RU2485978C1 - Porous calcium phosphate cement - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine. What is disclosed is a porous calcium phosphate hydraulic cement for bone tissue restoration, containing p-tricalcium phosphate powder, monocalcium phosphate monohydrate, and a tempering liquid representing 7-9% aqueous solution of citric acid; also, a cement powder comprises calcium carbonate granules in the following proportions (wt %): β-tricalcium phosphate - 67-75, monocalcium phosphate monohydrate -20-22, calcium carbonate granules - 3-13. The tempering liquid and cement powder are related as 0.75.

EFFECT: calcium phosphate cements are characterised by a combination of an ability to reaction hardening, an ability to be shaped, biocompatibility, the absence of toxic side effects, as well as a potential to be replaced by the newly formed bone tissue.

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Description

The invention relates to medicine and relates to cement materials for plastic reconstruction of damaged bone tissue. Calcium-phosphate cements are obtained on the basis of a reaction-hardening powder mixture (RPS) of two or more calcium phosphates and a solidifying liquid (GC). The starting powder is a mixture of acidic and basic phosphates. When GIs are added to the mixture, the components begin to interact with each other through the liquid phase by the dissolution-precipitation mechanism with the formation of neutral (pH ~ 7) phosphates. A mixture of “acidic” (monocalcium phosphate monohydrate) and “basic” (α- or β-tricalcium phosphate) calcium phosphates and calcium sulfate hemihydrate is used as the initial mixture. Water, aqueous solutions of phosphates of alkali metals or magnesium (Moseley, et al. US Patent 8025903; Barralet et al. US Patent 7473312) are used as the coolant. When a mixture of calcium phosphate powders is mixed with a coolant, a dough-like mass is formed, which eventually coarsens to form a strong cement stone consisting of crystalline brushite.

The proposed materials can be used as cement pastes for filling bone maxillofacial and dental defects. Calcium-phosphate cements used in medicine should have a range of properties, such as biocompatibility, osteoconductivity and biodegradation rate, consistent with the processes of osteogenesis, the strength of the hardened cement, sufficient to bear minimal loads in the process of formation of own bone tissue. The advantages of these materials include, firstly, their ability to fill defects of the most complex configuration and volume, and secondly, the low invasiveness of interventions, that is, the possibility of introducing these materials in injection form directly into the defect area under ultrasound or X-ray control without extensive surgical interventions and the possibility of 3D fixation.

The disadvantage of these materials is the low porosity, which does not contribute to the integration of cement with the surrounding bone tissue. The absence of large interconnected pores disrupts the circulation of fluid inside the cement stone, and the absence of small pores dramatically reduces the adhesion of cells on the cement surface. The closest in technical essence and result to the proposed method is US patent No. 7754246 Moseley and others. The components of the cement powder are calcium sulfate hemihydrate, β-tricalcium phosphate, monocalcium phosphate monohydrate. Glycolic acid neutralized with sodium hydroxide is used as a fatty acid. The interaction of calcium sulfate hemihydrate and fatty acid forms calcium sulfate dihydrate. β-tricalcium phosphate and monocalcium phosphate monohydrate react with each other with the formation of brushite. Brushite and calcium sulfate dihydrate form a cement stone. After cement is implanted into the bone tissue, calcium sulfate dihydrate is relatively rapidly resorbed, resulting in the formation of pores. To increase the strength of cement, TKF granules are introduced into the composition of the powder. However, the authors of the patent do not indicate the total porosity and pore size, while these values are most important when evaluating the rate of cement resorption. The result of this invention is not a porous cement stone, the authors indicate that the pores in the cement stone are formed only after the resorption of one of the components, while it is not clear whether the integrity of the cement stone is preserved or it breaks into separate parts. The porosity of the implanted material is one of the decisive factors affecting its osteoconductivity.

The problem to which the present invention is directed, is to optimize the composition of the cement powder to increase porosity and increase the pore size of the cement stone after hardening.

The technical result of the invention is to increase the porosity of calcium phosphate cement to 40-60% while maintaining strength at the level of 10-15 MPa.

The technical result is achieved by the fact that in porous calcium phosphate cement for bone repair, containing β-tricalcium phosphate powder, monocalcium phosphate monohydrate and a shutter fluid, according to the invention, the shutter fluid is a 7-9% aqueous citric acid solution, and cement powder additionally contains granules of calcium carbonate in the following components (wt.%):

β-tricalcium phosphate 67-75 monocalcium phosphate monohydrate 20-22 granules of calcium carbonate 3-13

The ratio of mixing fluid: cement powder is 0.75.

The essence of the invention lies in the fact that during the interaction of citric acid, which is part of the mixing fluid, and granules of calcium carbonate, which are part of the cement powder, gaseous carbon dioxide is released, which creates a system of interconnected pores in the cement. Calcium citrate formed as a result of this interaction enhances the strength of the resulting cement stone.

A decrease in the concentration of citric acid solution below 7% sharply reduces the porosity of the cement stone, while an increase in the concentration of citric acid above 9% leads to a decrease in the pH of the cement after setting to 5.5.

The increase compared with the prototype porosity of calcium phosphate cement with a total porosity of 40-60% and a pore size of less than 1 μm to 10 μm, having a strength in the range of 10-15 MPa, is achieved by introducing 3-13% of the mass of the cement powder . granules of calcium carbonate and use as a closing liquid 7-9% aqueous solution of citric acid.

Example 1

4.02 g of β-tricalcium phosphate are mixed with 1.32 g of monocalcium phosphate monohydrate and with 0.66 g of granules of calcium carbonate 50-100 μm in size, 5.33 g of an 8% aqueous citric acid solution are added. The ratio of fatty acids: P = 0.75. Mixing is carried out on glass with a plastic spatula at 25 ° C for 5-7 minutes. The pasty mass formed after mixing is molded in a cylindrical form with a diameter of 8 mm, after 10 minutes the formed sample is removed from the mold and placed in a thermostat at 37 ° C and 100% humidity for a day. After 24 hours, the sample has a compressive strength of 10 MPa, open porosity is 45%, and the average pore size is 5-8 microns.

Example 2

4.02 g of β-tricalcium phosphate are mixed with 1.32 g of monocalcium phosphate monohydrate and 0.4 g of granules of calcium carbonate with a size of 50-100 μm, 4.3 g of 9% aqueous citric acid solution are added. The ratio of fatty acids: P = 0.75. Mixing is carried out on glass with a plastic spatula at 25 ° C for 5-7 minutes. The pasty mass formed after mixing is molded in a cylindrical form with a diameter of 8 mm, after 10 minutes the formed sample is removed from the mold and placed in a thermostat at 37 ° C and 100% humidity for a day. After 24 hours, the sample has a compressive strength of 15 MPa, open porosity is 15%, the average pore size is 3-5 microns. With a decrease in the number of granules of calcium carbonate in the cement powder, the open porosity decreases below the declared value.

Example 3

4.9 g of β-tricalcium phosphate are mixed with 1.05 g of monocalcium phosphate monohydrate and 1.05 g of granules of calcium carbonate of 50-100 μm in size, 5.25 g of an 8% aqueous citric acid solution are added. The ratio of fatty acids: P = 0.75. Mixing is carried out on glass with a plastic spatula at 25 ° C for 5-7 minutes. The mass formed after mixing is molded in a cylindrical form with a diameter of 8 mm, after 10 minutes, the formed sample is removed from the mold, the sample crumbled. An increase in the number of granules of calcium carbonate leads to an increase in pH above 8.5, as a result of which the cement loses its ductility and strength.

Example 4

4.02 g of β-tricalcium phosphate are mixed with 1.32 g of monocalcium phosphate monohydrate and 0.66 g of granules of calcium carbonate with a size of 50-100 μm, add 3.0 g of a 7% aqueous solution of citric acid (ratio ZL: P = 0 ,5). Mixing is carried out on glass with a plastic spatula at 25 ° C for 5-7 minutes. The pasty mass formed after mixing is molded in a cylindrical form with a diameter of 8 mm, after 10 minutes the formed sample is removed from the mold and placed in a thermostat at 37 ° C and 100% humidity for a day. After 24 hours, the sample has a compressive strength of less than 1 MPa, open porosity is 30%, and the average pore size is 5-8 microns. A decrease in the ratio of coolant: cement powder of less than 0.75 leads to a sharp drop in the strength of the cement sample and to a decrease in porosity below the stated value.

Claims (1)

Porous calcium phosphate bone repair cement containing β-tricalcium phosphate powder, monocalcium phosphate monohydrate and a mixing fluid, wherein the mixing fluid is a 7-9% aqueous citric acid solution, and the cement powder further comprises calcium carbonate granules with the following content of components, wt.%:
β-tricalcium phosphate 67-75 monocalcium phosphate monohydrate 20-22 granules of calcium carbonate 3-13
the ratio of the mixing fluid: cement powder is 0.75.