CN113769160A - Thermo-sensitive microsphere and ready-to-use thermo-sensitive calcium phosphate cement thereof - Google Patents
Thermo-sensitive microsphere and ready-to-use thermo-sensitive calcium phosphate cement thereof Download PDFInfo
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Abstract
The invention discloses a temperature-sensitive microsphere and ready-to-use calcium phosphate cement thereof, and a preparation method of the temperature-sensitive microsphere is characterized by comprising the following steps: 1) adding citric acid into the water solution to prepare a citric acid solution with the concentration of 0.15-0.35 mol/L to obtain a water phase; 2) weighing 100mg of the following components in a weight ratio of 0.5-1.5:0.2-0.5: 0.1-0.4: dissolving 0.4-0.8 chitosan, polyvinyl alcohol, sophorolipid, and polypropyl acrylamide in 20-40ml dichloromethane to form oil phase, mixing 8-12ml water phase and 20-40ml oil phase, and ultrasonic dispersing for 1-3min to obtain emulsion; 3) and then stirring for 2-4h at low temperature, and removing the organic solvent to obtain the temperature-sensitive microspheres. The bone cement contains the temperature-sensitive microspheres, so that good cohesive force can be obtained, the bone cement has enough storage time, the temperature-sensitive microspheres are not released in the storage process, and the curing liquid can be released after injection to promote the curing inside the bone cement.
Description
Technical Field
The invention belongs to the field of medical materials, relates to microspheres and bone cement thereof, and particularly relates to temperature-sensitive microspheres and ready-to-use temperature-sensitive calcium phosphate bone cement thereof.
Background
Repair of hard tissue defects has been a difficult problem for surgeons and patients. Due to the similarity in biology and physico-chemical aspects of calcium phosphate cement and human skeleton and tooth, calcium phosphate cement is widely used in the repair and replacement of hard tissues. Alternative biomaterials are powders, granules or blocks. The calcium phosphate cement only needs percutaneous injection treatment and does not need open surgery, so the calcium phosphate cement can be used for hard tissue defect.
Injectable Calcium Phosphate Cement (ICPC) has good injectability, rapid in-situ setting, ease of molding into complex geometries, and good biocompatibility, and has become an urgent need for repair of hard tissues.
In order to facilitate the handling by the physician, anhydrous premixed calcium phosphate cements have been developed to simplify the use of traditional calcium phosphate cements and to reduce the impact of the setting reaction on the delivery process. However, since the anhydrous premixed bone cement does not contain a curing liquid, the bone cement needs to be cured after being injected into a defect site and then contacted with a body fluid, which results in that the internal curing speed of the bone cement is slower than the external curing speed, thereby prolonging the curing time and weakening the mechanical properties of the bone cement. To date, it has been difficult to obtain anhydrous premixed bone cements with good cohesion, adequate shelf life and adequate mechanical properties, which has hindered their use in clinical applications.
The temperature-sensitive poly (isopropyl acrylamide) (PNIPAAm) has hydrophilic and hydrophobic groups in the molecule, and the temperature-sensitive microcapsule containing the PNIPAAm shrinks and becomes hydrophobic when the temperature is higher than LCST (lower critical solution temperature, about 32 ℃), the solvent wrapped in the microcapsule is released, and the microcapsule is stretched when the temperature is lower than LCST (lower critical solution temperature, about 32 ℃) and shows hydrophilic property.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide the ready-to-use temperature-sensitive bone cement, which contains temperature-sensitive microspheres, can obtain good cohesive force and ensure that the bone cement has enough storage time, the temperature-sensitive microspheres do not release curing liquid in the storage process, and the curing liquid can be released after injection to promote the curing inside the bone cement.
The invention provides a temperature-sensitive microsphere, which comprises the following preparation methods:
1) adding citric acid into the water solution to prepare a citric acid solution with the concentration of 0.15-0.35 mol/L to obtain a water phase;
2) weighing 100mg of the following components in a weight ratio of 0.5-1.5:0.2-0.5: 0.1-0.4: dissolving 0.4-0.8 chitosan, polyvinyl alcohol, sophorolipid, and polypropyl acrylamide in 20-40ml dichloromethane to form oil phase, mixing 8-12ml water phase and 20-40ml oil phase, and ultrasonic dispersing for 1-3min to obtain emulsion;
3) and then stirring for 2-4h at low temperature, and removing the organic solvent to obtain the temperature-sensitive microspheres.
Preferably, the microspheres have a diameter of 10-100 μm.
Preferably, the preparation method comprises the following steps:
1) adding citric acid into the water solution to prepare a citric acid solution with the concentration of 0.15-0.25 mol/L to obtain a water phase;
2) weighing 100mg of the following components in a weight ratio of 0.5-1:0.2-0.3: 0.1-0.3: dissolving chitosan, polyvinyl alcohol, sophorolipid and polypropyl acrylamide 0.4-0.5 in dichloromethane 20-40ml to form oil phase, mixing water phase 8-10ml and oil phase 20-30ml, and ultrasonic dispersing for 1-2min to obtain emulsion;
3) then stirring for 2-3h at low temperature, removing the organic solvent, and obtaining temperature-sensitive microspheres;
preferably, the preparation method comprises the following steps:
1) adding citric acid into the aqueous solution to prepare 0.25mol/L citric acid solution to obtain a water phase;
2) weighing 100mg of the following components in a weight ratio of 1:0.3: 0.2: dissolving 0.5 chitosan, polyvinyl alcohol, sophorolipid and polypropyleneacrylamide in 30ml dichloromethane to form an oil phase, mixing 10ml water phase and 30ml oil phase, and performing ultrasonic dispersion for 2min to obtain an emulsion;
3) and then stirring for 3 hours at low temperature, and removing the organic solvent to obtain the temperature-sensitive microspheres.
Sophorolipid (SL) is a microbial secondary metabolite produced by candida using sugar, vegetable oil, and the like as carbon sources through a fermentation process under certain conditions. Sophorolipid is a glycolipid biosurfactant. It has the general properties of solubilization, emulsification, wetting, foaming, dispersion, surface tension reduction and the like of the conventional surfactant.
The invention also provides calcium phosphate cement, which comprises solid-phase powder and liquid-phase components, and is characterized in that the solid-phase powder comprises the following components in parts by mass: 60-80 parts of calcium phosphate powder; 5-15 parts of temperature sensitive microspheres, wherein the liquid phase component comprises the following components in parts by mass: 30-60 parts of a non-aqueous solvent; preferably, the solid-phase powder comprises the following components in parts by mass: 60-70 parts of calcium phosphate powder; 5-10 parts of temperature-sensitive microspheres according to any one of claims 1-3, wherein the liquid phase component comprises the following components in parts by mass: 40-50 parts of a nonaqueous solvent.
Preferably, the liquid phase component comprises the following components in parts by mass: 30-60 parts of a non-aqueous solvent; the non-aqueous solvent is one or more selected from glycerol, polyethylene glycol 600 or dimethyl silicone oil.
Preferably, the solid-phase powder comprises the following components in parts by mass: 70 parts of calcium phosphate powder; 10 parts of temperature-sensitive microspheres;
the liquid phase component comprises the following components in parts by mass: 50 parts of a nonaqueous solvent; the non-aqueous solvent is glycerol.
Preferably, the calcium phosphate in the solid phase powder is selected from one or more of tricalcium phosphate, tetracalcium phosphate, octacalcium phosphate, anhydrous calcium hydrophosphate, calcium hydrophosphate dihydrate, calcium biphosphate, calcium pyrophosphate, hydroxyapatite, fluorapatite, strontium apatite and carbonate-containing apatite.
Preferably, the calcium phosphate powder is alpha-tricalcium phosphate with the particle size of 10-200 mu m;
the invention also provides a preparation method of the calcium phosphate bone cement, which comprises the following steps: mixing calcium phosphate and temperature sensitive microsphere to obtain solid phase powder, adding liquid phase component to obtain paste, and storing the paste sample in a container at 4-50 deg.C under sealed condition.
The invention also provides application of the bone cement, which is characterized in that direct injection filling is carried out by a filling mode or by adopting an injector.
Has the advantages that:
1) the temperature-sensitive microspheres prepared by the method have good encapsulation efficiency, good permeability resistance at normal temperature, and no dissolution of the microspheres by glycerol.
2) The bone cement provided by the invention contains the temperature-sensitive microspheres, so that good cohesive force can be obtained, the bone cement has enough storage time, the microspheres do not release wrapped curing liquid in the storage process of the temperature-sensitive microspheres, and the curing liquid can be released to promote the curing inside the bone cement after injection.
3) The curing time of the bone cement is close to that of the existing bone cement, the use is convenient, the field configuration is not needed, and the pollution risk is avoided.
Detailed Description
To better illustrate the objects, aspects and advantages of the present invention, the present invention will be further described with reference to specific examples.
Sophorolipid, cas No.: 148409-20-5, available from Shanghai-Fei Biotechnology, Inc.
Chitosan, molecular weight 200-;
polyvinyl alcohol, molecular weight 12-18 kD;
example 1, preparation method of temperature sensitive microsphere:
1) adding citric acid into the aqueous solution to prepare 0.25mol/L citric acid solution to obtain a water phase;
2) weighing 100mg of the following components in a weight ratio of 1:0.3: 0.2: dissolving 0.5 of chitosan, polyvinyl alcohol, sophorolipid and polypropyleneacrylamide in 30ml of dichloromethane to serve as an oil phase, mixing 10ml of water phase with 30ml of oil phase, and performing ultrasonic dispersion for 2min to obtain emulsion;
3) and then stirring for 3 hours at low temperature, and removing the organic solvent to obtain the temperature-sensitive microspheres. 20-80 μm.
Example 2, a method for preparing temperature-sensitive microspheres:
1) adding citric acid into the aqueous solution to prepare 0.15mol/L citric acid solution to obtain a water phase;
2) weighing 100mg of the following components in a weight ratio of 0.6:0.2: 0.1: dissolving 0.4 ml of chitosan, polyvinyl alcohol, sophorolipid and polypropyleneacrylamide in 20ml of dichloromethane to form an oil phase, mixing 8ml of water phase and 20ml of oil phase, and performing ultrasonic dispersion for 1min to obtain an emulsion;
3) and then stirring for 2 hours at low temperature, and removing the organic solvent to obtain the temperature-sensitive microspheres. The diameter of the microspheres is 30-100 μm.
Example 3, preparation method of temperature sensitive microsphere:
1) adding citric acid into the aqueous solution to prepare 0.35mol/L citric acid solution to obtain a water phase;
2) weighing 100mg of the following components in a weight ratio of 1.2:0.4: 0.3: dissolving 0.6 chitosan, polyvinyl alcohol, sophorolipid and polypropyleneacrylamide in 40ml dichloromethane to form an oil phase, mixing 12ml water phase and 40ml oil phase, and performing ultrasonic dispersion for 3min to obtain an emulsion;
3) and then stirring for 4 hours at low temperature, and removing the organic solvent to obtain the temperature-sensitive microspheres. The diameter of the microsphere is 10-60 μm.
Example 4
In one embodiment of the calcium phosphate cement of the present invention, the cement comprises a solid-phase powder and a liquid-phase component;
the solid-phase powder comprises the following components in parts by mass: 60 parts of calcium phosphate powder; 5 parts of temperature-sensitive microspheres prepared in example 1; the calcium phosphate powder is alpha-tricalcium phosphate with the particle size of 10-200 mu m; the liquid phase component comprises the following components in parts by mass: 40 parts of a solvent; the solvent is glycerol.
Example 5
In one embodiment of the calcium phosphate cement of the present invention, the cement comprises a solid-phase powder and a liquid-phase component;
the solid-phase powder comprises the following components in parts by mass: 70 parts of calcium phosphate powder; 10 parts of temperature-sensitive microspheres prepared in example 1; the calcium phosphate powder is alpha-tricalcium phosphate with the particle size of 10-200 mu m; the liquid phase component comprises the following components in parts by mass: 70 parts of a solvent; the solvent is glycerol.
Example 6
In one embodiment of the calcium phosphate cement of the present invention, the cement comprises a solid-phase powder and a liquid-phase component;
the solid-phase powder comprises the following components in parts by mass: 70 parts of calcium phosphate powder; 10 parts of temperature-sensitive microspheres prepared in example 2; the calcium phosphate powder is alpha-tricalcium phosphate with the particle size of 10-200 mu m; the liquid phase component comprises the following components in parts by mass: 50 parts of a solvent; the solvent is glycerol.
Example 7
In one embodiment of the calcium phosphate cement of the present invention, the cement comprises a solid-phase powder and a liquid-phase component;
the solid-phase powder comprises the following components in parts by mass: 70 parts of calcium phosphate powder; 10 parts of temperature-sensitive microspheres prepared in example 3; the calcium phosphate powder is alpha-tricalcium phosphate with the particle size of 10-200 mu m; the liquid phase component comprises the following components in parts by mass: 50 parts of a solvent; the solvent is glycerol.
Example 8
In one embodiment of the calcium phosphate cement of the present invention, the cement comprises a solid-phase powder and a liquid-phase component;
the solid-phase powder comprises the following components in parts by mass: 80 parts of calcium phosphate powder; 15 parts of temperature-sensitive microspheres prepared in example 1; the calcium phosphate powder is alpha-tricalcium phosphate with the particle size of 10-200 mu m; the liquid phase component comprises the following components in parts by mass: 60 parts of a solvent; the solvent is glycerol.
Comparative example 1
This comparative example is substantially the same as example 5 except that the preparation method of the temperature-sensitive microspheres in comparative example 1 is different.
The preparation method of the thermo-sensitive microsphere comprises the following steps:
1) adding citric acid into the aqueous solution to prepare 0.25mol/L citric acid solution to obtain a water phase;
2) weighing 100mg of the mixture in a weight ratio of 1: 0.5: dissolving 0.5 of chitosan, polyvinyl alcohol and polypropyl acrylamide in 10ml of water phase and 30ml of dichloromethane serving as oil phase, and performing ultrasonic dispersion for 2min to obtain emulsion;
3) and then stirring for 3 hours at low temperature, and removing the organic solvent to obtain the temperature-sensitive microspheres. The diameter of the temperature sensitive microsphere is 20-80 μm.
Comparative example 2
This comparative example is substantially the same as example 5 except that the preparation method of the temperature-sensitive microspheres in comparative example 2 is different.
The preparation method of the thermo-sensitive microsphere comprises the following steps:
1) adding citric acid into the aqueous solution to prepare 0.25mol/L citric acid solution to obtain a water phase;
2) weighing 100mg of the mixture in a weight ratio of 1: 0.5: dissolving 0.5 chitosan, sophorolipid, and polypropyleneacrylamide in 10ml water phase and 30ml dichloromethane as oil phase, and ultrasonic dispersing for 2min to obtain emulsion;
3) and then stirring for 3 hours at low temperature, and removing the organic solvent to obtain the temperature-sensitive microspheres. The diameter of the temperature sensitive microsphere is 20-80 μm.
Comparative example 3
This comparative example is substantially the same as example 5 except that the preparation method of the temperature-sensitive microspheres in comparative example 3 is different.
The preparation method of the thermo-sensitive microsphere comprises the following steps:
1) adding citric acid into the aqueous solution to prepare 0.25mol/L citric acid solution to obtain a water phase;
2) weighing 100mg of the following components in a weight ratio of 1.3: 0.2: dissolving 0.5 polyvinyl alcohol, sophorolipid, and polypropylenyl acrylamide in 10ml water phase and 30ml dichloromethane as oil phase, and ultrasonically dispersing for 2min to obtain emulsion;
3) and then stirring for 3 hours at low temperature, and removing the organic solvent to obtain the temperature-sensitive microspheres. The diameter of the temperature sensitive microsphere is 20-80 μm.
Comparative example 4
This comparative example is substantially the same as example 5 except that the preparation method of the temperature-sensitive microspheres in comparative example 4 is different.
The preparation method of the thermo-sensitive microsphere comprises the following steps:
1) adding citric acid into the aqueous solution to prepare 0.25mol/L citric acid solution to obtain a water phase;
2) weighing 100mg of the mixture in a weight ratio of 1:0.3: 0.2:0.5 of chitosan, polyvinyl alcohol, guar gum and polypropyl acrylamide are dissolved in 10ml of water phase and 30ml of dichloromethane serving as oil phase, and ultrasonic dispersion is carried out for 2min to obtain emulsion;
3) and then stirring for 3 hours at low temperature, and removing the organic solvent to obtain the temperature-sensitive microspheres.
Comparative example 5
This comparative example is substantially the same as example 5 except that comparative example 5 does not contain temperature sensitive microspheres.
The following performance tests were performed on the calcium phosphate cements prepared in examples 4 to 8 and comparative examples 1 to 4.
1. Fluidity of the resin
According to the 7.2 test in the standard YY0717-2009 of the people's republic of china medical practice, 0.05ml of bone cement was delivered using a graduated syringe, placed in the center of a glass plate, and 180s after tempering, the second glass plate was placed in the middle of the top of the filler, followed by the weight block, to give a total applied mass of 120 g. The weight was removed in 10min and the maximum and minimum diameters of the filler were measured.
As a result, as shown in Table 1, the products of examples 4 to 8 had good flowability, and the samples of examples 4 to 8 had a disc diameter of 26mm at the maximum and 24mm at the minimum in the flowability test.
2. Curing time
The bone cements of examples 4 to 8 and comparative examples 1 to 5 were filled into small paper rings having a diameter of 8mm and a height of 12mm, and both ends of the paper rings were closed with plastic films. In each example, 3 samples are prepared, 30 samples are counted, the prepared samples are immersed in a culture dish filled with SBF solution, the culture dish is placed in a constant temperature and humidity box with 37 ℃ and 100% humidity, the SBF solution can permeate into bone cement through paper sheets, the setting time is measured by a Vicat instrument, during measurement, a Vicat needle is in contact with the surface of the cement, screws are tightened, the cement is suddenly loosened within 1s-2s, the Vicat needle vertically and freely sinks into cement paste, the sinking distance of each time is recorded, the operation is repeated once every 0.1h, and when the sinking of the needle body into the cement paste is not more than 1mm, the initial setting time is set.
3. Compressive strength
The bone cements of examples 4 to 8 and comparative examples 1 to 5 were filled into small paper rings having a diameter of 8mm and a height of 12mm, and both ends of the paper rings were closed with plastic films. The bone cement was immersed in a petri dish containing an SBF solution, the petri dish was placed in a constant temperature and humidity chamber with a humidity of 100% and a temperature of 37 ℃, the bone cement was taken out after 3 days of immersion, the compressive strength was measured by a universal material testing machine, and the loading rate was 1mm/min, and the results are shown in table 1.
TABLE 1
The diameter of the temperature sensitive microspheres is 10-100 μm, as described above, the flowability of the bone cement is not affected after the temperature sensitive microspheres are added to the bone cement, the flowability of the bone cement prepared in examples 4-8 is close to that of comparative example 5 which does not contain the temperature sensitive bone cement, and the flowability of the bone cement prepared in comparative examples 1-5 is inferior to that of examples 4-8 due to the different formulation methods of the temperature sensitive microspheres.
The initial setting time of the examples 4 to 8 is lower than that of the comparative examples 1 to 5, which shows that the temperature-sensitive microspheres release the curing liquid after being placed in the SBF solution, and can promote the curing of the bone cement, thereby shortening the setting time, the compressive strength of the examples 4 to 8 is higher than that of the comparative examples 1 to 5, which shows that the temperature-sensitive microspheres can release the curing liquid at about 37 ℃ to promote the internal curing of the bone cement, and thus the compressive strength of the bone cement is improved.
4. Storage time:
the samples of examples 4 to 8 and comparative examples 1 to 4 were placed in a sealed container and stored at room temperature for 30 days, 2 months, 6 months, and 12 months, and the phases of the samples were observed.
TABLE 2 product Performance test results
| Group of | 30 days | 2 month | 6 month | 12 month |
| Example 4 | Product is not solidified | Product is not solidified | Product is not solidified | Product is not solidified |
| Example 5 | Product is not solidified | Product is not solidified | Product is not solidified | Product is not solidified |
| Example 6 | Product is not solidified | Product is not solidified | Product is not solidified | Product is not solidified |
| Example 7 | Product is not solidified | Product is not solidified | Product is not solidified | Product is not solidified |
| Example 8 | Product is not solidified | Product is not solidified | Product is not solidified | Product is not solidified |
| Comparative example 1 | Partial curing of the product | Partial curing of the product | Partial curing of the product | Partial curing of the product |
| Comparative example 2 | Partial curing of the product | Partial curing of the product | Partial curing of the product | Partial curing of the product |
| Comparative example 3 | Partial curing of the product | Partial curing of the product | Partial curing of the product | Partial curing of the product |
| Comparative example 4 | Partial curing of the product | Partial curing of the product | Partial curing of the product | Partial curing of the product |
The products of examples 4-8 are stored for 12 months, the product performance is the same as that of the products just prepared, and the temperature-sensitive microspheres in the placing process of comparative examples 1-4 can release curing liquid due to permeability, so that the bone cement is cured in the storage process, and the storage effect is influenced. The permeability of the temperature-sensitive microspheres can be influenced by the proportion of the chitosan, the polyvinyl alcohol, the sophorolipid and the polypropyl acrylamide, and the temperature-sensitive microspheres can be kept in a completely sealed state at normal temperature according to the proportion of the temperature-sensitive microspheres, so that the anhydrous state of the bone cement is maintained.
Finally, it should be noted that the above embodiments are only used for illustrating the technical solutions of the present invention and not for limiting the protection scope of the present invention, and although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions can be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.
Claims (10)
1. The temperature-sensitive microsphere is characterized by comprising the following preparation methods:
1) adding citric acid into the water solution to prepare a citric acid solution with the concentration of 0.15-0.35 mol/L to obtain a water phase;
2) weighing 100mg of the following components in a weight ratio of 0.5-1.5:0.2-0.5: 0.1-0.4: dissolving chitosan 0.4-0.8, polyvinyl alcohol, sophorolipid, and polypropyl acrylamide in 20-40ml dichloromethane to form oil phase, mixing 8-12ml water phase and 20-40ml oil phase, and ultrasonic dispersing for 1-3min to obtain emulsion;
3) and then stirring for 2-4h at low temperature, and removing the organic solvent to obtain the temperature-sensitive microspheres.
2. Temperature-sensitive microspheres according to claim 1, wherein the microspheres have a diameter of 10-100 μm.
3. The temperature-sensitive microsphere according to claim 1, which comprises the following preparation method:
1) adding citric acid into the water solution to prepare a citric acid solution with the concentration of 0.15-0.25 mol/L to obtain a water phase;
2) weighing 100mg of the following components in a weight ratio of 0.5-1:0.2-0.3: 0.1-0.3: dissolving chitosan, polyvinyl alcohol, sophorolipid and polypropyl acrylamide 0.4-0.5 in dichloromethane 20-40ml to form oil phase, mixing water phase 8-10ml and oil phase 20-30ml, and ultrasonic dispersing for 1-2min to obtain emulsion;
3) then stirring for 2-3h at low temperature, removing the organic solvent, and obtaining temperature-sensitive microspheres;
preferably, the preparation method comprises the following steps:
1) adding citric acid into the aqueous solution to prepare 0.25mol/L citric acid solution to obtain a water phase;
2) weighing 100mg of the following components in a weight ratio of 1:0.3: 0.2: dissolving 0.5 chitosan, polyvinyl alcohol, sophorolipid and polypropyleneacrylamide in 30ml dichloromethane to form an oil phase, mixing 10ml water phase and 30ml oil phase, and performing ultrasonic dispersion for 2min to obtain an emulsion;
3) and then stirring for 3 hours at low temperature, and removing the organic solvent to obtain the temperature-sensitive microspheres.
4. The calcium phosphate bone cement comprises solid-phase powder and liquid-phase components, and is characterized in that the solid-phase powder comprises the following components in parts by mass: 60-80 parts of calcium phosphate powder; 5-15 parts of temperature-sensitive microspheres according to any one of claims 1-3, wherein the liquid phase component comprises the following components in parts by mass: 40-60 parts of a non-aqueous solvent; preferably, the solid-phase powder comprises the following components in parts by mass: 60-70 parts of calcium phosphate powder; 5-10 parts of temperature-sensitive microspheres according to any one of claims 1-3, wherein the liquid phase component comprises the following components in parts by mass: 40-50 parts of a nonaqueous solvent.
5. The calcium phosphate cement according to claim 4, wherein the liquid phase component comprises the following components in parts by mass: 30-60 parts of a non-aqueous solvent; the non-aqueous solvent is one or more selected from glycerol, polyethylene glycol 600 or dimethyl silicone oil.
6. The calcium phosphate cement according to claim 4, wherein the solid phase powder comprises the following components in parts by mass: 70 parts of calcium phosphate powder; 10 parts of temperature-sensitive microspheres according to any one of claims 1 to 3;
the liquid phase component comprises the following components in parts by mass: 50 parts of a nonaqueous solvent; the non-aqueous solvent is glycerol.
7. The calcium phosphate cement of claim 4, wherein the calcium phosphate in the solid phase powder is selected from one or more of tricalcium phosphate, tetracalcium phosphate, octacalcium phosphate, calcium hydrogen phosphate anhydrous, calcium hydrogen phosphate dihydrate, calcium dihydrogen phosphate, calcium pyrophosphate, hydroxyapatite, fluorapatite, strontium apatite, and carbonate-containing apatite.
8. The calcium phosphate cement of claim 4, wherein the calcium phosphate powder is α -tricalcium phosphate having a particle size of 10 to 200 μm.
9. The preparation method of the calcium phosphate bone cement is characterized by comprising the following steps: mixing calcium phosphate and temperature sensitive microsphere to obtain solid phase powder, adding liquid phase component to obtain paste, and storing the paste sample in a container at 4-25 deg.C.
10. Use of a bone cement according to any of claims 4-8, characterised in that the filling is performed by direct injection by means of filling or by means of a syringe.
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