目的 優(yōu)化丹酚酸B （SalB）-丹參酮Ⅱ_A（TSNⅡ_A）-甘草次酸（GA）（STG）微乳凝膠的處方工藝，并考察微針給藥對(duì)其促透和抗炎藥效的影響。方法 以微乳凝膠的綜合評(píng)分為響應(yīng)值，選取卡波姆用量、微乳用量、pH值作為考察因素，通過Box-Behnken響應(yīng)面法篩選最佳處方工藝。采用透皮擴(kuò)散試驗(yàn)儀考察STG微乳凝膠、STG微乳凝膠+微針（長(zhǎng)度分別為500、750、1 000μm）給藥的體外經(jīng)皮滲透特性，高效液相色譜（HPLC）測(cè)定TSNⅡ_A、Sal B和GA的含量。采用10%蛋清誘導(dǎo)小鼠足腫脹考察STG微乳凝膠（每次l g，每天2次，給藥3 d）、STG微乳凝膠+微針（長(zhǎng)度分別為500、750、1000μm）背部給藥的抗炎作用，同時(shí)考察給藥7d對(duì)小鼠皮脂腺斑組織的作用。結(jié)果 STG微乳凝膠的最佳制備工藝中卡波姆用量為1.00%、微乳用量為0.10 g、pH值為6，制備的STG微乳凝膠中含TSNⅡ_A、SalB、GA分別為0.18、1.05、1.53 mg·g^-1。與TSNⅡ_A比較，SalB和GA的透皮吸收較好；STG微乳凝膠經(jīng)過與不同長(zhǎng)度微針配合使用后的累積透皮量：STG微乳凝膠+1 000μm微針組>STG微乳凝膠+700μm微針組>STG微乳凝膠+500μm微針組>STG微乳凝膠組；3種藥物在皮膚中的滯留量相對(duì)較高。與空白凝膠組比較，STG微乳凝膠組小鼠足腫脹度有所減輕，但無(wú)顯著性差異；與STG微乳凝膠組比較，STG微乳凝膠+微針組小鼠足腫脹程度均明顯減輕，以1 000μm微針組作用最顯著（P<0.05、0.01）。小鼠皮脂腺斑組織HE染色結(jié)果表明，與空白凝膠組比較，各組小鼠皮脂腺數(shù)目減少且體積變小，以微針長(zhǎng)度1 000μm組效果最顯著。結(jié)論 STG微乳凝膠+微針給藥具有良好的透皮特性和緩釋效果，發(fā)揮抗炎及控制皮脂腺分泌作用，微針長(zhǎng)度與透皮率的增加呈正相關(guān)。

Objective To optimize the formulation of salvianolic acid B(Sal B)-tanshinone Ⅱ_A(TSN Ⅱ_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, 1 000μm in length), and the contents of Sal B, TSN Ⅱ_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, 1 000 μm, 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 TSN Ⅱ_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+1 000 μm microneedle group> STG microemulsion gel+700 μm microneedle group> STG microemulsion gel+500 μm 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 1 000 μm 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 1 000 μm 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.

R283.6