世界科学技术-中医药现代化
世界科學技術-中醫藥現代化
세계과학기술-중의약현대화
WORLD SCIENCE AND TECHNOLOGY-MODERNIZATION OF TRADITIONAL CHINESE MEDICINE
2014年
10期
2190-2196
,共7页
管辉达%王秀丽%林珈好%徐昕%褚福浩%王玉蓉
管輝達%王秀麗%林珈好%徐昕%褚福浩%王玉蓉
관휘체%왕수려%림가호%서흔%저복호%왕옥용
甘草次酸衍生物%甘草次酸%丹参酮ⅡA%丹酚酸B%复方脂质体%处方优化%体外释放
甘草次痠衍生物%甘草次痠%丹參酮ⅡA%丹酚痠B%複方脂質體%處方優化%體外釋放
감초차산연생물%감초차산%단삼동ⅡA%단분산B%복방지질체%처방우화%체외석방
Glycyrrhetinic acid derivative%glycyrrhetinic acid%tanshinone IIA%salvianolic acid B%compound li-posomes%preparation optimization%in vitro release
目的：合成两亲性导向分子甘草次酸衍生物3-琥珀酸-30-硬脂醇甘草次酸酯（18-GA-Suc），研究其掺入甘草次酸-丹参酮ⅡA-丹酚酸B复方脂质体（GTS-Lip）的制备工艺，并考察其体外释放规律。方法：采用1HNMR和13CNMR表征18-GA-Suc的结构，通过单因素考察确定18-GA-Suc的投料量，低速离心法测定其掺入比率，比较修饰前后复方脂质体的理化性质，以平衡透析法考察甘草次酸衍生物受体靶向的甘草次酸-丹参酮ⅡA-丹酚酸B复方脂质体（Suc-GTS-Lip）中3种成分的体外释放规律。结果：优化的处方工艺为：18-GA-Suc投料量为膜材的10%（mol·mol-1），掺入比率为96.58%。Suc-GTS-Lip形态圆整，分布均匀，其中甘草次酸（GA）、丹参酮ⅡA（TSN）和丹酚酸B（SalB）的平均包封率分别为86.15%，81.70%，91.05%，平均粒径为128.7 nm，平均Zeta电位为-15.5mV。GA和TSN体外释放规律符合Higuchi方程，SalB体外释放规律符合Hixon-crowell方程。结论：甘草次酸衍生物（18-GA-Suc）能在脂质体膜上成功表达，本脂质体制备工艺稳定，GA、TSN和SalB 3种成分在体外均具有一定的缓释作用，为进一步研究其肝靶向性奠定了基础。
目的：閤成兩親性導嚮分子甘草次痠衍生物3-琥珀痠-30-硬脂醇甘草次痠酯（18-GA-Suc），研究其摻入甘草次痠-丹參酮ⅡA-丹酚痠B複方脂質體（GTS-Lip）的製備工藝，併攷察其體外釋放規律。方法：採用1HNMR和13CNMR錶徵18-GA-Suc的結構，通過單因素攷察確定18-GA-Suc的投料量，低速離心法測定其摻入比率，比較脩飾前後複方脂質體的理化性質，以平衡透析法攷察甘草次痠衍生物受體靶嚮的甘草次痠-丹參酮ⅡA-丹酚痠B複方脂質體（Suc-GTS-Lip）中3種成分的體外釋放規律。結果：優化的處方工藝為：18-GA-Suc投料量為膜材的10%（mol·mol-1），摻入比率為96.58%。Suc-GTS-Lip形態圓整，分佈均勻，其中甘草次痠（GA）、丹參酮ⅡA（TSN）和丹酚痠B（SalB）的平均包封率分彆為86.15%，81.70%，91.05%，平均粒徑為128.7 nm，平均Zeta電位為-15.5mV。GA和TSN體外釋放規律符閤Higuchi方程，SalB體外釋放規律符閤Hixon-crowell方程。結論：甘草次痠衍生物（18-GA-Suc）能在脂質體膜上成功錶達，本脂質體製備工藝穩定，GA、TSN和SalB 3種成分在體外均具有一定的緩釋作用，為進一步研究其肝靶嚮性奠定瞭基礎。
목적：합성량친성도향분자감초차산연생물3-호박산-30-경지순감초차산지（18-GA-Suc），연구기참입감초차산-단삼동ⅡA-단분산B복방지질체（GTS-Lip）적제비공예，병고찰기체외석방규률。방법：채용1HNMR화13CNMR표정18-GA-Suc적결구，통과단인소고찰학정18-GA-Suc적투료량，저속리심법측정기참입비솔，비교수식전후복방지질체적이화성질，이평형투석법고찰감초차산연생물수체파향적감초차산-단삼동ⅡA-단분산B복방지질체（Suc-GTS-Lip）중3충성분적체외석방규률。결과：우화적처방공예위：18-GA-Suc투료량위막재적10%（mol·mol-1），참입비솔위96.58%。Suc-GTS-Lip형태원정，분포균균，기중감초차산（GA）、단삼동ⅡA（TSN）화단분산B（SalB）적평균포봉솔분별위86.15%，81.70%，91.05%，평균립경위128.7 nm，평균Zeta전위위-15.5mV。GA화TSN체외석방규률부합Higuchi방정，SalB체외석방규률부합Hixon-crowell방정。결론：감초차산연생물（18-GA-Suc）능재지질체막상성공표체，본지질체제비공예은정，GA、TSN화SalB 3충성분재체외균구유일정적완석작용，위진일보연구기간파향성전정료기출。
This article was aimed to study the preparation process of glycyrrhetinic acid (GA)-tanshinone IIA (TSN)-salvianolic acid B (SalB) compound liposomes with 3-succinic-30-stearyl glycyrrhetinic acid (18-GA-Suc) which is one of amphiphilicglycyrrhetinic acid derivatives as targeting molecule. The structure of the targeting molecule was validated by 1H-NMR and 13C-NMR methods. The feed ratio of 18-GA-Suc was optimized through single factor test and the incorporation ratio of 18-GA-Suc was determined by low-speed centrifugation. Meanwhile, physicochemi-cal properties between Suc-GTS-Lip and GTS-Lip were compared. In vitro release studies of three components in Suc-GTS-Lip were conducted by equilibrium dialysis method. The results showed that the optimum conditions were when the feed ratio of 18-GA-Suc was 10%lipid liposomal membrane (mol·mol-1). It revealed that the incorpora-tion ratio of 18-GA-Suc was 96.58%, and the encapsulation efficiencies of GA, TSN, and SalB were about 86.15%, 81.70%, and 91.05%, respectively. In addition, the Suc-GTS-Lip was spherical and uniformly dispersed with parti-cle size of 128.7 nm and zeta potential of-15.5 mV. The release model of GA and TSN was fitted well with Higuchi equation, while SalB was fitted well with Hixon-crowell equation. It was concluded that Glycyrrhetinic acid deriva-tives (18-GA-Suc) can be successfully expressed in the liposome membrane, and the optimal preparation method of Suc-GTS-Lip was stable. All three components encapsulated into liposomes had sustained-release effects, which laid a good foundation for its further study about liver-targeting.
