丁苯酞治疗脑缺血的研究现状

脑缺血是一种常见的中枢神经系统疾病,预后差。丁苯酞具有确切治疗脑缺血的作用,通过保护神经细胞、保护线粒体、抗氧化应激和抗炎等作用治疗脑缺血,与常规溶栓治疗比较具有优势,但其水溶性差,生物利用度不高,成为丁苯酞新剂型研发的关键问题,临床常用的丁苯酞类药物剂型主要有注射液、软胶囊和片剂等;丁苯酞通常联合依达拉奉、阿替普酶、血栓通、阿司匹林等协同增效发挥治疗作用;丁苯酞环糊精包合物、微球、胶束和微胞新型制剂有望成为未来丁苯酞治疗脑缺血的最佳给药形式。     

丁苯酞-磺丁基-β-环糊精包合物的制备与表征

目的 制备丁苯酞-磺丁基-β-环糊精包合物,并考察其结构和性能。方法 采用冷冻干燥法制备包合物,用紫外分光光度法测定其包合率、含量、溶解度、溶出度。通过薄层色谱法、紫外光谱法、红外光谱法、差示扫描量热-热重联用法,验证包合物结构的形成。通过相溶解度法,确定最佳包合比例。通过溶出试验考察形成包合物后丁苯酞溶出速率的变化。结果 丁苯酞与磺丁基-β-环糊精可形成摩尔比为1∶1的包合物,包合率为(56.70±1.5)%,平均含量为(5.02±1.6)%。结论 制备丁苯酞-磺丁基-β-环糊精包合物的方法简单易行,并且可以有效提高丁苯酞在水中的溶解性和溶出速度。     

观察丁苯酞联合胞磷胆碱钠治疗脑卒中后认知功能障碍的临床效果

目的:研究脑卒中后认知功能障碍使用丁苯酞联合胞磷胆碱钠的临床治疗效果。方法:选取2019年5月—2020年3月在本院治疗的200例脑卒中后认知功能障碍患者为研究对象,使用随机法分为观察组和对照组,每组100例。对照组使用丁苯酞进行治疗,观察组在对照组基础上口服胞磷胆碱钠,对比两组治疗的效果以及认知功能恢复时间、住院时间、住院花费。结果:观察组治疗效果明显高于对照组,认知功能恢复时间、住院时间、住院花费两组数据有明显差异(P<0.05)。结论:对于脑卒中后认知功能障碍,应该使用丁苯酞联合胞磷胆碱钠进行治疗,这样能够加快恢复速度,减少复发的可能性。     

胞磷胆碱联合丁苯酞软胶囊治疗脑梗死后血管性痴呆的效果及对心理状态的影响

目的 探讨胞磷胆碱联合丁苯酞软胶囊治疗脑梗死后血管性痴呆(VD)临床疗效及对患者相关血清指标、心理状态的影响.方法 回顾性分析2018年1月—2019年12月收治的脑梗死后VD患者96例,根据治疗方案分为观察组和对照组,各48例.2组均给予常规治疗,对照组在常规治疗基础上口服胞磷胆碱钠片,观察组在对照组基础上口服丁苯酞...     

脑血管病治疗药物丁苯酞注射液的药理与临床研究评价

丁苯酞是我国原创的抗脑缺血新化学实体药物,属国家I类新药,具有保护线粒体和改善微循环的独特作用。丁苯酞软胶囊剂目前在临床用于急性缺血性脑卒中的治疗。丁苯酞注射液的开发弥补了丁苯酞软胶囊剂在治疗中尚存在的一些不足,如吞咽困难患者服药不便及口服生物利用度不理想。现对其药理作用、药动学、药物经济学以及对急性缺血性脑卒中的疗效和安全性进行综述。     

丁苯酞对心源性栓塞脑梗死的疗效观察

目的本文研究丁苯酞治疗心源性栓塞脑梗死的疗效。方法 80例心源性栓塞的患者随机分为两组,治疗组予丁苯酞、改善循环、华法林抗凝治疗,对照组予改善循环、华法林抗凝。于基线时及治疗后12 d,行NIHSS、Barthel指数测定,并进行比较。结果治疗后丁苯酞组和对照组NIHSS均有下降,丁苯酞组下降更为明显(P<0.05),丁苯酞组和对照组Barthel指数均有上升,但丁苯酞组上升更为明显(P<0.05)。结论丁苯酞可以减轻心源性栓塞脑梗死患者的神经功能缺损程度及生活活动功能。     

2010年我国十大重磅新药盘点

1丁苯酞氯化钠注射液制造商:石药集团恩必普药业有限公司入选理由:丁苯酞软胶囊是我国历史上第三个自主开发的国家一类新药,也是国际上首个作用于急性缺血性脑卒中多个病理环     

丁苯酞对慢性应激大鼠海马组织氧化应激及炎症因子的影响

目的探讨丁苯酞对由应激引起的海马组织氧化应激及炎症因子的影响及其可能的作用机制。方法SD大鼠随机分为4组:对照组、丁苯酞组、模型组、抑郁+丁苯酞组。模型组和抑郁+丁苯酞组给予慢性应激造模,丁苯酞组单独给予20 mg/(kg·d)的丁苯酞,对照组给予相同体积的玉米油。7周后,对大鼠的行为学进行考察,并观察海马组织IL-6、TNF-α、IL~(-1)β的表达及SOD、MDA的变化。结果丁苯酞改善了应激对大鼠行为学的改变,同时也抑制了抑郁模型大鼠海马组织IL-6、TNF-α、IL~(-1)β的表达,缓解了氧化应激。结论本研究首次在抑郁摸型大鼠中直接证明了丁苯酞有潜在的抗抑郁作用,且其机制可能与其抗氧化及免疫调节作用有关。     

聚氯乙烯输液器对左旋丁苯酞的吸附作用考察

目的:考察左旋丁苯酞在聚氯乙烯(PVC)输液器中的吸附情况。方法:用0.9%氯化钠注射液与左旋丁苯酞注射液混合,制备成低、高浓度的左旋丁苯酞/氯化钠注射液,模拟临床静脉滴注,流经PVC输液器,在120min内不同时间段收集流出的样品,用高效液相色谱串联质谱(LC-MS/MS)法测定左旋丁苯酞浓度,并分别与流经输液器前(0min)的结果进行比较。结果:低、高浓度左旋丁苯酞/氯化钠注射液流经输液器前、后浓度有显著性差异(P<0.05)。结论:PVC输液器对左旋丁苯酞有吸附作用,临床应用时应考虑配备合适的输液器。     

丁苯酞的药理作用与临床评价

目的：评价丁苯酞药理作用及临床作用。方法：收集和查找文献资料，从药理作用、药动学、国内外的临床研究、药物相互作用、药物不良反应5个方面全面评价丁苯酞。结果：详细地评价了丁苯酞的作用机制及临床应用。结论：丁苯酞是国家及一类新药，是我国目前治疗缺血性脑血管病（脑梗死等）的一剂良药。     

Mechanism of the action of tenside on permeation through lipid membranes

The permeability of lipid-collodium membranes is altered by the effect of cationic and anionic tensids. Then ionic and nonionic substances may permeate unselectively. This alteration is irreversible. Three ways of transport across membranes exists in presence of tensids: permeation by solubility into the lipid, transport into water on ionized groups of tensids and with water into micells of tensids, which permeate the membranes.     

丁苯酞治疗一氧化碳迟发性脑病荟萃分析

目的:系统性评价丁苯酞治疗一氧化碳中毒性脑病的疗效.方法:在万方数据-数字化期刊群、中国期刊全文数据库(中国知网)、维普科技期刊数据库、PubMed、EMBase、ClinicalKey数据库中,检索2009年1月至2020年8月的相关研究,探索丁苯酞预防及治疗一氧化碳迟发性脑病的疗效.采用RevMan 5.3软件对各...     

Study on solubility improvement of lidocaine by ternary solid dispersion

In the present study, we aimed to probe the possibility of using mixed poloxamers as carriers to prepare ternary solid dispersion (SD) that facilitated solubility and dissolution rate of the poorly water soluble drug and compare with binary SD with single poloxamer. Lidocaine (LIC) was selected as a model drug, and poloxamer 188 (P188) and poloxamer 407 (P407) were utilized as single and mixed carriers. Depending on DSC and the dissolution testing, the appropriate ratio of SD prepared by melting method was optimized. Ternary and binary SD was characterized by DSC, XRD, SEM and FTIR. In vitro dissolution study, phase solubility study and saturated solubility study were performed to clarify solubilization from apparent phenomena and inherent reason. Moreover, stability study under different relative humidity (RH) was investigated. Physical characterizations of binary and ternary SD exhibited the formation of eutectic mixture and the presence of molecular interaction. Compared with the pure LIC, the dissolution rate and solubility of LIC in binary and ternary SDs were enhanced. The phase solubility study revealed an AL-type curve. Furthermore, the stability test indicated that ternary and binary SD was stable. The results of this study demonstrated that SD with mixed poloxamers could improve dissolution rate and solubility of poorly water-soluble drug.     

丁苯酞下调血清脂蛋白相关磷脂酶A2改善急性大动脉#br# 粥样硬化型脑梗死患者预后的临床观察#br#

目的　探讨丁苯酞能否通过调节急性大动脉粥样硬化型（LAA）脑梗死患者血清脂蛋白相关磷脂酶A2（Lp-PLA2）、颈动脉内膜中层厚度（IMT）而改善患者预后。方法　选择急性LAA脑梗死患者60例,随机分为丁苯酞组及对照组,每组30例。丁苯酞组予静脉滴注丁苯酞注射液（100 mL/次,2次/日,连续14 d）,序贯口服丁苯酞软胶囊（0.2 g/次,3次/日,连续11.5个月）,对照组静脉滴注生理盐水（100 mL/次,2次/日,连续14 d）。所有患者均于治疗前及治疗12个月后检测血清Lp-PLA2水平;行颈部血管超声检测IMT并采用美国国立卫生研究院卒中量表（NIHSS）评估患者神经功能缺损情况。结果　2组患者治疗后的Lp-PLA2水平比治疗前均有所下降,但丁苯酞组Lp-PLA2水平下降较对照组更为明显（P＜0.01）。治疗12个月后,丁苯酞组患者IMT值低于对照组（P＜0.05）。2组患者治疗后NIHSS评分均明显下降,但丁苯酞组下降更为显著（P＜0.01）。结论　丁苯酞治疗可以降低血清Lp-PLA2水平,进而缓解动脉粥样硬化进展,改善急性LAA脑梗死患者的预后。     

红霉素自乳化制剂处方研究

目的研究红霉素自乳化制剂(EM-SMEDDS),探求其最佳处方配比。方法测定红霉素在各种油相、乳化剂和组乳化剂中的溶解度,选择溶解度高者备用;采用滴定法绘制了油-乳化剂/助乳化剂-水体系伪三元相图,确定处方组成比例;考察加料顺序对EM-SMEDDS平均粒径和粒径分布的影响。采用均匀设计考察制备温度、混合乳化剂各组成比例、载药量与油相所占比例对平均粒径、粒径分布的影响,采用平均粒径、粒径分布、分散时间为评价指标,筛选出EM-SMEDDS的优化处方。结果处方中油相十四酸异丙酯(IPM)、聚氧乙烯蓖麻油(Cremophor EL)与聚乙二醇-8-甘油辛酸/癸酸酯(Labrasol)组成的混合乳化剂可以获得较好的乳化效果。制备方法为首先制备混合乳化剂,其次将混合乳化剂与油相混匀,最后加入药物,所得EM-SMEDDS乳滴平均粒径小于50 nm。结论红霉素自乳化制剂的最佳处方比例,以IPM为油相,油相与混合乳化剂质量比为3∶7,混合乳化剂中LAS与Cremophor E质量比为7∶13,载药量为10%。     

Genistein-loaded poloxamer 403/407 mixed micelles: preparation and pharmacokinetic study in rats

In the present study, we aimed to prepare poloxamer 403/407 mixed micelles in order to improve the solubility and oral bioavailability of genistein.Genistein was incorporated in the mixed poloxamer micelles by thin-film hydration method, and its physicochemical properties, including particle size, zeta potential, entrapment efficiency and drug loading, were investigated.In vitro release of genistein from the mixed micelles was monitored by dialysis method, and pharmacokinetic study of genistein loaded mixed micelles was carried out in rats. We found that the particle size and zeta potential of mixed micelles were (20.31±0.43) nm and (–8.94±0.35) mV, with encapsulation efficiency 90.59%±0.67% and drug loading 7.74%±0.05%. Solubility of genistein in mixed micelles reached 3.80 mg/mL, which was about 130 times higher than that in water.Genistein-loaded mixed micelles showed sustained release characteristics in vitro with no burst release phenomenon, but it was faster than suspension.The AUC_0–t andAUC_0–∞ of mixed micelles were 196.74% and 204.62% greater than that of genisein suspension, respectively.Consequently,poloxamer 403/407 mixed micelles significantly improved the solubility and oral bioavailability of genistein, which could be used as an effective drug delivery system for oral administration of poorly soluble drugs.     

Enhanced oral bioavailability of flurbiprofen by combined use of micelle solution and inclusion compound

The main purpose of this study was to evaluate the effect of a mixed drug solution containing a surfactant and β-cyclodextrin (β-CD) on the solubility and bioavailability of a poorly watersoluble drug, flurbiprofen. Solubility, dissolution and in vivo pharmacokinetics of flurbiprofen in the presence of surfactant, β-CD or mixture of surfactant and β-CD were investigated. Among the surfactants tested, Tween 80 produced the highest improvement in the aqueous solubility of flurbiprofen. The solubility of flurbiprofen increased linearly as a function of β-CD, resulting in B8 type that suggested a formation of inclusion complex in a molar ratio of 1:1. The solubility of flurbiprofen increased further when Tween 80 was included in addition to β-CD, suggesting that a micelle formation in the presence of Tween 80 was the likely reason for additional increase. Furthermore, the data suggested that Tween 80 did not interfere with the inclusion interaction between flurbiprofen and β-CD. The solubility of flurbiprofen was the highest in the mixed system containing 1.3 mM β-CD and 0.3% w/v Tween 80, and the maximum solubility of 160 μg/mL was achieved. Consistent with the enhanced solubility, the plasma exposure (both AUC and Cmax) of flurbiprofen when dosed as the mixed system was significantly higher (as much as 2 to 3-fold) than that without surfactant or β-CD, with surfactant alone, or with β-CD alone. Therefore, the mixed system consists of surfactant and β-CD could be used as an effective oral dosage form to improve bioavailability of poorly water soluble drugs such as flurbiprofen.     

Solubility of drugs in aqueous solutions. Part 3: multicomponent mixed solvent

The results obtained previously by Ruckenstein and Shulgin [Int. J. Pharm. 258 (2003a) 193; Int. J. Pharm. 260 (2003b) 283] via the fluctuation theory of solutions regarding the solubility of drugs in binary aqueous mixed solvents were extended in the present paper to multicomponent aqueous solvents. The multicomponent mixed solvent was considered to behave as an ideal solution and the solubility of the drug was assumed small enough to satisfy the infinite dilution approximation.An expression derived for the activity coefficient of a solid solute in a multicomponent solvent was used to obtain an equation for the solubility of a drug in terms of its solubilities in two subsystems of the multicomponent solvent and their molar volumes. Ultimately the solubility can be expressed in terms of those in binary or even in individual solvents and their molar volumes.The method was applied to the solubility of tioconazole and 19-Nor-1alpha,25-dihydrovitamin D(2) in several ternary and in a quaternary aqueous mixed solvents. The predicted solubilities were compared with experimental data and good agreement was found.     

The effects of pH and mixed solvent systems on the solubility of oxytetracycline

The solubility of oxytetracycline (OTC) in aqueous and mixed solvent systems was studied. The effects of pH and cosolvent composition on the solubility and apparent dissociation constants (pKa') of OTC were determined by a solubility method. The pKa' values of OTC in each mixed solvent system were estimated and used to generate expressions for predicting drug solubility in each cosolvent as a function of pH. Cosolvent systems of PEG 400, propylene glycol, glycerin, and 2-pyrrolidone were studied in the pH range of 2.5-9. Solubility results showed increased solubility with increased cosolvent concentration, especially in 2-pyrrolidone solvent systems. These results also showed that cosolvents enhanced drug solubility through either their effects on polarity of the solvent medium or complex formation with OTC. Aqueous and mixed solvent systems at lower pH values resulted in higher OTC solubilization because the drug existed primarily in its cationic form. A mass balance equation including all ionic species of OTC allowed for estimation of the intrinsic solubilities and pKa' values in each solvent system. pKa' values and intrinsic solubility of the OTC zwitterion increased with increasing cosolvent content. These parameters allowed prediction of drug solubility within the pH range and cosolvent concentrations used in this study.     

丁苯酞对卵白蛋白所致支气管哮喘豚鼠的影响

目的　探讨丁苯酞对卵白蛋白所致支气管哮喘豚鼠模型的影响。方法　采用卵白蛋白经致敏与激发两步来复制支气管哮喘豚鼠模型,通过药物干预,观测丁苯酞对哮喘豚鼠的行为学、肺功能、BALF中炎性细胞、肺组织病理学及IgE的影响。结果　30、60、120mg?kg_-1丁苯酞能降低哮喘豚鼠的哮喘行为学评分、肺组织湿干重比值、BALF中炎性细胞及血清T-IgE水平,改善肺功能,缓解肺组织病理学变化(P＜0.05, 0.01)。结论　丁苯酞具有缓解肺部炎症而治疗支气管哮喘的作用。