肠溶生物粘附微丸的制备与检测及对STZ诱导的T2DM大鼠的治疗作用

发布时间：2018-02-21 16:11

本文关键词： 二型糖尿病肥胖症生物粘附胃转流术 GIP GLP-1 胰岛β细胞　出处：《上海师范大学》2015年硕士论文　论文类型：学位论文

【摘要】：糖尿病是一种较为常见的慢性疾病,可以引起多种并发症。二型糖尿病患者通常还具有体重超标的状况。现如今治疗糖尿病并发肥胖症有一种专门的方法,即通过外科手术,通常是采用胃转流手术。这些手术被证实具有良好的效果,但是其还具有一定的危险性,同时也会对患者产生较大的痛苦。对此本课题希望能够开发一种口服药物,达到外科手术的目的并减少患者的痛苦。药物的原料拟选用卡波姆934P及一系列具有粘附效果的辅料,并对其进行肠溶包衣,使其能够在预定的环境下分解形成生物黏附膜而在其他环境下保持细小的干燥颗粒状态,最终阻断食物糜同活跃的近端小肠壁接触,达到类似外科手术的目的。本课题分为三部分,第一是制备药物微球,从原材料的选择开始,至包衣完成后对颗粒进行包衣质量检测,以确定其能够在所需的预定情况下发挥作用。第二部分是对药物微球形成的生物黏附膜进行体外测试,本文通过体外的快速溶解测试、稳定性及膨胀度测试、粘附力测试以及葡萄糖透过率测试四个方面进行测定,对其安全性和可行性进行一个直观分析,确定了其对服药者不会产生不良后果而造成死亡。第三部分是对药物进行体内测试,主要对糖尿病的一些症状及体内激素的分泌变化进行研究,通过对体重和血糖的研究判定其对糖尿病症状的改善情况,对葡萄糖依赖性胰岛素释放肽(GIP)和胰高血糖素样肽1(GLP-1)的研究以确定其发挥作用时对机体产生的影响,通过对病理性研究,观察病变组织的切片以确定服药后实验动物的器官是否因为药物的用而避免了被体内高血糖环境的毒害。研究发现,药物能够在一定程度上代替外科手术的作用,在体外检测阶段可以认定其对后期的实验动物不会造成致死性的影响,以及其可能会产生的一些治疗作用。体内检测阶段则通过治疗发现实验动物因STZ诱导产生的糖尿病引起的体重下降及血糖过高均得到缓解,同时降低GIP的过量分泌,减少了其对胰岛β细胞的拮抗作用,打开其同GLP-1的共用刺激通路,使GLP-1发挥作用,最终修复胰岛细胞,对糖尿病起到一定的治疗作用。本实验通过创新性的对外科手术治疗肥胖型II型糖尿病患者的治疗方案进行改进,能够在达到一定效果的同时,减少患者在治疗中所受痛苦。在肥胖型II型糖尿病较为高发的当下,该研究所带来的经验或许能够为治疗此疾病带来一种全新的手段。
[Abstract]:Diabetes is a common chronic disease that can cause multiple complications. Type 2 diabetics often have overweight conditions. Nowadays, there is a special way to treat diabetes with obesity, that is, through surgery. Gastric bypass surgery is usually used. These operations have proved to have good results, but they are also dangerous and can cause greater pain to patients. This study hopes to develop an oral drug. In order to achieve the purpose of surgery and reduce the pain of patients, the raw materials of the drug were selected as carbomer 934P and a series of adherent excipients, and they were coated with enteric dissolution. Allowing it to break down in a predetermined environment to form a bioadhesive film and to maintain a small dry particle state in other environments, ultimately blocking the contact between the food surimi and the active proximal wall of the intestine, This task is divided into three parts: the first is the preparation of drug microspheres, starting with the selection of raw materials, and testing the coating quality of the particles after the coating is finished. The second part is to test the biofilm formed by drug microspheres in vitro. In this paper, the rapid dissolution test, stability test and expansion test in vitro are carried out. The adhesion test and glucose transmittance test were carried out in four aspects, and the safety and feasibility of the test were analyzed intuitively. The third part is to test the drug in vivo, mainly to study the symptoms of diabetes and the changes of hormone secretion in the body. Through the study of body weight and blood sugar to determine the improvement of diabetic symptoms, the study of glucose-dependent insulin releasing peptide (GIPP) and glucagon like peptide 1 (GLP-1) to determine its effect on the body. By studying the pathophysiology, the pathological tissue sections were observed to determine whether the organs of the experimental animals were prevented from being poisoned by the hyperglycemia environment because of the use of the drug. Drugs can take the place of surgery to some extent, and can be determined in vitro testing that they will not cause fatal effects on later experimental animals. In vivo, it was found that the weight loss and hyperglycemia caused by STZ induced diabetes in experimental animals were alleviated, and the excessive secretion of GIP was also reduced. It reduced its antagonistic effect on islet 尾 cells, opened up its common stimulating pathway with GLP-1, and enabled GLP-1 to play a role in the final repair of islet cells. This experiment can improve the surgical treatment of obese type II diabetes patients, and achieve a certain effect at the same time. Reduce pain in treatment. At a time when obese type II diabetes is more prevalent, the experience of the study may offer a new way to treat the disease.
【学位授予单位】：上海师范大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.1

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