本研究採用熱高壓均質機製備脂質體包埋美白成分，分成兩部分，其一為利用田口法尋找影響脂質載體之因子，後進行最佳操作條件之驗證，第二部分為進行經皮吸收實驗。脂質載體是由夏威夷豆油、棕櫚蠟、四種界面活性劑(Tween 80、Poloxamer 188、癸基葡萄糖苷、Span 80)、四種美白成分(4-正丁基間苯二酚、苯乙基間苯二酚、甘草萃取物、薑黃素)、卵磷脂、戊二醇及水等組成，操作變數為界面活性劑種類與濃度、美白成分種類與濃度及卵磷脂濃度等五種變數，各取四水準，採用田口法規畫出16組實驗，再將實驗數據進行田口法S/N比尋求粒徑、界面電位及結晶度等最佳操作條件及參數重要性順序。檢測後載體之粒徑範圍為139.6~692.2nm，界面電位範圍為-22.5~-50.5mV，結晶度範圍為11.28%~30.7%。經田口分析發現，影響粒徑的重要性順序為E(美白成分濃度)>C(美白成分種類)>D(卵磷脂濃度)>B(界面活性劑濃度)>A(界面活性劑種類)，最佳操作條件為A4B1C3D3E1；影響界面電位的重要性順序為A>B>E>D>C，最佳操作條件為A3B4C4D2E2；影響結晶度的重要性順序為C>A>E>B>D，最佳操作條件為A3B2C4D2E3；而包埋率皆為99%以上，為高包埋率之載體。經最佳操作條件應證，粒徑最佳之數據為132.6nm，界面電位最佳之數據為-59.2mV，結晶度最佳之數據為4.36%，皆符合田口分析。第二部分為進行經皮吸收實驗，取最佳操作條件之3組與固定美白濃度2%之4組為實驗組別，實驗時間為12小時，每2小時取樣1次，取樣後進行HPLC分析樣品面積與換算樣品濃度，計算樣品藥物累積量與擴散通量，再以質量均衡模式與初斜率法計算樣品其擴散係數並比較之。以質量均衡模式所得擴散係數範圍為5.26×10-16~4.55×10-15 m2/s；以初斜率法所得之擴散係數範圍為9.03×10-16~2.45×10-15 m2/s之間。各組間的差異為成分及濃度影響所造成的，而方法之間的差異，則須進一步探討。

In this study, a hot high pressure homogenizer is used to prepare lipid carriers microencapsulating whitening ingredients, and the process consisted of two parts: firstly, this study finds the factors affecting the lipid carrier by the Taguchi method and then to verify the best operating conditions; secondly, this study conducts a percutaneous absorption experiment. The lipid carrier is comprised of Macadamia nut oil, carnauba wax, 4 surfactants (Tween 80, Poloxamer 188, Decyl Glucoside, Span 80), 4 whitening ingredients (4-Butylresorcinol, Phenylethyl resorcinol, Licorice extract, curcumin), lecithin, 1,2-Pentanediol and water. The operating variables are the surfactant type and concentration, whitening ingredient type and concentration, and lecithin concentration, and 4 levels are selected for each variable. 16 experiments are made by Taguchi method, and the S/N ratio is calculated based on the experimental data to obtain the best operating conditions, such as particle size, zeta potential and crystallinity, and the importance of parameters. After the test, the particle size of the carrier ranges from 139.6nm to 692.2nm, the interface potential ranges from -22.5mV to -50.5mV and the crystallinity ranges from 11.28%to 30.7%. According to the Taguchi analysis, the order of variables affecting particle size is E(whitening ingredient concentration) > C(whitening ingredient type)>D(lecithin concentration)>B(surfactant concentration)>A(surfactant type), and the best operating condition is A4B1C3D3E1; the order of variables affecting zeta potential is A>B>E>D>C, and the best operating condition is A3B4C4D2E2; the order of variables affecting crystallinity is C>A>E>B>D, and the best operating condition is A3B2C4D2E3. The encapsulating rates are all higher than 99%, showing that the carrier has a high encapsulation efficiency. According to the best operating conditions, the best particle size is 132.6nm, the best zeta potential is -59.2mV and the best crystallinity is 4.36%, which conformed to the Taguchi analysis. The second part is to conduct a percutaneous absorption experiment. 3 groups with the best operating conditions and 4 groups with a fixed whitening ingredient concentration of 2% are selected as the experimental groups. The experiment time is 12 hours, and samples are taken every 2 hours. After sampling, the HPLC is used to analyze the sample area and concentrations, and to calculate the drug sample accumulation and diffusion flux. And then, the diffusion coefficients of the samples are calculated and compared based on the mass balance model and by the initial slope method. The diffusion coefficients are between 5.26×10-16 and 4.55×10-15 m2/s based on the mass balance model and between 9.03×10-16 and 2.45×10-15 m2/s by the initial slope method. The differences among groups are caused by ingredients and concentrations, and the differences among methods shall be further discussed.

摘要 i
ABSTRACT iii
誌謝 v
目錄 vi
表目錄 xi
圖目錄 xiii
第一章 緒論 1
1.1 前言 1
1.2 研究背景 5
1.3 研究目的 6
1.4 研究架構 7
第二章 文獻回顧 8
2.1 奈米脂質載體發展史 8
2.2 奈米結構脂質載體類型 11
2.2.1 缺陷形(Imperfect type) 11
2.2.2 無定形型(Amorphous type) 12
2.2.3 複合型(Multiple type) 13
2.3 複合型奈米結構脂質載體特性 14
2.4 奈米結構脂質載體製備方法 17
2.4.1 乳化-溶劑蒸發法 17
2.4.2 微乳法 17
2.4.3 W/O/W乳化法 18
2.4.4 高壓均質法 18
2.4.5 高速剪切均質/超音波震盪法 20
2.5 目前專利趨勢 21
2.6 固態脂質 23
2.6.1 棕櫚蠟 23
2.6.2 Compritol 888 ATO 24
2.6.3 蜂蠟 24
2.7 液態脂質 25
2.8 美白成分 26
2.8.1 4-正丁基間苯二酚 26
2.8.2 苯乙基間苯二酚 26
2.8.3 薑黃素 27
2.8.4 甘草萃取物 27
2.9 界面活性劑 28
2.9.1 陽離子型界面活性劑 28
2.9.2 陰離子型界面活性劑 28
2.9.3 兩性型界面活性劑 28
2.9.4 非離子型界面活性劑 29
2.10 卵磷脂 29
2.11 皮膚構造 30
2.11.1 表皮層(Epidermis) 31
2.11.2 真皮層(Dermis) 31
2.11.3 皮下組織(Hypodermis) 31
2.12 經皮吸收實驗 32
2.12.1 藥物傳輸方式 32
2.12.1.1 經由附屬器官穿透 33
2.12.1.2 分子吸附於角質層表面 33
2.12.1.3 穿透角質層及其他表皮組織層 33
2.12.2 經皮吸收實驗方法 33
2.13 田口實驗設計方法 34
2.13.1 信號/雜訊比(S/N比) 35
2.13.2 參數設計 36
2.13.3 直交表(Orthogonal Arrays) 36
第三章 經皮吸收擴散模式 37
3.1 擴散係數 37
3.1.1 質量均衡模式 37
3.1.2 初斜率法模式 40
3.2 藥物累積量 41
3.3 擴散通量 42
第四章 實驗步驟及方法 43
4.1 藥品及實驗儀器 43
4.1.1 實驗藥品 43
4.1.2 實驗設備 44
4.1.3 分析儀器 44
4.2 實驗設計 45
4.2.1 田口實驗設計 45
4.2.2 經皮吸收實驗 46
4.3 實驗裝置 47
4.3.1 高壓均質機(High Pressure Homogenization) 47
4.3.2 透皮擴散實驗儀 48
4.4 分析儀器原理 50
4.4.1 動態散射奈米級團簇分析儀 50
4.4.2 界面電位分析儀 51
4.4.3 Q600同步熱分析儀 53
4.4.4 高效液相層析儀 54
4.5 實驗步驟與方法 55
4.5.1 美白脂質載體之製備方法 55
4.5.2 粒徑分析 56
4.5.3 界面電位分析 57
4.5.4 結晶度分析 57
4.5.5 高效液相層析儀分析 58
4.5.6 經皮吸收實驗 59
4.6實驗流程圖 60
第五章 結果與討論 61
5.1 粒徑分析 61
5.2 界面電位分析 65
5.3 結晶度分析 69
5.4 包埋率分析 72
5.4.1 4-正丁基間苯二酚檢量線製作 73
5.4.2 苯乙基間苯二酚檢量線製作 74
5.4.3 甘草萃取液檢量線製作 75
5.4.4 薑黃素檢量線製作 76
5.4.5 包埋率分析與計算 77
5.5 田口分析 79
5.5.1 影響粒徑參數分析 79
5.5.2 影響界面電位參數分析 81
5.5.3 影響結晶度大小參數分析 83
5.6 最佳驗證組 86
5.7 經皮吸收實驗 88
5.7.1 最佳組經皮吸收實驗 88
5.7.1.1 最佳組藥物之擴散係數 89
5.7.1.2 最佳組藥物累積量 91
5.7.1.3 最佳組藥物擴散通量 93
5.7.2 相同濃度之經皮吸收實驗 95
5.7.2.1 相同濃度之藥物擴散係數 96
5.7.2.2相同濃度之藥物累積量 99
5.7.2.3 相同濃度之藥物擴散通量 101
5.7.3 初斜率法分析經皮吸收數據 103
5.7.3.1 初斜率法分析最佳組數據 103
5.7.3.2 初斜率法分析相同濃度數據 106
5.7.4 數據分析 109
5.7.5 模擬經皮吸收 110
第六章 結論 113
參考文獻 115
附錄 124
A 實驗組之粒徑與界面電位波峰圖 125
B 實驗組之DSC圖譜 144
符號(公式)說明 154

[1] Puglia, C., Blasi, P., Rizza, L., Schoubben, A., Bonina, F., Rossi, C., & Ricci, M. (2008). Lipid nanoparticles for prolonged topical delivery: an in vitro and in vivo investigation. Int J Pharm, 357(1-2), 295-304.
[2] Teichmann, A., Jacobi, U., Weigmann, H. J., Sterry, W., & Lademann, J. (2005). Reservoir function of the stratum corneum: development of an in vivo method to quantitatively determine the stratum corneum reservoir for topically applied substances. Skin pharmacol physiol, 18(2), 75-80.
[3] Gallarate, M., Carlotti, M. E., Trotta, M., & Bovo, S. (1999). On the stability of ascorbic acid in emulsified systems for topical and cosmetic use. Int J Pharm, 188(2), 233-241.
[4] Coimbra, M., Isacchi, B., van Bloois, L., Torano, J. S., Ket, A., Wu, X., & Bilia, R. (2011). Improving solubility and chemical stability of natural compounds for medicinal use by incorporation into liposomes. Int J Pharm, 416(2), 433-442.
[5] Flanagan, J., & Singh, H. (2006). Microemulsions: a potential delivery system for bioactives in food. Crit Rev Food Sci Nutr, 46(3), 221-237.
[6] Müller, R. H., Radtke, M., & Wissing, S. A. (2002a). Nanostructured lipid matrices for improved microencapsulation of drugs. Int J Pharm, 242(1-2), 121-128.
[7] Müller, R. H., Mehnert, W., Lucks, J. S., Schwarz, C., & Zur Mühlen, A. (1995). Solid lipid nanoparticles (SLN): an alternative colloidal carrier system for controlled drug delivery. Eur J Pharm Biopharm, 41(1), 62-69.
[8] Kokardekar, R., & Mody, H. (2011). Solid lipid nanoparticles: A drug carrier system. Chron Young Sci, 2(1), 26-26.
[9] Müller, R. H., Radtke, M., & Wissing, S. A. (2002b). Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Delivery Rev, 54, S131-S155.
[10] Müller, R. H., Mäder, K., & Gohla, S. (2000). Solid lipid nanoparticles (SLN) for controlled drug delivery–a review of the state of the art. Eur J Pharm Biopharm, 50(1), 161-177.
[11] Freitas, C., & Müller, R. H. (1999). Correlation between long-term stability of solid lipid nanoparticles (SLN™) and crystallinity of the lipid phase. Eur J Pharm Biopharm, 47(2), 125-132.
 
[12] Teeranachaideekul, V., Müller, R. H., & Junyaprasert, V. B. (2007). Encapsulation of ascorbyl palmitate in nanostructured lipid carriers (NLC)—effects of formulation parameters on physicochemical stability. Int J Pharm, 340(1-2), 198-206.
[13] Hu, F. Q., Jiang, S. P., Du, Y. Z., Yuan, H., Ye, Y. Q., & Zeng, S. (2006). Preparation and characteristics of monostearin nanostructured lipid carriers. Int J Pharm, 314(1), 83-89.
[14] Saupe, A., Wissing, S. A., Lenk, A., Schmidt, C., & Müller, R. H. (2005). Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC)–structural investigations on two different carrier systems. Bio-Med Mater Eng, 15(5), 393-402.
[15] 趙仕芝，董義偉，(2013)一種複合美白劑納米結構脂質載體及其製備方法，上海韓束化妝品有限公司，CN103251539A。
[16] 劉祖惠，譚中岳，陳秋玲，鄭宇婷，陳玲玉，陳怡蓁，(2015)，應用生技產業年鑑2015，財團法人生物技術開發中心，第86頁。
[17] Kalia, R., (2019). Transdermal drug delivery system market by type (patches and semisolid formulations), Applications (pain management, central nervous system disorders, hormonal applications, cardiovascular diseases), End User, and Region Global Forecast to 2023, Markets and Markets Research Private Ltd,.
[18] Balázs, B., Vizserálek, G., Berkó, S., Budai-Szűcs, M., Kelemen, A., Sinkó, B., & Csányi, E. (2016). Investigation of the efficacy of transdermal penetration enhancers through the use of human skin and a skin mimic artificial membrane. J Pharm Sci, 105(3), 1134-1140.
[19] Oresajo, C., Yatskayer, M., & Hansenne, I. (2008). Clinical tolerance and efficacy of capryloyl salicylic acid peel compared to a glycolic acid peel in subjects with fine lines/wrinkles and hyperpigmented skin. J Cosmet Dermat, 7(4), 259-262.
[20] 李智軒，4-正丁基間苯二酚之包埋與分析技術開發，碩士論文，龍華科技大學化工與材料工程所，桃園(2015)。
[21] Thornfeldt, C. (2005). Cosmeceuticals containing herbs: fact, fiction, and future. Dermatol Surg, 31, 873-881.
[22] Phatak, A. A., & Chaudhari, P. D. (2013). Development and evaluation of nanostructured lipid carrier (NLC) based topical delivery of an anti-inflammatory drug. J Pharm Res, 7(8), 677-685.
[23] Müller, R. H., Petersen, R. D., Hommoss, A., & Pardeike, J. (2007). Nanostructured lipid carriers (NLC) in cosmetic dermal products. Adv Drug Delivery Rev, 59(6), 522-530.
 
[24] Begoun Paula, Cosmetic Ingredient Guidebook, Dacombook publisher, (2008).
[25] Kaijser, A., Dutta, P., & Savage, G. (2000). Oxidative stability and lipid composition of macadamia nuts grown in New Zealand. Food Chem, 71(1), 67-70.
[26] Mitri, K., Shegokar, R., Gohla, S., Anselmi, C., & Müller, R. H. (2011). Lipid nanocarriers for dermal delivery of lutein: preparation, characterization, stability and performance. Int J Pharm, 414(1-2), 267-275.
[27] 陳賢政，以藍薊油製備奈米結構脂質載體最佳參數探討，碩士論文，龍華科技大學工程技術研究所，桃園 (2011)。
[28] Han, F., Li, S., Yin, R., Liu, H., & Xu, L. (2008). Effect of surfactants on the formation and characterization of a new type of colloidal drug delivery system: nanostructured lipid carriers. Colloids Surf A, 315(1-3), 210-216.
[29] Lin, X., Li, X., Zheng, L., Yu, L., Zhang, Q., & Liu, W. (2007). Preparation and characterization of monocaprate nanostructured lipid carriers. Colloids Surf A, 311(1-3), 106-111.
[30] Fang, J. Y., Fang, C. L., Liu, C. H., & Su, Y. H. (2008). Lipid nanoparticles as vehicles for topical psoralen delivery: solid lipid nanoparticles (SLN) versus nanostructured lipid carriers (NLC). Eur J Pharm Biopharm, 70(2), 633-640.
[31] Xia, Q., Saupe, A., Müller, R. H., & Souto, E. B. (2007). Nanostructured lipid carriers as novel carrier for sunscreen formulations. Int J Cosmet Sci, 29(6), 473-482.
[32] Bangham, A. D. (1993). Liposomes: the Babraham connection. Chem Phys Lipids, 64(1-3), 275-285.
[33] Souto, E. B., Wissing, S. A., Barbosa, C. M., & Müller, R. H. (2004). Evaluation of the physical stability of SLN and NLC before and after incorporation into hydrogel formulations. Eur J Pharm Biopharm, 58(1), 83-90.
[34] Hatziantoniou, S., Deli, G., Nikas, Y., Demetzos, C., & Papaioannou, G. T. (2007). Scanning electron microscopy study on nanoemulsions and solid lipid nanoparticles containing high amounts of ceramides. Micron, 38(8), 819-823.
[35] Radtke, M., & Müller, R. H. (2001). Nanostructured lipid drug carriers. New Drugs, 2, 48-52.
[36] Tamjidi, F., Shahedi, M., Varshosaz, J., & Nasirpour, A. (2013). Nanostructured lipid carriers (NLC): A potential delivery system for bioactive food molecules. Innovative Food Sci Emerging Technol, 19, 29-43.
 
[37] Liedtke, S., Wissing, S., Müller, R. H., & Mäder, K. (2000). Influence of high pressure homogenisation equipment on nanodispersions characteristics. Int J Pharm, 196(2), 183-185.
[38] Üner, M., & Yener, G. (2007). Importance of solid lipid nanoparticles (SLN) in various administration routes and future perspectives. Int J Nanomed, 2(3), 289.
[39] Chen, P. C., Huang, J. W., & Pang, J. (2013). An investigation of optimum NLC-sunscreen formulation using taguchi analysis. J Nanomater, 9, 1-10.
[40] Sjöström, B., & Bergenståhl, B. (1992). Preparation of submicron drug particles in lecithin-stabilized o/w emulsions I. Model studies of the precipitation of cholesteryl acetate. Int J Pharm, 88(1-3), 53-62.
[41] Gasco, M. R. (1993). U.S. Patent No. 5,250,236. Washington, DC: U.S. Patent and Trademark Office.
[42] Hildebrand, G. E., & Tack, J. W. (2000). Microencapsulation of peptides and proteins. Int J Pharm, 196(2), 173-176.
[43] Hu, F. Q., Yuan, H., Zhang, H. H., & Fang, M. (2002). Preparation of solid lipid nanoparticles with clobetasol propionate by a novel solvent diffusion method in aqueous system and physicochemical characterization. Int J Pharm, 239(1-2), 121-128.
[44] Heurtault, B., Saulnier, P., Pech, B., Proust, J. E., & Benoit, J. P. (2002). A novel phase inversion-based process for the preparation of lipid nanocarriers. Pharm Res, 19(6), 875-880.
[45] Pietkiewicz, J., & Sznitowska, M. (2004). The choice of lipids and surfactants for injectable extravenous microspheres. Die Pharmazie-An Int J Pharm Sci, 59(4), 325-326.
[46] Wissing, S. A., Kayser, O., & Müller, R. H. (2004). Solid lipid nanoparticles for parenteral drug delivery. Adv Drug delivery Rev, 56(9), 1257-1272.
[47] Pardeike, J., Hommoss, A., & Müller, R. H. (2009). Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products. Int J Pharm, 366(1-2), 170-184.
[48] Misran, M. B., Tiew, S. X., & Woo, J. O. (2016). U.S. Patent Application No. 14/952,291.
[49] Blanco, A. R., Bondi, M. L., & Cavallaro, G. (2017). U.S. Patent Application No. 15/517,018.
[50] Faivre, V., Lesieur, S., Ollivon, M., Ouattara, M., & CONG, T. T. (2017). U.S. Patent No. 9,757,337. Washington, DC: U.S. Patent and Trademark Office.
[51] Chen, L. (2017). U.S. Patent No. 9,820,996. Washington, DC: U.S. Patent and Trademark Office.
 
[52] Tonge, S., & Harper, A. (2017). U.S. Patent Application No. 15/642,780.
[53] Harandi, O., & Kahvejian, A. (2019) U.S. Patent Application No. 2019-0062788A1.
[54] Prestidge, C. A., & Joyce, P. M. (2019). U.S. Patent No. 10,463,626. Washington, DC: U.S. Patent and Trademark Office.
[55] Duhalt, R. V., & Sanchez, L. P. S. (2019). U.S. Patent No. 10,480,012. Washington, DC: U.S. Patent and Trademark Office.
[56] Horstmann, M., Sameti, M., & Jung, T. (2019). U.S. Patent No. 10,292,942. Washington, DC: U.S. Patent and Trademark Office.
[57] 趙坤山，張效銘，(2006)，化妝品化學，台北，五南圖書出版股份有限公司，第97-100頁。
[58] Gokce, E. H., Korkmaz, E., Dellera, E., Sandri, G., Bonferoni, M. C., & Ozer, O. (2012). Resveratrol-loaded solid lipid nanoparticles versus nanostructured lipid carriers: evaluation of antioxidant potential for dermal applications. Int J Nanomed, 7, 1841.
[59] Fathi, M., Varshosaz, J., Mohebbi, M., & Shahidi, F. (2013). Hesperetin-loaded solid lipid nanoparticles and nanostructure lipid carriers for food fortification: preparation, characterization, and modeling. Food Bioprocess Technol, 6(6), 1464-1475.
[60] Barthelemy, P., Laforet, J. P., Farah, N., & Joachim, J. (1999). Compritol® 888 ATO: an innovative hot-melt coating agent for prolonged-release drug formulations. Eur J Pharm Biopharmaceutics, 47(1), 87-90.
[61] 徐照程，鐘薇萱，(2013)，經奈米脂質載體包覆之防曬劑及其應用，綠祚國際有限公司，TW201321019。
[62] Schwarz, J. C., Baisaeng, N., Hoppel, M., Löw, M., Keck, C. M., & Valenta, C. (2013). Ultra-small NLC for improved dermal delivery of coenyzme Q10. Int J Pharm, 447(1-2), 213-217.
[63] Mendes, A. I., Silva, A. C., Catita, J. A. M., Cerqueira, F., Gabriel, C., & Lopes, C. M. (2013). Miconazole-loaded nanostructured lipid carriers (NLC) for local delivery to the oral mucosa: improving antifungal activity. Colloids Surf B, 111, 755-763.
[64] Czajkowska-Kośnik, A., Sznitowska, M., & Mirkowska, K. (2012). Self-emulsifying oils for ocular drug delivery. II. In vitro release of indomethacin and hydrocortisone. Acta Pol Pharm, 69(2), 309.
[65] Kolbe, L., Mann, T., Gerwat, W., Batzer, J., Ahlheit, S., Scherner, C., & Stäb, F. (2013). 4‐n‐butylresorcinol, a highly effective tyrosinase inhibitor for the topical treatment of hyperpigmentation. J Eur Acad Dermatol Venereol, 27, 19-23. 
[66] Vielhaber, G., Schmaus, G., Jacobs, K., Franke, H., Lange, S., Herrmann, M., & Koch, O. (2007). 4‐(1‐Phenylethyl) 1, 3‐benzenediol: a new, highly efficient lightening agent. Int J Cosmet Sci, 29(1), 65-66.
[67] Kim, B. S., Na, Y. G., Choi, J. H., Kim, I., Lee, E., Kim, S. Y., & Cho, C. W. (2017). The improvement of skin whitening of phenylethyl resorcinol by nanostructured lipid carriers. Nanomater, 7(9), 241.
[68] Jayaprakasha, G. K., Rao, L. J., & Sakariah, K. K. (2006). Antioxidant activities of curcumin, demethoxycurcumin and bisdemethoxycurcumin. Food chem, 98(4), 720-724.
[69] Strimpakos, A. S., & Sharma, R. A. (2008). Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials. Antioxid Redox Signaling, 10(3), 511-546.
[70] 孫啟棣，羥基苯酮及薑黃素脂質奈米載體特性分析，碩士論文，臺北醫學大學醫學科學研究所，臺北 (2009)。
[71] Tao, W., Duan, J., Zhao, R., Li, X., Yan, H., Li, J., & Tang, Y. (2013). Comparison of three officinal Chinese pharmacopoeia species of Glycyrrhiza based on separation and quantification of triterpene saponins and chemometrics analysis. Food chem, 141(3), 1681-1689.
[72] Shabkhiz, M. A., Eikani, M. H., Sadr, Z. B., & Golmohammad, F. (2016). Superheated water extraction of glycyrrhizic acid from licorice root. Food Chem, 210, 396-401.
[73] Kitagawa, I. (2002). Licorice root. A natural sweetener and an important ingredient in Chinese medicine. Pure Appl Chem, 74(7), 1189-1198.
[74] Mukhopadhyay, M., & Panja, P. (2008). A novel process for extraction of natural sweetener from licorice (Glycyrrhiza glabra) roots. Sep Purif Technol, 63(3), 539-545.
[75] Liu, H. M., Sugimoto, N., Akiyama, T., & Maitani, T. (2000). Constituents and their sweetness of food additive enzymatically modified licorice extract. J Agric Food Chem, 48(12), 6044-6047.
[76] Chin, Y. W., Jung, H. A., Liu, Y., Su, B. N., Castoro, J. A., Keller, W. J., & Kinghorn, A. D. (2007). Anti-oxidant constituents of the roots and stolons of licorice (Glycyrrhiza glabra). J Agric Food Chem, 55(12), 4691-4697.
[77] Cherng, J. M., Lin, H. J., Hung, M. S., Lin, Y. R., Chan, M. H., & Lin, J. C. (2006). Inhibition of nuclear factor κB is associated with neuroprotective effects of glycyrrhizic acid on glutamate-induced excitotoxicity in primary neurons. Eur J Pharm, 547(1-3), 10-21. 
[78] Li, X. H., Qi, Y., Cai, R. L., Liu, B., Song, Y., & Xie, C. (2010). Studies on the anti-inflammatory mechanism of total saponins of radix Glycyrrhiza in vitro. Chin J Exp Tradit Med Formulae, 5, 039.
[79] Li, P. (2010). Oleanane-type triterpene glucuronides from the roots of Glycyrrhiza uralensis Fischer. Planta Med, 76, 1457-1463 (2010).
[80] Ashfaq, U. A., Masoud, M. S., Nawaz, Z., & Riazuddin, S. (2011). Glycyrrhizin as antiviral agent against Hepatitis C Virus. J Transl Med, 9(1), 1-7.
[81] Gao, X., Zheng, Q., Sun, J., Wang, W., & Yang, X. (2011). Preparation of total licorice saponin and research on its hepatoprotective effect. Pharmacol Clin Chin Mater Med, 27, 79-81.
[82] 郁仁貽，(2000)，最新化妝品學，復文書局。
[83] 羅怡倩，(2010)，化妝品成分辭典，聯經出版事業股份有限公司。
[84] Garrand, V. A. (1985). Antimicrobial properties of a cocoamidopropyl betaine. Cosmet Toiletries, 100(2), 77-80.
[85] Egbaria, K., & Weiner, N. (1990). Liposomes as a topical drug delivery system. Adv Drug Delivery Rev, 5(3), 287-300.
[86] Otera, J. (2004). Toward ideal (trans) esterification by use of fluorous distannoxane catalysts. Acc Chem Res, 37(5), 288-296.
[87] Fiume, Z. (2001). Final report on the safety assessment of lecithin and hydrogenated lecithin. Int. J. Toxicol, 20(1), 21-45.
[88] Kydonieus, A. F., Wille, J. J., & Murphy, G. F. (2000). Fundamental concepts in transdermal delivery of drugs. Biochem Modulation Skin React. Transdermals, Topicals, Cosmetics. Boca Raton: CRC Press, Inc.
[89] 簡敏宸，以奈米結構脂質載體包覆活性物質之製備與分析研究，碩士論文，龍華科技大學，工程技術研究所，桃園 (2013)。
[90] Kim, M. S., Jeong, Y. Y., Park, S. G., & Kang, N. G. (2020). Age-dependent facial subcutaneous fat thickness by high-frequency medical diagnostic ultrasound system. Skin Res Technol, 26, 1-3 (2020).
[91] 許世昌，(1991)，解剖生理學初版，永大出版社，台北。
[92] Grégoire, S., Luengo, G. S., Hallegot, P., Pena, A. M., Chen, X., Bornschlögl, T., & Jeong, S. (2019). Imaging and quantifying drug delivery in skin–Part 1: Autoradiography and mass spectrometry imaging. Adv Drug Delivery Rev, 185, 162-193 (2019).
 
[93] Nasr, S., Rady, M., Gomaa, I., Syrovets, T., Simmet, T., Fayad, W., & Abdel-Kader, M. (2019). Ethosomes and lipid-coated chitosan nanocarriers for skin delivery of a chlorophyll derivative: A potential treatment of squamous cell carcinoma by photodynamic therapy. Int J Pharm, 568, 118528.
[94] Al Hanbali, O. A., Khan, H. M. S., Sarfraz, M., Arafat, M., Ijaz, S., & Hameed, A. (2019). Transdermal patches: Design and current approaches to painless drug delivery. Acta Pharm, 69(2), 197-215.
[95] Planz, V., Lehr, C. M., & Windbergs, M. (2016). In vitro models for evaluating safety and efficacy of novel technologies for skin drug delivery. J Controlled Release, 242, 89-104.
[96] Shahzad, Y., Louw, R., Gerber, M., & Du Plessis, J. (2015). Breaching the skin barrier through temperature modulations. J Controlled Release, 202, 1-13.
[97] Abd, E., Yousef, S. A., Pastore, M. N., Telaprolu, K., Mohammed, Y. H., Namjoshi, S., & Roberts, M. S. (2016). Skin models for the testing of transdermal drugs. Clin Pharmacol: Adv Appl, 8, 163.
[98] Raza, R., Mittal, A., Kumar, P., Alam, S., Prakash, S., & Chauhan, N. (2015). Approaches and evaluation of transdermal drug delivery system. Int J Drug Dev Res, 7(1), 222-233.
[99] 呂冠蓁，利用超臨界二氧化碳快速膨脹法製備奈米氧化物之研究，碩士論文，龍華科技大學，工程技術研究所，桃園 (2010)。
[100] 李輝煌，(2004)，田口方法品質設計的原理與實務，國立成功大學工程科學系。
[101] 小西省三，(1991)，田口式品質工程講座3品質評價SN比，中國生產力中心。
[102] Galazka, V. B., Dickinson, E., & Ledward, D. A. (2000). Influence of high pressure processing on protein solutions and emulsions. Curr Opin Colloid Interface Sci, 5(3-4), 182-187.
[103] Chuang, S. Y., Lin, Y. K., Lin, C. F., Wang, P. W., Chen, E. L., & Fang, J. Y. (2017). Elucidating the skin delivery of aglycone and glycoside flavonoids: How the structures affect cutaneous absorption. Nutr, 9(12), 1304.
[104] Kim, B. S., Na, Y. G., Choi, J. H., Kim, I., Lee, E., Kim, S. Y., & Cho, C. W. (2017). The improvement of skin whitening of phenylethyl resorcinol by nanostructured lipid carriers. Nanomater, 7(9), 241-253.
[105] Sui, W., Zhou, M., Xu, Y., Wang, G., Zhao, H., & Lv, X. (2020). Hydrothermal deglycosylation and deconstruction effect of steam explosion: Application to high-valued glycyrrhizic acid derivatives from liquorice. Food Chem, 307, 125558.
 
[106] Peng, S., Zhou, L., Cai, Q., Zou, L., Liu, C., Liu, W., & McClements, D. J. (2020). Utilization of biopolymers to stabilize curcumin nanoparticles prepared by the pH-shift method: Caseinate, whey protein, soy protein and gum Arabic. Food Hydrocolloids, 105963.
[107] Shen, C. H., & Springer, G. S. (1976). Moisture absorption and desorption of composite materials. J Compos Mater, 10(1), 2-20.
[108] Beringhier, M., Djato, A., Maida, D., & Gigliotti, M. (2018). A novel protocol for rapid identification of anisotropic diffusion properties of polymer matrix composite materials with complex texture. Compos Struct, 201, 1088-1096.
[109] Nadler, K. A., Kim, P., Huang, D. L., Xiong, W., & Continetti, R. E. (2019). Water diffusion measurements of single charged aerosols using H 2 O/D 2 O isotope exchange and Raman spectroscopy in an electrodynamic balance. Phys Chem Chem Phys, 21(27), 15062-15071.
[110] Kim, M. S., Jeong, Y. Y., Park, S. G., & Kang, N. G. (2020). Age-dependent facial subcutaneous fat thickness by high-frequency medical diagnostic ultrasound system. Skin Res Technol, 26, 1-3.
[111] Sakalauskienė, K., Valiukevičienė, S., Raišutis, R., & Linkevičiūtė, G. (2018). The significance of spectrophotometric image analysis for diagnosis of the melanocytic skin tumours in association with their thickness. Skin Res Technol, 24(4), 692-698.