TW202417003A - 皮膚外用劑組合物 - Google Patents
皮膚外用劑組合物 Download PDFInfo
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- TW202417003A TW202417003A TW112134821A TW112134821A TW202417003A TW 202417003 A TW202417003 A TW 202417003A TW 112134821 A TW112134821 A TW 112134821A TW 112134821 A TW112134821 A TW 112134821A TW 202417003 A TW202417003 A TW 202417003A
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Abstract
本發明之課題在於提供一種含有酯系類固醇及γ-穀維素並使兩種成分完全溶解,即便長期保存亦保持製劑穩定性及成分穩定性,抑制皮膚刺激而使用感優異之皮膚外用劑組合物。
本發明係關於一種皮膚外用劑組合物,其含有以下成分(A)~(C)。
(A)酯系類固醇
(B)γ-穀維素
(C)中鏈脂肪酸三甘油酯
Description
本發明係關於一種含有酯系類固醇之皮膚外用劑組合物。
以潑尼松龍戊酸酯醋酸酯為代表之酯系類固醇具有優異之抗炎作用,藉由外用於皮膚而廣泛用作濕疹/皮炎群、癢疹群、蟄傷、牛皮癬、掌蹠膿皰病等皮膚疾病之治療用藥。
已知該酯系類固醇易被水解,為了穩定地進行調配,需要設法使製劑抑制分解,又,存在不溶解於已知為軟膏基劑之凡士林等中之問題。就該觀點而言,報告有除調配類固醇及中鏈脂肪酸三甘油酯以外,還調配乳酸酯而製成軟膏劑之技術(專利文獻1);除調配類固醇及中鏈脂肪酸三甘油酯以外,還調配大量乙醇而製成液劑之技術(專利文獻2);除調配類固醇及極性油以外,還調配聚丙二醇而製成外用劑之技術(專利文獻3)。
另一方面,γ-穀維素係米糠中所含有之成分,先前已知有皮脂分泌促進作用、皮膚溫度上升作用、及血流量增大作用。又,亦作為美白劑等用於化妝料中。
然而,γ-穀維素對油劑之溶解性低,難以於含有油劑之外用劑中穩定地調配高濃度。作為提昇γ-穀維素之溶解性之嘗試,報告有向γ-穀維素中調配N-月桂醯-L-麩胺酸-2-辛基十二烷基二酯而製成外用劑之技術(專利文獻4)、向γ-穀維素中調配氫化磷脂及包含碳數8以上18以下之脂肪酸與二元醇之二酯而製成外用劑之技術(專利文獻5)。
[先前技術文獻]
[專利文獻]
[專利文獻1]日本專利特開平4-308530號公報
[專利文獻2]日本專利特開平5-178748號公報
[專利文獻3]日本專利特開2016-188187號公報
[專利文獻4]日本專利特開昭57-42621號公報
[專利文獻5]日本專利特開2008-231087號公報
[發明所欲解決之問題]
然而,由於上述含有酯系類固醇或γ-穀維素之皮膚外用劑使用特殊之界面活性劑或乙醇等溶劑,故而存在使表皮角質層中之細胞間脂質軟化而破壞皮膚屏障,從而無法充分達成製劑之本來目的即護膚的顧慮,於使用溶解性不充分之溶劑之情形時,存在以下顧慮:因長期保存而該等難溶成分析出,從而降低使用感,如塗抹於皮膚時有粗澀感等,進而使製劑不均勻。
又,酯系類固醇及γ-穀維素如上所述,均對油劑之溶解性較低,調配有該等兩者之皮膚外用劑並未製品化。
因此,本發明之課題在於提供一種含有酯系類固醇及γ-穀維素並使兩種成分完全溶解,即便長期保存亦保持製劑穩定性及成分穩定性,抑制皮膚刺激而使用感優異之皮膚外用劑組合物。
[解決問題之技術手段]
對此,本發明人為解決上述課題而進行了各種研究,首先,為了溶解酯系類固醇,需要對該類固醇使用大量中鏈脂肪酸三甘油酯,但出於對外用劑賦予皮脂分泌促進作用之目的而添加γ-穀維素後,意外判明酯系類固醇之溶解性得到提昇,可減少中鏈脂肪酸三甘油酯之調配量,結果發現可獲得上述2種成分完全溶解,即便長期保存亦保持製劑穩定性及成分穩定性,抑制皮膚刺激而使用感優異之皮膚外用劑組合物。又,亦發現若向其中調配高級醇,則長期保存後之製劑穩定性及使用感進一步提昇。
即,本發明提供以下發明[1]~[11]。
[1]一種皮膚外用劑組合物,其含有以下成分(A)~成分(C):
(A)酯系類固醇
(B)γ-穀維素
(C)中鏈脂肪酸三甘油酯。
[2]如[1]所記載之皮膚外用劑組合物,其中成分(B)相對於成分(A)之質量比(B/A)為2以上100以下。
[3]如[1]或[2]所記載之皮膚外用劑組合物,其中成分(C)相對於成分(B)之質量比(C/B)為6以上30以下。
[4]如[1]至[3]中任一項所記載之皮膚外用劑組合物,其中成分(A)之含量為0.01質量%以上0.5質量%以下,成分(B)之含量為0.1質量%以上3質量%以下,成分(C)之含量為3質量%以上30質量%以下。
[5]如[1]至[4]中任一項所記載之皮膚外用劑組合物,其進而含有成分(D)高級醇。
[6]如[5]所記載之皮膚外用劑組合物,其中成分(D)之含量為2質量%以上15質量%以下。
[7]如[1]至[6]中任一項所記載之皮膚外用劑組合物,其中成分(A)為選自地塞米松醋酸酯、潑尼松龍醋酸酯、潑尼松龍戊酸酯醋酸酯、氫化可體松丁酸酯、氫化可體松醋酸酯、可體松醋酸酯、及倍他米松戊酸酯中之1種或2種以上。
[8]如[1]至[6]中任一項所記載之皮膚外用劑組合物,其中成分(A)為潑尼松龍戊酸酯醋酸酯。
[9]如[5]至[8]中任一項所記載之皮膚外用劑組合物,其中成分(D)為碳數12以上22以下之鏈式脂肪族一元醇。
[10]如[1]至[9]中任一項所記載之皮膚外用劑組合物,其進而含有選自生育酚類、殺菌劑、局部麻醉劑、尿囊素、及抗組織胺劑中之1種以上。
[11]如[1]至[10]中任一項所記載之皮膚外用劑組合物,其進而含有選自除成分(C)及成分(D)以外之油劑、乳化劑、緩衝劑、螯合劑、多元醇、及水中之1種以上。
[發明之效果]
本發明之皮膚外用劑組合物使酯系類固醇及γ-穀維素兩者溶解而長期保持穩定,且使用感亦良好。
本發明係含有酯系類固醇及γ-穀維素之皮膚外用劑組合物,其一態樣為含有以下成分(A)~成分(C)之皮膚外用劑組合物。
(A)酯系類固醇
(B)γ-穀維素
(C)中鏈脂肪酸三甘油酯
成分(A)為酯系類固醇。酯系類固醇為存在於合成或天然之類固醇骨架中之至少1個羥基由脂肪酸等酯化而成之化合物,具有優異之抗炎作用。由於本發明之皮膚外用劑組合物含有該酯系類固醇,故而可用作濕疹/皮炎群、癢疹群、蟄傷、牛皮癬、掌蹠膿皰病等皮膚疾病之治療用藥。
作為酯系類固醇,只要為可用作皮膚外用劑之酯系類固醇即可,例如可例舉:氯倍他索丙酸酯、雙氟拉松醋酸酯、莫米松糠酸酯、倍他米松丁酸酯丙酸酯、醋酸氟輕松、二氟潑尼酯、安西奈德、雙氟可龍戊酸酯、氫化可體松丁酸酯丙酸酯、地潑羅酮丙酸酯、地塞米松醋酸酯、倍他米松戊酸酯、倍氯米松丙酸酯、潑尼松龍醋酸酯、潑尼松龍戊酸酯醋酸酯、阿氯米松丙酸酯、氯倍他松丁酸酯、氫化可體松丁酸酯、氫化可體松醋酸酯、可體松醋酸酯等。作為成分(A),可使用選自該等酯系類固醇中之1種或2種以上。
其中,較佳為地塞米松醋酸酯、潑尼松龍醋酸酯、潑尼松龍戊酸酯醋酸酯、氫化可體松丁酸酯、氫化可體松醋酸酯、可體松醋酸酯、倍他米松戊酸酯,更佳為潑尼松龍戊酸酯醋酸酯、氫化可體松丁酸酯、倍他米松戊酸酯,進而較佳為潑尼松龍戊酸酯醋酸酯。
關於成分(A)於本發明之皮膚外用劑組合物中之含量,就成分(A)之有效性之觀點而言,較佳為0.01質量%以上,更佳為0.05質量%以上,進而較佳為0.1質量%以上,又,就成分(A)於組合物中之溶解性之觀點而言,較佳為0.5質量%以下,更佳為0.4質量%以下,進而較佳為0.3質量%以下。例如較佳為0.01質量%以上0.5質量%以下,更佳為0.05質量%以上0.4質量%以下,進而較佳為0.1質量%以上0.3質量%以下。
成分(B)為γ-穀維素。γ-穀維素係米糠之脂質中所含之由阿魏酸與固醇縮合而成之酯之總稱。作為主成分,包含穀維素A(環阿烯醇阿魏酸酯)、穀維素C(24-亞甲基環木菠蘿烷醇阿魏酸酯)、菜油固醇阿魏酸酯等。由於本發明之皮膚外用劑組合物含有γ-穀維素,故而藉由其皮脂分泌促進作用,成分(A)之上述藥理作用得到提昇、加強。又,γ-穀維素意外地與成分(C)一同有助於提昇成分(A)之溶解性。
γ-穀維素除包含於米糠中以外,還包含於米胚芽油、玉米油、各種穀物油中,故而可使用自其等油分中提取者。又,亦可使用市售品。
關於成分(B)於本發明之皮膚外用劑組合物中之含量,就成分(B)之有效性之觀點而言,較佳為0.1質量%以上,更佳為0.4質量%以上,進而較佳為0.5質量%以上,又,就成分(B)於組合物中之溶解性之觀點而言,較佳為3質量%以下,更佳為2質量%以下,進而較佳為1.5質量%以下。例如較佳為0.1質量%以上3質量%以下,更佳為0.4質量%以上2質量%以下,進而較佳為0.5質量%以上1.5質量%以下。
成分(C)為中鏈脂肪酸三甘油酯。於本發明中,成分(C)主要有助於提昇成分(A)及成分(B)之溶解性,亦有助於提昇成分(A)及成分(B)之保存穩定性、製劑之保存穩定性及組合物之使用感。
中鏈脂肪酸三甘油酯通常係指碳數6以上12以下之脂肪酸三甘油酯。然而,由於天然之三甘油酯之結構脂肪酸中具有分佈,故而較佳為與以碳數6以上12以下之脂肪酸三甘油酯為主成分之醫藥品添加劑標準之中鏈脂肪酸三甘油酯或凖藥品原料標準之三(辛酸/癸酸)甘油酯相符合之中鏈脂肪酸三甘油酯。
關於成分(C)於本發明之皮膚外用劑組合物中之含量,就成分(A)及成分(B)於組合物中之溶解性、成分(A)及成分(B)之保存穩定性、製劑之保存穩定性之觀點而言,較佳為3質量%以上,更佳為6質量%以上,進而較佳為8質量%以上,又,就組合物之使用感之觀點而言,較佳為30質量%以下,更佳為20質量%以下,進而較佳為15質量%以下。例如較佳為3質量%以上30質量%以下,更佳為6質量%以上20質量%以下,進而較佳為8質量%以上15質量%以下。
於本發明中,如上所述,成分(B)有助於提昇成分(A)於組合物中之溶解性。就該觀點而言,成分(B)相對於成分(A)之質量比(B/A)較佳為2以上100以下,較佳為3以上50以下,進而較佳為4以上15以下。
又,成分(B)及成分(C)亦有助於提昇成分(A)於組合物中之溶解性。就該觀點而言,成分(C)相對於成分(B)之質量比(C/B)較佳為6以上30以下,更佳為8以上20以下,進而較佳為10以上15以下。
就提昇成分(A)及成分(B)於組合物中之長期保存穩定性、提昇成分(A)及成分(B)之溶解性及製劑之長期保存穩定性、以及提昇組合物之使用感之觀點而言,較佳為本發明之皮膚外用劑組合物中進而含有成分(D)高級醇。
高級醇通常係指碳數6以上之長鏈醇,本發明中較佳為使用碳數8以上24以下之鏈式脂肪族一元醇,更佳為使用碳數12以上22以下之鏈式脂肪族一元醇。具體而言,可例舉:月桂醇、肉豆蔻醇、鯨蠟醇、硬脂醇、花生醇、山萮醇、油醇等。
關於成分(D)於本發明之皮膚外用劑組合物中之含量,就提昇成分(A)及成分(B)於組合物中之長期保存穩定性、提昇成分(A)及成分(B)之溶解性及製劑之長期保存穩定性之觀點而言,較佳為2質量%以上,更佳為4質量%以上,進而較佳為6質量%以上,又,就提昇組合物之使用感之觀點而言,較佳為15質量%以下,更佳為12質量%以下,進而較佳為10質量%以下。例如較佳為2質量%以上15質量%以下,更佳為4質量%以上12質量%以下,進而較佳為6質量%以上10質量%以下。
本發明之皮膚外用劑組合物中,除上述成分以外,還可調配局部麻醉劑、殺菌劑、生育酚類、尿囊素、抗組織胺劑等其他有效成分;及除上述成分(C)及成分(D)以外之油劑、乳化劑、緩衝劑、螯合劑、多元醇、胺基酸類、水等。
作為局部麻醉劑,可例舉:利多卡因、狄布卡因、四卡因、羥基狄布卡因、布比卡因、甲哌卡因、丙胺卡因、對丁基胺基苯甲酸二乙基胺基乙酯等,其中較佳為利多卡因、狄布卡因,更佳為利多卡因。該等利多卡因、狄布卡因、四卡因等亦可使用鹽酸鹽。
關於局部麻醉劑於本發明之皮膚外用劑組合物中之含量,就成分(A)及成分(B)之溶解性、穩定性及局部麻醉作用之觀點而言,較佳為0.1質量%以上4質量%以下,更佳為0.2質量%以上3質量%以下,進而較佳為0.5質量%3質量%以下。
作為殺菌劑,可例舉:異丙基甲基苯酚、對羥基苯甲酸甲酯、對羥基苯甲酸乙酯、對羥基苯甲酸丙酯、對羥基苯甲酸丁酯、去氫乙酸鈉、對甲酚等。該等殺菌劑中,較佳為調配異丙基甲基苯酚作為殺菌劑。其他對羥基苯甲酸酯類等較佳為作為防腐劑進行調配。該等殺菌劑較佳為於本發明之皮膚外用劑組合物中含有0.02質量%以上1.0質量%以下,更佳為含有0.05質量%以上0.5質量%以下。
作為生育酚類,可例舉:生育酚、生育酚醋酸酯、生育酚菸鹼酸酯。生育酚類於本發明之皮膚外用劑組合物中之含量較佳為0.1質量%以上2質量%以下,較佳為0.1質量%以上1質量%以下。
尿囊素之化學名為5-脲基乙內醯脲,由於具有組織恢復作用等,故而用作護膚劑。關於尿囊素於本發明之皮膚外用劑組合物中之含量,就尿囊素之作用效果之觀點而言,較佳為0.1質量%以上1質量%以下,更佳為0.1質量%以上0.8質量%以下,進而較佳為0.1質量%以上0.5質量%以下。
作為抗組織胺劑,可例舉:苯海拉明、苯海拉明鹽酸鹽、氯苯那敏、氯苯那敏馬來酸鹽、二苯咪唑等。抗組織胺劑於本發明之皮膚外用劑組合物中之含量較佳為0.05質量%以上5質量%以下,更佳為0.1質量%以上3質量%以下,進而較佳為0.2質量%以上2質量%以下。
作為除上述成分(C)及成分(D)以外之油劑,可例舉:凡士林、角鯊烷、Plastibase、石蠟、液態石蠟、白蜂蠟、矽酮油等。
該等油劑較佳為於本發明之皮膚外用劑組合物中含有1質量%以上80質量%以下,更佳為含有3質量%以上80質量%以下,進而較佳為含有5質量%以上80質量%以下。
作為乳化劑,可例舉:聚氧乙烯氫化蓖麻油、聚氧乙烯山梨醇酐脂肪酸酯、甘油脂肪酸酯、聚氧乙烯脂肪酸酯、聚氧乙烯烷基醚、山梨醇酐脂肪酸酯、聚氧乙烯聚氧丙烯二醇等非離子性界面活性劑或月桂基硫酸鈉、鯨蠟基硫酸鈉等離子性界面活性劑,其中較佳為使用非離子性界面活性劑。乳化劑於本發明之皮膚外用劑組合物中之含量較佳為0.5質量%以上10質量%以下,更佳為0.5質量%以上8質量%以下。
作為緩衝劑,較佳為乳酸、檸檬酸、蘋果酸、酒石酸等脂肪族羥酸與其鹼金屬鹽之組合。
關於緩衝劑於本發明之皮膚外用劑組合物中之含量,就pH值調整作用之觀點而言,較佳為0.1質量%以上3質量%以下,更佳為0.2質量%以上2質量%以下,進而較佳為0.3質量%以上1.5質量%以下。
作為螯合劑,較佳為乙二胺四乙酸、乙二胺四乙酸鈉。關於螯合劑於本發明皮膚外用劑成物中之含量,較佳為0.1質量%以上2質量%以下,更佳為0.2質量%以上1質量%以下,進而較佳為0.2質量%以上0.8質量%以下。
作為多元醇,可例舉:甘油、1,3-丁二醇、丙二醇、二丙二醇、聚乙二醇等。該等多元醇較佳為於本發明之皮膚外用劑組合物中含有2質量%以上20質量%以下,更佳為含有4質量%以上10質量%以下。
水之含量較佳為於本發明之皮膚外用劑組合物中含有0質量%以上70質量%以下,更佳為含有0質量%以上60質量%以下。再者,較佳為於本發明之皮膚外用劑組合物之形態為油性軟膏劑之情形時實質上不含水,於乳霜(油中水型乳化物及水中油型乳化物均包含在內)之情形時含水。
進而,亦可向本發明之皮膚外用劑組合物中調配聚乙烯吡咯啶酮、羧甲基纖維素、膠體性水合矽酸鋁、三仙膠、刺槐豆膠、黃耆膠、瓜爾膠、明膠、阿拉伯膠、海藻酸、白蛋白等增黏劑。
本發明之外皮膚用劑組合物如上所述有油性軟膏劑之情形及乳霜之情形,於乳霜之情形時,就皮膚刺激性、成分之穩定性之方面而言,其pH值較佳為4以上6以下,更佳為4.5以上5.6以下,進而較佳為4.8以上5.4以下。pH值由上述緩衝劑進行調整。
本發明之皮膚外用劑組合物可藉由依照慣用方法均勻混合上述成分而製造。又,作為乳霜之本發明之皮膚外用劑組合物較佳為使添加有乳化劑之親油性成分及親水性成分分別加溫溶解於親油性基劑或水中,將後者添加至前者中並使用均質攪拌機等攪拌而乳化後,將其冷卻至常溫而製造。
由於本發明之皮膚外用劑組合物含有成分(A)酯系類固醇,故而可主要用作濕疹/皮炎群、癢疹群、蟄傷、牛皮癬、掌蹠膿皰病等皮膚疾病之治療用藥。可藉由適量塗抹至產生該等皮膚疾病之部位來使用。
本發明之皮膚外用劑組合物如上所述,成分(A)及成分(B)穩定溶解於組合物中,組合物長期穩定,塗抹至皮膚時之使用感亦良好。此處,成分(A)及成分(B)之穩定性可藉由用高效液相層析法(HPLC)測定長期保存後之組合物中之成分(A)及成分(B)是否分解來判定。又,關於長期之製劑之保存穩定性,可藉由對長期保存後之組合物之肉眼觀察及顯微鏡觀察來判定乳化狀態及有無析出物。又,關於使用感,可將長期保存後之組合物塗抹至皮膚,藉由官能評估來判定有無粗澀感、延展容易度、塗抹容易度。
[實施例]
繼而,舉出實施例來對本發明進行進一步詳細說明,但本發明並不限定於該等實施例。
實施例1~15及比較例1~5
以表1~3中所記載之配方依照慣用方法製造油性軟膏劑及乳霜劑。對於所得之製劑,由下述方法評估(1)成分穩定性、(2)製劑穩定性、及(3)使用感。又,亦進行該等評估之(4)綜合評估。將結果示於表1~3中。
(1)關於成分穩定性,藉由於嚴酷條件(50℃、1個月)下保存製劑以預測長期保存之情形時之化學變化,並以高效液相層析法(HPLC)測定製劑中之成分(A)及(B)是否分解,以下述基準進行評估。又,(2)關於製劑穩定性,進行將低溫設為5℃、將高溫設為40℃,並且每12小時急速改變1次保存溫度之所謂之溫度循環試驗,藉由對其保存1個月後之組合物之目視及顯微鏡觀察,以下述基準評估乳化狀態及有無析出物。又,(3)關於使用感,將於與如上所示之條件相同之溫度循環試驗中保存1個月後之組合物塗抹至皮膚,利用官能試驗以下述基準評估有無粗澀感、延展容易度、塗抹容易度。再者,(4)綜合評估係以下述基準,基於(1)成分穩定性、(2)製劑穩定性、及(3)使用感這3個項目之評估分5個等級進行評估。
(1)關於成分穩定性之評估(50℃,保存1個月後)
◎:成分(A)及(B)之殘存率均為97%以上
○:成分(A)及(B)之殘存率均為95%以上
△:成分(A)及(B)之殘存率均為90%以上
×:成分(A)及(B)中之任一者之殘存率未達90%
(2)關於製劑穩定性之評估(溫度循環試驗,保存1個月後)
◎: 目視未確認到相分離,顯微鏡觀察未確認到析出物。
又,關於乳霜劑,乳化狀態中未確認到變化。
○: 目視幾乎未確認到相分離,顯微鏡觀察幾乎未確認到析出物。
又,關於乳霜劑,乳化狀態中幾乎未確認到變化。
△:目視略微確認到相分離,或者顯微鏡觀察略微確認到析出物。
×:目視明顯確認到相分離,或者顯微鏡觀察明顯確認到析出物。
(3)關於使用感之評估(溫度循環試驗,保存1個月後)
◎:無粗澀感,易適度延展
○:幾乎無粗澀感,易延展
△:略微有粗澀感,或者稍硬而延展困難或稍軟而延展過度
×:明顯有粗澀感,或者非常硬而延展困難或液體化而延展過度
(4)關於綜合評估
A:3個項目均為◎
B:2個項目為◎,1個項目為○
C:2個項目或3個項目為○,無×及△
D:有1個×
E:有2個以上×
[表1]
成分名 | 實施例1 | 實施例2 | 實施例3 | 實施例4 | 實施例5 | 實施例6 | 實施例7 |
潑尼松龍戊酸酯醋酸酯 | 0.15 | 0.15 | 0.01 | 0.01 | |||
氫化可體松醋酸酯 | 0.25 | 0.5 | 0.4 | ||||
γ-穀維素 | 1 | 1 | 0.1 | 1 | 0.5 | 3 | 0.8 |
中鏈脂肪酸三甘油酯 | 15 | 15 | 3 | 15 | 8 | 30 | 8 |
硬脂醇 | 6 | 8.5 | 6 | 2 | 6 | 6 | 6 |
山萮醇 | 4 | 4 | 4 | ||||
鯨蠟醇 | 3 | 2 | |||||
月桂醇 | 2 | ||||||
聚氧乙烯花生醚 | 2 | 2 | 2 | 2 | 2 | ||
聚氧乙烯硬脂醚 | 2 | ||||||
白凡士林 | 5 | 75.35 | 5 | 5 | 5 | 5 | |
甘油 | 5 | 5 | 5 | 5 | 5 | 5 | |
1,3-丁二醇 | 5 | 5 | 5 | 5 | 5 | 5 | |
檸檬酸 | 適量 | 適量 | 適量 | 適量 | 適量 | 適量 | |
純化水 | 餘量 | 餘量 | 餘量 | 餘量 | 餘量 | 餘量 | |
合計(重量%) | 100 | 100 | 100 | 100 | 100 | 100 | 100 |
pH值 | 5.1 | - | 4.0 | 5.0 | 5.5 | 6.0 | 5.3 |
成分穩定性 | ◎ | ◎ | ◎ | ◎ | ○ | ○ | ◎ |
製劑穩定性 | ◎ | ◎ | ○ | ○ | ○ | ○ | ○ |
使用感 | ◎ | ○ | ○ | ○ | ○ | ○ | ○ |
綜合評估 | A | B | C | C | C | C | C |
[表2]
成分名 | 實施例8 | 實施例9 | 實施例10 | 實施例11 | 實施例12 | 實施例13 | 實施例14 | 實施例15 |
潑尼松龍戊酸酯醋酸酯 | 0.05 | 0.05 | 0.15 | 0.1 | 0.3 | 0.15 | 0.15 | 0.15 |
γ-穀維素 | 0.4 | 1.2 | 2 | 1.5 | 1 | 1 | 1 | 1 |
中鏈脂肪酸三甘油酯 | 7 | 15 | 20 | 15 | 12 | 10 | 10 | 10 |
硬脂醇 | 6 | 4 | 6 | 6 | 6 | 6 | 6 | 6 |
山萮醇 | 4 | 4 | 4 | 2 | ||||
利多卡因 | 2 | 2 | 2 | |||||
異丙基甲基苯酚 | 0.1 | 0.1 | 0.1 | |||||
生育酚醋酸酯 | 0.5 | 0.5 | 0.5 | |||||
尿囊素 | 0.25 | 0.25 | 0.25 | |||||
氯苯那敏馬來酸鹽 | 1 | 1 | 1 | |||||
聚氧乙烯花生醚 | 2 | 2 | 2 | 2 | 2 | |||
聚氧乙烯硬脂醚 | 2 | |||||||
硬脂酸聚烴氧酯 | 3 | |||||||
單硬脂酸甘油酯 | 1 | 3 | ||||||
聚氧乙烯氫化蓖麻油 | 2 | |||||||
白凡士林 | 5 | 5 | 5 | 5 | 5 | 5 | 4.5 | |
角鯊烷 | 10 | 5 | 2 | |||||
對羥基苯甲酸丁酯 | 0.15 | 0.15 | 0.15 | |||||
乙二胺四乙酸鈉 | 0.2 | 0.2 | 0.2 | |||||
甘油 | 5 | 5 | 5 | 5 | 5 | 10 | 8 | 8 |
1,3-丁二醇 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 |
檸檬酸 | 適量 | 適量 | 適量 | 適量 | 適量 | 適量 | 適量 | 適量 |
純化水 | 餘量 | 餘量 | 餘量 | 餘量 | 餘量 | 餘量 | 餘量 | 餘量 |
合計(重量%) | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 |
pH值 | 4.5 | 4.8 | 5.6 | 4.8 | 5.4 | 5.3 | 4.9 | 5.1 |
成分穩定性 | ◎ | ◎ | ○ | ◎ | ◎ | ◎ | ◎ | ◎ |
製劑穩定性 | ◎ | ◎ | ◎ | ◎ | ◎ | ◎ | ◎ | ◎ |
使用感 | ○ | ○ | ◎ | ◎ | ◎ | ○ | ◎ | ◎ |
綜合評估 | B | B | B | A | A | B | A | A |
[表3]
成分名 | 比較例1 | 比較例2 | 比較例3 | 比較例4 | 比較例5 |
潑尼松龍戊酸酯醋酸酯 | 0.15 | 0.15 | 0.15 | 0.15 | 0.15 |
γ-穀維素 | 0.5 | 0.5 | 0.5 | 1 | |
中鏈脂肪酸三甘油酯 | 10 | ||||
三肉豆蔻酸甘油酯 | 20 | ||||
己二酸二異丁酯 | 15 | ||||
硬脂醇 | 2 | 2 | 2 | ||
2-丁基-2-乙基-1,3-丙烷二醇 | 6 | ||||
二癸酸丙二醇酯 | 6 | ||||
甘油脂肪酸單酯 | 10 | ||||
聚氧乙烯硬脂醚 | 2 | 2 | 2 | ||
月桂醯麩胺酸二辛基十二烷基酯 | 10 | 10 | |||
白凡士林 | 5 | 5 | 5 | 5 | |
甘油 | 5 | 5 | 5 | 10 | 3 |
1,3-丁二醇 | 5 | 5 | 5 | 6 | 3 |
檸檬酸 | 適量 | 適量 | 適量 | 適量 | 適量 |
純化水 | 餘量 | 餘量 | 餘量 | 餘量 | 餘量 |
合計(重量%) | 100 | 100 | 100 | 100 | 100 |
pH值 | 5.1 | 5.1 | 5.1 | 5.1 | 5.1 |
成分穩定性 | ◎ | ◎ | ◎ | ◎ | ◎ |
製劑穩定性 | × | × | × | × | × |
使用感 | × | × | × | × | × |
綜合評估 | E | E | E | E | E |
根據表1~3可知,含有(A)酯系類固醇、(B)γ-穀維素、及(C)中鏈脂肪酸三甘油酯之本發明之皮膚外用劑組合物之成分(A)及(B)之溶解性良好,長期穩定,並且使用感亦良好。
Claims (11)
- 一種皮膚外用劑組合物,其含有以下成分(A)~成分(C): (A)酯系類固醇 (B)γ-穀維素 (C)中鏈脂肪酸三甘油酯。
- 如請求項1之皮膚外用劑組合物,其中成分(B)相對於成分(A)之質量比(B/A)為2以上100以下。
- 如請求項1之皮膚外用劑組合物,其中成分(C)相對於成分(B)之質量比(C/B)為6以上30以下。
- 如請求項1之皮膚外用劑組合物,其中成分(A)之含量為0.01質量%以上0.5質量%以下,成分(B)之含量為0.1質量%以上3質量%以下,成分(C)之含量為3質量%以上30質量%以下。
- 如請求項1至4中任一項之皮膚外用劑組合物,其進而含有成分(D)高級醇。
- 如請求項5之皮膚外用劑組合物,其中成分(D)之含量為2質量%以上15質量%以下。
- 如請求項1之皮膚外用劑組合物,其中成分(A)為選自地塞米松醋酸酯、潑尼松龍醋酸酯、潑尼松龍戊酸酯醋酸酯、氫化可體松丁酸酯、氫化可體松醋酸酯、可體松醋酸酯、及倍他米松戊酸酯中之1種或2種以上。
- 如請求項1之皮膚外用劑組合物,其中成分(A)為潑尼松龍戊酸酯醋酸酯。
- 如請求項5之皮膚外用劑組合物,其中成分(D)為碳數12以上22以下之鏈式脂肪族一元醇。
- 如請求項1之皮膚外用劑組合物,其進而含有選自生育酚類、殺菌劑、局部麻醉劑、尿囊素、及抗組織胺劑中之1種以上。
- 如請求項1之皮膚外用劑組合物,其進而含有選自除成分(C)及成分(D)以外之油劑、乳化劑、緩衝劑、螯合劑、多元醇、及水中之1種以上。
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