基于降低便秘副作用的碳酸钙D_(3)咀嚼片制剂处方优化的研究  

Optimization of Calcium Carbonate and Vitamin D_(3) Chewable Tablets Formulation Optimization of Calcium Carbonate D_(3) Chewable Tablet Formulation Based on Reducing Side Effects of Constipation

作　　者：李明丹 刘理 谢宇圆 朱恒 陈志 LI Mingdan;LIU Li;XIE Yuyuan(Hunan Research Center for Safety Evaluation of Drugs,Hunan Key Laboratory for Pharmacodynamics and Safety Evaluation of New Drugs,Changsha Pediatric Drug Research Technology Innovation Center,Changsha Hunan 410329)

机构地区：[1]湖南省药物安全评价研究中心&新药药效与安全性评价湖南省重点实验室&长沙市儿科用药研究技术创新中心,湖南长沙410329

出　　处：《医学临床研究》2024年第7期964-968,共5页Journal of Clinical Research

基　　金：湖南省企业科技创新创业团队(2021);湖南省科技领军人才计划(2024)。

摘　　要：【目的】探讨基于降低便秘副作用的碳酸钙D_(3)咀嚼片制剂处方优化方法。【方法】通过文献调研不同辅料对小鼠小肠运动的影响,选取5种不同辅料组成的市售产品,根据市售产品辅料组成实验室自制2种成品,通过小鼠小肠运动实验筛选出最优辅料组成。ICR小鼠随机分为8组,即空白对照组、401自制组、601自制组、金贝牌市售品组及已上市产品1组、2组、3组、4组,每组20只,雌雄各半,各组分别进行单次给药实验(给药1次)、重复给药实验(给药30 d),给药组给药剂量均为130 mg/kg(按钙含量计算),空白对照组给予相同体积纯水。实验期间每天观察小鼠一般表现和粪便性状;重复给药实验每周收集各组小鼠粪便,观察、拍照各组小鼠粪便性状,称各组6 h内粪便重量;单次给药实验、重复给药实验均在末次给药后进行肠推进实验,计算小鼠小肠墨汁推进率。【结果】不同辅料组成的碳酸钙D_(3)咀嚼片单次给药对小鼠小肠推进率均未见明显影响。重复给药30 d,与空白对照组比较,601自制组及已上市产品1组、2组、3组、4组小鼠可见粪便干燥,墨汁推进率明显降低(P<0.05);601自制组及已上市产品3组、4组小鼠给药3周、4周时粪便重量及已上市产品1组、2组小鼠给药4周粪便重量均明显减少(P<0.05);401自制组、金贝牌市售品组小鼠粪便性状、小肠推进率、粪便重量均未见明显影响。【结论】辅料组成中含有促排便成分的碳酸钙D_(3)咀嚼片可降低重复给药引起的便秘,不同促排便机制辅料可协同发挥作用,经过本研究比较,专利产品金贝牌碳酸钙D_(3)咀嚼片(浙江寰领科技有限公司,专利号CN112972408A)处方工艺最优,可有效降低重复给药引起的便秘。【Objective】To investigate the optimal method of calcium carbonate D_(3) chewable tablet formulation based on reducing side effects of constipation.【Methods】The effects of different excipients on small intestine movement of mice were investigated by literature,and 5 commercially available products composed of different excipients were selected.According to the excipients composition of commercially available products,2 kinds of finished products were made in the laboratory,and the optimal excipients composition was selected by mouse small intestine movement test.ICR mice were randomly divided into 8 groups according to body weight,namely blank control group,401 self-made group,601 self-made group,marketed product 1,2,3,4 group and Jinbei commercial product group,with 20 mice(half male and half female)in each group.Single administration test(once administration)and repeated administration test(30 days administration)were conducted respectively.The dose of mice in each administration group was 130 mg/kg(measured by calcium),and the corresponding volume of pure water was given to the blank control group.The general clinical manifestations and fecal characteristics of mice were observed every day during the experiment.The fecal properties of mice in each experimental group were observed and photographed every week in the repeated administration test groups,and the fecal weight was measured within 6 hours.Intestinal propulsion test was performed after the last administration in both single administration test and repeated administration test to calculate the intestinal ink propulsion rate of mice.【Results】Single administration of Calcium carbonate and vitamin D_(3) chewable tablets composed of different excipients had no significant effect on small intestinal propulsion rate in mice.After repeated administration for 30 days,compared with the blank control group,fecal dryness was observed in mice in 601 self-made group,marketed product 1,2,3,4 group,and the ink advancing rate was significantly reduced(P<0.05

关 键 词：便秘 碳酸钙 药用制剂 

分 类 号：R442.2[医药卫生—诊断学]