目的 探索苦參總生物堿（TA）磷脂復(fù)合物固體脂質(zhì)納米粒（TA-PC-SLN）的制備工藝及處方優(yōu)化，并對其進(jìn)行體外評價(jià)。方法 建立高效液相色譜（HPLC）法同時(shí)測定TA中4個(gè)指標(biāo)成分苦參堿（MT）、氧化苦參堿（OMT）、槐果堿（SC）、氧化槐果堿（OSC），并進(jìn)行方法學(xué)驗(yàn)證。稱取TA、卵磷脂共同溶于乙醇制備磷脂復(fù)合物；采用微乳法制備TAPC-SLN。采用超速離心結(jié)合HPLC法考察包封率和載藥量；比色法檢測粒徑分布及Zeta電位。以包封率和載藥量作為TAPC-SLN考察指標(biāo)，用星點(diǎn)-效應(yīng)面法優(yōu)化處方，同時(shí)評價(jià)TA-PC-SLN的體外釋放。結(jié)果 HPLC色譜條件為：DIKMA C₁₈色譜柱（250 mm×4.6 mm，5 μm）；流動(dòng)相為乙腈-0.05 moL/L的KH₂PO₄（含2 mL/L三乙胺）溶液，梯度洗脫，洗脫條件為0 min （6%乙腈）→35 min （13%乙腈）→40 min （6%乙腈），檢測波長為220 nm。TA-PC-SLN的平均粒徑為（126.1±3.89） nm，粒徑分布（PDI）為（0.409±0.022），Zeta電位為（-30.9±7.37） mV；TA-PC-SLN最佳的制備工藝處方為：藥物磷脂復(fù)合物與水相（泊洛沙姆，大豆卵磷脂和聚乙二醇2 000組成）比例為1：1.75，大豆卵磷脂和聚乙二醇2 000比例為1：1.25，冰水分散相與微乳體積比例為9：1。TA-PC-SLN體外釋放速率低于TA。結(jié)論 制備出的TA-PC-SLN包封率可達(dá)到74%以上，載藥量可達(dá)到9%以上，并且實(shí)現(xiàn)了緩釋的目的。

Objective The preparation and formulation optimization of solid lipid nanoparticles of total alkaloids of Sophora flavesicum (TA-PC-SLN) were explored and completed, and the in vitro evaluation of the solid lipid nanoparticles was conducted. Methods HPLC was used to establish a method for simultaneous determination of four index components——matrine (MT), oxymatrine (OMT), sophocarpine (SC), oxysophocarpine (OSC) in TA. The methodology was validated. TA and lecithin were dissolved in ethanol to prepare phospholipid complex, and TA-PC-SLN was prepared by microemulsion method. The entrapment efficiency and drug loading were determined by ultracentrifugation combined with HPLC, and the particle size distribution and zeta potential were determined by colorimetry. The inclusion rate and drug loading were used as the indexes. The formulation was optimized by the star-point effect-surface method, and the dissolution rate of TA-PC-SLN was evaluated in vitro. Results HPLC conditions:DIKMA C₁₈ column (250 mm×4.6 mm, 5 μm); mobile phase:acetonitrile-0.05 mol/L KH₂PO₄ (containing 2 mL/L triethylamine) solution, gradient elution, elution conditions:0 min (6% acetonitrile) → 35 min (13% acetonitrile) → 40 min (6% acetonitrile); detection wavelength:220 nm. The average particle size of ta-pc-sln was (126.1 ±3.89) nm, PDI was (0.409 ±0.022), and zeta potential was (-30.9 ±7.37) mV; The optimal formulation was:the ratio of the pharmaceutical phospholipid complex to the aqueous phase (polloxam, soybean lecithin and polyethylene glycol 2000) was 1:1.75, the ratio of soybean lecithin to polyethylene glycol 2000 was 1:1.25, and the ratio of the ice-water dispersed phase to the volume of microemulsion was 9:1. The release rate of solid lipid nanoparticles was much lower than that of total alkaloids of sophora flavescens. Conclusion TA-PC-SLN can achieve the encapsulation rate of over 74% and the drug load of over 9%, the aim of slow release of total alkaloids of sophora flavescens was realized.

R945

黑龍江省自然科學(xué)基金項(xiàng)目（H2016057、H2017066）