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Method for separating and purifying amoxicillin trihydrate

A technology for amoxicillin and hydrate, which is applied in the field of separation and purification, can solve the problems of shortening the validity period and shelf life of amoxicillin preparations, yellowing, and affecting the storage time of amoxicillin trihydrate, and achieves easy industrial production and low cost , cheap effect

Inactive Publication Date: 2012-07-25
HEBEI UNIVERSITY OF SCIENCE AND TECHNOLOGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The type and amount of impurities remaining in the amoxicillin trihydrate obtained by this method are relatively large, which seriously affects the storage time of the amoxicillin trihydrate, causing yellowing and degradation of the amoxicillin trihydrate in a short period of time. Phenomenon, which seriously shortens the validity period and shelf life of amoxicillin preparations

Method used

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  • Method for separating and purifying amoxicillin trihydrate
  • Method for separating and purifying amoxicillin trihydrate
  • Method for separating and purifying amoxicillin trihydrate

Examples

Experimental program
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Effect test

Embodiment 1

[0032] Add 2L of methanol to 38L of amoxicillin hydrochloride aqueous solution (concentration: 0.6g / mL), add 11.4g of tetramethylammonium bromide, and use 25.87L of dilute ammonia water with a concentration of 10% in the range of 3°C-6°C Adjust the pH value of the solution to 4.8, keep the temperature of the solution at 1°C-4°C, grow the crystal for 1 hour, precipitate amoxicillin trihydrate, separate by centrifugation, wash the crystal with 2L of 3% methanol aqueous solution, and then wash with 3L of methanol , after centrifugal separation and vacuum drying, 23.32kg of amoxicillin trihydrate can be obtained, with a yield of 97.6%, and a content of 99.72% by HPLC external standard method.

[0033] HPLC method: use octadecyl bonded silica gel as filler; mobile phase A is 0.05mol / L phosphate buffer (get 0.05mol / L potassium dihydrogen phosphate solution, adjust pH value with 2mol / L sodium hydroxide solution to 5.0)-acetonitrile (99:1); mobile phase B is 0.05mol / L phosphate buffer...

Embodiment 2

[0037] Add 1.8L of ethanol to 23L of amoxicillin hydrochloride aqueous solution (concentration: 0.7g / mL), add 16.1g of diethylethanolammonium chloride, and dilute with a concentration of 10% in the range of 2°C to 6°C. Adjust the pH value of the solution to 4.82 with 17.57L of ammonia water, keep the temperature of the solution at 4°C-7°C to grow the crystal for 0.5h, precipitate amoxicillin trihydrate, centrifuge, wash the crystal with 1.8L of 5% ethanol aqueous solution, and then Then wash with 2.5 L of ethanol, centrifuge and vacuum dry to obtain 16.18 kg of amoxicillin trihydrate with a yield of 96% and a content of 99.81% by the HPLC external standard method. The HPLC method is the same as in Example 1.

Embodiment 3

[0039] Add 3L of isopropanol to 30L of amoxicillin hydrochloride aqueous solution (concentration: 0.5g / mL), add 1.5g of methyltriethylammonium chloride, and use concentration of 10% in the range of 3°C-6°C Adjust the pH value of the solution to 4.9 with 15.71L of dilute ammonia water, keep the temperature of the solution at 2°C-4°C and grow the crystal for 1.7h. Amoxicillin trihydrate is precipitated, separated by centrifugation, and washed with 2.6L of 10% isopropanol aqueous solution. The crystals were then washed with 2.8L of isopropanol, centrifuged and vacuum-dried to obtain 15.38 kg of amoxicillin trihydrate with a yield of 98% and a content of 99.85% by the HPLC external standard method. The HPLC method is the same as in Example 1.

[0040] like figure 1 The Amoxicillin trihydrate HPLC collection of illustrative plates prepared for embodiment 3

[0041] like image 3 It is the comparison chart of the HPLC spectrum of amoxicillin trihydrate prepared in Example 3 and C...

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Abstract

The invention discloses a method for separating and purifying amoxicillin trihydrate, which comprises the following steps: adding certain amount of organic solvent and quaternary ammonium salts in an aqueous amoxicillin acid salt solution, and adjusting the pH value of the solution with an alkaline solution under low temperature to the isoelectric point of amoxicillin; continuing to maintain the temperature of the solution at 2-8 DEG C and growing the grain for some time, and separating out the amoxicillin trihydrate; and allowing the sample to be sequentially washed by a water-containing organic solvent and a pure organic solvent to obtain an amoxicillin trihydrate crystal. The method of the invention has simple operation, the impurities of the obtained amoxicillin trihydrate have the fewest types and quantity, the obtained amoxicillin trihydrate has the best quality, and the used organic solvents have low prices, so the method has low cost and is easy for industrialization production.

Description

technical field [0001] The invention relates to the technical field of separation and purification, in particular to a method for separation and purification of amoxicillin trihydrate. Background technique [0002] Amoxicillin is (2S, 5R, 6R)-3,3-dimethyl-6-[(R)-(-)-2-amino-2-(4-hydroxyphenyl)acetamido]-7- Oxo-4-thia-1-azabicyclo(3,2,0)heptane-2-carboxylic acid hydrate, hardly soluble in water and methanol, very insoluble in ethanol, almost insoluble in acetone, chloroform and benzene . Amoxicillin is an oral raw material drug, which is characterized by strong bactericidal power, low toxicity, and good inhibitory effect on Escherichia coli and Proteus. [0003] Amoxicillin is currently prepared by chemical synthesis (mixed anhydride-condensation-hydrolysis-crystallization) and biological fermentation, no matter which method is used, it must be purified. Among them, isoelectric point crystallization is one of the important reasonable and effective purification methods. Th...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D499/68C07D499/18
Inventor 孙凤霞牛玉环刘敬涛
Owner HEBEI UNIVERSITY OF SCIENCE AND TECHNOLOGY
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