RU2552756C1 - Method for producing carbonate hydroxyl apatite granules in gelatine matrix - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: what is presented is a method for producing carbonate hydroxyl apatite granules consisting in mixing carbonate hydroxyl apatite powder with aqueous solution of gelatine 5 wt % in ratio of the power 1 g to the solution 7.5 ml until smooth; the produced mixture is dispersed through a capillary of a diameter of 1÷2 mm into vegetable oil cooled down to a temperature of T₁=-1÷0°C; the produced granules are decanted from the oil and washed with a mixture of ethanol and acetone in ratio 2:1, dried at a temperature of T₂=25÷27°C in the air for t=5÷7 hours to hold a spherical shape. The carbonate hydroxyl apatite granules held their spherical shape within the range of 400-800°C, have a diameter of 1-2 mm, specific surface within the range of 32-0.04 m²/g and mesopore volume within the range of 0-0.098 cm³/g.

EFFECT: maintaining the qualities.

1 tbl, 3 ex

Description

The invention relates to the field of medicine and the creation of new biomedical materials that can be used to create biphasic composites based on carbonate hydroxylapatite and a polymer organic matrix, when filling bone defects in traumatology and orthopedics, maxillofacial surgery and surgical dentistry.

A known method for producing porous spherical hydroxylapatite granules (Min-Ho Hon, Jun-Sik Son, Kwang-Mahn Kim, Myungho Han, Daniel S. Oh, Yong-Keun Lee Drug-loaded porous spherical hydroxyapatite granules for bone regeneration // J Mater Sci : Mater Med V. 22, 2011. P. 349-355), in which a suspension of hydroxylapatite is prepared, 3% high molecular weight polyvinyl alcohol, 3% carboxymethyl cellulose and 5% ammonium polyacrylate are used as a binder and to improve sintering. For the manufacture of granules, hydroxylapatite suspensions were obtained by gradually increasing the ratio of H ₂ O / hydroxylapatite (1.5, 2, and 4), gradually increasing the NaCl content of 3, 15, and 30 wt.%. The suspension was mixed in several stages at a low speed of 1000 rpm. The temperature of the suspension was brought to room temperature at a low stirring speed. When the suspension became homogeneous, the rotation speed was increased to 5000 rpm and the suspension was stirred for 10 hours at this rotation speed, the temperature of the suspension was also reduced to 15 ° C during high speed mixing. The disadvantages of this method include the complexity of sample preparation and the formation of hydroxylapatite granules, adding to the suspension of synthetic components that are foreign to the human body.

The closest in technical essence to the claimed is a method for the manufacture of porous ceramic granules of calcium phosphates (patent RU 2299869 C1, C04B 35/447, C04B 35/626, A61L 27/12), which consists in the preliminary synthesis of calcium phosphate powder with a ratio of Ca / P from 1.5 to 1.67, the preparation of a suspension with a 10% gelatin solution in a ratio of 0.5-3 ml gelatin solution per 1 g of powder at a solution temperature of 10-39 ° C. A suspension of HA in an aqueous solution of gelatin was dispersed in a neutral liquid medium of vegetable oil, the mixture was stirred with a paddle mixer with a rotation speed of 100-1500 rpm. Under the influence of surface tension, spherical granules were formed, which were washed, dried and subjected to heat treatment at a temperature of 900-1250 ° C.

The disadvantages include the use of certain calcium phosphates, which do not correspond to the inorganic component of human bone tissue, as well as the use of high heat treatment temperatures, the mixing time is not indicated.

The task of the invention is to develop a method for producing granules of carbonate hydroxylapatite in a gelatin matrix.

The specified technical result consists in the fact that a method for producing granules of carbonate hydroxylapatite is proposed, which consists in mixing carbonate hydroxylapatite powder with 5 wt.% Aqueous gelatin solution in a ratio of 1 g of powder to 7.5 ml of solution to a homogeneous mass, the resulting mixture is dispersed through a capillary with a diameter of 1-2 mm in vegetable oil, cooled to a temperature of T ₁ = -1 ÷ 0 ° C, then the obtained granules are decanted from the oil and washed with a mixture of ethyl alcohol and acetone in a ratio of 2: 1, then dried at a temperature Atura T ₂ = 25 ÷ 27 ° C in air, for a time t = 5 ÷ 7 hours, to maintain a spherical shape.

Then, the properties of the obtained granules were studied: the dispersed composition of the obtained granules, using a sieve analysis, the specific surface, which is one of the most important characteristics of solid porous materials.

Example 1

The carbonate hydroxylapatite powder is mixed with a 5 wt.% Aqueous gelatin solution at a ratio of 0.2 g of powder to 1.5 ml of the solution to a homogeneous mass, then the resulting mixture is dispersed for 4 minutes through a 1 mm diameter capillary into 100 ml vegetable oil, cooled to 0 ° C, using 200 g of ice mixed with 10 g of CaCl ₂ , the obtained granules are decanted from oil and washed with a mixture of ethyl alcohol and acetone (10 ml and 5 ml, respectively), then dried at 25 ° C in air.

Example 2

The carbonate hydroxylapatite powder is mixed with a 5 wt.% Aqueous gelatin solution at a ratio of 0.4 g of the powder to 3 ml of the solution to a homogeneous mass, then the resulting mixture is dispersed for 8 minutes through a 1 mm diameter capillary into 100 ml vegetable oil, cooled to -1 ° C, using 200 g of ice mixed with 10 g of CaCl ₂ , the granules obtained are decanted from oil and washed with a mixture of ethyl alcohol and acetone (10 ml and 5 ml, respectively), then dried at 26 ° C in air.

Example 3

The carbonate hydroxylapatite powder is mixed with a 5 wt.% Aqueous solution of gelatin at a ratio of 0.8 g of powder to 6 ml of solution to a homogeneous mass, then the resulting mixture is dispersed for 16 minutes through a 1 mm diameter capillary into 100 ml vegetable oil, cooled to -1 ° C, using 200 g of ice mixed with 10 g of CaCl ₂ , the obtained granules are decanted from oil and washed with a mixture of ethyl alcohol and acetone (10 ml and 5 ml, respectively), then dried at a temperature of 27 ° C in air.

To determine the optimal gelatin content in an aqueous solution, we studied the properties of the obtained granules: the dispersed composition of the obtained granules using sieve analysis, the specific surface, which is one of the most important characteristics of solid porous materials.

The specific surface was calculated according to the Brunauer, Emmett and Teller (BET) equation, which is one of the most common and generally accepted at present. The specific surface area and porosity of the samples were measured by the BET method (S _BET-N2 ) on a Gemini 2365 analyzer by adsorption of a standard nitrogen gas at 77.4 K. The specific surface area was measured from 0.5 to 999 m ² / g. The limit of permissible relative measurement error of the specific surface in the multiple measurement mode is not more than 5% (Table 1).

Based on the data in Table 1, the granules obtained at a gelatin concentration of 5% by mass have the largest specific surface area and volume of mesopores. With an increase in gelatin concentration from 5-15, a sharp drop in the specific surface and the volume of mesopores is observed, which negatively affects the functional properties of the obtained products.

Thus, the claimed method allows to obtain granules based on carbonate hydroxylapatite in a protein matrix of gelatin with a diameter of 1-2 mm, a specific surface area of 32-0.04 m ² / g, a mesopore volume of 0-0.098 cm ³ / g, an average pore size of 10 to 20 nm.

Claims (1)

A method of producing granules of carbonate hydroxylapatite, which consists in mixing carbonate hydroxylapatite powder with 5 wt.% Aqueous gelatin in a ratio of 1 g of powder to 7.5 ml of solution to a homogeneous mass, the resulting mixture is dispersed through a capillary with a diameter of 1 ÷ 2 mm in vegetable oil, cooled to a temperature of T ₁ = -1 ÷ 0 ° C, then the obtained granules are decanted from oil and washed with a mixture of ethyl alcohol and acetone in a ratio of 2: 1, then dried at a temperature of T ₂ = 25 ÷ 27 ° C in air over time t = 5 ÷ 7 hours.