摘要
目的优化丹酚酸B(SalB)-丹参酮ⅡA(TSNⅡA)-甘草次酸(GA)(STG)微乳凝胶的处方工艺,并考察微针给药对其促透和抗炎药效的影响。方法以微乳凝胶的综合评分为响应值,选取卡波姆用量、微乳用量、pH值作为考察因素,通过Box-Behnken响应面法筛选最佳处方工艺。采用透皮扩散试验仪考察STG微乳凝胶、STG微乳凝胶+微针(长度分别为500、750、1000μm)给药的体外经皮渗透特性,高效液相色谱(HPLC)测定TSNⅡ_(A)、Sal B和GA的含量。采用10%蛋清诱导小鼠足肿胀考察STG微乳凝胶(每次l g,每天2次,给药3 d)、STG微乳凝胶+微针(长度分别为500、750、1000μm)背部给药的抗炎作用,同时考察给药7d对小鼠皮脂腺斑组织的作用。结果STG微乳凝胶的最佳制备工艺中卡波姆用量为1.00%、微乳用量为0.10 g、pH值为6,制备的STG微乳凝胶中含TSNⅡ_(A)、SalB、GA分别为0.18、1.05、1.53 mg·g^(-1)。与TSNⅡ_(A)比较,SalB和GA的透皮吸收较好;STG微乳凝胶经过与不同长度微针配合使用后的累积透皮量:STG微乳凝胶+1000μm微针组>STG微乳凝胶+700μm微针组>STG微乳凝胶+500μm微针组>STG微乳凝胶组;3种药物在皮肤中的滞留量相对较高。与空白凝胶组比较,STG微乳凝胶组小鼠足肿胀度有所减轻,但无显著性差异;与STG微乳凝胶组比较,STG微乳凝胶+微针组小鼠足肿胀程度均明显减轻,以1000μm微针组作用最显著(P<0.05、0.01)。小鼠皮脂腺斑组织HE染色结果表明,与空白凝胶组比较,各组小鼠皮脂腺数目减少且体积变小,以微针长度1000μm组效果最显著。结论STG微乳凝胶+微针给药具有良好的透皮特性和缓释效果,发挥抗炎及控制皮脂腺分泌作用,微针长度与透皮率的增加呈正相关。
Objective To optimize the formulation of salvianolic acid B(Sal B)-tanshinoneⅡ_(A)(TSNⅡ_(A))-glycyrrhetinic acid(GA)(STG)microemulsion gel and investigate the impact of microneedle administration on its penetration promoting and antiinflammatory effects.Methods The comprehensive score of the microemulsion gel was taken as the response value,the dosage of carbomer,dosage of microemulsion and pH value were selected as the investigation factors,and the preparation method was screened by the Box-Behnken response surface method.A transdermal diffusion tester was used to investigate the in vitro percutaneous penetration characteristics of STG microemulsion gel and STG microemulsion gel plus microneedle(500,750,1000μm in length),and the contents of Sal B,TSNⅡ_(A),and GA were determined by HPLC.The anti-inflammatory effect of STG microemulsion gel(1 g each time,twice a day,for 3 days),STG microemulsion gel+microneedles(length of 500,750,1000μm,respectively)were administered on the back was investigated by 10%egg white-induced swelling in mice and investigate its effect on mouse sebaceous plaque tissue through seven days of microneedle administration.Results The best preparation process of STG gel were carbomer dosage 1.00%,microemulsion dosage 0.10 g,pH 6.The content of TSN II_(A),Sal B and GA were 0.18,1.05 and 1.53 mg·g^(-1),respectively.Compared with TSNⅡ_(A),the transdermal absorption of Sal B and GA was better.The cumulative transdermal volume of STG microemulsion gel combined with different lengths of microneedles:STG microemulsion gel+1000μm microneedle group>STG microemulsion gel+700μm microneedle group>STG microemulsion gel+500μm microneedle group>STG microemulsion gel group.The retention of the three drugs in the skin was relatively high.Compared with the blank gel group,the degree of foot swelling in the STG microemulsion gel group was reduced,but there was no significant difference.Compared with STG microemulsion gel group,the degree of foot swelling in STG microemulsion gel+microneedle group was significantly reduced,and the effect of 1000μm microneedle group was the most significant(P<0.05,0.01).The results of HE staining showed that compared with the blank gel group,the number and volume of sebaceous glands in each group were decreased,and the effect of microneedle length 1000μm group was the most significant.Conclusion STG microemulsion gel+micronedle administration has good transdermal characteristics and sustained release effect,which can exert anti-inflammatory and control sebaceous gland secretion.The length of micronedle is positively correlated with the increase of transdermal rate.
作者
曹凤媚
胡等慧
CAO Fengmei;HU Denghui(The Third Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510360,China;Beijing University of Chinese Medicine,Beijing 102488,China)
出处
《药物评价研究》
CAS
2022年第10期2039-2048,共10页
Drug Evaluation Research
关键词
丹酚酸B
丹参酮ⅡA
甘草次酸
微乳凝胶
微针
抗炎
皮脂腺
salvianolic acid B
tanshinoneⅡA
glycyrrhetinic acid
microemulsion gel
microneedles
anti-inflammatory
sebaceous glands
作者简介
第一作者:曹凤媚(1981-),女,本科,主管中药师,主要从事中药质量控制研究。Tel:13826251220,E-mail:cjbo0210@126.com。
