黄柏配方颗粒抑菌性的中和方法探究

doi:10.3976/j.issn.1002-4026.20260014

摘要/Abstract

摘要： 为探究黄柏配方颗粒抑菌活性的中和方式，为具抑菌活性中药配方颗粒的质量控制和药品标准的完善提供理论和数据支持，采用两类方法（平皿法和薄膜过滤法）、两类中和剂（“3%聚山梨酯80 + 0.3%卵磷脂”和10%羟丙基-β-环糊精）及三个稀释级（1:10、1:100和1:500）的不同组合，测试每种组合中5种试验菌株的加菌回收比值。结果表明，在较低稀释级1:10和1:100，加入两类中和剂的平皿法和薄膜过滤法均无法使金黄色葡萄球菌和白色念珠菌的加菌回收比值满足要求；在1:500稀释级，平皿法中3%聚山梨酯80和0.3%卵磷脂无法完全中和黄柏配方颗粒中抑菌成分对白色念珠菌的抑菌性，需结合薄膜过滤法才可满足回收比值范围（0.5~2.0）；使用羟丙基-β-环糊精时，平皿法（1:500）可满足要求。本文建立的黄柏配方颗粒的微生物检查方法，方法稳定、可靠，为药品标准完善提供了数据支持；两种中和剂的效果为抑菌性中药配方颗粒抑菌性的中和提供了参考。

关键词: 黄柏, 中药配方颗粒, 微生物限度, 抑菌活性, 中和剂

Abstract: To explore neutralization methods for antibacterial activity of Phellodendri chinensiscortex Chinese medicine formula granules (CMFG) as well as to provide theoretical and data support for the quality control of antibacterial CMFG and the improvement of pharmaceutical standards, different approaches were used to eliminate the antibacterial activity ofP. chinensiscortex CMFG. Two microbial enumeration methods (plate-count, PC, and membrane filtration, MF), two neutralizers (a combination of 3% polysorbate 80 and 0.3% lecithin, and 10% hydroxypropyl-β-cyclodextrin, HP-β-CD), and three dilution levels (1:10, 1:100, and 1:500) were used in this study. Recovery ratios of five test strains were measured for each combination. Results revealed that at lower dilution levels of 1:10 and 1:100, neither PC nor MF methods with either neutralizers could achieve acceptable inoculum recovery ratios (0.5~2.0) forStaphylococcus aureusandCandida albicans. At higher dilution level of 1:500, 3% polysorbate 80 and 0.3% lecithin combined with the PC method could not completely neutralize the antibacterial components inP. chinensiscortex CMF againstC. albicans, and only when combined with the MF method could the recovery ratio meet the required range (0.5~2.0). Conversely, HP-β-CD at the dilution level of 1:500 achieved satisfactory recovery ratios (0.5~2.0) for all five strains when the PC method was used. Accordingly, a microbial examination method for P. chinensiscortex CMFG compliant with theChinese Pharmacopoeia2025 was established. This method has been validated as stable and reliable, providing robust data support for refining its quality standards. Moreover, the effectiveness of the two neutralizers provides a practical reference for neutralizing the antibacterial activity of traditional CMFG with inherent antibacterial properties.

Key words: Phellodendri chinensiscortex, Chinese medicinal formula granule, microbial limit, antibacterial activity, neutralizer

中图分类号:

R 917

安春艳, 赵一懿, 陈卓, 牛振东. 黄柏配方颗粒抑菌性的中和方法探究[J]. 山东科学, 0, (): 1-.

AN Chunyan, ZHAO Yiyi, CHEN Zhuo, NIU Zhendong. Study on the neutralization method for the antibacterial activity of Phellodendri chinensiscortex Chinese medicine formula granules[J]. Shandong Science, 0, (): 1-.

参考文献

[1] 国家药典委员会.中华人民共和国药典2025年版四部 [M]，北京: 中国医药科技出版社, 2025.

[2] 国家药品监督管理局. 国家药品标准 YBZ-PFKL-2021063 黄柏配方颗粒 [S]. 2021:1-3.

[3] 国家药品监督管理局. 国家药监局关于发布中药标准管理专门规定的公告 [EB/OL]. (2024-07-09) [2025-06-18]. https://www.gov.cn/zhengce/zhengceku/202407/content_6962491.htm.

[4] 国家药品监督管理局. 国家药监局关于发布《中药配方颗粒质量控制与标准制定技术要求》的通告 [EB/OL]. (2021-01-26) [2025-06-18]. https://www.gov.cn/zhengce/zhengceku/2021-02/11/content_5586817.htm.

[5] 张博, 张婷, 王树春. 黄柏的化学成分、质量分析方法及药理作用研究 [J]. 现代医药卫生, 2013, 29(10): 1505-1507. DOI: 10.3969/j.issn.1009-5519.2013.10.031.

[6] 夏帅, 马立艳, 谢苗荣. 盐酸小檗碱对金黄色葡萄球菌体外抗菌活性的研究 [J]. 临床和实验医学杂志, 2022, 21(07): 673-678. DOI: 10.3969/j.issn.1671－4695.2022.07.001.

[7] ZORIĆ N, KOSALEC I, TOMIĆ S, et al. Membrane ofCandida albicansas a target of berberine[J]. BMC Complementary and Alternative Medicine, 2017, 17(1): 268. DOI:10.1186/s12906-017-1773-5.

[8] HUANG X X, ZHENG M Y, YI Y L, et al. Inhibition of berberine hydrochloride onCandida albicansbiofilm formation[J]. Biotechnology Letters, 2020, 42(11): 2263-2269. DOI:10.1007/s10529-020-02938-6.

[9] 马欣, 成妍, 马蓉丽. 黄柏萃取物的抑菌活性及其正丁醇萃取物化学成分分析 [J]. 现代食品科技, 2021, 37(04): 96-101. DOI: 10.13982/j.mfst.1673-9078.2021.4.1060.

[10] FAN T, GUO W, SHAO T, et al. Design, synthesis and evaluation of phenylthiazole and phenylthiophene pyrimidindiamine derivatives targeting the bacterial membrane [J]. Eur J Med Chem, 2020, 190: 112141. DOI: 10.1016/j.ejmech.2020.112141.

[11] WANG R F, YU S J, ZHAO X X, et al. Design, synthesis, biological evaluation and molecular docking study of novel thieno [3, 2-d] pyrimidine derivatives as potent FAK inhibitors[J]. European Journal of Medicinal Chemistry, 2020, 188: 112024. DOI:10.1016/j.ejmech.2019.112024.

[12] FANG Z Y, LI Y N, ZHENG Y Y, et al. Antibacterial activity and mechanism of action of a thiophenyl substituted pyrimidine derivative[J]. RSC Advances, 2019, 9(19): 10739-10744.

[13] HUANG X X, YI Y L, YONG J Y, et al. Inhibitory effect of berberine hydrochloride againstCandida albicansand the role of the HOG-MAPK pathway[J]. The Journal of Antibiotics, 2021, 74(11): 807-816. DOI:10.1038/s41429-021-00463-w.

[14] ZHAO T, ZHANG K, SHI G X, et al. Berberine inhibits the adhesion ofCandida albicansto vaginal epithelial cells[J]. Frontiers in Pharmacology, 2022, 13: 814883. DOI:10.3389/fphar.2022.814883.

[15] XIE Y F, LIU X S, ZHOU P R.In vitroantifungal effects of berberine againstCandidaspp. in planktonic and biofilm conditions[J]. Drug Design, Development and Therapy, 2020, 14: 87-101. DOI:10.2147/DDDT.S230857.

[16] TONG Y J, ZHANG J Y, SUN N, et al. Berberine reverses multidrug resistance inCandida albicansby hijacking the drug efflux pump Mdr1p[J]. Science Bulletin, 2021, 66(18): 1895-1905. DOI:10.1016/j.scib.2020.12.035.

[17] TSUJII T, KAWADA-MATSUO M, MIGITA H, et al. Antibacterial activity ofPhellodendronbark againstStreptococcusmutans[J]. Microbiology and Immunology, 2020, 64(6): 424-434. DOI:10.1111/1348-0421.12787.

[18] 张诚, 刘汝银, 杨开泰, 等. 中药治疗耐药性脊柱结核的研究进展 [J]. 颈腰痛杂志, 2025, 46(01): 191-196. DOI: 10.3969/j.issn.1005-7234.2025.01.035.

[19] 杨轶涵, 毛娅芯, 徐新平. 中药协同抗真菌药物抗隐球菌的研究进展 [J]. 微生物学报, 2025, 65(02): 537-550. DOI: 10.13343/j.cnki.wsxb.20240533.

[20] 吴先昊, 陈芳军, 黎云颖, 等. 中药复配剂及其乳膏的体外抑菌效果观察 [J]. 中国消毒学杂志, 2025, 42(03): 165-167. DOI: 10.11726/j.issn.1001-7658.2025.03.002.

[21] 黄芷珊, 吴思玚, 赵丽凤, 等. 中药抗肺炎物质基础的研究进展[J]. 国外医药(抗生素分册), 2025, 46(3): 171-178. DOI:10.13461/j.cnki.wna.005674.

[22] 袁芳草, 吴然, 李倩, 等. “癣净擦剂”对红色毛癣菌的体外抑菌实验研究[J]. 中国真菌学杂志, 2024, 19(6): 573-578.

[23] 余达浪, 谢明. 中草药抗白色念珠菌作用的研究进展 [J]. 大连医科大学学报, 2024, 46(06): 528-534. DOI: 10.11724/jdmu.2024.06.09.

[24] 任柱平, 汪依航, 王金艳, 等. 中药蒲公英抗幽门螺杆菌活性检测及网络药理学分析 [J]. 贵州医科大学学报, 2024, 49(10): 1455-63+70. DOI: 10.19367/j.cnki.2096-8388.2024.10.007.

[25] LIU B G, XIE M, DONG Y, et al. Antimicrobial mechanisms of traditional Chinese medicine and reversal of drug resistance: a narrative review [J]. Eur Rev Med Pharmacol Sci, 2022, 26(15): 5553-55561. DOI: 10.26355/eurrev_202208_29426.

[26] 栾兆棠, 王永传, 魏红, 等. 中药拮抗细菌耐药性研究进展[J]. 临床医药实践, 2025, 34(1): 51-54. DOI:10.16047/j.cnki.cn14-1300/r.2025.01.008. 7860.

[27] 吴莹辉, 廖鹏达, 孔勇杰. 中医药诊治多重耐药菌的研究进展[J]. 中医临床研究, 2024, 16(26): 132-136.

[28] 马婧涵, 林英, 何洪, 等. 黄芩消除产碳青霉烯酶肺炎克雷伯菌耐药质粒的研究[J]. 标记免疫分析与临床, 2024, 31(8): 1513-1517.

[29] 符语恬, 周国威, 冯萧, 等. 多重耐药菌在中医普外溃疡创面的定植现状、传播途径及中医防控策略研究进展[J]. 中国病原生物学杂志, 2026, 21(5): 696-700. DOI:10.13350/j.cjpb.260526.

[30] 姬俊, 刘婷婷, 牛萌萌, 等. 卵磷脂和聚山梨酯-80联用在中药制剂抑菌活性中的中和作用 [J]. 中国药师, 2017, 20(03): 586-588. DOI: 10.3969/j.issn.1008-049X.2017.03.058.

[31] 孙伟, 刘文杰, 崔颖, 等. β-环糊精在喹诺酮类抗生素药品微生物限度检查方法建立中的应用 [J]. 药物分析杂志, 2013, 33(01): 18-21+9. DOI: 10.16155/j.0254-1793.2013.01.026.

[30] 姬俊, 刘婷婷, 牛萌萌, 等. 卵磷脂和聚山梨酯-80联用在中药制剂抑菌活性中的中和作用[J]. 中国药师, 2017(3): 586-588.