Search

CN-121991141-A - Iron removing method for anthracycline

CN121991141ACN 121991141 ACN121991141 ACN 121991141ACN-121991141-A

Abstract

The invention belongs to the technical field of medicines, in particular to an iron removing method for anthracyclines, which uses macroporous cationic resin and treating agent to remove iron in anthracyclines, the method can improve the purity of the product, obviously improve the quality of the anthracycline product and is simple to operate. The reaction yield and purity are stable, and the method is suitable for industrial production.

Inventors

  • LIU ZHONG
  • ZHU ANGUO
  • YUAN GUOCHUN

Assignees

  • 鲁南制药集团股份有限公司

Dates

Publication Date
20260508
Application Date
20241106

Claims (9)

  1. 1. A method for removing iron from anthracycline includes such steps as adding the anthracycline containing iron to reactor, dissolving in water, adding treating agent, stirring, adding macroporous cationic resin, stirring, detecting the concentration of iron ions, removing iron, stopping stirring, suction filtering, collecting filtrate, and post-treating.
  2. 2. The method according to claim 1, wherein the anthracycline is one of daunorubicin hydrochloride, doxorubicin hydrochloride, idarubicin hydrochloride, epirubicin hydrochloride.
  3. 3. The method according to claim 1, wherein the mass ratio of water to anthracycline is 10-500:1, preferably 100-300:1.
  4. 4. The synthesis method according to claim 1, wherein the amount of the treating agent is 0.1% -10%, preferably 0.2% -1% of the amount of the anthracycline compound.
  5. 5. The method according to claim 1, wherein the treating agent is one of vitamin C, vitamin E, catechol, hydroquinone, sodium bisulphite, sodium sulfite, sodium dithionite, sodium metabisulfite, preferably vitamin C, sodium bisulphite.
  6. 6. The method according to claim 1, wherein the ratio of anthracycline compound to macroporous cationic resin is 1:0.01-10g/ml, preferably 1:1-5g/ml.
  7. 7. The method according to claim 1, wherein the macroporous cationic resin is IRA200 (Na) or IR-120(H)。
  8. 8. The method according to claim 1, wherein the temperature-controlled stirring temperature is 0-30 ℃, preferably 15-30 ℃.
  9. 9. The synthesis method according to claim 1, wherein the filtrate is subjected to aftertreatment, the filtrate is concentrated to gel under reduced pressure at 40-50 ℃, the temperature is maintained, absolute ethanol is slowly dripped, stirring is carried out, the temperature is reduced to 15-30 ℃ until the anthracycline compound is separated out, and the corresponding quality-qualified anthracycline compound is obtained through suction filtration.

Description

Iron removing method for anthracycline Technical Field The invention belongs to the technical field of medicines, and particularly relates to an iron removal method for anthracyclines. Background Anthracyclines have the characteristics of anthracyclines and glycosyl ligands and are widely used clinically to treat breast cancer, acute and non-lymphocytic leukemias, chronic lymphocytic leukemias, non-hodgkin's lymphomas, and other solid cancers. Common anthracycline antitumor drugs are daunorubicin, doxorubicin, idarubicin, epirubicin, pirarubicin, valrubicin, and the like. Anthracycline molecules themselves have some ability to complex metal ions. The following structure is disclosed as in US4138480 a: In which the letter "Me" is denoted as a metal ion, it can be seen that the metal ion can be complexed from 3 sites. Thus, such compounds often result in an overdose of the glowing residue. Particularly, in the production process, if the materials are contacted with iron ions in pipelines, reaction kettles and other contact equipment, the phenolic characteristic color development and the color change are generated, and the orange red is changed into black red, so that corresponding iron complexes are generated. CN201010150067.5 relates to a preparation method of daunorubicin, which comprises the steps of fermentation liquor filtration, macroporous resin adsorption purification and ethylenediamine tetraacetate complexation impurity removal, wherein the technical effects of daunorubicin purification are good by controlling the pH value, pretreatment of the fermentation liquor and a resin column and the like, the impurity B is reduced to below 0.5%, and the ignition residue is reduced to below 0.1%. The metal ion competing for complexation with ethylenediamine tetraacetate needs to be adjusted to be alkaline in pH. Effectively reduces the burning residue. At present, in the purification process of anthracyclines, most of the anthracyclines are subjected to resin purification, elution, concentration, extraction and other steps, and most of impurities are removed through resin adsorption. The free metal ions in the reactant can be adsorbed for removing impurities, but some complexes are difficult to remove, so that the burning residues are out of standard. Particularly, the complex formed by the iron ions and the anthracyclines, therefore, a simple and convenient iron removal method for the anthracyclines, which is suitable for industrialization, is urgently needed to be researched. Disclosure of Invention Aiming at the problems existing in the prior art, the invention provides an iron removal method for anthracyclines. The method has simple operation, avoids the complicated steps of resin column adsorption and elution, has low production cost and is very suitable for industrial production. The specific technical scheme of the invention is as follows: Adding iron-containing anthracycline compound into a reaction vessel at room temperature, adding water for dissolution, adding a treating agent, stirring uniformly, adding macroporous cationic resin, stirring at a controlled temperature, detecting the concentration of iron ions until the iron ions are qualified, stopping stirring after iron removal, carrying out suction filtration, collecting filtrate, and carrying out post-treatment on the filtrate to obtain the anthracycline compound with qualified quality. Preferably, the anthracycline compound is one of daunorubicin hydrochloride, doxorubicin hydrochloride, idarubicin hydrochloride and epirubicin hydrochloride. Preferably, the mass ratio of water to anthracycline is 10-500:1, preferably 100-300:1. Preferably, the amount of the treating agent is 0.1% -10%, preferably 0.2% -1% of the amount of the anthracycline compound. Preferably, the treating agent is one of vitamin C, vitamin E, catechol, hydroquinone, sodium bisulphite, sodium sulfite, sodium dithionite and sodium metabisulfite, and preferably vitamin C and sodium bisulphite. Preferably, the mass volume ratio of the anthracycline compound to the macroporous cationic resin is 1:0.01-10g/ml, preferably 1:1-5g/ml. Preferably, the macroporous cationic resin isIRA 200 (Na) orIR-120(H)。 Preferably, the temperature-controlled stirring temperature is from 0 to 30℃and particularly preferably from 15 to 30 ℃. Preferably, the filtrate is subjected to aftertreatment, namely the filtrate is concentrated to gel under reduced pressure at 40-50 ℃, the temperature is maintained, absolute ethyl alcohol is slowly dripped into the filtrate, stirring is carried out, the temperature is reduced to 15-30 ℃ until the anthracycline compound is separated out, and the corresponding quality-qualified anthracycline compound is obtained through suction filtration. Preferably, the anthracycline is used in an amount of 1:5 to 50g/ml, preferably 1:15 to 20g/ml, by mass/volume ratio to absolute ethanol. Compared with the prior art, the invention has the technical effects that: (1) The invention