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Single crystal of 14-dehydroxyl-13-dehydroandrographolidume-12-calcium sulfonate acetone solvate, and preparation method thereof

A technology of andrographolide and acetone solvent is applied in the field of drug crystal form research, which can solve the problems of difficult crystallization and purification, complex substances, difficult product quality control, etc., and achieves the effects of good crystallinity and stable solvate properties.

Active Publication Date: 2020-09-08
ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In our research work, we found that because the related substances of 14-dehydroxy-13-dehydroandrographolide-12-sulfonate sodium are complex and easy to form hydrates, it is difficult to crystallize and purify, and the product quality control is difficult. It is urgent to find ways to increase its purity

Method used

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  • Single crystal of 14-dehydroxyl-13-dehydroandrographolidume-12-calcium sulfonate acetone solvate, and preparation method thereof
  • Single crystal of 14-dehydroxyl-13-dehydroandrographolidume-12-calcium sulfonate acetone solvate, and preparation method thereof
  • Single crystal of 14-dehydroxyl-13-dehydroandrographolidume-12-calcium sulfonate acetone solvate, and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

experiment example 1

[0044] Add 41.5g (0.1mol) of 14-dehydroxyl-13-dehydroandrographolide-12-sulfonic acid (97.1% content) and 3.7g (0.05mol) of calcium hydroxide (analytically pure) to 500mL of water, 60 Heat at ℃ for 10 minutes to obtain a clear solution. Then, keep at 60℃, add 500mL of acetone, stop heating, naturally cool to 50℃, keep at 50℃ for 2 hours, naturally cool to 20℃, crystallize for 30 hours, filter, filter The cake was vacuum-dried overnight at room temperature to obtain 36.9 g of a single crystal of uniform and stable 14-dehydroxy-13-dehydroandrographolide-12-sulfonate calcium acetone solvate. Yield 70.2%, content 99.95% (HPLC, Figure 7 ,Table 2).

[0045] Table 2 HPLC test results of single crystal of 14-dehydroxy-13-dehydroandrographolide-12-sulfonate calcium acetone solvate

[0046] Peak Results

[0047] name RT area Height USP Resolution USP Plate Count %Area 1 7.674 2491 342 2.532020e+004 0.03 2 8.504 734 96 4.298152e+000 3.0...

experiment example 2

[0069] Add 83.0 g (0.2 mol) of 14-dehydroxyl-13-dehydroandrographolide-12-sulfonic acid (content 97.1%) and 7.4 g (0.1 mol) of calcium hydroxide (analytical pure) to 900 mL of water, 60 Heated at ℃ for 12 minutes to obtain a clear solution, then, kept at 60℃, added 900mL of acetone, stopped heating, naturally cooled to 50℃, kept at 50℃ for 2 hours, naturally cooled to 20℃, crystallized for 36 hours, filtered, filtered The cake was vacuum dried overnight at room temperature to obtain 75.6 g of a single crystal of 14-dehydroxy-13-dehydroandrographolide-12-sulfonate calcium acetone solvate which was uniform and stable. Yield 71.9%, content 99.95% (HPLC, Figure 7 ).

[0070] The single crystal of 14-dehydroxy-13-dehydroandrographolide-12-sulfonate calcium acetone solvate prepared according to the method of above-mentioned experimental example 2, its crystal structure and characteristics are as follows figure 1 , as shown in 3 and 5, the content is as Figure 7 shown.

experiment example 3

[0072] 14-dehydroxy-13-dehydroandrographolide-12-sulfonic acid (content 97.1%) 207.5g (0.5mol) and calcium hydroxide (analytical pure) 18.5g (0.25mol) were added to 2300mL water, 60 Heated at ℃ for 18 minutes to obtain a clear solution, then kept at 60℃, added 2300mL of acetone, stopped heating, naturally cooled to 50℃, kept at 50℃ for 2 hours, naturally cooled to 20℃, crystallized for 48 hours, filtered, filtered The cake was vacuum dried overnight at room temperature to obtain 187.9 g of a single crystal of 14-dehydroxy-13-dehydroandrographolide-12-sulfonate calcium acetone solvate which was uniform and stable. Yield 71.5%, content 99.95% (HPLC, Figure 7 ).

[0073] The single crystal of 14-dehydroxy-13-dehydroandrographolide-12-sulfonate calcium acetone solvate prepared according to the method of above-mentioned experimental example 3, its crystal structure and characteristics are as follows figure 1 , as shown in 3 and 5, the content is as Figure 7 shown.

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Abstract

The invention discloses a single crystal of 14-dehydroxyl-13-dehydroandrographolidume-12-calcium sulfonate acetone solvate, a preparation method and application thereof, and belongs to the field of drug crystal form research. According to the invention, the 14-dehydroxyl-13-dehydroandrographolidume-12-calcium sulfonate acetone solvate single crystal is obtained by adopting an acid-alkali reaction-crystallization coupling method, wherein the chemical formula of the single crystal is C40H64CaO17S2.C3H6O.4(H2O), the crystal structure belongs to a monoclinic system, the space group is P1 21 1, a is 18.2539 angstroms, b is 15.3118 angstroms, c is 18.3718 angstroms, alpha is 90 degrees, beta is 91.2637 degrees, gamma is 90 degrees, V is 5133.65 angstroms<3> and Z is 4. The 14-dehydroxyl-13-dehydroandrographolidume-12-calcium sulfonate acetone solvate has a good crystallization property, and can be used for preparing a bulk drug of an effective component, namely 14-dehydroxyl-13-dehydroandrographolidume-12-sodium sulfonate, of a clinically-used medicine Lianbizhi.

Description

technical field [0001] The invention relates to a new single crystal of 14-dehydroxyl-13-dehydroandrographolide-12-sulfonate calcium acetone solvate salt, a preparation method and application, and belongs to the field of drug crystal form research. Background technique [0002] Andrographolide is a diterpene lactone compound extracted from the whole herb or leaves of the traditional Chinese medicine Andrographolide, and its structure is shown in Formula 1. Andrographolide has antibacterial and antiviral biological activities, and is known as a natural antibiotic drug. Due to the poor water solubility of andrographolide, it is usually only administered orally. In order to increase its water solubility, the chemical structure of andrographolide is modified to obtain the water-soluble compound 14-dehydroxy-13-dehydroandrographolide-12-sulfonate sodium (Sodium AndrographolideHydrogen Sulfite, Formula 2), also known as sodium andrographolide bisulfite, is the active ingredient o...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D307/58C30B29/54C30B7/08
CPCC07D307/58C30B29/54C30B7/08C07B2200/13
Inventor 李雯丁远民鲁婉莹常英杰李瑞鹏余鸿垚闫大钞关永风杨双双刘宏民
Owner ZHENGZHOU UNIV