【作者】 张玲；

【导师】 刘新泳； 王翀；

【作者基本信息】 山东大学 ， 制药工程（专业学位）， 2012， 硕士

【摘要】 近年来我国便秘的发病率呈快速增长之势,受便秘困扰的患者数量庞大,然而临床治疗便秘药物的现状却不尽如人意,数量少、品种老化,疗效不理想,处于被冷落的境地。目前我国治疗便秘的药物主要以泻药为主,如硫酸钠和蓖麻油等。腹泻可因感染、炎症、药物、手术、食物、转运过程改变和精神因素等多种因素所引起。聚卡波菲钙能够双向调节腹泻、便秘等症状,开发本品可以为广大患者提供更好的临床用药。该产品在胃内酸性条件下可使钙游离而变成聚卡波菲,聚卡波菲不被人体吸收,由于聚卡波菲具有在小肠内和大肠内等中性条件下具有吸水而膨润凝胶化的特性,服用本品后12-72小时诱发肠运动,因此改善肠易激综合征的腹泻、便秘、腹痛及腹胀等消化道症状。聚卡波菲钙为消化作用的效应物,通过吸收水份,使病人肠道内的湿润程度恢复正常,进而治疗腹泻。同时本品为增容性(bulk-forming)轻泻剂,可产生膨胀,以利于便秘的治疗。本论文立足于解决聚卡波菲钙从实验室转化成工业化生产过程中存在的系列问题。通过对调节剂用量的研究、母液套用处理、粘壁料的处理、钙化终点研究、吸水力的研究、老化温度和时间的研究、洗涤用水研究、废水处理研究、成品干燥研究、浸泡时间等方面的研究,通过反复实验得出最佳工艺条件：(1)调节剂的最佳用量为0.014-0.016ml/100g丙烯酸；(2)母液可以多次套用不改变原来液体的性质；(3)通过改善调节剂的用量及高纯N2替代普通N2,并采用未重蒸的工业丙烯酸来取代重蒸的丙烯酸等方法来减少甚至去除粘壁料；(4)钙化终点研究：通过调pH至6.0来控制反应终点,可有效地减少成品中钙含量不合格批次的产生。(5)老化温度和老化时间：采用73～80℃为老化温度完全可以达到工艺要求,这样既降低了生产难度,又降低了能耗,进一步降低了生产成本。钙化反应老化时间3小时与6小时对成品质量无明显差别,且随老化时间的延长,CPC的颗粒越来越重,逐渐沉在瓶底,进而粘成一团,会给工业化生产放料带来了困难。因此可以通过缩短老化时间解决这些问题。(6)洗涤用水研究：采用自来水替代纯化水作为反应和洗涤用水,可以达到工艺要求,同时也降低了生产成本。(7)废水处理：采用石灰乳取代CaCO3来处理产生的废水(8)成品干燥研究：只需干燥3h即可达到料脆易研碎的效果。(9)浸泡时间研究：为提高劳动生产率,缩短工艺时间,我们采用了浸泡2.5h的工艺。通过对调节剂用量、钙化终点、粘壁料等等影响因素的研究,使聚卡波菲钙的工艺基本满足了工业化生产的要求。通过对改进工艺所得的成品IR、X-射线粉末衍射、热重、吸水力和钙含量的测定等分析,确定能够得到理想的聚卡波菲钙产品,而且工艺改进后的产品质量较以前有较大提高。更多还原

【Abstract】 In China, the morbidity of constipation has rapidly increased in recent years. Although many patients are troubled by constipation, the condition of emplastic is negative. The emplastic was ignored for its small quantity, old types and negative effects. Laxatives, such as sodium sulphate and castor oil, are the main drugs used to treat constipation in China. Diarrhea can be caused by many factors:infection, inflammation, drugs, surgery, food, changes in the transit process, spiritual factors, etc. Calcium Polycarbophi are effective on bi-directional regulation of diarrhea, constipation and other symptoms. The exploitation of this product can provide better clinical treatment to the majority of patients. The product allows calcium dissociate and turn into Polycarbophi under the acidic condition in the stomach. Polycarbophi can not be absorbed by the body. The Polycarbophi swells and gelates in the neutral condition of the small intestine and large intestine. Thus, the bowel movements will activate after taking the drug twenty to seventy-two hours. The Calcium Polycarbophi improves the irritable bowel syndrome, diarrhea, constipation, abdominal pain, bloating and other gastrointestinal symptoms. This product is the effector of digestion. The moisture of a patient’s intestinal canal will return to normal after the drug absorbing water, and then treat diarrhea. Because this product is a kind of bulk-forming laxative, which can cause swelling, it is beneficial to the treatment of constipation.The aim of this paper is to solve the problems in the transformation, from the laboratory into the industrial production process, of Calcium Polycarbophi. After studing on dosage adjustment, the mother liquor, sticky wall materials, calcification, water absorption, aging temperature and time, washing water, wastewater treatment, finished product drying, soak time, etc. The optimal process has been obtained.(1)0.014-0.016ml/100g of crylic acid is the best quantity for dosage adjustment.(2) There is no effect for several reused mother liquor.(3) Sticky wall materials is reduced or removed though changing the dosage adjustment, high purity nitrogen and undistilled industrial crylic acid.(4) The calcification reaction end—point is controlled according to PH=6.0, which is reduced the unqualified production.(5) The best aging temperature is73～80℃, which is not only reduced production difficulty, but also reduced energy intensity and cost. There is no obvious difference of aging time for3h or6h. As the time extension, the particles of CPC are bigger than before, which gathered and sticked in the bottle bottom. The difficulty for industrial production is solved by shorting aging time.(6) Tap water is used for reaction and washing instead of purified water, which could reduce cost of production.(7) Lime milk is used for wastewater treatment instead of CaCO3.(8) The finished product is fragile and triturated after drying for3h.(9)2.5h is the best time for soak time in order to increase product efficiency and reduce time.The process satisfied the industrial requirements after studying on process optimization for Calcium Polycarbophi production. By the analysis of measuring the IR, X-ray powder diffraction, thermogravimetry, water absorption, and calcium content of the improved products, the desired Calcium Polycarbophi were confirmed to achieved and quality of the product greatly improved than before.更多还原