Calcium levofolinate is the calcium salt of levofolinic acid, levofolinic acid is an isomer of 5-formyltetrahydrofolate (ie folinic acid), and another form of folinic acid is dl-LV. The Calcium levofolinate in the body cannot be used, just to delay the metabolism of LV in the body, make it persist for a long time, and reduce the metabolic pathway of L-LV in the body, and weaken the effect of L-LV.
Calcium L-leucovorin is a new anti-tumor drug, mainly used to treat osteosarcoma after high-dose methotrexate treatment and the symptoms related to folic acid antagonism. Levoleucovorin can also be used to treat giant cell anemia caused by folic acid deficiency. It can also be used in combination with fluorouracil to prolong the survival of patients with advanced colon cancer or relieve symptoms.
Pharmaceutical Applications
Levoleucovorin is the biologically active substance of calcium folinate, and calcium folinate is a diastereomeric mixture of 5-formyl derivatives of tetrahydrofolate (THF). Calcium folinate 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 groups in the body. L-leucovorin (L-5 leucovorin) is rapidly metabolized (5,10-methyltetrahydrofolate, 5,10-leucovorin tetrahydrofolate) to L-5-methyltetrahydrofolate. L-5-methyltetrahydrofolate can be metabolized into 5,10-methylenetetrahydrofolate through other pathways of , and 5,10-methylenetetrahydrofolate is irreversibly converted through the catalytic reduction of PDAH2 and NADPH coenzymes. It is 5-methyltetrahydrofolate. The use of folinic acid can counteract the therapeutic effects and toxicity of hydrochloric acid antagonists that inhibit dihydrofolate reductase (such as methotrexate). Leucovorin can also enhance the efficacy and toxicity of fluoropyrimidine (such as 5-fluorouracil) in tumor treatment. Simultaneous use of folinic acid does not change the pharmacokinetic process of 5-fluorouracil in plasma.
Levoleucovorin calcium is mainly used as an adjuvant drug for tumor chemotherapy in addition to megaloblastic anemia caused by various reasons. (1) The rescue therapy of high-dose methotrexate combined with levofolinate calcium is used to counter the resistance of tumor cells to methotrexate, and it can also antagonize the toxicity of methotrexate to normal cells; (2) Left sub The combination of calcium folic acid and 5‑Fu enhances its therapeutic effect and prolongs the survival time of palliative treatment of advanced colorectal cancer.
1) Add tetrahydrofolate, a reduction product of raw material folic acid, to formic acid for formylation with trifluoroacetic acid as a catalyst, and place it at a temperature of 10°C-30°C (room temperature) for 10-24 hours Afterwards, 5,10-methylenetetrahydrofolate is obtained; then hydrochloric acid is added, so that the formylation intermediate-5,10-methylenetetrahydrofolate is precipitated in the form of hydrochloride;2) Reconstitute the precipitated hydrochloride of 5,10-methylenetetrahydrofolate with formic acid, add hydrochloric acid and recrystallize to precipitate refined products of 5,10-methylenetetrahydrofolate;3) Suspend the recrystallized 5,10-methylenetetrahydrofolate hydrochloride in water, add an aqueous solution of a medium strong base such as piperazine to make a buffer system, and then add a medium strong base such as piperazine or strong Adjust the pH value of the ring-opening reaction system to 5.5-7.5 with an aqueous base such as sodium hydroxide, perform heating to hydrolyze the ring-opening, and directly add anhydrous CaCl2 equal to the weight (w/w) of the intermediate to the solution after ring-opening, and Adjust the pH value to 5.5-8.5, place it, the precipitated solid is calcium levofolinate;4) The precipitated calcium levofolinate is recrystallized with water to obtain a refined product of calcium levofolinate.
L-Folinic acid is a reduced folic acid and isomer of DL-folinic acid . DL-Folinic acid is a racemic mixture of D-folinic acid and L-folinic acid that has been used to prevent toxicity following therapy with high-dose methotrexate , to enhance the antitumor activity of 5-fluorouracil , and as a folate supplement. Clinical studies demonstrate that formulations containing L-folinic acid have similar efficacy and tolerability as those contianing DL-folinic acid and have been used interchangeably for modification of antitumor activity of 5-fluorouracil, while D-folinic acid is inactive.
Off-White to Light Beige Amorphous Powder
intermediate from Folic Acid metabolism
It is an intermediate product of the metabolism of Folic Acid; the active form into which that acid is converted in the body, ascorbic acid being a necessary factor in the conversion process.
Calcium levofolinate is a pharmaceutical drug that is used in biological studies for the treatment of colorectal cancer.
