Ganciclovir recovery method

A technology of ganciclovir and recovery methods, which is applied in the field of preparation and recovery of pharmaceutical raw materials, can solve the problems of difficulty in sewage treatment, poor product quality, and difficulty in recovery quality, and achieve reduced recrystallization times, less crystallization times, and considerable economic benefits Effect

Active Publication Date: 2010-10-06
SHANGHAI YIWEI INDAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Ganciclovir is a multi-step chemical reaction, and some process intermediate steps involve isomer resolution, so the yield is low-cost and high. The domestic process mainly uses 2,9-diacetylguanine as the starting material, and 1, 3-dichloromethoxyl-2-propoxymethanol acetate carries out condensation reaction, carries out esterolysis reaction with acetic anhydride again, hydrolyzes and refines to obtain Ganciclovir crude product, finally four crystallization purifications can reach pharmacopoeia standard again, but It cannot meet the requirements of the United States Pharmacopoeia for related substances, which also restricts the export of this product. Therefore, finding a method for recovering the mother liquor of ganciclovir can not only improve the quality of drug use for Chinese people, enhance drug safety, but also make the export of this product more profitable. considerable economic benefits
In addition, during the purification and crystallization process of ganciclovir, a large amount of mother liquor is produced, the concentration is not high, but the recovery quality is difficult to meet the requirements. If 100 kg of ganciclovir is produced, about ten tons of mother liquor will be produced, and about 50 kg of the product will be discarded. It is wasted in vain, and it also brings certain difficulties to sewage treatment
At present, the mother liquor produced by the production of ganciclovir is directly concentrated and then cooled to crystallize. The quality of the obtained product is very poor and must be recrystallized many times. Therefore, finding an efficient recovery method will greatly reduce the production cost of ganciclovir. , while reducing waste and environmental pollution in the production process

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Produce 2000 liters of mother liquors when producing ganciclovir, purity is 92%, maximum impurity 6.8%, the solubility under normal temperature of general ganciclovir aqueous solution neutral condition is 5 grams per liter, so contain ganciclovir about 10 kg, concentrate to dryness first, add 20 liters of 7% sodium hydroxide solution, heat up at 35°C, stir and slowly add 7% sodium hydroxide solution. Add a total of about 37 liters of sodium hydroxide solution, then add 2 kg of activated carbon, keep stirring for 2 hours, filter to obtain a clarified filtrate, raise the temperature of the filtrate to 50°C, and add ethanol dropwise at a rate of 70 liters / h, crystals appear in the feed liquid , when it becomes turbid, stop adding ethanol, continue to add ethanol after half an hour, add 222 liters of ethanol in total, slowly cool down to 15°C after adding ethanol, filter to obtain the wet product of ganciclovir sodium salt, the purity of sampling is 98.6%, the maximum The i...

Embodiment 2

[0020] The mother liquor produced in the production of ganciclovir, generally, the solubility of ganciclovir in aqueous solution under neutral conditions and normal temperature is 5 g / liter, and the production of 100 kg of ganciclovir can produce about 10,000 liters of such mother liquor in total, which is dissolved in ganciclovir About 50 kilograms of clovir, sampling detection, the purity of ganciclovir in the mother liquor is 90.2%, and the maximum impurity is 7.9%. Concentrate the mother liquor to dryness first, add 70 liters of 7% sodium hydroxide solution, raise the temperature to 35°C, stir and slowly add 7% sodium hydroxide solution, the pH of the seasoning solution is 13.2, and the feed solution is basically clear, 7% Add about 98 liters of sodium hydroxide solution in total, then add 5 kg of activated carbon, keep stirring for 2 hours, filter to obtain a clarified filtrate, raise the temperature of the filtrate to 50°C, and add ethanol dropwise at a rate of 200 liters...

Embodiment 3

[0022] A method for recovering the mother liquor of ganciclovir. The mother liquor of ganciclovir is concentrated to a certain concentration, alkalized by an alkaline solution, crystallized by adding an organic solvent, dissolved in an aqueous solution after filtration, neutralized by adding hydrochloric acid, and slowly dissolved by heating Cooling and crystallization can obtain high-purity ganciclovir.

[0023] The method specifically includes the following steps:

[0024] a. After concentrating the mother liquor of ganciclovir, adjust the pH to 10.0 with 0.1% sodium hydroxide alkaline solution, so that ganciclovir becomes a salt and is easily soluble in water. Stir at 60°C for 10 minutes at an insulated temperature, and add the raw material solution. Activated carbon containing 10% by weight of ganciclovir, adding activated carbon can absorb some impurities and ensure the filtering effect, stir for 1 hour, and filter; to remove some insoluble impurities.

[0025] b. Heat t...

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PUM

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Abstract

The invention relates to a ganciclovir recovery method, which comprises the steps that ganciclovir mother solution is concentrated, alkaline solution is added to adjust pH value to 10.0-13.5, temperature is kept to be constant at 20-60 DEG C for 10-60 minutes, active carbon is added and agitation is conducted for 1-3h, filtration is conducted, organic solution is added in filtrate to precipitate white crystals, filtration is conducted, filter cakes are dissolved in deionized water, hydrochloric acid is added to regulate pH value to 5-6, solid sediment is precipitated, after the solid sediment is heated and dissolved, the temperature of the solid sediment is slowly decreased by 0-30 DEG C to precipitate crystals, and the crystals are filtered and dried to obtain high-purity ganciclovir products. Compared with the prior art, the invention has the advantages of simple operation, high yield, low cost, no pollution and the like.

Description

technical field [0001] The invention relates to the preparation and recovery of pharmaceutical raw materials, in particular to a recovery method of ganciclovir. Background technique [0002] Ganciclovir is an acyclic nucleoside antiviral drug, which is active against all herpes viruses, and its activity against E-B virus (EBV) and cytomegalovirus (CMV) is greater than that of acyclovir. Its mechanism of action is similar, and its selectivity to viruses is higher, but its toxicity to mammals is less; And anti-SARS virus etc. also have certain effect. Ganciclovir is a multi-step chemical reaction, and some process intermediate steps involve isomer resolution, so the yield is low-cost and high. The domestic process mainly uses 2,9-diacetylguanine as the starting material, and 1, 3-dichloromethoxyl-2-propoxymethanol acetate carries out condensation reaction, carries out esterolysis reaction with acetic anhydride again, hydrolyzes and refines to obtain Ganciclovir crude product...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D473/18
Inventor 秦永忠章培俊
Owner SHANGHAI YIWEI INDAL
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