pH值对替硝唑葡萄糖注射液降解产物的影响

目的：考察pH值对替硝唑葡萄糖注射液降解产物的影响,指导制剂的开发和生产。方法：制备不同pH值注射液样品,采用重氮化偶合比色法测定NO2^-的浓度,用HPLC面积归一法测定有机降解物峰面积百分比。结果：随pH值的升高,NO2^-的浓度和有机降解物峰面积百分比均有不同程度的增加,其中有机降解物增加较为明显。结论：注射剂pH值应控制在3．5～5．0之间。     

灭菌温度、pH值、等渗调节剂对替硝唑注射液降解产物的影响

目的 :考察灭菌温度、pH值、等渗调节剂对替硝唑注射液降解产物的影响 ,指导制剂的开发和生产。 方法 :制备不同灭菌温度、pH值、等渗调节剂的注射液样品 ,采用重氮化偶合比色法测定NO-2 的浓度 ,HPLC面积归一法测定有机降解物峰面积百分比。结果 :随灭菌温度、pH值的升高 ,NO-2 的浓度和有机降解物峰面积百分比均有不同程度的增加 ,其中pH值影响较大 ,有机降解物增加较为明显。结论 :注射剂 pH值应控制在3.5～ 5 .0之间 ,灭菌条件以 110℃ 30min为佳 ,以氯化钠调节等渗是可行的     

pH值对盐酸吡硫醇水溶液稳定的影响

目的考察pH值对盐酸吡硫醇水溶液稳定性的影响.方法用恒温加速试验法,测定不同温度下不同pH值时盐酸吡硫醇降解的速率常数,得到不同pH值时的降解活化能及不同温度下的最稳定pH值.结果在不同温度下,当pH2时,盐酸吡硫醇水溶液相对最稳定;随着pH值升高,水溶液稳定性迅速降低.结论适当调整溶液的pH值可以显著改善盐酸吡硫醇的化学稳定性,为其制剂学研究提供了部分依据.     

pH值对盐酸吡硫醇水溶液稳定性的影响

目的:考察pH值对盐酸吡硫醇水溶液稳定性的影响。方法:用恒温加速试验法,测定不同温度下不同pH值时盐酸吡硫醇降解的速率常数,得到不同pH值时的降解活化能及不同温度下的最稳定pH值。结果:在不同温度下,当pH2时,盐酸吡硫醇水溶液相对最稳定;随着pH值升高,水溶液稳定性迅速降低。结论:适当调整溶液的pH值可以显著改善盐酸吡硫醇的化学稳定性,为其制剂学研究提供了部分依据。     

壳聚糖-巯基醋酸偶合物的制备及结构分析

目的制备一种新型生物粘附材料-壳聚糖-巯基醋酸偶合物,并对其结构进行分析。方法以N-羟基丁二酰亚胺(NHS)作催化剂,采用新的合成工艺制备壳聚糖-巯基醋酸偶合物,并测定了偶合物中巯基的含量,同时对偶合物进行了元素分析和红外光谱测定。结果制备得到了巯基含量为1034μmol.g-1的壳聚糖-巯基醋酸偶合物,阐明了该材料的结构特征。结论新的合成工艺可行,材料的结构可用红外光谱来表征。     

阿魏酸钠注射液的稳定性研究

目的：考察不同pH值及强光、高温等因素对阿魏酸钠注射液稳定性的影响，并对阿魏酸钠注射液进行加速试验考察。方法：将不同pH值的阿魏酸钠注射液在100％：恒温中静置30分钟，观察其降解率随时间变化情况；分别在4500b强光照射及．40℃、60℃高温条件下放置10天，观察阿魏酸钠注射液的各项指标变化情况；在30℃加速试验条件下放置3个月，考察阿魏酸钠注射液的稳定性。结果：药液pH值升高，阿魏酸钠的降解速度加快；强光及高温条件下放置10天，阿魏酸钠注射液的pH值、含量及有关物质均有不同程度的改变；30℃加速试验3个月，其pH值略有上升，含量有较明显改变。结论：阿魏酸钠注射液的稳定性受，pH值影响，且在光照及高温下不稳定。本品应避免光照及高温受热，宜低温贮存。     

河豚毒素处方前初步研究

目的 考察河豚毒素（TTX）在不同溶剂中的溶解性及稳定性，以及温度和pH值对稳定性的影响。方法 配制TTX不同介质的溶液，采用高效液相色谱法（HPLC）测定其在不同温度、不同pH缓冲液中的浓度，分析计算其溶解度及稳定性。结果 TTX在pH值为3.5时溶解度最大，随着pH值增加其溶解度逐渐降低。TTX在强碱条件下降解最为迅速，在70 ℃条件下、0.1 mol/L的氢氧化钠溶液中，20 min即完全降解。稳定性试验结果同样证明TTX在碱性条件下的稳定性最差，在37 ℃、pH值=7.4的磷酸缓冲盐溶液（PBS）中，TTX浓度在1~10 h时开始持续降低，28天降解率为88.07±0.27%。结论 TTX易溶于pH值=3.5的酸性水溶液，几乎不溶于碱性水溶液。其稳定性与温度、介质pH值密切相关，在酸性水溶液中较为稳定，在碱性条件下易降解，温度升高会加速其降解过程。     

血管活性肠肽化学及生物学稳定性研究

目的:考察血管活性肠肽(vasoactive intestinal peptide,VIP)的化学及生物学的稳定性,为VIP的制剂学研究提供依据。方法:考察VIP在不同pH值(2.0,4.0,7.0,9.0,11.0,13.0)、不同离子强度溶液、不同温度以及人工胃液和人工肠液中的稳定性,用HPLC法检测VIP含量变化。结果:VIP的稳定性具有pH依赖性,VIP在酸性及中性条件下稳定,pH≤7时几乎无降解,但VIP在碱性条件下不稳定,pH=13时30min已完全降解;离子强度对其稳定性无影响;VIP在冷冻条件下稳定性良好,在冷藏条件下低浓度存在降解;VIP在人工胃液和人工肠液中降解迅速,0 min即完全降解,无法检测到主药峰。结论:VIP化学及生物学的稳定性差,口服无效。     

HPLC-DAD-ESI-MS~n法研究红花注射液中羟基红花黄色素A和脱水红花黄色素B的稳定性及降解过程(英文)

红花是一种常用中药,红花注射液广泛地应用于临床治疗心脑血管疾病。本研究应用HPLC-DAD-ESI-MSn方法研究红花注射液中两种主要物质,羟基红花黄色素A和脱水红花黄色素B的稳定性及降解过程。考察了光照、温度、pH值对二者稳定性的影响。结果表明,羟基红花黄色素A和脱水红花黄色素B在温度大于60°C,pH≤3.0或>7.0时易发生降解且最终降解产物为对羟基桂皮酸,而光照对其影响不大。本研究应用LC-MS对其降解产物及降解过程进行推导,首次描述了两种物质的降解途径。此外ADP诱导的血小板凝集实验结果显示脱水红花黄色素B降解以后会大大降低红花注射液的抗凝活性。建议红花注射液生产及储存过程中应严格控制温度和pH值。     

知母皂苷BⅡ在模拟人体胃肠道环境及生物样品中的稳定性研究

目的 考察知母皂苷BⅡ在不同生理pH介质和生物样品中的体外稳定性。方法 取知母皂苷BⅡ分别在不同生理pH介质（pH 1.2,6.8,7.4,8.0）的缓冲液、人工胃液、无蛋白酶人工胃液、人工肠液、无蛋白酶人工肠液介质和离体生物介质中进行孵育,利用HPLC测定不同介质中知母皂苷BⅡ的含量变化,考察知母皂苷BⅡ的降解情况及酶稳定性。结果 知母皂苷BⅡ在不同生理pH介质溶液中9 h内未发生明显降解,在离体大鼠大肠和小肠及其内容物中发生明显降解。结论 知母皂苷BⅡ在模拟人体胃肠道环境的溶液中很稳定,不会发生明显降解,在大鼠大肠及其内容物和小肠及其内容物中发生明显降解,不受胃蛋白酶和胰蛋白酶的影响,受肠道菌群作用的影响。     

Studies on the carboxymethyl chitosan-containing liposomes for their stability and controlled release of dapsone.

Stable liposomes containing carboxymethyl chitosan (CMC) were prepared and characterized. CMC was introduced in the phosphatidyl choline (PC) liposomes by different methods; firstly, CMC in a free state in the aqueous phase; secondly as a coat (coupled); and finally as a conjugate of dapsone. The stability of liposomes was assessed by their disintegration in ethanol and surfactants. Both hydrophilic bromothymol blue and lipophilic dapsone were encapsulated in these liposomes and their in vitro release studies were carried out at 37 degrees C using different media, namely, phosphate buffer (pH 7.4), 0.02 N-HCl and 1% mouse plasma. The conjugate of dapsone with CMC present in PC liposomes gave the best results in its stability as compared to other modified liposomes. The release data of dapsone also confirmed the results of the stability studies on liposomes. CMC-dapsone conjugate released the dapsone much slower in all three media than did PCCMC and PCCMC-coat liposomes.     

注射用替加环素的制备、质量控制及稳定性考察

目的:制备注射用替加环素,并建立其质量控制方法及考察其稳定性。方法:筛选制备条件、辅料和中间体溶液的pH值,确定注射用替加环素的制备工艺和处方组成;采用高效液相色谱法测定其含量及有关物质,并对制剂进行稳定性考察(影响因素、加速试验和长期留样试验(24个月))。结果:制备条件以2～8℃为宜,处方中选用乳糖为赋形剂,其与主药用量比为2:1,中间体溶液的pH以7·5～8·5为宜;替加环素进样量线性范围为0·103～10·30μg(r=0·9999,n=7);低、中、高浓度平均回收率为99·9%、100·2%、100·2%,RSD=1·20%、0·50%、0·72%。稳定性考察期内各指标未见明显变化。结论:该制剂处方工艺可行,质量可控,稳定性较好。     

Improvement of warfarin biopharmaceutics by conjugation with poly(ethylene glycol)

One of the most used and useful polymers, poly(ethylene glycol) (PEG) was used as a carrier for warfarin. The drug–polymer conjugate was freely water soluble at room temperature. The hydrolytic stability of the PEG–warfarin was investigated at physiological pH and confirmed the stability of the conjugate. In vivo release studies demonstrated a good release of parent drug, without the initial high plasma level of warfarin.     

肿瘤趋向性N-(2-羟丙基)甲基丙烯酰胺聚合物-米托蒽醌接合物研究肿瘤趋向性N-(2-羟丙基)甲基丙烯酰胺聚合物-米托蒽醌接合物研究

目的制备N-(2-羟丙基)甲基丙烯酰胺(HPMA)聚合物-米托蒽醌(DHAQ)接合物以提高DHAQ在实体瘤中的分布。方法采用DHAQ与四肽间隔基连接,再与HPMA进行自由基沉淀聚合反应的方法,合成目标接合物;考察了接合物在不同介质中的稳定性及荷瘤小鼠体内的分布情况。结果合成的接合物经UV,HPLC和FPLC鉴定为目标化合物。其总DHAQ含量为132.4 mg·g^-1接合物,游离DHAQ含量为3.5 mg·mg^-1接合物。摩尔质量19 000 g·mol^-1,分子量分布1.4。在不同pH磷酸盐缓冲液及血浆中较稳定,在肿瘤中的释药明显加快。与原药相比,接合物在荷瘤小鼠体内的分布明显不同。肿瘤中AUC为游离药物3倍;血液循环时间延长;在心脏中的分布明显减少。表明接合物具有一定的肿瘤趋向性,并能降低原药对心脏的毒性。结论将具有仲氨基的DHAQ连接于HPMA聚合物,能提高DHAQ在肿瘤中的分布,为实体瘤靶向高分子给药系统的研究提供新的思路。     

Folate-decorated maleilated pullulan–doxorubicin conjugate for active tumor-targeted drug delivery

A novel folate-decorated maleilated pullulan–doxorubicin conjugate (abbreviated as FA–MP–DOX) for active tumor targeting was set up. The structure of this conjugate was confirmed by ¹H NMR analysis. Furthermore, the conjugation efficiency, drug release property and stability of the conjugate were determined. The cellular uptake and cytotoxicity were assessed by using ovarian carcinoma A2780 cells as in vitro cell model. In vitro DOX release from FA–MP–DOX conjugate occurred at a faster rate at acidic pH compared to neutral pH (7.4). After 30 h of incubation at pH 2.5, 5.0 and 7.4 the released free DOX was about 68.71%, 50.08% and 26%, respectively. Based on the IC₅₀ values, the conjugate was found more effective with ovarian carcinoma A2780 cells than the parent drug after 48 h culture. These results suggested that FA–MP–DOX conjugate could be a promising doxorubicin carrier for its targeted and intracellular delivery.     

三维有序大孔壳聚糖/尼莫地平固体分散体的研究

目的制备孔径为470nm的三雏有序大孔壳聚糖／尼莫地平的固体分散体,研究其释药特点、稳定性和药动学。方法利用溶剂蒸发法制备固体分散体,通过药物释放试验考察固体分散体在模拟胃肠液介质中的释放行为;通过含量测定、X-射线衍射和溶出试验检查固体分散体的稳定性;大鼠分别给予自制固体分散体和市售片粉末,测定血药浓度。结果固体分散体在pH6.8的介质中的溶出度明显比pH1.2和pH4.5介质中高,在梯度pH介质中的释药曲线类似阶梯型;结晶度和溶出度在考察时间内基本无变化;自制固体分散体的AUC0.12h是市售制剂的1.91倍,具有长效作用。结论自制固体分散体稳定性良好,能够提高尼莫地平的大鼠口服生物利用度。     

Poly(HEMA-Zidovudine) conjugate: A macromolecular pro-drug for improvement in the biopharmaceutical properties of the drug

A macromolecular pro-drug of a known anti-viral agent Zidovudine (AZT) was synthesized and evaluated as a sustained drug delivery system. The pro-drug was synthesized by coupling the drug to 2-hydroxyethyl methacrylate (HEMA) through a succinic spacer to get a monomeric drug conjugate which was polymerized to obtain the polymeric pro-drug. The pr0-drug was subjected for in-vitro drug release study in buffers of pH 1.2 and 7.4. The hydrolytic stability of the pro-drug to pepsin was assessed in simulated gastric fluid (SGF, pH 1.2) and to α-chymotrypsin in simulated intestinal fluid (SIF, pH 7.4). The results showed that the drug release from the polymeric backbone takes place in a sustained manner over a period of 24?h, and the amount of drug released was comparatively higher at pH 7.4. Plasmatic hydrolysis studies of succinylzidovudine showed nearly complete release of AZT. At all pH conditions in the presence and absence of α-chymotrypsin, AZT was released preferentially in comparison with the succinyl derivative. The in-vivo release studies in rabbits after oral administration of AZT conjugate demonstrated a sustained release of parent drug over a period of 24?h. The pro-drug provided a significant increase in the area under the plasma concentration time curve as compared to free drug and extended the plasma half-life from 1.06?h to 8.08?h. This study suggested that, after oral administration, the drug–polymer conjugate can release AZT for prolonged periods, thus improving the pharmacokinetics of AZT and decreasing the fluctuation in plasma drug levels that can lead to toxicity.     

Determination of MAG-camptothecin, a new polymer-bound camptothecin derivative, and free camptothecin in dog plasma by HPLC with fluorimetric detection

A high throughput. selective and sensitive high-performance liquid chromatographic (HPLC) method for the determination of a water-soluble polymer-bound Camptothecin conjugate (MAG-CPT) and Camptothecin (CPT) in dog plasma has been developed and validated. The method involved the analysis of free and total CPT (free + polymer-bound). Free CPT (intact lactone plus carboxylate) was extracted from acidified plasma using Oasis SPE material in 96-well plates. For the assay of the total CPT, plasma proteins were first precipitated with methanol in a 96-well plate containing a 10-microm melt blown polypropylene membrane. The methanolic supernatant was separated and collected into a second 96-well plate by simply applying vacuum to the plate. After hydrolysis at pH 9.8 for 18 h and re-acidification, samples were injected directly from the collection plate onto the HPLC system. MAG-CPT concentration was then calculated by subtraction of free from total CPT. The LLOQs of the method were 1.17 ng/ml for free CPT and 103.10 ng/ml (as CPT equivalent) for MAG-CPT using 0.1 and 0.05 ml of plasma, respectively. Linearity, precision, accuracy and recovery of the method were evaluated. The stability of MAG-CPT in plasma alone and after its stabilisation was carefully evaluated. No interference from blank dog, mouse and human plasma was observed. The suitability of the method for in vivo samples was assessed by the analysis of samples obtained from dogs that had received a single and 5-day repeated dose of MAG-CPT.     

纳米硫凝胶的制备及质量控制

目的制备纳米硫凝胶,并建立其质量控制标准。方法液相法合成纳米硫,以卡波姆940为主要基质制备纳米硫凝胶,采用pH检测、含量测定、稳定性考察等方法控制凝胶质量,并进行皮肤刺激性试验。结果合成的纳米硫粒径为50～80 nm。纳米硫凝胶在室温下均匀细腻,流动性较好,pH为6.5,其含量和稳定性等均符合质量控制标准。结论纳米硫凝胶制备工艺可行,性质稳定,质量可控。     

雷公藤甲素及其氨基葡萄糖结合物的表观溶解度、表观油水分配系数和解离常数的测定

目的 测定雷公藤甲素及其氨基糖结合物的表观溶解度、表观油水分配系数和解离常数(pKTa).方法 采用平衡溶解度法、摇瓶法测定雷公藤甲素及其氨基糖结合物的表观溶解度和油水分配系数;采用分光光度指示剂法测定雷公藤甲素-氨基糖结合物的解离常数.结果 雷公藤甲素的表观溶解度随pH的增加而增加,其表观油水分配系数随pH的增加而降低,但变化并不显著.雷公藤甲素-氨基葡萄糖结合物的表观油水分布系数随pH的增加而增加,在纯水中的表观溶解度为1.9325±0.1373 g,pKT =5.938 ±0.191.结论 雷公藤甲素是一个难溶性的亲脂性化合物,而雷公藤甲素-氨基葡萄糖结合物是一个弱碱性的亲水性化合物.