JP7437503B2 - 高クラフト温度アニオン性界面活性剤を使用した皮膚症状の処置 - Google Patents
高クラフト温度アニオン性界面活性剤を使用した皮膚症状の処置 Download PDFInfo
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- JP7437503B2 JP7437503B2 JP2022535474A JP2022535474A JP7437503B2 JP 7437503 B2 JP7437503 B2 JP 7437503B2 JP 2022535474 A JP2022535474 A JP 2022535474A JP 2022535474 A JP2022535474 A JP 2022535474A JP 7437503 B2 JP7437503 B2 JP 7437503B2
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- 201000004700 rosacea Diseases 0.000 description 1
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 230000037393 skin firmness Effects 0.000 description 1
- 230000037067 skin hydration Effects 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- 229940080264 sodium dodecylbenzenesulfonate Drugs 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 229940045870 sodium palmitate Drugs 0.000 description 1
- 229940048842 sodium xylenesulfonate Drugs 0.000 description 1
- QUCDWLYKDRVKMI-UHFFFAOYSA-M sodium;3,4-dimethylbenzenesulfonate Chemical compound [Na+].CC1=CC=C(S([O-])(=O)=O)C=C1C QUCDWLYKDRVKMI-UHFFFAOYSA-M 0.000 description 1
- PNGBYKXZVCIZRN-UHFFFAOYSA-M sodium;hexadecane-1-sulfonate Chemical compound [Na+].CCCCCCCCCCCCCCCCS([O-])(=O)=O PNGBYKXZVCIZRN-UHFFFAOYSA-M 0.000 description 1
- GGXKEBACDBNFAF-UHFFFAOYSA-M sodium;hexadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCC([O-])=O GGXKEBACDBNFAF-UHFFFAOYSA-M 0.000 description 1
- NWZBFJYXRGSRGD-UHFFFAOYSA-M sodium;octadecyl sulfate Chemical compound [Na+].CCCCCCCCCCCCCCCCCCOS([O-])(=O)=O NWZBFJYXRGSRGD-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 229950006451 sorbitan laurate Drugs 0.000 description 1
- 235000011067 sorbitan monolaureate Nutrition 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 230000009182 swimming Effects 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 229940126703 systemic medication Drugs 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- KRIXEEBVZRZHOS-UHFFFAOYSA-N tetradecyl dihydrogen phosphate Chemical compound CCCCCCCCCCCCCCOP(O)(O)=O KRIXEEBVZRZHOS-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229940100611 topical cream Drugs 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 229960005294 triamcinolone Drugs 0.000 description 1
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
- KENFVQBKAYNBKN-UHFFFAOYSA-N trihexadecyl phosphate Chemical compound CCCCCCCCCCCCCCCCOP(=O)(OCCCCCCCCCCCCCCCC)OCCCCCCCCCCCCCCCC KENFVQBKAYNBKN-UHFFFAOYSA-N 0.000 description 1
- 229940072029 trilaureth-4 phosphate Drugs 0.000 description 1
- FDGZUBKNYGBWHI-UHFFFAOYSA-N trioctadecyl phosphate Chemical compound CCCCCCCCCCCCCCCCCCOP(=O)(OCCCCCCCCCCCCCCCCCC)OCCCCCCCCCCCCCCCCCC FDGZUBKNYGBWHI-UHFFFAOYSA-N 0.000 description 1
- 150000004072 triols Chemical class 0.000 description 1
- SVETUDAIEHYIKZ-IUPFWZBJSA-N tris[(z)-octadec-9-enyl] phosphate Chemical compound CCCCCCCC\C=C/CCCCCCCCOP(=O)(OCCCCCCCC\C=C/CCCCCCCC)OCCCCCCCC\C=C/CCCCCCCC SVETUDAIEHYIKZ-IUPFWZBJSA-N 0.000 description 1
- LEHFPXVYPMWYQD-XHIJKXOTSA-N ulobetasol Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H](C)[C@@](C(=O)CCl)(O)[C@@]2(C)C[C@@H]1O LEHFPXVYPMWYQD-XHIJKXOTSA-N 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
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Description
水中油型エマルション:製品は、疎水性成分の別個の相と、水及び場合により1種又は複数の極性親水性賦形剤、並びに溶媒、共溶媒、塩、界面活性剤、乳化剤、及び他の成分を含む連続水性相とを含む、エマルションであってもよい。これらのエマルションは、エマルションの安定化を助ける水溶性又は水膨潤性ポリマーを含んでいてもよい。
本発明による組成物は、皮膚浸透性又は配合物中に含有される他の賦形剤の活性を改質させる、1種又は複数の溶媒又は共溶媒を含んでいてもよい。溶媒としては、限定はされないが、エタノール、ベンジルアルコール、ブチルアルコール、ジエチルセバケート、ジエチレングリコールモノエチルエーテル、ジイソプロピルアジペート、ジメチルスルホキシド、酢酸エチル、イソプロピルアルコール、イソプロピルイソステアレート、イソプロピルミリステート、オレイルアルコール、ポリエチレングリコール、グリセリン、プロピレングリコール、及びSDアルコールが挙げられる。
本発明による組成物は、保湿のレベルを高めるさらなる保湿剤を含んでいてもよい。保湿剤は湿潤剤を含む親水性材料であってもよく、又は皮膚軟化剤を含む疎水性材料であってもよい。適切な保湿剤としては、限定はされないが、1,2,6-ヘキサントリオール、2-エチル-1,6-ヘキサンジオール、ブチレングリコール、グリセリン、ポリエチレングリコール200~8000、ブチルステアレート、セトステアリルアルコール、セチルアルコール、セチルエステルワックス、セチルパルミテート、ココアバター、ココナッツ油、シクロメチコン、ジメチコン、ドコサノール、エチルヘキシルヒドロキシステアレート、脂肪酸、グリセリルイソステアレート、グリセリルラウレート、グリセリルモノステアレート、グリセリルオレエート、グリセリルパルミテート、グリコールジステアレート、グリコールステアレート、イソステアリン酸、イソステアリルアルコール、ラノリン、鉱油、リモネン、中鎖トリグリセリド、メントール、ミリスチルアルコール、オクチルドデカノール、オレイン酸、オレイルアルコール、オレイルオレエート、オリーブ油、パラフィン、落花生油、ワセリン、プラスチベース-50W、及びステアリルアルコールが挙げられる。
特定の用途において、可溶性、膨潤性、又は不溶性の有機ポリマー増粘剤、例えば天然及び合成ポリマー又は無機増粘剤など、例えばアクリレートコポリマー、カルボマー1382、カルボマーコポリマータイプB、カルボマーホモポリマータイプA、カルボマーホモポリマータイプB、カルボマーホモポリマータイプC、アクリルアミド/ナトリウムアクリロイルジメチルタウレートコポリマー、カルボキシビニルコポリマー、カルボキシメチルセルロース、カルボキシポリメチレン、カラギーナン、グアーガム、ヒドロキシエチルセルロース、ヒドロキシプロピルセルロース、ミクロクリスタリンワックス、及びメチルセルロースなどにより増粘化された製品を製剤化することが望ましい場合がある。
本発明による組成物には、化粧用及び医薬用局所製品において従来から見られる、フィラー、担体、及び賦形剤などの追加成分が配合されていてもよい。限定はされないが、消泡剤、保剤(例えばp-ヒドロキシ安息香酸エステル、ベンジルアルコール、フェニル水銀塩、クロロクレゾール)、抗酸化剤、金属イオン封鎖剤、安定化剤、緩衝剤、pH調整剤(好ましくは酸性pHをもたらす薬剤、限定はされないがグルコノラクトン、クエン酸、乳酸、及びアルファヒドロキシ酸が挙げられる)、皮膚浸透エンハンサー、皮膚保護剤(限定はされないが、ワセリン、パラフィンワックス、ジメチコン、グリセリルモノイソステアレート、イソプロピルイソステアレート、イソステアリルイソステアレート、セチルアルコール、カリウムセチルホスフェート、セチルベヘネート、及びベヘン酸が挙げられる)、キレート化剤、膜形成剤、染料、顔料、希釈剤、膨化剤、芳香剤、エアロゾル生成剤、及び安定性又は美粧性を改善するための他の賦形剤を含む追加成分を、組成物へ添加してもよい。アルコールは炎症を生じさせ皮膚から水及び脂質を抽出することが知られているが、アルコールは、表皮バリア機能の改善の観点から高クラフト温度界面活性剤を含む配合物中に加えられてもよい。アルコールは、溶解性を改善し活性医薬品の吸収を高めるために加えられてもよい。
本発明による組成物は、限定はされないが、皮膚(局所的)、経皮及び粘膜(例えば舌下、頬側、鼻)を含む、任意の適切な投与経路により投与することができる。好ましい実施形態において、組成物が局所投与される。
組成物は1日に1回又は複数回投与することができ、好ましくは組成物は1日に1~2回投与される。
以下の配合にしたがって、クリームを調製した。
配合物1
白色ワセリン 10.0%w/w
イソプロピルパルミテート 5.0%w/w
クロダホスCES 10.0%w/w
ジエチレングリコールモノエチルエーテル(トランスクトールP) 25%w/w
メチルパラベン 0.2%w/w
プロピルパラベン 0.05%w/w
精製水 100まで適量(49.75%)
配合物2
白色ワセリン 10.0%w/w
イソプロピルパルミテート 5.0%w/w
クロダホスCES 10.0%w/w
ヘキシレングリコール 2.0%w/w
ジエチレングリコールモノエチルエーテル(トランスクトールP) 25.0%w/w
メチルパラベン 0.2%w/w
プロピルパラベン 0.05%w/w
精製水 100まで適量(47.75%)
配合物3
白色ワセリン 10.0%w/w
イソプロピルパルミテート 5.0%w/w
ナトリウムドデシルスルフェート 2.0%w/w
セテアリルアルコール 8.0%w/w
ヘキシレングリコール 2.0%w/w
ジエチレングリコールモノエチルエーテル(トランスクトールP) 25.0%w/w
メチルパラベン 0.2%w/w
プロピルパラベン 0.05%w/w
精製水 100まで適量(47.75%)
配合物4(米国特許第10,195,160号-表1のタピナロフ2bの配合物)
中鎖トリグリセリド 10.0%w/w
ステアレス-2 1.8%w/w
ステアレス-20 1.1%w/w
ポリソルベート80 1.5%w/w
プロピレングリコール 10.0%w/w
ジエチレングリコールモノエチルエーテル(トランスクトールP) 2.0%w/w
安息香酸 0.25%w/w
ブチルヒドロキシトルエン 0.1%w/w
二ナトリウムエチレンジアミンテトラ酢酸 0.1%w/w
クエン酸塩/クエン酸緩衝剤 0.27%w/w
精製水 100まで適量(64.68%)
配合物5(欧州特許第0786986号実施例14のエリデルクリームビヒクルの配合物)
モノ及びジグリセリド 2.0%w/w
中鎖トリグリセリド 15.0%w/w
ナトリウムセトステアリルスルフェート 1.0%w/w
プロピレングリコール 5.0%w/w
セチルアルコール 4.0%w/w
ベンジルアルコール 1.0%w/w
ステアリルアルコール 4.0%w/w
オレイルアルコール 10.0%w/w
クエン酸塩/クエン酸緩衝剤 0.05%w/w
10%NaOH又は10%HCl溶液 pH=5.3+0.3とするために必要に応じて
精製水 100まで適量(57.95%)
実施例2
0.0012グラムのセテス-10ホスフェート(Moravek社、ロット671-144-000-A-20190821-JHO)を秤量して20mLのガラスシンチレーションバイアルへ入れた。10.0113グラムの蒸留水をシンチレーションバイアルへ加え、バイアルを密栓し、水浴中に置いた。温度を徐々に36.0℃から56.0℃まで上昇させた。52.5℃で150分間平衡化させた後、セテス-10ホスフェートは溶解しておらず、強く振とうすると試料は泡立たなかった。界面活性剤はバイアルの底に沈殿したワックス状粒子として残った。53.0℃で435分間の平衡化の後、セテス-10ホスフェートは溶解しており、振とうすると試料は泡立った。0.012%セテス-10ホスフェート水溶液のクラフト温度は53.0℃であると決定された。
乳化剤を含有しある範囲のクラフト温度を有するクリーム配合物が表皮脂質を抽出する能力は、500ミクロンの目標厚さとなるように採取された切除したヒトの死体皮膚を使用して決定することができる。切除したヒトの皮膚は、米国組織バンクから凍結した状態で入手し、使用まで-20℃で保存した。0.503cm2の抽出面積を有し、0.01%ゲンタマイシンスルフェートを含有し32℃で温度制御された3.0mlの4%の水中BSA(レセプター溶液)で満たされたレセプターチャンバーを有する、直径が8mmの垂直フランツセルへ、皮膚を装入した。容積式ピペットを使用して、5マイクロリットル用量のクリームを各フランツセルへ加えた(皮膚組織1cm2あたり10mgのクリーム)。拡散セルを32±1℃の皮膚表面温度で維持した。24時間のインキュベーション後、皮膚表面をQチップで拭って(湿ったQチップ及び乾燥したQチップで3サイクル)塗布された試験物品の表面残渣を除去した。次いで皮膚表面を45℃の温水で3サイクル洗浄した。次いで皮膚組織をフランツセルから取り出し、テープ剥離を行った。最初の2回のテープ剥離片は廃棄した。テープ剥離プロセスをさらに15回続けた。15枚のテープ剥離片を収集し、液体クロマトグラフィータンデム質量分析法(LC/MS/MS)を使用して定量し、「角質層」とラベリングした。表皮及び真皮層はメスを使用して分離した。表皮を収集し、クロロホルム/メタノール混合物を含有する浴を使用して、残っている角質層及び表皮から脂質を抽出した。浴を集め、蒸発させ、HPLC/MS/MS分析による定量のための適切な移動相に溶解させた。
アトピー性皮膚炎臨床研究では、Eczema Area and Severity Index(皮膚炎面積及び重症度指数)(EASI)を認証された評価システムとして使用して、局所的に塗布された製品の有効性を測定する。EASIスコアはアトピー性皮膚炎の2つの側面:1)疾患の程度及び2)臨床兆候についての客観的な医師の見積もりを評価する。疾患の程度の採点は、影響を受けた皮膚のパーセンテージに関連づけられた0~6の数値スコアを割り当てることにより実行される。スコア0=皮膚の0%が影響を受けている;スコア1=皮膚の1~9%が影響を受けている;スコア2=皮膚の10~29%が影響を受けている;スコア3=皮膚の30~49%が影響を受けている;スコア4=皮膚の50~69%が影響を受けている;スコア5=皮膚の70~89%が影響を受けている、スコア6=皮膚の90~100%が影響を受けている。疾患の程度のスコアは、それぞれが0~3の段階で(0=なし、存在しない;1=軽度;2=中等度;3=重度)、4箇所の体の部位(頭及び首、胴体、上肢、及び下肢)についての、4つの臨床兆候(紅斑、硬結/丘疹形成、表皮剥離、及び苔癬化)の重症度の採点と併用される。中間のスコアが可能である。各々の体の部位は0~72の範囲のスコアを有することになり、最終的なEASIスコアは、これらの4つのスコアを平均する(頭及び首並びに上肢については0.2、胴体及び下肢については0.3を掛ける)ことにより得られることになる。したがって、最終的なEASIスコアはクリニックで患者が評価される各時点において0~72の範囲となる。「ベースラインからの変化のパーセンテージ」として報告されるEASIスコアは、局所用製品使用の時間経過に対して、アトピー性皮膚炎病害の改善又は悪化を臨床的に評価する標準的な方法である。例として、4週間の処置におけるEASI%CFBの1%の増加は、平均で、このクリームで処置されたすべての患者がアトピー性皮膚炎を悪化させたことを示唆する。代わりに、4週間の処置におけるEASI%CFBの55%の減少は、疾患の程度又は臨床兆候のいずれかにおける劇的な改善、又は典型的にはアトピー性皮膚炎病害の疾患の程度及び臨床兆候の両方における著しい改善を意味する。
本明細書は以下の発明の開示を包含する。
[項目1] 機能が低下した表皮バリアを処置する方法であって、高クラフト温度界面活性剤、保湿剤、及び水を含む組成物を、そのような処置を必要とする患者へ局所投与するステップを含み、前記組成物がロフルミラスト又は角質溶解薬を含まない、方法。
[項目2] 前記高クラフト温度界面活性剤が0.1~20%w/wの量である、項目1に記載の方法。
[項目3] 前記組成物が、水中油型エマルション、油中水型エマルション、マイクロエマルション又はナノエマルション、及び親水性又は疎水性軟膏からなる群から選択される、項目1に記載の方法。
[項目4] 前記組成物が、溶媒、保湿剤、ポリマー又は増粘剤、消泡剤、保存剤、抗酸化剤、金属イオン封鎖剤、安定化剤、緩衝剤、pH調整溶液、皮膚浸透エンハンサー、膜形成剤、染料、顔料、エアロゾル形成剤、及び芳香剤からなる群から選択される少なくとも1つの追加成分をさらに含む、項目1に記載の方法。
[項目5] 前記組成物が3.5~9.0のpHを有する、項目1に記載の方法。
[項目6] 前記組成物が局所投与に適した担体を含む、項目1に記載の方法。
[項目7] 前記組成物が活性医薬成分をさらに含む、項目1に記載の方法。
[項目8] 前記活性医薬品が、アントラリン、アザチオプリン、タクロリムス、コールタール、メトトレキサート、メトキサレン、乳酸アンモニウム、5-フルオロウラシル、プロピルトウラシル、6-チオグアニン、スルファサラジン、ミコフェノール酸モフェチル、フマル酸エステル、コルチコステロイド、コルチコトロピン、ビタミンD類似体、アシトレチン、タザロテン、シクロスポリン、レゾルシノール、コルヒチン、アダリムマブ、ウステキヌマブ、インフリキシマブ、抗生物質、ホスホジエステラーゼ-4阻害剤、及びそれらの組み合わせからなる群から選択される、項目7に記載の方法。
[項目9] 表皮バリアの機能が低下した前記患者が湿疹を患っている、項目1に記載の方法。
[項目10] 前記患者がアトピー性皮膚炎、接触皮膚炎、及び/又は脂漏性皮膚炎を患っている、項目9に記載の方法。
[項目11] 白色ワセリン、イソプロピルパルミテート、高クラフト温度界面活性剤、ジエチレングリコールモノエチルエーテル、メチルパラベン、プロピルパラベン、及び水を含む医薬組成物であって、ロフルミラスト又は角質溶解薬を含まない、医薬組成物。
[項目12] 前記高クラフト温度界面活性剤が、セトステアリルアルコール、ジセチルホスフェート、及びセテス-10ホスフェートの混合物である、項目11に記載の医薬組成物。
[項目13] ヘキシレングリコールをさらに含む、項目12に記載の医薬組成物。
[項目14] 前記高クラフト温度界面活性剤がアニオン性界面活性剤である、項目11に記載の医薬組成物。
[項目15] 前記高クラフト温度界面活性剤が48℃を超えるクラフト温度を有する、項目11に
記載の医薬組成物。
[項目16] 前記高クラフト温度界面活性剤が50℃を超えるクラフト温度を有する、項目15に記載の医薬組成物。
[項目17] 前記高クラフト温度界面活性剤が52℃を超えるクラフト温度を有する、項目16に記載の医薬組成物。
[項目18] 活性医薬成分を含有しない、項目11に記載の医薬組成物。
[項目19] 白色ワセリン 10.0%w/w
イソプロピルパルミテート 5.0%w/w
クロダホスCES 10.0%w/w
ジエチレングリコールモノエチルエーテル(トランスクトールP) 25%w/w
メチルパラベン 0.2%w/w
プロピルパラベン 0.05%w/w
精製水 100まで適量(49.75%)を含む組成物であって、活性医薬成分を含有しない、組成物。
[項目20] 白色ワセリン 10.0%w/w
イソプロピルパルミテート 5.0%w/w
クロダホスCES 10.0%w/w
ヘキシレングリコール 2.0%w/w
ジエチレングリコールモノエチルエーテル(トランスクトールP) 25.0%w/wメチルパラベン 0.2%w/w
プロピルパラベン 0.05%w/w
精製水 100まで適量(47.75%)を含む組成物であって、活性医薬成分を含有しない、組成物。
[項目21] 表皮脂質の抽出を減少させ且つ表皮バリア機能を高める方法であって、高クラフト温度界面活性剤、保湿剤、及び水を含む配合物を、そのような処置を必要とする患者へ局所投与するステップを含む、方法。
[項目22] 前記高クラフト温度界面活性剤がアニオン性界面活性剤である、項目21に記載の方法。
[項目23] 前記高クラフト温度界面活性剤が48℃を超えるクラフト温度を有する、項目21に記載の方法。
[項目24] 前記高クラフト温度界面活性剤が50℃を超えるクラフト温度を有する、項目23に記載の方法。
[項目25] 前記高クラフト温度界面活性剤が52℃を超えるクラフト温度を有する、項目24に記載の方法。
Claims (28)
- 表皮脂質の抽出を減少させる方法に使用するための、セテアリルアルコール、ジセチルホスフェート、及びセテス-10ホスフェートを含む乳化剤ブレンド、保湿剤、及び水を含む医薬組成物であって、前記方法が、前記組成物を、そのような処置を必要とする患者へ局所投与するステップを含み、前記組成物がロフルミラスト又は角質溶解薬を含まない、医薬組成物。
- 前記乳化剤ブレンドが0.1~20%w/wの量である、請求項1に記載の医薬組成物。
- 前記組成物が、水中油型エマルション、油中水型エマルション、マイクロエマルション又はナノエマルション、及び親水性又は疎水性軟膏からなる群から選択される、請求項1又は2に記載の医薬組成物。
- 前記組成物が、溶媒、保湿剤、ポリマー又は増粘剤、消泡剤、保存剤、抗酸化剤、金属イオン封鎖剤、安定化剤、緩衝剤、pH調整溶液、皮膚浸透エンハンサー、膜形成剤、染料、顔料、エアロゾル形成剤、及び芳香剤からなる群から選択される少なくとも1つの追加成分をさらに含む、請求項1~3のいずれか一項に記載の医薬組成物。
- 前記組成物が3.5~9.0のpHを有する、請求項1~4のいずれか一項に記載の医薬組成物。
- 前記組成物が局所投与に適した担体を含む、請求項1~5のいずれか一項に記載の医薬組成物。
- 前記組成物が活性医薬成分をさらに含む、請求項1~6のいずれか一項に記載の医薬組成物。
- 前記活性医薬品が、アントラリン、アザチオプリン、タクロリムス、コールタール、メトトレキサート、メトキサレン、乳酸アンモニウム、5-フルオロウラシル、プロピルトウラシル、6-チオグアニン、スルファサラジン、ミコフェノール酸モフェチル、フマル酸エステル、コルチコステロイド、コルチコトロピン、ビタミンD類似体、アシトレチン、タザロテン、シクロスポリン、レゾルシノール、コルヒチン、アダリムマブ、ウステキヌマブ、インフリキシマブ、抗生物質、ホスホジエステラーゼ-4阻害剤、及びそれらの組み合わせからなる群から選択される、請求項7に記載の医薬組成物。
- 前記患者が湿疹又は乾癬を患っている、請求項1~8のいずれか一項に記載の医薬組成物。
- 前記患者がアトピー性皮膚炎、接触皮膚炎、及び/又は脂漏性皮膚炎を患っている、請求項1~8のいずれか一項に記載の医薬組成物。
- 白色ワセリン、イソプロピルパルミテート、セテアリルアルコール、ジセチルホスフェート、及びセテス-10ホスフェートを含む乳化剤ブレンド、ジエチレングリコールモノエチルエーテル、並びに水を含む医薬組成物であって、ロフルミラスト又は角質溶解薬を含まない、表皮脂質の抽出を減少させることに使用するための医薬組成物。
- ヘキシレングリコールをさらに含む、請求項11に記載の医薬組成物。
- 前記乳化剤ブレンドがアニオン性界面活性剤である、請求項11又は12に記載の医薬組成物。
- 活性医薬成分を含有しない、請求項11~13のいずれか一項に記載の医薬組成物。
- 白色ワセリン 10.0%w/w
イソプロピルパルミテート 5.0%w/w
クロダホスCES 10.0%w/w
(セテアリルアルコール/ジセチルホスフェート/セテス-10ホスフェート)
ジエチレングリコールモノエチルエーテル(トランスクトールP) 25%w/w
精製水 100まで適量
を含む組成物であって、活性医薬成分を含有しない、組成物。 - 白色ワセリン 10.0%w/w
イソプロピルパルミテート 5.0%w/w
クロダホスCES 10.0%w/w
(セテアリルアルコール/ジセチルホスフェート/セテス-10ホスフェート)
ヘキシレングリコール 2.0%w/w
ジエチレングリコールモノエチルエーテル(トランスクトールP) 25.0%w/w
精製水 100まで適量
を含む組成物であって、活性医薬成分を含有しない、組成物。 - 表皮脂質の抽出を減少させ且つ表皮バリア機能を高める方法において使用するための、セテアリルアルコール、ジセチルホスフェート、及びセテス-10ホスフェートを含む乳化剤ブレンド、保湿剤、及び水を含む配合物であって、前記方法がそのような処置を必要とする患者へ配合物を局所投与するステップを含み、活性医薬成分を含まない、配合物。
- 前記乳化剤ブレンドがアニオン性界面活性剤である、請求項17に記載の配合物。
- 前記患者がアトピー性皮膚炎を患っている、請求項17又は18に記載の配合物。
- 前記患者が脂漏性皮膚炎を患っている、請求項17又は18に記載の配合物。
- 前記患者が乾癬を患っている、請求項17又は18に記載の配合物。
- 前記患者が尋常性乾癬を患っている、請求項17又は18に記載の配合物。
- 前記組成物がクリーム又はフォームである、請求項1~8のいずれか一項に記載の医薬組成物。
- ジエチレングリコールモノエチルエーテルをさらに含む、請求項1~8のいずれか一項に記載の医薬組成物。
- ジエチレングリコールモノエチルエーテルが25%w/wの量で含まれる、請求項24に記載の医薬組成物。
- 乳化剤ブレンドが10%w/wの量で含まれる、請求項2に記載の医薬組成物。
- へキシレングリコールが2%w/wの量で含まれる、請求項12に記載の医薬組成物。
- pHが4.0~8.0である、請求項5に記載の医薬組成物。
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US202063021400P | 2020-05-07 | 2020-05-07 | |
US63/021,400 | 2020-05-07 | ||
PCT/US2021/031144 WO2021226370A1 (en) | 2020-05-07 | 2021-05-06 | Treatment of skin conditions using high krafft temperature anionic surfactants |
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JP2012532871A (ja) | 2009-07-08 | 2012-12-20 | ダーミラ(カナダ),インコーポレーテッド | 皮膚疾患または病変の治療に有用なtofa類似体 |
JP2018203736A (ja) | 2017-06-07 | 2018-12-27 | アーキュティス・インコーポレーテッド | ロフルミラストの結晶成長の妨害 |
US20190365642A1 (en) | 2018-06-04 | 2019-12-05 | Arcutis, Inc. | Method and Formulation for Improving Roflumilast Skin Penetration Lag Time |
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NZ537308A (en) * | 2002-05-28 | 2009-09-25 | Nycomed Gmbh | Ophthalmological use of roflumilast for the treatment of diseases of the eye |
US20070066501A1 (en) * | 2005-09-21 | 2007-03-22 | Conopco, Inc., D/B/A Unilever | Process for enhancing squeaky skin feel of surfactant solution rinsed in water by proper selection of components |
US20070098660A1 (en) * | 2005-10-27 | 2007-05-03 | Jim Taneri | Methods and compositions for epilation |
JP2007119432A (ja) * | 2005-10-31 | 2007-05-17 | Ichimaru Pharcos Co Ltd | ペルオキシソーム増殖剤応答性受容体活性化剤 |
US20070258935A1 (en) * | 2006-05-08 | 2007-11-08 | Mcentire Edward Enns | Water dispersible films for delivery of active agents to the epidermis |
US8715700B2 (en) * | 2006-07-21 | 2014-05-06 | Dow Pharmaceutical Sciences, Inc. | Alpha hydroxy acid sustained release formulation |
FR2920967B1 (fr) * | 2007-09-14 | 2009-10-23 | Sederma Soc Par Actions Simpli | Utilisation de l'hydroxymethionine en tant qu'actif anti age |
WO2018144093A2 (en) * | 2016-11-03 | 2018-08-09 | Pinsky Mark A | Formulations for improved skin care |
US11129818B2 (en) * | 2017-06-07 | 2021-09-28 | Arcutis Biotherapeutics, Inc. | Topical roflumilast formulation having improved delivery and plasma half life |
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JP2012532871A (ja) | 2009-07-08 | 2012-12-20 | ダーミラ(カナダ),インコーポレーテッド | 皮膚疾患または病変の治療に有用なtofa類似体 |
JP2018203736A (ja) | 2017-06-07 | 2018-12-27 | アーキュティス・インコーポレーテッド | ロフルミラストの結晶成長の妨害 |
US20190365642A1 (en) | 2018-06-04 | 2019-12-05 | Arcutis, Inc. | Method and Formulation for Improving Roflumilast Skin Penetration Lag Time |
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KR20220074935A (ko) | 2022-06-03 |
AU2021268977A1 (en) | 2022-04-21 |
CA3153934A1 (en) | 2021-11-11 |
US20220211730A1 (en) | 2022-07-07 |
CA3153934C (en) | 2023-01-31 |
CN114641297A (zh) | 2022-06-17 |
IL292098A (en) | 2022-06-01 |
EP4021456A1 (en) | 2022-07-06 |
MX2022008735A (es) | 2022-09-19 |
BR112022007459A2 (pt) | 2022-11-29 |
US20230134782A1 (en) | 2023-05-04 |
WO2021226370A1 (en) | 2021-11-11 |
JP2023502539A (ja) | 2023-01-24 |
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