CN111467564B - Self-expansion composite bone cement and preparation method thereof - Google Patents
Self-expansion composite bone cement and preparation method thereof Download PDFInfo
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Abstract
The invention discloses self-expanding composite bone cement and a preparation method thereof, wherein a solid-phase component and a liquid-phase component are mixed according to the mass-volume ratio of 1g to 1.5 ml-1 g to 7.2 ml; the solid phase comprises the following raw materials in percentage by mass: 30-70% of polymethyl methacrylate-acrylic acid-anhydrous calcium hydrophosphate copolymer microsphere, 15-35% of anhydrous calcium hydrophosphate and 15-35% of tetracalcium phosphate, wherein the sum of the mass percentages of the components is 100%; the bone cement liquid phase is any one of distilled water, blood, normal saline, dilute acid, serum and phosphate solution. The self-expansion composite bone cement prepared by the invention has higher water expansion rate and better mechanical property, and is expected to become a bone cement with promising clinical application.
Description
Technical Field
The invention belongs to the technical field of biomedical materials and preparation methods thereof, and relates to self-expanding composite bone cement and a preparation method thereof.
Background
Polymethyl methacrylate (PMMA) bone cement is widely applied to the fields of dentistry, orthopedic surgery and the like, and is an injectable biomaterial with the widest orthopedic application range, the largest quantity and the largest dosage. However, since PMMA bone cement shrinks in volume to some extent when it is solidified, which causes a series of problems such as loosening, researchers have developed water-absorbable expansive bone cement for the problems of PMMA bone cement.
Chinese patent 'an injectable expansive type bone cement and a preparation method thereof' (application number: 201510344651.7, published: 2015.09.23, published: CN104922733A), discloses an injectable expansive type bone cement and a preparation method thereof, wherein the solid phase component of the injectable expansive type bone cement is a methyl methacrylate-acrylic acid copolymer, and the liquid phase component is obtained by mixing methyl methacrylate, N-dimethyl-p-toluidine and hydroquinone; the solid phase preparation method of the bone cement comprises the following steps: methyl Methacrylate (MMA) and Acrylic Acid (AA) are used as reaction monomers, and polymerization reaction is carried out under the action of an initiator and a cross-linking agent to generate methyl methacrylate-acrylic acid copolymer.
Chinese patent 'an injectable water-absorbing expansive bone cement with high expansion rate and a preparation method thereof' (application No. CN201810735161.3, published Japanese 2018.12.21, published No. CN109053968A) discloses a preparation method of an injectable water-absorbing expansive bone cement with high expansion rate, wherein polymethyl methacrylate-acrylic acid-polyethylene glycol modified graphene oxide copolymer, PMMA, benzoyl peroxide and barium sulfate are selected in a solid phase, hydroxyethyl methacrylate is introduced in a liquid phase, solid-liquid phases can synergistically absorb water to improve the water-absorbing expansive rate of the water-absorbing expansive bone cement, but polymerization reaction occurs in vitro in a solid-liquid mixing period of the bone cement, no aqueous solution is involved in the process, so that the water absorption time is short, the water absorption rate is reduced, and the expansive effect is uneven.
Chinese patent application No. CN201810037931.7, published Japanese No. 2018.06.22, published No. CN108187144A provides injectable expansive composite bone cement with a bone-like trabecula structure and a preparation method thereof. The composite bone cement consists of a powder material, a curing liquid and an expansion material, wherein the powder material and the expansion material are uniformly mixed according to a certain proportion, the curing liquid is added and uniformly stirred to obtain a composite bone cement slurry, the composite bone cement slurry is injected into a mould and then cured to obtain a composite bone cement cured body, and the prepared bone cement has excellent injection performance and can generate volume expansion in the solidification process, but the volume expansion rate is only 1-20%; the expansion ratio is low.
Therefore, finding a bone cement which can realize the overall expansion and has a high water-absorbing expansion rate is one of the important research points in the field of bone cement.
Disclosure of Invention
The invention aims to provide self-expanding composite bone cement, which solves the problems of low water absorption expansion rate and uneven expansion effect in the bone cement in the prior art.
The invention also aims to provide a preparation method of the composite bone cement, which solves the problems of low expansion rate and uneven expansion effect of the bone cement in the prior art.
The technical scheme adopted by the invention is that the self-expanding composite bone cement is prepared by mixing and stirring a solid-phase component and a liquid-phase component for 20-90 min according to the mass-volume ratio of 1g to 1.5-1 g to 7.2 ml; the solid phase comprises the following raw materials in percentage by mass: 30-70% of polymethyl methacrylate-acrylic acid-anhydrous calcium hydrophosphate copolymer microsphere, 15-35% of anhydrous calcium hydrophosphate and 15-35% of tetracalcium phosphate, wherein the sum of the mass percentages of the components is 100%; the bone cement liquid phase is any one of distilled water, blood, normal saline, dilute acid, serum and phosphate solution.
The invention is also characterized in that:
the solid phase comprises the following raw materials: 2.7-6.3 g of polymethyl methacrylate-acrylic acid-anhydrous calcium hydrophosphate copolymer microsphere, 1.35-3.15 g of anhydrous calcium hydrophosphate and 1.35-3.15 g of tetracalcium phosphate; the liquid phase of the bone cement is any one of distilled water, blood, normal saline, diluted acid, serum and phosphate solution, and the amount of the liquid phase is 13.50 ml-64.8 ml.
The invention adopts another technical scheme that the preparation method of the self-expansion composite bone cement specifically comprises the following steps:
step 1, preparing polymethyl methacrylate-acrylic acid-anhydrous calcium hydrophosphate copolymer microspheres;
step 2, preparing a solid phase of the self-expanding composite bone cement: uniformly mixing tetracalcium phosphate, anhydrous calcium hydrophosphate and the polymethyl methacrylate-acrylic acid-anhydrous calcium hydrophosphate copolymer microspheres prepared in the step 1 according to the proportion as required to obtain a solid phase of the self-expanding composite bone cement;
and 3, uniformly mixing the solid phase of the self-expanding composite bone cement obtained in the step 2 with the liquid phase component according to the solid-liquid ratio of 1g to 1.5 ml-1 g to 7.2ml, stirring for 20 min-90 min, and curing after injecting the bone cement to obtain the self-expanding composite bone cement.
The invention is also characterized in that:
the step 1 specifically comprises the following steps:
step 1.1, respectively measuring methyl methacrylate and acrylic acid, respectively adding 0.1-1.5 wt% of hydroquinone into the methyl methacrylate and the acrylic acid, and carrying out reduced pressure distillation;
step 1.2, weighing 5.622-19.589% of methyl methacrylate, 4.700-15.323% of acrylic acid, 0.061-0.364% of anhydrous calcium hydrophosphate, 0.972-1.457% of cross-linking agent N, N-methylene bisacrylamide, 1.214-2.127% of dispersant polyvinylpyrrolidone, 73.221-74.5% of deionized water and 0.243-0.607% of initiator azobisisobutyronitrile according to the proportion, wherein the sum of the mass percentages of the components is 100%;
step 1.3, adding methyl methacrylate, acrylic acid, anhydrous calcium hydrogen phosphate, a crosslinking agent N, N-methylene bisacrylamide, a dispersing agent polyvinylpyrrolidone, an initiator azobisisobutyronitrile and deionized water weighed in the step 1.2 into a four-neck flask in sequence for uniform mixing, wherein four necks in the four-neck flask are respectively connected with nitrogen, a magnetic stirring rod, a condenser tube and a thermometer, and continuously stirring and heating the obtained mixed solution to 35-55 ℃ for reaction for 20-60 min;
step 1.4, heating the mixed solution obtained in the step 1.3 to 60-80 ℃, and reacting the mixed solution at a constant temperature for 2-4 h in a nitrogen atmosphere to obtain a polymethyl methacrylate-acrylic acid-anhydrous calcium hydrogen phosphate copolymer;
and step 1.5, washing the polymethyl methacrylate-acrylic acid-anhydrous calcium hydrophosphate copolymer obtained in the step 1.4 by deionized water, drying the copolymer in a vacuum drying oven at the temperature of 60-80 ℃ to constant weight, and finally sieving the copolymer to obtain the polymethyl methacrylate-acrylic acid-anhydrous calcium hydrophosphate copolymer microspheres.
The invention is also characterized in that:
and (3) washing the polymethyl methacrylate-acrylic acid-anhydrous calcium hydrophosphate copolymer microspheres obtained in the step (1.5) in deionized water for 20-30 times, wherein the drying time is 26-30 h.
The particle size of the polymethyl methacrylate-acrylic acid-anhydrous calcium hydrophosphate copolymer microsphere obtained in the step 1.5 is 20-50 mu m.
The invention adopts another technical scheme that the self-expanding composite bone cement comprises a solid-phase component and a liquid-phase component according to the mass-volume ratio of 1g:1.5 ml-1 g:7.2 ml; the solid phase raw material composition comprises, by mass percentage, 15-35% of magnesium oxide, 15-35% of phosphate and 30-70% of polymethyl methacrylate-acrylic acid-magnesium oxide copolymer microspheres, wherein the sum of the mass percentages of the components is 100%; the bone cement liquid phase is any one of distilled water, blood, normal saline, dilute acid, serum and phosphate solution.
The invention is also characterized in that:
the phosphate in the raw material composition of the solid phase comprises: at least one of orthophosphate, hydrogen phosphate and dihydrogen phosphate.
The invention has the beneficial effects that: after the solid phase and the liquid phase are mixed, the solid phase undergoes hydration reaction, and the polymethyl methacrylate-acrylic acid-anhydrous calcium hydrogen phosphate (PMMA-PAA-PDCPA) copolymer microspheres continuously absorb water to expand, so that the water absorption time is prolonged, the prolonged water absorption time lays a foundation for improving the expansion performance, meanwhile, the inorganic bone cement components which are uniformly distributed inside and outside can enable the block to fully and comprehensively absorb water, the bone cement has the characteristic of integral water absorption expansion, the problems of low expansion rate and non-uniform expansion effect inside the bone cement are solved, and the interface combination of polymethyl methacrylate-acrylic acid-anhydrous calcium hydrogen phosphate (PMMA-PAA-PDCPA) copolymer microspheres and calcium phosphate bone cement solid phases is improved due to the anhydrous calcium hydrogen phosphate (DCPA) which is uniformly distributed inside and outside, improves the mechanical property of the composite bone cement and has better application prospect in clinic.
Detailed Description
The present invention will be described in detail with reference to the following embodiments.
The invention relates to self-expanding composite bone cement, which is prepared by mixing and stirring a solid-phase component and a liquid-phase component for 20-90 min according to the mass-volume ratio of 1g to 1.5-1 g to 7.2 ml; according to the mass percentage, the solid phase comprises the following raw materials: 30-70% of polymethyl methacrylate-acrylic acid-anhydrous calcium hydrophosphate copolymer microsphere, 15-35% of anhydrous calcium hydrophosphate and 15-35% of tetracalcium phosphate, wherein the sum of the mass percentages of the components is 100%; the bone cement liquid phase is any one of distilled water, blood, normal saline, dilute acid, serum and phosphate solution.
The solid phase comprises the following raw materials: 2.7-6.3 g of polymethyl methacrylate-acrylic acid-anhydrous calcium hydrophosphate copolymer microsphere, 1.35-3.15 g of anhydrous calcium hydrophosphate and 1.35-3.15 g of tetracalcium phosphate; the liquid phase of the bone cement is any one of distilled water, blood, normal saline, diluted acid, serum and phosphate solution, and the amount of the liquid phase is 13.50 ml-64.8 ml.
A preparation method of self-expansion composite bone cement specifically comprises the following steps:
step 1, preparing polymethyl methacrylate-acrylic acid-anhydrous calcium hydrophosphate copolymer microspheres;
step 2, preparing a solid phase of the self-expanding composite bone cement: uniformly mixing tetracalcium phosphate, anhydrous calcium hydrophosphate and the polymethyl methacrylate-acrylic acid-anhydrous calcium hydrophosphate copolymer microspheres prepared in the step 1 according to the proportion as required to obtain a solid phase of the self-expanding composite bone cement;
and 3, uniformly mixing the solid phase of the self-expanding composite bone cement obtained in the step 2 with the liquid phase component according to the solid-liquid ratio of 1g to 1.5 ml-1 g to 7.2ml, stirring for 20 min-90 min, and curing after injecting the bone cement to obtain the self-expanding composite bone cement.
The step 1 specifically comprises the following steps:
step 1.1, respectively measuring Methyl Methacrylate (MMA) and Acrylic Acid (AA), respectively adding 0.1-1.5 wt% of hydroquinone into the Methyl Methacrylate (MMA) and the Acrylic Acid (AA), and carrying out reduced pressure distillation;
step 1.2, respectively weighing 5.622-19.589% of Methyl Methacrylate (MMA), 4.700-15.323% of Acrylic Acid (AA), 0.061-0.364% of anhydrous calcium hydrogen phosphate (DCPA), 0.972-1.457% of cross-linking agent N, N-Methylene Bisacrylamide (MBA), 1.214-2.127% of dispersant polyvinylpyrrolidone (PVP), 73.221-74.5% of deionized water, 0.243-0.607% of initiator Azobisisobutyronitrile (AIBN), and the sum of the mass percentages of the components is 100%;
step 1.3, adding methyl methacrylate, acrylic acid, anhydrous calcium hydrogen phosphate, a crosslinking agent N, N-methylene bisacrylamide, a dispersing agent polyvinylpyrrolidone, an initiator azobisisobutyronitrile and deionized water weighed in the step 1.2 into a four-neck flask in sequence for uniform mixing, wherein four necks in the four-neck flask are respectively connected with nitrogen, a magnetic stirring rod, a condenser tube and a thermometer, and continuously stirring and heating the obtained mixed solution to 35-55 ℃ for reaction for 20-60 min for removing air;
step 1.4, heating the mixed solution obtained in the step 1.3 to 60-80 ℃, and reacting the mixed solution at a constant temperature for 2-4 h in a nitrogen atmosphere to obtain a polymethyl methacrylate-acrylic acid-anhydrous calcium hydrogen phosphate copolymer;
and step 1.5, washing the polymethyl methacrylate-acrylic acid-anhydrous calcium hydrophosphate PMMA-PAA-PDCPA copolymer obtained in the step 1.4 with deionized water, drying the copolymer in a vacuum drying oven at the temperature of 60-80 ℃ to constant weight, and finally sieving the copolymer to obtain the polymethyl methacrylate-acrylic acid-anhydrous calcium hydrophosphate copolymer microspheres.
And (3) washing the polymethyl methacrylate-acrylic acid-anhydrous calcium hydrophosphate copolymer microspheres obtained in the step (1.5) in deionized water for 20-30 times, wherein the drying time is 26-30 h.
The particle size of the polymethyl methacrylate-acrylic acid-anhydrous calcium hydrophosphate copolymer microsphere obtained in the step 1.5 is 20-50 mu m.
The invention can also be compounded with other inorganic bone cements such as magnesium phosphate bone cement, calcium sulfate and the like, and can also obtain good self-expansion effect. The self-expanding composite bone cement has solid phase component and liquid phase component in the weight/volume ratio of 1g to 1.5ml to 1g to 7.2 ml; the solid phase raw material composition comprises, by mass, 15-35% of magnesium oxide, 15-35% of phosphate and 30-70% of polymethyl methacrylate-acrylic acid-magnesium oxide copolymer microspheres, wherein the sum of the mass percentages of the components is 100%; the bone cement liquid phase is any one of distilled water, blood, normal saline, dilute acid, serum and phosphate solution.
The phosphate in the raw material composition of the solid phase comprises: at least one of orthophosphate, hydrogen phosphate and dihydrogen phosphate.
The invention relates to self-expansion composite bone cement and a preparation method thereof, and has the advantages that: the self-expansion organic/inorganic composite bone cement solid phase contains PMMA-PAA-PDCPA copolymer microspheres, the PMMA-PAA-PDCPA copolymer microspheres have a slightly cross-linked space grid structure, and PAA is a hydrophilic macromolecule and has a large amount of hydrophilic group hydroxyl groups, so that the composite bone cement can absorb a large amount of water molecules when in a water environment to realize integral water absorption expansion; meanwhile, the inorganic bone cement components which are uniformly distributed inside and outside can provide a microscopic water absorption channel for the copolymer microspheres in the bone cement while hydrating, so that the block can fully and comprehensively absorb water; and DCPA is enriched in the PMMA-PAA-PDCPA copolymer microspheres and on the surfaces of the PMMA-PAA-PDCPA copolymer microspheres, so that the interface bonding of the PMMA-PAA-PDCPA copolymer microspheres and the solid phase of calcium phosphate cement is improved, the mechanical property of the self-expanding organic/inorganic composite cement is improved, and the PMMA-PAA-PDCPA copolymer microspheres have better application prospect in clinic.
Example 1
Step 1, preparing PMMA-PAA-PDCPA copolymer microspheres:
preparing a PMMA-PAA-PDCPA copolymer by adopting a solution polymerization method: adding 0.1 wt% of hydroquinone into Methyl Methacrylate (MMA) and Acrylic Acid (AA) before use, and distilling under reduced pressure to remove a polymerization inhibitor; the reaction is carried out in a four-mouth flask, and four mouths of the four-mouth flask are respectively connected with nitrogen, a magnetic stirring rod, a condenser tube and a thermometer; respectively taking 5.622% of Methyl Methacrylate (MMA), 15.323% of Acrylic Acid (AA), 0.364% of anhydrous calcium hydrogen phosphate (DCPA), 1.457% of crosslinking agent N, N-Methylene Bisacrylamide (MBA), 2.127% of dispersant polyvinylpyrrolidone (PVP), 0.607% of initiator Azobisisobutyronitrile (AIBN), 74.5% of deionized water and 100% in total;
sequentially adding MMA, AA, DCPA, a crosslinking agent MBA solution, a dispersant PVP solution and an initiator AIBN solution into a four-neck flask for uniform mixing, continuously stirring the obtained mixed solution, and heating to 35 ℃ for reaction for 20 min; then heating the obtained mixed solution to 60 ℃; allowing the mixed solution to react for 2h at constant temperature in the nitrogen atmosphere to obtain PMMA-PAA-PDCPA copolymer microspheres; washing the PMMA-PAA-PDCPA copolymer microspheres with deionized water for 20 times, and drying in a vacuum drying box at the temperature of 60 ℃ for 26h to constant weight to obtain the PMMA-PAA-PDCPA copolymer microspheres with the particle size of 20 mu m.
And 2, preparing a solid phase of the self-expanding organic/inorganic composite bone cement. The solid phase component of the self-expanding organic/inorganic composite bone cement is composed of 15 percent of tetracalcium phosphate, 15 percent of anhydrous calcium hydrophosphate and 70 percent of PMMA-PAA-PDCPA copolymer microspheres prepared in the step 1 by mass percentage;
and 3, uniformly mixing the solid phase of the self-expanding organic/inorganic composite bone cement obtained in the step 2 with distilled water serving as a liquid phase component according to the solid-liquid ratio of 1g to 1.5ml, stirring for 20min, and curing after injecting the bone cement to obtain the self-expanding composite bone cement.
Example 2
Step 1, preparing PMMA-PAA-PDCPA copolymer microspheres:
preparing a PMMA-PAA-PDCPA copolymer by adopting a solution polymerization method: before using Methyl Methacrylate (MMA) and Acrylic Acid (AA), 1.5 wt% of hydroquinone was added and the polymerization inhibitor was distilled off under reduced pressure. The reaction is carried out in a four-mouth flask, and four mouths of the four-mouth flask are respectively connected with nitrogen, a magnetic stirring rod, a condenser tube and a thermometer; respectively taking 19.589% of Methyl Methacrylate (MMA), 4.700% of Acrylic Acid (AA), 0.061% of anhydrous calcium hydrogen phosphate (DCPA), 0.972% of crosslinking agent N, N-Methylene Bisacrylamide (MBA), 1.214% of dispersant polyvinylpyrrolidone (PVP), 0.243% of initiator Azobisisobutyronitrile (AIBN), 73.221% of deionized water and 100% in total;
sequentially adding MMA, AA, DCPA, a crosslinking agent MBA solution, a dispersant PVP solution and an initiator AIBN solution into a four-neck flask for uniform mixing, continuously stirring the obtained mixed solution, and heating to 55 ℃ for reaction for 60 min; then heating the obtained mixed solution to 80 ℃; allowing the mixed solution to react for 4 hours at constant temperature in the nitrogen atmosphere to obtain PMMA-PAA-PDCPA copolymer microspheres; washing the PMMA-PAA-PDCPA copolymer microspheres with deionized water for 30 times, and drying in a vacuum drying box at the temperature of 80 ℃ for 30 hours to constant weight to obtain the PMMA-PAA-PDCPA copolymer microspheres with the particle size of 50 mu m.
Step 2, preparing a solid phase of the self-expanding organic/inorganic composite bone cement: the solid phase component of the self-expanding organic/inorganic composite bone cement is composed of 35 percent of tetracalcium phosphate, 35 percent of anhydrous calcium hydrophosphate and 30 percent of PMMA-PAA-PDCPA copolymer microspheres prepared in the step 1 by mass percentage;
and 3, uniformly mixing the solid phase of the self-expanding organic/inorganic composite bone cement obtained in the step 2 with liquid phase component normal saline according to the solid-liquid ratio of 1g to 7.2ml, stirring for 90min, and solidifying the bone cement after injection to obtain the self-expanding organic/inorganic composite bone cement.
Example 3
Step 1, preparing PMMA-PAA-PDCPA copolymer microspheres:
preparing a PMMA-PAA-PDCPA copolymer by adopting a solution polymerization method: before using Methyl Methacrylate (MMA) and Acrylic Acid (AA), 1 wt% of hydroquinone was added and the polymerization inhibitor was distilled off under reduced pressure. The reaction is carried out in a four-mouth flask, and four mouths of the four-mouth flask are respectively connected with nitrogen, a magnetic stirring rod, a condenser tube and a thermometer; respectively taking MMA 12.606%, AA 10.012%, anhydrous calcium hydrogen phosphate (DCPA) 0.213%, cross-linking agent N, N Methylene Bisacrylamide (MBA) 1.215%, dispersant polyvinylpyrrolidone (PVP) 1.671%, initiator Azobisisobutyronitrile (AIBN) 0.425%, deionized water 73.858%, and 100% in total;
sequentially adding MMA, AA, DCPA, a crosslinking agent MBA solution, a dispersant PVP solution and an initiator AIBN solution into a four-neck flask for uniform mixing, continuously stirring the obtained mixed solution, and heating to 45 ℃ for reaction for 30 min; then heating the obtained mixed solution to 70 ℃; allowing the mixed solution to react for 4 hours at constant temperature in the nitrogen atmosphere to obtain PMMA-PAA-PDCPA copolymer microspheres; washing the PMMA-PAA-PDCPA copolymer microspheres with deionized water for 25 times, and drying in a vacuum drying box at 70 ℃ for 26h to constant weight to obtain the PMMA-PAA-PDCPA copolymer microspheres with the particle size of 40 mu m.
Step 2, preparing a solid phase of the self-expanding organic/inorganic composite bone cement: forming solid phase components of the self-expanding organic/inorganic composite bone cement by 25 percent of tetracalcium phosphate, 25 percent of anhydrous calcium hydrophosphate and 50 percent of PMMA-PAA-PDCPA copolymer microspheres prepared in the step 1 according to mass percentage;
and 3, uniformly mixing the solid phase of the self-expanding organic/inorganic composite bone cement obtained in the step 2 with liquid phase component serum according to the solid-liquid ratio of 1g to 4.5ml, stirring for 40min, and solidifying the bone cement after injection to obtain the self-expanding organic/inorganic composite bone cement.
Example 4
Step 1, preparing PMMA-PAA-PDCPA copolymer microspheres:
preparing a PMMA-PAA-PDCPA copolymer by adopting a solution polymerization method: before using Methyl Methacrylate (MMA) and Acrylic Acid (AA), 0.5 wt% of hydroquinone was added and the polymerization inhibitor was distilled off under reduced pressure. The reaction is carried out in a four-mouth flask, and four mouths of the four-mouth flask are respectively connected with nitrogen, a magnetic stirring rod, a condenser tube and a thermometer; respectively taking MMA 14.434%, AA 8.241%, anhydrous calcium hydrogen phosphate (DCPA) 0.162%, crosslinking agent N, N-Methylene Bisacrylamide (MBA) 1.334%, dispersing agent polyvinylpyrrolidone (PVP) 1.518%, initiator Azobisisobutyronitrile (AIBN) 0.364%, deionized water 73.947% and 100% in total;
sequentially adding MMA, AA, DCPA, a crosslinking agent MBA solution, a dispersant PVP solution and an initiator AIBN solution into a four-neck flask for uniform mixing, continuously stirring the obtained mixed solution, and heating to 45 ℃ for reaction for 40 min; then heating the obtained mixed solution to 65 ℃; allowing the mixed solution to react for 2.5h at constant temperature in the nitrogen atmosphere to obtain PMMA-PAA-PDCPA copolymer microspheres; washing the PMMA-PAA-PDCPA copolymer microspheres with deionized water for 27 times, and drying in a vacuum drying box at 65 ℃ for 27 hours to constant weight to obtain the PMMA-PAA-PDCPA copolymer microspheres with the particle size of 35 mu m.
Step 2, preparing a solid phase of the self-expanding organic/inorganic composite bone cement: the solid phase component of the self-expanding organic/inorganic composite bone cement is composed of 20 percent of tetracalcium phosphate, 20 percent of anhydrous calcium hydrophosphate and 60 percent of PMMA-PAA-PDCPA copolymer microspheres prepared in the step 1 by mass percentage;
and 3, uniformly mixing the solid phase of the self-expanding organic/inorganic composite bone cement obtained in the step 2 with liquid phase component blood according to the solid-liquid ratio of 1g to 5.8ml, stirring for 70min, and solidifying the bone cement after injection to obtain the self-expanding organic/inorganic composite bone cement.
Example 5
Step 1, preparing PMMA-PAA-PDCPA copolymer microspheres:
preparing a PMMA-PAA-PDCPA copolymer by adopting a solution polymerization method: before using Methyl Methacrylate (MMA) and Acrylic Acid (AA), 0.7 wt% of hydroquinone was added and the polymerization inhibitor was distilled off under reduced pressure. The reaction is carried out in a four-mouth flask, and four mouths of the four-mouth flask are respectively connected with nitrogen, a magnetic stirring rod, a condenser tube and a thermometer; respectively taking MMA 13.076%, AA 9.502%, anhydrous calcium hydrogen phosphate (DCPA) 0.213%, crosslinking agent N, N Methylene Bisacrylamide (MBA) 1.225%, dispersing agent polyvinylpyrrolidone (PVP) 1.623%, initiator Azobisisobutyronitrile (AIBN) 0.357%, deionized water 74.004% and 100% in total after vacuum distillation;
sequentially adding MMA, AA, DCPA, a crosslinking agent MBA solution, a dispersant PVP solution and an initiator AIBN solution into a four-neck flask for uniform mixing, continuously stirring the obtained mixed solution, and heating to 50 ℃ for reaction for 50 min; then heating the obtained mixed solution to 75 ℃; allowing the mixed solution to react for 3h at constant temperature in the nitrogen atmosphere to obtain PMMA-PAA-PDCPA copolymer microspheres; washing the PMMA-PAA-PDCPA copolymer microspheres with deionized water for 29 times, and drying in a vacuum drying box at 75 ℃ for 29 hours to constant weight to obtain the PMMA-PAA-PDCPA copolymer microspheres with the particle size of 45 mu m.
Step 2, preparing a solid phase of the self-expanding organic/inorganic composite bone cement: the solid phase component of the self-expanding organic/inorganic composite bone cement is composed of, by mass, 22.5% of tetracalcium phosphate, 22.5% of anhydrous calcium hydrophosphate and 55% of PMMA-PAA-PDCPA copolymer microspheres prepared in the step 1;
and 3, uniformly mixing the solid phase of the self-expanding organic/inorganic composite bone cement obtained in the step 2 with a liquid phase component diluted acid according to the solid-liquid ratio of 1g to 6.45ml, stirring for 55min, and injecting the bone cement and then curing to obtain the self-expanding organic/inorganic composite bone cement.
In the embodiment, compared with the traditional organic/inorganic bone cement, the test results of the water absorption rate, the expansion rate and the compressive strength of the composite bone cement are as follows:
from the above table, compared with the traditional PMMA bone cement and Calcium Phosphate (CPC) bone cement, the self-expanding organic/inorganic composite bone cement prepared by the invention has the advantages that the water absorption multiplying power and the volume change rate are obviously improved due to the introduction of PMMA-PAA-PDCPA copolymer microspheres, and the mechanical property is increased compared with the traditional CPC bone cement. In conclusion, the self-expanding organic/inorganic composite bone cement prepared by the invention has higher water-absorbing expansion rate and better mechanical property, and is expected to become a promising clinical application bone cement.
Claims (4)
1. The self-expanding composite bone cement is characterized in that the self-expanding composite bone cement is prepared by mixing and stirring a solid-phase component and a liquid-phase component for 20-90 min according to the mass-volume ratio of 1g to 1.5-1 g to 7.2 ml; the solid phase comprises the following raw materials in percentage by mass: 30-70% of polymethyl methacrylate-acrylic acid-anhydrous calcium hydrophosphate copolymer microsphere, 15-35% of anhydrous calcium hydrophosphate and 15-35% of tetracalcium phosphate, wherein the sum of the mass percentages of the components is 100%; the bone cement liquid phase is any one of distilled water, blood, normal saline, dilute acid, serum and phosphate solution;
the preparation method of the self-expansion composite bone cement specifically comprises the following steps:
step 1, preparing polymethyl methacrylate-acrylic acid-anhydrous calcium hydrophosphate copolymer microspheres; the method specifically comprises the following steps:
step 1.1, respectively measuring methyl methacrylate and acrylic acid, respectively adding 0.1-1.5 wt% of hydroquinone into the methyl methacrylate and the acrylic acid, and carrying out reduced pressure distillation;
step 1.2, respectively weighing 5.622-19.589% of methyl methacrylate, 4.700-15.323% of acrylic acid, 0.061-0.364% of anhydrous calcium hydrophosphate, 0.972-1.457% of cross-linking agent N, N-methylene bisacrylamide, 1.214-2.127% of dispersant polyvinylpyrrolidone, 73.221-74.5% of deionized water and 0.243-0.607% of initiator azobisisobutyronitrile according to a certain proportion, wherein the sum of the mass percentages of the components is 100%;
step 1.3, adding the methyl methacrylate, the acrylic acid, the anhydrous calcium hydrophosphate, the cross-linking agent N, N-methylene bisacrylamide, the dispersing agent polyvinylpyrrolidone, the initiator azobisisobutyronitrile and the deionized water which are weighed in the step 1.2 into a four-neck flask in sequence for uniform mixing, wherein four necks in the four-neck flask are respectively connected with nitrogen, a magnetic stirring rod, a condenser tube and a thermometer, and continuously stirring and heating the obtained mixed solution to 35-55 ℃ for reaction for 20-60 min;
step 1.4, heating the mixed solution obtained in the step 1.3 to 60-80 ℃, and reacting the mixed solution at constant temperature for 2-4 h in a nitrogen atmosphere to obtain the polymethyl methacrylate-acrylic acid-anhydrous calcium hydrophosphate copolymer;
step 1.5, washing the polymethyl methacrylate-acrylic acid-anhydrous calcium hydrophosphate copolymer obtained in the step 1.4 by deionized water, drying the copolymer in a vacuum drying oven at the temperature of 60-80 ℃ to constant weight, and finally sieving the copolymer to obtain polymethyl methacrylate-acrylic acid-anhydrous calcium hydrophosphate copolymer microspheres;
step 2, preparing a solid phase of the self-expanding composite bone cement: uniformly mixing tetracalcium phosphate, anhydrous calcium hydrophosphate and the polymethyl methacrylate-acrylic acid-anhydrous calcium hydrophosphate copolymer microspheres prepared in the step 1 according to a proportion as required to obtain a solid phase of the self-expanding composite bone cement;
and 3, uniformly mixing the solid phase of the self-expanding composite bone cement obtained in the step 2 with the liquid phase component according to the solid-liquid ratio of 1g to 1.5 ml-1 g to 7.2ml, stirring for 20 min-90 min, and injecting the bone cement and then curing to obtain the self-expanding composite bone cement.
2. The self-expandable composite bone cement as claimed in claim 1, wherein the solid phase is composed of: polymethyl methacrylate-acrylic acid-anhydrous calcium hydrophosphate copolymer microsphere is 2.7g to 6.3g, anhydrous calcium hydrophosphate is 1.35g to 3.15g, and tetracalcium phosphate is 1.35g to 3.15 g; the liquid phase of the bone cement is any one of distilled water, blood, normal saline, diluted acid, serum and phosphate solution, and the amount of the liquid phase is 13.50 ml-64.8 ml.
3. The self-expandable composite bone cement according to claim 1, wherein the polymethyl methacrylate-acrylic acid-anhydrous dibasic calcium phosphate copolymer microspheres obtained in the step 1.5 are washed in deionized water for 20 to 30 times, and the drying time is 26 to 30 hours.
4. The self-expandable composite bone cement as claimed in claim 1, wherein the particle size of the polymethylmethacrylate-acrylic acid-anhydrous dibasic calcium phosphate copolymer microspheres obtained in step 1.5 is between 20 and 50 μm.
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