Purifying method for etimicin sulfate

Abstract

The invention belongs to the field of medicines and relates to a purifying method for etimicin sulfate. The purifying method for etimicin sulfate provided by the invention comprises the following steps: 1) taking an etimicin sulfate solution and concentrating into an etimicin sulfate concentrated solution; 2) adding dilute sulphuric acid into the etimicin sulfate concentrated solution, thereby obtaining an etimicin sulfate concentrated solution; 3) adding active carbon in the etimicin sulfate concentrated solution, heating, stirring and filtering, thereby obtaining an etimicin sulfate refined solution; 4) adding the etimicin sulfate refined solution in a solvent, and stirring, thereby obtaining a mother solution rich in seed crystals; 5) adding another batch of etimicin sulfate refined solution prepared according to the steps 1-3 in the mother solution rich in seed crystals obtained in the step 4, controlling the temperature and standing by, thereby obtaining a crystal mixture of the etimicin sulfate; 6) mashing and filtering the crystal mixture of the etimicin sulfate, thereby obtaining a wet crystal of the etimicin sulfate; and 7) drying the wet crystal of the etimicin sulfate, thereby obtaining a high-purity etimicin sulfate crystal.

Description

Technical field

[0001] The invention belongs to the field of medicine, and relates to a method for purifying pharmaceutical compounds, in particular to a new method for purifying etimicin sulfate. Background technique

[0002] Etimicin sulfate is a new generation of semi-synthetic aminoglycoside antibiotic with independent intellectual property rights, which is highly efficient, low-toxic, and resistant to drug-resistant bacteria, developed by Chinese researchers. It is the only one that has obtained the national first-class new drug certificate. Anti-infective drugs.

[0003] Etimicin Sulfate Injection is suitable for sensitive Escherichia coli, Klebsiella pneumoniae, Serratia, Citrobacter, Enterobacter, Acinetobacter, Proteus, and hemophil Various infections caused by bacterium, Pseudomonas aeruginosa and Staphylococcus. Clinical studies have shown that this product has a good effect on the following infections: Respiratory tract infections: such as acute bronchitis, acute atta...

Examples

Embodiment 1

[0051] Example 1. Preparation method of the present invention

[0052] Take the etimicin solution separated by adsorption type macroporous resin with a purity of more than 90% and concentrate it to a concentration of 75% to obtain an etimicin concentrate. Add 30% dilute sulfuric acid with a concentration of 6mol / L to adjust to pH It is 5.8 to obtain etimicin sulfate concentrate, add 30% activated carbon, heat to 70°C, stir and keep for 1 hour, filter to obtain etimicin sulfate refined solution, cool to 2°C at 0.1L / min Slowly add 15L of solvent at the speed of acetone 21%, methanol 15%, ethanol 15%, diethyl ether 17%, ethyl acetate 20%, methyl butanone 12%, while constantly stirring, maintain the stirring speed 280rpm, and The temperature is lowered to 4°C and maintained for 60 minutes to obtain a mother liquor rich in seed crystals. The refined liquid of etimicin sulfate was cooled to 2℃, and added to the mother liquor rich in seed crystals at a rate of 1L / min, while stirring co...

Embodiment 2

[0053] Example 2. Preparation method of the present invention

[0054] Take the etimicin solution separated by adsorption type macroporous resin with a purity of more than 90% and concentrate it to a concentration of 72% to obtain an etimicin concentrate. Add 33% dilute sulfuric acid with a concentration of 7mol / L to adjust to pH It is 5.9 to obtain etimicin sulfate concentrate, add 33% activated carbon, heat to 75°C, stir and keep for 1.5 hours, filter to obtain etimicin sulfate refined solution, cool to 4°C, at 0.5L / min Add slowly to 18L of solvent at a speed of 5% water, 15% acetone, 10% methanol, 20% ethanol, 17% isopropanol, 21% hexane, and 12% ether. While stirring constantly, maintain the stirring speed at 200rpm , And lower the temperature to 4°C for 90 minutes to obtain a mother liquor rich in seed crystals. The refined liquid of etimicin sulfate was cooled to 4℃, and added to the mother liquor rich in seed crystals at a rate of 3L / min, while stirring continuously, main...

Embodiment 3

[0055] Example 3. Preparation method of the present invention

[0056] Take the etimicin solution separated by adsorption-type macroporous resin with a purity of more than 90% and concentrate it to a concentration of 70% to obtain an etimicin concentrate. Add 30% 5mol / L dilute sulfuric acid to adjust the pH Is 4.5 to obtain etimicin sulfate concentrate, add 40% activated carbon, heat to 90°C, stir and keep for 2 hours, filter to obtain etimicin sulfate refined solution, cool to 6°C at 0.3L / min Slowly add 20L of solvent, the solvent contains 8% water, 15% acetone, 15% methanol, 10% ethanol, 12% isopropanol, 15% ethyl ether, 10% methyl butanone, ethylene glycol monomethyl ether 15% while continuously stirring, maintaining a stirring speed of 250 rpm, and cooling to 6° C. for 120 minutes to obtain a mother liquor rich in seed crystals. The refined liquid of etimicin sulfate is cooled to 6°C, and added to the mother liquor rich in seed crystals at a speed of 5L / min, while constantly...

Technical field

[0001] The invention belongs to the field of medicine, and relates to a method for purifying pharmaceutical compounds, in particular to a new method for purifying etimicin sulfate. Background technique

[0002] Etimicin sulfate is a new generation of semi-synthetic aminoglycoside antibiotic with independent intellectual property rights, which is highly efficient, low-toxic, and resistant to drug-resistant bacteria, developed by Chinese researchers. It is the only one that has obtained the national first-class new drug certificate. Anti-infective drugs.

[0003] Etimicin Sulfate Injection is suitable for sensitive Escherichia coli, Klebsiella pneumoniae, Serratia, Citrobacter, Enterobacter, Acinetobacter, Proteus, and hemophil Various infections caused by bacterium, Pseudomonas aeruginosa and Staphylococcus. Clinical studies have shown that this product has a good effect on the following infections: Respiratory tract infections: such as acute bronchitis, acute atta...

Examples

Embodiment 1

[0051] Example 1. Preparation method of the present invention

[0052] Take the etimicin solution separated by adsorption type macroporous resin with a purity of more than 90% and concentrate it to a concentration of 75% to obtain an etimicin concentrate. Add 30% dilute sulfuric acid with a concentration of 6mol / L to adjust to pH It is 5.8 to obtain etimicin sulfate concentrate, add 30% activated carbon, heat to 70°C, stir and keep for 1 hour, filter to obtain etimicin sulfate refined solution, cool to 2°C at 0.1L / min Slowly add 15L of solvent at the speed of acetone 21%, methanol 15%, ethanol 15%, diethyl ether 17%, ethyl acetate 20%, methyl butanone 12%, while constantly stirring, maintain the stirring speed 280rpm, and The temperature is lowered to 4°C and maintained for 60 minutes to obtain a mother liquor rich in seed crystals. The refined liquid of etimicin sulfate was cooled to 2℃, and added to the mother liquor rich in seed crystals at a rate of 1L / min, while stirring co...

Embodiment 2

[0053] Example 2. Preparation method of the present invention

[0054] Take the etimicin solution separated by adsorption type macroporous resin with a purity of more than 90% and concentrate it to a concentration of 72% to obtain an etimicin concentrate. Add 33% dilute sulfuric acid with a concentration of 7mol / L to adjust to pH It is 5.9 to obtain etimicin sulfate concentrate, add 33% activated carbon, heat to 75°C, stir and keep for 1.5 hours, filter to obtain etimicin sulfate refined solution, cool to 4°C, at 0.5L / min Add slowly to 18L of solvent at a speed of 5% water, 15% acetone, 10% methanol, 20% ethanol, 17% isopropanol, 21% hexane, and 12% ether. While stirring constantly, maintain the stirring speed at 200rpm , And lower the temperature to 4°C for 90 minutes to obtain a mother liquor rich in seed crystals. The refined liquid of etimicin sulfate was cooled to 4℃, and added to the mother liquor rich in seed crystals at a rate of 3L / min, while stirring continuously, main...

Embodiment 3

[0055] Example 3. Preparation method of the present invention

[0056] Take the etimicin solution separated by adsorption-type macroporous resin with a purity of more than 90% and concentrate it to a concentration of 70% to obtain an etimicin concentrate. Add 30% 5mol / L dilute sulfuric acid to adjust the pH Is 4.5 to obtain etimicin sulfate concentrate, add 40% activated carbon, heat to 90°C, stir and keep for 2 hours, filter to obtain etimicin sulfate refined solution, cool to 6°C at 0.3L / min Slowly add 20L of solvent, the solvent contains 8% water, 15% acetone, 15% methanol, 10% ethanol, 12% isopropanol, 15% ethyl ether, 10% methyl butanone, ethylene glycol monomethyl ether 15% while continuously stirring, maintaining a stirring speed of 250 rpm, and cooling to 6° C. for 120 minutes to obtain a mother liquor rich in seed crystals. The refined liquid of etimicin sulfate is cooled to 6°C, and added to the mother liquor rich in seed crystals at a speed of 5L / min, while constantly...

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