分間かけて細胞を剥離させた。8mLの増殖培地を添加して、トリプシンを不活性化した。細胞を50mLの管に移し、850rpmで3分間遠心分離させて、培地を除去した。遠心分離後、細胞のペレットが、上清溶液から分離して管の底に形成された。上清を捨て、細胞ペレットを1mLの新鮮な増殖培地中で懸濁し、これに5μL(12.5μg)のFluo−4 AM(Molecular Probes、Inc.、Eugene,OR)カルシウム指示薬を添加し、穏やかに振盪しながら30分にわたってインキュベートした。Fluo−4 AMは、細胞内Ca2+濃度を100nM〜1μMの範囲で定量するために用いられる蛍光色素である。30分間の終わりに、45mLのアッセイ緩衝剤(1xHBSS(Hank’s Balanced Salt Solution)、20mMのHEPES(4−(2−ヒドロキシエチル)−1−ピペラジンエタンスルホン酸))を加えて、細胞を洗浄し、次いで得られた混合物を850rpmで3分間遠心分離させて、余分な緩衝剤及びFluo−4 AMカルシウム指示薬を除去した。
TRPA1が活性化されているかどうかを判定するために、TRPA1受容体配列(配列番号:2)で形質移入した細胞から、細胞内のカルシウムイオン(Ca2+)レベルを測定した。ヒトのTRPA1で安定に形質移入したHEK−293細胞を、5%のCO2に設定された哺乳動物細胞培養インキュベーター内で75cm2フラスコ内の増殖培地15mL(10%のFBS(ウシ胎児血清)、100μg/mLのペニシリン/ストレプトマイシン、100μg/mLのG418を追加した高グルコースDMEM(ダルベッコ変法イーグル培地))中で3日間、37℃にて増殖させた。手で穏やかに振盪しながら、10mLのPBS(リン酸緩衝生理食塩水)を添加することで細胞を剥離させ、50mL管に移し、850rpmで3分間遠心分離して、PBSを除去した。遠心分離後、細胞のペレットが、上清溶液から分離して管の底に形成された。上清を捨て、細胞ペレットを1mLの新鮮な増殖培地中で懸濁し、これに5μL(12.5μg)のFluo−4 AM(Molecular Probes,Inc.,)カルシウム指示薬を添加し、穏やかに振盪しながら30分にわたってインキュベートした。30分間の終わりに、45mLのアッセイ緩衝剤(1xHBSS(Hank’s Balanced Salt Solution)、20mMのHEPES(4−(2−ヒドロキシエチル)−1−ピペラジンエタンスルホン酸))を加えて、細胞を洗浄し、次いで得られた組み合わせを850rpmで3分間遠心分離させて、余分な緩衝剤及びFluo−4 AMカルシウム指示薬を除去した。
TRPV1が活性化されたかどうかを判定するために、TRPV1受容体配列(配列番号:1)で形質移入した細胞から、細胞内のカルシウムイオン(Ca+2)レベルを測定した。ヒトのTRPV1で安定に形質移入したHEK−239細胞を、5%のCO2に設定された哺乳動物細胞培養インキュベーター内で75cm2フラスコ内の増殖培地15mL(10%のFBS(ウシ胎児血清)、100μg/mLのペニシリン/ストレプトマイシン、100μg/mLのG418を追加した高グルコースDMEM(ダルベッコ変法イーグル培地))中で3日間、33℃にて増殖させた。PBS 10mL(リン酸緩衝生理食塩水)を添加し、手で穏やかに振盪することにより、細胞を剥離した。細胞を50mL管に移し、850rpmで3分にわたって遠心分離させて、PBSを除去した。遠心分離後、細胞のペレットが、上清溶液から分離して管の底に形成された。上清を捨て、細胞ペレットを1mLの新鮮な増殖培地中で懸濁し、これに5μL(12.5μg)のFluo−4 AM(Molecular Probes,Inc.、Eugene,OR)カルシウム指示薬を添加し、穏やかに振盪しながら30分にわたってインキュベートした。30分間の終わりに、45mLのアッセイ緩衝剤(1xHBSS(Hank’s Balanced Salt Solution)、20mMのHEPES(4−(2−ヒドロキシエチル)−1−ピペラジンエタンスルホン酸))を加えて、細胞を洗浄し、次いで得られた組み合わせを850rpmで3分間遠心分離させて、余分な緩衝剤及びFluo−4 AMカルシウム指示薬を除去した。
冷感剤活性の官能評価調査は、M.C.MeilgaardらのSensory Evaluation Techniques,4th Ed.(2007)に記載されている技術に倣って、パターン化された方法論を用いて行われた。表4(試料A〜G)のうち、香味料(ペパーミント)のある表1の試験化合物を10百万分率(ppm)含有する試料C〜G、及び化合物180(シクロヘキサンカルボキサミド,N−[4−(シアノメチル)フェニル]−5−メチル−2−(1−メチルエチル))100ppmを対照冷感剤として含む試料Bの歯磨剤を用いて、5人の試験員が2分間、歯磨きをした。試験員は、歯磨剤の喀出後、15mLのすすぎ液で口をすすいでから、喀出した。次に試験員は、表5に示すように、0(冷涼感なし)〜90の数字を割り当て、冷涼強度を評価した。
後述するように化合物28の2画分をグラム量で収集した。Sample Manager、Quaternary Solvent Manager、Tunable Ultraviolet(TUV)検出器、及びQDa質量検出型のシングル四重極質量分析器を装備した、Waters Acuity H Class超高速液体クロマトグラフ(UPLC)(Waters Corporation、Milford,MA)を使用して、LC−UV−MS法により、この化合物28の2つの画分の異性体含有量を同定した。分析及び特性評価の準備のため、各画分の固体試料を計量し、脱イオン水50%/メタノール50%(MeOH、HPLC等級、EMD Millipore Corporation、Billerica,MA製)からなり、更に0.1%のトリフルオロ酢酸(TFA、Sigma Aldrich Corporation、St.Louis,MO)も含有する溶液に溶解し約100μg/mLとした。
マウスウォッシュは従来法を用いて調製され、これは化合物28の画分1又は画分2を含み、冷却特性を評価する試験員に提供された。試験員は、マウスウォッシュを口の中で回し、1分後に喀出した。喀出後の時点をゼロと起算し、そこから12時間、すすぎ後の時間を計測した。次に、試験員は息を吸い込むときに経験した清涼感の知覚を等級付けし、口腔内及び唇周辺での冷涼感/爽快感について記録した。自己評価の尺度は、0(冷涼感なし)から100(最大の冷涼感)であった。
チューインガムの調製
表13に示すチューインガム製剤は、チューインガムベースが軟化するまで電子レンジで20秒ずつ加熱して溶解させることにより調製した。ステアリン酸マグネシウムをパラフィン紙片上に広げ、パラフィン紙のステアリン酸マグネシウムがコーティングされた部分に、軟化させたチューインガムベースを置いた。ガムベースをステアリン酸マグネシウムでコーティングして、手袋をした手で軟化するまで練った。ガムベースを押圧して、厚さ0.64cm(1/4インチ)の板状にした。粉末状の甘味料及び噴霧乾燥粉状の香味料を、ガムの表面の中心に添加した。粉末状の甘味料及び噴霧乾燥粉状の香味料の上に、液体香味料及び2滴の着色剤を添加し、液体香味料及び着色剤を噴霧乾燥粉状の香味料及び粉末状の甘味料に吸収させ、いかなる材料も減じずにガムベースに混入させた。必要に応じて電子レンジで加熱し、ガムベースを柔らかい状態に維持した。ガムベースを粘着させずに圧延し、更に少量の甘味料で外側をコーティングすることができるように、パラフィン紙の上にステアリン酸マグネシウム及び粉末状の甘味料(1.2グラム)を振り掛けた。ガムベースをステアリン酸マグネシウム及び粉末状の甘味料上に置いた。ステンレス鋼ビーカーをステアリン酸マグネシウムでコーティングし、これを使用して、初期甘味用のガムベースを外側に押圧/圧延した。成形用プレス機を使用して、ガムベースを細長い帯状に切断した後、垂直方向に再度切断し、およそ1.0グラム単位の立方体を得た。化合物28の画分1を含むバッチ用に、化合物28の画分1を液体香味料に添加し、上記のように調製して最終濃度を1ppmにした。
表16及び表17は、シェービング製剤組成物を示す。水溶性ポリマー(ポリエチレンオキシド、ヒドロキシエチルセルロース)を水に添加して、ポリマーが完全に溶解するまで(約30分)、撹拌することによって混合した。次に、水性混合物を加熱して、グリセリルオレエート、ソルビトール、及び脂肪酸を約60℃で添加し、加熱を継続しながら、十分に攪拌することによって混合した。80〜85℃でトリエタノールアミンを添加し、約20分間混合して、水性の石鹸相を形成した。水性の石鹸相を室温(およそ25℃)まで冷却した後、残りの成分(即ち、Lubrajel、グリセリン、芳香剤、着色剤、植物性薬品)を水性の石鹸相に添加し、十分に撹拌することにより混合して、ゲル濃縮物を形成した。水を必要に応じて添加してバッチ重量を100%にすることによって、蒸発による水分損失を補充した。次に、濃縮物を充填ライン内で加圧下にて揮発性後発泡剤と混合して、窒素圧力下でバルブを通してせん断し、底部気化エアゾール缶内に充填した。
2Amerchol Corp.(Piscataway,NJ)からPolyox WSR−301として入手可能。
3Amerchol Corp.(Piscataway,NJ)からPolyox WSR N−1 2Kとして入手可能。
4Micro Powders Inc.(Tarrytown,NY)からMicroslip 519として入手可能。
4Guardian Laboratories(Hauppauge,NY)から入手可能。
*QSは、用語「適量」を指し、処方全体の残部がこの物質で満たされる十分量を意味する。
以下の表18に示すシャンプー組成物を、従来法を使用して調製した。
1.ポリクアテルニウム−6:Lubrizolから商標名Merquat 100で供給される、約6.2meq/gの電荷密度及び分子量約150,000g/molを有するポリ(ジアリルジメチルアンモニウムクロリド)
2.ポリクアテルニウム−6:Lubrizolから商標名Merquat 106で供給される、約6.2meq/gの電荷密度及び分子量約15,000g/molを有するポリ(ジアリルジメチルアンモニウムクロリド)
3.ジンクピリチオン:約1〜10マイクロメートルの粒径を有する
4.炭酸亜鉛:約1〜10マイクロメートルの粒径を有する
5.アミノシリコーン:Momentive Performance Materialsから入手可能な、約10,000mPa・sの粘度を有し、以下の式:
(R1)aG3−a−Si−(−OSiG2)n−O−SiG3−a(R1)a
(式中、Gは、メチルであり、aは、1の整数であり、nは、400〜約600の数であり、R1は、一般式CqH2qLに従う一価のラジカルであり、式中、qは3の整数であり、Lは−NH2である)を有する終端アミノシリコーン。
*2の例、Lubrizolから入手可能なCarbopol Ultrez 30
*3の例、Seppic(Puteaux,France)製のSepigel 305
*4の例、Seppic製のSepiMax Zen
*5の例、AkzoNovel(Amsterdam,Netherlands)製のAmaze XT
*6の例、Jeen(Fairfield,New Jersey)製のJeesperse CPW−CG−02
*7の例、Akzo Nobel製のStructure Plus
*8aの例、Lonza Personal Care(Basel,Switzerland)製のZPT
*8bの例、Brueggemann Chemical(Newtown,PA)製の炭酸亜鉛
*9の例、Momentive(Waterford,NY)製のSilsoft 430ジメチコンコポリオール
*10の例、Evonik(Zurich、Switzerland)製のAbil Care 85
*11の例、Akzo Nobel製のCelquat H−100
*12の例、BASF(Ludwigshafen,Germany)製のLipofructyl Argan LS9779
*13の例、ISP Technologies(Wayne,New Jersey)製のPVP K−30
*14の例、Equistar Chemicals(Houston,TX)製のMicrothene FN 510−00
*15の例、Akzo Nobel製のDry Flo TS
*16の例、Rohm and Haas(Philadelphia,PA)製のNeolone 950
*17の例、BASF製のCremophor RH−40界面活性剤
*18の例、BASF製のNeutrol Te
*19の例、Dow Chemical(Houston,TX)製のTrolamine
*20の例、DuPont(Wilmington,DE)製のGlypure
Claims (14)
- 以下の構造:
Qは、H2、O、−OR1、−N(R1)2、−OPO(OR1)x、−PO(OR1)x、−P(OR1)xであり、ただしxは、1〜2であり、
Vは、NR1、O、−OPO(OR1)x、−PO(OR1)x、−P(OR1)xであり、ただしxは、1〜2であり、
Wは、H2、Oであり、
X、Yは、nが0である場合、H、アリール、ナフチルから独立して選択され、
X、Yは、nが1以上である場合、脂肪族CH2又は芳香族CHであり、Zは、脂肪族CH2、芳香族CH、又はヘテロ原子から選択され、
Aは、低級アルコキシ、低級アルキルチオ、アリール、置換アリール、又は溶融アリールであり、
立体化学は、*印のある位置で変異性である)
を含む、化合物。 - 前記化合物が、TRPA1、TRPV1、又はTRPM8のうちの少なくとも1つを活性化し、好ましくは、前記化合物が、濃度約5.2×10−5%で、a)濃度約30mMのWS5よりも高いTRPM8活性、b)濃度約50mMのアリルイソチオシアネートよりも高いTRPA1活性、及びc)濃度約350nMのカプサイシンよりも高いTRPV1活性を与える、請求項1に記載の化合物。
- 前記化合物が、濃度約5.2×10−5%で、
a)濃度約30mMのWS5と比較したときに、少なくとも約110%のTRPM8活性、
b)濃度約50mMのアリルイソチオシアネートと比較したときに、少なくとも約180%のTRPA1活性、及び
c)濃度約350nMのカプサイシンと比較したときに、少なくとも約100%のTRPV1活性
を与える、請求項2に記載の化合物。 - 前記活性化が細胞内カルシウムレベルを測定することにより決定され、好ましくは、細胞内カルシウムレベルの測定が蛍光色素を使用して行われる、請求項2又は3に記載の化合物。
- 前記化合物が、濃度約5.2×10−5%で、濃度約30mMのWS5よりも大きいTRPM8活性を与える、請求項2〜4のいずれか一項に記載の化合物。
- 請求項1〜5のいずれか一項に記載の化合物を含む、パーソナルケア組成物。
- 請求項1〜6のいずれか一項に記載の化合物の異性体のHPLC画分であって、前記異性体のHPLC画分が、濃度約12.2nMで、濃度約10μmのWS 5と比較して、10分でより高いTRPM8活性を有した、異性体のHPLC画分。
- 請求項1〜7のいずれか一項に記載の化合物とTRPM8作動薬とを含む、組成物。
- 前記TRPM8作動薬が、メントール、メンチルラクテート、N−エチル−ρ−メンタン−3−カルボキサミド、N−エトキシカルボニルメチル−ρ−メンタン−3−カルボキサミド、N−(4−メトキシフェニル)−ρ−メンタン−3−カルボキサミド、N−tert−ブチル−ρ−メンタン−3−カルボキサミド、N,2,3−トリメチル−2−イソプロピルブタナミド、N−(4−シアノメチルフェニル)−ρ−メンタンカルボキサミド、N−(4−スルファモイルフェニル)−ρ−メンタンカルボキサミド、N−(4−シアノフェニル)−ρ−メンタンカルボキサミド、N−(4−アセチルフェニル)−ρ−メンタンカルボキサミド、N−(4−ヒドロキシメチルフェニル)−ρ−メンタンカルボキサミド、N−(3−ヒドロキシ−4−メトキシフェニル)−ρ−メンタンカルボキサミド、イソプレゴール、及び/又は(−)−メントキシプロパン−1,2−ジオール、のうちの少なくとも1つを含む、請求項8に記載の組成物。
- 請求項1〜9のいずれか一項に記載の化合物と、TRPA1作動薬又はTRPV1作動薬のうちの少なくとも一方とを含む、組成物。
- 前記TRPA1作動薬が、アリルイソチオシアネート、メントール、過酸化物、サリチル酸メチル、ケイ皮アルデヒド、ベンジルアルコール、亜鉛塩、及び/又はバニリンイソブチレートのうちの少なくとも1つであり、好ましくは、前記TRPV1作動薬が、カプサイシン、ピペリン、バニリルブチルエーテル、バニリルエチルエーテル、メントール、過酸化物、亜鉛塩、又は抗ヒスタミン剤のうちの少なくとも1つである、請求項10に記載の組成物。
- 前記構造が、以下:
Qは、H2、O、−OR1、−N(R1)2、−OPO(OR1)x、−PO(OR1)x、−P(OR1)xであり、ただしxは、1〜2であり、
Vは、NR1、O、−OPO(OR1)x、−PO(OR1)x、−P(OR1)xであり、ただしxは、1〜2であり、
Wは、H2、Oであり、
X、Yは、nが0である場合、H、アリール、ナフチルから独立して選択され、
X、Yは、nが1以上である場合、脂肪族CH2又は芳香族CHであり、Zは、脂肪族CH2、芳香族CH、又はヘテロ原子から選択され、
Aは、低級アルコキシ、低級アルキルチオ、アリール、置換アリール、又は溶融アリールであり、
立体化学は、*印のある位置で変異性である)
を含む、請求項1に記載の化合物。 - 前記構造が、以下:
Qは、H2、O、−OR1、−N(R1)2、−OPO(OR1)x、−PO(OR1)x、−P(OR1)xであり、ただしxは、1〜2であり、
Vは、NR1、O、−OPO(OR1)x、−PO(OR1)x、−P(OR1)xであり、ただしxは、1〜2であり、
Wは、H2、Oであり、
X、Yは、nが0である場合、H、アリール、ナフチルから独立して選択され、
X、Yは、nが1以上である場合、脂肪族CH2又は芳香族CHであり、Zは、脂肪族CH2、芳香族CH、又はヘテロ原子から選択され、
Aは、低級アルコキシ、低級アルキルチオ、アリール、置換アリール、又は溶融アリールであり、
立体化学は、*印のある位置で変異性である)
を含む、請求項1に記載の化合物。
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- 2015-04-23 CN CN201580021015.9A patent/CN106458861B/zh not_active Expired - Fee Related
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2017
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JP2022511961A (ja) * | 2018-12-20 | 2022-02-01 | ザ プロクター アンド ギャンブル カンパニー | 改善された安定性を有する頭皮ケア組成物 |
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AU2015312408B2 (en) | 2018-02-01 |
US9974761B2 (en) | 2018-05-22 |
RU2016138746A (ru) | 2018-05-24 |
US20150306050A1 (en) | 2015-10-29 |
AU2015312408A1 (en) | 2016-10-27 |
US20150307447A1 (en) | 2015-10-29 |
US20170079939A1 (en) | 2017-03-23 |
AU2015249706A1 (en) | 2016-11-03 |
CA2944160A1 (en) | 2015-10-29 |
US20180228746A1 (en) | 2018-08-16 |
EP3134081A2 (en) | 2017-03-01 |
MX2016013617A (es) | 2017-02-28 |
WO2016036423A3 (en) | 2016-06-09 |
US9492411B2 (en) | 2016-11-15 |
BR112016024573A2 (pt) | 2017-08-15 |
US20170119639A1 (en) | 2017-05-04 |
MX2016013618A (es) | 2017-02-28 |
WO2016036423A2 (en) | 2016-03-10 |
CN106458861B (zh) | 2020-05-19 |
CN106232111A (zh) | 2016-12-14 |
WO2015164553A1 (en) | 2015-10-29 |
CA2946383A1 (en) | 2016-03-10 |
CN106458861A (zh) | 2017-02-22 |
KR20160136383A (ko) | 2016-11-29 |
RU2016138746A3 (ja) | 2018-05-24 |
EP3134081B1 (en) | 2020-04-22 |
EP3134080A1 (en) | 2017-03-01 |
BR112016024691A2 (pt) | 2017-08-15 |
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