脂肪乳注射液中甲氧基苯胺值检测方法的探讨

按国家药典委员会公布的甲氧基苯胺值检测方法,测定4种空白或载药脂肪乳注射液的甲氧基苯胺值,并分析该方法的影响因素及适用性.结果表明,脂肪乳注射液、中/长链脂肪乳注射液和丙泊酚注射液测得的甲氧基苯胺值均小于2.2,符合标准限度,且实测值的重复性良好.而脂溶性维生素注射液(Ⅱ)测得的甲氧基苯胺值异常偏大,可能是其中的多种维生素对检测方法有干扰.本研究还表明,脂肪乳注射液中甲氧基苯胺值检测方法受多种因素影响,包括供试品取样量、供试品水分残留量和乳剂的载药情况等.本法并非适用于所有脂肪乳注射液,载药脂肪乳注射液在检测前应评估其适用性.     

我院32例脂肪乳注射液不良反应报告分析

目的了解脂肪乳注射液不良反应的相关因素,合理使用脂肪乳注射液,减少其不良反应的发生。方法通过回顾性调查分析方法,对我院近5年来上报的32例脂肪乳注射液不良反应报告进行统计分析。结果与结论脂肪乳注射液不良反应以寒战、发热和心血管系统多见。医护人员应熟练掌握脂肪乳注射液的适应症和给药方法,加强脂肪乳注射液的用药监护。     

羟基喜树碱脂肪乳与市售注射液在家兔肝脏中分布的比较

目的考察羟基喜树碱（HCPT）自制脂肪乳和市售注射液静脉推注给药后,药物在家兔肝脏的分布。方法采用2步乳化法制备HCPT脂肪乳,静脉推注自制脂肪乳和市售注射液,采用HPLC法测定家兔肝脏药物含量。结果与市售注射液相比,给药0.5、1、3、4h后自制脂肪乳在肝脏中药物的浓度分别提高了3.0、3.4、7.1、8.4倍。结论以脂肪乳作为药物载体大幅度提高了羟基喜树碱在肝脏中的分布。     

静脉滴注脂肪乳致不良反应70例文献分析

目的分析脂肪乳注射液致不良反应的相关因素,促进临床合理用药。方法检索1994—2008年国内医药学期刊,共发现70例脂肪乳致不良反应病例,对此进行回顾性统计、分析。结果脂肪乳的不良反应主要为变态反应（22.86%）、发热（15.71%）,其次为肝、肾损害（12.86%）和中枢神经系统反应（10.00%）等。结论临床应用需熟练掌握脂肪乳的适应证和给药方法,特别应了解患者的基础性疾病,并加强监测,以减少不良反应的发生。     

中/长链脂肪乳不合理用药案例分析

目的：分析某院住院患者应用20％中/长链脂肪乳注射液的情况,对不合理用药典型案例进行分析,为该药的科学管理和临床合理用药提供参考.方法：对某院2012年使用20％中/长链脂肪乳注射液的出院病历进行用药合理性回顾分析.结果：2012年住院患者20％中/长链脂肪乳注射液的应用仍然存在不合理的现象,表现在适应证、用法用量、用药监测等方面.结论：20％中/长链脂肪乳注射液的临床应用需进一步加强管理,药学干预也需不断持续和改进.     

脂肪乳注射液不良反应25例临床调查

目的:了解脂肪乳注射液不良反应的相关因素,提高合理用药水平。方法:对我院2003年上报的脂肪乳剂不良反应报告进行回顾性调查。结果:脂肪乳注射液不良反应主要为发热,与患者年龄相关,与给药浓度似有一定关系,与性别无关。结论:医护人员熟练掌握脂肪乳注射液的适应证和给药方法,对于提高疗效和减少不良反应具有积极意义。     

脂肪乳在儿科应用的不良反应分析

脂肪乳作为肠外营养(PN)支持的重要组成部分,在临床应用中比较成熟,脂肪乳与一般溶液型注射液比较,不良反应的影响因素较多。本文围绕儿科临床应用脂肪乳不良反应进行分析,提示脂肪乳致过敏反应以首用速发型为主;但过敏性休克多发生在2h左右,影响不良反应发生的因素包括脂肪酸化学构成、剂量、药物浓度、输注速度、乳粒大小分布、甲氧基苯胺值和溶血磷脂,以期为儿科安全使用脂肪乳提供参考。     

脂肪乳注射液不良反应3例

脂肪乳注射液是肠外营养药,可提供人体营养所需的热量和必需脂肪酸,且无氨基酸和糖类溶液高渗透压的缺点,在临床上的使用越来越广泛。近期在临床使用中,发现不良反应3例,均为广州百特侨光医疗用品有限公司生产的20％中／长链脂肪乳注射液250mL（批号：GM0803065）,现报道如下。     

97例脂肪乳注射液致不良反应的文献分析

目的:探讨脂肪乳注射液所致不良反应的一般规律及特点,为其合理应用提供参考。方法:检索1990年1月～2010年4月的中文医药卫生期刊,对其报道的97例有关脂肪乳注射液不良反应作汇总性统计与分析。结果:脂肪乳注射液致不良反应,临床表现以变态反应为主,其他为脂肪超载综合征、中枢神经系统等不良反应;时间多发于2h以内,以首发型为主。结论:临床工作者应掌握脂肪乳注射液不良反应的特点,安全用药。     

1 500例肿瘤患者使用脂肪乳注射液的合理性分析

目的 调查肿瘤患者使用脂肪乳注射液的用药情况,为合理用药提供参考。方法 采用回顾分析法,从郑州大学附属肿瘤医院2016年1-12月所有使用脂肪乳注射液肿瘤患者的病例中随机抽取1500份,根据相关标准就脂肪乳的适应证、药物选择、配伍合理性、给药途径等方面进行专项点评。结果 调查的1 500例肿瘤患者中,以围手术期患者居多,占68.2%。528例用药不合理,占35.2%;其中,适应症不适宜占16.1%,药物选择不适宜占44.5%,用法用量不适宜占50.6%,配伍禁忌占18.3%。结论 该院脂肪乳注射液临床应用不合理现象较为明显,需采取措施强化该类药品的规范使用。     

静脉注射用载药脂肪乳的研究近况

静脉注射乳剂作为一种新型药物载体,相对于传统剂型,对药物具有增溶、保护而免于水解的作用,其应用日趋广泛。综述静脉注射用载药脂肪乳制备工艺的创新与发展、制备材料的研究与应用以及其制剂产品的研发。     

Effect of Injection Volume on the Pharmacokinetics of Oil Particles and Incorporated Menatetrenone after Intravenous Injection as O/W Lipid Emulsions in Rats

Oil-in-water lipid emulsions are promising drug carriers for lipophilic drugs, however, the pharmacokinetics after entering the circulation should be clarified at clinical injection volume in order to utilize them in a clinical situation. In the present study, the standard lipid emulsions, consisting of soybean oil, egg yolk phosphatides and menatetrenone with diameters of about 150nm, were prepared using a microfluidizer system. The pharmacokinetics of menatetrenone and the oil particles after intravenous injection as standard lipid emulsions at various injection volumes, from the clinical injection volume (0.1 ml/kg) to the experimental injection volume (3.0 ml/kg), were examined in rats.

The plasma concentrations of menatetrenone and the oil particles were similar after administration, showing that menatetrenone was not released even after entering the circulation. Menatetrenone was delivered to the liver and spleen at the clinical injection volume, and more menatetrenone was delivered to the liver at clinical injection volume compared with the experimental volume. Moreover, additional information on injection volume-dependency was also obtained from these findings. These results at various injection volumes suggested that the standard lipid emulsions can be utilized as a useful drug delivery system at the clinical injection volume, especially for liver and spleen targeting.     

Characterization, biodistribution and targeting evaluation of breviscapine lipid emulsions following intravenous injection in mice

Breviscapine lipid emulsions were prepared by a high speed dispersion-homogenization method with optimal formulation and technological method. The proportion of liposomes in breviscapine lipid emulsions, an important character for determining the behavior of drug in vivo belongs to which carriers, was less than 5%. Loading breviscapine into lipid emulsions did increase the breviscapine concentrations in plasma, retarded the clearance, and exhibited the properties of sustained-release concluded by pharmacokinetic parameters: after bolus administration, the elimination phase (t(1/2(β))?=?99.535) of lipid emulsions was 5.4-times longer than that of Injectio Breviscapine. The AUC(0→∞) (14.453-times), k(10) (0.047-times), Cl(s) (0.147-times), and MRT(0→∞) (17.766-times) values also confirmed this trend. The amount of drug in every tissue increased at different levels after intravenous administration of breviscapine lipid emulsions compared with Injectio Breviscapine. The relative exposure value of breviscapine lipid emulsions for plasma and lungs were 29.59 and 5.81, respectively, indicating that the exposure of breviscapine to plasma and lungs was significantly increased by entrapment in lipid emulsions. Other targeting evaluation indexes also proved the superiority of lipid emulsions carrier to deliver drug to the targeting region of vascular and lung diseases therapy.     

Preparation, characterization and evaluation of breviscapine lipid emulsions coated with monooleate-PEG-COOH

Series of monooleate-modified PEG with active carboxylic terminus on the other end (MO-PEG-COOH) were used to modify the lipid emulsions surface to prepare a sterically stabilized lipid emulsions for carrying Traditional Chinese Medicine - breviscapine. Based on the research of relationship between polymer structure and prolonged circulation activity, we developed an optimized formulation and a technological method to prepare the sterile and stable MO-PEG(10,000)-COOH (Bre-LE-PEG(10,000)) coated breviscapine lipid emulsions (Bre-LE) for intravenous administration. Follow the optimum preparation, the average particle size, polydispersity index, zeta potential, Ke value and content of final product were determined to be (207.1±8.5)nm, 0.197±0.005, (-33.6±2.0)mV, (21.1±2.3)% and (95.0±1.8)% respectively (n=3). The characteristics, stability and safety of Bre-LE-PEG(10,000) were also studied with Bre-LE as a control. Increased plasma concentration by surface modification of the lipid emulsions may enhance the pharmacological activity of breviscapine to promote blood circulation.     

Inhibition of liver metastasis by all-trans retinoic acid incorporated into O/W emulsions in mice

All-trans retinoic acid (ATRA) was incorporated into lipid emulsions in an attempt to alter its distribution characteristics and improve its inhibition of liver cancer metastasis. Lipid emulsions composed of egg phosphatidylcholine, cholesterol, and soybean oil were the optimized carriers for ATRA delivery, as shown by the submicron particle size and high incorporation efficiency. The particle size and zeta potential of ATRA incorporated into emulsions were about 133 nm and -11 mV, respectively. In vitro drug release study demonstrated that the release of ATRA from emulsions was sustained in the absence and present of bovine serum albumin, suggesting that ATRA was stable when incorporated in emulsions. After intravenous administration in mice, [3H]cholesteryl hexadecyl ether incorporated into emulsion, which is the inherent distribution of emulsions, accumulated gradually mainly in the liver. The blood concentration and hepatic accumulation of [3H]ATRA incorporated into emulsion was significantly higher than that of serum dissolving [3H]ATRA, which represent the original distribution characteristic of free ATRA. In a murine liver metastasis model by colon adenocarcinoma, the liver metastasis number and liver weight were significantly reduced and the survival time of mice was prolonged following intravenous injection of ATRA incorporated into emulsions.     

Application of slurry bridging experiments at controlled water activities to predict the solid-state conversion between anhydrous and hydrated forms using theophylline as a model drug

When mixed with parenteral nutrients as an all-in-one admixture, previous data have demonstrated that lipid emulsions composed of medium-chain triglycerides (MCTs) and long-chain triglycerides (LCTs) yield more stable formulations compared with those compounded with pure LCT lipid emulsions. We investigated the physical stability of various preparations of intravenous lipid emulsions as all-in-one admixtures. Each final lipid emulsion used to compound the all-in-one formulation was a 20% w/v mixture containing MCTs and LCTs as either a single emulsion containing both triglycerides, or an emulsion made extemporaneously from separate starting emulsions of pure MCT and LCT. The first emulsion was composed of a 50:50 (by weight) physical mixture of MCTs and LCTs, and consisted of 50% MCT:40% ω-6 LCT (soybean oil):10% ω-3 LCT (fish oil) that was available as a single 20% w/v lipid emulsion. The second and third emulsions were specially prepared from separate stock dispersions containing pure 20% w/v MCT and pure 20% w/v LCT (soybean oil) lipid emulsions, and were made in volume ratios of 75% MCT:25% ω-6 LCT and 50% MCT:50% ω-6 LCT, respectively. This was done in order to investigate whether the method of emulsion preparation and/or ratio of MCT to LCT influenced all-in-one admixture stability. Each all-in-one admixture was studied at four intervals over 30 h at room temperature conditions by light extinction (or obscuration) using a single-particle optical sensing (LE/SPOS) technique. The data, performed in duplicate at each interval, is expressed as the volume-weighted percent of fat (PFAT) globules >5 μm. The results confirm the stabilizing effects of MCTs when made as a physical oil mixture as a single lipid emulsion. However, stabilization is lost if the MCT and LCT emulsions are mixed from separate starting emulsions and then compounded as an all-in-one formulation. The extemporaneous mixing of commercial lipid emulsions is not recommended.     

含药静脉注射用脂肪乳剂的研究进展

介绍了静脉注射用脂肪乳剂在提高药物溶解度和稳定性、减轻药物不良反应、缓释、靶向给药和基因治疗等方面的研究进展.     

脂肪乳剂的临床应用进展

脂肪乳剂是肠外营养液中非蛋白能源之一,不仅能提供热能和必需脂肪酸,还能维持细胞结构和功能,影响机体免疫功能,有助于疾病康复。不同脂肪乳剂不同的代谢特点决定了其在临床的不同应用。本文对脂肪乳剂的临床应用进展作一综述。     

Diazepam submicron emulsions containing soya-bean oil and intended for oral or rectal delivery

Physically stable diazepam submicron emulsions were prepared using soya-bean oil. Diazepam concentration 4 mg/ml, suitable for rectal or oral delivery, was achieved in 20% emulsions. Mixture of egg lecithin (1.2%) and poloxamer (2.0%) has been chosen as the most suitable emulsifying agent. Composition of the emulsion may be supplemented with alpha-tocopherol and parabens. However, the system was not stable when either phenylethanol or chlorhexidine gluconate was added. Taste masking agents commonly used as food additives decreased stability of the preparation and were not efficient in elimination of a bitter taste of the drug-loaded emulsions.     

Efficacy and safety of an olive oil-based intravenous fat emulsion in adult patients on home parenteral nutrition

BACKGROUND: The most frequently used intravenous lipid emulsions are composed of 100% long chain triacylglycerols from soybean oil or of 50% long chain triacylglycerols-50% medium chain triacylglycerols. A newer emulsion, ClinOleic 20% containing 80% olive oil and 20% soybean oil, was suggested to reduce lipid peroxidation and immune function impairment. AIM: To assess ClinOleic 20%'s efficacy, safety and effect upon systemic inflammatory parameters in adults on home parenteral nutrition. METHODS: In stable home parenteral nutrition patients, the initial intravenous lipid emulsion was changed for ClinOleic 20%. Nutritional status, clinical and biological tolerance, and systemic inflammatory markers were analysed before and after 1 and 3 months of home parenteral nutrition, with ClinOleic 20% as intravenous lipid emulsion. RESULTS: Clinical and biological nutritional markers and inflammatory parameters did not differ between day 0 and month +3. There was no essential fatty acids deficiency. No side-effects were reported. Three of five patients presenting with migraine during home parenteral nutrition infusion at day 0 felt consistently better at month +3. CONCLUSIONS: ClinOleic 20% is safe and efficient in adult home parenteral nutrition. It maintains normal essential fatty acids status and did not influence inflammatory parameters. In contrast to studies in preterm infants or paediatric patients, no effect on vitamin E concentration or lipid peroxidation was observed.