Improvement in Wound Healing by Epidermal Growth Factor (EGF) Ointment. I. Effect of Nafamostat,Gabexate, or Gelatin on Stabilization and Efficacy of EGF

The healing effect of human epidermal growth factor (hEGF) on open wounds was studied in rats. No improvement in wound healing was found by topical application of EGF alone to open wound sites. We found an ointment containing EGF and a protease inhibitor, nafamostat mesilate or gabexate mesilate, or gelatin accelerated the healing rate of open wounds. Significant increases in the dry weight of the wound site granulation tissue, uronic acid (as an index of acid mucopolysaccharide) and hydroxyproline (as an index of collagen) were observed by treatment with EGF ointment containing nafamostat compared with the controls. The effects of the protease inhibitor on wound healing were dose dependent. Nafamostat was more efficient than gabexate or gelatin on wound healing. The degradation of ¹²⁵I-EGF in wound tissue homogenate was significantly decreased in the presence of a protease inhibitor, such as nafamostat or gabexate, or gelatin. These findings indicate that the stabilization of EGF at the wound site is an important factor in permitting the expression of its healing effects and suggest that the ointment containing EGF and a stabilizing agent would be a suitable dosage form for acceleration of wound repair.     

国产加贝酯耐受性试验研究

健康成年人自愿受试者１０例，随机分为３组，分别住院静脉注射加贝酯２００ｍｇ／ｄ、３００ｍｇ／ｄ、４００ｍｇ／ｄ。结果除高浓度（３００ｍｇ加贝酯溶于５％Ｇ－Ｓ５００ｍｌ）组，在滴速６０滴／ｍｉｎ时，１例出现局部发红，疼痛及２例于停药后１周出现轻度表浅静脉炎外，未发现过敏，血压下降，ＥＣＧ改变，肝、肾功能损伤等其它不良反应，说明国产加贝酯注射剂临床应用安全，成人每ｄ可用１００～４００ｍｇ，以１００～２００ｍｇ溶于５％葡萄糖液５００ｍｌ静滴为宜，但１０例中有６例（６０％）因药液外渗，引起局部刺激症状，故应尽量避免高浓度，快速静滴，并防止液体外溢皮下。     

Our Distal Aortic Perfusion System in Descending Thoracic and Thoracoabdominal Aortic Aneurysm Repairs

Abstract: We have used heparin-bonded partial cardio-pulmonary bypass to support distal aortic circulation during aortic cross-clamping. However, there were no cardiotomy reservoirs with fully reliable thromboresistance. To resolve this problem, a short-acting anticoagulant (nafamostat mesilate) was added into a cardiotomy reservoir. The present study was designed to evaluate the efficacy of our distal perfusion system. From May 1995 through the end of May 1996, 27 patients underwent descending thoracic and thoracoabdominal aortic aneurysm repairs with this adjunct, 4 being excluded from the experiment. Twenty patients who had undergone conventional partial cardiopulmonary bypass were defined as the control group. There were no significant differences between the 2 groups in the morbidity, mortality, gas transfer, or transfusion requirements despite the fact that more complicated surgical procedures (shown by a two-fold increase in the prevalence of reoperation) were required in the group that had received the current distal perfusion adjunct. the heparin-bonded group. In conclusion, our perfusion system is very effective for descending thoracic and thoracoabdominal aortic aneurysm repairs.     

A protease inhibitor attenuates gastric erosions and microcirculatory disturbance in the early period after thermal injury in rats

The effects of camostat mesilate, a synthetic serine protease inhibitor on gastric microcirculation and active oxygen species generated by leucocytes from the gastric and jugular veins in the early period after thermal injury were assessed. Male Wistar rats were anaesthetized and a 30% full skin-thickness dorsal burn was inflicted. Camostat mesilate (100 mg/kg) was dissolved in distilled water and administered orally to rats 40 min before thermal injury (the camostat group). The control animals (the vehicle group) were administered distilled water orally. Rolling leucocytes as well as Monastral blue B deposits in venules were observed using in vivo microscopy. Active oxygen species were measured by chemiluminescence. Camostat mesilate decreased the total length of gastric erosion, venular deposits of Monastral blue B, and rolling of leucocytes in venules, and relatively increased luminol-dependent chemiluminescence activity generated by zymosan-stimulated leucocytes 15 min after thermal injury. These results suggest that serine proteases are involved in the formation of gastric erosions and gastric microcirculatory disturbance in the early period after thermal injury.     

帕珠沙星合成中的Hofmann重排反应

将帕珠沙星的合成关键中间体(3S)—9—氟—10—(1—氨甲酰基环丙基)—3—甲基—7—氧代—2，3—二氢—7H—吡啶[1，2，3—de]—1，4—苯并嚼嗪—6—羧酸溶于甲醇钠／甲醇溶液中，于—40℃加溴进行Hofmann重排得到帕珠沙星。收率69％。     

消旋甲磺酸帕珠沙星的合成

目的：合成消旋甲磺酸帕珠沙星。方法：以市售合成氧氟沙星的中间体9，10-二氟-3-甲基-7-氧-2，3-二氢-7H-吡啶[1，2，3-d，e][1，4]苯并噁嗪-6-羧酸乙酯为起始原料，经过缩合反应、水解脱羧、相转移缩-环合、腈基水解和Hofmann降解得目标化合物。结果和结论：经^1H-NMR，MS和旋光活性测定，证明所得到的产物为消旋甲磺酸帕珠沙星。     

甲磺酸帕珠沙星对映异构体的拆分方法及其应用

目的:建立一种用手性流动相拆分并测定甲磺酸帕珠沙星对映异构体的方法。方法:使用HYPERSIL BDS C18柱(4.6mm×250 mm,5μm),流动相为含有3 mmol·L-1硫酸铜、6 mmol·L-1 D-苯丙氨酸的溶液-甲醇(78:22),流速为1 mL·min-1,在250nm检测。结果:R-(+)和S-(-)甲磺酸帕珠沙星的保留时间分别为8.1和9.7 min,分离度为2.2。结论:方法的重现性好,操作简单,可用于药品质量控制。     

高效液相色谱手性流动相法拆分帕珠沙星对映体

目的:对帕珠沙星对映体进行手性分离。方法:采用高效液相色谱手性流动相法,用ODS柱(4.6 mm×150 mm,10 μm),检测波长320 nm,流动相为甲醇-手性溶液(25:75,pH 3.0),流速1 mL·min-1。结果:右旋体最低检测限1.5 ng,重现 性好。结论:该法可用于帕珠沙星光学纯度检查。     

甲磺酸帕珠沙星氯化钠注射液治疗急性细菌性感染多中心临床研究

目的 评价甲磺酸帕珠沙星氯化钠注射液治疗临床常见细菌性感染的安全性和有效性。方法 用随机单盲平行对照多中心同步试验法。甲磺酸帕珠沙星氯化钠注射液(试验组)每次500mg，盐酸左氧氟沙星氯化钠注射液(对照组)每次400mg，均每日1次，静脉滴注，疗程均7～14天。共入选病例251例，其中：试验组122例，临床疗效评价病例115例，安全性评价例数122例；对照组129例，临床疗效评价病例122例，安全性评价例数129例。结果 2组临床总有效率分别为96．5％和98．4％；细菌清除率分别为98．9％和98．0％；药物不良反应发生率分别为11．5％和9．35％。结论 甲磺酸帕珠沙星氯化钠注射液治疗临床常见细菌性感染安全、有效。