Studies On Preparation Technology And Quality Standard Of Wusen Erlian Granules

ObjectiveViral myocarditis (VMC) is the common infectious myocardial disease clinically caused by multiple pathogenic factors. As the symptoms are concealed from the onset of VMC, it is prone to result in sudden cardiac death, which makes it more harmful. At present, there is no spectfic way available on treatment of VMC in the western medicine. So there is important realistic meaning to search for safer and more effective therapeutic drug. Wusen Erlian Decoction is a compound preparation that specializes in treating VMC. In order to facilitate the clinical application for patient, we convert Wusen Erlian Decoction into Wusen Erlian Granules. The prescription of Wusen Erlian Decoction is composed of fifteen kinds of Chinese herbal medicines, such as radix pseudostellariae, Salvia Miltrorrhiza, Panax notoginseng, scrophularia ningpoensis, Sophora flavescens, and so on. It has efficacy in boosting qi, nourishing yin, and ranquilizing mind. Based on the guidance of Traditional Chinese Medicine theory and properties of the medicinal materials in the prescription, we systematically study on the extraction technology, formulation screening, molding process, quality standard and stability, which providing safe, effective and easy intaking Wusen Erlian Granules for clinical treatment of VMC.Methods1. Research on extraction technology and pulverization technology:According to the properties of the medicinal materials in the prescription and the Traditional Chinese Medicine custom, thirteen kinds of herbs including radix pseudostellariae were prepared by the method of water extraction. We used orthogonal design with multifactor comprehensive evaluation to determine the best water-extracting technology. By comparing the effect of removing impurities from the water extract under different rotational speeds, we obtained the best impurity-removing technology. Based on the treatment method that Panax notoginseng and amber were directly used as medicines after pulverization, we studied the effect of pulverization on the solubility of total saponins in Panax notoginseng by HPLC method to determine the best pulverization technology.2. Research on preparation technology:Taking granules forming rate, moisture absorption rate, and taste as the indicators, we used orthogonal design with multifactor comprehensive evaluation to screen the best formulation. We used extrusion granulating method to make granules. The hygroscopicity, liquidity, and bulk density of the granules obtained were investigated. Then the pilot productions were carried out.3. Research on quality standard:We established the fingerprint of Wusen Erlian Granules by HPLC method. The fingerprint similarity analysis of10batches of products was carried out. The contents of four index ingredients such as salvianolic acid B, hesperidin, harpagoside, and berberine hydrochloride were simultaneously determined. Meanwhile, we established the TLC identification method of Panax notoginseng, Scrophularia ningpoensis, Coptis chinensis, and Glycyrrhiza uralensis. On this basis, quality inspection and stability study of Wusen Erlian Granules were carried out.Results1. Taking the contents of salvianolic acid B and harpagoside, and yield of dry extract as the indicators, we used orthogonal design with multifactor comprehensive evaluation to determine the best water-extracting technique as follows. The thirteen kinds of medicinal materials in the prescription except for Panax notoginseng and amber were decocted with water for twice. Ten times the amount of water was added at the first time. Then eight times was added at the second time. Each decoction lasted for one hour. Using single factor experiment, we identified the best impurity-removing technology that was high speed centrifugation under the condition of the rotating speed8,000r/min and the centrifugation time fifteen minutes. Using the content of panax notoginseng total saponins as the index, we determined the best pulverization technology of Panax notoginseng and amber as follows:comminution granularity100meshes.2. Taking granules forming rate, moisture absorption rate, and taste as the indicators, we used orthogonal design with multifactor evaluation comprehensively to screen the best formulation as follows. The water-extracting liquid was concentrated until the density of which reached1.25～1.30(60℃). The ratio of the concentrated extract and the excipients was dry extract:sucrose powder:dextrin1:2.7:1.3. By using granules forming rate as the indicator, we determined the best molding process as follows.70%alcohol was added into the concentrated extract and the excipients in the form of spray while stirring to make the soft material. The amount of ethanol was5%of that of the excipient. The stirring time was eight minutes. Then the soft material was put into swing granulator and passed through a14-mesh sieve to make into granules which were dried at80℃for four hours and passed through the14-mesh sieve again to harvest the granules finally. We studied the Wusen Erlian Granules’ physicochemical properties such as hygroscopicity, liquidity, and bulk density. The results conformed to the rules of China Pharmacopoeia (2010). Based on the studies mentioned above, we completed three batches of pilot productions. The yields of the granules and the metastasis rates of the effective ingredients conformed to the regulations.3. Fingerprint combined with multicomponent quantitative analysis method established by HPLC was simple and practicable. The Fingerprint had good precision, stability and reproducibility, which could comprehensively reflect the overall quality characteristics of Wusen Erlian Granules. The TLC method was selected to qualitatively identify Panax notoginseng, Scrophularia ningpoensis, Coptis chinensis, and Glycyrrhiza uralensis. The spots relevant were clear and specific compared with the reference medicinal materials. The conventional quality indicators such as heavy metals, arsenic salt, granularity, moisture, dissolubility, weight deviation and the limitation of microorganism conformed to the rules of China Pharmacopoeia (2010). The results of strong light and high temperature test showed that properties of the granules and contents of active constituents did not change significantly. In addition, we studied the stability including the aceelerated tests for six-month and the long term stability tests for eighteen-month. The indicators such as characters, identification, granularity, moisture, dissolubility, the limitation of microorganism, and contents of active constituents of relevant months did not change significantly, compared with that of zero months.ConclusionsThe extraction technology, pulverization technology, and preparation technology of Wusen Erlian Granules established in this stuy are reasonable, stable and simple. Fingerprint combined with multicomponent quantitative analysis and the TLC methods have strong specificity, simple operation and good repeatability, which can be regarded as advanced and reliable quality standard. The quality of Wusen Erlian Granules prepared is stable and controllable.