Freeze-dried powder injection containing leucovorin sodium and its preparing method

Abstract

The freeze dried powder for injection contains leucovorin sodium in 5-100wt% and freeze drying supplementary material in 0-95wt%, and the supplementary material includes excipient, buffering agent and / or isosmotic regulator. The preparation process and application in resisting tumor of the freeze dried powder for injection containing leucovorin sodium is also provided.

Description

technical field [0001] The invention relates to a freeze-dried drug, in particular to a freeze-dried powder preparation containing sodium folinate, which can be used to enhance and assist the curative effect of antitumor drugs. Background technique [0002] Folinic acid is the isometric racemate of the 5-formyl derivative of tetrahydrofolate (THF). The biologically active substance in the racemic form is L-form, called citric acid factor or levofolinic acid. Folinic acid does not need to be reduced by dihydrofolate reductase to directly participate in the biological reaction using folic acid as a carrier for transferring "one-carbon group" in vivo. L-folinic acid (L-5 leucovorin) is rapidly metabolized (5,10-methyltetrahydrofolate and 5,10-methylenetetrahydrofolate in that order) to L-5-methyltetrahydrofolate . L-5-methyltetrahydrofolate can be metabolized into 5,10-methylenetetrahydrofolate in turn through other pathways, and 5,10-methylenetetrahydrofolate is irreversibl...

AI Technical Summary

Problems solved by technology

[0003] Folinic acid is generally prepared in the form of calcium salts. Calcium folinate preparations for injection are generally divided into two types: freeze-dried and water-injected. However, in the process of clinical application, people found that although calcium folinate is easily soluble in water, However, the stability of its aqueous solution is not good, and it is easy to produce precipitation, which causes inconvenience in administration. More importantly, because folinic acid is mainly used in high-dose chemotherapy, that is, it is used in combination with 5-fu (5-fluorouracil). Calcium ions have side effects on the human heart, large doses of calcium folinate, the calcium ions will have side effects on the human body, so the general clinical dosage is up to 200mg / m 2 In many cases, this dose is not sufficient for treatment or adjuvant therapy (chemotherapy), at least not the optimal dose, and because calcium salts can produce precipitation with many drugs (such as 5-fu), so in the treatment (chemotherapy) The administered calcium folinate must be administered alone, which undoubtedly causes inconvenience to patients and also becomes a hidden danger in drug safety.

[0004] At present, sodium folinate water injection preparations for injection have also appeared in commercially available products. While the clinical efficacy of the sodium folinate water injection has been recognized, it has been found that the water injection dosage form has the defect that the product is unstable after being placed. The specific performance is that the content of the active ingredient in the aqueous injection preparation drops significantly, and the related substances (impurities) increase significantly, although it is inevitable in the preparation of the aqueous injection preparation. During the molding process, a pH buffer was added, and the pH value also changed significantly during the placement process, and the color became darker, etc., which brought a series of problems to the storage and application of the drug.