RU2607743C1 - Method of producing cation-substituted tricalcium phosphate - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to chemical and medical industries and can be used in production of initial biocompatible material, suitable for making dense and porous ceramics, applicable as scaffolds in engineering of bone tissue, targets for creation of coatings on metallic implants in surgery and dentistry and in other fields of medicine. Method of producing cation-substituted tricalcium phosphate is described by deposition of average calcium phosphates, formed during pouring off and constant mixing of aqueous solutions of calcium nitrate and disubstituted ammonium phosphate, taken in molar ratio of 3:2, at pH 7.0 with subsequent filtering of formed precipitate and its thermal treatment at temperatures of 700–1,300 °C. Wherein calculated amount of solutions of salts of nitrates or acetates, or chlorides of following elements is added to reaction mixture: iron, zinc, copper, sodium, potassium, strontium, barium bismuth, silicon at following ratio of reagents, mol%: calcium nitrate – 40–59.9, disubstituted ammonium phosphate – 40; salt – 0.1–20.

EFFECT: powders formed after thermal treatment are characterized by homogeneous phase composition, corresponding to whitlokite structure, finely dispersed state with particle size of 20 nm to 2 mcm and antimicrobial activity.

1 cl, 1 tbl, 4 ex

Description

The invention relates to the chemical and medical industries and can be used in the production of biocompatible starting materials suitable for the manufacture of dense and porous ceramics used as scaffolds in bone tissue engineering, targets for creating coatings on metal implants in surgery and dentistry and in other fields medicine.

Tricalcium phosphate powder (TCF) is used to produce ceramic materials used in medicine as durable bone implants and / or porous matrices for bone restoration. The main characteristics that determine the use of TCP are phase composition and dispersion. Reducing the particle size of TKF powders allows one to obtain materials with higher strength and higher resorbability, which contributes to the creation of reliable bone implants and porous matrices based on them for quick restoration of bone tissue. Due to the fact that often during operations and subsequent treatment, infection of the wound space occurs, which leads to the need for repeated operations, giving the material of the implant antimicrobial properties becomes an important task.

A known method of producing ROS by mixing solutions of diammonium phosphate and calcium nitrate. The mixture was bubbled with argon and kept at pH 11 for 48 hours at room temperature (J. Amer. Ceram. Soc. 1989, 72, No. 8, 1476-1478). However, despite the complexity of the technology, this method does not allow to obtain ROS in its pure form without impurities of other side-formed calcium phosphates, for example calcium-deficient calcium hydroxyapatite.

The closest in technical solution is the patent of the Russian Federation No. 2367633. A method of obtaining a nanoscale powder based on the tricalcium phosphate-hydroxyapatite system for the synthesis of ceramic biomaterials. The chemical interaction of calcium nitrate and ammonium hydrogen phosphate in a solution with the addition of ammonia is carried out, a wet powder is precipitated, washed successively with water, ethanol and toluene and calcined at 150-900 ° C to obtain a powder based on TCP, containing hydroxyapatite (HA), characterized by an atomic ratio of Ca / P from 1.48 to 1.69 and a specific surface area of at least 120-200 m ² / g. The disadvantage of this method is the absence of bactericidal properties of the resulting powder, as well as an undesirable admixture of HA, which is slowly absorbed in the body upon implantation of HA and ceramic implants obtained from this powder. In addition, the TCP powder obtained by this method does not exhibit antibacterial activity.

The technical result of the invention is to give the powder TKF and porous ceramic materials from it antibacterial activity and to obtain materials from TKF without impurities GA and other calcium phosphates (powders are characterized by a homogeneous phase composition corresponding to the structure of vitlokite), after heat treatment at 700-1300 ° C; particle size from 20 nm to 2 microns.

The technical result is achieved by the fact that in the method for producing cationically substituted tricalcium phosphate by precipitation of medium calcium phosphates formed by the merging and constant stirring of aqueous solutions of calcium nitrate and dibasic ammonium phosphate taken in a molar ratio of 3: 2, at pH 7.0, followed by filtering the resulting the precipitate and its heat treatment at temperatures of 700-1300 ° C, according to the invention, the calculated amount of solutions of salts of nitrates, or acetates, or chloride is added to the reaction mixture in the following elements: iron, zinc, copper, sodium, potassium, strontium, barium, bismuth, silicon, in the following ratio of reactants, mol.%:

calcium nitrate - 40-59.9

ammonium phosphate bisubstituted - 40

salt of iron, zinc, copper, sodium, potassium, strontium, barium, bismuth, silicon - 0.1-20

The powders formed after heat treatment at 700–1300 ° C are characterized by a homogeneous phase composition corresponding to the structure of vitlokite, a finely dispersed state with a particle size of 20 nm to 2 μm, and antimicrobial activity.

The presence of zinc, iron, copper ions in the obtained TKF powder provides antibacterial activity. A decrease in the ratio (calcium nitrate + metal salt) / ammonium phosphate of less than 1.5 leads to the appearance of a phase of calcium pyrophosphate in the material after heat treatment at 700 ° C, which is an undesirable component that makes it difficult to obtain ceramic from the obtained powder. With an increase in the ratio (calcium nitrate + metal salt) / ammonium phosphate greater than 1.5, and also with an increase in pH above 7.0, a HA phase is formed in the material after heat treatment, which is also undesirable.

Example 1

280 ml of a 0.5 mol / L calcium nitrate solution, 20 ml of a 0.5 mol / L zinc nitrate solution, 20 ml of a 25% aqueous ammonia solution were placed in a reactor with a propeller stirrer. From a dropping funnel, 200 ml of a solution of 0.5 mol / L di-substituted ammonium phosphate was added dropwise with stirring. The pH of the reaction mixture was maintained at 6.9 ± 0.1, by adding dropwise a 10% aqueous solution of ammonia. Stirring of the reaction mixture was continued for 60 minutes, after which the precipitate formed was filtered off, washed with distilled water and ethanol, and dried in an oven at 105 ° C. To determine the phase composition, the precipitate was calcined for 1 hour at 900 ° C. According to x-ray phase analysis, the main crystalline phase of the obtained powders is vitlokite, no pyrophosphate and HA impurities were detected.

Example 2

The material obtained analogously to example 1; the difference is that instead of 20 ml of a 0.5 mol / L zinc nitrate solution, 20 ml of a 0.5 mol / L copper acetate solution was introduced; material heat treatment temperature - 1300 ° C. According to x-ray phase analysis, the main crystalline phase of the obtained powders is vitlokite, no pyrophosphate and HA impurities were detected.

Example 3

The material obtained analogously to example 1; the difference is that instead of 20 ml of a 0.5 mol / L zinc nitrate solution, 20 ml of a 0.5 mol / L silver nitrate solution was injected; material heat treatment temperature - 700 ° C. According to x-ray phase analysis, the main crystalline phase of the obtained powders is vitlokite, no pyrophosphate and HA impurities were detected.

Example 4

The material obtained analogously to example 1; the difference is that instead of 20 ml of a solution of zinc nitrate with a concentration of 0.5 mol / l, 20 ml of a solution of iron chloride (III) with a concentration of 0.5 mol / l was introduced; material heat treatment temperature - 1100 ° C. According to x-ray phase analysis, the main crystalline phase of the obtained powders is vitlokite, no pyrophosphate and HA impurities were detected.

For all the obtained materials, the antibacterial activity was determined with respect to the E. Coli strain by placing a sample compressed from the obtained powder in a Petri dish with an E. Coli culture. The presence of antibacterial activity of the material was judged by the width of the bright ring formed around the sample (Table 1).

All samples shown in the table were obtained by pressing synthesized powders of substituted calcium phosphates, followed by sintering at a temperature of 1100 ° C.

Ag1 and Ag2 - silver-substituted TCF, silver content 0.34% wt., Parallel crops of E.Coli culture

Cu1 and Cu2 - copper-substituted TCF, copper content 0.20% wt., Parallel crops of E.Coli culture

Fe1 and Fe2 - iron-substituted TCF, iron content 0.50% wt., Parallel crops of E.Coli culture

Zn1 and Zn2 - zinc substituted TCF, zinc content 0.20% wt., Parallel crops of E.Coli culture

Claims (5)

A method of producing a cationically substituted tricalcium phosphate by precipitation of medium calcium phosphates formed by the merging and constant stirring of aqueous solutions of calcium nitrate and disubstituted ammonium phosphate, taken in a molar ratio of 3: 2, at pH 7.0, followed by filtration of the precipitate formed and its thermal treatment at temperature 700-1300 ° C, characterized in that the calculated amount of solutions of salts of nitrates, or acetates, or chlorides of the following elements is added to the reaction mixture: iron, zinc, copper, sodium . I, potassium, strontium, barium, bismuth, silicon, with the following ratio of reactants, mole%: calcium nitrate - 40-59.9 ammonium phosphate bisubstituted - 40 salt of iron, zinc, copper, sodium, potassium, strontium, barium, bismuth, silicon - 0.1-20, in this case, the powder formed after heat treatment at a temperature of 700-1300 ° C is characterized by a homogeneous phase composition corresponding to the structure of vitlokite, a finely dispersed state with a particle size of 20 nm to 2 μm and antimicrobial activity.