2%HPMC对兔眼内压及角膜内皮影响的实验研究

报导了2%羟丙基甲基纤维素(HPMC)、1%透明质酸钠(Na-HA)及平衡盐液(BSS)分别注入兔眼前房后,其眼内压、角膜内皮细胞数及内皮细胞形态的变化。证实自制2%HPMC 与进口1%Na-HA 性能基本相同,仅有一过性眼压升高,不损害角膜内皮,能在眼前节手术及人工晶体植入时有效地保护角膜内皮细胞。     

Développement d’un hydrogel autodurcissant in vivo, en perspective d’un usage biomédicalA new self-hardening gel in prospect of biomedical use

Since 1995, an injectable bone substitute is developed in our laboratory, it is based on a mix of an hydrogel (hydroxypropyl methylcellulose at 3%: cellulose ether) and biphasic calcium phosphate granules (MBCP^® : 60% hydroxyapatite, 40% β-tri calcium phosphate). This first generation of injectable bone substitute is a non-self-hardening past, nevertheless it owns a great osteoconductor potential. But it shows a tendency to the discharge by its initial composition, and involved limited clinical applications. An evolution of this product is presented in this article: the modification is generated by a new self-hardening hydrogel. This hydrogel is a cellulose ether grafted by silane and diluted in an aqueous solution at basic pH. Also it will be presented the general synthesis of this cellulose derivate, the dissolution condition and the self hardening principle in function of the pH and the temperature. As to conclude by preliminary tests, the biocompatibility in vivo and in vitro of the self-hardening hydrogel mixed with biphasic calcium phosphate granules will be studied.     

琥珀酸美托洛尔HPMC骨架片释放影响因素研究

以羟丙基甲基纤维素（HPMC）为骨架材料，乙基纤维素（EC）为阻滞剂，采用湿颗粒压片法制备琥珀酸美托洛尔亲水凝胶骨架片，考察HPMC用量、HPMC黏度、EC用量、制备方法、压片压力、释放介质及转速对琥珀酸美托洛尔（MS）骨架片体外释药的影响。结果表明，MS骨架片体外释药符合Higuchi方程，药物释放机制是骨架溶蚀和药物扩散的综合效应；HPMC用量与黏度、阻滞剂用量、制备方法、压片压力对释放速率均有显著性影响；释放介质的pH值及转速对释放速率无显著性影响。     

Glomerulosclerosis develops in Thy-1 nephritis under persistent accumulation of macrophages

To clarify the relationship between macrophages and development of glomerulosclerosis, the authors developed a new experimental nephritis model with macrophages persisting in Thy-1 nephritis. Methyl-cellulose was administered intraperitoneally in addition to the intravenous injection of the anti-Thy-1 antibody to Wistar rats. Foamy macrophages influxed into the lytic mesangium and stayed to form nodular aggregates. Mesangial cells proliferated with the formation of extracellular matrices around these nodular aggregates of macrophages. Immunohistochemical analyses revealed that alpha-smooth muscle actin (alpha-SMA) was expressed in the proliferative area around these nodules of foamy macrophages from day 7. Type I collagen and type IV collagen were also expressed around the foamy macrophages in correspondence with alpha-SMA expression from day 7. The electron microscopic study revealed that collagen fibrils were formed around the transformed mesangial cells. The expression of platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31), a marker of glomerular vasculature endothelial cells, was not found in the area occupied by the foamy macrophages, suggesting the impairment of glomerular reconstruction. Macrophages may participate in the progression of glomerulosclerosis in Thy-1 nephritis by enhancing the production of the extracellular matrix through transformed mesangial cells and preventing reconstruction of the capillary network.     

聚—（羟丙基、丙基）—天冬酰胺材料体外酶解及植入小鼠体内的观察

目的：观察4种不同摩尔比的聚－（羟丙基、丙基）－天冬酰胺材料在体外酶解和植入小鼠体内后的变化。方法;用木瓜蛋白酶和胰酶对材料作了体外酶解试验,用凝胶色谱法对降解物碎片作了测定;用光镜、扫描电镜、透射电镜等对材料在埋植部位、肝、肾组织内的降解碎片进行观察;对材料植入小鼠体内后的生化指标（血红蛋白、白细胞、谷丙转氨酶、肌酐作了测定。结果：聚－（羟丙基、丙基）－天冬酰胺材料在体外能被逐步酶解。在植入小鼠体内的5周内,在埋植部位、肝、肾组织内能观察到材料的碎片。结论：聚－（羟丙基、丙基）－天冬酰胺材料能在体内、外逐步降解,植入小鼠体内后对动物的血象、肝、肾功能无明显的影响,具有生物相容性。     

登革病毒甲基纤维素微量蚀斑技术的建立

目的建立登革病毒甲基纤维素微量蚀斑技术。方法将4株登革病毒接种于C6/36细胞内,5-7d后染色,观察蚀斑情况并计数。将测得值与组织培养半数感染量测定结果比较。结果登革病毒甲基纤维素微量蚀斑技术重复性好,比组织培养半数感染量法敏感。结论甲基纤维素徽量蚀斑技术可靠易行,可用于登革病毒滴定。     

Stabilization of Misoprostol with Hydroxypropyl Methylcellulose (HPMC) Against Degradation by Water

The stability of misoprostol oil is significantly improved in a hydroxypropyl methylcellulose (HPMC) dispersion (1:100). In order to assess the effect of water on misoprostol stability, the rate of misoprostol degradation was investigated in the misoprostol/HPMC dispersion at 55°C, along with the water sorption isotherm, under seven different relative humidity (RH) conditions ranging from 0 to 81%. The results indicated that the first-order rate constants of misoprostol degradation increased in a concave-up fashion as the water content of the dispersion increased. Below 30% relative humidity (2% water), the first-order rate constants of misoprostol degradation were found to be minimum. The results of the stability study were interpreted in terms of the changing structure of HPMC as it related to the mobility of water and misoprostol within the HPMC dispersion.     

盐酸二甲双胍缓释片处方筛选及工艺研究

对盐酸二甲双胍缓释片的处方及工艺进行筛选和研究。方法：根据释放度作为判断原则，对缓释骨架材料、填充剂、粘合剂、润滑剂及包衣材料的种类、规格、用量及工艺等进行了考察，并在此基础上采用正交试验1．9(3^4)方案对处方进行筛选。结果：以HPMC K100M及HPMC K15M作为盐酸二甲双胍缓释片的基本骨架材料，微晶纤维素作为填充剂，硬脂酸镁为润滑剂，4％HPMCE5的70％乙醇溶液适量作为粘合剂制成片芯，采用薄膜包衣法，以欧巴代的70％乙醇溶液作为薄膜包衣材料，制得盐酸二甲双胍缓释骨架片。结论：本制剂工艺简单，所用各种辅料均为国产化，成本低，制得盐酸二甲双胍缓释片释放度符合规定。     

醋酸羟丙基甲基纤维素琥珀酸酯的性能表征

 目的合成新型肠溶包衣材料醋酸羟丙基甲基纤维素琥珀酸酯(HPMCAS),并分析其结构特征和性能。方法采用红外光谱、紫外光谱、热重分析和化学分析等方法进行表征,测试HPMCAS在有机溶剂中的溶解情况、黏度、抗张强度和极限伸长率,并与日本的醋酸羟丙基甲基纤维素琥珀酸酯样品AS-LG进行比较。结果HPMCAS中酸性丁二酰基、乙酰基的含量与加入酸酐的量密切相关;二氯甲烷-乙醇等混合溶剂是HPMCAS的良溶剂;HPMCAS低于200℃时对热稳定,高于此温度后快速失重。结论其物化性质与日本样品AS-LG接近。     

Gamma scintigraphic evaluation of the fate of hydroxypropyl methylcellulose capsules in the human gastrointestinal tract

The fate (movement and disintegration) of hard novel hydroxypropyl methylcellulose (HPMC) two-piece capsules in the human gastrointestinal tract was investigated using a gamma scintigraphic imaging method. Two different prolonged-release formulations without an active ingredient were used. The capsules contained different viscosity grades of HPMC powder (HPMC K100 and HPMC K4M). The aim was to determine the main reason why the pharmacokinetic profiles of model drugs change when the diluent was changed to a higher viscosity grade. The results were compared with our previous pharmacokinetic studies with corresponding capsules containing metoclopramide hydrochloride or ibuprofen as a model drug. The first observation was that the HPMC capsules had a tendency to attach to the oesophagus. Therefore, it is recommended that the HPMC capsules as well as gelatine capsules be taken with a sufficient amount of water (150–200 ml) in an upright position and maintaining the upright position for several minutes. The viscosity grade of the HPMC did not affect the transit times of the capsules in the GI tract. The major differences between the two formulations were the complete disintegration times of the capsules and the spreading of the capsules to the large intestine. Most of the HPMC K100-based capsules were completely disintegrated during the 8 h study, whereas the HPMC K4M-based capsules still exhibited plug formations in the large intestine. Also the HPMC K100-based capsules spread better to the ascending colon than the HPMC K4M-based capsules. The faster disintegration of the HPMC K100-based capsules explains the differences in the pharmacokinetic profiles of the model drugs between the HPMC K100- and K4M-based capsules in our previous studies. The main absorption site of the drugs from the capsules studied here is probably the large intestine when taken in a fasting state.