TW202112360A - 外用劑組合物 - Google Patents
外用劑組合物 Download PDFInfo
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- TW202112360A TW202112360A TW109119885A TW109119885A TW202112360A TW 202112360 A TW202112360 A TW 202112360A TW 109119885 A TW109119885 A TW 109119885A TW 109119885 A TW109119885 A TW 109119885A TW 202112360 A TW202112360 A TW 202112360A
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- oil
- urea
- allantoin
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Abstract
本發明提供一種含有脲、酯系類固醇及尿囊素3種成分且穩定之水中油型乳化組合物。
本發明之水中油型乳化組合物含有以下成分(A)～(D)，且pH值為5～6。
(A)脲 0.5～10質量%、
(B)酯系類固醇 0.05～0.3質量%、
(C)尿囊素 0.1～1質量%、及
(D)胺基酸或其鹽 1～10質量%
Description
本發明係關於一種含有脲、酯系類固醇及尿囊素之外用劑組合物。
脲具有優異之增加角質之水分保持量之作用、改善乾燥性角化症中角質層之保水力下降之作用、溶解･剝離角質之作用，用於治療魚鱗癬、老年性乾皮症、異位性皮膚、進行性指掌角化症、足蹠部皸裂性皮膚炎、掌蹠角化症、毛髮苔蘚等。但是，已知於水之存在下，脲藉由酸、鹼、熱等容易分解，產生氨，因此尤其於含有水之乳霜劑等中產生氨臭，pH值上升，使得商品價值下降。
作為使此類含脲之製劑穩定化之方法，報告有添加尿囊素(專利文獻1)、添加胺基酸(專利文獻2、3)、添加乳酸(專利文獻4)等。
另一方面，以潑尼松龍醋酸戊酸酯為代表之酯系類固醇藉由皮膚外用而廣泛地用作濕疹･皮炎群、癢疹群、昆蟲叮咬、乾癬、掌蹠膿皰症等皮膚疾病之治療藥。該酯系類固醇亦容易被水解，穩定性存在問題，報告有於酯系類固醇中調配鹼性局部麻醉藥與檸檬酸、乳酸或蘋果酸而使其穩定化之技術(專利文獻5)、於酯系類固醇中調配薄荷腦、樟腦等與pH值調整劑之技術(專利文獻6)。
又，尿囊素具有組織恢復作用等，因此作為皮膚保護劑用於化妝品等。又，尿囊素亦具有容易被水解之性質，因此報告有調配乳酸而使其穩定化之技術(專利文獻7)。
[先前技術文獻]
[專利文獻]
[專利文獻1]日本專利特開昭52-109487號公報
[專利文獻2]日本專利特開昭59-134707號公報
[專利文獻3]日本專利特開昭61-30509號公報
[專利文獻4]日本專利特公昭47-47662號公報
[專利文獻5]日本專利特開2001-72603號公報
[專利文獻6]日本專利特開2005-350379號公報
[專利文獻7]日本專利特開2013-1651號公報
[發明所欲解決之問題]
如上所述，由於脲、酯系類固醇及尿囊素分別容易被水解，故而同時調配有該等3種成分之外用劑組合物未製品化。
因此，本發明之課題在於提供一種含有該等3種成分，且穩定、使用感優異之外用劑組合物。
[解決問題之技術手段]
因此，本發明人製造調配有上述3種成分之水中油型乳化組合物，對其穩定性進行銳意研究，結果發現藉由於上述3種成分中調配特定量之胺基酸或其鹽，將其pH值調整為5～6，而穩定地保持該等3種成分，從而完成本發明。
即，本發明提供以下[1]～[6]。
[1]一種水中油型乳化組合物，其含有以下成分(A)～(D)，且pH值為5～6。
(A)脲 0.5～10質量%、
(B)酯系類固醇 0.05～0.3質量%、
(C)尿囊素 0.1～1質量%、及
(D)胺基酸或其鹽 1～10質量%
[2]如[1]所記載之水中油型乳化組合物，其進而含有(E)羥酸或其鹽。
[3]如[1]或[2]所記載之水中油型乳化組合物，其進而含有(F)局部麻醉劑。
[4]如[1]至[3]中任一項所記載之水中油型乳化組合物，其進而含有(G)螯合劑。
[5]如[1]至[4]中任一項所記載之水中油型乳化組合物，其進而含有選自(H)維生素E、維生素E醋酸酯及維生素E菸鹼酸酯之維生素E類。
[6]如[1]至[5]中任一項所記載之水中油型乳化組合物，其進而含有選自殺菌劑、油性基劑、多元醇、乳化劑及水之1種或2種以上。
[發明之效果]
本發明可提供一種含有雖對皮膚疾病有用但分別穩定性存在問題之脲、酯系類固醇及尿囊素3種成分，且該等3種成分之穩定性得到保持之外用劑組合物。
本發明之水中油型乳化組合物之特徵在於含有以下成分(A)～(D)，且pH值為5～6。
(A)脲 0.5～10質量%、
(B)酯系類固醇 0.05～0.3質量%、
(C)尿囊素 0.1～1質量%、及
(D)胺基酸或其鹽 1～10質量%。
成分(A)係脲。就脲所具有之作用效果及穩定性之觀點而言，本發明組合物中之成分(A)之含量為0.5～10質量%，較佳為0.5～8質量%，更佳為1～8質量%，進而較佳為2～7質量%。
作為成分(B)酯系類固醇，只要為用作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、倍他米松丁酸丙酸酯、氟輕松醋酸酯、二氟潑尼酯、安西奈德、雙氟可龍戊酸酯、氫化可體松丁酸丙酸酯、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、潑尼松龍醋酸戊酸酯、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。
其中，較佳為地塞米松醋酸酯、潑尼松龍醋酸酯、潑尼松龍醋酸戊酸酯、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，更佳為潑尼松龍醋酸戊酸酯、氫化可體松丁酸酯、倍他米松戊酸酯，進而較佳為潑尼松龍醋酸戊酸酯。
就酯系類固醇之作用效果及穩定性之觀點而言，本發明組合物中之成分(B)之含量為0.05～0.3質量%，較佳為0.1～0.3質量%，更佳為0.1～0.25質量%。
成分(C)尿囊素之化學名為5-脲基乙內醯脲，就尿囊素之作用效果及穩定性之觀點而言，本發明組合物中之使用量為0.1～1質量%，較佳為0.1～0.8質量%，更佳為0.1～0.5質量%。
作為成分(D)胺基酸，可例舉α-胺基酸，具體而言，可例舉：甘胺酸、麩胺酸、天冬胺酸、精胺酸、丙胺酸或其等之鹽。其中，就成分(A)～(C)之穩定性之方面而言，較佳為甘胺酸、麩胺酸、丙胺酸，更佳為甘胺酸、丙胺酸。又，作為胺基酸之鹽，於酸性胺基酸之情形時，可使用鈉鹽、鉀鹽等鹼金屬鹽。於鹼性胺基酸之情形時，使用鹽酸鹽等。又，作為該等胺基酸，亦可使用L體、D體、DL體之任一者。又，可使用該等胺基酸之1種或組合使用2種以上。
就成分(A)～(C)之穩定性之觀點而言，本發明組合物中之成分(D)之含量為1～10質量%，較佳為2～8質量%，更佳為3～7質量%，進而較佳為4～6質量%。
就確保成分(A)～(C)之穩定性之方面而言，本發明組合物較佳為進而含有(E)羥酸或其鹽。作為羥酸，較佳為乳酸、檸檬酸、蘋果酸、酒石酸之脂肪族羥酸，更佳為乳酸、檸檬酸、蘋果酸，進而較佳為乳酸、檸檬酸。作為該等羥酸之鹽，可例舉：鈉鹽、鉀鹽等鹼金屬鹽。該等羥酸或其鹽可使用1種或組合使用2種以上。再者，該等羥酸或其鹽亦作為pH值調整劑發揮作用。
就成分(A)～(C)之穩定性之觀點而言，本發明組合物中之成分(E)之含量為0.5～3質量%，較佳為0.5～2質量%，更佳為0.5～1.5質量%。
就成分(A)～(C)之穩定性及抑制皮膚之發癢、疼痛、灼熱、刺激等之觀點而言，本發明組合物較佳為含有(F)局部麻醉劑。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(Oxy Dibucaine)、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。
就成分(A)～(C)之穩定性及局部麻醉作用之觀點而言，本發明組合物中之成分(F)之含量為0.1～4質量%，較佳為0.2～3質量%，更佳為0.5～3質量%，進而較佳為1～3質量%。
就成分(A)～(C)之穩定性之觀點而言，本發明組合物較佳為含有(G)螯合劑。作為(G)螯合劑，較佳為乙二胺四乙酸、乙二胺四乙酸鈉。就使成分(A)～(C)穩定化之方面而言，本發明組合物中之(G)螯合劑之含量為0.1～2質量%，較佳為0.2～1質量%，更佳為0.2～0.8質量%。
又，就成分(A)～(C)之穩定性之觀點而言，本發明組合物較佳為含有(H)選自維生素E、維生素E醋酸酯及維生素E菸鹼酸酯之維生素E類。該等成分(H)之中，較佳為使用維生素E醋酸酯。
就使成分(A)～(C)穩定化之觀點而言，本發明組合物中之成分(H)之含量為0.1～2質量%，較佳為0.1～1質量%。
又，就成分(A)～(C)之穩定性之觀點而言，本發明組合物較佳為含有(I)選自殺菌劑、油性基劑、多元醇、乳化劑及水之1種或2種以上。
此處，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、脫氫醋酸鈉、對甲酚等。該等殺菌劑於本發明組合物中較佳為含有0.05～0.8質量%，更佳為含有0.05～0.3質量%。
作為油性基劑，可例舉：凡士林、Plastibase、石蠟、液態石蠟、白蜂蠟、山萮醇、硬脂醇、鯨蠟醇、鯨蠟硬脂醇、硬脂酸、山萮酸、矽酮油等。該等油性基劑於本發明組合物中較佳為含有10～40質量%，更佳為含有10～35質量%，進而較佳為含有15～30質量%。
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。該等多元醇於本發明組合物中較佳為含有10～40質量%，更佳為含有10～30質量%。
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。本發明組合物中之乳化劑之含量較佳為1～15質量%，更佳為2～10質量%。
關於水之含量，於本發明組合物中較佳為含有30～60質量%，更佳為含有35～55質量%。
進而，本發明組合物中亦可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。
就確保成分(A)～(C)之穩定性之方面而言，本發明組合物之pH值為5～6。於pH值未達5或超過6之情形時，成分(A)～(C)之任一成分之穩定性變得不充分。較佳之pH值為5.1～5.9，更佳之pH值為5.1～5.6。為了將pH值調整為該等範圍，較佳為藉由添加上述(E)羥酸或其鹽而進行。此處，pH值係最終之水中油型乳化組合物之pH值。
本發明組合物係含有上述成分之水中油型乳化組合物，作為外用劑塗抹於皮膚時之使用感良好。該組合物較佳為以如下方式製造：依據常規方法，將添加有乳化劑之親油性成分與親水性成分分別分開加溫溶解於親油性基劑或水中，將後者添加於前者，使用均質攪拌機等進行攪拌使其乳化之後，將其冷卻至常溫。
本發明組合物由於上述成分(A)～(C)得以長時間穩定地保持，故而即便於長期保存後亦發揮上述成分(A)～(C)之優異之效果。
[實施例]
其次，例舉實施例對本發明詳細地進行說明，但本發明不受其任何限定。
實施例1～23及比較例1～4
依據常規方法製造表1～表6所記載之水中油型乳化組合物，於濕度60%、25℃下保存12個月，對各成分之穩定性、使用感等進行評價。將其結果示於表1～表6。其中，由5名官能檢查員對使用感、容器之膨脹、刺激性進行評價。
(1)有關脲之評價
利用液相層析法測定於25℃下保存12個月之後之殘存率。
◎：於25℃下保存12個月後殘存率為97%以上
〇：於25℃下保存12個月後殘存率為95%以上
△：於25℃下保存12個月後殘存率為93%以上
×：於25℃下保存12個月後殘存率未達93%
(2)有關酯系類固醇之評價
利用液相層析法測定於25℃下保存12個月之後之殘存率。
◎：於25℃下保存12個月後殘存率為97%以上
〇：於25℃下保存12個月後殘存率為95%以上
△：於25℃下保存12個月後殘存率為93%以上
×：於25℃下保存12個月後殘存率未達93%
(3)有關尿囊素之評價
利用液相層析法測定於25℃下保存12個月之後之殘存率。
◎：於25℃下保存12個月後殘存率為97%以上
〇：於25℃下保存12個月後殘存率為95%以上
△：於25℃下保存12個月後殘存率為93%以上
×：於25℃下保存12個月後殘存率未達93%
(4)pH值緩衝性
於25℃下保存12個月之後測定pH值，對其pH值上升進行評價。
◎：未達0.1
〇：0.1以上且未達0.2
△：0.2以上且未達0.3
×：0.3以上
(5)使用感係依據以下基準進行評價。
◎：非常容易塗抹
〇：容易塗抹
△：稍難塗抹
×：難以塗抹
(6)依據以下基準對容器之膨脹進行評價。
◎：完全未見
〇：幾乎未見
△：稍微可見
×：可見
(7)依據以下基準對刺激性進行評價。
◎：完全未感受到
〇：幾乎未感受到
△：稍微感受到
×：感受到
(8)依據以下基準對綜合評價進行評價。
◎：上述所有評價項目中均為◎評價
〇：無×評價之項目，且〇以上之評價項目有4個以上
△：無×評價之項目，且〇以上之評價項目有3個以下
×：×評價之項目有1個以上
[表1]
| 成分 | 實施例1 | 實施例2 | 實施例3 | 實施例4 | 實施例5 | |
| (A) | 脲 | 5 | 5 | 5 | 5 | 5 |
| (B) | 潑尼松龍醋酸戊酸酯 | 0.15 | 0.15 | 0.15 | 0.15 | 0.15 |
| (C) | 尿囊素 | 0.2 | 0.2 | 0.2 | 0.2 | 0.2 |
| (D) | 甘胺酸 | 2 | 2 | 2 | 2 | 2 |
| L-麩胺酸鈉 | - | - | - | - | - | |
| L-天冬胺酸 | - | - | - | - | - | |
| L-精胺酸 | - | - | - | - | - | |
| DL-丙胺酸 | 3 | 3 | 3 | 3 | 3 | |
| (E) | 乳酸 | 1 | 1 | 1 | 1 | 1 |
| 檸檬酸水合物 | - | - | - | - | - | |
| (F) | 利多卡因 | 2 | 2 | 2 | 2 | 2 |
| 利多卡因鹽酸鹽 | - | - | - | - | - | |
| (G) | 乙二胺四乙酸鈉 | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 |
| (H) | 維生素E醋酸酯 | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 |
| 異丙基甲基苯酚 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | |
| 對羥基苯甲酸丁酯 | 0.15 | 0.15 | 0.15 | 0.15 | 0.15 | |
| 純化水 | 適量 | 適量 | 適量 | 適量 | 適量 | |
| 甘油 | 10 | 10 | 10 | 10 | 10 | |
| 1,3-丁二醇 | 5 | 5 | 5 | 5 | 5 | |
| 三仙膠 | - | - | - | - | - | |
| 凡士林 | 10 | 5 | 4.5 | 5 | 10 | |
| 液態石蠟 | 10 | 10 | 10.5 | 10 | 10 | |
| 鯨蠟硬脂醇 | 6 | 4 | 4 | 4 | 6 | |
| 鯨蠟醇 | - | - | - | - | - | |
| 硬脂醇 | - | - | - | - | - | |
| 山萮醇 | - | 1 | 1 | 1 | - | |
| 硬脂酸甘油酯 | - | 2 | 3 | 4 | - | |
| 聚氧乙烯鯨蠟醚 | 3 | - | - | - | 3 | |
| 硬脂酸聚烴氧酯 | - | 4 | 3 | 2 | - | |
| pH值(利用乳酸/乳酸鈉進行調整) | 6.0 | 5.9 | 5.5 | 5.1 | 5.0 | |
| 有關脲之評價 | ◎ | ◎ | ◎ | 〇 | 〇 | |
| 有關類固醇之評價 | 〇 | 〇 | ◎ | ◎ | ◎ | |
| 有關尿囊素之評價 | △ | 〇 | ◎ | ◎ | ◎ | |
| pH值緩衝性(穩定性) | ◎ | ◎ | ◎ | ◎ | ◎ | |
| 使用感 | 〇 | 〇 | ◎ | 〇 | 〇 | |
| 容器之膨脹 | ◎ | ◎ | ◎ | 〇 | △ | |
| 刺激性 | ◎ | ◎ | ◎ | ◎ | ◎ | |
| 綜合評價 | 〇 | 〇 | ◎ | 〇 | 〇 |
[表2]
| 成分 | 實施例6 | 實施例7 | 實施例8 | 實施例9 | 實施例10 | |
| (A) | 脲 | 0.5 | 10 | 5 | 5 | 5 |
| (B) | 潑尼松龍醋酸戊酸酯 | 0.15 | 0.15 | 0.05 | 0.3 | 0.15 |
| (C) | 尿囊素 | 0.2 | 0.2 | 0.2 | 0.2 | 0.1 |
| (D) | 甘胺酸 | 2 | 2 | 2 | 2 | 2 |
| L-麩胺酸鈉 | - | - | - | - | - | |
| L-天冬胺酸 | - | - | - | - | - | |
| L-精胺酸 | - | - | - | - | - | |
| DL-丙胺酸 | 3 | 3 | 3 | 3 | 3 | |
| (E) | 乳酸 | 1 | 1 | 0.5 | 0.5 | 1 |
| 檸檬酸水合物 | - | - | - | - | - | |
| (F) | 利多卡因 利多卡因鹽酸鹽 | 2 - | 2 - | 2 - | 2 - | 2 - |
| (G) | 乙二胺四乙酸鈉 | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 |
| (H) | 維生素E醋酸酯 | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 |
| 異丙基甲基苯酚 | 0.1 | - | 0.1 | 0.1 | 0.1 | |
| 對羥基苯甲酸丁酯 | - | 0.15 | 0.15 | 0.15 | 0.15 | |
| 純化水 | 適量 | 適量 | 適量 | 適量 | 適量 | |
| 甘油 | 10 | 10 | 10 | 10 | 10 | |
| 1,3-丁二醇 | 5 | 5 | 5 | 5 | 5 | |
| 三仙膠 | - | - | 0.1 | - | - | |
| 凡士林 | 10 | 5 | 4.5 | 5 | 10 | |
| 液態石蠟 | 10 | 10 | 10.5 | 10 | 10 | |
| 鯨蠟硬脂醇 | 6 | 4 | 4 | 4 | 6 | |
| 鯨蠟醇 | - | - | - | - | - | |
| 硬脂醇 | - | - | - | - | - | |
| 山萮醇 | - | 1 | 1 | 1 | - | |
| 硬脂酸甘油酯 | 2 | 2.5 | 4 | 3 | - | |
| 聚氧乙烯鯨蠟醚 | - | - | - | - | 3 | |
| 硬脂酸聚烴氧酯 | 4 | 2.5 | 2 | 3 | - | |
| pH值(利用乳酸/乳酸鈉進行調整) | 5.1 | 5.9 | 6.0 | 6.0 | 5.5 | |
| 有關脲之評價 | 〇 | 〇 | ◎ | ◎ | ◎ | |
| 有關類固醇之評價 | ◎ | 〇 | △ | 〇 | ◎ | |
| 有關尿囊素之評價 | ◎ | 〇 | ◎ | ◎ | 〇 | |
| pH值緩衝性(穩定性) | ◎ | △ | ◎ | ◎ | ◎ | |
| 使用感 | 〇 | △ | △ | 〇 | △ | |
| 容器之膨脹 | ◎ | △ | ◎ | ◎ | ◎ | |
| 刺激性 | ◎ | △ | ◎ | ◎ | ◎ | |
| 綜合評價 | 〇 | △ | 〇 | 〇 | 〇 |
[表3]
| 成分 | 實施例11 | 實施例12 | 實施例13 | 實施例14 | 實施例15 | |
| (A) | 脲 | 5 | 5 | 5 | 5 | 5 |
| (B) | 潑尼松龍醋酸戊酸酯 | 0.15 | 0.15 | 0.15 | 0.15 | 0.15 |
| (C) | 尿囊素 | 1 | 0.2 | 0.2 | 0.2 | 0.2 |
| (D) | 甘胺酸 | 2 | 2 | 2 | 2 | 2 |
| L-麩胺酸鈉 | - | - | - | - | - | |
| L-天冬胺酸 | - | 3 | - | - | - | |
| L-精胺酸 | - | - | - | - | - | |
| DL-丙胺酸 | 3 | 3 | 3 | 3 | 3 | |
| (E) | 乳酸 | - | - | 1 | - | 1 |
| 檸檬酸水合物 | - | - | - | - | - | |
| (F) | 利多卡因 | 2 | - | - | - | 0.2 |
| 利多卡因鹽酸鹽 | - | - | - | 2 | - | |
| (G) | 乙二胺四乙酸鈉 | 0.5 | - | - | 0.5 | 0.5 |
| (H) | 維生素E醋酸酯 | 0.5 | 0.5 | - | 0.5 | 0.5 |
| 異丙基甲基苯酚 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | |
| 對羥基苯甲酸丁酯 | 0.15 | 0.15 | 0.15 | 0.15 | 0.15 | |
| 純化水 | 適量 | 適量 | 適量 | 適量 | 適量 | |
| 甘油 | 10 | 10 | 10 | 10 | 10 | |
| 1,3-丁二醇 | 5 | 5 | 5 | 5 | 5 | |
| 三仙膠 | - | - | - | - | - | |
| 凡士林 | 10 | 5 | 4.5 | 5 | 10 | |
| 液態石蠟 | 10 | 10 | 10.5 | 10 | 10 | |
| 鯨蠟硬脂醇 | 6 | 4 | 4 | 4 | 6 | |
| 鯨蠟醇 | - | - | - | - | - | |
| 硬脂醇 | - | - | - | - | - | |
| 山萮醇 | - | 1 | 1 | 1 | - | |
| 硬脂酸甘油酯 | - | - | 2.5 | 3.5 | 4 | |
| 聚氧乙烯鯨蠟醚 | 3 | 3 | - | - | - | |
| 硬脂酸聚烴氧酯 | - | - | 4.5 | 3 | 2 | |
| pH值(利用乳酸/乳酸鈉進行調整) | 5.5 | 5.9 | 5.9 | 5.1 | 5.1 | |
| 有關脲之評價 | △ | △ | ◎ | ◎ | ◎ | |
| 有關類固醇之評價 | ◎ | △ | △ | ◎ | ◎ | |
| 有關尿囊素之評價 | 〇 | △ | △ | ◎ | ◎ | |
| pH值緩衝性(穩定性) | △ | 〇 | 〇 | 〇 | 〇 | |
| 使用感 | 〇 | △ | 〇 | ◎ | 〇 | |
| 容器之膨脹 | ◎ | ◎ | ◎ | ◎ | ◎ | |
| 刺激性 | ◎ | △ | △ | ◎ | 〇 | |
| 綜合評價 | 〇 | △ | 〇 | 〇 | 〇 |
[表4]
| 成分 | 實施例16 | 實施例17 | 實施例18 | 實施例19 | 實施例20 | |
| (A) | 脲 | 5 | 5 | 5 | 5 | 5 |
| (B) | 潑尼松龍醋酸戊酸酯 | 0.15 | 0.15 | 0.15 | 0.15 | 0.15 |
| (C) | 尿囊素 | 0.2 | 0.2 | 0.2 | 0.2 | 0.2 |
| (D) | 甘胺酸 | 2 | 1 | 2 | 2 | 2 |
| L-麩胺酸鈉 | - | - | - | 4.5 | - | |
| L-天冬胺酸 | - | - | - | - | - | |
| L-精胺酸 | - | - | - | 0.4 | - | |
| DL-丙胺酸 | 3 | - | - | 3 | 3 | |
| (E) | 乳酸 | 1 | 1 | 1 | 1 | - |
| 檸檬酸水合物 | - | - | - | - | 1 | |
| (F) | 利多卡因 | 4 | 2 | 2 | 2 | 2 |
| 利多卡因鹽酸鹽 | - | - | - | - | - | |
| (G) | 乙二胺四乙酸鈉 | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 |
| (H) | 維生素E醋酸酯 | 0.5 | 0.5 | 0.5 | - | 0.5 |
| 異丙基甲基苯酚 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | |
| 對羥基苯甲酸丁酯 | 0.15 | 0.15 | 0.15 | 0.15 | 0.15 | |
| 純化水 | 適量 | 適量 | 適量 | 適量 | 適量 | |
| 甘油 | 10 | 10 | 10 | 10 | 10 | |
| 1,3-丁二醇 | 5 | 5 | 5 | 5 | 5 | |
| 三仙膠 | - | - | - | - | - | |
| 凡士林 | 10 | 5 | 4.5 | 5 | 10 | |
| 液態石蠟 | 10 | 10 | 10.5 | 10 | 10 | |
| 鯨蠟硬脂醇 | - | - | - | - | - | |
| 鯨蠟醇 | 2 | 2 | 2 | 2 | 2 | |
| 硬脂醇 | 3 | 3 | 3 | 3 | 3 | |
| 山萮醇 | - | - | - | - | - | |
| 硬脂酸甘油酯 | - | 2 | 2.5 | 3 | 4 | |
| 聚氧乙烯鯨蠟醚 | 3 | - | - | - | - | |
| 硬脂酸聚烴氧酯 | - | 4 | 3.5 | 3 | 2 | |
| pH值(利用乳酸/乳酸鈉進行調整) | 5.9 | 5.5 | 5.5 | 5.5 | 5.5 | |
| 有關脲之評價 | ◎ | ◎ | ◎ | △ | ◎ | |
| 有關類固醇之評價 | 〇 | ◎ | ◎ | ◎ | ◎ | |
| 有關尿囊素之評價 | 〇 | ◎ | ◎ | ◎ | ◎ | |
| pH值緩衝性(穩定性) | ◎ | △ | 〇 | ◎ | ◎ | |
| 使用感 | △ | 〇 | ◎ | △ | 〇 | |
| 容器之膨脹 | ◎ | 〇 | ◎ | ◎ | ◎ | |
| 刺激性 | ◎ | ◎ | ◎ | ◎ | 〇 | |
| 綜合評價 | 〇 | 〇 | 〇 | 〇 | 〇 |
[表5]
| 成分 | 實施例21 | 比較例1 | 比較例2 | 比較例3 | 比較例4 | |
| (A) | 脲 | 5 | 5 | 5 | 5 | 20 |
| (B) | 潑尼松龍醋酸戊酸酯 | 0.15 | 0.15 | 0.15 | 0.15 | 0.15 |
| (C) | 尿囊素 | 0.2 | 0.2 | 0.2 | 0.2 | 0.2 |
| (D) | 甘胺酸 | 2 | - | 2 | 2 | 2 |
| L-麩胺酸鈉 | 4.5 | - | - | 4.5 | 3 | |
| L-天冬胺酸 | - | - | 3 | - | 3 | |
| L-精胺酸 | 0.4 | - | - | 0.4 | - | |
| DL-丙胺酸 | 3 | - | 3 | 3 | 3 | |
| (E) | 乳酸 | 2 | 1 | 3 | - | 1 |
| 檸檬酸水合物 | - | - | - | - | - | |
| (F) | 利多卡因 | 2 | 2 | 2 | 2 | 2 |
| 利多卡因鹽酸鹽 | - | - | - | - | - | |
| (G) | 乙二胺四乙酸鈉 | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 |
| (H) | 維生素E醋酸酯 | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 |
| 異丙基甲基苯酚 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | |
| 對羥基苯甲酸丁酯 | 0.15 | 0.15 | 0.15 | 0.15 | 0.15 | |
| 純化水 | 適量 | 適量 | 適量 | 適量 | 適量 | |
| 甘油 | 10 | 10 | 10 | 10 | 10 | |
| 1,3-丁二醇 | 5 | 5 | 5 | 5 | 5 | |
| 三仙膠 | - | - | - | - | - | |
| 凡士林 | 10 | 5 | 4.5 | 5 | 10 | |
| 液態石蠟 | 10 | 10 | 10.5 | 10 | 10 | |
| 鯨蠟硬脂醇 | 6 | 4 | 4 | 4 | 6 | |
| 鯨蠟醇 | - | - | - | - | - | |
| 硬脂醇 | - | - | - | - | - | |
| 山萮醇 | - | 1 | 1 | 1 | - | |
| 硬脂酸甘油酯 | 2 | - | 3 | 4 | - | |
| 聚氧乙烯鯨蠟醚 | - | 3 | - | - | 3 | |
| 硬脂酸聚烴氧酯 | 4 | - | 3 | 2 | - | |
| pH值(利用乳酸/乳酸鈉進行調整) | 5.1 | 5.5 | 4.0 | 7.0 | 5.5 | |
| 有關脲之評價 | △ | ◎ | △ | △ | × | |
| 有關類固醇之評價 | ◎ | △ | ◎ | × | △ | |
| 有關尿囊素之評價 | ◎ | △ | ◎ | × | △ | |
| pH值緩衝性(穩定性) | ◎ | × | ◎ | ◎ | × | |
| 使用感 | △ | × | × | × | × | |
| 容器之膨脹 | ◎ | × | × | ◎ | × | |
| 刺激性 | 〇 | ◎ | × | ◎ | ◎ | |
| 綜合評價 | 〇 | × | × | × | × |
[表6]
| 成分 | 實施例22 | 實施例23 | |
| (A) | 脲 | 5 | 5 |
| (B) | 潑尼松龍醋酸戊酸酯 | - | - |
| 氫化可體松丁酸酯 | 0.05 | - | |
| 倍他米松戊酸酯 | - | 0.12 | |
| (C) | 尿囊素 | 0.2 | 0.2 |
| (D) | 甘胺酸 | 2 | 2 |
| DL-丙胺酸 | 3 | 3 | |
| (E) | 乳酸 | 1 | 1 |
| 檸檬酸水合物 | - | - | |
| (F) | 利多卡因 | 2 | 2 |
| 利多卡因鹽酸鹽 | - | - | |
| (G) | 乙二胺四乙酸鈉 | 0.5 | 0.5 |
| (H) | 維生素E醋酸酯 | 0.5 | 0.5 |
| 異丙基甲基苯酚 | 0.1 | 0.1 | |
| 對羥基苯甲酸丁酯 | 0.15 | 0.15 | |
| 純化水 | 適量 | 適量 | |
| 甘油 | 10 | 10 | |
| 1,3-丁二醇 | 5 | 5 | |
| 三仙膠 | - | - | |
| 凡士林 | 5 | 5 | |
| 液態石蠟 | 10 | 10 | |
| 鯨蠟硬脂醇 | 4 | 4 | |
| 鯨蠟醇 | - | - | |
| 硬脂醇 | - | - | |
| 山萮醇 | 1 | 1 | |
| 硬脂酸甘油酯 | - | 3 | |
| 聚氧乙烯鯨蠟醚 | 3 | - | |
| 硬脂酸聚烴氧酯 | - | 3 | |
| pH值(利用乳酸/乳酸鈉進行調整) | 5.0 | 5.5 | |
| 有關脲之評價 | 〇 | ◎ | |
| 有關類固醇之評價 | △ | 〇 | |
| 有關尿囊素之評價 | ◎ | ◎ | |
| pH值緩衝性(穩定性) | 〇 | ◎ | |
| 使用感 | 〇 | 〇 | |
| 容器之膨脹 | △ | ◎ | |
| 刺激性 | △ | 〇 | |
| 綜合評價 | 〇 | 〇 |
如表1～表6所記載，係如下所述之結果。
如表所示，若pH值較低，則刺激性變高，若pH值較高，則發生酯系類固醇及尿囊素之分解，故欠佳。又，關於(D)胺基酸，若添加量較少，則發生pH值之上升以及酯系類固醇及尿囊素之分解，故欠佳；若過多，則發生脲之分解，故欠佳。關於(A)脲，若超過10質量%，則刺激性變高，並且因脲之分解使得容器發生膨脹，故欠佳。另一方面，實施例中所示之水中油型乳化組合物與比較例相比，獲得良好之結果。
Claims (6)
- 一種水中油型乳化組合物，其含有以下成分(A)～(D)，且pH值為5～6： (A)脲 0.5～10質量%、 (B)酯系類固醇 0.05～0.3質量%、 (C)尿囊素 0.1～1質量%、及 (D)胺基酸或其鹽 1～10質量%。
- 如請求項1之水中油型乳化組合物，其進而含有(E)羥酸或其鹽。
- 如請求項1或2之水中油型乳化組合物，其進而含有(F)局部麻醉劑。
- 如請求項1或2之水中油型乳化組合物，其進而含有(G)螯合劑。
- 如請求項1或2之水中油型乳化組合物，其進而含有選自(H)維生素E、維生素E醋酸酯及維生素E菸鹼酸酯之維生素E類。
- 如請求項1或2之水中油型乳化組合物，其進而含有選自殺菌劑、油性基劑、多元醇、乳化劑及水之1種或2種以上。
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| JPS6030646B2 (ja) * | 1974-10-22 | 1985-07-17 | 興和株式会社 | 皮膚処理組成物の安定化方法 |
| JPS59134707A (ja) * | 1983-01-20 | 1984-08-02 | Shiseido Co Ltd | 皮膚化粧料 |
| JPS6130509A (ja) * | 1984-07-23 | 1986-02-12 | Shiseido Co Ltd | 皮膚外用剤 |
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