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本文以植烷三醇(phytantriol,PT)、乙醇(ethanol,ET)和水三组分体系制备原位立方液晶(in situ cubic liquid crystal,ISV_2),采用三元相图法优选出各向同性溶液,以可注射性、p H值、相转化最少吸水量、相转化时间作为指标优化处方;在ISV_2处方基础上加入维生素E醋酸酯(vitamin E acetate,Vit EA)制备原位六角相液晶(in situ hexagonal liquid crystal,ISH_2),以体外释药行为作为考察指标优化Vit EA的添加量;采用小角度X射线散射对ISV_2和ISH_2吸水相转化后的液晶结构进行表征;对ISV_2和ISH_2的流变学性质进行研究;采用动态透析法对ISV_2和ISH_2体外释药行为进行比较;以佐剂性关节炎大鼠作为模型动物,盐酸青藤碱(sinomenine hydrochloride,SMH)作为模型药物,考察ISH_2关节局部药动学。优选出的ISV_2(PT/ET/水,64∶16∶20,w/w/w;载药量为6 mg·g~(-1))可用于注射,p H值为5.20,相转化最少吸水量为63.33μL,相转化时间为4.21 s,体外可缓释SMH长达144 h。优选出的ISH_2(PT/Vit EA/ET/水,60.8∶3.2∶16∶20,w/w/w/w;载药量为6 mg·g~(-1))可用于注射,p H值为5.51,体外可缓释SMH长达240 h。大鼠关节腔局部药动学研究结果显示,ISH_2组与溶液组相比,其t_(1/2α)、t_(1/2β)、t_(max)和MRT_(0-∞)明显延长,ISH_2组的AUC_(0-∞)是溶液组的6.01倍。本研究制备的ISH_2关节腔给药后可在关节局部缓释药物,延长药物驻留时间,提高药物利用度,具有较好的应用前景。
In this paper, in situ cubic liquid crystal (ISV_2) was prepared by phytantriol (PT), ethanol (ET) and water three component systems. The isotropic Solution, injectability, p H value, minimum phase water absorption, phase conversion time as an indicator optimization prescription; based on the ISV_2 prescription vitamin E acetate (vitamin EA) prepared in situ hexagonal liquid crystal in situ hexagonal liquid crystal (ISH_2)) were used to optimize the amount of Vit EA added in vitro. The structure of the liquid crystal after ISV_2 and ISH_2 were transformed by small-angle X-ray scattering was characterized. The flow of ISV_2 and ISH_2 The study on the behavior of ISH_2 and ISH_2 in vitro was carried out by dynamic dialysis. Taking adjuvant arthritis rats as model animals and sinomenine hydrochloride (SMH) as model drug, the effects of ISH_2 joint Local pharmacokinetics. The optimal ISV_2 (PT / ET / water, 64:16:20, w / w / w; drug loading 6 mg · g -1) was suitable for injection with a p H value of 5.20 and a minimum phase transformation The amount of water absorbed was 63.33μL, the phase transformation time was 4.21 s, and the release of SMH in vitro was as long as 144 h. The preferred ISH_2 (PT / Vit EA / ET / water, 60.8: 3.2: 16:20, w / w / w / w; drug loading 6 mg · g -1) can be used for injection, p H Value of 5.51, in vitro release of SMH up to 240 h. The results of local pharmacokinetic study in rat articular cavities showed that t 1/2, t 1 / 2β, t max and MRT 0 -∞ in ISH 2 group were significantly longer than those in ISH 2 group and ISH 2 group The AUC_ (0-∞) of the group was 6.01 times that of the solution group. The preparation of ISH_2 joint cavity after administration of the local slow release of drugs in the joints to extend drug residence time and improve drug availability, has good application prospects.