| 引用本文: | 游翠玉,石锐,孙金钥,邓祥,王喜丹,邓文婷,张文娟.氢化可的松琥珀酸钠口服结肠靶向pH敏感型水凝胶的药动学与药效学研究[J].中国现代应用药学,2023,40(17):2427-2434. |
| YOU Cuiyu,SHI Rui,SUN Jinyao,DENG Xiang,WANG Xidan,DENG Wenting,ZHANG Wenjuan.Study on Pharmacokinetics and Pharmacodynamics of Oral Colon Targeted pH-Sensitive Hydrogel of Hydrocortisone Sodium Succinate[J].Chin J Mod Appl Pharm(中国现代应用药学),2023,40(17):2427-2434. |
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| 摘要: |
| 目的 对氢化可的松琥珀酸钠(hydrocortisone sodium succinate，HSS)口服结肠靶向pH敏感型水凝胶(oral colon targeted pH-sensitive hydrogel of HSS，HSS-GEL)进行药动学与药效学研究。方法 考察HSS-GEL与HSS在大鼠体内血药浓度变化；建立2,4,6-三硝基苯磺酸(2,4,6-trinitrobenzene sulfonic acid，TNBS)诱导小鼠溃疡性结肠炎(ulcerative colitis，UC)模型，以小鼠疾病活动指数(disease activity index，DAI)、结肠长度、髓过氧化酶活性(myeloperoxidase，MPO)和脏器指数为指标，考察了HSS-GEL的结肠炎治疗作用。结果 HSS-GEL的Tmax、Cmax和AUC与HSS比较均有统计学差异(P<0.01)，其中HSS-GEL的Tmax比HSS明显延长，药物吸收入血时间明显延后；HSS-GEL组Cmax与HSS的Cmax相比明显降低；HSS-GEL组AUC是同等剂量HSS的39.38%，表明将HSS制成HSS-GEL口服后药物入血量明显减少；造模后小鼠由于炎症反应，DAI、MPO活性和脏器指数均升高，结肠缩短，给予HSS-GEL治疗后，小鼠DAI、MPO活性和部分脏器指数与TNBS组相比均明显降低(P<0.05或P<0.01)；而TNBS+HSS-GEL组小鼠MPO活性和部分脏器指数降低程度明显大于TNBS+HSS组，表明HSS-GEL对TNBS诱导的小鼠UC有很好的治疗作用，且效果优于HSS。结论 制备的HSS-GEL具有良好的结肠靶向性与结肠炎治疗效果。 |
| 关键词: 氢化可的松琥珀酸钠 pH敏感 口服结肠靶向给药系统 血药浓度 药效学 |
| DOI：10.13748/j.cnki.issn1007-7693.20223138 |
| 分类号:R969.1 |
| 基金项目:陕西省重点研发计划一般项目(2020SF-334，2021SF-008) |
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| Study on Pharmacokinetics and Pharmacodynamics of Oral Colon Targeted pH-Sensitive Hydrogel of Hydrocortisone Sodium Succinate |
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YOU Cuiyu1, SHI Rui2, SUN Jinyao1, DENG Xiang1, WANG Xidan1, DENG Wenting1, ZHANG Wenjuan1
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1.Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China;2.Department of Pharmacy, Yuncheng Central Hospital, Yuncheng 044000, China
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| Abstract: |
| OBJECTIVE To study the pharmacokinetics and pharmacodynamics of oral colon targeted pH-sensitive hydrogel of hydrocortisone sodium succinate(HSS-GEL). METHODS The plasma concentration changes of HSS-GEL and HSS in the mice were investigated; 2, 4, 6-trinitrobenzene sulfonic acid(TNBS)-induced mouse model of ulcerative colitis(UC) was established, disease activity index(DAI), colon length, myeloperoxidase(MPO) and organ index were used as indicators to investigate the therapeutic effect of HSS-GEL on colitis. RESULTS The results showed that the Tmax, Cmax and AUC of HSS-GEL were significantly different from those of HSS(P<0.01). The Tmax of HSS-GEL was significantly longer than that of HSS, and the time of drug absorption into the blood was significantly delayed. The Cmax of HSS-GEL group was significantly lower than that of HSS. The AUC of the HSS-GEL group was 39.38% of the same dose of HSS, indicating that the amount of the drug absorbed into blood was significantly reduced after the HSS was made into HSS-GEL orally. After modeling, DAI, MPO activity and organ index were increased, while the colon was shortened due to the inflammatory reaction, with the treatment of HSS-GEL, DAI, MPO activity and some organ index of mice were significantly decreased comparing with TNBS group(P<0.05 or P<0.01). The degree of reduction of MPO activity and some organ indexes of the mice in the TNBS+HSS-GEL group were significantly greater than those in the TNBS+HSS group, indicating that HSS-GEL had good therapeutic effect on TNBS-induced ulcerative colitis, and the effect was better than that of HSS. CONCLUSION The HSS-GEL prepared has good colon targeting characteristic and colitis treatment effect. |
| Key words: hydrocortisone sodium succinate pH-sensitive oral colon-specific drug delivery system plasma concentration pharmacodynamics |
