高效液相色谱法测定多烯磷脂酰胆碱软胶囊中磷脂酰胆碱和溶血磷脂酰胆碱的含量

目的建立HPLC法测定多烯磷脂酰胆碱软胶囊中磷脂酰胆碱和溶血磷脂酰胆碱的含量以及有关物质方法。方法采用蒸发光散射检测器SEDEX55,MERCK的Li Chrospher 100 Diol-5色谱柱(125mm×4.0 mm,5μm);流动相A为正己烷-异丙醇-冰醋酸-三乙胺(814∶170∶15∶0.8),流动相B为异丙醇-超纯水-冰醋酸-三乙胺(844∶140∶15∶0.8),梯度洗脱。结果磷脂酰胆碱在0.912~2.736mg·mL~(-1),溶血磷脂酰胆碱在0.072~0.216 mg·mL~(-1)内与峰面积线性关系良好(R~2均为0.999)。磷脂酰胆碱的平均回收率为101.2%,RSD为1.3%;溶血磷脂酰胆碱的平均回收率为100.5%,RSD为1.9%。溶血磷脂酰胆碱的检测限为0.57μg。结论本检测方法专属性强,结果可靠,专属性强,重复性良好,可用于多烯磷脂酰胆碱软胶囊的质量评价。     

多烯磷脂酰胆碱注射液致剧烈头痛1例

1临床资料 患者，男，50岁，主因2008年2月末无诱因出现右耳听力下降，伴右耳疼痛，无耳鸣，颅脑MRI示颞骨肿物，于2008年3月25日入我院，诊断：B细胞淋巴瘤。该患者于2008年4月1日给予多烯磷脂酰胆碱注射液（成都天台山制药，批号071204）465mg＋5％葡萄糖注射液250mL以60滴·min^-1静脉输入。静脉输入多烯磷脂酰胆碱10min后患者诉头痛剧烈、     

HPLC-ELSD多烯磷脂酰胆碱质量标准研究

目的 建立多烯磷脂酰胆碱胶囊中多烯磷脂酰胆碱含量及溶血磷脂酰胆碱的限量检查.方法 丙二醇键合硅胶色谱柱(5μM,4.6 ×250 mm,Hanbon),柱温:55℃,流动相:A为正己烷-异丙醇-冰醋酸-三乙胺(814∶170∶15∶1.4),B为异丙醇-水-冰醋酸-三乙胺(844∶140∶15∶1.4),梯度洗脱,流速:1ml·min-1,蒸发光散射检测器物化温度50℃,蒸发温度90℃,载气流速2.0ml·min-1.结果 多烯磷脂酰胆碱在0.1～1 mg·mL-1范围内呈良好线性,r=0.9999;平均回收率为100.1%,RSD为1.7%;中间精密度RSD为1.4%;三批样品中多烯磷脂酰胆碱的标示量%分别为100.9%,99.84%,100.2%,溶血磷脂酰胆碱的含量占多烯磷脂酰胆碱表示量的3.9%,4.4%,3.9%.本样品中磷脂酰乙醇胺未检出.结论 所建立的方法可准确的测定胶囊中多烯磷脂酰胆碱的含量及溶血磷脂酰胆碱的限量检查,可用于该制剂的质量控制.     

多烯磷脂酰胆碱治疗慢性乙型肝炎临床观察

慢性乙型肝炎是由乙型肝炎病毒感染引起的以肝细胞损害为主的一种炎症反应和纤维化同时存在的全身性疾病,而纤维化是慢性乙肝难治及发展为肝硬化的重要环节,防治肝损害和减缓纤维化的进展对慢性乙肝的治疗和预后有重要意义,2009年1月～2012年12月间应用多烯磷脂酰胆碱治疗慢性乙型肝炎60例,现报告如下。     

多烯磷脂酰胆碱治疗酒精性肝病疗效观察

目的:观察多烯磷脂酰胆碱治疗酒精性肝病疗效及安全性。方法:79例均有5年以上饮酒史,每日饮酒量80～120g,随机分为治疗组和对照组,对照组应用甘利欣、维生素等治疗,治疗组在此基础上加用多烯磷脂酰胆碱465mg/日,疗程均为4周。结果:多烯磷脂酰胆碱对酒精性肝病肝功能复常显示良好治疗效果,临床症状明显好转,总有效率明显高于对照组。结论:多烯磷脂酰胆碱能有效治疗酒精性肝病,安全性好。     

HPLC测定多烯磷脂酰胆碱胶囊中的溶血磷脂酰胆碱

目的 采用HPLC-ELSD测定多烯磷脂酰胆碱胶囊中溶血磷脂酰胆碱的含量.方法 色谱柱为硅胶(250 mm×4.6mm,5 μm),流动相A为正己烷-异丙醇(3:4),流动相B为正己烷-异丙醇-水(3:4:0.75),梯度洗脱,流速为1.5 mL·min~(-1),空气流速为3.0 L·min~(-1),蒸发管温度为100 ℃.结果 溶血磷脂酰胆碱0.1～1.5 mg·mL~(-1)与峰面积呈良好的线性关系(r=0.9997),平均回收率为99.90%.结论 所用方法简便、专属性好,可用于多烯磷脂酰胆碱胶囊中溶血磷脂酰胆碱的含量检测.     

果糖冻干粉针及葡萄糖注射液与多烯磷脂酰胆碱注射液配伍后的微粒观察

目的 观察果糖冻干粉针、葡萄糖注射液分别与多烯磷脂酰胆碱注射液配伍前、后不溶性微粒的变化和配伍情况,为临床选择不同溶媒与多烯磷脂酰胆碱注射液配伍提供参考.方法 用pH计测定各溶液的pH,并按照"不溶性微粒检查法",采用ZWF-J6激光注射液微粒分析仪检查微粒的变化.结果 各溶液配伍后pH没有太大的变化,且溶液澄清,但多烯磷脂酰胆碱注射液与果糖冻干粉针配伍较多烯磷脂酰胆碱注射液与葡萄糖注射液配伍后的微粒数明显增加配伍后[直径≥10 mm的5%果糖注射液微粒数为(111.4±0.13)粒,10%果糖注射液为(154.90±2.31)粒,葡萄糖注射液为(5.40±0.20)粒,10%葡萄糖注射液为(25.00±10.00)粒;直径≥25 μm的微粒数分别为(2.00±0.35)粒、(2.20±0.00)、(0.10±0.01)、(0.20±0.04)粒]但未超过药典规定.结论 果糖冻干粉针可以与多烯磷脂酰胆碱注射液配伍,但要考虑对不溶性微粒数的控制.

Abstract：

Objective To observe the change of insoluble particles of fructose for injection and glucose solution after compatibility of polyene phosphatidylcholine injection. Methods The pH meter was used to determine the pH of each solution and the particles through usage of ZWF-J6 laser analyzer of particles of injection was checked according to "Insoluble Particles Test". Results There was little change of pH after compatibility of various solutions and each solution was clear,but more particles were found in fructose solution than those in glucose solution after compatibility of polyene phosphatidylcholine injection and none of them exceeded the criterion according to pharmacopoeia. Conclusion The compatibility of fructose for injection and polyene phosphatidylcholine injection is feasible,but the control of insoluble particles should be considered.     

多烯磷脂酰胆碱注射液致寒战并高热1例

患者,男,62岁,2个月前因进食肥腻食物后,无明显诱因出现右上腹痛于2011年8月20日入院,持续性钝痛,放射到腰背痛,严重时伴恶心、呕吐,经止酸、止痛等治疗好转,但症状反复,近日来上腹痛加重,伴恶心,无呕吐、咳嗽、心悸、胸痛、呼     

多烯磷脂酰胆碱辅助治疗小儿急性白血病临床观察

急性白血病占小儿恶性肿瘤的首位,严重危害儿童健康.目前,小儿急性白血病的治疗主要采取以化疗为主的综合治疗,而化疗药物则会加重肝脏及肾脏损害,化疗导致的肝肾功能异常使化疗间歇期延长,增加患者的经济负担,同时影响了患儿的长期生存,多年来我们在常规化疗同时加用阿拓莫兰保护肝脏,但无肾脏保护作用,我科在白血病患儿化疗同时应用多烯磷脂酰胆碱注射液预防和治疗药物性肝损害和肾损害,同时观察多烯磷脂酰胆碱对白血病细胞有无促进代谢及改善作用.     

多烯磷脂酰胆碱治疗慢性乙型肝炎63例效果观察

目的观察多烯磷脂酰胆碱治疗慢性乙型肝炎的疗效及安全性。方法观察多烯磷脂酰胆碱治疗慢性乙型肝炎63例治疗前、治疗1个月、停药后2周患者的症状、体征及常规生化指标的变化。结果多烯磷脂酰胆碱治疗1个月后,丙氨酸转氨酶、天冬氨酸转氨酶、γ谷氨酰胺转肽酶、总胆红素的水平均明显改善(P<0.05),停药后2周时仍较治疗1个月时有显着改善(P<0.05)。结论经临床研究结果表明,使用多烯磷脂酰胆碱能够对肝组织炎症进行抑制,对肝细胞进行了保护,延迟了肝纤维化的出现,对于治疗慢性乙型肝炎能取得较为满意的疗效,未见明显不良反应。     

柠檬苦素固体脂质纳米粒冻干粉的制备及质量评价

目的:制备柠檬苦素固体脂质纳米粒(LM-SLN)及冻干粉,并考察其体外释药性能。方法:采用薄膜超声法制备LM-SLN,以载药量及包封率为指标,借助均匀设计联合Box-Behnken法优化处方;采用Nano ZSE+MPT2粒度检测仪观测形态与粒径;透析法研究冻干粉体外释药行为。结果:处方工艺为柠檬苦素-硬脂酸-卵磷脂-4.5%泊洛沙姆188(10∶30∶35∶10),超声功率300 W,超声时间4 min;以5%甘露醇为冻干保护剂,于-20 ℃预冻12 h,转至-40 ℃以下冷冻干燥22 h。LM-SLN冻干粉呈类球形,结构均匀,包封率为79.38%、载药量为10.88%,平均粒径(182.4±0.2)nm,多分散系数(PDI)为0.290±0.013,Zeta电位为(-14.5±0.1)mV;原药12 h累积释放率为89.31%,LM-SLN冻干粉48 h为85.21%,48 h后释放趋于平缓。结论:LM-SLN处方工艺简单且重复性好,体外释放结果表明,LM-SLN冻干粉具有一定缓释作用。     

5-氟尿嘧啶壳聚糖纳米粒冻干粉的制备

目的 为研究5-氟尿嘧啶壳聚糖纳米粒冻干粉的制备工艺,提高5-氟尿嘧啶壳聚糖纳米粒的稳定性。方法 首先制备5-氟尿嘧啶壳聚糖纳米粒,并以外观和再分散性为指标,进行单因素考察并利用正交实验优化工艺。结果 5-氟尿嘧啶壳聚糖纳米粒冻干粉的最佳制备工艺为预冻时间24 h、冻干保护剂为甘露醇、用量为80 mg、浓度为10%。冻干前后包封率差异无统计学意义（P>0.05）,冻干后的粒径和冻干前相比有一定增大。结论 5-氟尿嘧啶壳聚糖纳米粒冻干粉有望成为新剂型。     

醋酸泼尼松龙脂质纳米球的制备

目的:制备高分散、高包封率的醋酸泼尼松龙脂质纳米球(PA-LN).方法:采用高速匀质法,制备脂质纳米球.探讨其制备工艺条件及影响因素.结果:制得的醋酸泼尼松龙脂质纳米球粒径在28.6 nm左右,粒度分布15～45 m;包封率大于70%.结论:本方法制备工艺简单,稳定性好,分散性好,包封率较高.     

芹菜素固体脂质纳米粒的制备

目的为芹菜素新型制剂的研究和开发提供实验基础。方法采用热熔超声法制备芹菜素固体脂质纳米粒;以包封率为指标,通过正交试验对处方进行优化。结果制备的纳米粒为类球形,包封率为63.11%,平均粒径为(135±18)nm,zeta电位为-18.90 mV,36 h体外累积释放95.74%。结论热熔超声法可用于制备芹菜素固体脂质纳米粒。     

槲皮素固体脂质纳米粒的制备

目的: 制备槲皮素固体脂质纳米粒并对其理化性质进行考察。方法: 采用乳化蒸发-低温固化法制备槲皮素固体脂质纳米粒,以正交设计优化处方和制备工艺,超滤法测定包封率,透射电子显微镜对其粒子形态进行观察,并使用激光粒度分析仪测定其粒径和Zeta电位。结果: 经处方优化制备的固体脂质纳米粒平均粒径为(124.2±0.371) nm,Zeta电位为(-22.3±0.315) mV,粒子形态均匀,无粘连,平均包封率为(89.3±1.209)%。结论: 制备槲皮素固体脂质纳米粒的工艺简便可行,包封率较高且纳米粒质量优良。     

青藤碱固体脂质纳米粒的制备

目的：以山嵛酸甘油酯为载体材料制备青藤碱固体脂质纳米粒并评价其质量。方法：采用乳化蒸发一低温固化法制备青藤碱固体脂质纳米粒，以正交设计优化其处方和制备工艺。对其粒径、形态、表面电位、包封率等理化性质进行研究，并考察其稳定性。结果：所制固体脂质纳米粒外观形态圆整，平均粒径为208．7nm，Zeta电位为-38．5mV，平均包封率为65．7％。4℃放置2个月，粒径、包封率无明显变化。结论：青藤碱固体脂质纳米粒的制备，为开发其新制剂奠定了实验基础。     

酮洛芬固体脂质纳米粒的制备

目的：微乳法制备固体脂质纳米粒,以酮洛芬作为模型药物,考查其载药性能。方法：通过对空白微乳粒径和稳定性考查,确定优化处方,将其保温分散于冷水中制备固体脂质纳米粒。对影响其质量的工艺因素和处方因素进行考查和优化设计,筛选最优处方。结果：制备固体脂质纳米粒的直接影响因素包括脂质用量、药物的用量、冷水相温度和微乳保温温度等,所得固体脂质纳米粒的平均粒径（143.9±1.2）nm,多分散系数为0.443。载药固体脂质纳米粒包封率为81.47%,载药量为8.16%。结论：该法稳定可靠,可用于酮洛芬固体脂质纳米粒的制备。     

Short- and long-term stability study of lyophilized solid lipid nanoparticles for gene therapy

Most studies in gene therapy are focused on developing more efficient non-viral vectors, ignoring their stability, even though physically and chemically stable vectors are necessary to achieve large easily shipped and stored batches. In the present work, the effect of lyophilization on the morphological characteristics and transfection capacity of solid lipid nanoparticles (LyoSLN) and SLN-DNA vectors (Lyo(SLN-DNA)) has been evaluated. The lyophilized preparations were stored under three different sets of temperature and humidity ICH conditions: 25 °C/60%RH, 30 °C/65%RH and 40 °C/75%RH. After lyophilization we found an increase in particle size which did not imply a reduction of “in vitro” transfection capacity. Stability studies of formulations lyophilized with trehalose showed that SLNs were physically stable during 9 months at 25 °C/60%RH and 6 months at 30 °C/65%RH. This stability was lost when harder conditions were employed (40 °C/75%RH). LyoSLNs maintained or increased the transfection efficacy (from 19% to approximately 40% EGFP positive cells) over time only at 25 °C/60%RH and 30 °C/65%RH. Lyo(SLN-DNA) resulted in almost no transfection under all conditions. LyoSLNs showed less DNA condensation capacity, whereas in Lyo(SLN-DNA) the plasmid became strongly bound, hampering the transfection. Furthermore, the storage of lyophilized lipoplexes stabilized with the disaccharide trehalose did not affect cell viability.     

Preparation and stabilization of nifedipine lipid nanoparticles

Design methods of nanoparticle formulations are divided into a break-down method and a build-up method. Furthermore, the former is further divided into dry and wet processes. For drug nanoparticle preparations, the wet process is generally employed, and organic solvents are used in most formulations. In this study, we investigated the preparation of nifedipine (NI) nanoparticles without using any organic solvent. NI nanoparticles with a mean particle size of approximately 50 nm could be prepared without organic solvent by a combination of roll mixing and high-pressure homogenization. The X-ray diffraction peak of the sample prepared by roll mixing was present at an identical position (2theta) to that of NI crystals, showing that no peak shift was induced by interaction with lipid. These findings clarified that most NI remained as crystals in lipid. To maintain the particle size of the nanoparticles in suspension for a long time, a method of adding gelatin powder to the NI-lipid nanoparticle suspension, dissolving the mixture by heating, and then solidifying by cooling was investigated. The mean particle size of the sample was about 55 nm, and that after heat-liquefaction of the NI-lipid nanoparticle suspension gelated at 5 degrees C for 24h was also about 55 nm, showing that the nanoparticle condition was retained.     

吡喹酮固体脂质纳米粒的研制

目的采用超声分散法制备吡喹酮固体脂质纳米粒,并考察制备过程中的主要影响因素。方法首先通过试验确定制备工艺参数,然后考察各处方因素对粒径大小和稳定性的影响,最后以包封率为评价指标,采用正交实验设计法确定最优处方。结果透射电镜测得纳米粒为类圆球状,粒径分布较均匀。动态光散射法测得样品的粒径为(100±21)nm,包封率为(79.3±0.69)%,平均zeta电位值为-66.3 mV。结论以山嵛酸甘油酯和乙酸丁酯为脂质材料,豆磷脂、泊洛沙姆188和硬脂酸钠为复配乳化剂,采用超声分散法可以简便、快速制得吡喹酮固体脂质纳米粒。