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Preparation method of organic amine salt and ammonia salt of candesartan

A technology of candesartan and sartan ammonium salt, which is applied in the field of drug development and can solve problems such as unsatisfactory absorption effect

Inactive Publication Date: 2015-02-18
BEIJING INSTITUTE OF TECHNOLOGYGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the bioavailability of candesartan cilexetil is increased to about 40%, the absorption effect is still unsatisfactory; (a) T.Miyabayashi, J.Chromatogr.B.1996,677,123-132; b) H. Stenhoff, J. Chromatogr. B. 1999, 731, 411-417; c) C. H. Gleiter, K. E. Morike, Clin. Pharmacokinet. 2002, 41, 7-17.)

Method used

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  • Preparation method of organic amine salt and ammonia salt of candesartan
  • Preparation method of organic amine salt and ammonia salt of candesartan
  • Preparation method of organic amine salt and ammonia salt of candesartan

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1-3

[0037] Embodiment 1-3: Preparation of candesartan ethylenediamine salt

[0038] Mix candesartan and 0.1M ethylenediamine aqueous solution, stir at room temperature for 4 hours, add 15mL of methanol to dissolve, filter, and the filtrate naturally volatilizes to obtain colorless massive crystals of candesartan ethylenediamine salt.

[0039] Table 1. Experimental parameters for the preparation of candesartan ethylenediamine salt.

[0040]

Embodiment 4-6

[0041] Example 4-6: Preparation of Candesartan 1,3-propanediamine salt

[0042] Mix candesartan and 0.1M 1,3-propylenediamine solution, stir at room temperature for 4 hours, add 15mL methanol to dissolve, filter, and the filtrate naturally volatilizes to obtain a colorless block of candesartan 1,3-propylenediamine salt crystals.

[0043] Table 2. Experimental parameters for the preparation of candesartan 1,3-propanediamine salt.

[0044]

Embodiment 7-9

[0045] Embodiment 7-9: Preparation of Candesartan Ammonium Salt

[0046] Mix candesartan and 0.5M ammonia solution, stir at room temperature for 4 hours, add 15mL of ethanol to dissolve, filter, and the filtrate naturally volatilizes to obtain colorless rhomboid candesartan ammonium salt crystals.

[0047] Table 3. Experimental parameters for the preparation of candesartan ammonium salt.

[0048]

[0049] Candesartan ethylenediamine salt, candesartan 1,3-propanediamine salt and candesartan ammonium salt were analyzed by X-ray single crystal diffraction (SXRD), X-ray powder diffraction (PXRD), Differential Scanning Calorimetry (DSC), Infrared (IR), 1 H NMR characterization, the results are as follows:

[0050] 1. X-ray single crystal diffraction (SXRD) test

[0051] Adopt X-ray single crystal structure testing and data analyzer, built-in Ultrax 18 fine focal spot rotation target generation and 2SATURN 724+CCD detectors, focal spot size 0.3×0.3mm 2 , the maximum generating ...

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Abstract

The invention discloses a preparation method of organic amine salt and ammonia salt of candesartan, and belongs to the field of medicinal development. The preparation method comprises the following steps: enabling candesartan to respectively react with ethylenediamine and 1,3-propane diamine or an ammonia water solution with a certain concentration, and respectively obtaining candesartan ethylenediamine salt, 1,3-candesartan propylene diamine, and candesartan ammonia salt, wherein the structures of the three candesartan salts are represented by means of SXRD (Silicon X-ray Reflective Display) and PXRD (Powder X-ray Diffraction). Proved by in-vivo biological activity tests of rats, the bioavailability of the three candesartan salts is obviously increased when compared with that of the original medicine. The preparation method disclosed by the invention provides a powerful technical support for development of the candesartan medicine.

Description

technical field [0001] The invention relates to a preparation method of candesartan organic amine salt and ammonia salt, belonging to the field of drug development. Background technique [0002] Candesartan is also known as candesartan cilexetil C8 intermediate, CV-11974. The chemical name is 2-ethoxy-3-[[4-[2-(1H-tetrazol-5-yl)phenyl]phenyl]methyl]-3H-benzimidazole-4-carboxylic acid, which is White crystalline powder. Candesartan is easily soluble in organic substances such as methanol and ethanol, but insoluble in water. Its substance number identification (CAS) number: 139481-59-7. The structural formula is as follows: [0003] [0004] Candesartan is a highly selective angiotensin II (AT 1 ) receptor antagonist, it through the AT with vascular smooth muscle 1 Receptor binding antagonizes the vasoconstriction of angiotensin II, thereby reducing peripheral vascular resistance and lowering blood pressure (a) C.H.Gleiter, Cardiovasc.Drug.Rev.2004, 22, 263–284; b) B.S...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D403/10
CPCC07D403/10
Inventor 迟瑛楠徐文婷胡长文
Owner BEIJING INSTITUTE OF TECHNOLOGYGY