Preparation and Quality Evaluation of Notoginsenoside R1 Phospholipid Complex
TIE Hong-yun, SHANG Yun-xia, WEI Xiao-hui*
The MOE Key Laboratory for Standardization of Chinese Medicines Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Abstract：OBJECTIVE To prepare notoginsenoside R1 (R1) phospholipid complex (R1-PC) under optimized conditions and conduct its quality evaluation, which belongs to class Ⅲ of biopharmaceuticals classification system (BCS) and has high water solubility, low permeability, and poor oral bioavailability, in order to improve its intestinal absorption. METHODS The phospholipid complex was prepared by solvent volatilization method. Taking the drug-lipid complex rate as the index, the reaction solvent, drug-lipid ratio and other influencing factors were optimized by single factor test. R1-PC was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and differential calorimetric scanning (DCS). At the same time, the oil-water partition coefficient, intestinal absorption rate and stability were also investigated. RESULTS Under the conditions of using tetrahydrofuran as solvent, R1-lecithin (molar ratio) of 1∶2, R1 concentration of 10 mg ·mL-1, reaction temperature at 40 ℃, and reaction time for 2 h, the recombination rate of R1-PC could reach 99.00%. SEM, XRD and DCS all verified the formation of R1-PC. The oil-water partition coefficient was 3.6 (in water) and 4.1 (in pH 6.8 buffer) times higher than that of R1, and the cumulative absorption of colon in vitro was significantly higher than that of crude drug (P<0.001). It was stable under the condition of high temperature and humidity, but unstable under strong light, and it was also stable at room temperature for 3 months. CONCLUSION The established preparation process of R1-PC is simple and feasible, with high recombination rate, significantly improved intestinal absorption and good stability, so it is suitable for industrial production.
CHEN H Y, CHEN A, LU F G, et al. Pharmacological research progress of total saponins from Panax notoginseng . Hunan J Tradit Chin Med (湖南中医药杂志), 2019, 35(1):154-157.
[2]
TAN L, TANG Q K, WANG S Z, et al. Research progress on pharmacological effects of Panax notoginseng saponin R1 . Chin Pharmacol Bull(中国药理学通报), 2018, 34(5):604-607.
[3]
CUI Y, ZHANG W J, ZHANG W L, et al. Preparation and physicochemical properties of ginsenoside Rb1 phospholipid complex . Pharm Clin Res(药学与临床研究), 2012, 20(6):510-514.
[4]
ZHANG J, DING L, WANG B, et al. Notoginsenoside R1 attenuates experimental inflammatory bowel disease via pregnane X receptor activation. J Pharmacol Exp Therapeu, 2015, 352(2):315.
[5]
HUANG B, HUANG C L, ZHANG C F, et al. Preparation, physicochemical properties and transdermal properties of vitamin C phospholipid complex . Chin J Pharm(中国医药工业杂志), 2008, 49(8):1121-1128.
[6]
ZHANG H Q, HAO H J, FAN M W, et al. Application of phospholipid complex in percutaneous and mucosal drug delivery system . Chin Tradit Pat Med (中成药), 2014, 4 (1): 153-157.
[7]
WU H Y, LONG X Y, CHEN L, et al. Phospholipid complex and its effect on biofilm penetration of active components of traditional Chinese medicine . Chin Tradit Herb Drugs(中草药), 2012, 43(2):393-398.
[8]
DAS M K, KALITA B. Design and evaluation of phospholipid complexes (phytosomes) of rutin for transdermal application . J Appl Pharm Sci, 2014, 4(10):51-57.
[9]
YAO Q E, SHI S J, ZHOU M, et al. Preparation, characterization and in vitro antitumor activity of vitamin C phospholipid complex and its nanoparticles . Chin J Pharm (中国医药工业杂志), 2016, 47(11):1408-1413.
[10]
YUE P F, YUAN H L, LI X Y, et al. Process optimization, characterization and evaluation in vivo of oxymatrine-phospholipid complex. Int J Pharm, 2010, 387(1-2):139-146.
[11]
MIAO Y, CHEN G, REN L. Preparation and evaluation of ziprasidone-phospholipid complex from sustained-release pellet formulation with enhanced bioavailability and no food effect. J Pharm Pharmacol, 2016, 68(2):185-194.
[12]
CHEN J T, WEN H L, HUANG H, et al. Preparation of Panax notoginseng saponins phospholipid complex . Asia-Pacific Tradit Med (亚太传统医药), 2015, 11(15):23-25.
[13]
KIDD P M. Bioavailability and activity of phytosome complexes from botanical polyphenols: the silymarin, curcumin, green tea, and grape seed extracts . Alternative Med Rev, 2009, 14(3):226-246.
[14]
MAITI K, MUKHERJEE K, GANTAIT A, et al. Curcumin-phospholipid complex: preparation, therapeutic evaluation and pharmacokinetic study in rats . Int J Pharm, 2007, 330(1-2):155-163.
[15]
XIAO Y Y, SONG Y M, CHEN Z P, et al. The preparation of silybin phospholipid complex and the study on its pharmacokinetics in rats . Int J Pharm, 2006, 307(1):77-82.
[16]
SIKARWAR M S, SHARMA S, JAIN A K, et al. Preparation, characterization and evaluation of marsupsin-phospholipid complex. AAPS Pharm, 2008, 9(1):129-137.
2020, Vol. 55 
