Pharmaceutical mechanism and control strategy for storage of ellagic acid stably in traditional Chinese medicine oral liquid
10.16438/j.0513-4870.2018-1131
- VernacularTitle:中药口服液中鞣花酸分子稳定储存的制剂学机制与调控策略
- Author:
Hao-zhou HUANG
1
;
Jun-zhi LIN
2
;
Xi-chuan WEI
1
;
Hong-yan MA
1
;
Hai-yan LIU
3
,
4
;
San-hu FAN
3
,
4
;
Wen-quan ZOU
5
;
Li HAN
1
;
Ding-kun ZHANG
1
Author Information
1. Key Laboratory Breeding Base of Systematic Research and Utilization on Chinese Material Medical Resources Co-founded by Sichuan Province and Ministry of Science and Technology, Pharmacy College, Chengdu University of TCM, Chengdu 611137, China
2. Central Laboratory, Teaching Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
3. Sanajon Pharmaceutical Group, Chengdu 610000, China
4. Sichuan Key Laboratory of Nutrition and Function of Dairy, Chengdu 610000, China
5. College of Chemistry, Sichuan University, Chengdu 610064, China
- Publication Type:Research Article
- Keywords:
ellagic acid;
traditional Chinese medicine;
oral liquid;
clarity;
colloid;
chemical precipitation
- From:
Acta Pharmaceutica Sinica
2019;54(4):737-745
- CountryChina
- Language:Chinese
-
Abstract:
Ellagic acid is ubiquitous in plants and is considered as a potential candidate for antioxidant and antineoplastic drugs. However, ellagic acid has poor solubility and precipitates easily even after initial solubilization. Improvement of its bioavailability has been a concern of pharmaceutical industry. It was found that storage in Sanlejiang oral liquid at low temperature keeps its stability. Ellagic acid is anomalous in a way that is easily soluble at low temperatures but precipitates at high temperatures. In order to reveal the mechanism of this phenomenon and develop precipitation prevention and control strategies, ellagic acid in Sanlejiang oral liquid was stored at high, medium and low temperatures for three months. The changes of composition and phase state of the whole system during storage were systematically tracked and studied by means of precipitation amount or morphology, HPLC chemical profile of supernatant versus precipitates, and comprehensive characterization of physical phase state. The results show that the amount of precipitation at low temperature is only 1/3 of that at normal room temperature. As the temperature rises, the sedimentation increases sharply. HPLC analyses of supernatant versus precipitates revealed that ellagic acid precipitation originated from two ways: chemical degradation and physical deposition. The chemical sedimentation is related to the hydrolysis of tannins under acidic condition, forming chebulagic acid and corilagin. Physical sedimentation is related to the decrease of the association degree and viscosity of polyphenol colloids when temperature rises. This study elucidated the stability mechanism of ellagic acid in liquid preparations of TCM, and provided the mechanistic basis for efficient utilization and solution prepartion of ellagic acid.
