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Zoledronic acid calcium complex and preparation method thereof

A technology of calcium zoledronate and zoledronic acid, which is applied in the field of biomedical materials, can solve problems such as adverse reactions and low concentration threshold, and achieves the effects of simple preparation method, moderate crystal growth rate and low stress

Inactive Publication Date: 2021-05-11
SOUTH CHINA UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the current bisphosphonic acid (or sodium salt) is relatively water-soluble, and the concentration threshold for its effective effect is very low, and it is easy to cause adverse reactions if it exceeds the threshold, so it can only be directly injected or loaded with a delivery system for sustained release. To some extent, it limits the application of bisphosphonates, which have significant osteogenic effects, in bone regeneration and repair.

Method used

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  • Zoledronic acid calcium complex and preparation method thereof
  • Zoledronic acid calcium complex and preparation method thereof
  • Zoledronic acid calcium complex and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] Take by weighing zoledronic acid (0.0082g, 0.03mmol) with a purity of 98%, and calcium chloride (0.0033g, 0.03mmol) with a purity of 98%, add it to 10mL of water, slowly drop into 0.1mol / L NaOH solution, and simultaneously Stir to make the solution clear and transparent and adjust the pH to 4, then transfer the solution to a vial, cover it, and tighten it, place the vial in an incubator, and react for 30 days at 20°C, then filter, wash, and dry to obtain Larger regular flat rectangular transparent crystals are zoledronic acid calcium complexes. Among them, the reaction time of the preparation process is negatively correlated with the reaction temperature, that is, the higher the temperature, the shorter the reaction time; As it goes up, the rectangle gets smaller and smaller.

[0020] figure 1 It is an optical microscope picture of the zoledronic acid calcium complex crystal, and it can be seen from the figure that the zoledronic acid calcium complex is a flat rectang...

Embodiment 2

[0024] Take by weighing zoledronic acid (0.0136g, 0.05mmol) with a purity of 98%, and calcium hydroxide (0.0074g, 0.1mmol) with a purity of 98%, add it to 10mL of water, slowly drop into 0.1mol / L NaOH solution, and simultaneously Stir to make the solution clear and transparent and adjust the pH to 4, then transfer the solution to a vial, cover it, and tighten it, place the vial in an incubator, react at 80°C for 20 days, then filter, wash, and dry to obtain Larger regular flat rectangular transparent crystals are zoledronic acid calcium complexes.

Embodiment 3

[0026] Weigh zoledronic acid (0.0272g, 0.1mmol) with a purity of 98% and calcium nitrate (0.0082g, 0.05mmol) with a purity of 98%, add to 10mL of water, slowly drop into 0.1mol / L NaOH solution, while stirring Make the solution clear and transparent and adjust the pH to 5, then transfer the solution to a 15mL reactor, cover it, and tighten it, place the reactor in a constant temperature box, react at 150°C for 7 days, then filter, wash, and dry to obtain Moderate regular flat rectangular transparent crystals are zoledronic acid calcium complexes.

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Abstract

The invention discloses a zoledronic acid calcium complex and a preparation method thereof. The chemical formula of the zoledronic acid calcium complex is Ca(Zol)(H2O).2H2O, wherein Ca represents calcium, Zol represents zoledronic acid, H2O represents water, the crystal system is a monoclinic system, the space group is P21 / N, the lattice constant beta is equal to 95.753 degrees, and z is equal to 4. The preparation method comprises the steps of by taking calcium salt and zoledronic acid as raw materials and deionized water as a solvent, adjusting the pH value to 4-5 by using a sodium hydroxide solution, standing at the temperature of 20-200 DEG C for 3-30 days, filtering, washing and drying to obtain a flat rectangular transparent crystal, namely, the zoledronic acid calcium complex. The preparation method is very simple, the crystal growth speed is moderate, the stress is small, the uniformity is good, the crystal has a very complete appearance, and the crystal has important potential application prospects in the fields of drug slow release, targeted transportation, bone tissue repair and the like.

Description

technical field [0001] The invention relates to the technical field of biomedical materials, in particular to a zoledronic acid calcium complex and a preparation method thereof. Background technique [0002] Coordination polymers are a class of compounds formed by the combination of metal ions and organic ligands through coordination bonds. In recent years, the development of coordination polymer chemistry has endowed it with new explorations and applications in the fields of design, synthesis, structure, and performance, and has gradually become a frontier and hot topic in organic, inorganic, materials, biology, and medical disciplines. Using the principle of molecular self-assembly to design and construct complexes with novel structures, so that they have specific biological functions, has important practical significance for their wide application in the field of biomedicine. [0003] Zoledronic acid is a bisphosphonic acid small-molecule drug widely used clinically in t...

Claims

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Application Information

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IPC IPC(8): C07F9/6506A61P19/00A61L27/54A61L27/02A61K47/52
CPCC07F9/6506A61P19/00A61K47/52A61L27/54A61L27/025C07B2200/13A61L2430/02A61L2300/216A61L2300/412A61L2300/602
Inventor 施雪涛壮琛柴牧原林佳义杨夕冉
Owner SOUTH CHINA UNIV OF TECH
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