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基于生物质的石蒜碱加兰他敏热分解动力学及储存期分析

Analysis on the thermal decomposition kinetics and storage period of biomass-based lycorine galanthamine.

作者信息

Qin Chong, Ling Weihong, Tian Chunlian

机构信息

Key Laboratory of Hunan for Forest Products and Chemical Industry Engineering, National and Local United Engineering Laboratory of Integrative Utilization Technology of Eucommia ulmoides, Jishou University, Zhangjiajie, China.

School of Chemistry, University of Melbourne, Parkville, VIC, Australia.

出版信息

Front Chem. 2023 Apr 5;11:1186711. doi: 10.3389/fchem.2023.1186711. eCollection 2023.

Abstract

As global ageing deepens and galanthamine is the preferred clinical drug for the treatment of mild to moderate Alzheimer's disease, it will be valuable to examine the behaviour and mechanism of galanthamine's thermal decomposition for its quality control, formulation process, evaluation of thermal stability, and expiry date in production. In order to study the pyrolysis of galanthamine hydrobromide with nitrogen as the carrier gas, a thermogravimetric-differential thermogravimetric technique (TG-DTG) was applied at a temperature rise rate of 10 K min and a volume flow rate of 35 mL min. The apparent activation energy and the prefactor ( = 224.45 kJ mol and = 47.40) of the thermal decomposition reaction of galanthamine hydrobromide were calculated according to the multiple heating rate method (Kissinger and Ozawa) and the single heating rate method (Coats-Redfern and Achar), and the most probable mechanism function was derived, and then the storage period was inferred from and . A three-dimensional diffusion mechanism was suggested to control the thermal decomposition of galanthamine hydrobromide in accordance with the Jander equation, random nucleation and subsequent growth control, corresponding to the Mample one-way rule and the Avrami-Erofeev equation. As a result, the thermal decomposition temperature of galanthamine hydrobromide gradually increased with the rate of temperature rise. From Gaussian simulations and thermogravimetric data, galanthamine hydrobromide decomposed at the first stage (518.25-560.75 K) to release HO, at the second stage (563.25-650.75 K) to generate CO, CO, NH and other gases, and finally at the third stage (653.25-843.25 K) to release CO. After 843.25 K, the residual molecular skeleton is cleaved to release CO and HO. According to the and presenting in the first stage of thermal decomposition, it is assumed that the storage life of galanthamine hydrobromide at room temperature 298.15 K is 4-5 years.

摘要

随着全球老龄化加剧,加兰他敏是治疗轻度至中度阿尔茨海默病的首选临床药物,研究加兰他敏热分解行为及机理对于其质量控制、制剂工艺、热稳定性评价及生产有效期具有重要意义。为研究以氮气为载气时氢溴酸加兰他敏的热解情况,采用热重-微商热重联用技术(TG-DTG),升温速率为10 K·min,体积流量为35 mL·min。根据多重升温速率法(基辛格法和小泽法)及单一升温速率法(科茨-雷德费恩法和阿查尔法)计算氢溴酸加兰他敏热分解反应的表观活化能和指前因子( = 224.45 kJ·mol且 = 47.40),推导最概然机理函数,进而根据两者推断储存期。依据扬德方程,提出三维扩散机理控制氢溴酸加兰他敏的热分解,对应随机成核及随后生长控制,符合曼普尔单向规则和阿弗拉米-埃罗费耶夫方程。结果表明,氢溴酸加兰他敏的热分解温度随升温速率逐渐升高。由高斯模拟和热重数据可知,氢溴酸加兰他敏在第一阶段(518.25 - 560.75 K)分解释放HO,在第二阶段(563.25 - 650.75 K)生成CO、CO、NH等气体,最后在第三阶段(653.25 - 843.25 K)释放CO。843.25 K后,残余分子骨架裂解释放CO和HO。根据热分解第一阶段的 和 ,推测氢溴酸加兰他敏在室温298.15 K下的储存寿命为4 - 5年。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f4c/10113435/0741464b6a44/fchem-11-1186711-g001.jpg

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