Medium-chain Triglyceride/long-chain Triglyceride Research Articles

Physical Stability of Medium-Chain Triglyceride/Long-Chain Triglyceride Emulsion Injections From 5 Manufacturers in High-Concentration Electrolyte-Based Total Nutrient Admixtures.

Lipid emulsion injections for parenteral nutrition are an important source of energy and essential fatty acids. Yet stability and compounding challenges remain. We compared the physicochemical stability of 5 commercial medium-chain triglyceride/long-chain triglyceride (MCT/LCT)-based lipid emulsions compounded in total nutrient admixtures (TNAs). Stability of the MCT/LCT-based TNAs was assessed when compounded with high concentrations of electrolytes. We measured mean droplet diameter (MDD), percentage of fat residing in globules ≥5 μm (PFAT5), pH, and osmolality immediately after compounding (time 0) and 6, 12, 18, 24, 36, 48, 60, and 72 hours later. Repeated-measures analyses of variance were used to evaluate changes in stability over time, and post hoc tests were used to assess group differences. Over 72 hours, MDD of TNAs ranged from 0.206 to 0.713 μm, PFAT5 from 0.58% × 10-3 to 43.18% × 10-3 , pH from 5.769 to 5.879, and osmolality from 1304 to 1357 mOsm/kg. MDDs and PFAT5s showed a tendency to increase gradually over the first 24 hours and then decrease or remained stable after that. We identified some significant differences in MDDs and PFAT5s among the 5 MCT/LCT-based TNAs, although all met the United States Pharmacopeia <729> standards. The stability of some commercial MCT/LCT-based TNAs under high concentrations of electrolytes exhibits differences over the 72 hours after compounding. Clinicians should pay attention, therefore, to possible performance differences of injectable lipid emulsions produced by different manufacturers when compounded in TNAs under high electrolyte concentrations.

INJECTION PAIN OF PROPOFOL IN CHILDREN WITH MEDIUM PLUS LONG CHAIN TRIGLYCERIDES AND LONG CHAIN PROPOFOL MIXED WITH LIGNOCAINE

Introduction: Propofol is widely accepted drug because of its rapid and smooth induction, short context-sensitive time, rapid terminal half-life time and low incidence of postoperative nausea and vomiting. It is used for sedation and anaesthesia for almost all types of surgeries. During a propofol injection, pain due to the long-chain triglyceride (LCT) emulsion is experienced by 70% of adults and up to 85% of children. Despite various strategies to reduce propofol injection pain, this still poses a clinical problem in adults and children, and the incidence reported to be 30–90%. A medium-chain triglyceride/long-chain triglyceride (MCT/LCT) emulsion has been advised to reduce injection pain as compared to propofol LCT in adults and teenagers&#x0D; Material and Methods: 100 children aged 5–13 years, in American Society Anaesthesiologists (ASA) class I or II, undergoing elective general anaesthesia without any contraindication to propofol anaesthesia were included in the study. Injection pain following injection propofol was assessed in all patients, but the anaesthetist was blinded for which formula was being used.&#x0D; Results: The demographic characteristics like age, sex, weight, amount of propofol given, ASA physical status and recovery period was calculated. No statistically significant difference was observed in both the groups. Incidence of pain and severe pain in LCT group was 24 (48%) and 7 (14%) respectively while incidence of pain and severe pain in MCT/LCT group was 15 (30%) and 1 (2%) respectively. Pain score was found less in group MCT / LCT.&#x0D; Conclusion: Medium plus long chain triglycerides and long chain propofol along with lignocaine significantly reduces the incidence as well as the severity of injection pain in the paediatric age group and can be used in children for sedation or induction of anaesthesia.

Effects of Lipid Emulsions in Parenteral Nutrition of Esophageal Cancer Surgical Patients Receiving Enteral Nutrition: A Comparative Analysis

Background: Olive oil-based lipid emulsion (LE) and medium chain triglyceride/long chain triglyceride (MCT/LCT) emulsion are both LEs with low ω-6 polyunsaturated fat acids (PUFAs) content. However, which one of these LEs is associated with a lower infection risk in patients receiving parenteral nutrition (PN) remains unclear. The aim of the study was to compare the effects of the two LEs in PN in esophageal cancer patients undergoing surgery. Methods: Patients with resectable esophageal carcinoma were recruited and allocated randomly to two groups. The test group was given enteral nutrition (EN) with PN containing olive oil-based LE after tumor resection for ≥7 days, and the patients in the control group were supported by EN with MCT/LCT emulsion-based PN after surgery for the same time period. Immunological markers and inflammatory indicators were tested and perioperative clinical outcomes were determined. The trial was registered in the Chinese Clinical Trial Register, number ChiCTR-TRC-13003562. 94 Patients were recruited, and grouped (olive oil-based LE, n = 46 and MCT/LCT, n = 48), matched for sex, age, body mass index, histological type, TNM stage, and nutrition risk screening (NRS) 2002 score. Results: There were no differences in perioperative fever (>38 °C), infectious complications, length of hospital stay (>14 days), length of critical care stay (>2 days), time for oral food intake, and in-hospital mortality between the two groups. The test group showed a higher increase in IgG level compared with the MCT/LCT group (p = 0.028). There was no difference in other immunological markers and inflammatory indicators between the two groups. Conclusion: PN containing olive oil-based or MCT/LCT LEs had similar effects on perioperative outcome, cell-mediated immune function and inflammatory response in esophageal cancer patients who had undergone surgery and were receiving EN.

Assessment of oxidative stress and antioxidant property using electron spin resonance (ESR) spectroscopy

The pathophysiology of hypertension or stroke is associated with an excess of ROS generation in the vascular system, and results in induction of various pathological cascades of cerebrovascular damage. We have demonstrated that electron spin resonance methods using a spin trap or spin probe will be useful for understanding redox status under conditions of oxidative stress in the spontaneously hypertensive rat or stroke-prone spontaneously hypertensive rat brain. We have used electron spin resonance imaging and noninvasive L-band electron spin resonance to characterize the higher degree of brain oxidative stress in the stroke-prone spontaneously hypertensive rat and spontaneously hypertensive rat than in the Wistar-Kyoto rat brain, and the lower extent of oxidative stress in the spontaneously hypertensive rat than in the stroke-prone spontaneously hypertensive rat brain. Indeed, we may be able to confirm propofol medium-chain triglyceride/long-chain triglyceride (MCT/LCT) as neuroprotective anesthesia and crocetin as antioxidant food factor against human stroke after screening for antioxidant properties in stroke models such as stroke-prone spontaneously hypertensive rat. Thus, our electron spin resonance biomedical application suggests that it could be used to assess antioxidant effects on oxidative stress in the brain using spontaneously hypertensive rat and stroke-prone spontaneously hypertensive rat. We hope that further advances in the instrumentation used for electron spin resonance imaging and the development of optimized nontoxic spin probes will make this technology even more promising for novel clinical prediction or noninvasive diagnosis of human stroke. After screening drugs or foods for antioxidant property using in vitro or in vivo electron spin resonance assessment, it will be possible to find and develop novel drugs or food factors with such properties for the prevention of stroke in the near future.

Direct Assessments of the Antioxidant Effects of Propofol Medium Chain Triglyceride/Long Chain Triglyceride on the Brain of Stroke-prone Spontaneously Hypertensive Rats Using Electron Spin Resonance Spectroscopy

Antioxidant anesthetics such as propofol (2,6-diisopropylphenol) directly inhibit lipid peroxidation via the generation of reactive oxygen species. Currently, there are no other studies regarding the direct effects of propofol medium chain triglyceride/long chain triglyceride (MCT/LCT) on reactive oxygen species generation or in experimental models of reactive oxygen species-induced oxidative stress in the brain. The authors investigated the effects of propofol MCT/LCT on reactive oxygen species (hydroxyl radical or superoxide) by electron spin resonance spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide. The effects of propofol MCT/LCT on oxidative stress in the brain of Wistar-Kyoto rats or stroke-prone spontaneously hypertensive rats were investigated by using an in vivo L-band electron spin resonance system to monitor the decay rate of 3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl as a nitroxyl spin probe. These studies provided direct evidence that propofol MCT/LCT inhibited hydroxyl radical generation, but not superoxide generation. Regarding the hydroxyl radical from the Fenton system, it is likely to be due to the scavenging effects of vehicle. Anesthesia with propofol MCT/LCT reduced the degree of the high oxidative stress in the brain of stroke-prone spontaneously hypertensive rats. The current data show that propofol, mixed with clinical reagents (propofol MCT/LCT), resulted in the down-regulation of high oxidative stress due to scavenging hydroxyl radical, as demonstrated by in vitro or in vivo electron spin resonance analysis. These results led to reduced levels of hydroxyl radical, formed by brain injury such as stroke, and may therefore provide advantages for neuroprotection during anesthesia for craniotomy, e.g., in cases of brain disease.

Efficacy of Medium-chain Triglycerides Compared with Long-chain Triglycerides in Total Parenteral Nutrition in Patients with Digestive Tract Cancer Undergoing Surgery

The objectives of this prospective, randomized study were to evaluate the efficacy and tolerability of the short-term use of medium-chain triglyceride/long-chain triglyceride (MCT/LCT) fat emulsions, and to compare the hematologic and biochemical effects of MCT/LCT fat emulsions with LCT fat emulsions in gastrointestinal (GI) tract cancer patients following surgery. Thirty patients with GI tract cancer requiring total parenteral nutrition (TPN) were equally randomized to receive MCT/LCT or LCT emulsions for 7 days. After 7 days, no sign of complications directly related to administration of fat emulsions was observed and there were no marked differences in anthropometry, length of hospital stay, and surgical complication rates between the two groups. However, MCT/LCT significantly improved plasma prealbumin concentration (p = 0.005). Changes in complements C3 and C4, total lymphocyte count, and immunoglobulins after TPN were not significantly different between the groups. Serum triglyceride and cholesterol levels remained constant. The serum insulin level in the MCT/LCT group was higher than in the LCT group (p = 0.048). Our data revealed that MCT/LCT fat emulsions significantly enhanced nutritional status in patients with GI tract cancer, indicated by higher prealbumin levels, which might be partially due to the higher circulating insulin levels in the MCT/LCT group.

Solubilizing poorly soluble antimycotic agents by emulsification via a solvent-free process.

The purpose of this study was to formulate itraconazole and ketoconazole as oil/water emulsions for parenteral delivery by using a solvent-free homogenization process, namely SolEmuls (solubilization by emulsification) technology. The drugs were incorporated in the commercial emulsion Lipofundin MCT 20%, composed of a medium-chain triglyceride/long-chain triglyceride (MCT/LCT) oil phase (1:1) and stabilized with 1.2% lecithin. Different parameters such as drug-loading capacity, long-term physical stability, and completeness of drug dissolution were investigated. Up to 10.0 mg/mL complete drug dissolution was achieved with itraconazole; at 20 mg/mL hybrid dispersion was obtained. Itraconazole-loaded emulsions were physically stable for 9 months (data up to now). Ketoconazole showed physical instability in the Lipofundin emulsion, which was stabilized with only 1.2% lecithin. Stabilization of ketoconazole-loaded emulsions was achieved using additionally Tween 80 as steric stabilizer. Higher concentrations of ketoconazole (ie, 10.0 mg/mL concentrated ketoconazole emulsions) were also produced with additional 2.0% Tween 80. Ketoconazole-loaded emulsions, 1 mg/mL, which were stabilized with 2.0% Tween 80, were stable for a period of 6 months. It can be concluded, after formulating amphotericin B and carbamazepine with SolEmuls technology, that SolEmuls was also applicable to the antimycotic agents itraconazole and ketoconazole, yielding IV-applicable emulsions with cost-effective production technologies.