Patent EA-003747-B1 (EA)
Title: Method of stabilizing aqueous pyrazoloacridone derivative solution
Inventor: TOMODA YUTAKA
IPC: C07D471/06
Filed: 1999-10-13
Abstract: 1. A method for stabilizing an aqueous solution containing a pyrazoloacridone derivative of formula (I): wherein R<1A>, R<1B>, R<1C> and R<1D> independently represent hydrogen, a C1-C6 alkyl group, -(CH2)p-X (wherein p is an integer of 1 to 6; and X represents a hydroxyl group, a C1-C6 alkoxy group, or -NR<2A>R<2B> (wherein R<2A> and R<2B> independently represent hydrogen, a C1-C6 alkyl group, -(CH2)m-Y (wherein m is an integer of 1 to 6; and Y represents a hydroxyl group, a C1-C6 alkoxy group, or -NR<3A>R<3B> (wherein R<3A> and R<3B> independently represent hydrogen or a C1-C6 alkyl group)), or R<2A> and R<2B> form a heterocyclic group together with the nitrogen atom adjacent thereto, including pyrrolidinyl, piperidino, piperazinyl, morpholino, thiomorpholino, quinolyl, pyrimidinyl, pyridazinyl, pyridyl, pyrrolyl, imidazolyl, pyrazolyl, or -CH((CH2)nOH)2 (wherein n is an integer of 1 to 5) or a pharmaceutically acceptable salt thereof, comprising adding an acid to said aqueous solution in a well-closed container, substituting the air in the container with an inert gas and sealing the container. 2. The method as claimed in claim 1, wherein the acid is an organic acid represented by the following formula (II): R<4>R<5>CH-COOH   (II) wherein R<4> represents hydrogen or hydroxy; and R<5> represents hydrogen, carboxy, or alkyl having from 1 to 3 carbon atoms which may be substituted with hydroxy or carboxy. 3. The method as claimed in claim 1, wherein the acid is lactic acid. 4. The method as claimed in any of claims 1 to 3, wherein the aqueous solution has a pH of 2 to 6. 5. The method as claimed in any of claims 1 to 4, wherein the inert gas is a nitrogen gas. 6. A well-closed container comprising an aqueous solution containing a pyrazoloacridone derivative represented by the following formula (I): wherein R<1A>, R<1B>, R<1C> and R<1D> independently represent hydrogen, a C1-C6 alkyl group, -(CH2)p-X (wherein p is an integer of 1 to 6; and X represents a hydroxyl group, a C1-C6 alkoxy group, or -NR<2A>R<2B> (wherein R<2A> and R<2B> independently represent hydrogen, a C1-C6 alkyl group, -(CH2)m-Y (wherein m is an integer of 1 to 6; and Y represents a hydroxyl group, a C1-C6 alkoxy group, or -NR<3A>R<3B> (wherein R<3A> and R<3B> independently represent hydrogen or a C1-C6 alkyl group)), or R<2A> and R<2B> form a heterocyclic group together with the nitrogen atom adjacent thereto, including pyrrolidinyl, piperidino, piperazinyl, morpholino, thiomorpholino, quinolyl, pyrimidinyl, pyridazinyl, pyridyl, pyrrolyl, imidazolyl, pyrazolyl, or -CH((CH2)nOH)2 (wherein n is an integer of 1 to 5) or a pharmaceutically acceptable salt thereof, and an acid, wherein the air in the well-closed container is substituted with an inert gas. 7. The well-closed container as claimed in claim 6 wherein said acid is an organic acid represented by the following formula (II): R<4>R<5>CH-COOH   (II) wherein R<4> represents hydrogen or hydroxy; and R<5> represents hydrogen, carboxy, or alkyl having from 1 to 3 carbon atoms which may be substituted with hydroxy or carboxy. 8. The well-closed container as claimed in claim 6, wherein the acid is lactic acid. 9. The well-closed container as claimed in any of claims 6 to 8, wherein the aqueous solution has a pH of 2 to 6. 10. The well-closed container as claimed in any of claims 6 to 9, wherein the inert gas is a nitrogen gas.