CN108714249B - Method for preparing calcium carbonate-chitosan three-dimensional bone screw material by urea solubilization method - Google Patents

Abstract

The invention discloses a method for preparing a calcium carbonate-chitosan three-dimensional bone screw material by a urea solubilization method, which comprises the following steps: adding anhydrous calcium chloride powder into a chitosan solution, and adding urea for solubilization to gradually dissipate the precipitate in the system from turbidity to a clear and transparent uniform solution. Injecting the obtained homogeneous solution into cylindrical mold composed of semipermeable membrane, and soaking in NaOH and Na₂CO₃And (3) in a mixed coagulation bath, demolding, washing and drying to obtain the calcium carbonate-chitosan three-dimensional bone screw material. The preparation process is simple and quick, the prepared chitosan-calcium carbonate composite material introduces inorganic particles into the three-dimensional ordered structure of the hydrogel, and the calcium carbonate has the characteristics of gradient distribution and inconsistent shape along the radial direction. The invention uses urea to solubilize calcium chloride powder, ensures the uniformity and stability of the mixed solution, ensures that the content of inorganic substances in the product can reach 95 percent, is close to natural products such as nacre and the like, and is expected to be applied to orthopedics clinic.

Description

Method for preparing calcium carbonate-chitosan three-dimensional bone nail material by urea solubilization

technical field

The invention relates to a method for preparing calcium carbonate-chitosan three-dimensional bone nail material by urea solubilization method.

Background technique

Shell nacre is a natural layered organic-inorganic composite biomaterial, in which the organic matrix content is about 5%, and the calcium carbonate content is as high as 95%. Nacre has a highly ordered "brick-mud" microstructure and superior strength and toughness. Its three-dimensional structure consists of a water-soluble protein layer grown on an insoluble polymer matrix (chitin), and this layer of protein can guide the formation of calcium carbonate crystals. In recent years, organic-inorganic biomimetic composites simulating the structure of shell nacre have gradually attracted extensive attention in the materials field.

Chitosan-calcium carbonate system is the focus of research on nacre-like organic-inorganic composites. Chitin is one of the important organic components in shells, while chitosan is a derivative of chitin, and the two have similar structures. Chitosan has better solubility and is more widely used in all walks of life and scientific research. Calcium carbonate is an inorganic mineral that widely exists in nature. Its crystal structure is easy to characterize and control. It is a commonly used model mineral in laboratory research on organic-inorganic composite materials.

Chitosan hydrogels with orderly structure and excellent performance can be prepared by in-situ precipitation method. Combined with in-situ mineralization of inorganic substances, calcium salt inorganic substances can be introduced, and calcium carbonate can promote the expansion and regeneration of bone tissue. . Therefore, the preparation of chitosan-calcium carbonate composite materials composed of shell-like nacre with high inorganic content has important scientific significance, and has a good application prospect in orthopedic clinic.

SUMMARY OF THE INVENTION

The purpose of the present invention is to provide a method for preparing calcium carbonate-chitosan three-dimensional bone nail material by urea solubilization method in view of the deficiencies of the prior art.

A method for preparing calcium carbonate-chitosan three-dimensional bone nail material by a urea solubilization method of the present invention comprises the following steps:

1) Weigh a certain mass of chitosan with a viscosity average molecular weight of 10,000-1.2 million and a degree of deacetylation of 60%-95% as a solute, and use an aqueous acetic acid solution with a volume fraction of 2%-20% as a solvent, and stir until completely Dissolve to prepare 2wt.%-10wt.% chitosan solution A;

2) Weigh a certain quality of anhydrous calcium chloride powder, add it to the chitosan solution A to form the mixture stock solution B; then add a certain amount of urea for solubilization, so that the precipitation in the system gradually dissipates, and the solution changes from turbidity to clear Transparent, until the light transmittance of the mixed solution measured by the WGT-S haze meter is greater than 90% to obtain a homogeneous mixed solution C;

3) The solution C was injected into a cylindrical mold composed of a semipermeable membrane, and immersed in a mixed coagulation bath of _NaOH , _Na2CO3 , where the NaOH concentration was 2wt.%-10wt.%, c(NaOH):c(Na ₂ CO ₃ ) is 1:1-3:1;

4) demoulding the obtained chitosan-based composite gel, repeatedly washing with deionized water until neutral, and drying to obtain a calcium carbonate-chitosan three-dimensional bone nail material.

In the above-mentioned technical scheme, the added amount of calcium chloride in step 2) is measured by the theoretical value of the ratio of the calcium carbonate (CaCO ₃ ) mass corresponding to the chitosan (CS) mass and the calcium ion, so that m (CS): _m (CaCO3) was 50:50-4:96.

The preparation process of the invention is simple and rapid, and the prepared chitosan-calcium carbonate composite material introduces a large number of inorganic particles under the condition of retaining the original three-dimensional ordered structure of the hydrogel, which is difficult by other organic-inorganic composite methods. realized. Calcium carbonate exists in the form of small calcite particles, calcium carbonate balls and small ball groups from the inside to the outside along the radial direction of the bone nail. The calcium carbonate has the characteristics of gradient distribution along the radial direction. The invention uses urea to solubilize the calcium chloride powder, which ensures the uniformity and stability of the mixed solution, so that the inorganic content in the product can be as high as 95%, which is close to natural products such as pearl oyster, and is expected to be used in orthopedic clinics.

Description of drawings

Fig. 1 is the scanning electron microscope picture of the calcium carbonate-chitosan three-dimensional bone nail made by the present invention, wherein (a), (b) and (c) are scanning photos of sliced from the inside to the outside along the radial direction of the bone nail, and (d) (e) and (f) are the morphology of calcium carbonate at the corresponding parts, respectively.

Detailed ways

The present invention is further described below in conjunction with specific examples.

Example 1:

1) Weigh 1 g of chitosan (viscosity average molecular weight of 10,000, deacetylation degree of 60%) into a 100 mL beaker, then add 9 mL of 2% acetic acid aqueous solution, and stir to obtain a 10 wt.% shell Glycan solution A;

2) Weigh a certain mass of anhydrous calcium chloride powder and add it to the chitosan solution A to form the mixture stock solution B. The added amount is measured by the theoretical value of the ratio of the mass of chitosan (CS) to the mass of calcium carbonate (CaCO ₃ ) corresponding to calcium ions, and m(CS):m(CaCO ₃ ) is 4:96. Then add a certain amount of urea for solubilization, until the light transmittance of the mixed solution measured by the WGT-S haze meter is greater than 90%, to obtain a homogeneous mixed solution C;

3) The solution C was injected into a cylindrical mold composed of a semi-permeable membrane and immersed in a mixed coagulation bath of NaOH, Na ₂ CO ₃ , where the NaOH concentration was 2 wt.%, c(NaOH):c(Na ₂ CO ₃ ) is 1:1;

4) demoulding the obtained chitosan-based composite gel, repeatedly washing with deionized water until neutral, and drying to obtain a chitosan-calcium carbonate three-dimensional bone nail material.

The inorganic content of the chitosan-calcium carbonate three-dimensional bone nail material prepared in this example is 95.6%.

Example 2:

1) Weigh 1 g of chitosan (viscosity average molecular weight is 200,000, deacetylation degree is 70%) and add it to a 100 mL beaker, then add 11.5 mL of acetic acid aqueous solution with a volume fraction of 5%, and stir to obtain 8 wt.% of chitosan. Chitosan solution A;

2) Weigh a certain mass of anhydrous calcium chloride powder and add it to the chitosan solution A to form the mixture stock solution B. The added amount is measured by the theoretical value of the ratio of the mass of chitosan (CS) to the mass of calcium carbonate (CaCO ₃ ) corresponding to calcium ions, and m(CS):m(CaCO ₃ ) is 15:85. Then add a certain amount of urea for solubilization, until the light transmittance of the mixed solution measured by the WGT-S haze meter is greater than 90%, to obtain a homogeneous mixed solution C;

3) The solution C was injected into a cylindrical mold composed of a semi-permeable membrane and immersed in a mixed coagulation bath of NaOH, Na ₂ CO ₃ , where the NaOH concentration was 4 wt.%, c(NaOH):c(Na ₂ CO ₃ ) is 1:1;

4) demoulding the obtained chitosan-based composite gel, repeatedly washing with deionized water until neutral, and drying to obtain a chitosan-calcium carbonate three-dimensional bone nail material.

The inorganic content of the chitosan-calcium carbonate three-dimensional bone nail material prepared in this example is 83.1%.

Example 3:

1) Weigh 1 g of chitosan (viscosity average molecular weight is 500,000, deacetylation degree is 80%) and add it to a 100 mL beaker, then add 19 mL of acetic acid aqueous solution with a volume fraction of 10%, and stir to obtain a 5 wt.% shell Glycan solution A;

2) Weigh a certain mass of anhydrous calcium chloride powder and add it to the chitosan solution A to form the mixture stock solution B. The added amount is measured by the theoretical value of the ratio of the mass of chitosan (CS) to the mass of calcium carbonate (CaCO ₃ ) corresponding to calcium ions, and m(CS):m(CaCO ₃ ) is 25:75. Then add a certain amount of urea for solubilization, until the light transmittance of the mixed solution measured by the WGT-S haze meter is greater than 90%, to obtain a homogeneous mixed solution C;

3) The solution C was injected into a cylindrical mold composed of a semi-permeable membrane and immersed in a mixed coagulation bath of NaOH, Na ₂ CO ₃ , where the NaOH concentration was 5 wt.%, c(NaOH):c(Na ₂ CO ₃ ) is 2:1;

4) demoulding the obtained chitosan-based composite gel, repeatedly washing with deionized water until neutral, and drying to obtain a chitosan-calcium carbonate three-dimensional bone nail material.

The inorganic content of the chitosan-calcium carbonate three-dimensional bone nail material prepared in this example is 74.4%.

Example 4:

1) Weigh 1 g of chitosan (viscosity average molecular weight of 1 million, deacetylation degree of 90%) into a 100 mL beaker, then add 24 mL of acetic acid aqueous solution with a volume fraction of 15%, and stir to obtain a 4 wt.% shell Glycan solution A;

2) Weigh a certain mass of anhydrous calcium chloride powder and add it to the chitosan solution A to form the mixture stock solution B. The added amount is measured by the theoretical value of the ratio of the mass of chitosan (CS) to the mass of calcium carbonate (CaCO ₃ ) corresponding to calcium ions, and m(CS):m(CaCO ₃ ) is 35:65. Then add a certain amount of urea for solubilization, until the light transmittance of the mixed solution measured by the WGT-S haze meter is greater than 90%, to obtain a homogeneous mixed solution C;

3) The solution C was injected into a cylindrical mold composed of a semi-permeable membrane and immersed in a mixed coagulation bath of NaOH, Na ₂ CO ₃ , where the NaOH concentration was 8 wt.%, c(NaOH):c(Na ₂ CO ₃ ) is 2:1;

4) demoulding the obtained chitosan-based composite gel, repeatedly washing with deionized water until neutral, and drying to obtain a chitosan-calcium carbonate three-dimensional bone nail material.

The inorganic content of the chitosan-calcium carbonate three-dimensional bone nail material prepared in this example is 63.2%.

Example 5:

1) Weigh 1 g of chitosan (viscosity average molecular weight is 1.2 million, deacetylation degree is 95%) and add it to a 100 mL beaker, then add 49 mL of 20% acetic acid aqueous solution, and stir to obtain a 2 wt.% shell Glycan solution A;

2) Weigh a certain mass of anhydrous calcium chloride powder and add it to the chitosan solution A to form the mixture stock solution B. The added amount is measured by the theoretical value of the ratio of the mass of chitosan (CS) to the mass of calcium carbonate (CaCO ₃ ) corresponding to calcium ions, and m(CS):m(CaCO ₃ ) is 50:50. Then add a certain amount of urea for solubilization, until the light transmittance of the mixed solution measured by the WGT-S haze meter is greater than 90%, to obtain a homogeneous mixed solution C;

3) The solution C was injected into a cylindrical mold composed of a semipermeable membrane, and immersed in a mixed coagulation bath of NaOH, Na ₂ CO ₃ , where the NaOH concentration was 10 wt.%, c(NaOH):c(Na ₂ CO ₃ ) is 3:1;

4) demoulding the obtained chitosan-based composite gel, repeatedly washing with deionized water until neutral, and drying to obtain a chitosan-calcium carbonate three-dimensional bone nail material.

The inorganic content of the chitosan-calcium carbonate three-dimensional bone nail material prepared in this example is 49.5%.

Example 6:

1) Weigh 1 g of chitosan (viscosity average molecular weight is 200,000, deacetylation degree is 70%) and add it to a 100 mL beaker, then add 11.5 mL of acetic acid aqueous solution with a volume fraction of 5%, and stir to obtain 8 wt.% of chitosan. Chitosan solution A;

2) Weigh a certain mass of anhydrous calcium chloride powder and add it to the chitosan solution A to form the mixture stock solution B. The added amount is measured by the theoretical value of the ratio of the mass of chitosan (CS) to the mass of calcium carbonate (CaCO ₃ ) corresponding to calcium ions, and m(CS):m(CaCO ₃ ) is 15:85. Precipitation occurred in mixed solution B, and in the case of not adding urea for solubilization, it always showed a turbid gel state, and subsequent operations such as coagulation, washing, and drying were not performed. It can be seen that the chitosan-calcium carbonate three-dimensional bone nail material could not be prepared without urea solubilization.

Claims (3)

1. a method for preparing calcium carbonate-chitosan three-dimensional bone-setting nail material by urea solubilization method, is characterized in that, in the described three-dimensional bone-setting nail material, calcium carbonate is with calcite small particles, carbonic acid from inside to outside along the bone screw radial direction. There are three forms of calcium globules and small globule groups, and calcium carbonate has the characteristics of gradient distribution along the radial direction, and the method includes the following steps: 1) Weigh a certain mass of chitosan with a viscosity-average molecular weight of 10,000-1.2 million and a degree of deacetylation of 60%-95% as a solute, and use an aqueous acetic acid solution with a volume fraction of 2%-20% as a solvent, and stir until completely Dissolve, prepare 2 wt.%-10 wt.% chitosan solution A; 2) Weigh a certain mass of anhydrous calcium chloride powder and add it to the chitosan solution A to form the mixture stock solution B; then add a certain amount of urea for solubilization until the mixture solution is measured by the WGT-S haze meter The transmittance is greater than 90% to obtain a homogeneous mixed solution C; 3) The solution C was injected into a cylindrical mold composed of a semipermeable membrane and immersed in a mixed coagulation bath of NaOH, _Na2CO3 , where the NaOH concentration was ₂ wt.%-10 wt.%, c(NaOH): c (Na ₂ CO ₃ ) is 1:1-3:1; 4) The obtained chitosan-based composite gel is demolded, washed repeatedly with deionized water until neutral, and dried to obtain a calcium carbonate-chitosan three-dimensional bone nail material. 2. The method for preparing calcium carbonate-chitosan three-dimensional bone nail material by urea solubilization method according to claim 1, wherein the amount of calcium chloride added is corresponding to the quality of chitosan (CS) and calcium ions The theoretical value of the mass ratio of calcium carbonate (CaCO ₃ ) is measured, m(CS): m(CaCO ₃ ) is 50:50-4:96. 3. The method for preparing calcium carbonate-chitosan three-dimensional bone nail material by urea solubilization method according to claim 1, it is characterized in that: the mass fraction of calcium carbonate in the calcium carbonate-chitosan three-dimensional bone nail material Up to 50%-95%.

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