资生汤加减治疗慢性萎缩性胃炎伴肠上皮化生的临床研究

观察资生汤加减治疗慢性萎缩性胃炎伴肠上皮化生的疗效及安全性。将147例符合条件的患者随机分为中药组、西药组和联合组,各49例。分别给予资生汤加减,法莫替丁和资生汤加减联合法莫替丁治疗,疗程均为30 d。观察各组患者治疗前后中医症状、胃黏膜病理积分和幽门螺杆菌转阴率;检测血清胃蛋白酶原I(PGI),胃蛋白酶原Ⅱ(PGⅡ),胃泌素-17(GAS-17)和内皮素-1(ET-1)的变化;比较有效率和安全性指标。结果联合组总有效率高于中药组和西药组(P0.05);联合组和中药组中医症状积分较西药组改善更为明显(P0.05);联合组胃黏膜病理积分,幽门螺杆菌转阴率和血清指标改善优于中药组和西药组(P0.05)。不良反应和心肝肾功能异常发生率比较,中药组(2例,4.8%)联合组(7例,15.2%)西药组(20例,41.3%)(P0.05)。血、尿常规异常发生率比较,中药组(7例,16.7%)联合组(14例,30.4%)西药组(24例,52.2%)(P0.05)。结果表明资生汤加减治疗慢性萎缩性胃炎伴肠上皮化生的总有效率与西药法莫替丁无明显差异,说明其具有有效性,且安全性评价优于法莫替丁;资生汤加减联合法莫替丁治疗慢性萎缩性胃炎伴肠上皮化生具有协同增效的作用,在一定程度上可以逆转胃黏膜的病理改变,疗效优于单用资生汤加减和法莫替丁。     

差热分析法考察辅料对法莫替丁的影响

目的：考察制剂中法莫替丁与辅料之间的相溶情况,为辅料筛选的合理性提供科学依据。方法：通过差热分析法（DTA）分别进行了热图谱扫描及热谱特征的分析。结果：各种辅料之间以及法莫替丁与所有的4种辅料具有很好的可混溶性。结论：制剂中的法莫替丁与辅料间无物理或化学变化,辅料对药物无不利影响。     

Pharmacokinetics of famotidine,a new H2-receptor antagonist,in relation to renal function

Summary The pharmacokinetics of a new, potent H₂-receptor antagonist, famotidine, 20 mg i.v. was studied in 7 subjects with normal renal function and in 24 patients with varying degrees of renal impairment. The volume of distribution at steady state was 1.14 l/kg in normal subjects and was not altered in renal failure. The half-life of elimination was 2.59 h in normal subjects and was unchanged in mild renal failure (creatinine clearance, CL_CR 90–60 ml/min/1.48 m²) but was increased to 4.72 h in moderate renal failure (CL_CR 60–30 ml/min/1.48 m²), and to 12.07 h in severe renal failure (CL_CR below 30 ml/min/1.48 m²). The cumulative urinary excretion and renal clearance of famotidine were correspondingly reduced in patients with impaired kidney function. In normal subjects and in patients with mild to moderate renal failure, about 70% of famotidine was excreted through the kidney, mainly by tubular secretion. In patients with a CL_CR above 60 ml/min/1.48 m² the normal daily dose of famotidine can be employed, but in those with a CL_CR between 60 and 30 ml/min/1.48 m² the dose should be reduced by half, and in patients with a CL_CR below 30 ml/min/1.48 m² a reduction by three quarters of the normal dose is recommended.     

法莫替丁分散片的研制及体外溶出特性

目的 :研制法莫替丁分散片 ,并考察其体外溶出特性。方法 :采用正交设计方法优选出制备的最佳条件。结果 :本品在1min内可完全崩解 ;体外溶出度表明 ,T50=0 56min。结论 :用优选处方制备的法莫替丁分散片比市售片崩解快 ,分散均匀。     

脒基硫脲合成新工艺

以双氰胺直接与硫代硫酸钠于常温下制成脒基硫脲，收率达90％以上，本法具有操作简单，收率高，成本低的优点，是一种经济的适于工业化生产的合成工艺。     

法莫替丁片剂在8个健康人体内的生物等效性评价

目的 :考察法莫替丁在正常人体内的药物动力学过程 ,评价 2种片剂的生物等效性。方法 :采用随机交叉自身对照设计 ,8例志愿受试者单剂量口服法莫替丁片A或B 4 0mg后 ,采用柱切换HPLC法测定血药浓度 ,MCPKP程序计算药物动力学参数 ,方差分析法评价生物等效性。结果 :法莫替丁的体内过程符合血管外一室开放模型 ,法莫替丁A及其对照品B的Tmax,Cmax,T12 k,AUC分别为 2 .0±s 0 .3h ,10 4± 33ng/mL ,2 .16± 0 .18h ,550± 188ng·h/mL和 2 .4± 0 .5h ,93± 2 8ng/mL ,2 .17±0 .10h ,562± 153ng·h/mL。两者间无显著性差异(P >0 .0 5)。结论 :片A与B生物等效 ,片A相对片B的生物利用度为 96%± 15%     

法莫替丁缓释片的制备工艺及其体外释放特性的研究

 目的:制备法莫替丁缓释片剂，并评价其释放特性。方法:用正交试验设计对片剂的处方、工艺进行筛选与优化，制备法莫替丁缓释片剂，浏定其释放特性。结果:以优选的处方、工艺所制备的片剂，体外释药性能良好，符 合Higuchi模型，持续释药达12 h以上。结论:该片剂处方合理，工艺简单，适合于工业化生产，可为消化性清疡病的临床防治提供一个新剂型。     

Comparative study of nizatidine and famotidine for maintenance therapy of erosive esophagitis

BACKGROUND: The therapeutic effect of combined administration of prokinetics and histamine H2 receptor antagonists (H2RA) in gastroesophageal reflux disease is reported to be superior to that of monotherapy with H2RA alone. In addition to its acid-suppressing effect, the H2RA nizatidine also has a prokinetic action by suppressing acetylcholine esterase. The present multicenter, randomized controlled study was performed to investigate whether nizatidine is superior to famotidine, which does not suppress acetylcholine esterase activity, in maintenance therapy for erosive esophagitis. In addition, the question as to whether the grade of erosive esophagitis affects the non-recurrence rate during the maintenance therapy with H2RA was also investigated. METHODS: Seventy-two patients with endoscopically healed erosive esophagitis after 8 weeks of initial treatment with proton pump inhibitors were randomly divided into two groups. Patients in the nizatidine group were treated with 150 mg nizatidine twice a day (b.i.d.), while patients in the famotidine group were treated with 20 mg famotidine b.i.d. for 6 months. At the end of therapy, and at the time when patients complained of symptoms, endoscopic investigations were repeated to find out whether the esophagitis had recurred. RESULTS: Nizatidine produced a significantly higher non-recurrence rate than famotidine (P = 0.049 in intention-to-treat [ITT] analysis). This difference of remission rate between nizatidine and famotidine was observed mainly in grade B esophagitis (P = 0.016 in ITT analysis). CONCLUSION: Nizatidine is a more effective H2RA than famotidine in the maintenance therapy of patients with reflux esophagitis.     

Famotidine Prevents Deep Histologic Lesions Induced by 0.6N HCl in Rat Gastric Mucosa: Role of Parietal Cells

The assessment of the protective actions of H₂-receptor antagonists against gastric mucosal lesions by necrotizing agents relies on the gross observation of the gastric mucosa only. We examined the activity of famotidine against 0.6 N HCl-induced damage and the role of parietal cells by light and transmission electron microscopy. Rats received famotidine 0.3–10 mg/kg intragastrically. Sixty minutes later 0.6 N HCl (1 ml/rat) was given and after an additional 30 min the stomachs were removed. Macroscopically visible lesions were measured. Histologic lesions were scored on the basis of the depth. The ultrastructure of parietal cells in the isthmus–neck region was examined. Pretreatment with famotidine resulted in a slight increase of macroscopically visible gastric lesions in response to HCl. While the extent of total histologic damage was not modified, the antisecretory dose significantly reduced only lesions deep within the mucosa. Famotidine alone determined the dose-dependent occurrence of a distinct parietal cell morphological state, suggestive of inhibition of the secretory system. A causal link between the protective effect on the region where parietal cells are located, the percentage of cells shifting to the inhibited morphological state, and the inhibitory effect on acid secretion is proposed.     

复方法莫替丁咀嚼片治疗酸相关性疾病引起的烧心、反酸等症状的多中心、随机、双盲、阳性药物平行对照临床试验

目的观察复方法莫替丁咀嚼片治疗酸相关性疾病引起的烧心、反酸等症状的疗效和安全性。方法采用多中心、随机、双盲、阳性药物平行对照的试验设计,240例患者按1：l比例随机进入试验组（A组）和对照组（B组）。A组：有症状时,先口服法莫替丁模拟胶囊1粒,后咀嚼复方法莫替丁咀嚼片1片。B组：有症状时,先口服法莫替丁胶囊1粒,后咀嚼复方法莫替丁模拟咀嚼片1片。无症状时,两组均于睡前先服用胶囊,后咀嚼片剂。试验药和对照药一日不超过2片或2粒。疗程7d。治疗前及治疗每天分别对烧心、反酸、上腹痛等症状进行评分,每剂服药后5、10、15、20、30、40、50、60、120min时进行观察。结果227例患者按方案完成研究,A组114例,B组113例。第l天：A组服药10min和15min后烧心症状的即刻缓解率分别为31．63％和4-4．90％,显著高于B组（P分别为0．0067和0．0370）;A组服药后10-60min内各时间点反酸、上腹痛症状的即刻缓解率均显著高于B组（P均〈0．05）;A组服药5min后总体症状的即刻缓解率为17．70％,至60min内各时间点总体症状的即刻缓解率均显著高于B组（P分别〈0．05）。第2—7天各症状的即刻缓解率与第1天类似。A组所有症状完全缓解时间在50min之内,治疗第1天和第2天,完全缓解时间分别为（46．57±27．39）min和（40．95±22．02）min,显著快于B组（P分别为0．0106和0．0062）。本研究发生不良事件7起,均在B组,A组无不良事件发生。结论复方法莫替丁咀嚼片较法莫替丁胶囊更快速缓解酸相关性疾病引起的烧心、反酸、上腹痛等症状。