CN102526798B - Injectable compound bone cement and preparation method thereof - Google Patents
Injectable compound bone cement and preparation method thereof Download PDFInfo
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- CN102526798B CN102526798B CN201210016275.5A CN201210016275A CN102526798B CN 102526798 B CN102526798 B CN 102526798B CN 201210016275 A CN201210016275 A CN 201210016275A CN 102526798 B CN102526798 B CN 102526798B
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Abstract
The invention discloses injectable compound bone cement and a preparation method thereof. The invention further discloses a kit for preparing the injectable compound bone cement. The kit comprises solid powder and a curing liquid, wherein the solid powder comprises calcium phosphate bone cement powder and chitosan microspheres; and the curing liquid contains glycerophosphate. The injectable compound bone cement is prepared by uniformly mixing the solid power with the curing liquid, has superior scattering resistance, superior injection performance, rapid self-curing performance, high compressive strength and high biocompatibility, and can be used for preparing a biomedical material applied to bone defect reconstruction, bone fracture treatment and bone repair.
Description
Technical field
The invention belongs to biomaterial for medical purpose field, be specifically related to Injectable compound bone cement test kit, Injectable compound bone cement and its preparation method and application.
Background technology
Along with the development of Minimally Invasive Surgery, as percutaneous operation, day by day need can direct injection biomaterial.Because its cured product is similar with natural bone inorganic phase composition, self-curable calcium phosphate bone cement (calcium phosphate cement, CPC) can be used as a kind of Minimally Invasive Surgery material, for bone defect repair.But current some shortcomings of injectable calcium phosphate bone cement, such as mechanical property is poor, be difficult to injection, in blood or liquid, easily defeated and dispersed, the hole that lacks bone cell growth etc. has all limited its wide clinical application.
In order to overcome these deficiencies, people adopt the performance that improves bone cement by adding variety classes additive.(the Structural characterization of phosphorylated chito san and their applications as effective additives of calcium phosphate cements.Biomaterials such as Wang little Hong, 2001.22 (16): 2247-2255) in the consolidation liquid of calcium phosphate bone cement, add water-soluble phosphorus acidify chitosan and improved the comprcssive strength of bone cement, but extended hardening time.Polymeric additive (chitosan, cellulose derivative) thus the cohesive force that can increase bone cement slurry is improved the anti-collapsibility performance (A.Cherng of bone cement slurry, et al.Effects of hydroxypropyl methylcellulose and other gelling agents on the handling properties of calcium phosphate cement.J Biomed MaterRes, 1997,35 (3): 273-277), but these additives delayed simultaneously bone cement solidify.The interpolation of sodium glycerophosphate or glycerol can improve the injection property of calcium phosphate bone cement, but (the L. Leroux that greatly extended hardening time, Z.H., M.Freche and J.L.Lacout, Effects of various adjuvants (lactic acid, glycerol and chitosan) on the injectability of a calcium phosphate cement.Bone 1999.25 (2): 31-34).Fiber (the H.H.K.Xu of various absorbable and degradables, et al.Strong and macroporous calcium phosphate cement:effects of porosity and fiber reinforcement on mechanical properties.J.Biomed.Mater.Res., 2001, 57 (3): 457-466) and microsphere (W.J.E.M.Habraken, et al.Introduction of enzymatically degradable poly (trimethylene carbonate) microspheres into an injectable calcium phosphate cement.Biomaterials, 2008, 29 (16): 2464-2476, Dong Limin etc., the preparation method of calcium phosphate bone cement that can degradation in vivo pore-forming, CN 1302821C) add in calcium phosphate bone cement, can improve the fracture toughness of bone cement, can in cement, produce again macropore by the degraded of fiber and microsphere simultaneously, be conducive to the conveying of nutrient substance in CPC firming body and growing into of cell, but the increase of fiber and chitosan microball content can cause the decline of reducing of bone-cement composite material comprcssive strength and injection property.Promote the interpolation (K.Ishikawa of firming agent sodium phosphate, et al.Properties and mechanisms of fast-setting calcium phosphate cements.J Mater.Sci.Mater.Med, 1995,6 (9): 528-533) can in shortening setting time of bone cement, but reduce the injection property of bone cement slurry.Therefore, these additives in improving a certain performance of bone cement, but easily cause the decline of another important performance of bone cement conventionally.
The common modification of multiple material is a kind of feasible way that improves in recent years capable of injecting bone cement performance.Burguera etc. replace calcium phosphate dibasic anhydrous (DCPA) with the higher dicalcium phosphate dehydrate of dissolubility (DCPD), also add hydroxypropyl emthylcellulose raising injectivity with sodium phosphate as curing accelerator simultaneously prepared a kind of injectable quick-setting bone cement (E.F.Burguera, et al.Weir.Injectable and rapid-setting calcium phosphate bone cement with dicalcium phosphate dihydrate.J Biomed Mater Res B Appl Biomater, 2006, 77 (1): 126-134).Xu etc. are by use DCPD, curing accelerator, gel, porogen and absorbable fibre simultaneously, prepare the eurypyloue bone cement (H.H.K.Xu of a kind of injectable tool, et al.Injectable and macroporous calcium phosphate cement scaffold.Biomaterials, 2006,7 (24): 4279-4287).But this common method of modifying need to add multiple additives simultaneously, with the corresponding bone cement different performance that improves, learn from other's strong points to offset one's weaknesses, could meet the clinical requirement of the various performances of CPC simultaneously.
Summary of the invention
The object of the present invention is to provide a kind of novel Injectable compound bone cement and preparation method thereof, not only there is good anti-collapsibility performance and injection property, and self-curing fast, advantages of higher compressive strength there is, in vivo degradable.
A first aspect of the present invention, provides a kind of Injectable compound bone cement test kit, and described test kit comprises pressed powder and consolidation liquid, and described pressed powder comprises calcium phoshate bone cement powder and crosslinked chitosan microsphere, in described consolidation liquid, contains sodium glycerophosphate.
In another preference, the described pressed powder in test kit and described consolidation liquid are 1: 1～3.5: 1 by mass volume ratio (g/mL).
In another preference, the described pressed powder in test kit and described consolidation liquid are 1.5: 1～3: 1 by mass volume ratio (g/mL).
In another preference, the described pressed powder in test kit and described consolidation liquid are 2: 1～2.5: 1 by mass volume ratio (g/mL).
In another preference, described pressed powder is made up of the component of following weight percent content:
Calcium phoshate bone cement powder 60～99%;
Crosslinked chitosan microsphere 1～40%.
In another preference, said pressed powder is made up of the component of following weight percent content:
Calcium phoshate bone cement powder 85～98%;
Crosslinked chitosan microsphere 2～15%.
In another preference, described pressed powder is made up of the component of following weight percent content:
Calcium phoshate bone cement powder 75～95%;
Crosslinked chitosan microsphere 5～25%.
In another preference, described calcium phoshate bone cement powder is a kind of in tricalcium phosphate, tetracalcium phosphate, OCP, calcium hydrogen phosphate, dalcium biphosphate, calcium metaphosphate, calcium pyrophosphate, hydroxyapatite or fluor-apatite or their mixture.
In another preference, described crosslinked chitosan microsphere is sulphuric acid crosslinked chitosan microsphere, phosphoric acid crosslinked chitosan microsphere or citric acid crosslinked chitosan microsphere, and mean diameter is 1～300 μ m.
In another preference, the preparation of described crosslinked chitosan microsphere comprises the following steps:
(1) chitosan solution is added drop-wise in NaOH solution or in NaOH-methanol mixed solution and condenses, collect microsphere, and then microsphere is scattered in to sulfuric acid solution or the phosphoric acid solution that concentration is 1～30% (w/v), process 1～24 hour; Collect microsphere, fully washing obtains chitosan microball after being dried; Or
(2) taking concentration as 5～30% (w/v) sulphuric acid is as cross-linking agent, at room temperature by making sulphuric acid crosslinked chitosan microsphere with the cross-linking reaction of chitosan solution, collect microsphere, fully washing obtains chitosan microball after being dried; Or
(3) taking concentration as 5～30% (w/v) citric acid is as cross-linking agent, at 40～60 DEG C, by making citric acid crosslinked chitosan microsphere with the cross-linking reaction of chitosan solution, collect microsphere, fully washing obtains chitosan microball after being dried.
In another preference, the aqueous solution that described consolidation liquid is sodium glycerophosphate or the normal saline solution of sodium glycerophosphate, the concentration of described sodium glycerophosphate is 0.1～0.4g/mL.
In another preference, in the normal saline solution of described sodium glycerophosphate, the concentration of normal saline is 0.85～0.9w/v%.
A second aspect of the present invention, provides a kind of Injectable compound bone cement, by pressed powder and consolidation liquid by mass volume ratio (g/mL) be 1: 1～3.5: 1 formulated, wherein,
Described pressed powder comprises calcium phoshate bone cement powder and crosslinked chitosan microsphere, in described consolidation liquid, contains sodium glycerophosphate.
In another preference, described pressed powder and described consolidation liquid are within 1.5: 1～3: 1, to be mixed with Injectable compound bone cement by mass volume ratio (g/mL).
In another preference, described pressed powder and described consolidation liquid are within 2: 1～2.5: 1, to be mixed with Injectable compound bone cement by mass volume ratio (g/mL).
In another preference, described pressed powder is made up of the component of following weight percent content:
Calcium phoshate bone cement powder 60～99%;
Crosslinked chitosan microsphere 1～40%.
In another preference, described pressed powder is made up of the component of following weight percent content:
Calcium phoshate bone cement powder 85～98%;
Crosslinked chitosan microsphere 2～15%.
In another preference, described pressed powder is made up of the component of following weight percent content:
Calcium phoshate bone cement powder 75～95%;
Crosslinked chitosan microsphere 5～25%.
In another preference, described calcium phoshate bone cement powder is a kind of in tricalcium phosphate, tetracalcium phosphate, OCP, calcium hydrogen phosphate, dalcium biphosphate, calcium metaphosphate, calcium pyrophosphate, hydroxyapatite or fluor-apatite or their mixture.
In another preference, described crosslinked chitosan microsphere is sulphuric acid crosslinked chitosan microsphere, phosphoric acid crosslinked chitosan microsphere or citric acid crosslinked chitosan microsphere.
In another preference, the mean diameter of described crosslinked chitosan microsphere is 1～500 μ m; Preferably, be 10～300 μ m; More preferably, be 50～200 μ m.
In another preference, the aqueous solution that described consolidation liquid is sodium glycerophosphate or the normal saline solution of sodium glycerophosphate, the concentration of described sodium glycerophosphate is 0.1～0.4g/mL.
In another preference, in the normal saline solution of described sodium glycerophosphate, the concentration of normal saline is 0.85～0.9w/v%.
A third aspect of the present invention, provides the preparation method of Injectable compound bone cement, comprises the steps:
Crosslinked chitosan microsphere is mixed homogeneously with calcium phoshate bone cement powder, add the consolidation liquid that contains sodium glycerophosphate, mix homogeneously, thus obtain Injectable compound bone cement; Or
Crosslinked chitosan microsphere is mixed homogeneously with the consolidation liquid that contains sodium glycerophosphate, then mix homogeneously with calcium phoshate bone cement powder, thereby obtain Injectable compound bone cement.
In another preference, the weight ratio of described calcium phoshate bone cement powder and crosslinked chitosan microsphere is 60～99: 1～40.
In another preference, the weight ratio of described calcium phoshate bone cement powder and crosslinked chitosan microsphere is 85～98: 2～15.
In another preference, the weight ratio of described calcium phoshate bone cement powder and crosslinked chitosan microsphere is 75～95: 5～25.
In another preference, described calcium phoshate bone cement powder is a kind of in tricalcium phosphate, tetracalcium phosphate, OCP, calcium hydrogen phosphate, dalcium biphosphate, calcium metaphosphate, calcium pyrophosphate, hydroxyapatite or fluor-apatite or their mixture.
In another preference, described crosslinked chitosan microsphere is sulphuric acid crosslinked chitosan microsphere, phosphoric acid crosslinked chitosan microsphere or citric acid crosslinked chitosan microsphere.
In another preference, the mean diameter of described crosslinked chitosan microsphere is 1～500 μ m; Preferably, be 10～300 μ m; More preferably, be 50～200 μ m.
In another preference, the aqueous solution that described consolidation liquid is sodium glycerophosphate or the normal saline solution of sodium glycerophosphate, the concentration of described sodium glycerophosphate is 0.1～0.4g/mL.
In another preference, in the normal saline solution of described sodium glycerophosphate, the concentration of normal saline is 0.85～0.9w/v%.
In another preference, the gross weight of described calcium phoshate bone cement powder and crosslinked chitosan microsphere and the mass volume ratio of described consolidation liquid are 1: 1～3.5: 1.
In another preference, the gross weight of described calcium phoshate bone cement powder and crosslinked chitosan microsphere and the mass volume ratio of described consolidation liquid are 1.5: 1～3: 1.
In another preference, the gross weight of described calcium phoshate bone cement powder and crosslinked chitosan microsphere and the mass volume ratio of described consolidation liquid are 2: 1～2.5: 1.
A fourth aspect of the present invention, provides the application of Injectable compound bone cement, the bio-medical material of repairing for the preparation of defect and restore, fractures, bone.
Injectable compound bone cement of the present invention, has good anti-collapsibility performance and injection property, and self-curing, has advantages of higher compressive strength fast.
In should be understood that within the scope of the present invention, above-mentioned each technical characterictic of the present invention and can combining mutually between specifically described each technical characterictic in below (eg embodiment), thus form new or preferred technical scheme.As space is limited, tire out and state no longer one by one at this.
Brief description of the drawings
Fig. 1 is the stereoscan photograph of sulphuric acid crosslinked chitosan microsphere.
Fig. 2 is the stereoscan photograph of the fresh section of Injectable compound bone cement.
Fig. 3 is the picture of Injectable compound bone cement.
Fig. 4 is the anti-collapsibility performance of Injectable compound bone cement in water.
Fig. 5 is Injectable compound bone cement anti-collapsibility performance in animal body.
Detailed description of the invention
Present inventor is through extensively and in depth research, unexpected discovery, the pressed powder that comprises crosslinked chitosan microsphere and calcium phoshate bone cement powder is mixed homogeneously with the consolidation liquid that contains sodium glycerophosphate, can obtain thering is good anti-collapsibility performance and injection property, and self-curing fast, there is the Injectable compound bone cement of advantages of higher compressive strength.On this basis, complete the present invention.
Design of the present invention is as follows:
Adopt crosslinked chitosan microsphere and sodium glycerophosphate to carry out common modified phosphate calcium bone cement, make sulphuric acid, phosphoric acid or citric acid crosslinked chitosan microsphere under the effect of weak base GP, carry out neutralization reaction, make original fine and close chitosan microball original position form porous aquagel microsphere, be evenly distributed in bone cement matrix, form hydrogel Ca ion to strong adsorption effect, can promote hydroxyapatite deposition, thereby shorten the setting time of bone cement; Hydrogel is combined closely with bone cement matrix, can reduce the porosity of bone cement, thereby improves the comprcssive strength of bone cement; Hydrogel can increase the caking property of bone cement slurry, improves the anti-collapsibility performance of bone cement; And phosphoglycerol radical ion can be adsorbed on the surface of the each composition of calcium phosphate bone cement, increase its surface charge, thereby improve the injection property of bone cement slurry.In addition, after the calcium phosphate composite bone cement of the common potentiation modification of crosslinked chitosan microsphere and sodium glycerophosphate implants, keep in early days relatively high intensity, the generation of gel micro-ball degraded afterwards micropore is convenient to the growth of osteocyte.
Crosslinked chitosan microsphere
Chitosan is a kind of natural polysaccharide derivant, the polysaccharide that the glucosamine being extracted by Crustacean and acetylglucosamine form.The advantages such as chitosan is the product of chitin deacetylase base, has wide material sources, with low cost, and there is good bioaffinity, biological degradability and ossification, and catabolite safety non-toxic.Hydroxyl and amino abundant on chitosan molecule chain make it be easy to carry out chemical modification and give several functions, are used widely in fields such as medicine, agricultural, light textile, daily use chemicals.Chitosan is prepared into polymer microsphere, makes the functional mutually compound of chitosan and polymer microsphere, can make it obtain larger application in fields such as biomedicines.
In the present invention, the chitosan using is not particularly limited, and conventionally, chitosan molecule amount is 10～100KDa, and preferably molecular weight is 20～80KDa; Deacetylation is generally 40～99%, is preferably 60～95%.
Crosslinked chitosan microsphere used herein refers to sulphuric acid crosslinked chitosan microsphere, phosphoric acid crosslinked chitosan microsphere or citric acid crosslinked chitosan microsphere, and the mean diameter of crosslinked chitosan microsphere is 1～300 μ m.
Crosslinked chitosan microsphere herein can adopt conventional technology as coacervation, emulsion-crosslinking method preparation method, and many documents are all reported to some extent.
One preferred embodiment in, chitosan solution is added drop-wise in NaOH solution or NaOH-methanol mixed solution in condense, collect microsphere, and then microsphere is scattered in to sulfuric acid solution or the phosphoric acid solution that concentration is 1～30% (w/v), process 1～24 hour; Collect microsphere, fully washing obtains sulphuric acid crosslinked chitosan microsphere or phosphoric acid cross-linked chitosan after being dried.
Another preferred embodiment in, taking concentration as 5～30% (w/v) sulphuric acid is as cross-linking agent, at room temperature by making microsphere with the cross-linking reaction of chitosan solution, fully washing after collecting, obtains chitosan sulfate microsphere after dry.
Another preferred embodiment in, taking concentration as 5～30% (w/v) citric acid is as cross-linking agent, at 40～60 DEG C, by making microsphere with the cross-linking reaction of chitosan solution, fully washing after collecting, obtains citric acid crosslinked chitosan microsphere after being dried.
Another preferred embodiment in, taking concentration as 5～30% (w/v) phosphoric acid is as cross-linking agent, at room temperature by making microsphere with the cross-linking reaction of chitosan, fully washing after collecting, obtains calcium phosphate-chitosan microsphere after dry.
Wherein, the experimental technique of not marked actual conditions, those skilled in the art, according to the condition of normal condition or bibliographical information, all can be known.
Calcium phosphate bone cement
Calcium phosphate bone cement is that a kind of novel bone reparation, bone are filled or bone alternate material, can contain calcium powder by calcium phosphate etc., and after consolidation liquid is in harmonious proportion, condensation cure obtains.
The calcium phoshate bone cement powder using in the present invention has no particular limits, the various synthos for bone tissue restoration or the compound phosphoric acid calcium salt of this area routine be can make, a kind of in tricalcium phosphate, tetracalcium phosphate, OCP, dalcium biphosphate, hydroxyapatite or fluor-apatite or their mixture are preferably.
10 microns of the mean diameter < of the synthos bone cement powder that the present invention uses.
Conventionally, the consolidation liquid of calcium phosphate bone cement can be the blood of distilled water, phosphoric acid,diluted, sodium phosphate, normal saline, operative site etc.Bone cement liquid phase ingredient more complicated, multiplex containing K
+, Na
+, Ca
2+and HPO
4 2-deng material, these ions are important component of skeleton and body fluid, the growth to bone and metabolism thereof play important regulating action.In consolidation liquid of the present invention, contain sodium glycerophosphate (sodium glycerophosphate), a kind of organic phosphorus compound, is also a kind of weak base, is typically used as the additive of cell culture fluid, has good biocompatibility.Phosphoglycerol sodium injection is usually used as a kind of phosphorus supplement of the intravenous nutrition of being grown up, in order to meet the human body every day of the metabolic demand to phosphorus.
Injectable compound bone cement
The present invention's common modification to calcium phosphate bone cement by chitosan microball and sodium glycerophosphate, utilize the interaction between positively charged chitosan microball and electronegative phosphoglycerol radical ion, realize the synergistic function of additive to calcium phosphate composite bone cement, prepare a kind of anti-collapsibility, injectable, fast setting, there is higher force and learn intensity Injectable compound bone cement that can degradation in vivo pore-forming.
Injectable compound bone cement of the present invention, is in harmonious proportion and is formed by pressed powder and consolidation liquid, and pressed powder comprises calcium phoshate bone cement powder and chitosan microball, contains sodium glycerophosphate in consolidation liquid.
In another preference, the mass volume ratio of pressed powder and consolidation liquid (g/mL) is 1: 1～3.5: 1.
Preferably, described pressed powder is made up of the component of following weight percent content:
Calcium phoshate bone cement powder 60～99%;
Crosslinked chitosan microsphere 1～40%.
More preferably, described pressed powder is made up of the component of following weight percent content:
Calcium phoshate bone cement powder 85～98%;
Crosslinked chitosan microsphere 2～15%.
Described crosslinked chitosan microsphere is sulphuric acid crosslinked chitosan microsphere, phosphoric acid crosslinked chitosan microsphere or citric acid crosslinked chitosan microsphere, and mean diameter is 1～300 μ m.
Described calcium phoshate bone cement powder has no particular limits, the various synthos for bone tissue restoration or the compound phosphoric acid calcium salt of this area routine be can use, a kind of in tricalcium phosphate, tetracalcium phosphate, OCP, dalcium biphosphate, hydroxyapatite or fluor-apatite or their mixture are preferably.
In another preference, the aqueous solution that described consolidation liquid is sodium glycerophosphate, the normal saline solution of sodium glycerophosphate, the concentration of described sodium glycerophosphate is 0.1～0.4g/mL.
Wherein, normal saline, refers to Physiology Experiment or the sodium chloride solution that conventional osmotic pressure equates with the osmotic pressure of animal or human's body blood plasma clinically, and concentration is 0.85～0.9w/v%.
Injectable compound bone cement of the present invention, can adopt injecting method to be applied to the aspects such as defect and restore, fractures, bone reparation; Also after can solidifying, implant.
Injectable compound bone cement test kit
Injectable compound bone cement test kit provided by the invention, comprises pressed powder and consolidation liquid, and described pressed powder comprises calcium phoshate bone cement powder and crosslinked chitosan microsphere, in described consolidation liquid, contains sodium glycerophosphate.
Preferably, described pressed powder is made up of the component of following weight percent content:
Calcium phoshate bone cement powder 60～99%;
Crosslinked chitosan microsphere 1～40%.
More preferably, described pressed powder is made up of the component of following weight percent content:
Calcium phoshate bone cement powder 85～98%;
Crosslinked chitosan microsphere 2～15%.
Described crosslinked chitosan microsphere is sulphuric acid crosslinked chitosan microsphere, phosphoric acid crosslinked chitosan microsphere or citric acid crosslinked chitosan microsphere, and mean diameter is 1～300 μ m.
Described calcium phoshate bone cement powder has no particular limits, the various synthos for bone tissue restoration or the compound phosphoric acid calcium salt of this area routine be can make, a kind of in tricalcium phosphate, tetracalcium phosphate, OCP, dalcium biphosphate, hydroxyapatite or fluor-apatite or their mixture are preferably.
In another preference, the aqueous solution that described consolidation liquid is sodium glycerophosphate, the normal saline solution of sodium glycerophosphate, the concentration of described sodium glycerophosphate is 0.1～0.4g/mL.
Wherein, normal saline, refers to Physiology Experiment or the sodium chloride solution that conventional osmotic pressure equates with the osmotic pressure of animal or human's body blood plasma clinically, and concentration is 0.85～0.9w/v%.
In another preference, the mass volume ratio of pressed powder and consolidation liquid (g/mL) is 1: 1～3.5: 1.
The preparation method of Injectable compound bone cement
In a preferred embodiment, the preparation method of Injectable compound bone cement provided by the invention, comprises the steps:
(1) chitosan microball is mixed homogeneously with calcium phoshate bone cement powder;
(2) add the consolidation liquid that contains sodium glycerophosphate (GP), mix homogeneously obtains Injectable compound bone cement.
In a preferred embodiment, the preparation method of Injectable compound bone cement provided by the invention, comprises the steps:
(1) chitosan microball is mixed homogeneously with the consolidation liquid that contains sodium glycerophosphate,
(2) add calcium phoshate bone cement powder, mix homogeneously, obtains Injectable compound bone cement.
In another preference, the weight ratio of described calcium phoshate bone cement powder and crosslinked chitosan microsphere is 60～99: 1～40.
In another preference, the weight ratio of described calcium phoshate bone cement powder and crosslinked chitosan microsphere is 85～98: 2～15.
In another preference, described crosslinked chitosan microsphere is sulphuric acid crosslinked chitosan microsphere, phosphoric acid crosslinked chitosan microsphere or citric acid crosslinked chitosan microsphere, and mean diameter is 1～300 μ m.
In another preference, described calcium phoshate bone cement powder has no particular limits, the various synthos for bone tissue restoration or the compound phosphoric acid calcium salt of this area routine be can make, a kind of in tricalcium phosphate, tetracalcium phosphate, OCP, dalcium biphosphate, hydroxyapatite or fluor-apatite or their mixture are preferably.
In another preference, the aqueous solution that described consolidation liquid is sodium glycerophosphate, the normal saline solution of sodium glycerophosphate, the concentration of described sodium glycerophosphate is 0.1～0.4g/mL.
Wherein, normal saline, refers to Physiology Experiment or the sodium chloride solution that conventional osmotic pressure equates with the osmotic pressure of animal or human's body blood plasma clinically, and concentration is 0.85～0.9w/v%.
In another preference, the gross weight of described calcium phoshate bone cement powder and crosslinked chitosan microsphere and the mass volume ratio of described consolidation liquid are 1: 1～3.5: 1.
Injectable compound bone cement of the present invention has good anti-collapsibility performance and injection property, quick self-curing performance, advantages of higher compressive strength and good biocompatibility, having solved traditional injectable CPC and had the defects such as water-resistance deficiency, injection property is poor, setting time is long, vivo degradation is slow, is a kind of Injectable bone repair material with extensive clinical practice potentiality.This material can be used for the treatment of osteoporotic fracture, can be used as reparation that various bones are damaged and the filling of root canal, also can be used for the timbering material of bone tissue engineer or the carrier material as medicament slow release.
The above-mentioned feature that the present invention mentions, or the feature that embodiment mentions can combination in any.All features that this case description discloses can with any composition forms use, each feature disclosing in description, can anyly provide the alternative characteristics of identical, impartial or similar object to replace.Therefore apart from special instruction, the feature disclosing is only the general example of equalization or similar features.
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment are only not used in and limit the scope of the invention for the present invention is described.The experimental technique of unreceipted actual conditions in the following example, the condition of conventionally advising according to normal condition or according to manufacturer.
Embodiment 1
The preparation of sulphuric acid cross-linked chitosan
Chitosan is dissolved in acetic acid solution, be mixed with 3% (w/v) chitosan solution, slowly join in the oil phase liquid paraffin body containing emulsifying agent, stir and form W/O emulsion, add 20% (w/v) sulfuric acid solution to be cross-linked, form sulphuric acid crosslinked chitosan microsphere, fully wash with acetone, dehydrated alcohol and water again, after lyophilization, obtain chitosan microball, microsphere complete shape and appearance, smooth surface densification (as shown in Figure 1), particle diameter is 5～20 μ m.
Embodiment 2
The preparation of phosphoric acid cross-linked chitosan
Chitosan is dissolved in acetic acid solution, be mixed with 1% (w/v) chitosan solution, and under high-pressure electrostatic effect, splash in NaOH-methanol mixed solution and condense, collect microsphere, and then microsphere is scattered in the phosphoric acid solution that concentration is 30% (w/v), process 20 hours; Collect microsphere, fully washing obtains phosphoric acid crosslinked chitosan microsphere after being dried, and microspherulite diameter is 80～120 μ m.
Embodiment 3
The preparation of citric acid cross-linked chitosan
Chitosan is dissolved in acetic acid solution, be mixed with 4% (w/v) chitosan solution, slowly join in the oil phase liquid paraffin body containing emulsifying agent, stir and form W/O emulsion, add 20% (w/v) citric acid solution, at 50 DEG C, carry out cross-linking reaction, make citric acid crosslinked chitosan microsphere, collect microsphere, fully washing obtains chitosan microball after being dried, and particle diameter is 30～50 μ m.
Embodiment 4
Injectable compound bone cement
Take the self-curable calcium phosphate bone cement powder that 3g is made up of calcium hydrogen phosphate, tetracalcium phosphate and hydroxyapatite, take the crosslinked chitosan microball of 0.3g sulphuric acid, and it is mixed homogeneously with bone cement powder, adding 1.5mL concentration is the phosphoglycerol sodium water solution of 0.3g/mL, fast modulation is even.
To mix well slurry and insert in mould and make batten, and be placed in 37 DEG C, 100% humidity environment and solidify, batten setting time is 5.5min, and after bone dry, its comprcssive strength is 28MPa.As shown in Figure 2, in the fresh section bone cement matrix of its firming body material, be uniform-distribution with the spherical porous structure of class.
The above-mentioned slurry of mixing well is packed in the syringe with internal diameter 1.6mm syringe needle fast, and as shown in Figure 3, slurry is easy to injection, and extrudate can keep continuous strip and not rupture.
By in slurry injected water, with the velocity fluctuation of 60r/min 5 minutes, as shown in Figure 4, slurry did not produce defeated and dispersed or slightly soluble phenomenon, and whole liquid presents clear state.
The above-mentioned slurry of mixing well is implanted in SD rat abdomen flesh bag by syringe, postoperative 1 week, cut off and cover the lip-deep skin of composite bone cement with shears, as shown in Figure 5, do not observe obvious powder defeated and dispersed.
Embodiment 5
Injectable compound bone cement
Take the self-curable calcium phosphate bone cement powder that 3g is made up of calcium hydrogen phosphate, tetracalcium phosphate and hydroxyapatite, take the crosslinked chitosan microball of 0.3g sulphuric acid, and it is mixed homogeneously with bone cement powder, adding 3mL concentration is the sodium glycerophosphate normal saline solution of 0.4g/mL, and wherein the concentration of normal saline is that 0.9% (w/v) fast modulation is even.
To mix well slurry and insert in mould and make batten, and be placed in 37 DEG C, 100% humidity environment and solidify, batten setting time is 11min, and after bone dry, its comprcssive strength is 8MPa.
The above-mentioned slurry of mixing well is packed in the syringe with internal diameter 1.6mm syringe needle fast, and slurry is easy to injection, and extrudate can keep continuous strip and not rupture.
By in slurry injected water, with the velocity fluctuation of 60r/min 5 minutes, slurry did not produce defeated and dispersed or slightly soluble phenomenon, and whole liquid presents clear state.
Above-mentioned slurry is implanted in SD rat abdomen flesh bag by syringe, postoperative 1 week, cut off and cover the lip-deep skin of composite bone cement with shears, do not observe obvious powder defeated and dispersed.
Embodiment 6
Injectable compound bone cement
Take the crosslinked chitosan microball of 0.45g sulphuric acid, adding 1.8mL concentration is the phosphoglycerol sodium water solution of 0.3g/mL, and fast modulation is even.Take the self-curable calcium phosphate bone cement powder that 3g is made up of calcium hydrogen phosphate, tetracalcium phosphate and hydroxyapatite, mix homogeneously with above-mentioned microsphere/phosphoglycerol sodium solution.
To mix well slurry and insert in mould and make batten, and be placed in 37 DEG C, 100% humidity environment and solidify, batten setting time is 6min, and after bone dry, its comprcssive strength is 15MPa.
The above-mentioned slurry of mixing well is packed in the syringe with internal diameter 1.6mm syringe needle fast, and slurry is easy to injection, and extrudate can keep continuous strip and not rupture.
By in slurry injected water, with the velocity fluctuation of 60r/min 5 minutes, slurry did not produce defeated and dispersed or slightly soluble phenomenon, and whole liquid presents clear state.
Above-mentioned slurry is implanted in SD rat abdomen flesh bag by syringe, postoperative 1 week, cut off and cover the lip-deep skin of composite bone cement with shears, do not observe obvious powder defeated and dispersed.
Embodiment 7
Injectable compound bone cement
Take the self-curable calcium phosphate bone cement powder that 3g is made up of tricalcium phosphate and hydroxyapatite, take the crosslinked chitosan microball of 0.06g sulphuric acid, and it is mixed homogeneously with bone cement powder, adding 1.5mL concentration is the normal saline solution of the sodium glycerophosphate of 0.2g/mL, wherein the concentration of normal saline is 0.85% (w/v), and fast modulation is even.
To mix well slurry and insert in mould and make batten, and be placed in 37 DEG C, 100% humidity environment and solidify, batten setting time is 7min, and after bone dry, its comprcssive strength is 9.5MPa.
The above-mentioned slurry of mixing well is packed in the syringe with internal diameter 1.6mm syringe needle fast, and slurry is easy to injection, and extrudate can keep continuous strip and not rupture.
By in slurry injected water, with the velocity fluctuation of 60r/min 5 minutes, slurry did not produce defeated and dispersed or slightly soluble phenomenon, and whole liquid presents clear state.
Above-mentioned slurry is implanted in SD rat abdomen flesh bag by syringe, postoperative 1 week, cut off and cover the lip-deep skin of composite bone cement with shears, do not observe obvious powder defeated and dispersed.
Embodiment 8
Injectable compound bone cement
Take the self-curable calcium phosphate bone cement powder that 3g is made up of calcium hydrogen phosphate, tetracalcium phosphate and hydroxyapatite, take the crosslinked chitosan microball of 0.06g sulphuric acid, and it is mixed homogeneously with bone cement powder, adding 1mL concentration is the normal saline solution of the sodium glycerophosphate of 0.3g/mL, wherein the concentration of normal saline is 0.9% (w/v), and fast modulation is even.
To mix well slurry and insert in mould and make batten, and be placed in 37 DEG C, 100% humidity environment and solidify, batten setting time is 5.5min, and after bone dry, its comprcssive strength is 18MPa.
The above-mentioned slurry of mixing well is packed in the syringe with internal diameter 1.6mm syringe needle fast, and slurry is easy to injection, and extrudate can keep continuous strip and not rupture.
By in slurry injected water, with the velocity fluctuation of 60r/min 5 minutes, slurry did not produce defeated and dispersed or slightly soluble phenomenon, and whole liquid presents clear state.
Above-mentioned slurry is implanted in SD rat abdomen flesh bag by syringe, postoperative 1 week, cut off and cover the lip-deep skin of composite bone cement with shears, do not observe obvious powder defeated and dispersed.
Embodiment 9
Injectable compound bone cement
Take the self-curable calcium phosphate bone cement powder that 3g is made up of calcium hydrogen phosphate, tetracalcium phosphate and hydroxyapatite, take the crosslinked chitosan microball of 0.3g phosphoric acid, and it is mixed homogeneously with bone cement powder, adding 1.5mL concentration is the sodium glycerophosphate normal saline solution of 0.3g/mL, and fast modulation is even.
To mix well slurry and insert in mould and make batten, and be placed in 37 DEG C, 100% humidity environment and solidify, batten setting time is 6min, and after bone dry, its comprcssive strength is 26MPa.
The above-mentioned slurry of mixing well is packed in the syringe with internal diameter 1.6mm syringe needle fast, and slurry is easy to injection, and extrudate can keep continuous strip and not rupture.
By in slurry injected water, with the velocity fluctuation of 60r/min 5 minutes, slurry did not produce defeated and dispersed or slightly soluble phenomenon, and whole liquid presents clear state.
Above-mentioned slurry is implanted in SD rat abdomen flesh bag by syringe, postoperative 1 week, cut off and cover the lip-deep skin of composite bone cement with shears, do not observe obvious powder defeated and dispersed.
Embodiment 10
Injectable compound bone cement
Take the self-curable calcium phosphate bone cement powder that 3g is made up of calcium hydrogen phosphate, tetracalcium phosphate and hydroxyapatite, take the crosslinked chitosan microball of 0.3g citric acid, and it is mixed homogeneously with bone cement powder, adding 1.5mL concentration is the phosphoglycerol sodium water solution of 0.3g/mL, and fast modulation is even.To mix well slurry and insert in mould and make batten, and be placed in 37 DEG C, 100% humidity environment and solidify, batten setting time is 5min, and after bone dry, its comprcssive strength is 30MPa.
The above-mentioned slurry of mixing well is packed in the syringe with internal diameter 1.6mm syringe needle fast, and slurry is easy to injection, and extrudate can keep continuous strip and not rupture.
By in slurry injected water, with the velocity fluctuation of 60r/min 5 minutes, slurry did not produce defeated and dispersed or slightly soluble phenomenon, and whole liquid presents clear state.
Above-mentioned slurry is implanted in SD rat abdomen flesh bag by syringe, postoperative 1 week, cut off and cover the lip-deep skin of composite bone cement with shears, do not observe obvious powder defeated and dispersed.
Embodiment 11
Injectable compound bone cement
Take the crosslinked chitosan microball of 0.3g sulphuric acid, adding 1.5mL concentration is the normal saline solution of the sodium glycerophosphate of 0.1g/mL, and wherein the concentration of normal saline is 0.9% (w/v), and fast modulation is even.Take the self-curable calcium phosphate bone cement powder that 3g is made up of calcium hydrogen phosphate, tetracalcium phosphate and hydroxyapatite, mix homogeneously with above-mentioned microsphere/phosphoglycerol sodium solution.
To mix well slurry and insert in mould and make batten, and be placed in 37 DEG C, 100% humidity environment and solidify, batten setting time is 15min, and after bone dry, its comprcssive strength is 20MPa.
The above-mentioned slurry of mixing well is packed in the syringe with internal diameter 1.6mm syringe needle fast, and slurry is easy to injection, and extrudate can keep continuous strip and not rupture.
By in slurry injected water, with the velocity fluctuation of 60r/min 5 minutes, slurry did not produce defeated and dispersed or slightly soluble phenomenon, and whole liquid presents clear state.
Above-mentioned slurry is implanted in SD rat abdomen flesh bag by syringe, postoperative 1 week, cut off and cover the lip-deep skin of composite bone cement with shears, do not observe obvious powder defeated and dispersed.
Embodiment 12
Injectable compound bone cement
Take the crosslinked chitosan microball of 0.3g phosphoric acid, adding 1.5mL concentration is the phosphoglycerol sodium water solution of 0.3g/mL, and fast modulation is even.Take the self-curable calcium phosphate bone cement powder that 3g is made up of tricalcium phosphate and hydroxyapatite, mix homogeneously with above-mentioned microsphere/phosphoglycerol sodium solution.
To mix well slurry and insert in mould and make batten, and be placed in 37 DEG C, 100% humidity environment and solidify, batten setting time is 5min, and after bone dry, its comprcssive strength is 23MPa.
The above-mentioned slurry of mixing well is packed in the syringe with internal diameter 1.6mm syringe needle fast, and slurry is easy to injection, and extrudate can keep continuous strip and not rupture.
By in slurry injected water, with the velocity fluctuation of 60r/min 5 minutes, slurry did not produce defeated and dispersed or slightly soluble phenomenon, and whole liquid presents clear state.
Above-mentioned slurry is implanted in SD rat abdomen flesh bag by syringe, postoperative 1 week, cut off and cover the lip-deep skin of composite bone cement with shears, do not observe obvious powder defeated and dispersed.
Embodiment 13
Injectable compound bone cement
Take the self-curable calcium phosphate bone cement powder that 3g is made up of calcium hydrogen phosphate, tetracalcium phosphate and hydroxyapatite, take the crosslinked chitosan microball of 0.45g citric acid, and it is mixed homogeneously with bone cement powder, adding 1.3mL concentration is the aqueous solution of the sodium glycerophosphate of 0.3g/mL, and fast modulation is even.
To mix well slurry and insert in mould and make batten, and be placed in 37 DEG C, 100% humidity environment and solidify, batten setting time is 6min, and after bone dry, its comprcssive strength is 32MPa.
The above-mentioned slurry of mixing well is packed in the syringe with internal diameter 1.6mm syringe needle fast, and slurry is easy to injection, and extrudate can keep continuous strip and not rupture.
By in slurry injected water, with the velocity fluctuation of 60r/min 5 minutes, slurry did not produce defeated and dispersed or slightly soluble phenomenon, and whole liquid presents clear state.
Above-mentioned slurry is implanted in SD rat abdomen flesh bag by syringe, postoperative 1 week, cut off and cover the lip-deep skin of composite bone cement with shears, do not observe obvious powder defeated and dispersed.
Embodiment 14
Injectable compound bone cement
Take the self-curable calcium phosphate bone cement powder that 3g is made up of tricalcium phosphate and fluor-apatite, take the crosslinked chitosan microball of 0.06g sulphuric acid, and it is mixed homogeneously with bone cement powder, adding 1mL concentration is the normal saline solution of the sodium glycerophosphate of 0.3g/mL, wherein the concentration of normal saline is 0.9% (w/v), and fast modulation is even.
To mix well slurry and insert in mould and make batten, and be placed in 37 DEG C, 100% humidity environment and solidify, batten setting time is 8min, and after bone dry, its comprcssive strength is 16MPa.
The above-mentioned slurry of mixing well is packed in the syringe with internal diameter 1.6mm syringe needle fast, and slurry is easy to injection, and extrudate can keep continuous strip and not rupture.
By in slurry injected water, with the velocity fluctuation of 80r/min 5 minutes, slurry did not produce defeated and dispersed or slightly soluble phenomenon, and whole liquid presents clear state.
Above-mentioned slurry is implanted in SD rat abdomen flesh bag by syringe, postoperative 1 week, cut off and cover the lip-deep skin of composite bone cement with shears, do not observe obvious powder defeated and dispersed.
Embodiment 15
Injectable compound bone cement
Take the crosslinked chitosan microball of 0.3g phosphoric acid, adding 1.5mL concentration is the phosphoglycerol sodium water solution of 0.3g/mL, and fast modulation is even.Take the self-curable calcium phosphate bone cement powder that 3g is made up of OCP, calcium metaphosphate and hydroxyapatite, mix homogeneously with above-mentioned microsphere/phosphoglycerol sodium solution.
To mix well slurry and insert in mould and make batten, and be placed in 37 DEG C, 100% humidity environment and solidify, batten setting time is 10min, and after bone dry, its comprcssive strength is 12MPa.
The above-mentioned slurry of mixing well is packed in the syringe with internal diameter 1.6mm syringe needle fast, and slurry is easy to injection, and extrudate can keep continuous strip and not rupture.
By in slurry injected water, with the velocity fluctuation of 60r/min 5 minutes, slurry did not produce defeated and dispersed or slightly soluble phenomenon, and whole liquid presents clear state.
Above-mentioned slurry is implanted in SD rat abdomen flesh bag by syringe, postoperative 1 week, cut off and cover the lip-deep skin of composite bone cement with shears, do not observe obvious powder defeated and dispersed.
Embodiment 16
Injectable compound bone cement
Take the crosslinked chitosan microball of 0.45g citric acid, adding 2.5mL concentration is the phosphoglycerol sodium water solution of 0.3g/mL, and fast modulation is even.Take the self-curable calcium phosphate bone cement powder that 3g is made up of tetracalcium phosphate, dalcium biphosphate and hydroxyapatite, mix homogeneously with above-mentioned microsphere/phosphoglycerol sodium solution.
To mix well slurry and insert in mould and make batten, and be placed in 37 DEG C, 100% humidity environment and solidify, batten setting time is 9min, and after bone dry, its comprcssive strength is 12MPa.
The above-mentioned slurry of mixing well is packed in the syringe with internal diameter 1.6mm syringe needle fast, and slurry is easy to injection, and extrudate can keep continuous strip and not rupture.
By in slurry injected water, with the velocity fluctuation of 100r/min 5 minutes, slurry did not produce defeated and dispersed or slightly soluble phenomenon, and whole liquid presents clear state.
Above-mentioned slurry is implanted in SD rat abdomen flesh bag by syringe, postoperative 1 week, cut off and cover the lip-deep skin of composite bone cement with shears, do not observe obvious powder defeated and dispersed.
Unless otherwise defined, the same meaning that all specialties that use in literary composition and scientific words and one skilled in the art are familiar.In addition, any method similar or impartial to described content and material all can be applicable in the inventive method.The use that better implementation method described in literary composition and material only present a demonstration.
All documents of mentioning in the present invention are all quoted as a reference in this application, are just quoted separately as a reference as each section of document.In addition should be understood that those skilled in the art can make various changes or modifications the present invention after having read above-mentioned teachings of the present invention, these equivalent form of values fall within the application's appended claims limited range equally.
Claims (9)
1. an Injectable compound bone cement test kit, it is characterized in that, described test kit comprises pressed powder and consolidation liquid, described pressed powder comprises calcium phoshate bone cement powder and crosslinked chitosan microsphere, in described consolidation liquid, contain sodium glycerophosphate, described crosslinked chitosan microsphere is sulphuric acid crosslinked chitosan microsphere, phosphoric acid crosslinked chitosan microsphere or citric acid crosslinked chitosan microsphere.
2. test kit as claimed in claim 1, is characterized in that, described pressed powder is made up of the component of following weight percent content:
Calcium phoshate bone cement powder 60～99%;
Crosslinked chitosan microsphere 1～40%.
3. test kit as claimed in claim 2, is characterized in that, described pressed powder is made up of the component of following weight percent content:
Calcium phoshate bone cement powder 85～98%;
Crosslinked chitosan microsphere 2～15%.
4. the test kit as described in claim 1～3 any one, it is characterized in that, described calcium phoshate bone cement powder is a kind of in tricalcium phosphate, tetracalcium phosphate, OCP, calcium hydrogen phosphate, dalcium biphosphate, calcium metaphosphate, calcium pyrophosphate, hydroxyapatite or fluor-apatite or their mixture.
5. test kit according to claim 1, is characterized in that, the preparation of described crosslinked chitosan microsphere comprises the following steps:
(1) chitosan solution is added drop-wise in NaOH solution or in NaOH-methanol mixed solution and condenses, collect microsphere, and then microsphere is scattered in to sulfuric acid solution or the phosphoric acid solution that concentration is 1～30% (w/v), process 1～24 hour; Collect microsphere, fully washing obtains chitosan microball after being dried; Or
(2) taking concentration as 5～30% (w/v) sulphuric acid is as cross-linking agent, at room temperature by making sulphuric acid crosslinked chitosan microsphere with the cross-linking reaction of chitosan solution, collect microsphere, fully washing obtains chitosan microball after being dried; Or
(3) taking concentration as 5～30% (w/v) citric acid is as cross-linking agent, at 40～60 DEG C, by making citric acid crosslinked chitosan microsphere with the cross-linking reaction of chitosan solution, collect microsphere, fully washing obtains chitosan microball after being dried.
6. the test kit as described in claim 1～3 any one, is characterized in that, the aqueous solution that described consolidation liquid is sodium glycerophosphate or the normal saline solution of sodium glycerophosphate, and the concentration of described sodium glycerophosphate is 0.1～0.4g/mL.
7. an Injectable compound bone cement, is characterized in that, by pressed powder and consolidation liquid by mass volume ratio (g/mL) be 1: 1～3.5: 1 formulated, wherein,
Described pressed powder comprises calcium phoshate bone cement powder and crosslinked chitosan microsphere, in described consolidation liquid, contains sodium glycerophosphate,
Wherein said crosslinked chitosan microsphere is sulphuric acid crosslinked chitosan microsphere, phosphoric acid crosslinked chitosan microsphere or citric acid crosslinked chitosan microsphere.
8. the preparation method of Injectable compound bone cement as claimed in claim 7, is characterized in that, comprises the steps:
Crosslinked chitosan microsphere is mixed homogeneously with calcium phoshate bone cement powder, add the consolidation liquid that contains sodium glycerophosphate, mix homogeneously, thus obtain Injectable compound bone cement; Or
Crosslinked chitosan microsphere is mixed homogeneously with the consolidation liquid that contains sodium glycerophosphate, then mix homogeneously with calcium phoshate bone cement powder, thereby obtain Injectable compound bone cement.
9. the application of Injectable compound bone cement as claimed in claim 7, is characterized in that, the bio-medical material of repairing for the preparation of defect and restore, fractures, bone.
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| CN103965510B (en) * | 2013-01-29 | 2017-03-29 | 上海高科生物工程有限公司 | Bone cement of controlled release high molecular weight protein and preparation method thereof |
| CN103920192B (en) * | 2014-04-04 | 2015-08-05 | 北京大学口腔医院 | The preparation method of the temperature sensitive pluralgel carrier of a kind of year bioactie agent and application |
| CN104857568B (en) * | 2015-05-29 | 2017-06-23 | 河南科技大学 | A kind of calcium orthophosphate base bone cement with anti-microbial property and preparation method thereof |
| CN105148320A (en) * | 2015-09-28 | 2015-12-16 | 河南工程学院 | Preparing method and application of medicine carrying hydroxyapatite porous microspheres |
| CN105731990B (en) * | 2016-02-01 | 2018-06-05 | 河南理工大学 | A kind of controlled degradation magnesium phosphate cement and its preparation method and application |
| CN107050523A (en) * | 2016-12-23 | 2017-08-18 | 江南大学 | A kind of preparation method of new β tricalcium phosphates/chitosan composite bionic hydrogel |
| CN108144115B (en) * | 2018-02-09 | 2020-07-07 | 重庆医科大学附属永川医院 | Injectable bone cement with continuous antibacterial and anti-inflammatory effects and preparation method thereof |
| CN108273129B (en) * | 2018-03-30 | 2020-12-11 | 暨南大学 | Anti-collapsibility and high-strength composite calcium phosphate bone cement and preparation method and application thereof |
| CN108635624B (en) * | 2018-04-25 | 2022-01-04 | 武汉理工大学 | Anti-collapsibility injectable magnesium phosphate-based bone cement |
| CN113082296B (en) * | 2021-04-26 | 2022-03-08 | 东南大学 | Calcium phosphate bone cement with good injectability and preparation method thereof |
| CN113769160A (en) * | 2021-08-23 | 2021-12-10 | 广州润虹医药科技股份有限公司 | Thermo-sensitive microsphere and ready-to-use thermo-sensitive calcium phosphate cement thereof |
| CN114344563B (en) * | 2022-01-28 | 2023-04-18 | 河南科技大学 | Material with antibacterial and bone-promoting properties and preparation method thereof |
| CN117531050A (en) * | 2022-08-02 | 2024-02-09 | 苏州大学 | Bone cement material and preparation method thereof |
| TWI833456B (en) * | 2022-11-18 | 2024-02-21 | 財團法人金屬工業研究發展中心 | Bone substitute composition and device to inject the same |
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| CN1302821C (en) * | 2005-08-26 | 2007-03-07 | 清华大学 | Preparation method of calcium orthophosphate bone cement degradable to pore in human body |
| CN101125219A (en) * | 2007-09-04 | 2008-02-20 | 山东大学 | Rapidly solidified calcium phosphate cement composite material and its preparation method |
| CN100548380C (en) * | 2008-03-05 | 2009-10-14 | 四川大学 | Long-acting slow-releasing medicine carrier material and preparation method thereof is repaired in the osteomyelitis treatment |
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