超细化对川芎药性的影响
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摘要
长期以来，中药传统的加工方法使得中药服药量大且肌体吸收率低，很难发挥其效能。研究表明，中药产生的药理效应不能唯一地归功于该药特有的化学组成，还与药物的物理状态密切相关。当药物颗粒粒径小到一定程度时，由于表面效应，药效可能会产生突发性改变，国内外学者已在毫微囊(nanocapsule)、纳米粒(nanoparticle)、纳米脂质体(hposome)等药物微粒和纳粒的研制开发中做了大量研究。徐辉碧等将普通矿物中药雄黄和石决明粉碎到纳米级，理化性质和疗效均发生了显著变化。但关于植物药机械超细粉碎以及超细化对药物显微特征结构和药效的影响少有报道，而超细粉碎技术与中药学的结合，是提高中药利用率和药效释放率的有效途径。
本实验选用MICROS超细粉碎机设备，以纤维性植物川芎为代表性实例，系统研究了中药超细粉碎的工艺过程、特点及影响超细粉碎效果的诸多因素。MICROS超细粉碎机主要通过多组高速自转的陶瓷粉碎环代替传统的球状粉碎介质，粉碎环伴随主轴的旋转产生离心力，在径向间隙范围内移动，一边挤压粉碎简内壁面，一边沿粉碎筒内壁面转动，对原料粒子施加较强的压缩力、剪切力，以达到对原料粒子挤压碾碎和分散的目的。实验研究表明，影响粉碎效果的因素除了粉碎系统本生的结构差异外，还有川芎原粉与水的质量比(C)、主轴转速(R)以及粉碎时间(t)等。得出最佳工艺条件：MICROS粉碎过程中，川芎原粉与水的质量比C值应控制在4％～6％；C值过小降低了粉碎效率，过大则使川芎分散性降低；主轴转速R=1200～1500r/min时，在极限速率允许范围内可达到较好粉碎效果；粉碎时间t≥30min时，川芎粒度明显减小，超过40 min己无明显变化。
对超细粉碎前后川芎显微结构观察比较得出：由于在粉碎过程中，药材受到强烈的正向挤压力和切向剪切力的作用，细胞壁被撕裂，大部分细胞已破碎，除了极少量小粒径淀粉粒、油室以及被细小化的草酸钙结晶可显现出外，其它各特征显微组织(如导管、木纤维、木栓细胞)均没有完整结构，混合在一起不能分辨，只能观察到细胞碎片，且各种成分在粉碎的同时，均匀混合，分散性较好。
武汉理工大学硕十学位论文
由于中药有效成分的溶出与药物在体内的生物利用度之间存在一定相
关性，考虑到川芍有效成分的多样性和复杂性，本实验选取代表性有效成分
阿魏酸体外溶出量的比较来说明MICROS对川芍药物活性的影响。实验发
现，MICROS超细粉碎后川芍中阿魏酸体外溶出量较川芍原粉提高36.4%。
另外，本实验还选取有效成分川芍嗦提取率的比较来说明超细化过程对川芍
药物活性的影响。研究表明，川芍嗦的提取率较川芍原粉中提高了32.2%。
综上所述，MICROS粉碎新技术不仅可以全成分保留川芍中有效活性
物，而且可以使细胞破壁，粒径达到亚微米尺度，这两者相互作用，增加了
川芍有效成分的溶出量与提取率。另外，在传统的中药川芍提取工艺中，因
长时间高温加热和浓缩过程，有效成分大量损失。而MICROS粉碎在常温
湿性环境下进行，对于川芍中受热易破坏和挥发的有效成分的损失可以降至
最低限度。显示了MICROS超微粉碎技术作为一项高新技术在中药加工中
特有的优势。
In this study, we prepared nano rhizoma chuanxiong by superfine technology. Pharmacological effect of Chinese tradition medicine are not only due to the special chemical components, but also closely connected with the physical state. Pharmacological effect might well change paroxysmal. It is critical of combining nanotechnology and Chinese traditional medicine to improve the utilization ratio and rapid releasing.
Using the super fine mill---MICROS, a typical Chinese traditional
medicine- rhizoma chuanxiong is ultrafine grinded. So much factors such as processing, properties, and the ultrafine effect are systematically studied. The main body of the MICROS comprises of a casing, revolving main shaft in the casing and several sub-shafts interlocked with the rotation of the main shaft. The ring moves radially as much as the clearance allows by being pressed toward the inside wall of the casing. At this moment, the ring rotates itself around the sub-shaft by the friction force of the wall surface. This means that as the ring revolves in the casing it also rotates. The particles are held between the revolving ring and wall surface are subjected to compressing force created by the centrifugal force of the ring and the friction created by the rotating ring. This process generates pul-verization and dispersion of the particles. The results show that besides structure diversity of grinding machine, the mass percent concentration C(%) , rotational speed R (r/min), time t (min) all have significant influence on the average grain diameter d (run). The optimum processing is : the mass percent concentration C is from 4% to 6% , rotational speed R is from 1200 to 1500 r/min, time t>30min is enough.
The integral optical microscope photos of chuanxiong contain all identified microscopic tissues. Optical microscope photos of chuanxiong after ultrafine grinding demonstrates that cell wall is broken and most cells are broken into pieces except that a few of small sized starch grain / Grease chamber and calcium oxalate crystal are still can be seen. The reason is medicine subject to
fierce forward extrusion and tangential shearing force during the course of grinding. Comparing with common pulverized powder, super fine mill can grid cells up to nearly nano-size, so cellular active components can contact dissolvent even can enter dissolvent completely. It can minimize the loss of active components.
The dissolution quantities in vitro of ferulic acid that one of active components of rhizoma chuanxiong is increased by MICROS processing. The dissolution quantities in vitro of ferulic acid before and after ultrafine grinding at the same complex external condition is calculated by external reference method. The results show that the dissolution quantities of super fine powder after ultrafine grinding is by 36.4% higher than that of original powder. The extraction quantities of TMP (tetram ethylpyrazine) before and after ultrafine grinding at the same complex external condition are calculated by external reference method. The results show that the quality of TMP from chuanxiong after ultrafine grinding is by 32.2% higher than that TMP from original chuanxiong.
In conclusions, ultrafine rhizoma chuanxiong was successfully prepared by MICROS in this paper. The influence of processing parameters on pharmic effect, the different properties between ultrafine rhizoma chuanxiong and originally fine powder were systematically studied by optical microscope, Zeta Potential Analyzer and high-performance liquid chromatography(HPLC). The results illustrated that the cellular tissue of rhizoma chuanxiong were broken into pieces and dispersed stably and homogeneously, in addition, the dissolution quantities in vitro of ferulic acid and the extraction quantities of TMP were accelerated by micros processing. Last, the work condition is under common temperature that can minimize the loss of active components.
本实验选用MICROS超细粉碎机设备，以纤维性植物川芎为代表性实例，系统研究了中药超细粉碎的工艺过程、特点及影响超细粉碎效果的诸多因素。MICROS超细粉碎机主要通过多组高速自转的陶瓷粉碎环代替传统的球状粉碎介质，粉碎环伴随主轴的旋转产生离心力，在径向间隙范围内移动，一边挤压粉碎简内壁面，一边沿粉碎筒内壁面转动，对原料粒子施加较强的压缩力、剪切力，以达到对原料粒子挤压碾碎和分散的目的。实验研究表明，影响粉碎效果的因素除了粉碎系统本生的结构差异外，还有川芎原粉与水的质量比(C)、主轴转速(R)以及粉碎时间(t)等。得出最佳工艺条件：MICROS粉碎过程中，川芎原粉与水的质量比C值应控制在4％～6％；C值过小降低了粉碎效率，过大则使川芎分散性降低；主轴转速R=1200～1500r/min时，在极限速率允许范围内可达到较好粉碎效果；粉碎时间t≥30min时，川芎粒度明显减小，超过40 min己无明显变化。
对超细粉碎前后川芎显微结构观察比较得出：由于在粉碎过程中，药材受到强烈的正向挤压力和切向剪切力的作用，细胞壁被撕裂，大部分细胞已破碎，除了极少量小粒径淀粉粒、油室以及被细小化的草酸钙结晶可显现出外，其它各特征显微组织(如导管、木纤维、木栓细胞)均没有完整结构，混合在一起不能分辨，只能观察到细胞碎片，且各种成分在粉碎的同时，均匀混合，分散性较好。
武汉理工大学硕十学位论文
由于中药有效成分的溶出与药物在体内的生物利用度之间存在一定相
关性，考虑到川芍有效成分的多样性和复杂性，本实验选取代表性有效成分
阿魏酸体外溶出量的比较来说明MICROS对川芍药物活性的影响。实验发
现，MICROS超细粉碎后川芍中阿魏酸体外溶出量较川芍原粉提高36.4%。
另外，本实验还选取有效成分川芍嗦提取率的比较来说明超细化过程对川芍
药物活性的影响。研究表明，川芍嗦的提取率较川芍原粉中提高了32.2%。
综上所述，MICROS粉碎新技术不仅可以全成分保留川芍中有效活性
物，而且可以使细胞破壁，粒径达到亚微米尺度，这两者相互作用，增加了
川芍有效成分的溶出量与提取率。另外，在传统的中药川芍提取工艺中，因
长时间高温加热和浓缩过程，有效成分大量损失。而MICROS粉碎在常温
湿性环境下进行，对于川芍中受热易破坏和挥发的有效成分的损失可以降至
最低限度。显示了MICROS超微粉碎技术作为一项高新技术在中药加工中
特有的优势。
In this study, we prepared nano rhizoma chuanxiong by superfine technology. Pharmacological effect of Chinese tradition medicine are not only due to the special chemical components, but also closely connected with the physical state. Pharmacological effect might well change paroxysmal. It is critical of combining nanotechnology and Chinese traditional medicine to improve the utilization ratio and rapid releasing.
Using the super fine mill---MICROS, a typical Chinese traditional
medicine- rhizoma chuanxiong is ultrafine grinded. So much factors such as processing, properties, and the ultrafine effect are systematically studied. The main body of the MICROS comprises of a casing, revolving main shaft in the casing and several sub-shafts interlocked with the rotation of the main shaft. The ring moves radially as much as the clearance allows by being pressed toward the inside wall of the casing. At this moment, the ring rotates itself around the sub-shaft by the friction force of the wall surface. This means that as the ring revolves in the casing it also rotates. The particles are held between the revolving ring and wall surface are subjected to compressing force created by the centrifugal force of the ring and the friction created by the rotating ring. This process generates pul-verization and dispersion of the particles. The results show that besides structure diversity of grinding machine, the mass percent concentration C(%) , rotational speed R (r/min), time t (min) all have significant influence on the average grain diameter d (run). The optimum processing is : the mass percent concentration C is from 4% to 6% , rotational speed R is from 1200 to 1500 r/min, time t>30min is enough.
The integral optical microscope photos of chuanxiong contain all identified microscopic tissues. Optical microscope photos of chuanxiong after ultrafine grinding demonstrates that cell wall is broken and most cells are broken into pieces except that a few of small sized starch grain / Grease chamber and calcium oxalate crystal are still can be seen. The reason is medicine subject to
fierce forward extrusion and tangential shearing force during the course of grinding. Comparing with common pulverized powder, super fine mill can grid cells up to nearly nano-size, so cellular active components can contact dissolvent even can enter dissolvent completely. It can minimize the loss of active components.
The dissolution quantities in vitro of ferulic acid that one of active components of rhizoma chuanxiong is increased by MICROS processing. The dissolution quantities in vitro of ferulic acid before and after ultrafine grinding at the same complex external condition is calculated by external reference method. The results show that the dissolution quantities of super fine powder after ultrafine grinding is by 36.4% higher than that of original powder. The extraction quantities of TMP (tetram ethylpyrazine) before and after ultrafine grinding at the same complex external condition are calculated by external reference method. The results show that the quality of TMP from chuanxiong after ultrafine grinding is by 32.2% higher than that TMP from original chuanxiong.
In conclusions, ultrafine rhizoma chuanxiong was successfully prepared by MICROS in this paper. The influence of processing parameters on pharmic effect, the different properties between ultrafine rhizoma chuanxiong and originally fine powder were systematically studied by optical microscope, Zeta Potential Analyzer and high-performance liquid chromatography(HPLC). The results illustrated that the cellular tissue of rhizoma chuanxiong were broken into pieces and dispersed stably and homogeneously, in addition, the dissolution quantities in vitro of ferulic acid and the extraction quantities of TMP were accelerated by micros processing. Last, the work condition is under common temperature that can minimize the loss of active components.
引文
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