Article(id=1322923082784047198, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322923011518628427, articleNumber=null, orderNo=null, doi=10.13193/j.issn.1673-7717.2025.03.014, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=null, receivedDateStr=null, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1793339041658, onlineDateStr=2026-10-30, pubDate=1741536000000, pubDateStr=2025-03-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793339041658, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793339041658, creator=13701087609, updateTime=1793339041658, updator=13701087609, issue=Issue{id=1322923011518628427, tenantId=1146029695717560320, journalId=1255847919539208197, year='2025', volume='43', issue='3', pageStart='1', pageEnd='258', issueExtLink='null', onlineDate='null', pubDate='1741536000000', pubDateStr='2025-03-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1793339024666, creator='13701087609', updateTime=1793340602374, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322929628976906432, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322923011518628427, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322929628981100737, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322923011518628427, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=85, endPage=91, ext={EN=ArticleExt(id=1322923083249614945, articleId=1322923082784047198, tenantId=1146029695717560320, journalId=1255847919539208197, language=EN, title=Study on Ratio of Modified Sanhuang Xiexin Decoction(加味三黄泻心汤)for External Use and Pharmacodynamic Evaluation of Microemulsion Gel on Acne Based on Orthogonal Test, columnId=1256183361521967297, journalTitle=Chinese Archives of Traditional Chinese Medicine, columnName=Target on National Project, runingTitle=null, highlight=null, articleAbstract=
Objective

To study the antibacterial effect of eight kinds of Chinese drugs in vitro,screen the best compound ratio for external use to treat acne and prepare compound microemulsion gel for in vivo pharmacodynamic study of acne model in mice.

Methods

Propionibacterium acnes and Staphylococcus aureus were selected as target bacteria,and the diameter of inhibition zone and minimum inhibitory concentration(MIC)of eight Chinese drugs were determined by filter paper method. Orthogonal test was used to optimize the compound ratio. The physical and chemical properties of microemulsion and microemulsion gel were comprehensively evaluated by preparing microemulsion with pseudo ternary phase diagram as evaluation index. A mouse acne model was established by injecting Propionibacterium acnes into the back,and the blank group,model group,positive drug group,microemulsion gel group and compound microemulsion gel group were set up. Histopathological changes were observed by HE and Masson staining,and the levels of inflammatory factors[interleukin-1β(IL-1β),interleukin-10(IL-10)and tumor necrosis factor-(TNF-α)]in serum were detected by enzyme-linked immunosorbent assay(ELISA).

Results

The results showed that all the eight Chinese drugs had different antibacterial effects,among which Huanglian(Coptidis Rhizoma)had the best antibacterial effect on Propionibacterium acnes and Gancao(Glycyrrhizae Radix et Rhizoma)had the best antibacterial effect on Staphylococcus aureus,with MIC of 31.25 mg mL-1. The orthogonal test results showed that the sterilization rate of Dahuang(Rhei Radix et Rhizoma)(250 mg mL-1),Huanglian(Coptidis Rhizoma)(250 mg mL-1),Huangqin(Scutellariae Radix)(125 mg mL-1)and Gancao(Glycyrrhizae Radix et Rhizoma)(62.5 mg mL-1)was the best when the ratio was 4∶4∶2∶1. According to the pseudo-ternary phase diagram,the final microemulsion formula was Tween-80(3 g),PEG 400(6 g),isopropyl myristate(1 g)and distilled water(12 g),and 1% carbomer 940 was added according to the mass ratio,and the microemulsion gel was obtained after full swelling,and the compound microemulsion gel was obtained by replacing the water phase with the compound extract of the Chinese medicine compound. The pharmacodynamic experiment showed that compared with those of the blank group,the skin tissue of the model group showed obvious pathological changes,and the contents of IL-1β,IL-10 and TNF-αin serum increased significantly(P<0.01). Compared with those in the model group,the pathological changes in the drug group were relieved to varying degrees,and the contents of serum inflammatory factors were decreased,especially those in the compound microemulsion gel group(P<0.01).

Conclusion

The compound of Dahuang(Rhei Radix et Rhizoma),Huanglian(Coptidis Rhizoma),Huangqin(Scutellariae Radix)and Gancao(Glycyrrhizae Radix et Rhizoma)has obvious bacteriostatic effect. The preparation of the compound microemulsion gel has a good therapeutic effect on acne model in mice,and can effectively alleviate acne inflammation caused by Propionibacterium acnes.

, authors=Jinjing LIANG, Xinxue YANG, Rui DONG, authorsList=Jinjing LIANG, Xinxue YANG, Rui DONG, authorCompany=null, correspAuthors=Rui DONG, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1322923093747957912, articleId=1322923082784047198, tenantId=1146029695717560320, journalId=1255847919539208197, language=CN, title=基于正交试验研究外用加味三黄泻心汤配比及微乳凝胶对痤疮的药效学评价, columnId=1256183362172142382, journalTitle=中华中医药学刊, columnName=国家项目点击, runingTitle=null, highlight=null, articleAbstract=
目的

研究八味中药的体外抑菌效果,筛选出外用治疗痤疮的最佳复方配比,制备复方微乳凝胶用于小鼠痤疮模型的体内药效学研究。

方法

选取痤疮丙酸杆菌和金黄色葡萄球菌为目标菌,采用滤纸片法测定八味中药的抑菌圈直径和最小抑菌浓度(MIC);采用正交试验法优化复方配比;以伪三元相图为评价指标制备微乳,对微乳及微乳凝胶理化性质进行综合评价;采用背部注射痤疮丙酸杆菌建立小鼠痤疮模型,设置空白组、模型组、阳性药组、微乳凝胶组和复方微乳凝胶组,通过HE和Masson染色观察组织病理改变,酶联免疫吸附试验(ELISA)检测血清中炎症因子白介素1β(IL-1β)、白介素10(IL-10)和肿瘤坏死因子-α(TNF-α)水平。

结果

结果表明八味中药均有不同程度的抑菌效果,其中黄连对痤疮丙酸杆菌的抑菌效果最好,甘草对金黄色葡萄球菌的抑菌效果最好,MIC均为31.25 mg/mL。正交试验结果表明,大黄、黄连、黄芩、甘草以250、250、125、62.5 mg/mL,即配比为4∶4∶2∶1时杀菌率最佳。根据伪三元相图得到最终微乳处方为吐温-80 3 g,聚乙二醇400 6 g,肉豆蔻酸异丙酯1 g,蒸馏水12 g,按质量比加入1%卡波姆940,充分溶胀后得到微乳凝胶,将水相用中药复方提取液代替得到复方微乳凝胶。药效学实验表明,与空白组相比,模型组小鼠皮肤组织出现明显的病理改变,血清中IL-1β、IL-10、TNF-α含量显著增高(P<0.01);与模型组相比,给药组病理性改变有不同程度的缓解,血清炎症因子含量降低,其中复方微乳凝胶组改善效果最显著(P<0.01)。

结论

以大黄、黄连、黄芩、甘草配伍的复方具有明显的抑菌作用,制备复方微乳凝胶对小鼠痤疮模型有良好的治疗作用,可以有效缓解痤疮丙酸杆菌引发的痤疮炎症反应。

, authors=梁进京, 杨新雪, 董蕊, authorsList=梁进京, 杨新雪, 董蕊, authorCompany=null, correspAuthors=董蕊, authorNote=

梁进京(1994-),男,甘肃定西人,硕士在读,研究方向:中药药理学。

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董蕊(1975-),女,吉林长春人,副教授,硕士研究生导师,博士,研究方向:天然产物化学与药理活性。E-mail:。
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梁进京(1994-),男,甘肃定西人,硕士在读,研究方向:中药药理学。

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梁进京(1994-),男,甘肃定西人,硕士在读,研究方向:中药药理学。

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PLoSOne,2017,8(8):72923., articleTitle=A small peptide with therapeutic potential for inflammatory acne vulgaris, refAbstract=null)], funds=[Fund(id=1322923119693922592, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923082784047198, awardId=ZYBZH-Y-JL-25, language=CN, fundingSource=国家中药标准化项目(ZYBZH-Y-JL-25), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1322923096218402972, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923082784047198, xref=null, ext=[AuthorCompanyExt(id=1322923096226791581, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923082784047198, companyId=1322923096218402972, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=College of Chinese Materia Medica,Jilin Agricultural University,Changchun 130118,Jilin,China), AuthorCompanyExt(id=1322923096235180190, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923082784047198, companyId=1322923096218402972, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=吉林农业大学中药材学院,吉林 长春 130118)])], figs=[ArticleFig(id=1322923102094622923, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923082784047198, language=EN, label=null, caption=null, figureFileSmall=f0oERWk4m2jMGkrB690q1w==, figureFileBig=bet9n+h0yzUCyjb9a18JJQ==, tableContent=null), ArticleFig(id=1322923102442750157, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923082784047198, language=CN, label=图1, caption=8味中药提取物对痤疮丙酸杆菌和金黄色葡萄球菌的抑菌圈直径结果(n=3,mm)

注:1黄连、2大黄、3甘草、4黄柏、5黄芩、6白芍、7枳实、8金银花、A空白对照、B阴性对照、C阳性对照。

, figureFileSmall=f0oERWk4m2jMGkrB690q1w==, figureFileBig=bet9n+h0yzUCyjb9a18JJQ==, tableContent=null), ArticleFig(id=1322923104535707857, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923082784047198, language=EN, label=null, caption=null, figureFileSmall=vHSuqElkJ3ShwMQujTdpmg==, figureFileBig=D0AGrAnbfHsVb70Usj8BDg==, tableContent=null), ArticleFig(id=1322923104623788243, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923082784047198, language=CN, label=图2, caption=8味中药提取物对痤疮丙酸杆菌和金黄色葡萄球菌的MIC检测结果(n=3,mg·mL-1)

注:A大黄、B黄柏、C黄芩、D金银花、E黄连、F甘草、G白芍、H枳实。

, figureFileSmall=vHSuqElkJ3ShwMQujTdpmg==, figureFileBig=D0AGrAnbfHsVb70Usj8BDg==, tableContent=null), ArticleFig(id=1322923104699285716, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923082784047198, language=EN, label=null, caption=null, figureFileSmall=n4ILCG7mFpMaMz4UeQyldQ==, figureFileBig=o+GjTKt2FJhjMFNETJvDQw==, tableContent=null), ArticleFig(id=1322923104976109781, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923082784047198, language=CN, label=图3, caption=中药及复方对痤疮丙酸杆菌和金黄色葡萄球菌的杀菌率

注:*与空白组相比,P<0.05;**与空白组相比,P<0.01;#与三黄泻心汤组相比,P<0.05;##与三黄泻心汤组相比,P<0.01。A空白、B大黄、C黄连、D黄芩、E甘草、F F1、G F2、H三黄泻心汤。

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注:**与生理盐水组相比,P<0.01。

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注:##与空白组相比,P<0.01;*与模型组相比,P<0.05;**与模型组相比,P<0.01。

, figureFileSmall=Ig8DMt6SoPLY4BwmNFJbiQ==, figureFileBig=NQGgrxeItGx4j/0KVTsxZg==, tableContent=null), ArticleFig(id=1322923114270687492, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923082784047198, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
中药提取物抑菌圈/(mm)
痤疮丙酸杆菌金黄色葡萄球菌
甘草9.77±1.8211.10±2.24
大黄12.32±1.2713.88±1.05
黄连13.83±2.8914.56±1.24
黄柏9.50±2.648.11±2.43
黄芩9.85±1.5415.28±3.13
金银花7.32±1.079.16±2.16
枳实10.52±1.299.13±1.43
白芍7.98±0.9812.98±1.63
空白对照00
阴性对照00
阳性对照18.00±1.3913.61±2.86
), ArticleFig(id=1322923115021467910, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923082784047198, language=CN, label=表1, caption=

8味中药提取物对痤疮丙酸杆菌和金黄色葡萄球菌的抑菌圈直径结果(n=3,)

, figureFileSmall=null, figureFileBig=null, tableContent=
中药提取物抑菌圈/(mm)
痤疮丙酸杆菌金黄色葡萄球菌
甘草9.77±1.8211.10±2.24
大黄12.32±1.2713.88±1.05
黄连13.83±2.8914.56±1.24
黄柏9.50±2.648.11±2.43
黄芩9.85±1.5415.28±3.13
金银花7.32±1.079.16±2.16
枳实10.52±1.299.13±1.43
白芍7.98±0.9812.98±1.63
空白对照00
阴性对照00
阳性对照18.00±1.3913.61±2.86
), ArticleFig(id=1322923115449286921, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923082784047198, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
中药提取物MIC/(mg/mL)
痤疮丙酸杆菌金黄色葡萄球菌
甘草62.5031.25
大黄125.00125.00
黄连31.25125.00
黄柏250.00250.00
黄芩125.0062.50
金银花250.00500.00
枳实500.00500.00
白芍125.00125.00
), ArticleFig(id=1322923115889688844, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923082784047198, language=CN, label=表2, caption=

8味中药提取物对痤疮丙酸杆菌和金黄色葡萄球菌的MIC检测结果(n=3)

, figureFileSmall=null, figureFileBig=null, tableContent=
中药提取物MIC/(mg/mL)
痤疮丙酸杆菌金黄色葡萄球菌
甘草62.5031.25
大黄125.00125.00
黄连31.25125.00
黄柏250.00250.00
黄芩125.0062.50
金银花250.00500.00
枳实500.00500.00
白芍125.00125.00
), ArticleFig(id=1322923116300730638, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923082784047198, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
菌种水平大黄黄连黄芩甘草
P.acnes162.515.62562.5031.250
2125.031.250125.0062.500
3250.062.500250.00125.000
S.aureus162.562.50031.2515.625
2125.0125.00062.5031.250
3250.0250.000125.0062.500
), ArticleFig(id=1322923117944897808, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923082784047198, language=CN, label=表3, caption=

痤疮丙酸杆菌和金黄色葡萄球菌正交试验因素水平

, figureFileSmall=null, figureFileBig=null, tableContent=
菌种水平大黄黄连黄芩甘草
P.acnes162.515.62562.5031.250
2125.031.250125.0062.500
3250.062.500250.00125.000
S.aureus162.562.50031.2515.625
2125.0125.00062.5031.250
3250.0250.000125.0062.500
), ArticleFig(id=1322923118364328212, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923082784047198, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
试验号大黄黄连黄芩甘草空白抑菌圈/(mm)
P.acnesS.aureus
1111119.12±0.027.18±0.02
2122229.76±0.177.80±0.17
31333312.89±0.3510.91±0.35
42112310.94±0.067.54±0.06
52223111.87±0.097.80±0.09
62331212.46±0.0810.37±0.08
7312329.26±0.219.43±0.21
83231314.91±0.0510.58±0.05
93312114.89±0.0112.87±0.01
101132210.15±0.0311.17±0.03
11121339.89±0.027.65±0.02
121321111.56±0.1411.32±0.14
132121312.88±0.158.54±0.15
142232113.63±0.069.55±0.06
152313213.98±0.0312.36±0.03
163133112.81±0.0810.83±0.08
173211213.84±0.319.97±0.31
183322311.05±0.0412.68±0.04
均值K121.1221.7224.2221.8024.92
K225.2524.6322.1324.6523.47
K325.5925.6125.6225.5123.57
R4.463.893.493.701.45
最优组合(F1)DH3、HL3、HQ3、GC3
均值K118.6818.3119.1919.0319.32
K218.7317.7919.2820.1420.54
K322.2023.5021.1420.4319.75
R3.525.711.951.391.22
最优组合(F2)DH3、HL3、HQ3、GC3
), ArticleFig(id=1322923118502740246, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923082784047198, language=CN, label=表4, caption=

正交试验设计结果(n=3)

, figureFileSmall=null, figureFileBig=null, tableContent=
试验号大黄黄连黄芩甘草空白抑菌圈/(mm)
P.acnesS.aureus
1111119.12±0.027.18±0.02
2122229.76±0.177.80±0.17
31333312.89±0.3510.91±0.35
42112310.94±0.067.54±0.06
52223111.87±0.097.80±0.09
62331212.46±0.0810.37±0.08
7312329.26±0.219.43±0.21
83231314.91±0.0510.58±0.05
93312114.89±0.0112.87±0.01
101132210.15±0.0311.17±0.03
11121339.89±0.027.65±0.02
121321111.56±0.1411.32±0.14
132121312.88±0.158.54±0.15
142232113.63±0.069.55±0.06
152313213.98±0.0312.36±0.03
163133112.81±0.0810.83±0.08
173211213.84±0.319.97±0.31
183322311.05±0.0412.68±0.04
均值K121.1221.7224.2221.8024.92
K225.2524.6322.1324.6523.47
K325.5925.6125.6225.5123.57
R4.463.893.493.701.45
最优组合(F1)DH3、HL3、HQ3、GC3
均值K118.6818.3119.1919.0319.32
K218.7317.7919.2820.1420.54
K322.2023.5021.1420.4319.75
R3.525.711.951.391.22
最优组合(F2)DH3、HL3、HQ3、GC3
), ArticleFig(id=1322923118787952920, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923082784047198, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
菌种名称方差来源SSdfMSF值P值
痤疮丙酸杆菌修正模型53.346a105.3355.4910.017
大黄18.54529.2729.5440.010**
黄连12.28726.1436.3230.027*
黄芩9.25624.6284.7640.049*
甘草11.28325.6415.8060.033*
空白1.97620.9881.0170.410*
误差6.80150.972
总计2649.50818
修正后总计60.14717
金黄色葡萄球菌方差来源SSdfMSF值P值
修正模型48.580a104.8583.7810.045
大黄12.24026.1204.7630.049*
黄连29.942214.97111.6510.006**
黄芩3.62821.8141.4120.305*
甘草1.62720.8130.6330.559
空白1.14320.5720.4450.658
误差8.99451.285
总计1833.85318
修正后总计57.57517
), ArticleFig(id=1322923118964113690, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923082784047198, language=CN, label=表5, caption=

正交试验方差分析

, figureFileSmall=null, figureFileBig=null, tableContent=
菌种名称方差来源SSdfMSF值P值
痤疮丙酸杆菌修正模型53.346a105.3355.4910.017
大黄18.54529.2729.5440.010**
黄连12.28726.1436.3230.027*
黄芩9.25624.6284.7640.049*
甘草11.28325.6415.8060.033*
空白1.97620.9881.0170.410*
误差6.80150.972
总计2649.50818
修正后总计60.14717
金黄色葡萄球菌方差来源SSdfMSF值P值
修正模型48.580a104.8583.7810.045
大黄12.24026.1204.7630.049*
黄连29.942214.97111.6510.006**
黄芩3.62821.8141.4120.305*
甘草1.62720.8130.6330.559
空白1.14320.5720.4450.658
误差8.99451.285
总计1833.85318
修正后总计57.57517
), ArticleFig(id=1322923119039611164, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923082784047198, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组方杀菌率/(%)
痤疮丙酸杆菌金黄色葡萄球菌
大黄72.12±0.0864.31±0.09
黄连81.97±0.1166.50±0.04
黄芩55.52±0.0562.24±0.12
甘草85.88±0.0368.61±0.17
F187.78±0.0787.63±0.05
F291.22±0.0195.85±0.10
三黄泻心汤88.49±0.0469.84±0.11
), ArticleFig(id=1322923119224160541, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923082784047198, language=CN, label=表6, caption=

单味中药及其复方对痤疮丙酸杆菌和金黄色葡萄球菌杀菌率(n=3)

, figureFileSmall=null, figureFileBig=null, tableContent=
组方杀菌率/(%)
痤疮丙酸杆菌金黄色葡萄球菌
大黄72.12±0.0864.31±0.09
黄连81.97±0.1166.50±0.04
黄芩55.52±0.0562.24±0.12
甘草85.88±0.0368.61±0.17
F187.78±0.0787.63±0.05
F291.22±0.0195.85±0.10
三黄泻心汤88.49±0.0469.84±0.11
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基于正交试验研究外用加味三黄泻心汤配比及微乳凝胶对痤疮的药效学评价
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梁进京 , 杨新雪 , 董蕊
中华中医药学刊 | 国家项目点击 2025,43(3): 85-91
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中华中医药学刊 |国家项目点击 2025 , 43 (3) : 85 -91
基于正交试验研究外用加味三黄泻心汤配比及微乳凝胶对痤疮的药效学评价
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梁进京, 杨新雪, 董蕊
作者信息
  • 吉林农业大学中药材学院,吉林 长春 130118
通讯作者:
董蕊(1975-),女,吉林长春人,副教授,硕士研究生导师,博士,研究方向:天然产物化学与药理活性。E-mail:。
作者简介:

梁进京(1994-),男,甘肃定西人,硕士在读,研究方向:中药药理学。

Study on Ratio of Modified Sanhuang Xiexin Decoction(加味三黄泻心汤)for External Use and Pharmacodynamic Evaluation of Microemulsion Gel on Acne Based on Orthogonal Test
Jinjing LIANG, Xinxue YANG, Rui DONG
Affiliations
  • College of Chinese Materia Medica,Jilin Agricultural University,Changchun 130118,Jilin,China
出版时间: 2025-03-10 doi: 10.13193/j.issn.1673-7717.2025.03.014
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目的

研究八味中药的体外抑菌效果,筛选出外用治疗痤疮的最佳复方配比,制备复方微乳凝胶用于小鼠痤疮模型的体内药效学研究。

方法

选取痤疮丙酸杆菌和金黄色葡萄球菌为目标菌,采用滤纸片法测定八味中药的抑菌圈直径和最小抑菌浓度(MIC);采用正交试验法优化复方配比;以伪三元相图为评价指标制备微乳,对微乳及微乳凝胶理化性质进行综合评价;采用背部注射痤疮丙酸杆菌建立小鼠痤疮模型,设置空白组、模型组、阳性药组、微乳凝胶组和复方微乳凝胶组,通过HE和Masson染色观察组织病理改变,酶联免疫吸附试验(ELISA)检测血清中炎症因子白介素1β(IL-1β)、白介素10(IL-10)和肿瘤坏死因子-α(TNF-α)水平。

结果

结果表明八味中药均有不同程度的抑菌效果,其中黄连对痤疮丙酸杆菌的抑菌效果最好,甘草对金黄色葡萄球菌的抑菌效果最好,MIC均为31.25 mg/mL。正交试验结果表明,大黄、黄连、黄芩、甘草以250、250、125、62.5 mg/mL,即配比为4∶4∶2∶1时杀菌率最佳。根据伪三元相图得到最终微乳处方为吐温-80 3 g,聚乙二醇400 6 g,肉豆蔻酸异丙酯1 g,蒸馏水12 g,按质量比加入1%卡波姆940,充分溶胀后得到微乳凝胶,将水相用中药复方提取液代替得到复方微乳凝胶。药效学实验表明,与空白组相比,模型组小鼠皮肤组织出现明显的病理改变,血清中IL-1β、IL-10、TNF-α含量显著增高(P<0.01);与模型组相比,给药组病理性改变有不同程度的缓解,血清炎症因子含量降低,其中复方微乳凝胶组改善效果最显著(P<0.01)。

结论

以大黄、黄连、黄芩、甘草配伍的复方具有明显的抑菌作用,制备复方微乳凝胶对小鼠痤疮模型有良好的治疗作用,可以有效缓解痤疮丙酸杆菌引发的痤疮炎症反应。

痤疮  /  加味三黄泻心汤  /  正交试验  /  抑菌实验  /  微乳凝胶  /  药效学
Objective

To study the antibacterial effect of eight kinds of Chinese drugs in vitro,screen the best compound ratio for external use to treat acne and prepare compound microemulsion gel for in vivo pharmacodynamic study of acne model in mice.

Methods

Propionibacterium acnes and Staphylococcus aureus were selected as target bacteria,and the diameter of inhibition zone and minimum inhibitory concentration(MIC)of eight Chinese drugs were determined by filter paper method. Orthogonal test was used to optimize the compound ratio. The physical and chemical properties of microemulsion and microemulsion gel were comprehensively evaluated by preparing microemulsion with pseudo ternary phase diagram as evaluation index. A mouse acne model was established by injecting Propionibacterium acnes into the back,and the blank group,model group,positive drug group,microemulsion gel group and compound microemulsion gel group were set up. Histopathological changes were observed by HE and Masson staining,and the levels of inflammatory factors[interleukin-1β(IL-1β),interleukin-10(IL-10)and tumor necrosis factor-(TNF-α)]in serum were detected by enzyme-linked immunosorbent assay(ELISA).

Results

The results showed that all the eight Chinese drugs had different antibacterial effects,among which Huanglian(Coptidis Rhizoma)had the best antibacterial effect on Propionibacterium acnes and Gancao(Glycyrrhizae Radix et Rhizoma)had the best antibacterial effect on Staphylococcus aureus,with MIC of 31.25 mg mL-1. The orthogonal test results showed that the sterilization rate of Dahuang(Rhei Radix et Rhizoma)(250 mg mL-1),Huanglian(Coptidis Rhizoma)(250 mg mL-1),Huangqin(Scutellariae Radix)(125 mg mL-1)and Gancao(Glycyrrhizae Radix et Rhizoma)(62.5 mg mL-1)was the best when the ratio was 4∶4∶2∶1. According to the pseudo-ternary phase diagram,the final microemulsion formula was Tween-80(3 g),PEG 400(6 g),isopropyl myristate(1 g)and distilled water(12 g),and 1% carbomer 940 was added according to the mass ratio,and the microemulsion gel was obtained after full swelling,and the compound microemulsion gel was obtained by replacing the water phase with the compound extract of the Chinese medicine compound. The pharmacodynamic experiment showed that compared with those of the blank group,the skin tissue of the model group showed obvious pathological changes,and the contents of IL-1β,IL-10 and TNF-αin serum increased significantly(P<0.01). Compared with those in the model group,the pathological changes in the drug group were relieved to varying degrees,and the contents of serum inflammatory factors were decreased,especially those in the compound microemulsion gel group(P<0.01).

Conclusion

The compound of Dahuang(Rhei Radix et Rhizoma),Huanglian(Coptidis Rhizoma),Huangqin(Scutellariae Radix)and Gancao(Glycyrrhizae Radix et Rhizoma)has obvious bacteriostatic effect. The preparation of the compound microemulsion gel has a good therapeutic effect on acne model in mice,and can effectively alleviate acne inflammation caused by Propionibacterium acnes.

acne  /  Modified Sanhuang Xiexin Decoction(加味三黄泻心汤)  /  orthogonal test  /  bacteriostasis experiment  /  microemulsion gel  /  pharmacodynamics
梁进京, 杨新雪, 董蕊. 基于正交试验研究外用加味三黄泻心汤配比及微乳凝胶对痤疮的药效学评价. 中华中医药学刊, 2025 , 43 (3) : 85 -91 . DOI: 10.13193/j.issn.1673-7717.2025.03.014
Jinjing LIANG, Xinxue YANG, Rui DONG. Study on Ratio of Modified Sanhuang Xiexin Decoction(加味三黄泻心汤)for External Use and Pharmacodynamic Evaluation of Microemulsion Gel on Acne Based on Orthogonal Test[J]. Chinese Archives of Traditional Chinese Medicine, 2025 , 43 (3) : 85 -91 . DOI: 10.13193/j.issn.1673-7717.2025.03.014
痤疮是一种毛囊皮脂腺单位的慢性炎症性皮肤病,主要表现为丘疹、粉刺、囊肿、结节、脓疱及瘢痕,多发于15~25岁青年男女[1]。现代医学认为:痤疮的发生主要和皮脂腺的大量分泌、微生物稳态失调、毛囊皮脂腺导管的异常角化和炎症因子等有关[2]。其中痤疮丙酸杆菌、金黄色葡萄球菌、化脓性葡萄球菌、表皮葡萄球菌是痤疮发病的主要致病性微生物,病原体侵入人体皮肤,在外因素的诱导下导致痤疮丙酸杆菌异常增殖,使皮肤菌群失衡[3]。临床上治疗寻常型痤疮一般使用抗生素、激素等药物,由于这类药物对细菌的耐药性和副反应的出现,使用某种单一治疗方法的效果往往不尽如人意[4]。因此,从天然植物中挖掘安全高效的功能性组分防治痤疮已成为当前重要的研究方向。
三黄泻心汤来源于《金匮要略》,大黄、黄连和黄芩组成,属于汤剂,有泻火解毒,燥湿泄热的功效,外证疮疡,临床应用在原方基础上加味治疗痤疮[5]。现代药理研究表明三黄泻心汤具有抑菌抗炎作用,在临床治疗寻常痤疮显示出良好效果和优势。通过对中医治疗寻常型痤疮的药方整理得知黄连、甘草、大黄、黄柏、黄芩、白芍、黄芪等寒性药、苦味药、甘味药出现的频率较高,以归肝经、肺经、脾经的药味较多[6]。从抑制寻常痤疮的病原菌痤疮丙酸杆菌的视角来探寻治疗寻常痤疮有效的中药,具有良好的前景。现代药理研究表明,三黄泻心汤对痤疮丙酸杆菌有良好的体外抑菌作用[7]。陈永虎等[8]研究发现三黄泻心汤可通过多成分、多靶点、多通路的调控对炎症具有良好的治疗效果。刘晓敏等[9]研究了三黄祛痘凝胶的功效和安全性,通过体外实验表明其对痤疮致病菌具有良好的抑菌作用,并且对兔耳痤疮模型具有良好的治疗效果。
本文从现代医学角度将传统的三黄泻心汤通过加味组成复方,前期通过体外抑菌实验证明此方对痤疮丙酸杆菌和金黄色葡萄球菌确有抑菌疗效。经过复方筛选和复方配比的优化,将中药复方制备成微乳凝胶,将微乳和凝胶的优势相结合,以提高生物相容性和药物利用率促进药物吸收利用。利用痤疮丙酸杆菌建立小鼠痤疮模型,观察复方微乳凝胶对痤疮模型的炎症改善效果,探讨复方微乳凝胶治疗痤疮的药效,为中医药治疗寻常型痤疮提供新的依据和思路。
大黄(Rheum palmatum L.)、黄柏(Cortex Phellodendri Chinensis)、黄芩(Scutellaria baicalensis Georgi)、金银花(Lonicera japonica Thunb.)、黄连(Coptis chinensis Franch.)、甘草(Glycyrrhiza uralensis Fisch.)、白芍(Radix Paeoniae Alba)、枳实(Citrus aurantium L.)购自吉林省长春市宏检大药房。药材经吉林农业大学包海鹰教授鉴定。
痤疮丙酸杆菌(BNCC330605 Propionibacterium acnes,P.acnes)、金黄色葡萄球菌(BNCC186335 Staphylococcus aureus,S.aureus)购自北纳生物。
RE100-S旋转蒸发仪(大龙兴创实验仪器),KQ-300DE型数控超声波清洗器(昆山市超声仪器有限公司),THZ-98AB恒温振荡器(上海一恒科学仪器有限公司),SW-CJ-1FD洁净工作台(苏州安泰空气技术有限公司),SPL-250生化培养箱(天津市莱玻特仪器设备有限公司),LDZM-60L-I立式高压蒸汽灭菌器(上海申安医疗器械厂),SHB-ⅢA循环水式多用真空泵(长春吉豫科教仪器设备有限公司),厌氧盒(日本三菱),HBY001厌氧产气包、厌氧培养袋、脑浸心液肉汤培养基(BHI)(青岛海博),乙醇(京试,分析纯),NaCl(泉瑞试剂,辽宁),酵母提取物、蛋白胨、琼脂(上海麦克林生化科技股份有限公司)、吐温-80(安耐吉化学,货号:E080730)、聚乙二醇400(阿拉丁生化科技股份有限公司,货号:L2122277)、肉豆蔻酸异丙酯(萨恩化学技术有限公司,货号:A020852)、卡波姆940(河南万邦化工科技有限公司,货号:FN06416),肿瘤坏死因子-α(TNF-α)、白介素-10(IL-10)、白介素-1β(IL-1β)检测试剂盒(晶美有限公司,货号:J2163-A)。
根据文献报道[10]称取各中药饮片10 g,粉碎过80目筛,置于200 mL锥形瓶中,按1∶10料液比加入75%乙醇,浸泡30 min后,60 Hz超声提取两次,每次60 min,合并滤液,抽滤提取液用旋转蒸发仪减压浓缩除去溶媒,用蒸馏水定容至10 mL,使药液浓度相当于生药量1 g/mL,备用。
采用纸片扩散法测定抑菌圈直径[11],取1.4的中药提取物1 mL浸泡滤纸片8 h,高压灭菌,备用。取浓度为1×107 cfu/mL的供试菌液100μL滴加铺板,再将含药滤纸片贴于平板,以PBS为空白对照,无菌蒸馏水为阴性对照,配置浓度为10 mg/mL的环丙沙星为阳性对照,37℃恒温培养箱中培养12 h。抑菌圈直径以<7 mm表示无抑菌作用,>7 mm表示有抑菌作用。
采用二倍稀释法将药物稀释至浓度为500、250、125、62.5、31.25、15.625 mg/mL,将滤纸片置于不同浓度溶液中8 h,121℃高压灭菌15 min,用无菌PBS做空白对照,取100μL供试菌液铺板,再将滤纸片贴于平板上,痤疮丙酸杆菌置于厌氧培养盒中加厌氧产气包培养,37℃恒温培养箱培养16~18 h,观察抑菌圈直径,其中最小抑菌圈所对应的药液浓度为MIC[12]。
选择大黄(DH)、黄连(HL)、黄芩(HQ)、甘草(GC)为复方组成,选用抑菌圈直径作为正交试验的评价指标,各单味中药为考察因素,建立正交表,确定最佳配伍比例。
细菌生物膜是一种由细菌聚集在一起形成的复杂结构,其表面被黏附的多种物质所包覆,具有很强的耐药性和抗原性[13]。通过,扫描电镜观察加味三黄泻心汤对痤疮丙酸杆菌和金黄色葡萄球菌细胞膜的影响。
通过伪三元相图法确定微乳凝胶的制备工艺[14]。油相为肉蔻酸异丙酯,乳化剂为吐温-80,助乳化剂为聚乙二醇400,Km值为3∶1、2∶1、1∶1、1∶2和1∶3(Km=乳化剂的质量/助乳化剂的质量),混合后即为乳化剂相。将油相与乳化剂相分别按1∶9、2∶8、3∶7、4∶6、5∶5、6∶4、7∶3、8∶2、9∶1的比例混合。磁力搅拌下,缓慢滴加水相,至溶液澄清不再变化即得微乳,称定质量,计算水相质量。以油相、Km和水相作为伪三元相图的3个顶点,根据伪三元相图微乳区域大小,评价乳化效果。将微乳中水相用2.5项下得到的中药复方代替,得到复方微乳液,取10 mL制备所得的微乳,加入0.5%,1.0%,1.5%卡波姆-940,搅拌充分溶胀12~16 h,向溶液中加入三乙醇胺调节pH值至4~5,即得微乳凝胶,低温保存,备用[15]。
取适量微乳,利用布鲁克海文粒径仪分别测量其粒径分布、多分散指数(PDI)和Zeta电位。
把复方微乳稀释后滴加在铜网上,静置后用滤纸吸干,再滴加2%磷钨酸复染,烘干后利用透射电镜观察其形态。
将24只ICR小鼠[许可证号SCXK(吉)2018-0007]分为空白组、模型组、阳性组、微乳凝胶组、复方微乳凝胶组、毒理组,运用Kligman法对小鼠进行痤疮模型建立,对小鼠进行脱毛处理,然后用50%油酸100μL涂抹于小鼠背部,每隔一天小鼠皮下注射1×108的痤疮丙酸杆菌20μL,连续14 d后停止造模,可见小鼠皮肤粗糙,出现囊肿,连续给药20 d,给药量1 g/只,每天早晚各一次,观察小鼠皮肤形态变化。模型建立成功后,于给药第一天开始,每隔5 d拍照观察痤疮形态变化[16-17]。
皮肤组织于4%多聚甲醛溶液固定后,常规脱水处理,石蜡包埋,切片,HE染色,将染色后的切片梯度乙醇脱水,封片,显微镜观察病理变化。
切片在离子水中浸泡后,脱色至白色,浸泡到马松染色剂中,纯乙醇脱水,封片,显微镜观察病理变化。通过Masson染色进一步评估每组胶原蛋白的沉积和成熟。
实验小鼠眼球取血,离心得到血清,按照空白组、模型组、给药组,根据ELISA试剂盒说明书,检测血清中TNF-α、IL-1β、IL-10表达水平。
结果显示,八味中药对痤疮丙酸杆菌的抑菌圈均>7 mm,除金银花和白芍之外,其他六味中药对金黄色葡萄球菌的抑菌圈均>7 mm。其中,黄连对痤疮丙酸杆菌的抑菌圈直径最大,为(13.83±2.89)mm,黄芩对金黄色葡萄球菌的抑菌圈最大,为(15.28±3.13)mm。通过抑菌圈直径可知,除金银花和白芍外,其他中药对细菌生长具有显著抑制作用,如插页ⅩⅣ图1、表1所示。
结果表明,八味中药对痤疮丙酸杆菌抑菌效果最好的是黄连,其MIC为31.25 mg/mL,甘草为62.5 mg/mL,大黄、黄芩和白芍为125 mg/mL。对金黄色葡萄球菌抑菌效果最好的是甘草,其MIC为31.25 mg/mL,黄芩为62.5 mg/mL,大黄、黄连和白芍为125 mg/mL。综合考虑每味中药的抑菌效果,除原方中三味中药以外,其他五味中药中甘草的MIC最小,具有较强的抑菌效果,且甘草与原方没有配伍禁忌,故选择大黄、黄连、黄芩、甘草为复方即加味三黄泻心汤进行后续研究,如插页ⅩⅣ图2、表2所示。
如表3所示建立正交表,其中大黄(DH)、黄连(HL)、黄芩(HQ)、甘草(GC)用缩写表示。通过正交试验K值和R值,确定痤疮丙酸杆菌的最优组合为DH3、HL3、HQ3、GC3,DH>HL>GC>HQ,其对应浓度为250、62.5、250、125 mg·mL-1,配比为4∶1∶4∶2,金黄色葡萄球菌的最优组合为DH3、HL3、HQ3、GC3,HL>DH>HQ>GC。对应浓度为250、250、125、62.5 mg·mL-1,配比为4∶4∶2∶1。
通过上述方差分析得到的4种中药对痤疮丙酸杆菌和金黄色葡萄球菌的最优组方分别为F1和F2。方差分析和显著性水平结果可知,整体模型P<0.05,表明所用模型差异显著统计学意义。大黄、黄连、黄芩、甘草提取物对痤疮丙酸杆菌的抑菌活性有显著性影响;大黄、黄连提取物对金黄色葡萄球菌的抑菌活性有显著性影响,而黄芩、甘草提取物对金黄色葡萄球菌抑菌活性无显著性影响。见表4-表6。
取6个离心管,将各中药提取物稀释至最小抑菌浓度,每个试管加中药提取物0.8 mL,取1×107 cfu/mL供试菌液0.2 mL加入到试管中,PBS做空白对照,混合均匀后分别取100 μL均匀涂布于平板上,在37℃恒温培养箱中培养12 h,记录每个平板中的菌落数,与空白组对比,计算中药及其复方的杀菌率[18]。由插页ⅩⅤ图3可知,中药及复方对痤疮丙酸杆菌和金黄色葡萄球菌有抑制作用,给药后细菌数量明显减少,复方F2对痤疮丙酸杆菌和金黄色葡萄球菌的抑菌效果最好,杀菌率分别为(91.22±0.01)%、(95.85±0.10)%,且复方比三黄泻心汤的抑菌效果更好,对两种菌,F2组三黄泻心汤组具有显著性,说明与原方相比,加药后通过配比研究得到的外用处方具有更好地抑菌作用,即选定F2为最佳处方,用于后续研究。
将中药复方定容至50 mL容量瓶,用蒸馏水二倍稀释至不同浓度,即V1、V2、V3、V4、V5、V6,测定中药复方对两种细菌最小抑菌浓度,当浓度为V3时,无抑菌效果,故复方最小抑菌浓度为V2(即220 mg/mL)(插页ⅩⅤ图4)。
由插页ⅩⅥ图5可知,给药后中药复方能够破坏生物膜中的聚集物质和黏附物质,从而抑制细菌生长,而空白组和PBS组细菌形态完整,说明加味三黄泻心汤通过破坏细菌细胞壁结构和改变细胞膜的通透性来抑制细菌的生长。
通过伪三元相图确定了Km比值及油相与混合乳化剂的比值,用于微乳组方的筛选。以肉豆蔻酸异丙酯为油相,吐温-80为表面活性剂,聚乙二醇为助表面活性剂,进行微乳组方的滴定。在常温下,建立伪三元相图,混合表面活性剂与助表面活性剂(Km比值为3∶1、2∶1、1∶1、1∶2和1∶3),与油相以不同比例混合,然后逐滴加水相,观察混合物体系的变化,记录临界点时加水量。澄清透明的混合物被认定为微乳。使用OriginPro 9.0软件绘制伪三元相图,确定微乳区域。根据伪三元相图微乳区域大小,选择最佳的油相Km。以吐温-80和聚乙二醇1∶2混合,油相肉豆蔻酸异丙酯与混合乳化剂1∶9时得到澄清且透明的微乳,作为后续研究(图6)。
如插页ⅩⅥ图7所示,当加入凝胶剂为1%时,所得微乳凝胶黏度适中,易于涂布。
结果发现最佳配比的微乳的透光率为(93.77±0.01)%,平均粒径为(66.32±3.55)nm,PDI为(0.11±0.01),Zeta电位为(-0.66±0.14)mV。
结果表明微乳为类球状,表面无聚集,粒径约80 nm,与粒径测定结果一致(图8)。
甲硝唑凝胶为阳性对照,分别取1 g复方微乳凝胶和甲硝唑凝胶至含有1 mL浓度1×107 cfu/mL的供试菌液离心管中,37℃、120 r培养4 h,取100μL均匀涂布于平板,37℃培养12 h,菌落计数。如插页ⅩⅥ图9所示,复方微乳凝胶能够有效抑制细菌生长。
健康的雄性ICR小鼠(5周龄,体质量16~18 g)来自长春亿斯实验动物有限公司,并获得质量证书编号为SCXK(吉)2018-0007。本研究的所有实验均获得了吉林农业大学实验动物伦理委员会的批准,所有的实验动物研究都遵循吉林农业大学实验动物伦理委员会制定的《实验动物管理条例》。将24只ICR小鼠分为空白组、模型组、阳性组、微乳凝胶组、复方微乳凝胶组、毒理组,运用Kligman法对小鼠进行痤疮模型建立,对小鼠进行脱毛处理,然后用50%油酸100μL涂抹于小鼠背部,每隔一天小鼠皮下注射1×108的痤疮丙酸杆菌20μL,连续14 d后停止造模,可见小鼠皮肤粗糙,出现囊肿,连续给药20 d,给药量1 g/只,每天早晚各1次,观察小鼠皮肤形态变化,通过H & E染色观察病理学变化,毒理组不做处理,按照同样方法给药[16]。给药20 d后痤疮的治疗效果如插页ⅩⅦ图10所示,空白组小鼠皮肤组织形态结构完整,表面覆有薄层角质层,表皮层较薄,皮肤光滑,各区域正常。与空白组比较,模型组表皮明显增厚,皮下间质内大量腺体增生。与模型组比较,阳性对照组(甲硝唑凝胶)、复方微乳凝胶组组织病理形态得到改善。
用药20 d后,对各组小鼠进行组织病理学检查,其心、肝、脾、肺、肾等脏器组织均未见病理改变,各组均未见水肿、表皮增生、角化等现象。与对照组比较,复方微乳凝胶组未见任何异常,对主要脏器无显著不良影响,为比较安全的外用药物(插页ⅩⅧ图11)。
皮肤组织于4%多聚甲醛溶液固定后,常规脱水处理,石蜡包埋,切片,HE染色,将染色后的切片梯度乙醇脱水,封片,显微镜观察病理变化。如插页ⅩⅨ图12所示,空白组皮肤组织表皮较薄,鳞状上皮细胞排列整齐,血管、脂肪组织、毛囊及皮脂腺等清晰可见,无明显病理改变;与空白组相比,模型组表皮增厚明显,角质化物沉积,毛囊萎缩,有大量炎性细胞浸润;阳性药组、微乳凝胶组和复方微乳凝胶组表皮增厚、组织增生及炎性细胞浸润情况均有不同程度的减轻。其中复方微乳凝胶组结构较为清晰,表皮轻微增厚,组织增生程度较轻,仅有轻微炎症细胞浸润。
切片在离子水中浸泡后,脱色至白色,浸泡到马松染色剂中,纯乙醇脱水,封片,显微镜观察病理变化。通过Masson染色进一步评估每组胶原蛋白的沉积和成熟。如插页ⅩⅨ图13所示,用复方微乳凝胶处理的皮肤表面显示出较有序和较好的胶原蛋白沉积。与模型组相比,阳性药组、复方微乳凝胶组中发现更多的胶原纤维,并在给药后20 d逐渐形成网络结构。
由图14可知,与空白组相比,模型组TNF-α、IL-1β和IL-10的含量显著升高(P<0.01)。与模型组比较,给药组小鼠血清中TNF-α、IL-1β和IL-10含量均有不同程度的降低,其中尤以复方微乳凝胶组以及阳性组炎症因子含量降低最为显著,差异有统计学意义(P<0.05)。
随着中药复方制剂的不断发展,微乳已成为今后研究发展的方向之一,微乳具有载药能力强、稳定性高等特点,适合作各种中药提取物的给药载体,然而流动性强影响其对痤疮的治疗效果,加入凝胶剂后,可以增加黏附性,提高利用率[19-20]。本实验主要运用于外用处方,在用药安全的前提下,制备复方微乳凝胶。复方中大黄、黄连、黄芩具有疏风清热、泻火解毒的作用,其主要活性成分能够抑制细菌的生长,缓解炎症和感染[21-23],甘草则具有调和诸药之性的作用,甘草中黄酮类化合物具有很好地抑菌作用,能够增强方剂的功效,外用于热毒上火、炎症感染所导致的寻常痤疮[24]。
在痤疮的治疗过程中,大多采用抗生素治疗,效果虽好,但容易使皮肤产生耐药性[25]。在长期治疗过程中,中药因其具有多成分、多靶点的特点,在外用治疗痤疮中展现出独特优势[26]。痤疮的发病机制复杂,研究证实,炎症在痤疮的发生、发展和消退中起着举足轻重的作用[27]。研究发现,痤疮丙酸杆菌是角质形成细胞释放IL-1β的强效诱导剂,呈剂量依赖性。IL-10、IL-6和TNF-α等细胞因子也参与痤疮的炎症反应[28]。此外,痤疮丙酸杆菌是激活toll样受体的重要因素,TLR的激活引发机体产生免疫应答,释放多种炎症细胞因子,这些细胞因子的大量释放会引起皮肤的炎症反应,从而导致痤疮的炎性反应出现[29]。因此,痤疮相关的病理变化与TNFα、IL-1β和IL-10的表达密切相关[30]。
本研究通过抑菌实验,筛选出中药复方。利用单因素实验优化微乳凝胶制备工艺。结果显示,复方微乳凝胶剂外观性状良好,耐热性、稳定性理想,对痤疮丙酸杆菌和金黄色葡萄球菌有确切的抑制作用。组织染色和ELISA结果显示,模型组小鼠皮肤组织出现明显的病理改变,血清中TNF-α、IL-1β和IL-10含量显著高于空白组(P<0.01);复方微乳凝胶给药治疗后病理性改变有不同程度的缓解,血清炎症因子含量显著降低(P<0.01)。因此,在这项研究中,复方微乳凝胶可能通过抑制痤疮丙酸杆菌介导的炎症因子TNF-α、IL-1β和IL-10的表达,从而发挥有效其抗炎作用。
综上所述,本研究通过古方结合现代研究得到的新复方制成的复方微乳凝胶,对小鼠痤疮模型具有一定的治疗效果,为痤疮研究提供新思路。
  • 国家中药标准化项目(ZYBZH-Y-JL-25)
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2025年第43卷第3期
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doi: 10.13193/j.issn.1673-7717.2025.03.014
  • 首发时间:2026-10-30
  • 出版时间:2025-03-10
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国家中药标准化项目(ZYBZH-Y-JL-25)
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    吉林农业大学中药材学院,吉林 长春 130118

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董蕊(1975-),女,吉林长春人,副教授,硕士研究生导师,博士,研究方向:天然产物化学与药理活性。E-mail:。
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2种不同金属材料的力学参数
科
Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)
属
Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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