本文關(guān)鍵詞： 二型糖尿病 肥胖癥 生物粘附 胃轉(zhuǎn)流術(shù) GIP GLP-1 胰島β細(xì)胞　出處：《上海師范大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

【摘要】：糖尿病是一種較為常見的慢性疾病,可以引起多種并發(fā)癥。二型糖尿病患者通常還具有體重超標(biāo)的狀況�，F(xiàn)如今治療糖尿病并發(fā)肥胖癥有一種專門的方法,即通過外科手術(shù),通常是采用胃轉(zhuǎn)流手術(shù)。這些手術(shù)被證實(shí)具有良好的效果,但是其還具有一定的危險(xiǎn)性,同時(shí)也會對患者產(chǎn)生較大的痛苦。對此本課題希望能夠開發(fā)一種口服藥物,達(dá)到外科手術(shù)的目的并減少患者的痛苦。藥物的原料擬選用卡波姆934P及一系列具有粘附效果的輔料,并對其進(jìn)行腸溶包衣,使其能夠在預(yù)定的環(huán)境下分解形成生物黏附膜而在其他環(huán)境下保持細(xì)小的干燥顆粒狀態(tài),最終阻斷食物糜同活躍的近端小腸壁接觸,達(dá)到類似外科手術(shù)的目的。本課題分為三部分,第一是制備藥物微球,從原材料的選擇開始,至包衣完成后對顆粒進(jìn)行包衣質(zhì)量檢測,以確定其能夠在所需的預(yù)定情況下發(fā)揮作用。第二部分是對藥物微球形成的生物黏附膜進(jìn)行體外測試,本文通過體外的快速溶解測試、穩(wěn)定性及膨脹度測試、粘附力測試以及葡萄糖透過率測試四個(gè)方面進(jìn)行測定,對其安全性和可行性進(jìn)行一個(gè)直觀分析,確定了其對服藥者不會產(chǎn)生不良后果而造成死亡。第三部分是對藥物進(jìn)行體內(nèi)測試,主要對糖尿病的一些癥狀及體內(nèi)激素的分泌變化進(jìn)行研究,通過對體重和血糖的研究判定其對糖尿病癥狀的改善情況,對葡萄糖依賴性胰島素釋放肽(GIP)和胰高血糖素樣肽1(GLP-1)的研究以確定其發(fā)揮作用時(shí)對機(jī)體產(chǎn)生的影響,通過對病理性研究,觀察病變組織的切片以確定服藥后實(shí)驗(yàn)動物的器官是否因?yàn)樗幬锏挠枚苊饬吮惑w內(nèi)高血糖環(huán)境的毒害。研究發(fā)現(xiàn),藥物能夠在一定程度上代替外科手術(shù)的作用,在體外檢測階段可以認(rèn)定其對后期的實(shí)驗(yàn)動物不會造成致死性的影響,以及其可能會產(chǎn)生的一些治療作用。體內(nèi)檢測階段則通過治療發(fā)現(xiàn)實(shí)驗(yàn)動物因STZ誘導(dǎo)產(chǎn)生的糖尿病引起的體重下降及血糖過高均得到緩解,同時(shí)降低GIP的過量分泌,減少了其對胰島β細(xì)胞的拮抗作用,打開其同GLP-1的共用刺激通路,使GLP-1發(fā)揮作用,最終修復(fù)胰島細(xì)胞,對糖尿病起到一定的治療作用。本實(shí)驗(yàn)通過創(chuàng)新性的對外科手術(shù)治療肥胖型II型糖尿病患者的治療方案進(jìn)行改進(jìn),能夠在達(dá)到一定效果的同時(shí),減少患者在治療中所受痛苦。在肥胖型II型糖尿病較為高發(fā)的當(dāng)下,該研究所帶來的經(jīng)驗(yàn)或許能夠?yàn)橹委煷思膊硪环N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.
【學(xué)位授予單位】：上海師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R587.1

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