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Composition for inhibiting or dissolving calcium oxalate stones as well as preparation method and application of composition

A composition, the technology of calcium oxalate, applied in the field of medicine, can solve the problems of very large irritation of the urothelium, irritation of the urinary tract mucosa, and susceptibility to infection, and achieve the effects of increasing catalytic efficiency, preventing stone recurrence, and high safety

Active Publication Date: 2020-07-17
周定兰
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The direct stone-dissolving fluids that have been used clinically are divided into alkalizing agents, alcoholizing agents, thiol agents and chelating agents. These solvents are chemical reagents and rely on strong acids and bases, strong salt ions, etc. to dissolve the formed stones , while dissolving stones, it is very irritating to the urothelium, and patients cannot tolerate it, so it cannot be widely used clinically; in addition, because the stone dissolution process takes a long time, it is very easy to be infected, the most serious of which is systemic Septicemia, leading to epididymitis, perinephric abscess and pyelonephritis; another side effect is the irritation and corrosion of the urinary tract mucosa, the process of stone dissolution must be closely monitored to avoid serious complications

Method used

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  • Composition for inhibiting or dissolving calcium oxalate stones as well as preparation method and application of composition
  • Composition for inhibiting or dissolving calcium oxalate stones as well as preparation method and application of composition
  • Composition for inhibiting or dissolving calcium oxalate stones as well as preparation method and application of composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Example 1: Preparation of immobilized oxalate decarboxylase magnetic particles by physical method

[0037] In the present invention, polyacrylamide, protein, cellulose, chitosan, alginic acid, polylactic acid-glycolic acid copolymer and other macromolecular materials that can undergo cross-linking reactions can be used to prepare immobilized oxalate decarboxylase. Example Taking microcrystalline cellulose as the carrier of magnetic particles, the preparation process of immobilized oxalate decarboxylase magnetic particles by adsorption method is illustrated to illustrate the preparation process of immobilized oxalate decarboxylase.

[0038] 1. Preparation process

[0039] Disperse 5 g of microcrystalline cellulose in 120 g of N,N-dimethylacetamide, place the mixture in an oil bath and heat to 150°C with constant stirring, and disperse for 30 min. Subsequently, the temperature of the mixture was lowered to 100° C., 8 g of LiCl was added and mixed uniformly, and stirred f...

Embodiment 2

[0045] Example 2: Preparation of immobilized oxalate decarboxylase magnetic particles by chemical method

[0046] In the present invention, magnetic beads containing amino groups, carboxyl groups, N-hydroxysuccinimide groups, aldehyde groups, epoxy groups, maleimide groups, etc. that can be covalently bonded to proteins can be used to immobilize oxalic acid The preparation of decarboxylase magnetic particles, this embodiment uses the carboxyl-coupled Fe 3 0 4 Taking the immobilization of oxalate decarboxylase on magnetic beads as an example, the preparation process of immobilized oxalate decarboxylase is described.

[0047] 1. Immobilize oxalate decarboxylase on the surface of carboxyl group magnetic beads

[0048] 1.1 Preparation process

[0049] (1) Select carboxyl group magnetic beads with a particle size of 0.2-2 μm and remove the storage solution; wash with deionized water and reaction buffer (100mM MES, pH6.0) respectively, and remove the supernatant through magnetic ...

Embodiment 3

[0064] Example 3: Tolerance urine inhibition test of oxalate degrading enzyme

[0065] The action environment of the composition of the present invention is the urine in the human urinary system, therefore, the anti-inhibition performance of the immobilized oxalate decarboxylase is the key to whether the composition can function efficiently. In this embodiment, the main inhibitory factors (chloride ion, urea, and pH) in human urine are used as screening conditions, and four kinds of oxalate decarboxylases immobilized by physical adsorption method in Example 1 and carboxylated magnetic beads in Example 2 to filter. The specific conditions are: the activity of the immobilized oxalate decarboxylase under 200mM NaCl; 50mM urea; pH3.5-pH7.5.

[0066] Table 4 Tolerance test of different oxalate decarboxylases (physical adsorption) to urine inhibitory components

[0067]

[0068]

[0069] Note: Oxalate decarboxylase A is from Bacillus subtilis, oxalate decarboxylase B is from...

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Abstract

The invention relates to a composition for inhibiting or dissolving calcium oxalate stones as well as a preparation method and application of the composition. The composition comprises an immobilizedoxalate decarboxylase that can catalyze a decarboxylation reaction of oxalic acid or / and an oxalate, and the immobilized oxalate decarboxylase is prepared by immobilizing oxalate decarboxylase on a magnetic particle carrier. The composition provided by the invention has the function of inhibiting the growth of the calcium oxalate stones or dissolving the calcium oxalate stones, and has the advantages of mildness, good tolerance and high safety, and a patient has no trauma or pain when the composition is applied to treat kidney stones; and when the composition provided by the invention is applied to treat the calcium oxalate stones, the oxalate decarboxylase can be fixed in a renal pelvis by applying a magnetic field to continuously degrade oxalic acid in urine, so that the action time andefficiency of enzyme are increased, after the treatment is completed, the magnetic field is removed, and immobilized enzyme magnetic beads can be excreted with the urine; and after the composition isused in combination with drugs for regulating the pH of the urine, the effects of degrading the oxalic acid and dissolving the stones can be enhanced.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to a composition for inhibiting or dissolving calcium oxalate stones, a preparation method and application thereof. Background technique [0002] Kidney stones cause suffering to tens of millions of people worldwide and cost tens of billions of dollars in economic losses every year. In the United States, about 5 million people enter the emergency room every year because of kidney stones, which is one of the seven major hospitalization diseases, with an annual economic loss of more than 5 billion US dollars and an annual growth rate of 7-11%. The situation in China is similar to that of the United States ; In addition, kidney stones are also complications of many modern diseases (such as diabetes, obesity, etc.). However, 80% of all kidney stones are calcium oxalate stones. [0003] So far, there is no treatment that can make the stones smaller and finally excreted without damaging ...

Claims

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Application Information

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IPC IPC(8): A61K9/00A61K47/02A61K38/51A61K41/00A61P13/04A61P13/00A61P13/12
CPCA61K9/0009A61K47/02A61K38/51C12Y401/01002A61K41/00A61P13/04A61P13/00A61P13/12
Inventor 周定兰
Owner 周定兰
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