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Refinement technique of hydromorphone acid salt

A technology of hydromorphone and acid salt, which is applied in the field of refining technology of hydromorphone acid salt, can solve the problems of unsatisfactory refining effect, small amount of refining, cumbersome methods, etc., and achieve the reduction of impurity content and increase of yield , The effect of simple process

Active Publication Date: 2013-11-27
YICHANG HUMANWELL PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] At present, the refining method of hydromorphone acid salt in the prior art: the amount of refining is very small, the method is relatively cumbersome (such as: chromatographic column separation, multiple recrystallization,), and the refining effect is not ideal

Method used

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  • Refinement technique of hydromorphone acid salt

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Add 68.5g of hydromorphone and 270mL of hydrochloric acid (hydrochloric acid (V):purified water (V)=2:3) into the salt-forming reaction bottle, stir and dissolve at 45°C. The solution was transferred to the crystallization tank. Cool down to 5°C, stir and precipitate a large amount of solids, then add 840ml of absolute ethanol and 1260L of anhydrous diethyl ether in sequence, stir and crystallize for 2 hours. Filter, mix reagents (84ml of absolute ethanol, 126ml of anhydrous ether, wash the filter cake, wash until the filtrate pH=6~7, put it in an oven and dry under reduced pressure at 45°C for 6 hours to obtain 70.0g of crude hydromorphone hydrochloride.

[0034] Add 280mL of purified water into the refined decolorization tank, raise the temperature to 35°C, then add 70.0g of crude hydromorphone hydrochloride, stir to completely dissolve, add 2g of medicinal charcoal, and then add about 0.15mL of dilute hydrochloric acid (hydrochloric acid (V): Purified water (V) = 1:...

Embodiment 2

[0036] Add 60.0g of hydromorphone and 200mL of dilute hydrochloric acid (hydrochloric acid (V):purified water (V)=2:3) into the reaction flask, stir and dissolve at 40°C. The solution was transferred to the crystallization tank. Cool down to -5°C, stir to precipitate a large amount of solids, add 440ml of absolute ethanol and 440ml of anhydrous isopropyl ether in sequence, stir and crystallize for 1 hour. Filter, wash the filter cake with a mixed reagent (40ml of absolute ethanol, 60ml of anhydrous isopropyl ether), wash until the filtrate pH=6~7, put it in an oven and dry under reduced pressure at 42°C for 6 hours to obtain crude hydromorphone hydrochloride 63.5 g.

[0037] Add 180mL of purified water into the refined decolorization tank, raise the temperature to 40°C, then add 63.5g of crude hydromorphone hydrochloride, stir to completely dissolve, add 1.5g of medicinal charcoal, and then add about 0.10mL of dilute hydrochloric acid (hydrochloric acid (V) : Purified water ...

Embodiment 3

[0039]Add 70.0g of hydromorphone and 230mL of dilute hydrobromic acid (hydrobromic acid (V):purified water (V)=2:3) into the salt-forming reaction bottle, stir and dissolve at 45°C. The solution was transferred to the crystallization tank. Cool down to 10°C, stir and precipitate a large amount of solids, then add 840ml of absolute ethanol and 840ml of ethyl ether in turn, and stir for 1.5 hours to crystallize. Filter, wash the filter cake with a mixed reagent (70ml of absolute ethanol, 210ml of absolute ether), wash until the filtrate pH=6~7, put it in an oven and dry under reduced pressure at 45°C for 6 hours to obtain crude hydromorphone hydrobromide 72.0 g.

[0040] Add 280mL of purified water into the refined decolorization tank, raise the temperature to 40°C, then add 72g of crude hydromorphone hydrobromide, stir to completely dissolve, add 1.5g of medicinal charcoal, and then add about 0.20mL of dilute hydrobromic acid (hydrogen Bromic acid (V): purified water (V) = 1:...

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Abstract

The invention aims to overcome the defects in the prior art, and provides a new refinement method of hydromorphone acid salt. The method comprises the following steps: a. adding hydromorphone and dilute acid into a reaction kettle, and dissolving by stirring at 30-60 DEG C; cooling to 15--5 DEG C, stirring to precipitate abundant solid, adding alcohol and ether, and stirring to crystallize for 0.5-3 hours; filtering, washing until the pH value of the filtrate is 6-7, and drying in a drying oven to obtain a hydromorphone acid salt crude product; b. adding purified water into a refinement decolorization tank, heating to 30-60 DEG C, adding the hydromorphone acid salt crude product, stirring until the hydromorphone acid salt crude product is completely dissolved, adding medicinal carbon, adding dilute acid, and decolorizing at the constant temperature of 30-60 DEG C for 10-30 minutes; filtering, washing the filter cake with purified water, merging the washing liquid and filtrate, distilling under reduced pressure, refrigerating at 5+ / -5 DEG C to crystallize for more than 8 hours; and filtering, washing the filter cake with 95% ethanol, drying in a drying oven to obtain the hydromorphone acid salt.

Description

Technical field: [0001] The invention relates to a refining process, in particular to a refining process of hydromorphone acid salt. Background technique: [0002] There are many kinds of hydromorphone acid salts, and the acid can be inorganic acid or organic acid, such as HCl, HBr, HI, H 2 SO4,CH 3 COOH, oxalic acid, citric acid, etc., the most common of which is hydromorphone hydrochloride. [0003] The chemical name of hydromorphone hydrochloride is (-)-4,5α-epoxy-3-hydroxyl-17-methylmorphinan-6-one hydrochloride, and its chemical structure is: [0004] [0005] Hydromorphone hydrochloride is an opioid analgesic, a derivative of morphine, which mainly acts on μ receptors, and its analgesic potency is 8 times that of morphine. It has been used in the treatment of severe pain related to cancer, postoperative, obstetrics, and neurology in Europe and North America. [0006] Current patents mainly focus on the synthetic method of hydromorphone hydrochloride, for example...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D489/04
Inventor 张建勋杨家柱郑炜曾华荣周雪平于飞熊秀林
Owner YICHANG HUMANWELL PHARMA
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