How to use nitrates

Nitrates are old drugs, available in many formulations, that are effective in relieving symptoms in various CAD syndromes as well as congestive heart failure. Nitrate tolerance is the major problem limiting nitrate efficacy and use by physicians. Currently, an intermittent dosing strategy is the only practical way to limit the development of tolerance or attenuation of nitrate actions.     

硝酸舍他康唑栓治疗外阴阴道假丝酵母菌病28例

［摘要］目的评价硝酸舍他康唑栓治疗外阴阴道假丝酵母菌病的疗效及安全性。方法采用随机双盲对照试验。治疗组及对照组各30例,分别外用硝酸舍他康唑栓300 mg和克霉唑栓500 mg,用药1或2次。停药后（7±1） d及28～35 d时进行观察。结果治疗组28例、对照组30例纳入分析,治疗组和对照组停药后（7±1） d临床有效率分别为89.29%,86.67%（P＞0.05）;用药结束后28～35 d时的临床有效率分别为81.48%,66.67%（P＞0.05）;均未发生与药物相关的不良反应。结论硝酸舍他康唑栓治疗外阴阴道假丝酵母菌病有效,安全。     

壳聚糖包覆的硝酸毛果芸香碱眼用亚微乳的研究

本文设计了一种壳聚糖包覆的硝酸毛果芸香碱眼用亚微乳(chitosan-coated pilocarpine nitrate submicroemulsion,CS-PN/SE),旨在开发一种新型的具有黏膜黏附性的亚微乳眼部给药系统,以延长药物在眼表滞留时间,促进药物的眼部吸收。以中长链甘油三酯(medium chain triglycerides,MCT)为油相,Tween 80为主乳化剂,采用高速剪切工艺制备硝酸毛果芸香碱亚微乳(pilocarpine nitrate submicro emulsion,PN/SE),进一步采用孵育法制备CS-PN/SE,并利用星点设计-效应面优化法进行处方优化。对其粒径、zeta电位、包封率和微观形态进行表征,以新西兰白兔为动物模型,评价了CS-PN/SE在兔眼表滞留特性以及缩瞳作用。眼表滞留特性评价结果显示,与硝酸毛果芸香碱溶液剂组(pilocarpine nitrate solution,PNs)和PN/SE组相比,CS-PN/SE组在眼表的清除率下降,KCS-PN/SE为(0.006 4±0.000 3)min-1,平均驻留时间(mean residence tim...     

RP-HPLC法测定硝酸毛果芸香碱滴眼液的有关物质

目的:建立反相高效液相色谱法测定硝酸毛果芸香碱滴眼液的有关物质。方法:采用色谱柱Shimadzu RP,C18柱(150 mm×4.6 mm,5μm);流动相为甲醇-含0.002 mol/L磷酸二氢铵和0.001 8 mol/L四丁基氢氧化铵的水溶液(30∶70),进行变流速梯度洗脱;检测波长为220 nm。结果:硝酸毛果芸香碱主成分峰与杂质峰的分离度均符合要求,硝酸毛果芸香碱的检出限为4 ng。结论:该方法简便、准确、灵敏度高,适用于硝酸毛果芸香碱滴眼液的有关物质分析。     

硝酸咪康唑乳膏处方筛选及工艺

根据基质的HLB值,设计适合工业化生产的O/W型硝酸咪康唑乳膏处方,采用离心、耐热、耐寒等试验对处方进行筛选,又经中试放大,最终确定处方6为生产工艺处方。产品符合《中国药典》2010版二部有关规定。     

肾蒂淋巴管结扎术和RPIS治疗术后复发性重症乳糜尿的疗效

目的:探讨肾蒂淋巴管结扎术和硝酸银肾孟灌注硬化(RPIS)治疗术后复发性重症乳糜尿的疗效。方法:46例术后复发性重症乳糜尿患者分为两组,采用2%硝酸银肾孟硬化灌注14例(RPIS组)和肾蒂淋巴管结扎术32例,比较两组的成功率、复发率及并发症的发生率。结果:肾蒂淋巴管结扎术疗效优于RPIS,两组成功率和2年内复发率差异有统计学意义(P<0.01),并发症发生率差异有统计学意义(P<0.05)。结论:开放性肾蒂淋巴管结扎术是治疗术后复发性重症乳糜尿首选。     

Evaluation of solid lipid microparticles produced by spray congealing for topical application of econazole nitrate

Objectives The aims of this study were to evaluate the suitability of the spray congealing technique to produce solid lipid microparticles (SLMs) for topical administration and to study the skin permeation of a drug from SLMs compared with solid lipid nanoparticles (SLNs). Methods Econazole nitrate was used as model drug and Precirol ATO 5 as the lipidic carrier. SLMs and SLNs were both prepared at 5: 1, 10: 1 and 12.5: 1 lipid: drug weight ratios and characterised in terms of particle size, morphology, encapsulation efficiency and chemical analysis of the particle surface. SLMs and SLNs were also incorporated into HPMC K 100M hydrogels for ex‐vivo drug permeation tests using porcine epidermis. Key findings SLMs had particle sizes of 18–45 μm, while SLNs showed a mean diameter of 130–270 nm. The encapsulation efficiency was 80–100%. Permeation profiles of econazole nitrate were influenced by both particle size (significant difference until 9 h) and the amount of lipid. Conclusions The results confirm the usefulness of SLNs as carriers for topical administration and suggest the potential of SLMs for the delivery of drugs to the skin.     

Nitroflurbiprofen, a nitric oxide-releasing cyclooxygenase inhibitor, improves cirrhotic portal hypertension in rats

BACKGROUND & AIMS: We studied whether administration of nitroflurbiprofen (HCT-1026), a cyclooxygenase inhibitor with nitric oxide (NO)-donating properties, modulates the increased intrahepatic vascular tone in portal hypertensive cirrhotic rats. METHODS: In vivo hemodynamic measurements (n = 8/condition) and evaluation of the increased intrahepatic resistance by in situ perfusion (n = 5/condition) were performed in rats with thioacetamide-induced cirrhosis that received either nitroflurbiprofen (45 mg/kg), flurbiprofen (30 mg/kg, equimolar concentration to nitroflurbiprofen), or vehicle by intraperitoneal injection 24 hours and 1 hour prior to the measurements. Additionally, we evaluated the effect of acute administration of both drugs (250 micromol/L) on the intrahepatic vascular tone in the in situ perfused cirrhotic rat liver (endothelial dysfunction and hyperresponsiveness to methoxamine) and on hepatic stellate cell contraction in vitro. Typical systemic adverse effects of nonsteroidal anti-inflammatory drugs, such as gastrointestinal ulceration, renal insufficiency, and hepatotoxicity, were actively explored. RESULTS: In vivo, nitroflurbiprofen and flurbiprofen equally decreased portal pressure (8 +/- 0.8 and 8.4 +/- 0.1 mm Hg, respectively, vs 11.8 +/- 0.6 mm Hg) and reduced the total intrahepatic vascular resistance. Systemic hypotension was not aggravated in the different treatment groups (P = .291). In the perfused cirrhotic liver, both drugs improved endothelial dysfunction and hyperresponsiveness. This was associated with a decreased hepatic thromboxane A(2)-production and an increased intrahepatic nitrate/nitrite level. In vitro, nitroflurbiprofen, more than flurbiprofen, decreased hepatic stellate cells contraction. Flurbiprofen-treated rats showed severe gastrointestinal ulcerations (bleeding in 3/8 rats) and nefrotoxicity, which was not observed in nitroflurbiprofen-treated cirrhotic rats. CONCLUSIONS: Treatment with nitroflurbiprofen, an NO-releasing cyclooxygenase inhibitor, improves portal hypertension without major adverse effects in thioacetamide-induced cirrhotic rats by attenuating intrahepatic vascular resistance, endothelial dysfunction, and hepatic hyperreactivity to vasoconstrictors.     

氟康唑联合咪康唑栓治疗念珠菌性阴道炎临床分析

目的：观察氟康唑联合咪康唑栓治疗念珠菌性阴道炎（假丝酵母菌病）的临床疗效。方法：100例念珠菌性阴道炎患者随机分为治疗组和对照组,每组50例。治疗组患者口服氟康唑及阴道应用咪康唑栓,对照组患者单纯口服氟康唑;观察两组患者的临床疗效及真菌清除率。结果：治疗组和对照组的治疗有效率分别为94.00%和86.00%、真菌清除率分别为98%和92%,两组治疗有效率和真菌清除率比较差异具有显著性（P〈0.05）。结论：氟康唑联合咪康唑栓治疗念珠菌性阴道炎疗效好、安全性高、耐受性好。     

Yields of β-hydroxynitrates,dihydroxynitrates, and trihydroxynitrates formed from OH radical-initiated reactions of 2-methyl-1-alkenes

Yields of β-hydroxynitrates, dihydroxynitrates, and trihydroxynitrates, in particles formed from OH radical-initiated reactions of C₉-C₁₅ 2-methyl-1-alkenes in the presence of NO_x were measured by using a thermal desorption particle beam mass spectrometer coupled to a high-performance liquid chromatograph with a UV-visible (UV-vis) detector. Yields of β-hydroxynitrates and dihydroxynitrates increased with carbon number primarily due to enhanced gas-to-particle partitioning before reaching plateaus at ≈C₁₄-C₁₅, where the compounds were essentially entirely in the particle phase. Plateau yields of β-hydroxynitrates, dihydroxynitrates, and trihydroxynitrates were 0.183 ± 0.005, 0.045 ± 0.005, and 0.034 ± 0.005, and, after normalization for OH radical addition to the C = C double bond, were 0.225 ± 0.007, 0.055 ± 0.006, and 0.042 ± 0.006. The fractions of 1-hydroxy and 2-hydroxy β-hydroxynitrate isomers were 0.90/0.10. Yields measured here and in our previous study of reactions of linear internal alkenes and linear 1-alkenes indicate that, for these alkene classes, the relative branching ratios for forming tertiary, secondary, and primary β-hydroxyalkyl radicals by OH radical addition to the C = C double bond are 4.3/1.9/1.0, and the branching ratios for forming β-hydroxynitrates from reactions of tertiary, secondary, and primary β-hydroxyperoxy radicals with NO are 0.25, 0.15, and 0.12. The effects of H₂O vapor and NH₃ on yields were also explored.