基于君臣药主成分质量分数与临床疗效关系的消肿I号膏剂质控研究

doi:10.5246/jcps.2023.09.063

中国药学(英文版) ›› 2023, Vol. 32 ›› Issue (9): 764-771.DOI: 10.5246/jcps.2023.09.063

• 【药事管理与临床药学专栏】 • 上一篇下一篇

基于君臣药主成分质量分数与临床疗效关系的消肿I号膏剂质控研究

金实¹^,²^,³, 李成银¹^,²^,³, 景欣悦⁴, 彭蕴茹⁵^,⁶, 董少华¹^,²^,³, 孙婉瑾¹^,²^,³^,^*()

1. 湖北省中医院, 湖北武汉 430061
2. 湖北中医药大学附属医院, 湖北武汉 430061
3. 湖北省中医药研究院, 湖北武汉 430074
4. 南京中医药大学, 江苏南京 210023
5. 南京中医药大学附属中西医结合医院，江苏南京 210028
6. 江苏省中医药研究院, 江苏南京 210028

收稿日期:2023-03-12 修回日期:2023-04-23 接受日期:2023-06-21 出版日期:2023-09-30 发布日期:2023-09-30
通讯作者: 孙婉瑾
作者简介:
+ Tel.: +86-27-88920270, E-mail: sunwanjin@126.com
基金资助:
Basic Research Funds for Public Research Institutes at the Central Level (Grant No. YZ-1850) and National Training Project for Traditional Chinese Medicine Technology Inheritance Talent (Grant No. (2023)96).

Study on quality control of Xiaozhong Ointment NO. 1 based on the relationship between quality fractions of main components in monarch and minister drugs and the clinical efficacy

Shi Jin¹^,²^,³, Chengyin Li¹^,²^,³, Xinyue Jing⁴, Yunru Peng⁵^,⁶, Shaohua Dong¹^,²^,³, Wanjin Sun¹^,²^,³^,^*()

1 Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan 430061, Hubei, China
2 Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan 430061, Hubei, China
3 Hubei Province Academy of Traditional Chinese Medicine, Wuhan 430074, Hubei, China
4 Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China
5 Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu, China
6 Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu, China

Received:2023-03-12 Revised:2023-04-23 Accepted:2023-06-21 Online:2023-09-30 Published:2023-09-30
Contact: Wanjin Sun

摘要/Abstract

摘要：

本研究以HPLC法测定消肿I号膏剂中君药白首乌中告达庭和臣药阿魏中阿魏酸的质量分数, 并通过多批次样品质量分数和药效之间的规律拟定质控范围。采用Waters X-Bridge C₁₈柱 (150 mm × 4.6 mm, 5 μm)色谱柱分离, 柱温为30 ℃, 流动相为乙腈–0.1%的磷酸水溶液, 梯度洗脱, 流速为1 mL/min; PDA检测器检测波长为210 nm; 进样量10 μL。采用NRS法表示疼痛强度。疼痛缓解百分比= (A – B)/A × 100% (A = 用药前评分; B = 用药后评分), 疼痛缓解程度分为0–4度。经过方法学研究, 测定了10批样品中君药白首乌的主要成分告达庭和臣药阿魏中的主要成分阿魏酸平均质量分数, 并记录了使用上述10批样品患者的疼痛缓解程度。质量分数较低的两组在疼痛缓解程度也低于其他组。另有5批患者使用后疼痛缓解程度达到3度的样品, 其质量分数均大于10批的平均值减SD值。因此, 拟定质量控制范围为告达庭质量分数不小于0.4087 mg/g, 阿魏酸质量分数不小于0.8511 mg/g。本方法准确、灵敏、简便且重现性好, 依据君臣药主要成分质量分数与疗效关系, 拟定了质控范围, 为该对抗癌性疼痛的中药内病外治制剂的质量控制和进一步研究提供了科学基础。

关键词: 消肿I号膏剂, 质量控制, 疼痛等级量表, 告达庭, 阿魏酸

Abstract:

In the present study, we aimed to determine the mass fractions of caudatin in cynanchum auriculatum, a component of monarch drug, and ferulic acid in ferulae resina, a component of minister drug, in Xiaozhong Ointment NO.1 using high-performance liquid chromatography (HPLC). The relationship between the mass fractions and clinical efficacy, which was expressed by the degree of pain relief, was explored in several batches of samples to establish the quality control ranges of active ingredients. A Waters X-Bridge column (250 mm × 4.6 mm, 5 μm) was used for separation at 30 °C. The optimized mobile phase consisted of acetonitrile and a 0.1% phosphoric acid water solution and was delivered by gradient elution at a flow rate of 1.0 mL/min. The PDA detector was set at 210 nm, and the injection volume was 10 μL. The intensity of pain was indicated using the Numeric Rating Scale (NRS) method. The percentage of pain relief was calculated using the formula (A – B)/A × 100%, where A and B are the pre- and post-medication scores, respectively. The pain relief degrees were categorized into 0–4 degrees. After the methodology study, the mass fractions of caudatin and ferulic acid were obtained from 10 batches of samples, and the percentage reductions in NRS were recorded in the patients using these samples. The results showed that the two groups with lower mass fractions also achieved lower percentage decreases in NRS than the other groups. An additional five batches of samples were tested, and the mass fractions were greater than the averages minus the standard deviation of the previous 10 batches. Therefore, the proposed quality control ranges were that the mass fractions of caudatin and ferulic acid should not be less than 0.4087 and 0.8511 mg/g, respectively. This accurate, sensitive, convenient, and reproducible HPLC method and the research on the consistent correlation between mass fraction and clinical efficacy laid a foundation for better quality control and further mechanism study of this preparation.

Key words: Xiaozhong Ointment NO. 1, Quality control, Pain intensity numerical rating scale, Caudatin, Ferulic acid

Supporting:

金实, 李成银, 景欣悦, 彭蕴茹, 董少华, 孙婉瑾. 基于君臣药主成分质量分数与临床疗效关系的消肿I号膏剂质控研究[J]. 中国药学(英文版), 2023, 32(9): 764-771.

Shi Jin, Chengyin Li, Xinyue Jing, Yunru Peng, Shaohua Dong, Wanjin Sun. Study on quality control of Xiaozhong Ointment NO. 1 based on the relationship between quality fractions of main components in monarch and minister drugs and the clinical efficacy[J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(9): 764-771.

图/表 4

Figure 1. The chromatogram of the reference solution. “a” represents ferulic acid, and “b” represents caudatin.

Figure 2. The chromatogram of the negative samples and test solution. (1) Negative sample A (without cynanchum auriculatum), peak “a” represents ferulic acid; (2) Negative sample B (without ferulae resina), peak “b” represents caudatin; (3) Negative sample C (without cynanchum auriculatum and ferulae resina); (4) Test solution, peak “a” represents ferulic acid, and peak “b” represents caudatin.

Table 1. Recovery rate.

Table 2. Mass fractions and percentage decrease in NRS score of caudatin and ferulic acid in Xiaozhong Ointment NO. 1.

参考文献 18

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基于君臣药主成分质量分数与临床疗效关系的消肿I号膏剂质控研究

Study on quality control of Xiaozhong Ointment NO. 1 based on the relationship between quality fractions of main components in monarch and minister drugs and the clinical efficacy

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