Research Of Left Leucovorin Calcium Injection Preparation Process And Quality

Calcium folinate, its chemical name is (-)-N-[4[[[(6S)-2-amino-5-formyl-1,4,5,6,7,8-six hydrogen-4-oxo-6-pteridine base] methyl] amino] benzoyl glutamic acidfive]-L calcium salt hydrate. The molecular formula is C20H21CaN7O75H2O. Calciumfolinate is folic acid reduced the formylation derivatives, Department of folic acid in vivoactivated form (see " folic acid "). Methotrexate folic acid antagonist role is combined withdihydrofolate reductase and block the conversion of folic acid to tetrahydrofolic acid salt.Serious toxic effects caused by treatment with calcium folinate clinical commonly used in theprevention of excessive or high dose of methotrexate after injection. When oral folic acid poorefficacy, but also for megaloblastic anemia sprue, malnutrition, pregnancy or infancy caused,but for vitamin B12deficiency anemia does not apply. In recent years the application ofcalcium folinate as adjuvant treatment for colon, rectal cancer, combined with fluorouracil,can prolong the survival time of. Calcium folinate effect but also has the obvious adversereaction, the study found calcium folinate, pharmacological effects of calcium levofolinateand calcium folinate in roughly the same, but it uses small dose, just half of calcium folinate,the side effect is small, single pharmacologically active enantiomer, side effects greatlyreduce. Safety, better curative effect, avoid the competitive impact of calcium folinate activityinto cells play a role, and to avoid the right leucovorin inactive accumulate in the body, so theclinically more calcium levofolinate.This paper is focused on the use of freeze-dry technology is designed and developed withcalcium folinate lyophilization injection, and quality control, establish a HPLC method fordetermination of calcium folinate basic physical chemical properties and freeze drying agent,determination of related substances content; the method of high sensitivity, strong specificity,absolute recovery was99.25±0.53%.In the preformulation study, the effect of different PH on the solution, effects of rawmaterials dissolved and the influence on the stability of solution, also examines the effects ofdifferent amount and types of materials, in the process of research focuses on theconfigurationof the temperature, the process of ultrafiltration, freeze drying process. Optimized from the aspects of formulation and process of two factors, ultimately determine the prescription,optimize the formulation: calcium folinate54mg, mannitol30mg, water for injection5ml.And the prescription of pilot study.The establishment of quality control to the left folinic acid in raw materials and finishedproducts in terms of quality control and quality standards, related substances and itsmethodology, impurity content and methodology of determination and comparison ofleucovorin calcium.