A purification process of medicine for treating deep fungal infection

A deep fungus and drug technology, applied in the direction of sugar derivatives, sugar derivatives, organic chemistry, etc., can solve the problems of complex process, high cost, low yield, etc., and achieve simple pretreatment, high yield, and good adsorption effect. Effect

Active Publication Date: 2016-03-30
SHANGHAI NEW ASIA PHARMA
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The technical problem to be solved by the present invention is to provide a purification process for the treatment of deep fungal infection medicaments for the original low yield, complex process and high cost. Macroporous resins of different polarities are selected to adsorb amphotericin B Impurities in to achieve purification effect

Method used

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  • A purification process of medicine for treating deep fungal infection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Step 1: Put 8.47g (1 billion total) of amphotericin B into 150mlDMF and 200ml80% methanol water solvent, adjust the pH to 2.0-4.0 with citric acid, and dissolve it, and filter the dissolved solution to obtain a clear filtrate;

[0023] Step 2: Pretreat resin A and resin B with DMF and methanol. Resin A adopts AM-7 type resin and resin B adopts AM-18 type resin. Take 170ml AM-7 type resin and 230ml AM-18 type resin respectively for wet loading In a chromatographic column with a column diameter ratio of 12.5:1, pass the filtrate through the mixed resin column, and control the outflow rate to 2-10ml / min; then add the filtrate obtained through the column to a mixed solvent of 100ml dichloromethane and 100ml water for injection , adjust the pH to 4.0-6.0 with triethylamine, and crystallize; after crystallization, put the solution in a water bath and slowly heat it to 35-45°C, and keep it for 18-24 hours to grow crystals.

[0024] Step 3: Suction filter the obtained crystal g...

Embodiment 2

[0027] Step 1: Put 462.96g (50 billion total) of amphotericin B into 10LDMF and 10L of 80% methanol water solvent, adjust the pH to 2.0-4.0 with citric acid, dissolve it, and filter the dissolved solution to obtain a clear filtrate;

[0028] Step 2: Pretreat the HPD-100 and HPD-500 macroporous resins with DMF and methanol, respectively, measure 11.4L of HPD-100 and 13.6L of HPD-500 resin wet-loaded with a column diameter ratio of 12.5 : In the chromatographic column of 1, the filtrate obtained in step 1 is passed through the mixed resin column, and the flow rate of control is 2~10ml / min; then the filtrate obtained by passing the column is added in the mixed solvent of 10L dichloromethane and 12.5L water for injection , adjust the pH to 4.0-6.0 with citric acid, and crystallize; after crystallization, keep the crystal growth tank at 35-45°C and let the crystal grow for 18-24 hours.

[0029] Step 3: Suction filter the crystal growth solution obtained in Step 2, send it to an ove...

Embodiment 3

[0032] Step 1: Put 847.46g (100 billion total) of amphotericin B into 18LDMF and 20L methanol (80%) solvent, adjust the pH to 2.0-4.0 with citric acid to dissolve it, and filter the dissolved solution to obtain a clear filtrate ;

[0033] Step 2: Pretreat the HPD-100 and HPD-500 macroporous resins with DMF and methanol respectively, and measure 17.8L of HPD-100 and 22.2L of HPD-500 resin respectively, and the column diameter ratio is 12.5 : In the chromatographic column of 1, the filtrate obtained in step 1 is passed through the mixed resin column, and the flow rate of control is 2-10ml / min; the filtrate obtained by passing the column is added in the mixed solvent of 15L dichloromethane and 20L water for injection, Use citric acid to adjust the pH to 4.0-6.0, and then crystallize; after crystallization, keep the crystal growth tank at 35-45°C, and let the crystal grow for 18-24 hours.

[0034] Step 3: Filter the crystal growth solution obtained, and send the crystallization t...

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Abstract

The invention discloses a technology for purifying medicines for treating deep fungal infection. The technology is characterized in that the technology comprises the following steps: 1, adding one-hundred-million amphotericin B to a mixed solvent of dimethyl formamide and a 180% methanol solution, and adjusting the pH value of the resulting solution; 2, preprocessing a macroporous absorbent resin A and a macroporous absorbent resin B which have different polarities with the dimethyl formamide and ethanol, mixing the resin A with the resin B according to a resin A / resin B ratio of 3:4-5:6, packing the resulting mixed resin to a chromatographic column having a column length-diameter ratio of 12.5:1 through using a wet packing method to obtain a mixed resin column, allowing a filtrate obtained in step 1 to pass through the mixed resin column, mixing the filtrate passing through the mixed resin column with dichloromethane and injection water according to a ratio of the amphotericin B to the dichloromethane to the injection water of one hundred million:10-20ml:10-25ml, adjusting the pH of the resulting solution with an acid or an alkali to 4.0-6.0, crystallizing, maintaining the temperature at 35-45DEG C after crystal generation, and carrying out crystal growing through allowing crystals to stand for 18-24h; and 3, carrying out suction filtration on the solution obtained after the crystal growing, and drying at 40-60DEG C for 24-30h to obtain products. The technology solves problems of low yield, complex technology and high cost of traditional recrystallization methods, and solves disadvantages of use of a single resin to purify, long column passing time, large resin consumption amount, and unsatisfactory effect.

Description

technical field [0001] The invention relates to a refinement and purification process of a crude drug, in particular to a purification process in the production process of a drug crude drug for treating deep fungal infections. Background technique [0002] Amphotericin B (Amphotericin B) is produced by Streptomyces nodosus (Streptomycesnodosus), the first confirmed effective macromolecular polyene antibiotic for fungal infections. It has a broad antibacterial spectrum and is the first choice for the clinical treatment of deep fungal infections. drug. Its chemical name is [0003] [1R-(1R*, 3S*, 5R*, 6R*, 9R*, 11R*, 15S*, 16R*, 17R*, 18S*, 19E, 21E, 23E, 25E, 27E, 29E, 31E, 33R* , 35S*, 36R*, 37S*)]-33-[(3-amino-3,6-dideoxy-β-D-mannopyranosyl)oxy]-1,3,5,6,9, 11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxobicyclo-[33.3.1]nonacosane-19,21,23,25, 27,29,31-heptacene-36-carboxylic acid, the chemical structure is as follows [0004] [0005] Although the producti...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07H17/08C07H1/06
Inventor 池王胄宋庭李仁勤孙常悖石永胜张玉莲
Owner SHANGHAI NEW ASIA PHARMA
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