川芪眼用微乳原位凝胶与普通原位凝胶的制剂学表征及组织分布比较
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摘要
目的:考察微乳在川芪微乳原位凝胶中的作用,为相关眼用制剂的研发提供参考。方法:通过川芪微乳原位凝胶与川芪普通原位凝胶的平行比较确定微乳的作用,包括制剂学表征及组织分布研究。结果:川芪微乳原位凝胶、普通原位凝胶的平均粒径分别为(38. 20±0. 13),(985±37) nm。微乳在微乳原位凝胶复合体系中仍能保持其纳米载体的特性。在大鼠眼组织中,3个指标成分川芎嗪、藁本内酯及黄芪甲苷只有藁本内酯可被检测到;川芪微乳原位凝胶中藁本内酯在角膜、玻璃体及视网膜上均能检测到,而川芪普通原位凝胶的藁本内酯只能在角膜中被检测到,且含量极低。3个指标成分中藁本内酯的油水分配系数常用对数(lg P) 2. 87,在理想的眼用药物油水分配系数范围内(lg P=2. 0～3. 0),同时微乳提高了该成分在角膜各组织的分配浓度。结论:微乳纳米载体的特性可增加藁本内酯类成分的溶解性,使其在角膜外的泪液中有更好的分配,到达角膜时具有较高的浓度,形成角膜浓度梯度,从而通过跨眼屏障将药物由前眼部位输送到到后眼部位。
Objective: In this paper,the effect of microemulsion in Chuanqi ophthalmic microemulsion in situ gel was investigated. Method: The effect of microemulsion was confirmed by the parallel comparison between the Chuanqi microemulsion in situ gel and normal in situ gel, including study of pharmaceutical characterization and tissue distribution. Result: The average particle sizes of Chuanqi microemulsion in situ gel and normal in situ gel were(38. 20 ± 0. 13) nm and(985 ± 37) nm,respectively. Microemulsion could maintain the properties of nanocarrier in a microemulsion in situ gel composite system. The result of tissue distribution study showed that only ligustilide could be detected. This was related to the nature of these three indicator components(ligustrazine,ligustilide and astragaloside A). The common logarithm of oil and water partition coefficient of ligustilide(lg P) was 2. 87,which was consistent with the range of lg P of ideal ophthalmic drugs(lg P = 2. 0-3. 0). The ligustilide from Chuanqi microemulsion in situ gel could be detected in the cornea,vitreous body and retina,and this compound from normal in situ gel could only be detected in the cornea with low content. At the same time, microemulsion could increase the content of ligustilide in corneal tissues. Conclusion: The characteristics of microemulsion nanocarriers can increase the solubility of ligustilide,compared with normal in situ gel,it can be better distributed in the tears outside the corneal,it reaches the cornea with a higher concentration,and forms a corneal concentration gradient,and ligustilide is transported from the anterior ocular region to the posterior ocular region through the transocular barrier.
Objective: In this paper,the effect of microemulsion in Chuanqi ophthalmic microemulsion in situ gel was investigated. Method: The effect of microemulsion was confirmed by the parallel comparison between the Chuanqi microemulsion in situ gel and normal in situ gel, including study of pharmaceutical characterization and tissue distribution. Result: The average particle sizes of Chuanqi microemulsion in situ gel and normal in situ gel were(38. 20 ± 0. 13) nm and(985 ± 37) nm,respectively. Microemulsion could maintain the properties of nanocarrier in a microemulsion in situ gel composite system. The result of tissue distribution study showed that only ligustilide could be detected. This was related to the nature of these three indicator components(ligustrazine,ligustilide and astragaloside A). The common logarithm of oil and water partition coefficient of ligustilide(lg P) was 2. 87,which was consistent with the range of lg P of ideal ophthalmic drugs(lg P = 2. 0-3. 0). The ligustilide from Chuanqi microemulsion in situ gel could be detected in the cornea,vitreous body and retina,and this compound from normal in situ gel could only be detected in the cornea with low content. At the same time, microemulsion could increase the content of ligustilide in corneal tissues. Conclusion: The characteristics of microemulsion nanocarriers can increase the solubility of ligustilide,compared with normal in situ gel,it can be better distributed in the tears outside the corneal,it reaches the cornea with a higher concentration,and forms a corneal concentration gradient,and ligustilide is transported from the anterior ocular region to the posterior ocular region through the transocular barrier.
引文
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[12]杜茂波,刘亚梅,何爱萍,等.川芪眼用微乳原位凝胶的流变学及释放动力学分析[J].中国实验方剂学杂志,2017,23(24):23-27.
[2] Chastain J E,Sanders M E,Curtis M A,et al.Distribution of topical ocular nepafenac and its active metabolite amfenac to the posterior segment of the eye[J]. Exp Eye Res,2016,145:58-67.
[3] Di Tommaso C,Bourges J L,Valamanesh F,et al. Novel micelle carriers for cyclosporin A topical ocular delivery:in vivo cornea penetration,ocular distribution and efficacy studies[J]. Eur J Pharm Biopharm,2012,81(2):257-264.
[4] Tajika T,Isowaki A,Sakaki H. Ocular distribution of difluprednate ophthalmic emulsion 0. 05%in rabbits[J]. J Ocul Pharmacol Ther,2011,27(1):43-49.
[5] SHEN J,DENG Y,JIN X,et al. Thiolated nanostructured lipid carriers as a potential ocular drug delivery system for cyclosporine A:improving in vivo ocular distribution[J]. Int J Pharm,2010,402(1/2):248-253.
[6]孙考祥,彭绍民,孙大卫,等.双氯酚酸钠滴眼液的眼内组织分布及药代动力学[J].中国临床药理学杂志,2001,17(2):118-120.
[7]汤成泳,李卿,周远大,等.麝香滴眼液在家兔眼内组织中的分布及药代动力学研究[J].中成药,2010,32(4):581-585.
[8]李彬.与年龄有关的黄斑变性[J].国外医学·眼科学分册,1994,18(1):8-21.
[9]王玉国,高宇.年龄相关性黄斑变性的研究进展[J].航空航天医学杂志,2007,18(1):57-59.
[10]刘家琦,李凤鸣.实用眼科学[M]. 3版.北京:人民卫生出版社,2010:164-165.
[11]杜茂波,沈硕,陈强,等.粒径法筛选微乳固体型表面活性剂[J].中国实验方剂学杂志,2015,21(22):137-139.
[12]杜茂波,刘亚梅,何爱萍,等.川芪眼用微乳原位凝胶的流变学及释放动力学分析[J].中国实验方剂学杂志,2017,23(24):23-27.