Nisoldipine compound and novel preparation method thereof

A nisoldipine compound technology, applied in the field of nisoldipine compound and its new preparation method, can solve the problems affecting the quality of preparation products, the purity of the drug does not meet the requirements, and the content of substances increases, and achieve the effect of improving clinical adverse reactions

Inactive Publication Date: 2012-06-13
HAINAN MEILAN SMITH KLINE PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In fact, the general recrystallization purification technology is difficult to obtain high-purity nisoldipine, so the method of the prior art is not easy to obtain high-yield and high-purity nisoldipine, resulting in high cost and toxic residue of the drug, which affects the quality of the preparation product
[0009] In addition, when the compound is improperly stored or stored for too long, the content of the active ingredient

Method used

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  • Nisoldipine compound and novel preparation method thereof
  • Nisoldipine compound and novel preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0052] The refining of embodiment 1 nisoldipine

[0053] Dissolve 10 g of the crude product of nisoldipine with a purity of 96.52% in 40 ml of acetone, stir to make it completely dissolved, then add 0.2 g of activated carbon, stir and adsorb at 40°C for 15 minutes, filter for decarburization, and collect the filtrate; after concentrating under reduced pressure at 60°C Then add 10g of neutral alumina and stir evenly, add to the upper end of the prepared chromatographic column after evaporating the solvent, and then carry out separation and purification with a preparative chromatographic column, wherein the mobile phase used in the chromatographic column is acetone with a volume ratio of 30:50:20 : Mixed solution of ethanol: water, flow rate 1ml / min, stationary phase filler is ICN neutral alumina with a particle size of 18-32μm and a pore size of 6nm, column temperature is room temperature, wavelength 237nm, column pressure 1.0MPa, collect and elute liquid, and then concentrated...

Embodiment 2

[0057] The refining of embodiment 2 nisoldipine

[0058] Dissolve 10 g of nisoldipine crude product with a purity of 96.52% in 100 ml of acetone, stir to make it completely dissolved, then add 0.1 g of activated carbon, stir and adsorb at 50°C for 10 minutes, filter for decarburization, and collect the filtrate; after concentrating under reduced pressure at 50°C Then add 10g of neutral alumina and stir evenly, evaporate the solvent and add to the upper end of the prepared chromatographic column, then use the preparative chromatographic column to separate and purify the filtrate, wherein the mobile phase used in the chromatographic column is 30:50:20 by volume Acetone: ethanol: mixed solution of water, flow rate 2ml / min, stationary phase filler is particle diameter 50-200 μ m, pore diameter 6nm Baker column chromatography special neutral alumina, column temperature is room temperature, wavelength 237nm, column pressure 2.5MPa , collect the eluate, and then concentrate it under ...

Embodiment 3

[0062] The refining of embodiment 3 nisoldipine

[0063] Dissolve 10 g of the crude product of nisoldipine with a purity of 96.52% in 60 ml of acetone, stir to make it completely dissolved, then add 0.3 g of activated carbon, stir and adsorb at 45°C for 10 minutes, filter for decarburization, and collect the filtrate; after concentrating under reduced pressure at 55°C Then add 15g of neutral alumina and stir evenly, evaporate the solvent and add to the upper end of the prepared chromatographic column, then use the preparative chromatographic column to separate and purify the filtrate, wherein the mobile phase used in the chromatographic column is 30:50:20 by volume Acetone: ethanol: mixed solution of water, flow rate 1.7ml / min, stationary phase filler is ICN neutral alumina with a particle size of 18-32 μm and a pore size of 6 nm, the column temperature is room temperature, the column pressure is 2.0 MPa, and the wavelength is 237 nm. Collect the eluent, then concentrate it un...

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Abstract

The invention discloses a high purity nisoldipine compound, which comprises the following steps: (1) dissolving a certain amount of rough nisoldipine products in an organic solvent, adding activated carbon into the organic solvent to absorb and filter, collecting filtrate, and reducing pressure and concentrating to obtain primary purified nisoldipine; (2) separating and purifying the primary purified nisoldipine by using a preparation type chromatographic column, and collecting eluent to obtain secondary purified nisoldipine; and (3) decompressing and concentrating the eluent, adding water while stirring, performing heating and backflow, performing cooling and crystallization, and centrifugally washing and drying precipitated crystals to obtain tertiary purified nisoldipine. By means of the method, the nisoldipine produced has high purity, the toxic and side effects of prepared pharmaceuticals for treating hemorrhagic cerebrovascular diseases, high blood pressure and the like are reduced, product quality of preparation is improved, and the high purity nisoldipine compound is suitable for large-scale industrialization production.

Description

technical field [0001] The invention relates to a nisoldipine compound and a new preparation method thereof, which can obtain a high-purity nisoldipine compound and belongs to the technical field of medicine. Background technique [0002] Nisoldipine, yellow crystalline powder, chemical name: (±)-2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydro-3,5- Methyl picolinate isobutyl, molecular formula: C 20 h 24 N 2 o 6 , molecular weight: 388.41, the structural formula is as follows: [0003] [0004] Nisoldipine is currently the long-acting dihydropyridine calcium antagonist with the strongest selective vasodilation effect. Since the advent of nifedipine in 1971, more than 20 new drugs have been successfully developed. These drugs have the same mechanism of action (inhibition of Ca entry into tissue cells). Due to the difference in the binding properties of each compound to the receptor, the tissue selectivity is also different, and the pharmacological activity exhibited is a...

Claims

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Application Information

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IPC IPC(8): C07D211/90A61P9/10A61P9/12
Inventor 杨明贵公长春罗亭飞李云娟
Owner HAINAN MEILAN SMITH KLINE PHARMA
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