盐酸地尔硫（艹卓）凝胶的研究

发布时间：2018-03-10 08:04

本文选题：肛裂　切入点：地尔硫革　出处：《湖北中医药大学》2014年硕士论文　论文类型：学位论文

【摘要】：背景：肛裂是一种在临床上十分常见的肛肠疾病,其临床症状主要表现为便痛、便血。目前认为主要发病机制是由于肛门处括约肌高度紧张而导致肛管静息压力增加,继而进一步诱发肛管后中线供血不良而导致缺血性的溃疡。盐酸地尔硫(?)是一种苯并硫氮杂(?)类化合物,为钙离子通道阻滞剂,口服时药物通过血液转运、分布,抑制心脏与血管平滑肌去极化时的钙离子内流从而发挥其药理作用,临床上常用于心动过速、心绞痛和高血压的治疗。最近国外研究显示局部应用盐酸地尔硫革,能够使肛管平滑肌松弛,降低肛管内静息压力,减轻便血、便痛等临床症状；扩张血管,改善缺血区供血,从而达到治疗肛裂的效果。方法：本课题以羟丙基甲基纤维素作为凝胶基质,采用溶胀法制备凝胶。通过单因素实验考查羟丙基甲基纤维素的浓度对凝胶黏度的影响,筛选出适宜凝胶羟丙基甲基纤维素的浓度范围。通过正交实验设计,以粘度、离心稳定性、体外释放度作为指标,筛选出盐酸地尔硫(?)凝胶的最佳的处方。采用高效液相色谱法,对所制备盐酸地尔硫(?)凝胶进行含量测定,并且通过专属性试验验证含量测定方法的可靠性。对所制备的盐酸地尔硫(?)凝胶进行初步稳定性试验,考察在室温条件下放置3个月所制备凝胶的性状、pH、含量以及有关物质的变化情况。结果：处方筛选结果表明,最佳处方中盐酸地尔硫(?)、羟丙基甲基纤维素、甘油和丙二醇的用量分别为2%、2%、15%、10%,并加入0.3%对羟基苯甲酸乙酯作为防腐剂。含量测定结果表明盐酸地尔硫(?)在10μg/mL90μg/mL浓度范围内,峰面积与浓度呈良好的线性关系,平均回收率为101.0%,RSD=1.08%。通过专属性试验证明,高温、光照、强酸、强碱、氧化等不同条件下强制降解的杂质以及空白凝胶对主药盐酸地尔硫(?)的含量测定均无影响。初步稳定性试验结果表明盐酸地尔硫(?)凝胶在室温下放置3个月,凝胶的性状为无色透明的半固体制剂,pH值变化不大,在5.6～6.1之间。含量在97.9%-100.2%之间,有关物质在0.51%-2.85%之间。
[Abstract]:Background:. Anal fissure is a very common anorectal disease in clinic, and its clinical symptoms are mainly stool pain and bloody stool. At present, it is believed that the main mechanism of anal fissure is the increase of resting anal pressure due to high tension of anal sphincter. In turn, anus posterior midline blood supply is induced to lead to ischemic ulcers. Dilthion Hydrochloride? Is a benzothiazepine? ) compounds, calcium channel blockers, which are transported and distributed through the blood during oral administration, inhibit the influx of calcium ions during depolarization of the heart and vascular smooth muscle and thus play a pharmacological role, and are commonly used in tachycardia clinically. Treatment of angina pectoris and hypertension. Recent foreign studies have shown that local application of diltiazem hydrochloride can relax the smooth muscle of the anal canal, reduce the resting pressure in the anal canal, relieve the clinical symptoms such as bloody stool and stool pain, dilate blood vessels, and improve the blood supply in the ischemic area. So as to achieve the effect of anal fissure treatment. Methods:. In this paper, hydroxy propyl methyl cellulose was used as gel matrix to prepare gel by swelling method, and the effect of concentration of hydroxypropyl methyl cellulose on gel viscosity was investigated by single factor experiment. The optimum concentration range of hydroxy propyl methylcellulose was screened out by orthogonal design, and the viscosity, centrifugation stability and release rate in vitro were used as indexes to screen diltiazone hydrochloride? ) the best formulation of gel. Determination of diltiazone hydrochloride by HPLC. The content of the gel was determined and the reliability of the method was verified by specific test. A preliminary stability test was carried out to investigate the changes of pH, content and related substances of gel prepared at room temperature for 3 months. Results:. The results showed that the best prescription was diltidine hydrochloride? The dosage of HPMC, Glycerol and Propylene Glycol were 2 and 10, respectively, and 0.3% ethyl p hydroxybenzoate was added as preservative. ) within the range of 10 渭 g / mL 90 渭 g / mL, the peak area and concentration showed a good linear relationship, and the average recovery was 101.0% RSD 1.08.The specificity test proved that high temperature, light, strong acid, strong alkali, Under different conditions, such as oxidation, impurity degradation and blank gel to the main drug diltiazem hydrochloride? The results of preliminary stability test showed that diltithione hydrochloride had no effect on the determination of Diltidine hydrochloride. When the gel was stored at room temperature for 3 months, the pH value of semisolid preparation with colorless and transparent properties changed little, ranging from 5.6 to 6.1, the content of gel was between 97.9- 100.2%, and the related substance was between 0.51-2.85%.
【学位授予单位】：湖北中医药大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R943

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