Pharmaceutical composition containing 5'-Ara-C-O-amino ester

Abstract

The invention provides a composition for oral pharmaceuticals, using 5'-Ara-C-O-amino ester or its salt as an active ingredient. According to dissolution testing, a second method in the appendix XC of the second part of Chinese pharmacopoeia edition 2010, the dissolution of the active ingredient of the composition is higher than or equal to 80% in 15 min, by using 900 ml of water as a dissolving medium at a rotation speed of 50 rpm. Organic acids are added into a prescription of the composition, a certain ratio of the organic acids is maintained, and thus the stability of pharmaceutical composition is substantially improved. A short-term stability test presents no increase in impurity.

Description

technical field [0001] The present invention relates to the field of pharmaceutical compositions comprising cytarabine prodrugs as active ingredients. More specifically, the present invention relates to an oral pharmaceutical composition, which contains cytarabine 5'-0-amino acid ester as an active ingredient, and the absolute bioavailability after oral administration can reach more than 60%. Background technique [0002] The chemical name of cytarabine is 1-β-D-arabinofuranosyl-4-amino-2(1H)-cytosine. Cytarabine can be converted into active cytarabine triphosphate in the body. Cytarabine triphosphate inhibits DNA polymerase and infiltrates DNA in a small amount, thereby preventing DNA synthesis and inhibiting cell growth. Cytarabine is one of the most effective drugs clinically used in the treatment of acute myeloid leukemia, acute lymphoblastic leukemia and lymphoma. Cytarabine also has antiviral effects and is used to treat various herpes virus infections. In nervous s...

AI Technical Summary

Problems solved by technology

[0004] However, there are some disadvantages in intravenous administration: the drug is highly irritating to the skin and subcutaneous tissue. If it leaks out of the vein, it can cause phlebitis and surrounding tissue necrosis; the injection of foreign particles or air can cause embolism, and drug contamination can easily cause infection; Directly entering the blood, prone to various side reactions such as allergies, poisoning, etc.; too fast to overload the circulation, prone to acute heart failure, pulmonary edema and other critical illnesses

[0006] However, the molecular polarity of cytarabine is very large, which leads to poor membrane permeability of the small intestine, and is easily inactivated by deamination of cytosine nucleoside deaminase in the gastrointestinal mucosa and liver, resulting in the oral bioavailability of cytarabine very low (about 20%)

But there is no report about the oral preparation of this class of prodrugs

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