脂肪乳剂在全合一营养液中的稳定性研究

目的对长链脂肪乳注射液及中／长链脂肪乳注射液,分别配制成各种全合一(All-in-One)营养混合液,进行脂肪乳剂乳粒稳定性的对比研究。     

不同脂肪乳在肠外营养液中稳定性的研究

目的观察肠外营养液配制后在不同存放温度条件下脂肪乳的稳定性。方法采用规范化肠外营养液配制, 共配制24袋肠外营养液, 随机分为两组, A组12袋配方中脂肪乳为20%中/长链脂肪乳注射液(C6-24), B组12袋配方中脂肪乳为20%中/长链脂肪乳注射液(C8-24), 检测时间点为配制完成后24、48、72 h, 观察两组在2～8℃, 23～25℃和35～37℃中外观、营养液pH值和脂质过氧化。结果两组在4℃、25℃和36℃条件下分别放置24、48、72 h后, 外观均无明显变化, pH值差异无统计学意义(P>0.05), 脂质过氧化差异无统计学意义(P>0.05)。结论两种脂肪乳在不同存放条件下pH值、脂肪颗粒大小、脂质过氧化产物方面都较为稳定, 能够为进行静脉营养支持患者提供营养物质需求。     

"全合一"静脉营养液中电解质对脂肪乳稳定性的影响

"全合一"静脉营养液在临床上普遍使用,事实证明它是很安全和非常方便的.但脂肪乳剂在"全合一"静脉营养液中的稳定性问题始终让人担忧.由于病人的治疗需要,我们常常往"全合一"静脉营养液中加入一定量钾、钠、氯等一价离子,有些病人还需要补充钙、镁等二价离子.人们已从生物物理学上知道,这些电解质对脂肪乳剂的稳定性是有影响的 .输入颗粒较大的脂肪乳滴有可能栓塞毛细血管,但临床医师对此并没有给予足够的重视. 近期,我们对我院使用的"全合一"静脉营养液用光学显微镜对脂肪乳滴大小进行了观察, 终于了解到一些电解质对脂肪乳稳定性的影响,现报告如下:     

不同存放方式对肠外营养液稳定性影响的研究

目的:研究不同存放方式对全肠外营养(TPN)液稳定性的影响。方法:将两种配方的药物注入一次性肠外营养(PN)输液袋内配置成TPN液,分别在4℃、20~25℃和37℃三种条件下存放。放置于4℃条件下的营养液于0、1、2、3和5 d后取样,放置于20~25℃和37℃条件下的营养液于0、1、2和3 d后取样。观察外观性状,测定p H值、渗透浓度、脂肪颗粒直径和有无细菌生长等。结果:两种配方的全合一营养液在4℃、20~25℃和37℃三种条件下各观察期内肉眼上外观无明显变化、培养结果均无细菌生长,p H值、渗透浓度均在安全可用范围。放置4℃下的全合一营养液,在1和2 d内脂肪乳无直径1μm的脂肪颗粒。存放3和5 d后,脂肪颗粒平均直径仍在安全范围内,但有超过10%1μm,且大于存放0 d(P0.05)。放置于20~25℃、37℃下的全合一营养液,1 d脂肪颗粒直径在安全范围内。存放2、3 d仍在安全范围,但明显0 d(P0.05)。脂肪颗粒直径1μm的超过10%。结论:使用一次性PN输液袋配制的TPN液,在4℃保存2 d,22~25℃和37℃保存1 d的稳定性均较好。     

丙氨酰-谷氨酰胺在全合一肠外营养液中的稳定性

目的 观察丙氨酰-谷氨酰胺对全合一肠外营养液稳定性尤其是脂肪乳剂稳定性的影响。方法将丙氨酰-谷氨酰胺分别加入3种不同配方的全合一肠外营养液中，在不同温度下、24小时内取样观察外观变化，测定pH值、渗透压值。观察脂肪乳剂在加入丙氨酰-谷氨酰胺后颗粒大小及形态有无改变并计算平均粒径。结果不同配方全合一肠外营养液加入丙氨酰-谷氨酰胺后，其外观、pH值、渗透压值未见明显改变，脂肪乳剂颗粒大小及形态亦无明显变化。临床应用100人次，未见不良反应。结论丙氨酰-谷氨酰胺可加入全合一肠外营养液中进行配伍使用。     

含维生素E的中/长链脂肪乳注射液临床应用进展

脂肪乳剂是全胃肠外营养(TPN)中的重要组成部分.随着TPN在临床营养治疗中的广泛应用,脂肪乳剂也逐渐由长链脂肪乳(LCT)发展至中/长链脂肪乳(MCT/LCT).MCT具有水解、氧化快而完全,不依赖肉毒碱转运,对免疫系统影响少,且不易在肝内和外周组织中浸润等优点.但其中仍含有一定量的多不饱和脂肪酸,易受体内自由基的攻击而产生脂质过氧化,进而损害脂质、DNA和蛋白质,造成组织和器官的损伤.因此,许多学者主张在MCT/LCT剂中添加一定量的维生素E,以防止脂肪乳剂脂质过氧化的发生,从而保证临床安全、合理地使用脂肪乳剂进行营养治疗的同时,有效地避免发生不良反应.以下主要对含维生素E的MCT/LCT注射液在临床的应用作一综述.     

鱼油脂肪乳和20%中/长链脂肪乳干预博莱霉素致大鼠肺纤维化效果的比较

目的:探讨鱼油脂肪乳和20%中/长链脂肪乳注射液干预博莱霉素致大鼠肺纤维化的不同效果。方法:将120只大鼠随机分成正常组(等渗盐水)、对照组(博莱霉素所致大鼠肺纤维化模型)、20%中/长链脂肪乳组和ω-3PUFA组。在实验第7、14和21天分别取左肺下叶,用免疫组化检测转化生长因子-β(TGF-β1)和γ干扰素(IFN-γ)表达,右肺下叶组织行H-E染色病理观察;同时测定各组大鼠血清中白细胞介素-4(IL-4)和IFN-γ含量。结果:①ω-3PUFA组大鼠肺泡炎症和肺纤维化程度均较对照组和MCT/LCT组轻;②对照组和MCT/LCT组大鼠在实验第7、14和21天的肺组织TGF-β1染色呈强阳性,IFN-γ染色较淡,而ω-3PUFA组TGF-β1、IFN-γ染色及定量表达则相反(P﹤0.01),第7、14和21天,TGF-β1定量表达逐渐减少,IFN-γ逐渐增加(P﹤0.05)。③对照组和MCT/LCT组大鼠第7、14和21天血清IL-4含量较高,IFN-γ含量较低;而ω-3PUFA组则相反(P﹤0.01),第7、14和21天IL-4含量逐渐减低,IFN-γ含量逐渐增加(P﹤0.05)。结论:鱼油脂肪乳可下调大鼠肺组织TGF-β1,降低IL-4含量,上调肺组织IFN-γ的表达,其减轻肺纤维化的作用优于中/长链脂肪乳注射液。     

长链脂肪乳剂及中/长链脂肪乳剂水解速率的比较研究

目的：比较长链脂肪乳剂、物理混合的中／长链脂肪乳剂及结构脂肪乳剂的水解速率。方法：应用1、^14C甘油棕榈酸标记的长链三酰甘油（LCT）和2，3－^3H甘油辛酸标记的中链三酰甘油（MCT），分别标记Intralipid,Lipofundin及Structolipid，在体外添加缓冲液、脂蛋白酯酶和肝酯酶后，置37℃温箱中水浴、卵育。采用气相色谱仪测定核素核记的各种脂肪酸及三酰甘油浓度，游离脂肪酸浓度用放射性核素扫描计数测定，通过计算培养液中^14C标记的长链脂肪酸及^3H标记的中链脂肪酸分别在^14C标记LCT及^3H标记MCT中的比例。来计算三种脂肪乳剂的水解率。结果：物理混合的中／长链脂肪乳剂及结构脂肪乳剂的水解程度明显高于长链脂肪乳剂，差异有统计学意义。物理混合的中／长链脂肪乳剂水解程度高于结构脂肪乳剂，但在水解程度及水解速度上却无统计学差异。结论：物理混合的中／长链脂肪乳剂及结构脂肪乳剂的水解率明显高于长链脂肪乳剂。     

30%英脱利匹特配制全合一营养液的稳定性和疗效

高浓度脂肪乳剂30％英脱利匹特，不仅为肠外营养提供与血浆等渗和更浓缩的能源，而且，因磷脂与甘油三酯的比值(PL／TG)低于其他脂肪乳剂，故更有利于在体内的代谢和利用。现用低磷脂脂肪乳剂配成全合一营养液(All—in—one，或Total nutrient admixture，TNA)，观察其稳定性、疗效和不良反应。     

不同葡萄糖浓度全合一营养液体外稳定性评估

目的 评估不同时间点添加不同葡萄糖浓度全合一营养液的稳定性,为提高临床应用的安全性提供可靠依据.方法 根据临床应用情况,设计5组不同配方静脉营养液,其中葡萄糖终浓度分别为5％、10％、15％、20％和25％,其他营养素浓度每组相同.配制后的营养液于室温下（25±2）℃储存,分别在0、12、24、48、72 h时观察营养液外观变化,应用扫描电镜测量脂肪颗粒大小,并行营养液渗透浓度和pH值测定.结果 （1）肉眼观察各组营养液配制后0、12、24、48、72 h无颜色变化,未观察到沉淀、分层现象.（2）每组全合一营养液在不同时间点脂肪颗粒平均粒径值差异无统计学意义（F组内=1.255,P=0.324; F组间 =0.025,P=0.998; F交互=1.005,P=0.489）.72 h内,各组脂肪颗粒平均直径均＜0.5 μm,各组均未见到直径＞5.0 μm的脂肪颗粒.（3） 72 h内,所有营养液pH值波动于6.08 ±0.00～6.37±0.01之间.不同时间点5组营养液间pH值比较差异有统计学意义（F组内=3 452.846,P=0.000; F组间=4 655.250,P=0.000; F交互=1.952,P=0.079）.（4） 72 h内,所有营养液平均渗透浓度波动于（609.3±2.3）～（1 625.2±3.5） mOsm/L之间.不同时间点5组营养液间平均渗透浓度比较差异有统计学意义（F组内=176 195.911,P=0.000; F组间=14.732,P=0.006; F交互 =1.203,P=0.343）.结论 全合一营养液中葡萄糖终浓度为5％ ～ 15％时,脂肪颗粒、pH值和渗透压均在安全范围内.     

手术后病人对不同脂肪乳剂清除的影响

在创伤状态下,比较研究10% Intralipid和10% Lipofundin在血中的清除情况.结果显示,应用Lipofundin时,血中TG浓度4小时恢复至输前水平,TCH浓度与输前水平一致;应用Intralipid时,血中TG浓度6小时,TCH浓度2小时恢复至输前水平.结果显示:在一般创伤情况下,人体均能很好地清除外源性脂肪,但Lipofundin在血中的清除比Intralipid快,建议在高脂血症倾向的病人中,选用Lipofundin较为合理.     

糖尿病患者中链和长链甘油三酯乳剂的清除比较

比较胰岛素非依赖性糖尿病患者中/长链甘油三酯(MCT/LCT)混合乳剂和长链甘油三酯(LCT)乳剂的清除率。每组各6例,在4小时输入脂肪期间,MCT/LCT组血甘油三酯达稳定状态。动力学参数表明MCT/LCT乳剂有着明显较小的表观分布容积和较短的半衰期。两种乳剂对血糖浓度也有不同的影响。在葡萄糖和脂肪代谢紊乱时,如需行含脂肪的肠外营养,应优先选择MCT/LCT混合乳剂。     

静脉输注长链及中/长链脂肪乳剂对脂蛋白代谢的影响

目的比较静脉输注长链(LCT)及中长链(MCT/LCT)脂肪乳剂时血浆脂蛋白代谢.方法选择12例健康志愿者进行前瞻性随机交叉对照研究, 连续输注MCT/LCT或LCT6小时(0.20g TG.Kg-1@h-1),测定研究前及输注中4h、6h、8h、12h及24h时血清TG、FFA,PL、FC、CE浓度以及血浆各脂蛋白成份.结果脂肪乳剂输注过程中,MCT/LCT组血清甘油三酯(TG)浓度明显低于LCT组,而血浆FFA浓度约为LCT组的3倍(p<0.001), MCT/LCT 的半衰期明显短于[LCT (68(12)分钟vs.(116(18)分钟,p<0.05].LCT组血浆游离胆固醇浓度明显高于MCT/LCT 组(p<0.05),而血浆胆固醇酯(CE)浓度在研究过程中两组均无明显变化.结论MCT/LCT的水解、代谢清除率要明显高于LCT,MCT/LCT输注时TG与LDL之间转换率较高,脂肪颗粒较少获取CE,其残余颗粒的清除也高于LCT.     

MCT/LCT emulsion ameliorate liver fat deposition in insulin-treated diabetic rats receiving total parenteral nutrition

This study was designed to investigate the effects of high energy infusion and insulin treatment on plasma and liver lipids in diabetic rats receiving total parenteral nutrition (TPN). Diabetes was induced in rats by streptozotocin. The diabetic rats were assigned to two TPN groups to receive either long chain triglyceride (LCT) or medium chain triglyceride (MCT)/LCT (1:1) as a fat source. The TPN solutions were isonitrogenous, isocaloric and identical in nutrient composition except for the fat emulsion. All rats received the TPN solution at an energy level of 35|kcal/100|g of body weight. The LCT and MCT/LCT groups were further divided into two subgroups, depending on whether they were treated with insulin. The results demonstrated that, between the MCT/LCT and LCT groups, no differences were observed in body weight and nitrogen retention, as well as the concentrations of plasma glucose, nonesterified fatty acids, beta-hydroxybutyrate, and total cholesterol. Diabetic TPN rats without insulin treatment had weight loss and negative nitrogen balance during the experiment. Diabetic TPN rats treated with insulin, however, demonstrated less weight loss and positive nitrogen retention. Insulin treated groups had significantly higher liver fat content than did those without insulin treatment. Furthermore, liver fat content was significantly higher in the LCT group than in the MCT/LCT group among insulin treated TPN rats. These results suggest that compared with the LCT emulsion, infusion of the MCT/LCT emulsion ameliorated liver fat deposition in insulin-treated diabetic rats receiving TPN.     

Comparison of metabolic clearance rates of MCT/LCT and LCT emulsions in diabetics

In seven moderately overweight noninsulin-dependent diabetics with slightly elevated triglyceride levels, disappearance rates of infused medium chain triglyceride/long chain triglyceride (MCT/LCT) and long chain triglyceride (LCT) emulsions were compared. Five metabolically healthy volunteers served as controls. During a 3-hr lipid infusion, serum triglycerides reached a steady state with both emulsions in the healthy controls, whereas, in diabetic patients, steady state triglyceride levels were seen only with MCT/LCT. After the end of the lipid infusion, the longest half-life value in the decline of triglyceride levels was found with LCT in diabetics, whereas significantly shorter and quite similar half-life values were found with LCT in healthy controls and with MCT/LCT in diabetics. As expected, the shortest half-life for serum triglycerides was found in healthy controls after MCT/LCT-infusion. Virtually the same differences in serum concentrations and in half-life times were seen with free fatty acids. According to these data, if needed, parenteral nutrition with lipids in states of disturbed glucose and lipid metabolism may preferentially be done with MCT/LCT emulsions.     

新生儿肝功能障碍时不同脂肪乳剂对血脂和肝功能影响的比较研究

目的 :比较中 /长链和长链脂肪乳剂对肝功能障碍新生儿血脂和肝功能的影响。　方法 :将 40例血清胆红素水平≥ 5 1.3μmol/L(3mg % )的新生儿随机分成两组 ,分别应用中 /长链脂肪乳剂 (MCT/LCT组 ,2 0 %Lipo fundin)和长链脂肪乳剂 (LCT组 ,2 0 %Intralipid) ,剂量均为 2 g/ (kg·d) ,持续 1周。在实验前、后分别抽血测定血脂和肝功能。　结果 :两组总胆固醇无显著变化 ,甘油三酯在LCT组升高 ,在MCT/LCT组下降 ,与实验前相比均无显著差异 ,组间比较MCT/LCT非常显著地低于LCT组。胆红素在两组均显著下降 ,但MCT/LCT组下降比LCT组更加显著。γ GT和ALP在LCT组无明显改变 ,但在MCT/LCT组却有显著降低 ,并显著低于LCT组。　结论 :在危重新生儿合并有肝功能障碍时 ,应用中 /长链脂肪乳剂显著优于长链脂肪乳剂。     

Changes of hepatic morphology during parenteral nutrition with lipid emulsions containing LCT or MCT/LCT quantified by ultrasound.

Fatty infiltration of the liver with cholestasis is one of the complications of total parenteral nutrition (TPN). The cause has not yet been determined. It seems probable, however, that these alterations could be prevented when a mixture of medium- and long-chain triglycerides (MCT/LCT) is used as a fat component instead of the application of long-chain emulsions (LCT) alone. To determine whether this could also be demonstrated morphologically in man, 14 patients needing TPN (25 kcal/kg BW x day, carbohydrate 45%, fat 35%, protein 20%) were examined by ultrasound in order to compare liver size and gray-scale value before and after 7 days of TPN. Seven of the patients were randomly administered a MCT/LCT emulsion as their fat intake, the other seven were exclusively given LCT. There were no changes in liver size and gray-scale value in the MCT/LCT-group, whereas both parameters showed a significant rise in the patients with LCT (size: 10.4 +/- 1.4 to 11.5 +/- 1.4 cm; gray-scale value: 9.3 +/- 1.0 to 11.6 +/- 0.7). These data suggest that TPN, administered with a mixture of MCT/LCT emulsions as fat components, could reduce the risk of hepatic dysfunction such as cholestasis and fatty infiltration of the liver.     

Parenteral nutrition using MCT/LCT or LCT: Effect on the fatty acid composition of plasma triglycerides and platelet phospholipids

Plasma triglyceride fatty acids and platelet phospholipid fatty acids were compared in 20 malnourished patients before and after 8-10 days of total parenteral nutrition which included either a conventional lipid emulsion (LCT) or a new emulsion containing medium chain triglyercides (MCT/LCT). The use of both lipid emulsions altered the fatty acid profiles. The percentage of linoleic acid in the plasma triglycerides increased with both lipid emulsions, but more markedly with LCT. The median percentage after LCT was 25.9 (range 16.9-31.5) which was significantly higher (p < 0.01) than after MCT/LCT - 14.8 (range 6.1-20.2), or in healthy volunteers. After 8-10 days on MCT/LCT the fatty acid profile retained some features of the malnourished state, despite correction of the linoleic acid content. The percentage of linolenic and arachidonic acid in the platelet phospholipids tended to be lower than after LCT use, and the percentage of linoleic acid was significantly less (p < 0.01), the median (range) being 8.2 (4.5-23.8) after MCT/LCT and 11.7 (4.8-16.0) on LCT. Short term use of MCT/LCT emulsion may correct the fatty acid changes of malnutrition rather more slowly and results in a different fatty acid profile to that seen after LCT use. Whether this has any clinical effects is unclear.     

Lipoprotein metabolism during and after a 6-h infusion ofMCT/LCT vs LCT emulsion in man

We studied, in man, the intravascular metabolism of two lipid emulsions differing in their triglyceride (TG) fatty acid pattern. One emulsion was composed exclusively of soy bean long-chain triglycerides (LCT), the other of a mixture containing a (1:1, wt:wt) ratio of medium-chain triglycerides (MCT) and LCT (MCT/LCT). Both emulsions contained 10% TG and 1.2% of the same egg yolk phospholipid emulsifier. Six healthy volunteers received both emulsions, in random order, at a rate of 0.2 g TG/kg.h for 6 h. An interval of 2 weeks separated the tests. Although the MCT/LCT emulsion provided 39% more TG molecules than the pure LCT emulsion, plasma TG increased to similar levels, indicating a faster elimination of MCT/LCT. The rise of plasma non esterified fatty acids was greater with MCT/LCT (P < 0.001). LDL-TG enrichment was higher with MCT/LCT (P < 0.025) while net transfer of TG to HDL was similar with both emulsions. Cholesteryl ester (CE) enrichment in the 'VLDL' fraction (largely composed of emulsion particles) was markedly less during MCT/LCT than LCT infusions (P < 0.01). CE enrichment of the 'VLDL' fraction persisted up to 6 h after cessation of both lipid infusions. In conclusion, TG from MCT/LCT emulsion appear to be eliminated faster than LCT during an in vivo infusion in man. In accordance with our previous in vitro data, MCT/LCT infusion was associated with a higher transfer of TG to LDL and in a reverse manner, with a lesser acquisition of CE by emulsion particles as compared to LCT infusion.     

早期肠内喂养MCT/LCT改善烧伤病人高代谢的临床研究

目的　通过比较烧伤病人早期肠内喂养含MCT/LCT与只含LCT的肠内营养制剂对烧伤后高代谢的不同影响 ,探讨MCT/LCT改善烧伤后代谢状态的作用及可能机制。方法　选取 3 0例TBSA >3 0 %的烧伤病人 ,并随机分为两组 ,一为Fresubin75 0MCT组 (F组 ) ,即饲以含MCT/LCT的肠内营养制剂Fresubin 75 0MCT ;另一组为Nutrison组 (N组 ) ,即饲以只含LCT的肠内营养制剂Nutrison。于伤后 2 4h内进行完全肠内营养支持 ,共支持 10d。在PBD1、4、7、10分别观察了两组患者影响代谢的严重因子的变化情况 (包括血浆胰岛素、胰高血糖素、肿瘤坏死因子 (TNF)及皮质醇。尿 3 -甲基组氨酸排泄率 )。结果　烧伤后机体分解代谢增加 ,两组相比血浆皮质醇水平无显著差异 ;F组患者血浆胰岛素与胰高血糖素浓度的比值明显升高 ,尿 3 -甲基组氨酸排泄率及血浆TNF明显下降。结论　含MCT/LCT的肠内营养制剂较只含LCT者 ,能促进烧伤后机体合成激素的分泌 ,减少肌肉蛋白分解排出量 ,从而改善烧伤病人代谢状况 ,并有利于提高全身营养及免疫状况 ,促进创面愈合