曼陀罗子提取物对Beagle犬长期毒性实验研究

目的 观察Beagle犬连续口服曼陀罗子提取物(MTL)的长期毒性反应. 方法Beagle犬24只,随机分为空白对照组及低、中、高剂量药物组,每组6只. 低、中、高剂量药物组分别给予MTL 40,80,160 mg.kg^-1.d^-1,po,qd,连续3个月,空白对照组给予羧甲基纤维素钠. 末次给药24 h每组处死4只犬,停药后恢复2周每组再处死2只犬,分别检测血液学、血液生化学等指标,测定脏器系数,进行系统尸检、脏器组织病理学检查. 结果 中、高剂量药物组犬给药后出现活动先增多后减少、扩瞳、口干、呕吐等症状;与空白对照组比较,中、高剂量药物组犬体质量明显降低,血小板计数、淋巴细胞数目、肌酸磷酸激酶明显升高,粒细胞数目明显降低;组织病理学检查无明显变化. 结论 MTL连续口服给予Beagle犬 3个月,对犬中枢神经系统、消化系统、血液系统、心脏有一定毒性. MTL对Beagle犬安全剂量不高于40 mg•kg^-1•d^-1(相当于生药388 mg.kg^-1.d^-1).     

比格犬下颌骨微种植体的置入部位和方法

背景：比格犬下颌骨解剖结构复杂,微种植体置入位置不恰当会造成微种植体周骨量不足和微种植体松脱。 目的：观察比格犬下颌骨相应解剖结构及微种植体的置入部位和方法。 方法：取成年雄性比格犬尸体下颌骨,测量下颌第二双尖牙牙尖至下颌第一磨牙远中颊尖的长度;下颌第二、三、四双尖牙和第一磨牙根分叉度及牙根分叉处距离下颌神经管的垂直高度;于牙槽嵴下4,6 mm处用游标卡尺测量下颌第二、三、四双尖牙和第一磨牙颊舌向牙槽嵴厚度和近远中根的水平距离。 结果与结论：下颌第二双尖牙牙尖至下颌第一磨牙远中颊尖的长度平均为52.70 mm;距离下颌神经管的垂直高度最远的是第一磨牙,最近的是第四双尖牙,根分叉度最大的是第一磨牙,最小的是第四双尖牙。下颌第二、三、四双尖牙和第一磨牙的颊舌向骨质厚度随着距离牙槽嵴顶深度的增加而增加。在距离牙槽嵴顶4,6 mm的深度,下颌第二、三、四双尖牙和第一磨牙近远中根的水平距离均大于5 mm,且随着距离牙槽嵴深度的增加而增加。说明比格犬下颌第二双尖牙至第一磨牙牙槽骨段骨质结构均匀。在距离牙槽嵴顶4~6 mm深度,单颗牙自身近远中牙根之间足以提供微种植体置入所需骨量。     

牙周炎犬种植体周围炎动物模型建立

目的利用牙周炎beagle犬建立一种近似人类临床种植体周围炎的动物模型。方法在6只年龄1周岁,全身健康的Beagle犬牙颈部龈缘水平结扎丝线3个月,形成牙周炎动物模型后,植入种植体并分别于第1天、第3天、第7天、第14天、1月末、2月末和3月末检查实验动物的种植体周围状况。结果所有动物实验侧种植体周围均形成近似人类临床种植体周围炎的实验性种植体周围炎,但严重程度不一。结论在牙周炎Beagle犬可成功建立与临床实际近似的种植体周围炎模型,成功率高,可为临床研究提供帮助。     

左氧氟沙星在腹部开放性创伤合并人工海水浸泡致低体温Beagle犬中药动学研究

目的建立Beagle犬海水浸泡致低体温及合并腹部开放性创伤动物模型;研究并比较左氧氟沙星在海水浸泡致低体温及合并腹部开放性创伤Beagle犬动物模型及正常Beagle犬的药物动力学。方法 12只Beagle犬随机分为3组,每组4只。组1为正常对照组,组2为低体温模型组,组3为腹部开放性创伤合并低体温模型组。给药方案为：左氧氟沙星25 mg/kg,静脉输注,60m in输注完毕。SPSS程序进行统计学处理。结果组1动物给药前后72 h体温正常,为（37.20±0.27）℃;组2和组3海水浸泡后体温明显下降,最低分别为（30.00±1.12）℃和（29.8±1.03）℃。组2、组3与组1比较,消除半衰期、药物峰浓度以及药时曲线下面积明显增加,清除率有所降低。相同时间点血药浓度比较,组2、组3均高于组1。组2与组3间药物动力学参数及药物浓度均无差异。结论在72 h内海水浸泡致低体温状况可导致左氧氟沙星药物动力学特性变化,腹部开放性创伤的影响不显著。     

Development of a method for determination of osmotic pump controlled-release tablets of lorcaserin hydrochloride in beagle dog plasma and its application to pharmacokinetic study北大核心CSCD

Aim To develop an UPLC-MS/MS method to determine the concentration of lorcaserin hydrochloride in beagle plasma, and study the pharmacokinetics of osmotic pump controlled-release tablets of lorcaserin hydrochloride. Methods A randomized crossover design was used, carbamazepine as the internal standard(IS), and plasma protein precipitation with acetonitrile. The chromatographic was Phenomenex Polar C18 column(100 mm×2. 1 mm, 3 μm), and acetonitrile - water(containing 10 mmol·L-1 ammonium acetate and 0.1% formic acid)(40:60, V/V)was mobile phase. Multiple reaction monitoring mode and electrospray positive ionization were used to detect lorcaserin hydrochloride. The MS/MS ion transitions were monitored at m/z 196.2→129.2 for lorcaserin hydrochloride and m/z 237→194.1 for carbamazepine, respectively. Results The linear range was 1 to 500 μg·L-1(r=0.999 2), the extraction recovery rate ranged from 87.70% to 89.70%, the precision RSD was 9.7%. The accuracy and matrix effect met the requirements, and the stability of lorcaserin hydrochloride was good in -20 ℃ refrigerator for 45 d, repeated freezing and thawing for three times, placed at room temperature for 24 h, and the disposed samples placed in automatsampler for 6 h were stable. The main pharmacokinetic parameters of the controlled-release tablet and immediate-release tablet were as follows:Tmax was(8.00±1.27)h and(1.00±0.13)h, Cmax was(70.56±3.73)μg·L-1 and(176.33±16.73)μg·L-1, and AUC0-t was(966.33±7.56)μg·h·L-1 and(973.05±69.09)μg·h·L-1, respectively. Conclusions The established UPLC-MS/MS method can be used to study the pharmacokinetics of lorcaserin hydrochloride in the plasma of beagle dogs, and osmotic pump controlled-release tablets has sustained release effect. © 2023 Publication Centre of Anhui Medical University. All rights reserved.