METHOD: α-tocopherol monoester of MFA (TMMA) and α-tocopherol di-ester of MFA (TDMA) were synthesized by esterification reaction and were subjected to various in vivo characterizations.
RESULTS: Masking of the carboxylate group of MFA with the proposed pro-moieties significantly (p<0.05) delayed the onset of tonic-clonic seizure in mice. Besides, the intraperitoneal administration of TMMA and TDMA in mice produced significantly (p<0.05) stronger anti-inflammatory effects in the carrageenan-induced paw edema test and greater anti-nociceptive effect in the acetic acid-induced writhing test than MFA at an equimolar dose of 20 mg/kg. Treatment with TMMA and TDMA caused a significant (p<0.05) inhibition of pain at 1st and 2nd phases of formalin-induced licking test in mice, whereas treatment with MFA inhibited the 2nd phase only. Pretreatment with naloxone and flumazenil significantly (p<0.05) reversed the anti-nociceptive effect of MFA, TMMA and TDMA in the acetic acid-induced writhing test. In addition, treatment with TMMA and TDMA caused significantly (p<0.05) a higher inhibition of pain in the glutamate-induced licking response in mice than MFA.
CONCLUSION: Masking the carboxylate moiety of MFA by α-tocopherol and α-tocopherol acetate has a great potential for reducing CNS toxicity, enhancing the therapeutic efficacy and altering the mode of anti-nociceptive action.
OBJECTIVE: The main objective of this study was to optimize the production of NPG diesters and to characterize the optimized esters with typical chemical, physical and electrical properties to study its potential as insulating oil.
METHODS: The transesterification reaction between HOPME and NPG was conducted in a 1L three-neck flask reactor at specified temperature, pressure, molar ratio and catalyst concentration. For the optimization, four factors have been studied and the diester product was characterized by using gas chromatography (GC) analysis. The synthesized esters were then characterized with typical properties of transformer oil such as flash point, pour point, viscosity and breakdown voltage and were compared with mineral insulating oil and commercial NPG dioleate. For formulation, different samples of NPG diesters with different concentration of pour point depressant were prepared and each sample was tested for its pour point measurement.
RESULTS: The optimum conditions inferred from the analyses were: molar ratio of HOPME to NPG of 2:1.3, temperature = 182°C, pressure = 0.6 mbar and catalyst concentration of 1.2%. The synthesized NPG diesters showed very important improvement in fire safety compared to mineral oil with flash point of 300°C and 155°C, respectively. NPG diesters also exhibit a relatively good viscosity of 21 cSt. The most striking observation to emerge from the data comparison with NPG diester was the breakdown voltage, which was higher than mineral oil and definitely in conformance to the IEC 61099 limit at 67.5 kV. The formulation of synthesized NPD diesters with VISCOPLEX® pour point depressant has successfully increased the pour point of NPG diester from -14°C to -48°C.
CONCLUSION: The reaction time for the transesterification of HOPME with NPG to produce NPG diester was successfully reduced to 1 hour from the 14 hours required in the earlier synthesis method. The main highlight of this study was the excess reactant which is no longer methyl ester but the alcohol (NPG). The optimum reaction conditions for the synthesis were molar ratio of 2:1.13 for NPG:HOPME, 182°C, 0.6 mbar and catalyst concentration of 1.2 wt%. The maximum NPG diester yield of 87 wt% was consistent with the predicted yield of 87.7 wt% obtained from RSM. The synthesized diester exhibited better insulating properties than the commercial products especially with regards to the breakdown voltage, flash point and moisture content.