CN102526798A - Injectable compound bone cement and preparation method thereof - Google Patents
Injectable compound bone cement and preparation method thereof Download PDFInfo
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- CN102526798A CN102526798A CN2012100162755A CN201210016275A CN102526798A CN 102526798 A CN102526798 A CN 102526798A CN 2012100162755 A CN2012100162755 A CN 2012100162755A CN 201210016275 A CN201210016275 A CN 201210016275A CN 102526798 A CN102526798 A CN 102526798A
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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 the biomaterial for medical purpose field, be specifically related to injectable composite bone cement test kit, injectable composite bone cement.
Background technology
Along with the development of Minimally Invasive Surgery, perform the operation like percutaneous, but need the biomaterial of direct injection day by day.Because its cured product is similar with the inorganic phase composition of natural bone, (calcium phosphate cement CPC) can be used as a kind of Minimally Invasive Surgery material to the self-curable calcium phosphate bone cement, is used for the bone defect repair.Yet present some shortcomings of injectable calcium phosphate bone cement are relatively poor such as mechanical property, be difficult to inject, in blood or liquid, be prone to defeated and dispersed, as to lack osteocyte growth hole etc. and all limited its wide clinical application.
In order to overcome these deficiencies, people adopt the performance that improves bone cement through interpolation variety classes additive.(Structural characterization of phosphorylated chito san and their applications as effective additives of calcium phosphate cements.Biomaterials such as Wang Xiaohong; 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, yet prolonged hardening time.Polymeric additive (chitosan, cellulose derivative) thus the cohesive force that can increase the 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 have delayed the curing of bone cement simultaneously.The interpolation of sodium glycerophosphate or glycerol can improve the injection performance of calcium phosphate bone cement; (the L. Leroux that but prolonged hardening time greatly; 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.; But the method for preparing of the calcium phosphate bone cement of degradation in vivo pore-forming; CN 1302821C) add in the calcium phosphate bone cement, can improve the fracture toughness of bone cement, the degraded through fiber and microsphere simultaneously can produce macropore again in cement; Help the conveying of nutrient substance in the CPC firming body and growing into of cell, but the increase of fiber and chitosan microball content can cause reducing of bone-cement composite material comprcssive strength and inject performance decrease.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 when shortening the setting time of bone cement, but reduce the injection performance of bone cement slurry.Therefore, these additives when improving a certain performance of bone cement, but are prone to cause the decline of another important performance of bone cement usually.
The common modification of multiple material is a kind of feasible way that improves the injectable bone cement performance in recent years.The higher dicalcium phosphate dehydrate (DCPD) of usefulness dissolubility such as Burguera replaces calcium phosphate dibasic anhydrous (DCPA), with sodium phosphate as curing accelerator and add hydroxypropyl emthylcellulose raising injectivity simultaneously and 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 through use DCPD, curing accelerator, gel, porogen and absorbable fibre simultaneously; Prepared the bone cement (H.H.K.Xu that a kind of injectable has macropore; Et al.Injectable and macroporous calcium phosphate cement scaffold.Biomaterials; 2006,7 (24): 4279-4287).But this common method of modifying need add multiple additives simultaneously, with the corresponding bone cement different performance that improves, learns from other's strong points to offset one's weaknesses, and could satisfy 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 composite bone cement and preparation method thereof, not only have good anti-collapsibility performance and injection performance, and self-curing fast, advantages of higher compressive strength had, in vivo degradable.
First aspect of the present invention provides a kind of injectable composite bone cement test kit, and said test kit comprises pressed powder and consolidation liquid, and said pressed powder comprises calcium phosphate bone cement powder and crosslinked chitosan microsphere, contains sodium glycerophosphate in the said consolidation liquid.
In another preference, said pressed powder in the test kit and said consolidation liquid are 1: 1～3.5: 1 by mass volume ratio (g/mL).
In another preference, said pressed powder in the test kit and said consolidation liquid are 1.5: 1～3: 1 by mass volume ratio (g/mL).
In another preference, said pressed powder in the test kit and said consolidation liquid are 2: 1～2.5: 1 by mass volume ratio (g/mL).
In another preference, said pressed powder is made up of the component of following weight percent content:
Calcium phosphate 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 phosphate bone cement powder 85～98%;
Crosslinked chitosan microsphere 2～15%.
In another preference, said pressed powder is made up of the component of following weight percent content:
Calcium phosphate bone cement powder 75～95%;
In another preference, said calcium phosphate bone cement powder is a kind of in tricalcium phosphate, tetracalcium phosphate, OCP, calcium hydrogen phosphate, dalcium biphosphate, calcium metaphosphate, calcium pyrophosphate, hydroxyapatite or the 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 said crosslinked chitosan microsphere may further comprise the steps:
(1) be added drop-wise to chitosan solution in the NaOH solution or NaOH-methanol mixed solution in condense, collect microsphere, and then microsphere be scattered in sulfuric acid solution or the phosphoric acid solution that concentration is 1～30% (w/v), handled 1～24 hour; Collect microsphere, promptly get chitosan microball after the thorough washing drying; Or
(2) be that 5～30% (w/v) sulphuric acid is cross-linking agent with concentration, at room temperature make the sulphuric acid crosslinked chitosan microsphere, collect microsphere, promptly get chitosan microball after the thorough washing drying through cross-linking reaction with chitosan solution; Or
(3) be that 5～30% (w/v) citric acid is a cross-linking agent with concentration, under 40～60 ℃, make the citric acid crosslinked chitosan microsphere, collect microsphere, promptly get chitosan microball after the thorough washing drying through cross-linking reaction with chitosan solution.
In another preference, said consolidation liquid is the aqueous solution of sodium glycerophosphate or the normal saline solution of sodium glycerophosphate, and the concentration of said sodium glycerophosphate is 0.1～0.4g/mL.
In another preference, in the normal saline solution of said sodium glycerophosphate, the concentration of normal saline is 0.85～0.9w/v%.
Second aspect of the present invention provides a kind of injectable composite bone cement, by pressed powder and consolidation liquid by mass volume ratio (g/mL) be 1: 1～3.5: 1 formulated, wherein,
Said pressed powder comprises calcium phosphate bone cement powder and crosslinked chitosan microsphere, contains sodium glycerophosphate in the said consolidation liquid.
In another preference, said pressed powder and said consolidation liquid are to be mixed with the injectable composite bone cement in 1.5: 1～3: 1 by mass volume ratio (g/mL).
In another preference, said pressed powder and said consolidation liquid are to be mixed with the injectable composite bone cement in 2: 1～2.5: 1 by mass volume ratio (g/mL).
In another preference, said pressed powder is made up of the component of following weight percent content:
Calcium phosphate 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 phosphate bone cement powder 85～98%;
Crosslinked chitosan microsphere 2～15%.
In another preference, said pressed powder is made up of the component of following weight percent content:
Calcium phosphate bone cement powder 75～95%;
In another preference, said calcium phosphate bone cement powder is a kind of in tricalcium phosphate, tetracalcium phosphate, OCP, calcium hydrogen phosphate, dalcium biphosphate, calcium metaphosphate, calcium pyrophosphate, hydroxyapatite or the 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, said consolidation liquid is the aqueous solution of sodium glycerophosphate or the normal saline solution of sodium glycerophosphate, and the concentration of said sodium glycerophosphate is 0.1～0.4g/mL.
In another preference, in the normal saline solution of said sodium glycerophosphate, the concentration of normal saline is 0.85～0.9w/v%.
The third aspect of the invention provides the method for preparing of injectable composite bone cement, comprises the steps:
Crosslinked chitosan microsphere and calcium phosphate bone cement powder mixes is even, add the consolidation liquid that contains sodium glycerophosphate, mix homogeneously, thus obtain the injectable composite bone cement; Or
With crosslinked chitosan microsphere and the consolidation liquid mix homogeneously that contains sodium glycerophosphate, even with the calcium phosphate bone cement powder mixes again, thus obtain the injectable composite bone cement.
In another preference, the weight ratio of said calcium phosphate bone cement powder and crosslinked chitosan microsphere is 60～99: 1～40.
In another preference, the weight ratio of said calcium phosphate bone cement powder and crosslinked chitosan microsphere is 85～98: 2～15.
In another preference, the weight ratio of said calcium phosphate bone cement powder and crosslinked chitosan microsphere is 75～95: 5～25.
In another preference, said calcium phosphate bone cement powder is a kind of in tricalcium phosphate, tetracalcium phosphate, OCP, calcium hydrogen phosphate, dalcium biphosphate, calcium metaphosphate, calcium pyrophosphate, hydroxyapatite or the 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, said consolidation liquid is the aqueous solution of sodium glycerophosphate or the normal saline solution of sodium glycerophosphate, and the concentration of said sodium glycerophosphate is 0.1～0.4g/mL.
In another preference, in the normal saline solution of said sodium glycerophosphate, the concentration of normal saline is 0.85～0.9w/v%.
In another preference, the gross weight of said calcium phosphate bone cement powder and crosslinked chitosan microsphere and the mass volume ratio of said consolidation liquid are 1: 1～3.5: 1.
In another preference, the gross weight of said calcium phosphate bone cement powder and crosslinked chitosan microsphere and the mass volume ratio of said consolidation liquid are 1.5: 1～3: 1.
In another preference, the gross weight of said calcium phosphate bone cement powder and crosslinked chitosan microsphere and the mass volume ratio of said consolidation liquid are 2: 1～2.5: 1.
Fourth aspect of the present invention provides the application of injectable composite bone cement, is used to prepare the bio-medical material of defect and restore, fractures, bone reparation.
Injectable composite bone cement of the present invention has good anti-collapsibility performance and injection performance, 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 hereinafter can mutual combination between specifically described each technical characterictic in (like embodiment), thus constitute new or optimized technical scheme.As space is limited, this tired no longer one by one stating.
Description of 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 composite bone cement.
Fig. 3 is the picture of injectable composite bone cement.
Fig. 4 is the anti-collapsibility performance of injectable composite bone cement in water.
Fig. 5 is an injectable composite bone cement anti-collapsibility performance in animal body.
The specific embodiment
The present inventor is through extensively and in depth research; The unexpected discovery; The pressed powder and the consolidation liquid mix homogeneously that contains sodium glycerophosphate that will comprise crosslinked chitosan microsphere and calcium phosphate bone cement powder; Can obtain having good anti-collapsibility performance and injection performance, and self-curing fast, the injectable composite bone cement with advantages of higher compressive strength.On this basis, accomplish the present invention.
Design of the present invention is following:
Adopt crosslinked chitosan microsphere and sodium glycerophosphate to come 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 the chitosan microball original position of original densification form the porous aquagel microsphere, be evenly distributed in the bone cement matrix, form the hydrogel that the Ca ion is had the strong adsorption effect; Can promote the hydroxyapatite deposition, thereby shorten the setting time of bone cement; Hydrogel and bone cement matrix bond are tight, can reduce the porosity of bone cement, thereby improve 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 the phosphoglycerol radical ion can be adsorbed on the surface of each composition of calcium phosphate bone cement, increases its surface charge, thereby improves the injection performance 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 higher relatively intensity in early days, gel micro-ball degraded afterwards produces the growth that micropore is convenient to osteocyte.
Crosslinked chitosan microsphere
Chitosan is a kind of natural polysaccharide derivant, the polysaccharide that glucosamine that is extracted by Crustacean and acetylglucosamine are formed.Advantages such as chitosan is the product of chitin deacetylase base, has wide material sources, and is with low cost, and have good bioaffinity, biological degradability and ossification, and catabolite safety non-toxic.Hydroxyl that enriches on the chitosan molecule chain and amino make it be easy to carry out chemical modification and give multiple function, are used widely in fields such as medicine, agricultural, light textile, daily use chemicals.Preparation of Chitosan is become polymer microsphere, make the functional mutually compound of chitosan and polymer microsphere, can make it obtain bigger application in fields such as biomedicines.
In the present invention, the not special restriction of employed chitosan, usually, the chitosan molecule amount is 10～100KDa, more excellent molecular weight is 20～80KDa; Deacetylation is generally 40～99%, and more excellent is 60～95%.
Crosslinked chitosan microsphere used herein is meant 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.
The crosslinked chitosan microsphere of this paper can adopt conventional technology such as coacervation, emulsion-crosslinking method method for preparing, and many documents are report to some extent all.
One preferred embodiment in, with chitosan solution be added drop-wise in the NaOH solution or NaOH-methanol mixed solution in condense, collect microsphere, and then microsphere be scattered in sulfuric acid solution or the phosphoric acid solution that concentration is 1～30% (w/v), handled 1～24 hour; Collect microsphere, promptly get sulphuric acid crosslinked chitosan microsphere or phosphoric acid cross-linked chitosan after the thorough washing drying.
Another preferred embodiment in, be that 5～30% (w/v) sulphuric acid is cross-linking agent with concentration, at room temperature make microsphere through cross-linking reaction with chitosan solution, collect the back thorough washing, promptly get the sulphuric acid chitosan microball after the drying.
Another preferred embodiment in, be that 5～30% (w/v) citric acid is a cross-linking agent with concentration, under 40～60 ℃, make microsphere through cross-linking reaction with chitosan solution, collect the back thorough washing, promptly get the citric acid crosslinked chitosan microsphere after the drying.
Another preferred embodiment in, be that 5～30% (w/v) phosphoric acid is cross-linking agent with concentration, at room temperature make microsphere through cross-linking reaction with chitosan, collect the back thorough washing, promptly get the calcium phosphate-chitosan microsphere after the drying.
Wherein, the experimental technique of not marked actual conditions, those skilled in the art all can be known according to the condition of normal condition or bibliographical information.
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 condensation cure obtains after consolidation liquid is in harmonious proportion.
The calcium phosphate bone cement powder that uses among the present invention has no particular limits; This area conventional various synthos that are used for bone tissue restoration or compound phosphoric acid calcium salt be can make, a kind of in tricalcium phosphate, tetracalcium phosphate, OCP, dalcium biphosphate, hydroxyapatite or the fluor-apatite or their mixture are preferably.
Mean diameter＜10 of the synthos bone cement powder that the present invention uses micron.
Usually, 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 is many with containing K
+, Na
+, Ca
2+And HPO
4 2-Deng material, these ions are important component of skeleton and body fluid, and the growth and the metabolism thereof of bone played important regulatory role.Contain sodium glycerophosphate (sodium glycerophosphate) in the consolidation liquid of the present invention, a kind of organic phosphorus compound also is a kind of weak base, as the additive of cell culture fluid, has excellent biological compatibility usually.The phosphoglycerol sodium injection is usually as a kind of phosphorus supplement of the intravenous nutrition of being grown up, in order to satisfy the human body every day of the metabolic demand to phosphorus.
The injectable composite bone cement
The present invention is through the common modification to calcium phosphate bone cement of chitosan microball and sodium glycerophosphate; Utilize the interaction between positively charged chitosan microball and the electronegative phosphoglycerol radical ion; Realize the synergistic function of additive, but prepare a kind of anti-collapsibility, injectable, fast setting, have the injectable composite bone cement of higher mechanical strength and degradation in vivo pore-forming calcium phosphate composite bone cement.
Injectable composite bone cement of the present invention is formed by pressed powder and consolidation liquid mediation, and pressed powder comprises calcium phosphate bone cement powder and chitosan microball, contains sodium glycerophosphate in the 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 phosphate 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 phosphate 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 phosphate bone cement powder has no particular limits; This area conventional various synthos that are used for bone tissue restoration or compound phosphoric acid calcium salt be can use, a kind of in tricalcium phosphate, tetracalcium phosphate, OCP, dalcium biphosphate, hydroxyapatite or the fluor-apatite or their mixture are preferably.
In another preference, said consolidation liquid is the aqueous solution of sodium glycerophosphate, the normal saline solution of sodium glycerophosphate, and the concentration of said sodium glycerophosphate is 0.1～0.4g/mL.
Wherein, normal saline is meant the sodium chloride solution that Physiology Experiment or osmotic pressure commonly used clinically equate with the osmotic pressure of animal or human's body blood plasma, and concentration is 0.85～0.9w/v%.
Injectable composite bone cement of the present invention can adopt injecting method to be applied to aspects such as defect and restore, fractures, bone reparation; Implant after also can solidifying.
Injectable composite bone cement test kit
Injectable composite bone cement test kit provided by the invention comprises pressed powder and consolidation liquid, and said pressed powder comprises calcium phosphate bone cement powder and crosslinked chitosan microsphere, contains sodium glycerophosphate in the said consolidation liquid.
Preferably, described pressed powder is made up of the component of following weight percent content:
Calcium phosphate 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 phosphate 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 phosphate bone cement powder has no particular limits; This area conventional various synthos that are used for bone tissue restoration or compound phosphoric acid calcium salt be can make, a kind of in tricalcium phosphate, tetracalcium phosphate, OCP, dalcium biphosphate, hydroxyapatite or the fluor-apatite or their mixture are preferably.
In another preference, said consolidation liquid is the aqueous solution of sodium glycerophosphate, the normal saline solution of sodium glycerophosphate, and the concentration of said sodium glycerophosphate is 0.1～0.4g/mL.
Wherein, normal saline is meant the sodium chloride solution that Physiology Experiment or osmotic pressure commonly used clinically equate with the osmotic pressure of animal or human's body blood plasma, 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 method for preparing of injectable composite bone cement
In a preferred embodiment, the method for preparing of injectable composite bone cement provided by the invention comprises the steps:
(1) chitosan microball and calcium phosphate bone cement powder mixes is even;
(2) add the consolidation liquid that contains sodium glycerophosphate (GP), mix homogeneously obtains the injectable composite bone cement.
In a preferred embodiment, the method for preparing of injectable composite bone cement provided by the invention comprises the steps:
(1) with chitosan microball and the consolidation liquid mix homogeneously that contains sodium glycerophosphate,
(2) add the calcium phosphate bone cement powder, mix homogeneously obtains the injectable composite bone cement.
In another preference, the weight ratio of said calcium phosphate bone cement powder and crosslinked chitosan microsphere is 60～99: 1～40.
In another preference, the weight ratio of said calcium phosphate 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 phosphate bone cement powder has no particular limits; This area conventional various synthos that are used for bone tissue restoration or compound phosphoric acid calcium salt be can make, a kind of in tricalcium phosphate, tetracalcium phosphate, OCP, dalcium biphosphate, hydroxyapatite or the fluor-apatite or their mixture are preferably.
In another preference, said consolidation liquid is the aqueous solution of sodium glycerophosphate, the normal saline solution of sodium glycerophosphate, and the concentration of said sodium glycerophosphate is 0.1～0.4g/mL.
Wherein, normal saline is meant the sodium chloride solution that Physiology Experiment or osmotic pressure commonly used clinically equate with the osmotic pressure of animal or human's body blood plasma, and concentration is 0.85～0.9w/v%.
In another preference, the gross weight of said calcium phosphate bone cement powder and crosslinked chitosan microsphere and the mass volume ratio of said consolidation liquid are 1: 1～3.5: 1.
Injectable composite bone cement of the present invention has good anti-collapsibility performance and injection performance, quick self-curing performance, advantages of higher compressive strength and excellent biological compatibility; Having solved traditional injectable CPC and had defectives such as water-resistance is not enough, injection poor-performing, setting time is long, vivo degradation is slow, is a kind of injectable bone repair materials with extensive clinical practice potentiality.This material can be used for the treatment of osteoporotic fracture, can be used as the filling of damaged reparation of various bones and root canal, also can be used for the timbering material of bone tissue engineer or as the carrier material of medicament slow release.
The above-mentioned characteristic that the present invention mentions, or the characteristic that embodiment mentions can combination in any.All characteristics that this case description is disclosed can with any composition forms and usefulness, each characteristic that is disclosed in the description can anyly provide the alternative characteristics of identical, impartial or similar purpose to replace.Therefore removing has special instruction, the characteristic that is disclosed to be merely 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 only to be used to the present invention is described and be not used in the restriction scope of the present invention.The experimental technique of unreceipted actual conditions in the following example is usually according to the normal condition or the condition of advising according to manufacturer.
Embodiment 1
The preparation of sulphuric acid cross-linked chitosan
Chitosan is dissolved in the acetic acid solution, is mixed with 3% (w/v) chitosan solution, slowly join in the oil phase liquid paraffin body that contains emulsifying agent; Stir and form the W/O emulsion, adding 20% (w/v) sulfuric acid solution carries out crosslinked, forms the sulphuric acid crosslinked chitosan microsphere; Reuse acetone, dehydrated alcohol and water thorough washing promptly get chitosan microball, the microsphere complete shape and appearance after the lyophilization; Smooth surface fine and close (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 the acetic acid solution; Be mixed with 1% (w/v) chitosan solution, and under the high-pressure electrostatic effect, splash in the NaOH-methanol mixed solution and condense, collect microsphere; And then microsphere is scattered in the phosphoric acid solution that concentration is 30% (w/v), handled 20 hours; Collect microsphere, promptly get the phosphoric acid crosslinked chitosan microsphere after the thorough washing drying, microspherulite diameter is 80～120 μ m.
Embodiment 3
The preparation of citric acid cross-linked chitosan
Chitosan is dissolved in the acetic acid solution, is mixed with 4% (w/v) chitosan solution, slowly join in the oil phase liquid paraffin body that contains emulsifying agent; Stir and form the W/O emulsion, add 20% (w/v) citric acid solution, under 50 ℃, carry out cross-linking reaction; Make the citric acid crosslinked chitosan microsphere; Collect microsphere, promptly get chitosan microball after the thorough washing drying, particle diameter is 30～50 μ m.
Embodiment 4
The injectable composite bone cement
Take by weighing the self-curable calcium phosphate bone cement powder that 3g is made up of calcium hydrogen phosphate, tetracalcium phosphate and hydroxyapatite; Take by weighing the crosslinked chitosan microball of 0.3g sulphuric acid; And with itself and bone cement powder mix homogeneously, 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 and process batten in the mould, and place 37 ℃, 100% humidity environment to solidify, batten setting time is 5.5min, and its comprcssive strength is 28MPa behind the bone dry.As shown in Figure 2, the spherical porous structure of type of being uniform-distribution with in the fresh section bone cement matrix of its firming body material.
The above-mentioned slurry of mixing well is packed in the syringe of band 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 do not rupture.
Slurry is injected water, and with the velocity fluctuation of 60r/min 5 minutes, as shown in Figure 4, slurry did not produce defeated and dispersed or the slightly soluble phenomenon, and whole liquid presents the clear state.
The above-mentioned slurry of mixing well is implanted in the SD rat abdomen flesh bag through syringe, 1 week of postoperative, cut off with shears and to cover the lip-deep skin of composite bone cement, as shown in Figure 5, it is defeated and dispersed not observe obvious powder.
The injectable composite bone cement
Take by weighing the self-curable calcium phosphate bone cement powder that 3g is made up of calcium hydrogen phosphate, tetracalcium phosphate and hydroxyapatite; Take by weighing the crosslinked chitosan microball of 0.3g sulphuric acid; And with itself and bone cement powder mix homogeneously; 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 and process batten in the mould, and place 37 ℃, 100% humidity environment to solidify, batten setting time is 11min, and its comprcssive strength is 8MPa behind the bone dry.
The above-mentioned slurry of mixing well is packed in the syringe of band internal diameter 1.6mm syringe needle fast, and slurry is easy to injection, and extrudate can keep continuous strip and do not rupture.
Slurry is injected water, and with the velocity fluctuation of 60r/min 5 minutes, slurry did not produce defeated and dispersed or the slightly soluble phenomenon, and whole liquid presents the clear state.
Above-mentioned slurry is implanted in the SD rat abdomen flesh bag through syringe, 1 week of postoperative, cut off with shears and to cover the lip-deep skin of composite bone cement, it is defeated and dispersed not observe obvious powder.
The injectable composite bone cement
Take by weighing 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 by weighing the self-curable calcium phosphate bone cement powder that 3g is made up of calcium hydrogen phosphate, tetracalcium phosphate and hydroxyapatite, with above-mentioned microsphere/phosphoglycerol sodium solution mix homogeneously.
To mix well slurry and insert and process batten in the mould, and place 37 ℃, 100% humidity environment to solidify, batten setting time is 6min, and its comprcssive strength is 15MPa behind the bone dry.
The above-mentioned slurry of mixing well is packed in the syringe of band internal diameter 1.6mm syringe needle fast, and slurry is easy to injection, and extrudate can keep continuous strip and do not rupture.
Slurry is injected water, and with the velocity fluctuation of 60r/min 5 minutes, slurry did not produce defeated and dispersed or the slightly soluble phenomenon, and whole liquid presents the clear state.
Above-mentioned slurry is implanted in the SD rat abdomen flesh bag through syringe, 1 week of postoperative, cut off with shears and to cover the lip-deep skin of composite bone cement, it is defeated and dispersed not observe obvious powder.
Embodiment 7
The injectable composite bone cement
Take by weighing the self-curable calcium phosphate bone cement powder that 3g is made up of tricalcium phosphate and hydroxyapatite; Take by weighing the crosslinked chitosan microball of 0.06g sulphuric acid; And with itself and bone cement powder mix homogeneously; Adding 1.5mL concentration is the normal saline solution of the sodium glycerophosphate of 0.2g/mL, and wherein the concentration of normal saline is 0.85% (w/v), and fast modulation is even.
To mix well slurry and insert and process batten in the mould, and place 37 ℃, 100% humidity environment to solidify, batten setting time is 7min, and its comprcssive strength is 9.5MPa behind the bone dry.
The above-mentioned slurry of mixing well is packed in the syringe of band internal diameter 1.6mm syringe needle fast, and slurry is easy to injection, and extrudate can keep continuous strip and do not rupture.
Slurry is injected water, and with the velocity fluctuation of 60r/min 5 minutes, slurry did not produce defeated and dispersed or the slightly soluble phenomenon, and whole liquid presents the clear state.
Above-mentioned slurry is implanted in the SD rat abdomen flesh bag through syringe, 1 week of postoperative, cut off with shears and to cover the lip-deep skin of composite bone cement, it is defeated and dispersed not observe obvious powder.
Embodiment 8
The injectable composite bone cement
Take by weighing the self-curable calcium phosphate bone cement powder that 3g is made up of calcium hydrogen phosphate, tetracalcium phosphate and hydroxyapatite; Take by weighing the crosslinked chitosan microball of 0.06g sulphuric acid; And with itself and bone cement powder mix homogeneously; Adding 1mL concentration is the normal saline solution of the sodium glycerophosphate of 0.3g/mL, and wherein the concentration of normal saline is 0.9% (w/v), and fast modulation is even.
To mix well slurry and insert and process batten in the mould, and place 37 ℃, 100% humidity environment to solidify, batten setting time is 5.5min, and its comprcssive strength is 18MPa behind the bone dry.
The above-mentioned slurry of mixing well is packed in the syringe of band internal diameter 1.6mm syringe needle fast, and slurry is easy to injection, and extrudate can keep continuous strip and do not rupture.
Slurry is injected water, and with the velocity fluctuation of 60r/min 5 minutes, slurry did not produce defeated and dispersed or the slightly soluble phenomenon, and whole liquid presents the clear state.
Above-mentioned slurry is implanted in the SD rat abdomen flesh bag through syringe, 1 week of postoperative, cut off with shears and to cover the lip-deep skin of composite bone cement, it is defeated and dispersed not observe obvious powder.
Embodiment 9
The injectable composite bone cement
Take by weighing the self-curable calcium phosphate bone cement powder that 3g is made up of calcium hydrogen phosphate, tetracalcium phosphate and hydroxyapatite; Take by weighing the crosslinked chitosan microball of 0.3g phosphoric acid; And with itself and bone cement powder mix homogeneously; 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 and process batten in the mould, and place 37 ℃, 100% humidity environment to solidify, batten setting time is 6min, and its comprcssive strength is 26MPa behind the bone dry.
The above-mentioned slurry of mixing well is packed in the syringe of band internal diameter 1.6mm syringe needle fast, and slurry is easy to injection, and extrudate can keep continuous strip and do not rupture.
Slurry is injected water, and with the velocity fluctuation of 60r/min 5 minutes, slurry did not produce defeated and dispersed or the slightly soluble phenomenon, and whole liquid presents the clear state.
Above-mentioned slurry is implanted in the SD rat abdomen flesh bag through syringe, 1 week of postoperative, cut off with shears and to cover the lip-deep skin of composite bone cement, it is defeated and dispersed not observe obvious powder.
Embodiment 10
The injectable composite bone cement
Take by weighing the self-curable calcium phosphate bone cement powder that 3g is made up of calcium hydrogen phosphate, tetracalcium phosphate and hydroxyapatite; Take by weighing the crosslinked chitosan microball of 0.3g citric acid; And with itself and bone cement powder mix homogeneously; 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 and process batten in the mould, and place 37 ℃, 100% humidity environment to solidify, batten setting time is 5min, and its comprcssive strength is 30MPa behind the bone dry.
The above-mentioned slurry of mixing well is packed in the syringe of band internal diameter 1.6mm syringe needle fast, and slurry is easy to injection, and extrudate can keep continuous strip and do not rupture.
Slurry is injected water, and with the velocity fluctuation of 60r/min 5 minutes, slurry did not produce defeated and dispersed or the slightly soluble phenomenon, and whole liquid presents the clear state.
Above-mentioned slurry is implanted in the SD rat abdomen flesh bag through syringe, 1 week of postoperative, cut off with shears and to cover the lip-deep skin of composite bone cement, it is defeated and dispersed not observe obvious powder.
Embodiment 11
The injectable composite bone cement
Take by weighing 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 by weighing the self-curable calcium phosphate bone cement powder that 3g is made up of calcium hydrogen phosphate, tetracalcium phosphate and hydroxyapatite, with above-mentioned microsphere/phosphoglycerol sodium solution mix homogeneously.
To mix well slurry and insert and process batten in the mould, and place 37 ℃, 100% humidity environment to solidify, batten setting time is 15min, and its comprcssive strength is 20MPa behind the bone dry.
The above-mentioned slurry of mixing well is packed in the syringe of band internal diameter 1.6mm syringe needle fast, and slurry is easy to injection, and extrudate can keep continuous strip and do not rupture.
Slurry is injected water, and with the velocity fluctuation of 60r/min 5 minutes, slurry did not produce defeated and dispersed or the slightly soluble phenomenon, and whole liquid presents the clear state.
Above-mentioned slurry is implanted in the SD rat abdomen flesh bag through syringe, 1 week of postoperative, cut off with shears and to cover the lip-deep skin of composite bone cement, it is defeated and dispersed not observe obvious powder.
Embodiment 12
The injectable composite bone cement
Take by weighing 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 by weighing the self-curable calcium phosphate bone cement powder that 3g is made up of tricalcium phosphate and hydroxyapatite, with above-mentioned microsphere/phosphoglycerol sodium solution mix homogeneously.
To mix well slurry and insert and process batten in the mould, and place 37 ℃, 100% humidity environment to solidify, batten setting time is 5min, and its comprcssive strength is 23MPa behind the bone dry.
The above-mentioned slurry of mixing well is packed in the syringe of band internal diameter 1.6mm syringe needle fast, and slurry is easy to injection, and extrudate can keep continuous strip and do not rupture.
Slurry is injected water, and with the velocity fluctuation of 60r/min 5 minutes, slurry did not produce defeated and dispersed or the slightly soluble phenomenon, and whole liquid presents the clear state.
Above-mentioned slurry is implanted in the SD rat abdomen flesh bag through syringe, 1 week of postoperative, cut off with shears and to cover the lip-deep skin of composite bone cement, it is defeated and dispersed not observe obvious powder.
Embodiment 13
The injectable composite bone cement
Take by weighing the self-curable calcium phosphate bone cement powder that 3g is made up of calcium hydrogen phosphate, tetracalcium phosphate and hydroxyapatite; Take by weighing the crosslinked chitosan microball of 0.45g citric acid; And with itself and bone cement powder mix homogeneously; 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 and process batten in the mould, and place 37 ℃, 100% humidity environment to solidify, batten setting time is 6min, and its comprcssive strength is 32MPa behind the bone dry.
The above-mentioned slurry of mixing well is packed in the syringe of band internal diameter 1.6mm syringe needle fast, and slurry is easy to injection, and extrudate can keep continuous strip and do not rupture.
Slurry is injected water, and with the velocity fluctuation of 60r/min 5 minutes, slurry did not produce defeated and dispersed or the slightly soluble phenomenon, and whole liquid presents the clear state.
Above-mentioned slurry is implanted in the SD rat abdomen flesh bag through syringe, 1 week of postoperative, cut off with shears and to cover the lip-deep skin of composite bone cement, it is defeated and dispersed not observe obvious powder.
Embodiment 14
The injectable composite bone cement
Take by weighing the self-curable calcium phosphate bone cement powder that 3g is made up of tricalcium phosphate and fluor-apatite; Take by weighing the crosslinked chitosan microball of 0.06g sulphuric acid; And with itself and bone cement powder mix homogeneously; Adding 1mL concentration is the normal saline solution of the sodium glycerophosphate of 0.3g/mL, and wherein the concentration of normal saline is 0.9% (w/v), and fast modulation is even.
To mix well slurry and insert and process batten in the mould, and place 37 ℃, 100% humidity environment to solidify, batten setting time is 8min, and its comprcssive strength is 16MPa behind the bone dry.
The above-mentioned slurry of mixing well is packed in the syringe of band internal diameter 1.6mm syringe needle fast, and slurry is easy to injection, and extrudate can keep continuous strip and do not rupture.
Slurry is injected water, and with the velocity fluctuation of 80r/min 5 minutes, slurry did not produce defeated and dispersed or the slightly soluble phenomenon, and whole liquid presents the clear state.
Above-mentioned slurry is implanted in the SD rat abdomen flesh bag through syringe, 1 week of postoperative, cut off with shears and to cover the lip-deep skin of composite bone cement, it is defeated and dispersed not observe obvious powder.
Embodiment 15
The injectable composite bone cement
Take by weighing 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 by weighing the self-curable calcium phosphate bone cement powder that 3g is made up of OCP, calcium metaphosphate and hydroxyapatite, with above-mentioned microsphere/phosphoglycerol sodium solution mix homogeneously.
To mix well slurry and insert and process batten in the mould, and place 37 ℃, 100% humidity environment to solidify, batten setting time is 10min, and its comprcssive strength is 12MPa behind the bone dry.
The above-mentioned slurry of mixing well is packed in the syringe of band internal diameter 1.6mm syringe needle fast, and slurry is easy to injection, and extrudate can keep continuous strip and do not rupture.
Slurry is injected water, and with the velocity fluctuation of 60r/min 5 minutes, slurry did not produce defeated and dispersed or the slightly soluble phenomenon, and whole liquid presents the clear state.
Above-mentioned slurry is implanted in the SD rat abdomen flesh bag through syringe, 1 week of postoperative, cut off with shears and to cover the lip-deep skin of composite bone cement, it is defeated and dispersed not observe obvious powder.
Embodiment 16
The injectable composite bone cement
Take by weighing 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 by weighing the self-curable calcium phosphate bone cement powder that 3g is made up of tetracalcium phosphate, dalcium biphosphate and hydroxyapatite, with above-mentioned microsphere/phosphoglycerol sodium solution mix homogeneously.
To mix well slurry and insert and process batten in the mould, and place 37 ℃, 100% humidity environment to solidify, batten setting time is 9min, and its comprcssive strength is 12MPa behind the bone dry.
The above-mentioned slurry of mixing well is packed in the syringe of band internal diameter 1.6mm syringe needle fast, and slurry is easy to injection, and extrudate can keep continuous strip and do not rupture.
Slurry is injected water, and with the velocity fluctuation of 100r/min 5 minutes, slurry did not produce defeated and dispersed or the slightly soluble phenomenon, and whole liquid presents the clear state.
Above-mentioned slurry is implanted in the SD rat abdomen flesh bag through syringe, 1 week of postoperative, cut off with shears and to cover the lip-deep skin of composite bone cement, it is defeated and dispersed not observe obvious powder.
Only if definition separately, the same meaning that employed all specialties and scientific words and one skilled in the art are familiar with in the literary composition.In addition, any with the institute similar content of putting down in writing or the equalization method and material all can be applicable in the inventive method.The usefulness that preferable implementation method described in the literary composition and material only present a demonstration.
All documents in that the present invention mentions are all quoted as a reference in this application, are just quoted such as a reference separately as each piece document.Should be understood that in addition after having read above-mentioned teachings of the present invention, those skilled in the art can do various changes or modification to the present invention, these equivalent form of values fall within the application's appended claims institute restricted portion equally.
Claims (10)
1. an injectable composite bone cement test kit is characterized in that said test kit comprises pressed powder and consolidation liquid, and said pressed powder comprises calcium phosphate bone cement powder and crosslinked chitosan microsphere, contains sodium glycerophosphate in the said consolidation liquid.
2. test kit as claimed in claim 1 is characterized in that, said pressed powder is made up of the component of following weight percent content:
Calcium phosphate bone cement powder 60～99%;
Crosslinked chitosan microsphere 1～40%.
3. test kit as claimed in claim 2 is characterized in that, said pressed powder is made up of the component of following weight percent content:
Calcium phosphate bone cement powder 85～98%;
Crosslinked chitosan microsphere 2～15%.
4. like each described test kit of claim 1～3; It is characterized in that said calcium phosphate bone cement powder is a kind of in tricalcium phosphate, tetracalcium phosphate, OCP, calcium hydrogen phosphate, dalcium biphosphate, calcium metaphosphate, calcium pyrophosphate, hydroxyapatite or the fluor-apatite or their mixture.
5. like each described test kit of claim 1～3, it is characterized in that described crosslinked chitosan microsphere is sulphuric acid crosslinked chitosan microsphere, phosphoric acid crosslinked chitosan microsphere or citric acid crosslinked chitosan microsphere.
6. chitosan microball according to claim 6 is characterized in that, the preparation of said crosslinked chitosan microsphere may further comprise the steps:
(1) be added drop-wise to chitosan solution in the NaOH solution or NaOH-methanol mixed solution in condense, collect microsphere, and then microsphere be scattered in sulfuric acid solution or the phosphoric acid solution that concentration is 1～30% (w/v), handled 1～24 hour; Collect microsphere, promptly get chitosan microball after the thorough washing drying; Or
(2) be that 5～30% (w/v) sulphuric acid is cross-linking agent with concentration, at room temperature make the sulphuric acid crosslinked chitosan microsphere, collect microsphere, promptly get chitosan microball after the thorough washing drying through cross-linking reaction with chitosan solution; Or
(3) be that 5～30% (w/v) citric acid is a cross-linking agent with concentration, under 40～60 ℃, make the citric acid crosslinked chitosan microsphere, collect microsphere, promptly get chitosan microball after the thorough washing drying through cross-linking reaction with chitosan solution.
7. like each described test kit of claim 1～6, it is characterized in that said consolidation liquid is the aqueous solution of sodium glycerophosphate or the normal saline solution of sodium glycerophosphate, the concentration of said sodium glycerophosphate is 0.1～0.4g/mL.
8. an injectable composite 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,
Said pressed powder comprises calcium phosphate bone cement powder and crosslinked chitosan microsphere, contains sodium glycerophosphate in the said consolidation liquid.
9. the method for preparing of injectable composite bone cement as claimed in claim 8 is characterized in that, comprises the steps:
Crosslinked chitosan microsphere and calcium phosphate bone cement powder mixes is even, add the consolidation liquid that contains sodium glycerophosphate, mix homogeneously, thus obtain the injectable composite bone cement; Or
With crosslinked chitosan microsphere and the consolidation liquid mix homogeneously that contains sodium glycerophosphate, even with the calcium phosphate bone cement powder mixes again, thus obtain the injectable composite bone cement.
10. the application of injectable composite bone cement as claimed in claim 8 is characterized in that, is used to prepare the bio-medical material of defect and restore, fractures, bone reparation.
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Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103920192A (en) * | 2014-04-04 | 2014-07-16 | 北京大学口腔医院 | Preparation method and application of bioactive factor loaded temperature-sensitive composite gel carrier |
| CN103965510A (en) * | 2013-01-29 | 2014-08-06 | 上海高科生物工程有限公司 | Bone cement capable of controllably releasing macromolecule proteins, and preparation method thereof |
| CN104857568A (en) * | 2015-05-29 | 2015-08-26 | 河南科技大学 | Calcium phosphate-based bone cement with antibacterial 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 |
| CN105731990A (en) * | 2016-02-01 | 2016-07-06 | 河南理工大学 | Degradation-controllable magnesium phosphate cement and preparation method and application thereof |
| 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 |
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| 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 |
| CN114344563A (en) * | 2022-01-28 | 2022-04-15 | 河南科技大学 | Material with antibacterial and bone-promoting properties and preparation method thereof |
| WO2024027650A1 (en) * | 2022-08-02 | 2024-02-08 | 苏州大学 | Bone cement material and method for preparing same |
| 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 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004087229A2 (en) * | 2003-04-04 | 2004-10-14 | Ta Contrast Ab | Bone cement compositions |
| CN1736928A (en) * | 2005-08-26 | 2006-02-22 | 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 |
| US20080188946A1 (en) * | 2003-04-11 | 2008-08-07 | Etex Corporation | Osteoinductive bone material |
| CN101244275A (en) * | 2008-03-05 | 2008-08-20 | 四川大学 | Long-acting sustained-release medicaments for treating and renovating bone disease and preparation thereof |
| CN101934095A (en) * | 2010-08-31 | 2011-01-05 | 赵亮 | Injectable strengthened phosphate lime/hydrogel microcapsule tissue engineering bone as well as preparation method and application thereof |
-
2012
- 2012-01-18 CN CN201210016275.5A patent/CN102526798B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004087229A2 (en) * | 2003-04-04 | 2004-10-14 | Ta Contrast Ab | Bone cement compositions |
| CN1798588A (en) * | 2003-04-04 | 2006-07-05 | Ta对比公司 | Bone cement compositions |
| US20080188946A1 (en) * | 2003-04-11 | 2008-08-07 | Etex Corporation | Osteoinductive bone material |
| CN1736928A (en) * | 2005-08-26 | 2006-02-22 | 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 |
| CN101244275A (en) * | 2008-03-05 | 2008-08-20 | 四川大学 | Long-acting sustained-release medicaments for treating and renovating bone disease and preparation thereof |
| CN101934095A (en) * | 2010-08-31 | 2011-01-05 | 赵亮 | Injectable strengthened phosphate lime/hydrogel microcapsule tissue engineering bone as well as preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| 扈延龄 等: "复合rhBMP-2壳聚糖微球可注射磷酸钙骨水泥制备及成骨性能研究", 《中国矫形外科杂志》, vol. 18, no. 20, 31 October 2010 (2010-10-31) * |
| 苗军 等: "磷酸钙骨水泥可注射性的研究进展", 《中国修复重建外科杂志》, vol. 19, no. 7, 31 July 2005 (2005-07-31) * |
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