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A kind of ipratropium bromide monohydrate

A technology of ipratropium bromide and monohydrate, which is applied in the field of medicinal chemistry and crystal form of ipratropium bromide, can solve the problems of inapplicability to large-scale production, cumbersome operation steps, poor chemical stability, etc., and achieve good chemistry The effect of stability, high crystal purity and good solubility

Active Publication Date: 2022-05-13
LUNAN PHARMA GROUP CORPORATION
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the two technical schemes disclosed in this document can prepare and obtain ipratropium bromide crystals, the former method requires the use of supercritical CO 2 And continuous high-pressure supply, these conditions have high requirements on equipment, so it is impossible to obtain high-purity crystals stably, and the operation steps of these two methods are relatively cumbersome, and the conditions are relatively harsh, and small-scale preparation in the laboratory can achieve , but not suitable for large-scale production
In addition, this document has not carried out careful research on the stability and solubility of the corresponding crystal forms of ipratropium bromide.
There is poor chemical stability in the Ipratropium bromide prepared by the existing technology, and the problem of easy deterioration. After research, it is found that the impurity content of the existing Ipratropium bromide will increase with the increase of ambient temperature in the solution state. And increase, thereby have greatly influenced product purity, this problem also brings certain potential problem to the storage or use of different third detropammonium bromide

Method used

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  • A kind of ipratropium bromide monohydrate
  • A kind of ipratropium bromide monohydrate
  • A kind of ipratropium bromide monohydrate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Add 1g of ipratropium bromide powder sample to 20ml of N,N-dimethylformamide, heat to 50°C, stir to dissolve and add 1.5ml of purified water dropwise to obtain a clear solution; slowly add 20ml of THF to In the clarified solution, the dropping time is 30 minutes, stirred and cooled to crystallize (control the cooling rate at 0.5°C / min), after cooling down to 5-15°C, stand for crystallization under temperature control for 48 hours, filter, and vacuum dry at 50°C for 10 hours Ipratropium bromide monohydrate was obtained with a yield of 93.26% and a purity of 99.96%.

Embodiment 2

[0049] Add 1g of ipratropium bromide powder sample to 20ml of dimethyl sulfoxide, heat to 40°C, stir to dissolve and add 1.5ml of purified water dropwise to obtain a clear solution; slowly add 20ml of acetone dropwise to the clear solution, Add dropwise for 30 minutes, stir and cool to crystallize (control the cooling rate at 0.5°C / min), cool down to 5-15°C, let stand for crystallization under temperature control for 48 hours, filter, and vacuum dry at 40°C for 14 hours to obtain ipratropium Ammonium bromide monohydrate, yield 91.31%, purity 99.95%.

Embodiment 3

[0051] Add 1g of ipratropium bromide powder sample to 20ml of N,N-dimethylacetamide, heat to 60°C, stir to dissolve and add 1.5ml of purified water dropwise to obtain a clear solution; slowly drop 20ml of ethyl acetate Add it into the clear solution, add dropwise for 30 minutes, stir and cool to crystallize (control the cooling rate at 0.5°C / min), cool down to 5-15°C, set the temperature to stand for crystallization for 48 hours, filter, vacuum at 60°C After drying for 13 hours, ipratropium bromide monohydrate was obtained with a yield of 92.11% and a purity of 99.94%.

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Abstract

The invention provides an ipratropium bromide monohydrate and a preparation method thereof. The specific steps are: after adding ipratropium bromide into a benign solvent, heat and stir to dissolve and add a certain amount of purified water dropwise, after the solution is clarified, add a poor solvent dropwise, and obtain high-purity ipratropium bromide through programmed cooling and crystallization Ammonium bromide monohydrate. The preparation method of the invention has the advantages of simple operation, high product yield and high purity, and the ipratropium bromide monohydrate provided by the invention has good solubility and chemical stability, and is suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, in particular to the technical field of ipratropium bromide crystal form, specifically ipratropium bromide monohydrate, its preparation method and application. Background technique [0002] Ipratropium bromide monohydrate (Ipratropium Bromide), the chemical name is (1R, 3r, 5s, 8r)-3-[[(2RS)-3-hydroxy-2-phenylpropoxy]oxo]-8- Methyl-8-(1-methylethyl)-8azabicyclo[3,2,1]octane bromide monohydrate, it is white or off-white crystalline powder, CAS number: 66985-17- 9, its structural formula is as follows: [0003] [0004] Ipratropium bromide is a kind of anticholinergic drug, it has higher selectivity to bronchial smooth muscle M receptor, has stronger relaxation effect to bronchial smooth muscle, and the effect on respiratory tract gland and cardiovascular system is relatively weak. weak. Ipratropium bromide can be used to prevent and treat bronchial asthma and asthmatic chronic br...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D451/10A61P11/06A61K31/46
CPCC07D451/10A61P11/06C07B2200/13
Inventor 翟立海王聚聚郭立红黄超
Owner LUNAN PHARMA GROUP CORPORATION