一水合羟苯磺酸钙的制备及结构分析

目的　制备一水合羟苯磺酸钙并进行结构鉴定。方法　在不加溶剂的情况下,直接用浓硫酸磺化对苯二酚再与CaCO3成盐,在一定条件下脱水制得了产物一水合羟苯磺酸钙,产物结构经IR, ¹H -NMR, ¹³C-NMR,MS,TGA,DSC及粉末X 衍射确证。结果　精制品在1. 33kPa, 80℃下干燥4h,得本品一水合物。TGA,DSC及粉末X 射线衍射表明,本品一水合物与二水合物谱图完全不同。结论　简化了反应操作,提高了反应收率,减少了环境污染。     

羟苯磺酸钙的药理作用及临床应用

羟苯磺酸钙化学名称2.5-二羟基苯磺酸钙-水合物.2001年在中国上市以来,在临床上的应用不断拓宽,现将羟苯磺酸钙的药理作用及临床应用介绍如下. 1药理作用 1.1羟苯磺酸钙具有抑制血管活性物质(组胺、5-羟色胺、缓激肽、透明质酸酶、前列腺素)对微血管引起的高通透作用,减少血管内膜损伤,改善基底膜胶原的生物合成,也使毛细血管壁渗透性得到改善,提高红细胞的柔韧性,使血液黏滞度降低,淋巴回流得到改善,从而减低微血管壁病理性高通透性.     

西洛他唑-对羟基苯甲酸共晶制备新工艺

目的制备西洛他唑-对羟基苯甲酸共晶(物质的量之比1∶1)。方法采用混悬液结晶法,以西洛他唑和对羟基苯甲酸为原料,硝基甲烷或乙腈为溶剂,室温条件下快速搅拌1 h,抽滤,干燥,即得目标产物。结果与结论应用X-射线粉末衍射(XRPD)、热重分析(TGA)、差示扫描量热分析(DSC)、红外光谱分析(IR)、单晶X-射线衍射(SCXRD)对本实验合成的西洛他唑-对羟基苯甲酸共晶物进行了表征。     

头孢替唑钠的结晶性研究

目的探讨头孢替唑钠的结晶特性。方法利用单晶X射线衍射、粉末X射线衍射、DSC和TGA等理化分析方法,分析不同条件得到的头孢替唑钠晶体。结果头孢替唑钠晶体为头孢替唑钠一水合物,至少有I型和II型两种不同的晶型;水分子在不同的头孢替唑钠晶格中有不同的结合状态。结论不同结晶条件下得到的头孢替唑钠一水合物的晶格结构略有差异,并影响晶体的热稳定性。I型晶体较II型晶体对热稳定。     

RP-HPLC法测定羟苯磺酸钙的有关物质

目的：对试行标准中羟苯磺酸钙反相高效液相色谱法有关物质进行讨论,并利用LC—Ms对其光降解产物进行初步分析。方法：色谱条件：色谱柱：SHIMADZU VP—ODS C18（4．6mm×150mm,5μm）;流动相：0．05mol·L^-1磷酸二氢铵-乙腈（98：2）;流速：1．0mL·min^-1;进样量为10斗L;检测波长为300nm;柱温：30℃。质谱条件：负离子电离（ESI-）方式,毛细管电压：2．5kv;椎孔电压：20V;源温：105℃;脱溶剂温度：400℃;脱溶剂气流速：400L·h^-1;二级扫描时碰撞能量：20eV（降解产物）,10ev和20eV（羟苯磺酸钙）。结果：此条件下,羟苯磺酸钙中已知杂质氢醌和其他各降解产物与主成分的分离度和检测灵敏度均可满足试验要求,羟苯磺酸钙和已知杂质氢醌的检测限均为5ng。采用LC—MS／MS初步推断了羟苯磺酸钙光降解产物的化学结构。结论：本方法简便、快捷,可用于羟苯磺酸钙中有关物质的检查。     

氟康唑的多晶型及转化研究

目的对氟康唑的多晶型及其相互转化进行分析研究。方法采用红外光谱仪(IR)、近红外光谱仪(NIR)、拉曼光谱仪(RM)、X-射线粉末衍射仪(XRD)、差示扫描量热仪(DSC)和热重分析仪(TGA)对氟康唑的晶型进行了研究,并考察了温度、湿度、溶剂和研磨对其晶型转化的影响。结果 X-射线粉末衍射法作为晶型判定方法,10个厂家18批氟康唑的晶型有Ⅱ型、Ⅲ型和一水合物晶型;在不同的温度、湿度和结晶溶剂中Ⅱ型和一水合物晶型可相互转化,在氯仿中结晶和高温熔融可得到I型结晶。结论氟康唑不同晶型谱学特征显著,可对氟康唑晶型进行质量控制,各晶型间可以相互转化并确定了转化条件。     

米力农的差示扫描量热分析与热重分析

目的:研究心血管药物米力农晶体的吸附水、结晶水、熔点、晶型变化等理化性质.方法:用差示扫描量热分析(DSC)和热重分析(TGA)法研究其热变化,采用X-射线粉末衍射实验研究其晶型变化.结果与结论:米力农样品不含结晶水.试样从201.04℃开始失重,脱去吡啶环,并有对应的吸热峰产生;在293.06℃发生微小吸热反应,可能是样品中的少量亚稳态晶体组分发生熔化反应,或是发生了微小的晶型转变;最后,到达314.66℃(熔点)开始熔化,随即样品发生完全分解反应.     

羟苯磺酸钙引起发热

1例63岁男性糖尿病与高血压患者长期服用降糖药和降血压药.患者因视网膜出血服用羟苯磺酸钙0.5 g,1次/d.8 d后,患者出现发热(38.8℃)和疲乏.停用羟苯磺酸钙和对症治疗后,患者恢复正常.再次给予羟苯磺酸钙再次出现发热,共反复发生4次.羟苯磺酸钙使用期间,其他药物未停用.     

胆维丁原料中共晶与游离态维生素D3和胆固醇含量的定量分析

通过差示扫描量热分析(DSC)、拉曼光谱及粉末X射线衍射(PXRD)发现胆维丁原料中存在共晶现象,并对其进行表征.采用粉末X-射线衍射(PXRD)建立了共晶与游离态维生素D3和胆固醇含量的定量分析方法.     

羟苯磺酸钙联合丹红注射液治疗非增殖型糖尿病视网膜病变(DR)的临床疗效及安全性

目的:分析羟苯磺酸钙与丹红注射液联合治疗非增殖型糖尿病视网膜病变(DR)的临床疗效及安全性.方法:应用数字随机方法,从本院眼科2014年11月~2015年11月收治的非增殖型DR患者中随机选择120例展开分组研究,一组为A组,另一组为B组,每组60例.A组采取羟苯磺酸钙进行治疗,B组实施羟苯磺酸钙与丹红注射液联合治疗,比较两组疗效和治疗安全性.结果:两组在用药安全性方面比较无显著差异,P>0.05,但B组临床疗效优于A组,P<0.05,差异有统计学意义.结论:羟苯磺酸钙与丹红注射液联合治疗非增殖型DR疗效显著,用药安全性高,应用价值高.     

羟苯磺酸钙联合海昆肾喜胶囊治疗糖尿病肾病疗效观察

目的探讨采用羟苯磺酸钙联合海昆肾喜胶囊治疗糖尿病肾病的临床疗效。方法选择2007年2月～2010年6月在笔者所在医院收治的糖尿病肾病患者80例,给予羟苯磺酸钙联合海昆肾喜胶囊治疗,就临床结果进行回顾性分析。结果联合治疗组的治疗总有效率(80.00%)高于其余两组,三者差异有统计学意义(P<0.05),3组患者治疗前Scr和BUN等指标差异无统计学意义(P>0.05)。治疗结束后,比较UAE和Scr水平,联合治疗组较单用海昆肾喜组或单用羟苯磺酸钙组下降幅度更显著(P<0.05)。联合治疗组患者出现1例腹泻;其余两组患者未发生其他并发症。结论两种药物联合运用可优势互补,延缓肾脏损伤过程,延缓肾功能下降速度。     

羟苯磺酸钙和缬沙坦联合治疗对老年早期糖尿病肾病患者ET和CysC的影响

目的观察缬沙坦和羟苯磺酸钙联合治疗对老年早期糖尿病肾病(DN)患者内皮素(ET)和血清胱抑素C(CysC)的影响。方法选择老年2型糖尿病早期肾病患者76例均分为4组,每组19例。对照组:给予常规治疗;羟苯磺酸钙(安多明)组:安多明0.25 g,bid,po;缬沙坦(代文)组:代文80 mg,qd,po;羟苯磺酸钙+缬沙坦组(联合组):安多明0.25 g,bid,po+代文80 mg,qd,po。观察治疗前、治疗1个月及6个月后各组患者ET和胱抑素C的水平变化。结果羟苯磺酸钙组:治疗后Fib水平较治疗前明显下降(P<0.05);缬沙坦组:治疗后血压水平明显下降(P<0.01);联合组:治疗后血压及Fib水平均明显下降(P<0.01及P<0.05)。治疗1个月后,三组治疗组ET和胱抑素C水平较治疗前明显下降(P<0.05),三组治疗组与对照组比较,上述指标差异有统计学意义(P<0.05);治疗6个月后,三组治疗组ET和胱抑素C水平较治疗前水平进一步下降(P<0.01),与对照组比较,差异有统计学意义(P<0.01)。结论羟苯磺酸钙和缬沙坦联合治疗,可以降低老年早期糖尿病肾病患者ET和血清胱抑素C的水平。联合用药的效果明显优于药物单用的疗效。     

Antioxidant properties of calcium dobesilate in ischemic/reperfused diabetic rat retina.

Calcium dobesilate possesses antioxidant properties and protects against capillary permeability by reactive oxygen species in the rat peritoneal cavity, but whether a similar action can take place in the diabetic rat retina is unknown. We investigated the oral treatment of diabetic rats with calcium dobesilate on the prevention of free radical-mediated retinal injury induced by ischemia/reperfusion (90 min ischemia followed by 3 min and/or 24 h of reperfusion). Streptozotocin-induced diabetic rats were orally treated with 50 and 100 mg/kg of calcium dobesilate for 10 days (n=12 in each group). In the first series of studies, calcium dobesilate was found to significantly reduce the maldistribution of ion content in diabetic ischemic/reperfused rat retina. Thus, in diabetic rats treated with 100 mg/kg/day calcium dobesilate, ischemia/reperfusion provoked: (i) 27.5% increase in retinal Na(+) content compared to 51.8% in the vehicle-treated group (P<0.05), and (ii) 59.6% increase in retinal Ca(2+) content compared to 107.1% in vehicle-treated animals (P<0.05). In the second series of studies, calcium dobesilate was found to significantly protect diabetic rat retina against inhibition of Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)-ATPase activities by ischemia/reperfusion (54% and 41% reduction, respectively, with 100 mg/kg of calcium dobesilate) and also against changes in retinal ATP, reduced glutathione (GSH), and oxidized glutathione (GSSG) contents. In the third series of experiments, rats treated with 100 mg/kg of calcium dobesilate reduced the hydroxyl radical signal intensity to 41% (measured by electron paramagnetic resonance), induced by ischemia/reperfusion in diabetic rat retina. Finally, 100 mg/kg calcium dobesilate significantly reduced retinal edema (measured by the thickness of the inner plexiform layer) in diabetic rats. In conclusion, oral treatment with calcium dobesilate significantly protected diabetic rat retina against oxidative stress induced by ischemia/reperfusion. Whether the antioxidant properties of calcium dobesilate explain, at least in part, its beneficial therapeutic effects in diabetic retinopathy deserves further investigation.     

芪明颗粒与羟苯磺酸钙胶囊治疗糖尿病网膜病变的成本-效用分析

目的：对芪明颗粒和羟苯磺酸钙胶囊治疗糖尿病视网膜病变进行成本-效用分析。方法：采用Markov状态转换模型．采用文献法获得转换概率数据,模拟芪明颗粒和羟苯磺酸钙胶囊治疗的糖尿病视网膜病变患者5年的成本和效用。结果：第一年芪明颗粒组总人均医疗成本为2631．44元．比羟苯磺酸钙胶囊组的3243．24元低611．80元,芪明颗粒组人均生命质量得分为0．8218,比羟苯磺酸钙胶囊组的0．8153高出0．0065。芪明颗粒组成本较低,效用较高,明显具有经济性。第2—5年的成本一效用分析结果也支持这一结论。结论：芪明颗粒与羟苯磺酸钙胶囊相比．治疗单纯型糖尿病视网膜病变具有较好成本一效用。     

Platelet aggregation inhibition with calcium dobesilate

In 52 patients with pathologically increased platelet aggregation the effect of a 4-day oral treatment of 500 mg, 1000 mg and 1500 mg calcium dobesilate (Dexium 500) on spontaneous platelet aggregation was assessed using PAT III of Breddin. In comparison to placebo 1500 mg calcium dobesilate reduced platelet aggregation significantly, 1000 mg and 500 mg calcium dobesilate, however, didn't influence platelet aggregation.     

Chronic venous insufficiency of the lower limbs: suitability of transcutaneous blood gas monitoring as an endpoint to evaluate the outcome of pharmacological treatment with calcium dobesilate

This pilot clinical trial was designed to further investigate the effects of calcium dobesilate in the treatment of chronic venous insufficiency (CVI) by means of a novel endpoint, transcutaneous oxygen pressure (TcPO2), and to evaluate the suitability of this endpoint for future research. Patients with mild to moderate CVI without active ulcers were randomized to receive calcium dobesilate 1000 mg/day, 2000 mg/day or placebo for 12 weeks. The primary efficacy endpoint was TcPO2 in the distal third of the internal side of the leg. Secondary endpoints included assessment of venous reflux and clinical symptoms. Patients in the dobesilate 1000 mg/day and placebo groups showed a mild increase in TcPO2 (adjusted mean change 2.67 mmHg and 1.56 mmHg, respectively), while those treated with 2000 mg/day of the active drug showed a decrease (adjusted mean change -0.53 mmHg). Conversely, clinical symptoms and venous reflux improved in all groups, especially with dobesilate, but differences with placebo were not significant. Treatment was very well tolerated. Although the absence of significant differences prevented confirmation of sensitivity, a trend favoring calcium dobesilate in clinical and hemodynamic parameters was observed. This improvement was not reflected by TcPO2.     

Pharmacokinetics of calcium dobesilate in beagle dogs after repeated administration

Many pharmacological findings suggest that repeated intravenous administration of calcium dobesilate improves myocardial lymphatic drainage, accelerates removal of degradation products and other toxic substances by increasing the number of functioning lymphatics and thus limits infarct size after experimental coronary artery occlusion. The aim of the present study was to investigate the relationship between the blood levels of calcium dobesilate and the pharmacological effect described above using the same dosage schedule. During the first six hours after intravenous administrations, at one hour interval, of three doses each of 100 mg/kg of calcium dobesilate, the average plasma level ranged from 414 micrograms/ml to 95 micrograms/ml with a plateau between the second and fourth hour. During this period, which is the most crucial for the ischemic myocardium, the effect of calcium dobesilate attained its optimum as evidenced by a statistically significant increase in the number of lymphatics visualized by lymphangiography and the reduction of infarct size measured by planimetry, by weight or by tomography. The plasma levels before the 18th hour were still higher than 10 micrograms/ml but no measurable calcium dobesilate was detected in the plasma at the 20th hour which indicates total elimination of the drug from the blood and thus precluding any risk of accumulation. The present results confirm that the doses of calcium dobesilate used in the pharmacological studies correspond to an adequate blood level.     

羟苯磺酸钙对糖尿病大鼠肾脏表达E-选择素的影响

目的探讨羟苯磺酸钙对肾小球E-选择素(E-selectin)表达的影响和对糖尿病肾病大鼠的保护作用。方法22只大鼠行左肾切除术后,取6只作为正常对照组,另外16只单次腹腔注射1%链脲佐菌素制备糖尿病大鼠模型。其中12只大鼠造模成功,并将其随机分成糖尿病对照组和羟苯磺酸钙治疗组各6只,羟苯磺酸钙治疗组灌胃给予羟苯磺酸钙100mg.kg-1.d-1,正常对照组和糖尿病对照组每天灌胃给予相同体积的纯化水。用免疫组化和Westernblot法检测12周后E-selectin表达的改变。结果与正常对照组比较,糖尿病对照组和羟苯磺酸钙治疗组E-selectin表达增加(P<0.01);而羟苯磺酸钙治疗组E-selectin表达显著低于糖尿病对照组(P<0.01)。结论羟苯磺酸钙可抑制糖尿病大鼠E-selectin的表达,延缓糖尿病肾病的发生、发展。     

两种药物治疗糖尿病视网膜病变的成本-效果分析

目的 :研究进口与国产羟苯磺酸钙治疗糖尿病视网膜病变的成本 -效果。方法 :采用疗效观察和成本 -效果分析方法对进口与国产羟苯磺酸钙进行经济学评价。结果与结论 :进口与国产羟基磺酸钙治疗糖尿病视网膜病变的效果相近 ,但国产品是更经济的选择。