中藥濃縮製劑品質管控之探討-以麻杏甘石湯為例

A Quality Control Study on Concentrated Preparation of Traditional Chinese Medicine, an Illustration of Ma-Xing-Gan-Shi-Tang

郭文蓉(Wen-Jung Kuo)

指導教授 ： 顏銘宏

高雄醫學大學/藥學院/藥學系碩士在職專班/碩士(2015年)

https://doi.org/10.6832/KMU.2015.00084

摘要

台灣GMP藥廠製造的中藥濃縮製劑須符合行政院衛生福利部之標準。本研究以衛福部所訂定之檢驗規範為依據，選擇常使用於肺熱咳嗽的複方中藥濃縮製劑—以麻杏甘石湯為例，於民國102年7月至9月間收集九家台灣GMP中藥廠之41件批次的資料，針對重金屬限量標準檢測、微生物檢驗、薄層層析（TLC）鑑別檢查及五大項基本檢查之檢驗報告加以分析評估，另外亦分析麻杏甘石湯指標成分含量所訂定的規格及其檢測值均一性之探討，以及浸膏賦形劑含量的比值及每瓶總浸膏含量進行分析比較，期盼能找出優缺點。

結果顯示五大項基本檢查各藥廠的檢驗規格互有高低，但均同為檢驗合格（符合廠規）。薄層層析鑑別檢查依規定需附上二種以上的薄層層析鑑別檢查資料，本調查各廠家所附之檢查品項百分比皆達75 %。總重金屬及個別重金屬的限量，各廠家雖符合標準，但所使用的方法偵測極限值 (MDL) 皆不同，或未詳細說明。微生物限量檢測各中藥廠之相對標準偏差值 (RSD) > 85 %，但在大腸桿菌Escherichia coli及沙門氏桿菌Salmonella species則皆未檢出。中藥濃縮製劑指標成分含量，Ephedrine HCl+Pseudoephedrine HCl含量從28.52±4.46 mg/day至69.75±11.11 mg/day (n=6)，其RSD值 > 30 %；Glycyrrhizic acid含量從16.61±5.71 mg/day至63.29±7.70 mg/day (n=8)，其RSD值 > 32 %，顯示不同廠牌之間的指標成分含量差距太大。

從本研究的分析結果顯示在重金屬及微生物檢測方面，各中藥廠之檢驗結果均符合衛生福利部之規定，為麻杏甘石湯的毒理安全提供安全指標。方劑中藥材的指標成分是最重要的品質評價標準，在本研究有6家廠商（佔66.7 %）以君藥麻黃之Ephedrine HCl+Pseudoephedrine HCl當做其含量標準，若使用非方劑的主要成分，例如甘草之Glycyrrhizic acid作為其含量標準，無法以此來代表濃縮製劑中整個方劑的品質。因此中藥濃縮製劑指標成分應以君藥為指標成分的選擇，以維護其品質及療效。此外，依據衛生福利部規定指標成分之檢測值須落在標誌量±50 %範圍內，各中藥廠雖均符合規定，但各廠間含量差距太大，以Ephedrine HCl+Pseudoephedrine HCl含量為例，其RSD值 > 30 %。依本研究的分析結果，建議衛生福利部能訂定一致性的規範，使各中藥廠能有所依循，並得以保障產品品質，維護民眾治病之療效。

關鍵字

中藥濃縮製劑 ； 麻杏甘石湯 ； 重金屬檢驗 ； 微生物檢驗

並列摘要

On concentrated preparation of traditional Chinese medicine (CP-TCM) in Taiwan, the GMP pharmaceutical companies should agree with the standard of the Ministry of Health and Welfare. In this study, we were based on these criterion and we illustrated a CP-TCM named Ma-Xing-Gan-Shi-Tang (MXGST) which is often used in the hot type asthma. We collected forty-one batches from nine GMP pharmaceutical companies in Taiwan between July 2013 and September 2013. Then this study analyzed heavy metal limit test, microbiological limit test, thin layer chromatography (TLC) identification and five basic analytical tests. And we assessed test values and specifications’ uniformity from the target compounds. Then we assessed the ratio of extracts to excipients and total extract contents from CP-TCM of various manufacturers. And we hope to identify the strengths and weaknesses.
The results showed that the five basic analytical test specifications were different among various manufacturers, but they were all passed (in accordance with manufacturer’s policy). At least more than 50 % constituents of traditional Chinese medicine in each CP-TCM must be appended according to the regulation, and the check items of each manufacturer were achieved over 75 % in this investigation. The total and individual heavy metal limit test, although the results were passed but the method detection limit (MDL) of each manufacturer was different or not described. In total aerobic microbial count limit test, the relative standard deviation (RSD) value was more than 85 %. Then the Escherichia coli and Salmonella species count were not detected. The contents of target compounds such as ephedrine HCl+pseudoephedrine HCl was 28.52±4.46~69.75±11.11 mg/day (n=6), then the RSD value was more than 30 %, and glycyrrhizic acid was 16.61±5.71 mg/day~63.29 ±7.70 mg/day (n=8), then the RSD value was more than 32 %. These results showed that the contents of target compounds differ wide among different manufacturers.
In this study, each manufacturer’s test value was passed by the Ministry of Health and Welfare in heavy metal limit test and microbiological limit test. These could provide safe indicators for toxicological safety. The contents of herbal target compounds are the most important quality evaluation in Chinese medicine formula. In MXGST, ephedrine HCl+pseudoephedrine HCl of the active herb “Ma Huang” was the main target compound, and there were six manufacturers (66.7 % of all manufactures) taking this as target compound. Excluding the main herb, the other target compounds were unable to represent the quality of preparation, in instance of: glycyrrhizic acid of “Gan Cao”. So we should choose the target compounds of the main herb to be the qualitative index of concentrated Chinese medicinal preparation. In accordance with the Ministry of Health and Welfare, test values should fall within the range of ± 50 % specifications from the target compounds. Although each manufacturer was passed, but the contents of target compounds differ wide among different manufacturers. For example the contents of ephedrine HCl+pseudoephedrine HCl, the RSD value was more than 30 %. In this result, we recommend the Ministry of Health and Welfare to establish consistent policy and this can be comply with pharmaceutical companies, therefore to ensure the quality of products and maintain curative effect.

並列關鍵字

concentrated preparation of traditional Chinese medicine ； Ma-Xing-Gan-Shi-Tang ； heavy metal limit test ； microbiological limit test

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