CN115400272B - Calcium sulfate-calcium phosphate-silicon dioxide ternary bone cement and preparation method thereof - Google Patents
Calcium sulfate-calcium phosphate-silicon dioxide ternary bone cement and preparation method thereof Download PDFInfo
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Abstract
The invention relates to a calcium sulfate-calcium phosphate-silicon dioxide ternary bone cement and a preparation method thereof. The calcium sulfate bone cement comprises a solid phase and a liquid phase, wherein the solid phase is formed by mixing the following raw materials in parts by weight: 30-90 parts of calcium phosphate silicon dioxide mixture and 10-70 parts of calcium sulfate powder; the calcium sulfate powder comprises calcium sulfate hemihydrate, and the grain size range of the calcium sulfate hemihydrate is 1-65 mu m; the particle size of the calcium phosphate silica mixture ranges from 1 to 250 μm. According to the invention, the particle size of the calcium phosphate silicon dioxide, the crystal form of the calcium sulfate hemihydrate and the particle size are finely regulated and controlled, so that the curing time, the mechanical strength and the injection performance of the bone cement can be regulated and controlled in a large range, the used calcium sulfate hemihydrate is prepared under the conditions of normal temperature and normal pressure, the energy is saved, the environment is protected, the bone cement is suitable for mass production, and the calcium sulfate-calcium phosphate-silicon dioxide ternary bone cement is a bone cement very suitable for clinical use.
Description
Technical Field
The invention relates to the field of biomedical materials, in particular to calcium sulfate-calcium phosphate-silicon dioxide ternary bone cement and a preparation method thereof.
Background
Bone cement is a biomedical material which can be used for filling bone gaps or bone defects and has self-coagulation property, and is widely applied to filling treatment of artificial joints, vertebral fracture, bone defects and the like. With the continuous trend of the aging level of the population in China, the number of patients with orthopedic diseases is continuously increased, and the demand for bone cement is increasing. Currently, polymethyl acrylate bone cement (PMMA), calcium phosphate bone cement (CPC), calcium sulfate bone cement (CSC) and the like are available on the market, but they all have respective disadvantages. For example, a large amount of heat is released in the curing process of PMMA bone cement, and the PMMA bone cement is not degradable and has no bioactivity after being implanted into a human body; CPC bone cement and CSC bone cement have the characteristic of rapid degradation although having certain biological activity. The calcium sulfate bone cement has good self-curing property, convenient use and low cost, and various products are visible on the market, such as GeneX bone cement (CPC and CSC mixture) and STIMULAN bone cement (CSC) developed by Biocomposition, england, osteoset bone cement (CSC) of Wright company in the United states, which are suitable for bone defect filling, minimally invasive surgery treatment and the like, and have wide application, but the biological activity is not outstanding, and the effect of promoting bone regeneration cannot be achieved. Thus, it is necessary to increase the bioactivity of calcium sulfate-based bone cements without degrading other properties.
The calcium phosphate silicon dioxide mixture is a biomedical material with good biological activity, degradability and absorption and good biocompatibility, can provide calcium ions and phosphate ion sources required by bone osteogenesis of human body after being implanted into the human body, can mineralize on the surface of the material to form hydroxyapatite, promotes the adhesion, proliferation and osteogenesis differentiation of cells, and is hopeful to greatly promote the bone regeneration speed. However, calcium phosphate silica mixtures are difficult to injection mold and require compounding with other adjuvants to achieve injection molding capability.
Calcium sulfate hemihydrate, which is a bone repair material already in clinical use, has complementarity to the calcium phosphate silica mixture. The calcium phosphate-silica mixture is introduced into the self-curing system of calcium sulfate hemihydrate, so that the osteoinductive property of the bone cement can be improved, and the regeneration capacity of bone tissues can be promoted. However, in the existing calcium phosphate-silica mixture and calcium sulfate composite bone cement, the injection performance, the collapsibility resistance and the mechanical performance of the bone cement can not reach good levels only by simple compounding of the calcium phosphate-silica mixture and calcium sulfate hemihydrate, and the clinical use requirements can be met by a large amount of improvement space.
Disclosure of Invention
Based on the above, the invention aims to provide the calcium sulfate-calcium phosphate-silicon dioxide ternary bone cement and the preparation method thereof, and the bone cement realizes good mechanical property, solidification property, collapsibility and injectability by reasonably compounding the particle size of the calcium phosphate-silicon dioxide mixture, the particle size of the calcium sulfate hemihydrate and the crystal morphology.
The aim is achieved by the following technical scheme.
In a first aspect of the present invention, there is provided a calcium sulfate-calcium phosphate-silica ternary bone cement comprising a solid phase and a liquid phase; the solid phase is formed by mixing the following raw materials in parts by weight: 30-90 parts of calcium phosphate silicon dioxide mixture and 10-70 parts of calcium sulfate powder; the liquid phase is water for injection, phosphate buffer solution or phosphate solution;
the calcium sulfate powder comprises calcium sulfate hemihydrate, and the particle size range of the calcium sulfate hemihydrate is 1-65 mu m.
The calcium sulfate hemihydrate is a mixture of flaky and short columnar crystal forms, and the proportion of the calcium sulfate hemihydrate is as follows in parts by weight: 70-99 parts of flaky calcium sulfate hemihydrate and 1-30 parts of short columnar calcium sulfate hemihydrate.
In some of these embodiments, the calcium sulfate hemihydrate has a particle size of 1 to 65 μm, preferably 6 to 25 μm.
In some embodiments, the calcium sulfate powder further comprises at least one of calcium sulfate dihydrate and anhydrous calcium sulfate, and the calcium sulfate powder comprises the following components in parts by weight: 85-100 parts of calcium sulfate hemihydrate, 0-10 parts of calcium sulfate dihydrate and 0-5 parts of anhydrous calcium sulfate.
In some embodiments, the calcium sulfate powder comprises the following components in parts by weight: 90-100 parts of calcium sulfate hemihydrate and 0-10 parts of calcium sulfate dihydrate.
In some of these embodiments, the calcium phosphate silica mixture has a composition of: x (SiO) 2 )y(Ca k P m O n ) The method comprises the steps of carrying out a first treatment on the surface of the Wherein x is 40-60 mol%, y is 40-60 mol%, and the molar ratio of calcium and phosphorus elements is 1.5-2, wherein k is 3-4; further preferably, x is 45-55 mol%, y is 45-55 mol%, and the molar ratio of calcium and phosphorus elements is 1.6-1.8, wherein k is 3-4; .
In some embodiments, the solid phase is formed by mixing the following raw materials in parts by weight: 30-90 parts of calcium phosphate silicon dioxide mixture and 10-70 parts of calcium sulfate powder.
In some embodiments, the solid phase is formed by mixing the following raw materials in parts by weight: 40-60 parts of calcium phosphate silicon dioxide mixture and 40-60 parts of calcium sulfate powder.
In some of these embodiments, the calcium phosphate silica mixture has a particle size of 1 to 250 μm, preferably 3 to 150 μm.
In some of these embodiments, the mass to volume ratio of the solid phase to the liquid phase is 1g: (0.2-2) ml.
In some embodiments, drugs, growth factors, such as gentamicin, active vitamin D3, bone Morphogenic Proteins (BMPs), and the like, may also be included in the ternary bone cement.
In a second aspect, the present invention provides a method for preparing the calcium sulfate-calcium phosphate-silica ternary bone cement, comprising the following steps: and fully mixing the calcium sulfate powder and the calcium phosphate silicon dioxide mixture to obtain solid phase powder, and mixing the obtained solid phase with the liquid phase to obtain the calcium sulfate bone cement containing the calcium phosphate silicon dioxide mixture.
In a third aspect, the invention provides an application of the calcium sulfate-calcium phosphate-silica ternary bone cement in bone defect repair materials.
In some of these embodiments, the bone defect repair material is a bone defect repair material for non-load bearing bone defect repair of limbs and/or the spine.
In some of these embodiments, the repair includes filling and/or reconstruction.
In some of these embodiments, the bone defect repair material is a bone defect repair material for delayed healing or non-union of a fractured bone of a joint fusion comminuted fracture, or for replacement and revision of a filled joint after bone tumor surgery.
Compared with the prior art, the invention has the following beneficial effects:
according to the invention, through fine regulation and control of the particle size of the calcium phosphate-silica mixture, the crystal form of calcium sulfate hemihydrate and the particle size, the powerful regulation and control of the curing time, the mechanical strength and the injectability of the bone cement are realized under the condition that no performance auxiliary agent is added, the setting time is adjustable within 2-30 min under the condition that the bone cement is injectable, the mechanical strength is adjustable within 2-38 MPa, the loading capacity of the calcium phosphate-silica mixture in the bone cement is increased to 90%, the content of the calcium phosphate-silica mixture in the bone cement is increased, the biological activity of the bone cement is increased to a great extent, the collapse problem possibly occurring after the degradation of calcium sulfate is effectively avoided, the bone defect part is fully filled, and the bone healing effect is promoted.
Furthermore, the calcium sulfate-calcium phosphate-silicon dioxide ternary bone cement has good biological activity and biocompatibility, can induce osteogenesis and promote the growth of tissues around bones, can form firm chemical bonding with the bone tissues after being implanted, can regulate and control the degradation rate by adjusting the content of a calcium phosphate-silicon dioxide mixture in the bone cement, can adjust the degradation time within 1-24 months, and can finally screen out bone cement materials matched with the growth rate of human bones.
Drawings
FIG. 1 is the results of the mechanical properties test of the bone cement solid in example 1;
FIG. 2 is an XRD pattern of in vitro deposited HA from the bone cement of example 1;
FIG. 3 is a graph showing the effect of injectability of the bone cement of example 1;
FIG. 4 is the results of the mechanical properties test of the bone cement of example 2;
FIG. 5 is the results of the mechanical properties test of the solid bone cement of example 3;
FIG. 6 is a graph showing the effect of injectability of the bone cement of example 3;
FIG. 7 is a graph showing the anti-collapsibility effect of the bone cement of example 3;
FIG. 8 is a graph showing the effect of the bone cement of example 1 after curing;
FIG. 9 is a photograph of example 1 bone cement after 11 weeks of degradation in simulated body fluid SBF;
fig. 10 is a graph of experimental data of in vitro simulated degradation of the bone cement of example 1.
Detailed Description
The experimental methods of the present invention, in which specific conditions are not specified in the following examples, are generally conducted under conventional conditions or under conditions recommended by the manufacturer. The various chemicals commonly used in the examples are commercially available.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.
The terms "comprising" and "having" and any variations thereof, are intended to cover a non-exclusive inclusion. For example, a process, method, apparatus, article, or device that comprises a list of steps is not limited to the elements or modules listed but may alternatively include additional steps not listed or inherent to such process, method, article, or device.
In the present invention, the term "plurality" means two or more. "and/or", describes an association relationship of an association object, and indicates that there may be three relationships, for example, a and/or B, and may indicate: a exists alone, A and B exist together, and B exists alone. The character "/" generally indicates that the context-dependent object is an "or" relationship.
The invention discovers that in the existing preparation method of calcium sulfate bone cement containing a calcium phosphate silicon dioxide mixture, the research on the coupling relation of crystal forms and particle sizes of the calcium sulfate hemihydrate and the calcium phosphate silicon dioxide mixture is insufficient, the potential great influence of the crystal forms and the particle sizes of the calcium sulfate hemihydrate on the bone cement performance is ignored, in order to make up the defect of the bone cement performance, performance auxiliary agents such as sodium carboxymethyl cellulose are generally added to enhance the mechanical performance, and sodium hyaluronate is added to improve the injection performance. In addition, only a small amount of calcium phosphate and silicon dioxide mixture can be loaded in the bone cement prepared by the traditional compounding method, the degradation rate of calcium sulfate hemihydrate is high, the degradation time of the calcium sulfate bone cement with low content of the calcium phosphate and silicon dioxide mixture is high, and the bone cement is easy to collapse into particles in the later period of degradation.
Based on the above, the invention provides a novel preparation method of calcium sulfate bone cement containing a calcium phosphate silicon dioxide mixture, which is characterized in that the crystal form and the particle size of calcium sulfate hemihydrate are regulated and controlled, and then the calcium phosphate silicon dioxide mixture with proper particle size is selected to be matched with the calcium phosphate bone cement. After the solid-phase powder is mixed with the liquid phase, the prepared bone cement has excellent collapsibility, injectability and mechanical properties, a break is found from the traditional solution, the safety and stability of the bone cement are improved, and the clinical application value of the whole scheme is greatly improved.
The specific technical scheme is as follows:
a calcium sulfate-calcium phosphate-silica ternary bone cement comprising a solid phase and a liquid phase; the solid phase is formed by mixing the following raw materials in parts by weight: 30-90 parts of calcium phosphate silicon dioxide mixture and 10-70 parts of calcium sulfate powder; the liquid phase is water for injection, phosphate buffer solution or phosphate solution
The calcium sulfate powder comprises calcium sulfate hemihydrate, and the particle size range of the calcium sulfate hemihydrate is 1-65 mu m;
preferably, the calcium sulfate hemihydrate has a particle size of 1 to 65 μm, more preferably 6 to 25 μm.
The calcium sulfate hemihydrate is a mixture of flaky and short columnar crystal forms, and the proportion of the calcium sulfate hemihydrate is as follows in weight percent: 70-99 parts of flaky calcium sulfate hemihydrate, 1-30 parts of short columnar calcium sulfate hemihydrate, and more preferably 90-99 parts of flaky calcium sulfate hemihydrate and 1-10 parts of short columnar calcium sulfate hemihydrate.
Preferably, the calcium sulfate powder removes calcium sulfate hemihydrate, and further comprises at least one of calcium sulfate dihydrate and anhydrous calcium sulfate, wherein the calcium sulfate powder comprises the following components in parts by weight: 85-100 parts of calcium sulfate hemihydrate, 0-10 parts of calcium sulfate dihydrate and 0-5 parts of anhydrous calcium sulfate, wherein the two are not 0 at the same time.
Preferably, the calcium sulfate powder comprises the following components in parts by weight: 90-100 parts of calcium sulfate hemihydrate and 1-10 parts of calcium sulfate dihydrate.
Or 85-100 parts of calcium sulfate hemihydrate, 1-10 parts of calcium sulfate dihydrate and 1-5 parts of anhydrous calcium sulfate.
Preferably, the composition of the calcium phosphate silica mixture is: x (SiO) 2 )y(Ca k P m O n ) The method comprises the steps of carrying out a first treatment on the surface of the Wherein x is 40-60 mol%, y is 40-60 mol%, the molar ratio of calcium and phosphorus elements is 1.5-2, wherein 3-4, and further preferably, x is 45-55 mol%, y is 45-55 mol%, and the molar ratio of calcium and phosphorus of calcium phosphate is 1.6-1.8, wherein 3-4.
Preferably, the solid phase is formed by mixing the following raw materials in parts by weight: 40-60 parts of calcium phosphate silicon dioxide mixture and 40-60 parts of calcium sulfate powder.
Preferably, the solid phase is formed by mixing the following raw materials in parts by weight: 45-55 parts of calcium phosphate silicon dioxide mixture and 45-55 parts of calcium sulfate powder.
Preferably, the solid phase is prepared from the following raw materials in parts by weight: 45-55 parts of calcium phosphate silicon dioxide mixture, 40-50 parts of calcium sulfate hemihydrate and 1-5 parts of calcium sulfate dihydrate.
Preferably, in the preparation of the calcium sulfate hemihydrate, the mass-volume ratio of the calcium sulfate powder to the water is 1g (0.5-20 ml), preferably 1g (0.5-10 ml), preferably 1g (0.5-5 ml).
Preferably, the liquid phase is water for injection, phosphate buffer or dihydrogen phosphate solution.
Preferably, the mass-to-volume ratio of the solid phase to the liquid phase is: 1g: (0.2-2) ml, specifically, may be 1g:2ml,1g:1ml,1g:0.9ml,1g:0.8ml,1g:0.7ml,1g:0.6ml,1g:0.5ml,1g:0.4ml,1g:0.3ml,1g:0.2ml, and a range of values between any two of the above values.
Preferably, the particle size of the calcium phosphate silica mixture is from 1 to 250. Mu.m, preferably from 3 to 150. Mu.m.
Preferably, the calcium sulfate bone cement can also comprise medicines and growth factors. Such as antibiotics, analgesics, etc.
The present invention will be described in further detail with reference to specific examples.
Example 1
A calcium sulfate-calcium phosphate-silica ternary bone cement prepared by the following method:
(1) Preparation of a calcium phosphate silicon dioxide mixture, according to the proportion of the calcium phosphate silicon dioxide mixture, respectively taking phytic acid, tetraethoxysilane and calcium nitrate tetrahydrate as precursors of P, si and Ca ions, and preparing 54.2 percent of SiO by adopting a conventional sol-gel method 2 -45.8％(Ca 1.6 PO 4.1 ) The blocky calcium phosphate silicon dioxide mixture is crushed and sieved, and the calcium phosphate silicon dioxide mixture with the average particle size of about 106 mu m is selected for standby.
(2) Mixing the calcium phosphate-silica mixture of the step (1) and calcium sulfate hemihydrate with the average particle diameter of about 18 mu m, wherein the proportion of the flaky crystal form is 99 parts, the proportion of the short columnar crystal form is 1 part, and the solid phase powder of the bone cement is obtained according to the proportion of 5:5 (g/g). To be used forThe solid-liquid ratio is 1:0.4 (g/ml), injection water is added, the mixture is rapidly stirred into a viscous state and then molded, the setting time of the bone cement is 7-9 min, and the injectability and the collapsibility resistance are good. Under the condition of room temperature, the compressive strength of the bone cement is 8-9 MPa (as shown in figure 1, the abscissa represents the strain (%) of the bone cement, the ordinate represents the compressive strength (MPa) of the bone cement) after curing for 1 day, a large amount of hydroxyapatite is generated after placing the bone cement into SBF simulated body fluid for 3 days (as shown in figure 2), and the peak areas of HA at-26 DEG and-32 DEG are integrated to obtain the peak area S of the bone cement 1 The amorphous peaks of 12 DEG to 38 DEG are also integrated to obtain the peak areas S 0 Approximately use S 1 /S 0 To estimate the relative amount of HA deposition, resulting in S 1 /S 0 =11.5%, indicating that bone cement has good in vitro bioactivity. The bone cement is put into simulated body fluid for degradation experiments, and after 7 days, the compressive strength is greater than 15MPa, and the bone cement can provide enough mechanical support in the later stage of bone growth.
Example 2
The calcium phosphate silica mixture prepared in example 1, flaky calcium sulfate hemihydrate having an average particle diameter of 18 μm, short columnar calcium sulfate hemihydrate having an average particle diameter of about 7 μm, were mixed in a ratio of 20:21:9 (g/g/g) to obtain a bone cement solid phase powder. Injection water was added at a solid-to-liquid ratio of 1:0.34 (g/ml), and the mixture was rapidly stirred to a viscous state, followed by molding. The setting time of the bone cement is 5-7 min, and the bone cement has injectability and good collapsibility resistance. And under the condition of room temperature, the compressive strength of the bone cement is 17-18 MPa after curing for 3 days. The test results are shown in fig. 4.
Example 3
A calcium sulfate-calcium phosphate-silica ternary bone cement prepared by the following method:
a calcium phosphate silica mixture having a particle size of 1 to 25 μm was prepared according to the method for preparing a calcium phosphate silica mixture in example 1.
The prepared calcium phosphate silicon dioxide mixture with the particle size of 1-25 mu m and the calcium sulfate hemihydrate powder with the average particle size of 7 mu m are mixed according to the proportion of 9:1 (g/g), then 10 percent sodium dihydrogen phosphate solution with the mass percentage concentration is added according to the solid-to-liquid ratio of 1:0.5 (g/ml), the mixture is quickly stirred and then transferred into a mould, the setting time of the bone cement is 30min, the compression strength of the bone cement is more than 18MPa after curing at room temperature for 3 days, and the bone cement is injectable and has good collapsibility. The solid bone cement after solidification is leached with pure water for 24 hours at 37 ℃ according to the proportion of 0.1g/ml, and the pH value of the solution is 7. The results of the mechanical strength test and the injectable performance/anti-collapsibility effect are shown in figures 5, 6 and 7 respectively.
Example 4
A calcium sulfate-calcium phosphate-silica ternary bone cement prepared by the following method:
(1) A calcium phosphate silica mixture having an average particle diameter of 6 μm was prepared in accordance with the preparation method of the calcium phosphate silica mixture in example 1.
The calcium phosphate silica mixture prepared in example 4, short column-shaped calcium sulfate hemihydrate powder with average particle size of 7 μm were mixed in a ratio of 8:2 (g/g), then a 5% sodium dihydrogen phosphate solution with mass percent concentration was added in a solid-to-liquid ratio of 1:0.5 (g/ml), and after rapid stirring, the mixture was transferred to a mold, and the initial setting time of bone cement was 25min. The compression strength is more than 24MPa after 3 days of curing at room temperature. The solid bone cement after solidification is leached with pure water for 24 hours at 37 ℃ according to the proportion of 0.1g/ml, and the pH value of the solution is 7.
Comparative example 1
The difference between this comparative example and example 1 is that all of the calcium sulfate hemihydrate is short columnar calcium sulfate hemihydrate, and the average particle diameter is about-7. Mu.m.
The mixture of calcium sulfate hemihydrate and calcium phosphate silica prepared by the method is prepared according to the method in the example 1, and the compressive strength of the mixture is 2MPa after being cured at room temperature for 1 day, and the initial setting time is 20min. The injectability and anti-collapsibility of bone cement are poor.
Comparative example 2
According to the information disclosed in the embodiments 2 and 1 of the specifications of the patent CN201911054575.0 and the CN201610248345.8, the content of the bioactive glass (the calcium phosphate silicon dioxide mixture) in the solid phase powder is in the range of 30-40 parts, and although organic matters (such as carboxymethyl cellulose, chitosan and the like) are added as the bone cement performance auxiliary agent in the preparation process of the bone cement so as to enhance the mechanical property, injectability and collapsibility, the mechanical property of the bone cement in the two patents is lower than that of the bone cement in the embodiment 2 of the invention, namely, the bone cement in the two patents is respectively 11MPa and 6MPa. It is explained that better effect can be achieved by fine regulation and control of particle sizes and crystal forms of two substances in the solid phase powder.
Comparative example 3
A calcium phosphate silica mixture having a particle size of 250 to 350 μm was prepared according to the method for preparing a calcium phosphate silica mixture in example 3.
The calcium phosphate-silica mixture prepared by the method and calcium sulfate are prepared according to the method in the example 3, the compressive strength of the composite bone cement cured at room temperature for 3 days is less than 5MPa, and the injectability and the collapsibility of the bone cement are poor. The two powder particle sizes are not matched, and the prepared bone cement has poor overall performance, which indicates that the particle size has larger influence on the overall performance of the bone cement.
Comparative example 4
The tetracalcium phosphate Ca with the grain diameter of 1-25 mu m is selected 4 P 2 O 9 I.e. calcium phosphate silica mixture x (SiO 2 )y(Ca k P m O n ) Wherein x is 0, y is 1, and the molar ratio of calcium to phosphorus of the calcium phosphate is k/m=2. Mixing the tetracalcium phosphate with calcium sulfate with the average particle size of 7 mu m according to the weight ratio of 9:1 (g/g) to obtain solid phase powder, and then according to the solid-liquid ratio of 1:0.5 (g/ml) mixing the solid-phase powder with sodium dihydrogen phosphate solution with the mass percentage concentration of 5% or 10% to obtain the bone cement, wherein the curing time of the bone cement is 5-10 min, and the mechanical strength of the bone cement is less than 2MPa, and the bone cement has no injectability and poor collapsibility resistance.
1. Determination of degradation Property of bone Cement
The cement containing the calcium phosphate silica mixture sulfuric acid was prepared as in example 1, transferred in a viscous state to a syringe, and injected as an injectable cement by the syringe, and the effect is shown in fig. 3. The crystal form of the calcium sulfate hemihydrate prepared in the comparative example 1 is in a short column shape, and although the crystal form is strong in mechanical property after being solidified by adding water, the crystal form is poor in collapsibility and injectability mechanical property after being compounded with the calcium phosphate silicon dioxide mixture, and the advantages of the crystal form and the calcium sulfate hemihydrate cannot be fully exerted by the compound of the crystal form and the calcium sulfate hemihydrate.
Calcium sulfate cements containing a mixture of calcium phosphate and silica were prepared as in example 1, allowed to fully set, and then placed into a simulated body fluid SBF for degradation performance testing, as shown in fig. 8, 9, and 10. After 11 weeks of degradation in simulated body fluid SBF, the degradation rate did not exceed 60% and the diameter of the bone cement pieces did not change substantially before and after degradation, d=10.0 mm.
The technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.
The above examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.
Claims (10)
1. A calcium sulfate-calcium phosphate-silica ternary bone cement, comprising a solid phase and a liquid phase; the solid phase is formed by mixing the following raw materials in parts by weight: 30-90 parts of calcium phosphate silicon dioxide mixture and 10-70 parts of calcium sulfate powder; the liquid phase is water for injection or phosphate solution;
the particle size of the calcium phosphate silicon dioxide mixture is 1-250 mu m;
the calcium sulfate powder comprises calcium sulfate hemihydrate, and the particle size of the calcium sulfate hemihydrate is 1-65 mu m;
the calcium sulfate hemihydrate is a mixture of flaky and short columnar crystal forms, and the proportion of the calcium sulfate hemihydrate is as follows in parts by weight: 70-99 parts of flaky calcium sulfate hemihydrate and 1-30 parts of short columnar calcium sulfate hemihydrate.
2. The calcium sulfate-calcium phosphate-silica ternary bone cement according to claim 1, wherein the calcium sulfate powder further comprises at least one of calcium sulfate dihydrate and anhydrous calcium sulfate, and the calcium sulfate powder comprises the following components in parts by weight: 85-100 parts of calcium sulfate hemihydrate, 0-10 parts of calcium sulfate dihydrate and 0-5 parts of anhydrous calcium sulfate, wherein the two are not 0 at the same time.
3. The calcium sulfate-calcium phosphate-silica ternary bone cement of claim 1, wherein the composition of the calcium phosphate silica mixture is: x (SiO) 2 )y(Ca k P m O n ) The method comprises the steps of carrying out a first treatment on the surface of the Wherein x is 40-60 mol%, y is 40-60 mol%, and the molar ratio of calcium and phosphorus elements is 1.5-2, wherein k is 3-4.
4. The calcium sulfate-calcium phosphate-silica ternary bone cement according to claim 1, wherein the calcium phosphate-silica mixture has a particle size of 1 to 250 μm.
5. The ternary calcium sulfate-calcium phosphate-silica bone cement according to any one of claims 1 to 4, wherein the mass to volume ratio of the solid phase to the liquid phase is 1g (0.2 to 2) mL.
6. The ternary calcium sulfate-calcium phosphate-silica cement according to any one of claims 1 to 4, wherein the cement may further comprise a drug.
7. The calcium sulfate-calcium phosphate-silica ternary bone cement according to any one of claims 1 to 4, wherein the solid phase is formed by mixing the following raw materials in parts by weight: 45-55 parts of calcium phosphate silicon dioxide mixture, 40-50 parts of calcium sulfate hemihydrate and 1-5 parts of calcium sulfate dihydrate.
8. The method for preparing the calcium sulfate-calcium phosphate-silica ternary bone cement according to any one of claims 1 to 7, comprising the following steps:
and fully mixing the calcium sulfate powder and the calcium phosphate silicon dioxide mixture to obtain solid phase powder, and mixing the obtained solid phase with the liquid phase to obtain the calcium sulfate-calcium phosphate-silicon dioxide ternary bone cement.
9. Use of the ternary calcium sulfate-calcium phosphate-silica bone cement of any one of claims 1-7 in the preparation of a bone defect repair material.
10. The use according to claim 9, wherein the bone defect repair material is a bone defect repair material for delayed healing or repair of bone nonunion of joint fusion comminuted fracture bone, or for replacement and revision of a bone tumor post-operative filling joint.
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| US5462722A (en) * | 1991-04-17 | 1995-10-31 | Liu; Sung-Tsuen | Calcium phosphate calcium sulfate composite implant material |
| US20030055512A1 (en) * | 2001-05-21 | 2003-03-20 | Genin Francois Y. | Calcium based neutral and bioresorbable bone graft |
| US7507257B2 (en) * | 2003-02-04 | 2009-03-24 | Wright Medical Technology, Inc. | Injectable resorbable bone graft material, powder for forming same and methods relating thereto for treating bone defects |
| CN100406072C (en) * | 2006-07-18 | 2008-07-30 | 中国科学院上海硅酸盐研究所 | Bio-activity tricalcium silicate/semi water calcium sulphate composite self-solidification material, preparation and application |
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| CN102049062B (en) * | 2009-10-30 | 2014-07-09 | 华东理工大学 | Injectable efficient suspended stable calcium phosphate cement and preparation method and application thereof |
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