Method for purifying orlistat

A technology of orlistat and organic solvents, which is applied in the field of preparing high-quality orlistat, can solve the problems of serious environmental pollution, unreachable, increased production costs, etc., and achieve the effects of simple process, high production efficiency and stable operation

Active Publication Date: 2011-04-13
HISUN PHARMACEUTICAL (HANGZHOU) CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This recrystallization method has the disadvantages of large solvent consumption, low yield, serious environmental pollution, etc., which will inevitably greatly increase the production cost.
Moreover, in terms of product quality, the impurity requirements of ICH cannot be met, that is, the content of known impurities is less than or equal to 0.15%, and the content of unknown impurities is below 0.10%.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] The prepared column is DAC300, the filler is 10 μm C18, the total volume of the column is 13.5Kg, the volume is 17L, the height of the column is 25.6cm, and the pressure of the column is 190bar. The chromatographic content of orlistat raw materials is 94.23%. The wet material is 64Kg (about 30Kg orlistat after calibration). Add 130L of anhydrous methanol and 2Kg of activated carbon, stir to dissolve, decolorize, filter, and the concentration of the dissolved decolorization solution is 110mg / ml . The process adopts two-stage preparation, and the first column adopts 93% methanol solution as the mobile phase, the elution flow rate is 2500ml / min, and the single loading amount is 11g / Kg filler, that is, 150g orlistat (injection speed 300mg / ml, injection time 4.5min). A total of 4800L of orlistat eluate was collected and concentrated to obtain 272L of concentrated solution with a concentration of 95.6mg / ml and a chromatographic content of orlistat of 97.54%; 90% methanol s...

Embodiment 2

[0042] Prepare the column model DAC200, the filler is 10 μm C18, the total amount of the column is 6Kg, the volume is 8L, and the height of the column is 25.2cm. The chromatographic content of orlistat raw materials is 92.11%. The wet material is 32Kg (about 12Kg orlistat after calibration). Add 80L of anhydrous methanol and 1Kg of activated carbon, stir to dissolve, decolorize, and filter to obtain a dissolved decolorization solution with a concentration of 96.8mg / ml. The process adopts two-stage preparation. For the first time, it is eluted with 93% methanol solution, the elution flow rate is 1500ml / min, and the single loading amount is 10g / Kg filler, that is, 60g orlistat. The orlistat collected for the first time on the column The sate eluate was concentrated and crystallized in a single tank to obtain 29.42Kg of wet material, about 10.47Kg of orlistat was calibrated, and the chromatographic content was 97.02%. Then, the orlistat wet material obtained from the first colu...

Embodiment 3

[0044] Prepare the column model DAC100, use 10μm C18 filler, pack a total amount of 1.5Kg, and pack a height of 25.8 cm. Orlistat raw material 100g, chromatographic content 97.69%, was dissolved by stirring with 90% methanol solution, and filtered. The process adopts a first-level preparation, using 90% methanol solution as the mobile phase for elution, the elution flow rate is 300ml / min, and the single loading amount is 5g / Kg filler, that is, 7.5g orlistat, and the collected orlistat is eluted The liquid was concentrated under reduced pressure with a rotary evaporator at a temperature below 30°C, and then crystallized at a temperature of 0-5°C for 8 hours, and 181g of wet material was obtained by suction filtration. The maximum impurity content was 0.104% by HPLC detection. Dissolved with n-heptane, crystallized, and dried to obtain 76.3g of the finished product. After testing, the maximum impurity chromatographic content was 0.095%, and the orlistat chromatographic content w...

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Abstract

The invention relates to a method for purifying an organic compound, in particular to a method for preparing high-quality orlistat and a process thereof. By adopting the process disclosed by the invention for separating and preparing the high-quality orlistat with a dynamic axial compression preparation column, the chromatography content of the orlistat can reach more than 99.0% when the content of the orlistat is tested by adopting a high performance liquid chromatography, the content of known impurities is less than or equal to 0.15%, the content of unknown impurities is less than 0.10%, and the invention is completely in line with high quality requirements on ICH (The International Conference on Harmonization of Technical Requirements for Registration of pharmaceuticals for Human use).

Description

technical field [0001] The invention relates to a method for purifying an organic compound, in particular to a method for preparing high-quality orlistat and a process thereof. Background technique [0002] Orlistat (Orlistat) is a hydrogenated derivative of the natural product Lipstatin (lipstatin) of the genus Streptomyces, and its chemical name is S-2-formamido-4-methylpentanoic acid (S-)- 1-{[(2S,3S)-3-Hexyl-4-oxo-2-ethoxy]methyl}dodecyl ester. Orlistat is a weight-loss drug developed by Hoffmey-Roche Co., Ltd. in Basel, Switzerland. It is a long-acting and potent specific gastrointestinal fat inhibitor, through the combination of gastric lipase and pancreatic fat in the stomach and small intestine The active serine part of the enzyme forms a covalent bond to inactivate the enzyme to play a therapeutic role. The inactivated enzyme cannot hydrolyze the fat in the food, mainly triglycerides, into absorbable free fatty acids and monoacylglycerols. Undigested triglycerides...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D305/12A61P3/04
Inventor 朱国荣应雪肖邓传亮王希泮鑫亮
Owner HISUN PHARMACEUTICAL (HANGZHOU) CO LTD
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