CN106139253B - The bone cement that the composition of composite bone cement can be formed and formed by it - Google Patents
The bone cement that the composition of composite bone cement can be formed and formed by it Download PDFInfo
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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Abstract
The present invention provides the bone cement that can be formed the composition of composite bone cement and be formed by it, and the composition includes the composition and tuna fishbone dust/hyaluronate microspheres for forming polymethyl acrylate bone cement；It is in terms of 100% by the gross weight of composition comprising tuna fishbone dust/hyaluronate microspheres that mass fraction is 8%~60%；Microballoon is the microballoon being prepared using tuna fishbone dust and hyaluronic acid as raw material, wherein, it is in terms of 100% by the total weight of tuna fishbone dust and hyaluronic acid, the mass fraction of tuna fishbone dust is 30%~70%, and the mass fraction of hyaluronic acid is 30%~70%.Composition provided by the invention is to joined the tuna fishbone dust/hyaluronate microspheres for promoting bone uptake on the basis of can form PMMA bone cement compositions, and gained bone cement has many advantages, such as excellent bioactivity, biocompatibility, osseointegration character.
Description
Technical field
The invention belongs to medical instruments fields, and in particular to one kind can form the composition of composite bone cement and be formed by it
Bone cement.
Background technique
Bone cement is a kind of medical material for being widely used in bone surgery, and bone cement is usually by pulvis and liquid phase two parts group
At being mixed in a certain ratio can be cured at room temperature, the position of replacement joint or filling be placed it in, wait react
After arthrodesis or bone defect can be repaired.Since bone cement has syringeability, minor operation can be reduced to greatest extent
The area of wound accelerates rehabilitation speed, mitigates patient suffering, so being usually used in the packing material and timbering material of bone tissue, rises
It is the indispensable a member of bone tissue application material to supporting role.Since early 1960s bone cement comes out, mainly
Bone cement type have bioceramic bone cement, polymethyl methacrylate (PMMA) bone cement, calcium phosphate bone cement and hydroxyl
Apatite bone cement etc..
Currently, clinical application is most widely polymethyl acrylate (PMMA) bone cement.Traditional poly- methyl propylene
Sour methyl esters (PMMA) bone cement can be used for the Bone Defect Repari implantation of supporting part in spite of preferable mechanical property, and with plant
Entering material has stronger binding force, but it cannot directly induce bone growth, and the interface binding power between host bone is low,
It is easy to loosen, forms excessively high heat localization temperature when solidifying and easily cause surrounding tissue and spinal cord injury etc..Drawbacks described above limitation
Application range of the PMMA bone cement as treatment osteoporosis packing material.And after solidifying, PMMA material matrix is more
Densification, surface do not have stomata, to be unfavorable for growing into for tissue, osseointegration character is poor.Therefore, PMMA bone water how is improved
Mud makes it not only retain its excellent mechanical property, but also can promote bone growth, increases the knot between host's osteocyte
With joint efforts；Reduce the highest solidification temperature in its solidification process；And/or improvement PMMA material does not have stomata, is unfavorable for tissue and grows into
Defect be this field important subject.
Studies have shown that the strong chemical bonding of one kind is established between artificial substituting material and natural bone tissue it is necessary in material
Class bone transition zone is formed between material and bone, i.e., it is similar to bone tissue ingredient (calcium phosphorus).Apatite materials, if calcium phosphate is made pottery, hydroxyl phosphorus
Lime stone, tricalcium phosphate are contacted with solution containing phosphate, can be with class bone inorganic constituents, thus with bone shape in bone tissue Surface Creation
At firm chemical bonding.Phosphorus ash stone bone renovating material have excellent bioactivity and osteoconductive energy, can repair by
Bone is damaged, there is excellent Bone Defect Repari performance.
Strontium-incorporated hydroxyapatite (Sr-HA) is on the basis of hydroxyapatite, with calcium in strontium substituted hydroxy apatite structure
Position be prepared.Compared with traditional apatite, strontium-incorporated hydroxyapatite not only has bioactivity, and osteoconductive and bone are repaired
Renaturation energy, and there is superior osteogenic ability, it can be as the therapeutic agent of osteoporosis.Strontium (Sr) is in the intracorporal bone of people
There is double action in bone metabolic process, inhibits osteoclastic absorption while New born formation can be stimulated.Strontium (Sr) is from strontium hydroxyl phosphorus
Slow release enters local bone defect in grey stone substrate, promotes to inhibit osteoclastic absorption at Bone Defect Repari, can obtain preferably
Bone Defect Repari performance.
Living marine resources are one very huge, need the living resources deeply developed.Deep-sea tuna is exactly wherein
A kind of Typical Representative.Tuna fish-bone calcareous and phosphorus matter resource, minerals and determination of trace element result rich in
Show that tuna fish-bone not only contains a large amount of calcium and phosphorus, also such as containing other a variety of microelements that can effectively facilitate skeletonization
Strontium, boron, zinc, silicon, sodium, magnesium, copper, iron etc., and the content of strontium is significantly larger than in terrestrial animal.Calcium P elements be bone, tooth and
The important component of cartilaginous tissue, sodium, magnesium, zinc and iron also help to improve human immunity, maintain normal cell metabolism and participate in closing
At hemoglobin etc..And strontium is then the important microelement of skeletal metabolism, has stronger osteogenic ability, can treat sclerotin and dredge
Pine.Tuna is derived from deep-sea, and the pollution being subject to is seldom, is practically free of noxious material such as heavy metal element As, Pb, Hg and Cd etc.,
With excellent safety in utilization.Therefore, using deep-sea tuna as Research foundation, to deep-sea tuna fish-bone this kind ocean fishing
Industry waste carries out deep processing, obtains the natural bioactive ocean inorganic mineral that main component is strontium-incorporated hydroxyapatite, deep
Extra large tuna fishbone dust.The study found that the deep-sea tuna fishbone dust obtained by calcining deep-sea tuna fish-bone is than synthesis
Strontium active material has the ability of stronger osteoblast differentiation and proliferation.
CN104841016A discloses a kind of tuna fish-bone powder material and its preparation method and application, which shows by it
The tuna fish-bone powder material that method is prepared is good to osteoblastic proliferation effect, is a kind of excellent bioactive materials,
With stronger rush osteogenic ability.
Summary of the invention
In view of the defect of existing PMMA bone cement, the main purpose of the present invention is to provide one kind can form Composite Bone water
The composition of mud and the composite bone cement formed by it, at least one aspect in effectively solving the above problems.
As previously mentioned, tuna fishbone dust is a kind of excellent bioactive materials, with stronger rush osteogenic ability
Material, thus, if tuna fishbone dust can be introduced into PMMA bone cement, develop NEW TYPE OF COMPOSITE bone cement, it will have biography
The incomparable advantage of the PMMA bone cement of system, such as bioactivity, the effect of osteoacusis and induced osteogenesis, radiopacity with
And with the good osseointegration character of bone tissue.
Tuna fish-bone powder material is prepared by CN104841016A in an experiment in inventor, it is intended to mix it with PMMA
Conjunction prepares composite material, however discovery tuna fish-bone powder material can not uniformly mix in PMMA in testing.
By repeatedly Process Exploration and verifying, after a large amount of experimental work, inventor use hyaluronic acid, and by its
Microballoon is formed with tuna fishbone dust, efficiently solves the technical problem, the invention firstly uses tuna fishbone dusts and transparent
Matter acid has been made into microballoon, wherein tuna fishbone dust is wrapped in hyaluronic acid, this microballoon packing technology can be in tuna fish
Layer of transparent matter acid transition zone is established between bone meal and PMMA, mixes tuna fishbone dust with the uniform of PMMA.
Thus, on the one hand, the present invention provides a kind of composition that can form composite bone cement, wherein the composition packet
Containing the composition and tuna fishbone dust/hyaluronate microspheres for forming polymethyl acrylate (PMMA) bone cement；With described
The total weight that the composition of composite bone cement can be formed is 100% meter comprising the tuna fish that mass fraction is 8%~60%
Bone meal/hyaluronate microspheres, for example including 10%~50%, 15%~45%, 20%~40%, 25%~35% or 25%~
30% equal tuna fishbone dust/hyaluronate microspheres；
Tuna fishbone dust/the hyaluronate microspheres are prepared using tuna fishbone dust and hyaluronic acid as raw material
Microballoon, wherein by the total weight of tuna fishbone dust and hyaluronic acid be 100% in terms of, the quality of the tuna fishbone dust
Score is 30%~70%, such as 40%~60%, 50%~60% etc.；The mass fraction of the hyaluronic acid be 30%~
70%, such as 40%~60%, 50%~60% etc.；
Preferably, the partial size of the tuna fishbone dust/hyaluronate microspheres is 30 μm~500 μm, such as 40 μm~400
μm, 60 μm~350 μm, 100 μm~250 μm, 100 μm~200 μm, 160 μm~180 μm etc..
Tuna fishbone dust of the present invention is the fishbone dust being prepared by the fish-bone of tuna, including but not limited to
Technical solution disclosed in CN104841016A obtains tuna fish-bone powder material.
The composition of the present invention for forming polymethyl acrylate (PMMA) bone cement is the existing poly- methyl of formation
The composition of methyl acrylate bone cement, as previously mentioned, the composition generally includes solid phase pulvis and solidify liquid, in solid phase pulvis
Polymethyl methacrylate is generally included, generally includes methyl methacrylate in solidify liquid.
Hyaluronic acid used in the present invention is a kind of acid mucopolysaccharide.Hyaluronic acid is with its unique molecular structure and physics and chemistry
Matter shows a variety of important physiological functions in body, such as lubricating joint, adjusts the permeability of vascular wall, regulatory protein matter,
Water-Electrolyte diffusion and operating, promote wound healing etc..The present composition is formed into bone cement, and be injected into vivo after,
Hyaluronic acid used can leave hole after being degraded and absorb afterwards in vivo in situ, be conducive to cell and grow into what is organized, guarantee
Material can be with the better strand cable incarceration of host's bon e formation.
The composition that the present invention can form composite bone cement is combined in existing formation PMMA bone cement
It joined tuna fishbone dust/hyaluronate microspheres on the basis of object.The addition of tuna fishbone dust, imparts composite bone cement
Good bioactivity can enhance the combination of composite bone cement and host bone after being implanted into human body, have preferable Integrated implant
Energy；The addition of hyaluronic acid is conducive to cell and tissue so that hole can be formed in situ after implanting in composite bone cement
It grows into.Tuna fishbone dust not only contains calcium and phosphorus, also containing the other a variety of microelement that can effectively facilitate skeletonization such as strontiums,
Zinc, silicon, sodium, magnesium, copper, iron etc., and the content of strontium is higher, can effectively induction of bone growth.After implanting, in addition to that can discharge
Out outside the skeletal metabolisms important element such as strontium (Sr), calcium (Ca), phosphorus (P), a variety of microelements for effectively facilitating skeletonization such as magnesium, silicon
It can be precipitated in the form of an ion, the growth of osteocyte can be stimulated, there is preferable Bone Defect Repari effect；Tuna fishbone dust can have
Effect ground adhesion protein and cell, and it is converted into a part of bone tissue.Simultaneously experiments indicate that being formed by the composition
Composite bone cement also there is the mechanical strength to match with bone, combine tuna fishbone dust, hyaluronic acid and poly- methyl
The performance of methyl acrylate (PMMA), to achieve the effect that in terms of promoting Bone Defect Repari be more good.
In addition to especially indicating, ratio of the present invention or score each mean mass ratio or mass fraction.
Preferentially, as a specific embodiment of the invention, the composition of composite bone cement can be formed described in sheet
Total weight be 100% meter, be previously formed polymethyl acrylate bone cement composition include mass fraction be 6.4%~
59.625% polymethyl methacrylate powder, such as 10%~55%, 15%~50%, 20%~45%, 25%~
40%, 30%~40% etc.；The polymerization initiator that mass fraction is 0.2%~3%, such as 0.5%~2.5%, 0.8%~
2.0%, 1.0%~1.5% etc.；Mass fraction be 24.25%~59.94% methyl methacrylate, such as 25%~55%,
30%~50%, 35%~45%, 40%~45% etc.；And the polymeric activator that mass fraction is 0.025%~1.8%,
Such as 0.05%~1.5%, 0.10%~1.2%, 0.5%~1.5%, 0.5%~1.0% etc.；
Preferably, the partial size of the polymethyl methacrylate powder is 40 μm~80 μm, such as 40 μm~60 μm, 50 μm
~70 μm, 60 μm~80 μm etc.；
Preferentially, the polymerization initiator includes dibenzoyl peroxide；The polymerization activator includes N, N- dimethyl
Para-totuidine；
Selectively, the composition further includes drug, it is preferable that the drug includes antibiotic medicinal powder, such as sulfuric acid
Gentamicin or rifampin medicinal powder；Preferably, solid phase pulvis described in every 1g loads the drug of 2~300mg.
Above-mentioned composition is prepared and to form composite bone cement or slurry and can make its biomechanical strength, bioactivity, biology
Compatibility, syringeability and setting time reach excellent balance.In addition, present inventors have unexpectedly found that, it is formed by above-mentioned composition
The highest solidification temperature of composite bone cement slurry be substantially reduced, significantly reduce in bone cement application process to surrounding tissue and
The damage of spinal cord.
The amount priority acccess control of present composition each component may make the bone formed by the composition in aforementioned range
Cement slurry and excellent balance is reached by the multiple performance of its bone cement formed.Such as tuna fishbone dust/hyaluronic acid
Microballoon priority acccess control is in aforementioned range, when the mechanical property that its additional amount excessively will affect composite bone cement cannot be applied instead
In Bone Defect Repari field.The same priority acccess control of the additional amount of PMMA is in aforementioned range, although simple polymethyl methacrylate
(PMMA) bone cement has certain biocompatibility and higher mechanical property, but PMMA additional amount is excessively high will affect Composite Bone
The bioactivity of cement.In another example the additional amount of monomer MMA, polymerization initiator and polymerization activator are preferably controlled in aforementioned range
It is interior.During self-curing is realized in monomer MMA and PMMA copolymerization, the participation of polymerization initiator and polymerization activator is needed.Work as component
In polymerization initiator and when inappropriate polymerization activator content, the composite bone cement slurry or solidification speed of the injectable of invention
It is excessively slow to spend fast or curing rate.Curing rate is too fast, and in operation, bone cement cannot be timely implanted by user
In vivo；When curing rate is excessively slow, the bone cement slurry not being fully cured is easy to be broken up by blood flow or body fluid, causes embolism, right
Patient causes life danger, therefore appropriate composition designs so that the composite bone cement slurry of injectable has optimal clinic to make
With physicochemical property and technological difficulties of the invention.By the adjusting of each component additional amount, so that by composition of the present invention
The complex cement of formation not only has good biomechanical strength, also has good bioactivity and biocompatibility, institute
Bone growth promotion element such as strontium, calcium, phosphorus etc. can be released in vivo by obtaining the tuna fishbone dust in composite bone cement matrix, and
Can pneumoradiography it is not necessary that additional developer (such as barium sulfate, zirconium oxide) is added have safer service performance.
Specific embodiment according to the present invention, in composition of the present invention, the tuna fishbone dust/hyalomitome
Sour microballoon is prepared as follows to obtain:
(a) aqueous solution containing the tuna fishbone dust and the hyaluronic acid, the shape preferably at 30 DEG C~50 DEG C are formed
At the aqueous solution；
(b) step (a) obtained aqueous solution is spray-dried in 100~150 DEG C of temperature ranges, the gold is made
Marlin fishbone dust/hyaluronate microspheres；
Preferably, pass through the size of the size Control microballoon of the concentration and nozzle of adjusting solution.
Based on being described above, the present invention also can provide a kind of composition that can form composite bone cement, wherein the composition
Including solid phase pulvis and solidify liquid；It is the quality point of the solid phase pulvis in terms of 100% by the sum of solid phase pulvis and solidify liquid weight
Number is 40%~75%, such as 45%~70%, 50%~65%, 55%~60% etc.；The mass fraction of the solidify liquid is
25%~60%, such as 30%~60%, 35%~55%, 40%~50%, 45%~50% etc.；
It is in terms of 100% by the weight of the solid phase pulvis comprising the tuna fish-bone that mass fraction is 20%~80%
Powder/hyaluronate microspheres, such as 30%~70%, 40%~60%, 50%~60% tuna fishbone dust/hyaluronic acid are micro-
Ball；
Tuna fishbone dust/the hyaluronate microspheres are prepared using tuna fishbone dust and hyaluronic acid as raw material
Microballoon, wherein by the total weight of tuna fishbone dust and hyaluronic acid be 100% in terms of, the quality of the tuna fishbone dust
Score is 30%~70%, such as 40%~60%, 50%~60% etc.；The mass fraction of the hyaluronic acid be 30%~
70%, such as 40%~60%, 50%~60% etc.；
Preferably, the partial size of the tuna fishbone dust/hyaluronate microspheres is 30 μm~500 μm, such as 40 μm~400
μm, 60 μm~350 μm, 100 μm~250 μm, 100 μm~200 μm, 160 μm~180 μm etc.；
Selectively, the solid phase pulvis further includes drug, it is preferable that the drug includes antibiotic medicinal powder, such as sulphur
Sour gentamicin or rifampin medicinal powder；Preferably, solid phase pulvis described in every 1g loads the drug of 2~300mg；
Preferably, the tuna fishbone dust/hyaluronate microspheres are prepared as follows to obtain:
(a) aqueous solution containing the tuna fishbone dust and the hyaluronic acid is formed；
(b) step (a) obtained aqueous solution is spray-dried in 100~150 DEG C of temperature ranges, the gold is made
Marlin fishbone dust/hyaluronate microspheres；
Preferably, pass through the size of the size Control microballoon of the concentration and nozzle of adjusting solution.
As a specific embodiment of the invention, it is in terms of 100% by the weight of the solid phase pulvis, further includes quality
The polymethyl methacrylate powder that score is 16%~79.5%, such as 20%~75%, 25%~70%, 30%~65%
Deng polymethyl methacrylate powder；And the polymerization initiator that mass fraction is 0.5%~4%, such as 0.5%~3.5%,
1.0%~3.0%, 1.5%~2.5% etc. polymerization initiator；
Preferably, the partial size of the polymethyl methacrylate powder is 40 μm~80 μm, such as 40 μm~60 μm, 50 μm
~70 μm, 60 μm~80 μm etc.；
Preferably, the polymerization initiator includes dibenzoyl peroxide.
It is 40%~75% when controlling the mass percent of the solid phase pulvis in the composition, the solidify liquid
Mass fraction is 25%~60%；The tuna fishbone dust/mass percent of the hyaluronate microspheres in solid phase pulvis be
20%~80%, mass percent of the polymethyl methacrylate in solid phase pulvis is 16%~79.5%, described
, it can be achieved that the excellent balance of aforementioned each performance when mass percent of the polymerization initiator in solid phase pulvis is 0.5%~4%.
It is in terms of 100% by the weight of the solidify liquid comprising mass fraction as a specific embodiment of the invention
The polymerization activator that methyl methacrylate and mass fraction for 97%~99.9% are 0.1%~3%；
Preferably, the polymerization activator includes N, N- dimethyl-p-toluidine.
On the other hand, the present invention provides a kind of composite bone cement slurry, is by shape described in aforementioned composition of the present invention
The fishbone dust of tuna described in composition and corresponding technical solution at polymethyl acrylate bone cement/hyaluronic acid is micro-
The composite bone cement slurry of injectable is made in the composition that ball mixing can form composite bone cement；Or
It is the composite bone cement slurry that the composition of the present invention for forming composite bone cement is made to injectable；
Wherein, in corresponding technical solution, the tuna fishbone dust/hyaluronate microspheres, the polymethyl methacrylate powder
And the polymerization initiator is added in the form of pulvis, the methyl methacrylate and the polymeric activator are with liquor
Form is added；Or
It is by the composition of the present invention for forming composite bone cement the solid phase pulvis and the solidification
Liquid mixing, forms the composite bone cement slurry of injectable.
Preferably, the above-mentioned mixed time is 1~2min.
In another aspect, the present invention provides a kind of composite bone cement, it is composite bone cement slurry solidification 5 of the present invention
~25min is obtained.The polymerization reaction generation composite bone cement occurs for each component in slurry.
From the foregoing, it will be observed that the present invention provides a kind of composite bone cement slurry of injectable and the Composite Bone water formed by it
Mud, the raw material for forming the composite bone cement slurry of the injectable may include solid phase pulvis and solidify liquid, solid phase pulvis and solidification
Liquid obtains composite bone cement by polymerization reaction.
As a specific embodiment of the invention, the preparation method of composite bone cement slurry and composite bone cement includes such as
Lower step:
(1) preparation of solid phase pulvis
The preparation of tuna fishbone dust:
Tuna fish-bone to be cleaned, after crushing, through gradually temperature-raising method, high-temperature calcination fish-bone regulates and controls temperature to 850 DEG C,
Gradually quickly organic phase is volatilized, remains inorganic constituents；
The key point of this step is the regulation by temperature, the crystallinity of fish-bone inorganic phase is controlled, to prevent inorganic crystalline substance
Body accompany temperature increase caused by crystal grain grow up, and then influence degradation rate.Sintered fishbone dust using vibrating pulverizer,
The equipment such as airslide disintegrating mill, vibration screen-dividing machine are further crushed and classified, and obtain tuna fishbone dust powder；
The preparation of tuna fishbone dust/hyaluronate microspheres
Hyaluronic acid is dissolved in water, 40 DEG C are uniformly mixed for temperature constant magnetic stirring 1~3 hour, then by the tuna of preparation
Fishbone dust is gradually added into hyaluronic acid solution, again 40 DEG C temperature constant magnetic stirring 2~5 hours, it is to be mixed uniformly after, utilize spray
Mist drier drying-granulating prepares tuna fishbone dust/hyaluronate microspheres, and wherein the size of microballoon is by adjusting the dense of solution
The size Control of degree and nozzle；
Tuna fishbone dust/hyaluronate microspheres, polymethyl methacrylate powder, polymerization initiator are mixed, obtained
Solid phase pulvis；Wherein, the polymerization initiator includes dibenzoyl peroxide；Tuna fishbone dust/the hyaluronate microspheres
Mass percentage in solid phase pulvis is 20%~80%, and the polymethyl methacrylate powder is in solid phase pulvis
Weight percentage is 16%~79.5%, and weight percentage of the polymerization initiator in solid phase pulvis is 0.5%
~4%；
(2) preparation of solidify liquid:
Polymerization activator is added in liquid methyl methacrylate, is uniformly mixed, obtains solidify liquid, wherein is described poly-
Closing activator includes N, N- dimethyl-p-toluidine；
(3) preparation of the composite bone cement slurry of injectable:
The mass percent that the solid phase pulvis and the solidify liquid weight gross weight are accounted for according to the solid phase pulvis is 40%
~75%, it is 20%~60% that the solidify liquid, which accounts for the solid phase pulvis and the mass percent of the solidify liquid weight gross weight,
Solid phase pulvis obtained above and solidify liquid are mixed, the composite bone cement slurry of injectable is formed.
After the composite bone cement is the composite bone cement slurry for obtaining the injectable by step (3), keep it solid
Change what 5min~25min was obtained.
Preferably, in step (1), the partial size of the tuna fishbone dust/hyaluronate microspheres is 30 μm~500 μm.
Preferably, in step (1), the partial size of polymethyl methacrylate (PMMA) powder is 40 μm~80 μm.
Preferably, the solid phase pulvis further includes medicament powder.When medicament powder to be added in solid phase pulvis, mixed
Close solid phase.The medicament powder includes but is not limited to the antibiotic medicines such as gentamicin sulphate, rifampin.Preferably, the medicine
The useful load of powder is the medicament powder that 1g solid phase pulvis loads 2mg~300mg, and solid phase pulvis refers to not comprising drug herein
Powder.
Preferably, in step (2), weight percentage of the methyl methacrylate (MMA) in the solidify liquid
It is 97%~99.9%.
Preferably, in step (2), weight percentage of the polymerization activator in the solidify liquid be 0.1%~
3%.
Preferably, in step (3), the mixed time is 1min~2min.
The preparation method of the composite bone cement slurry of injectable provided by the invention, the solid phase powder and the solidify liquid
It at mixing initial stage, obtains being paste slurry, this paste slurry has plasticity and syringeability, and due to metering system
Sour methylmethacrylate monomer carries out Raolical polymerizable under the action of polymerization activator, polymerization initiator, obtains polymethylacrylic acid
The condensate of methyl esters, the paste slurry can voluntarily solidify, and form the solid with certain mechanical strength and Bone Defect Repari ability,
The solid is using the polymethyl methacrylate that polymerization reaction is formed as matrix, the tuna fishbone dust/hyalomitome
Sour microballoon is homogeneously dispersed in inside and the surface of described matrix to get composite bone cement is arrived.
By adjusting the composition of the solid phase powder and the solidify liquid, excellent mechanical performances can be prepared and had simultaneously
The composite bone cement or its slurry of good bioactivity, osteoacusis and repair ability.The preparation of the composite bone cement
Method is simple to operation, and moulding is convenient, polymerization temperature is low, and convenient for application, which has been provided simultaneously with tuna fish-bone
The excellent properties of powder, hyaluronic acid and PMMA.
In another aspect, the present invention provides composition or the composite bone cement slurry or described compound of the present invention
Bone cement is preparing the application in bone renovating material；Preferably, the bone renovating material include bone tissue packing material and/or
Timbering material.
Preferably, the application includes the following steps:
The composite bone cement slurry of injectable is prepared by abovementioned steps (1)~(3), then answering gained injectable
It closes bone cement slurry and pours into injector for medical purpose immediately, be injected into bone tissue position to be repaired.The application of composite bone cement of the present invention
Mode is simple, simplifies osseous surgery operation, convenient for reducing the pain of patient.
Compared with prior art, the invention has the following advantages:
(a) present invention is the waste to the fishing industry of ocean tuna, and tuna fish-bone carries out deep processing, added value
Height can not only promote the comprehensive utilization of aquatic products processing waste, improve the output value, but also can reduce the pollution to environment,
With preferable restoring ecological environment.
(b) composite bone cement composition provided by the invention is joined on the basis of PMMA bone cement
Tuna fishbone dust/the hyaluronate microspheres for promoting bone uptake, combine the property of tuna fishbone dust, hyaluronic acid and PMMA
Can, composite bone cement obtained has excellent bioactivity, biocompatibility, osseointegration character, can be used as Bone Defect Repari and controls
Treat integrated composite tissue engineering bracket.
(c) compared with traditional PMMA bone cement, composite bone cement of the invention, which has, to be substantially reduced
Highest solidification temperature, so as to avoid in traditional PMMA solidification process heat release the thermal damage caused by host tissue.
(d) compared with traditional PMMA bone cement, the compression strength of composite bone cement of the invention is bright
Aobvious is lower than traditional PMMA bone cement, but can more match the mechanical strength of bone, can be effectively reduced traditional
Mechanics screen effect of the PMMA bone cement to bone tissue.
(e) compared with traditional PMMA bone cement, after composite bone cement of the invention implants, material
After hyaluronic acid in material matrix is degraded and absorbs, hole can be formed in situ, to be conducive to cell and tissue grows into material
Matrix is expected, to guarantee that material can be with the better strand cable incarceration of host's bon e formation.
(f) preparation method of composite bone cement provided by the invention is simple to operation, and moulding is convenient, polymerization temperature is low, just
In application.
(g) composite bone cement of the present invention can also carrying medicament, can be further improved it in bone renovating material
Application effect, application mode is simple, simplifies osseous surgery operation, convenient for reducing the pain of patient.
Detailed description of the invention
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technical description to be briefly described, it should be apparent that, the accompanying drawings in the following description is only this
Some embodiments of invention for those of ordinary skill in the art without creative efforts, can be with
It obtains other drawings based on these drawings.
Fig. 1 a, Fig. 1 b are respectively the microscopic appearance and XRD spectrum for the tuna fishbone dust prepared in the embodiment of the present invention；
Fig. 2 is PMMA powder microscopic appearance and granular size used in the embodiment of the present invention 1；
Fig. 3 be the embodiment of the present invention 1 in preparation-obtained tuna fishbone dust/hyaluronate microspheres microscopic appearance and
Size；
Fig. 4 is the intensity test result figure of composite bone cement and control group bone cement in the embodiment of the present invention 1；
Fig. 5 is composite bone cement and highest solidification temperature in the solidification process of control group bone cement in the embodiment of the present invention 1
Result figure；
Fig. 6 is the cytotoxicity experiment knot of composite bone cement and blank group, the bone cement of control group in the embodiment of the present invention 1
Fruit figure；
Fig. 7 is the syringeability test result figure of the composite bone cement slurry of injectable in the embodiment of the present invention 2, wherein horizontal
Coordinate is the mass ratio of solid phase pulvis and solidify liquid；
Fig. 8 is the setting time test result figure of the composite bone cement slurry of injectable in the embodiment of the present invention 3, wherein horizontal
Coordinate is the mass ratio of solid phase pulvis and solidify liquid；
Fig. 9 is that composite bone cement made from the embodiment of the present invention 1 loads the vitro drug release song after gentamicin sulphate
Line.
Specific embodiment
Technical solution of the present invention is clearly and completely described below in conjunction with attached drawing.Obviously, described implementation
Example is only a part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, this field is common
Technical staff's every other embodiment obtained without creative efforts belongs to the model that the present invention protects
It encloses.
In following embodiment of the present invention, polymethyl methacrylate (PMMA) powder is using suspension polymerisation legal system
It is standby, but not limited to this.Specifically, comprising the following steps:
Under high velocity agitation, 0.5 gram of PVA is added in distilled water, 0.5 gram of dibenzoyl peroxide is added after a period of time
(BPO), 50 milliliters of methyl methacrylates (MMA) and 10 milliliters of methyl acrylate (MA) monomers are then added, are warming up to 70 DEG C,
Keep the temperature 20~30min；80 DEG C are continuously heating to, keeps the temperature 60~70min, then be warming up to 98 DEG C, keeps the temperature 30min.Gained is suspended
Liquid is poured into beaker and is stood, and is removed upper layer mother liquor, is washed filtering repeatedly with distilled water.Then filtered product will be washed to set
It is dry in 40 DEG C of baking oven, it is ground up, sieved after dry, obtains the white PMMA powder that granulometric range is 40~80 μm.
In following embodiment of the present invention, the tuna fish-bone powder material is high-temperature calcination preparation, but not limited to this.Tool
Body, comprising the following steps:
Tuna fish-bone is cleaned, after crushing, through gradually temperature-raising method, high-temperature calcination fish-bone.Temperature is regulated and controled to 850 DEG C,
Gradually quickly organic phase is volatilized, remains inorganic constituents.The key point of this step is the regulation by temperature, control fish-bone without
The crystallinity of machine phase, with prevent mineral crystal accompany temperature increase caused by crystal grain grow up, and then influence degradation rate.Sintering
Fishbone dust afterwards is further crushed and classified using equipment such as vibrating pulverizer, airslide disintegrating mill, vibration screen-dividing machines, chooses particle
Diameter is located at 10~20 μm of tuna fishbone dust powder, the microscopic appearance and XRD spectrum point of gained tuna fishbone dust powder
Not as shown in Fig. 1 a and Fig. 1 b.
In following embodiment of the present invention, the tuna fishbone dust/hyaluronate microspheres are spray drying process preparations, but not
It is limited to this.Specifically, comprising the following steps:
4g hyaluronic acid is dissolved in 40g water, 40 DEG C are uniformly mixed for temperature constant magnetic stirring 2 hours.Then 6g is pressed into above-mentioned side
The tuna fishbone dust of method preparation is gradually added into hyaluronic acid solution, again 40 DEG C temperature constant magnetic stirring 3 hours, to be mixed equal
After even, under the conditions of 120 DEG C, using spray dryer drying-granulating, prepare tuna fishbone dust that partial size is 30~500 μm/
Hyaluronate microspheres, wherein the mass percent of tuna fishbone dust is 60%, and the mass percent of hyaluronic acid is 40%.
Embodiment 1
The present embodiment provides the composition that can form composite bone cement and the bone cements formed by it, specifically, can embody
In the preparation method of following composite bone cements or its slurry, this method comprises the following steps:
Polymethyl methacrylate (PMMA) powder for being 40~60 μm by the partial size that preceding method is prepared is chosen,
The microscopic appearance and granular size of PMMA powder are shown in Fig. 2.The natural tuna fishbone dust that selection is prepared by preceding method/thoroughly
Bright matter acid microballoon, wherein the mass percent of tuna fishbone dust is 60%, and partial size is about 150 μm, and microscopic appearance is shown in Fig. 3 institute
Show.By natural tuna fishbone dust/hyaluronate microspheres obtained above and PMMA powder, polymerization initiator diphenyl peroxide first
Acyl (BPO) is mixed according to the mass ratio of 30%:68%:2%, and the solid phase pulvis of composite bone cement is obtained after sterilized；
(2) preparation of solidify liquid:
According to the mass percent of 0.1%:99.9% by N, N- dimethyl-p-toluidine (DMPT) and liquid metering system
Sour methyl esters (MMA) is uniformly mixed, and prepares the solidify liquid of composite bone cement；
(3) preparation of composite bone cement:
Solid phase pulvis obtained above and solidify liquid are taken, is according to mass percent by solid phase pulvis and solidify liquid
The ratio of 66.7%:33.3% carries out mixing 2 minutes, after mixing, forms the composite bone cement slurry of injectable, obtaining can
The composite bone cement slurry of injection.
The intensity test of 1 composite bone cement of effect example:
The composite bone cement slurry of injectable made from Example 1 is filled with solidifying 10min in mold, juxtaposition
It is conserved one day in 37 DEG C, the climatic chamber that humidity is 99%, using obtained composite bone cement product as experimental group sample；
Control group is the ratio for being 66.7%:33.3% according to mass percent by PMMA powder used in embodiment 1 and solidify liquid used
Example mixing, the PMMA bone cement being prepared (without tuna fishbone dust/hyaluronate microspheres PMMA bone cement).
Used experimental group, the cylindrical body that control sample is high 12 millimeters, 6 millimeters of diameter in intensity test.
The compression strength of sample is detected respectively using by almighty test machine, pressure head rate is 0.5mm/min.Compression is strong
(compression strength) result such as Fig. 4 is spent, the compressive strength of experimental group bone cement is 82.3 ± 3.2MPa, the resistance to compression of control group bone cement
Intensity is 94 ± 4.5MPa.The intensity of experimental group bone cement is less than control group bone cement, closer to the compression strength of bone, separately
(compression performance of experimental group bone cement reaches such bone cement as defined in standard YY 0459-2003/ISO 5833:2002 outside
Minimum standard (> 70MPa).
The highest solidification temperature of the composite bone cement slurry of 2 injectable of effect example in the curing process
The composite bone cement slurry of injectable made from Example 1 is as experimental group sample；Control group is by embodiment 1
In PMMA powder used and solidify liquid used mixed according to the ratio that mass percent is 66.7%:33.3%, be prepared
PMMA bone cement slurry (without tuna fishbone dust/hyaluronate microspheres PMMA bone cement slurry).
Bone cement slurry is placed in polyethylene mold, and test environment is 20 DEG C, utilizes micro- calorimeter (Voltcraft
Data-Logger K202, Conrad Electronics, Germany) the bone cement slurry of measurement experiment group and control group exists
Highest solidification temperature in solidification process.Highest solidification temperature result such as Fig. 5 of solidification process, the highest solidification temperature of experimental group
It is 74.38 ± 4.13 DEG C, and control group PMMA bone cement slurry is (without tuna fishbone dust/hyaluronate microspheres PMMA bone
Cement slurry) highest solidification temperature be 89.56 ± 6.86 DEG C, the highest solidification temperature of experimental group is significantly lower than control group.
The cytotoxicity test of 3 composite bone cement of effect example:
The composite bone cement slurry of injectable made from Example 1 is filled with solidifying 10min in mold, juxtaposition
It is conserved one day in 37 DEG C, the climatic chamber that humidity is 99%, using obtained composite bone cement product as experimental group sample；
Control group be then PMMA bone cement (without tuna fishbone dust/hyaluronate microspheres PMMA bone cement) its be by embodiment 1
PMMA powder used and solidify liquid used are mixed according to the ratio that mass percent is 66.7%:33.3%, are prepared
PMMA bone cement (without tuna fishbone dust/hyaluronate microspheres PMMA bone cement).
Used experimental group, control sample are 10 millimeters of diameter in cytotoxicity test, high 2 millimeters of disk.Institute
There is cytotoxicity test all to select leaching liquor test method according to GB/T16886.5-2003, according to GB/T14233.2-2005
The mtt assay recommended in " cell toxicity test " is tested.Detailed process is as follows:
(1) cell culture is carried out first: the L929 fibroblast frozen being taken recover-cultivate-pass on-cultivate
Process, (needed under normal condition 5-6 days) when cell reaches the third generation, it is stand-by to cell dissociation.
(2) followed by leaching liquor prepares: using leaching liquor test method, experiment with computing group, control group bone cement sample weight
The transformational relation of amount and surface area, using DMEM cell culture fluid (containing 15% fetal calf serum), to extract ratio 6cm2/ ml, 37
DEG C, the leaching liquor of experimental group, control group is prepared for 24 hours.
It is 1 × 10 by prepared density4The cell suspension inoculation of/ml is in 96 orifice plates, every 100 μ l of hole, and blank is arranged
Group (leaching liquor is not added in only cell culture fluid), experimental group, control group, every group is at least inoculated with 3 holes, is containing 5% carbon dioxide
Under the conditions of, after 37 DEG C of cultures for 24 hours, culture solution is discarded, blank group is exchanged with cell culture fluid, and experimental group and control group are used respectively respectively
It is exchanged from leaching liquor.It is placed in 5% carbon dioxide incubator after 37 DEG C of culture 72h, adds MTT to continue to cultivate 4h, in microplate reader
Absorbance is measured at 570nm and 630nm.Using the absorbance of blank group as standard, calculates opposite proliferation rate (RGR), sentenced according to RGR
The cell-cytotoxic reaction rank of disconnected experimental group and control sample.The test result of cytotoxicity such as Fig. 6, compared to the blank group,
The cell survival rate of experimental group and control group is above 80%, this illustrates that composite bone cement has lower cytotoxicity, i.e., good
Good biocompatibility.
Embodiment 2
The present embodiment provides the bone cements that can be formed composition and be formed by it, specifically, may be embodied in following Composite Bones
In the preparation method of cement or its slurry, this method comprises the following steps:
(1) preparation of solid phase pulvis:
Choose polymethyl methacrylate (PMMA) powder and grain that are 60-80 μm by the partial size that preceding method is prepared
Diameter is 40~80 μm of tuna fishbone dust/hyaluronate microspheres.By PMMA, tuna fishbone dust/hyaluronate microspheres and it polymerize
Initiator dibenzoyl peroxide (BPO) mixes according to the mass ratio of 60%:39%:1%, Composite Bone water is obtained after sterilized
The solid phase pulvis of mud；
(2) preparation of solidify liquid:
According to the mass percent of 1.5%:98.5% by N, N- dimethyl-p-toluidine (DMPT) and liquid metering system
Sour methyl esters (MMA) is uniformly mixed, and prepares the solidify liquid of composite bone cement；
(3) preparation of composite bone cement:
Solid phase pulvis obtained above and solidify liquid are taken, is according to mass percent respectively by solid phase pulvis and solidify liquid
40%:60%, 50%:50%, 60%:40%, 63%:33.3%, 75%:25% ratio (i.e. mass ratio be respectively 2:3,
1:1,3:2,2:1,3:1) mixing 1 minute is carried out, after mixing, obtain the composite bone cement slurry of 5 groups of injectables.
The syringeability of the composite bone cement slurry of 4 injectable of effect example is tested:
The composite bone cement slurry of 5 groups of injectables made from Example 2 utilizes injector for medical purpose characterization injectable
The syringeability energy of composite bone cement: the weight M0 of syringe, composite bone cement slurry are placed in syringe before precise is tested
In weight M1 and bone cement slurry squeeze out injector for medical purpose after weight M2, utilize formula J%=[(M1-M2) ÷ (M1-
M0)] × 100% come calculate injectable composite bone cement slurry syringeability energy J%, as a result see Fig. 7.
From figure 7 it can be seen that the composite bone cement slurry of all components has good syringeability energy.With Composite Bone
The content of solid phase pulvis increases in cement, and the syringeability of composite bone cement slurry first gradually increases, from 80.22 ± 3.76%
(mass ratio 2:3) increase be 98.98 ± 5.88% (mass ratio 2:1), in composite bone cement solid phase pulvis mass ratio into
One step increases, and the syringeability of composite bone cement slurry reduces, and is 84.16 ± 6.97 (mass ratio 3:1).Fig. 7 shows Ke Yitong
The mass ratio of solid phase pulvis and solidify liquid in composite bone cement is overregulated, the Composite Bone for being suitable for the injectable of clinical application is made
Cement slurry.
Embodiment 3
The present embodiment provides the composition that can form composite bone cement and the bone cements formed by it, specifically, can embody
In the preparation method of following composite bone cements or its slurry, this method comprises the following steps:
(1) preparation of solid phase pulvis:
Choose polymethyl methacrylate (PMMA) powder for being 60-80 μm by the partial size that preceding method is prepared, grain
Tuna fishbone dust/the hyaluronate microspheres and polymerization initiator dibenzoyl peroxide (BPO) that diameter is 100~200 μm, according to
The mass ratio of 5%:93.5%:1.5% mixes, and the solid phase pulvis of composite bone cement is obtained after sterilized；
(2) preparation of solidify liquid:
According to the mass percent of 3%:97% by N, N- dimethyl-p-toluidine (DMPT) and methyl methacrylate
(MMA) it is uniformly mixed, prepares the solidify liquid of composite bone cement；
(3) preparation of composite bone cement:
Solid phase pulvis obtained above and solidify liquid are taken, is according to mass percent respectively by solid phase pulvis and solidify liquid
40%:60%, 50%:50%, 60%:40%, 66.7%:33.3%, 75%:25% ratio (i.e. mass ratio is respectively 2:
3,1:1,3:2,2:1,3:1) mixing 1 minute is carried out, after mixing, after mixing, obtain the Composite Bone water of 5 groups of injectables
Slurry body.
The setting time of the composite bone cement slurry of 6 injectable of effect example is tested:
The composite bone cement slurry of 5 groups of injectables, is filled in mold made from Example 3, be placed in 37 DEG C,
It is conserved in the climatic chamber that humidity is 99%, when measuring the solidification of the composite bone cement slurry of injectable using cement consistency instrument
Between, as a result such as Fig. 8.
From figure 8, it is seen that with the increase of solid phase pulvis mass content in composite bone cement, composite bone cement slurry
Setting time gradually increase, increased to from 7.45 ± 0.76 minutes 9.76 ± 0.97 minutes.The Composite Bone of above 5 groups of injectables
Cement all meets the minimum standard of such bone cement setting time as defined in standard YY 0459-2003/ISO 5833:2002.
Application Example 1
The composite bone cement of injectable is used for pharmaceutical carrier, carries antibiotic medicine:
(1) the solid phase pulvis and solidify liquid of composite bone cement are prepared according to the method for embodiment 1；
(2) solid phase pulvis obtained above is uniformly mixed with antibiotic medicine-gentamicin sulphate, it is solid as mixing
Phase, the useful load of drug are as follows: 1g solid phase pulvis loads 100mg drug.Weigh 4g solid phase pulvis and 400mg antibiotic medicine-sulphur
The mixed powder of sour gentamicin, and solidify liquid made from 2g is measured, it is (i.e. mixed according to the solid phase pulvis containing gentamicin sulphate
Close solid phase) it is mixed with solidify liquid mass percent for 66.7% and 33.3%, preparation carries medicine composite bone cement slurry, will make
The load medicine composite bone cement slurry obtained is filled into mold, and 10 millimeters of diameter, high 2 millimeters of composite bone cement disc examination is made
Sample.
4 composite bone cement disc samples (parallel laboratory test) are soaked in the phosphate buffer solution (PBS) of 10ml, and
It is placed in 37 DEG C, the climatic chamber that humidity is 99%.With the extension of soaking time, the antibiolics in medicine composite bone cement is carried
Object-gentamicin sulphate can be gradually released in PBS, utilize the tired of the drug in high speed liquid chromatography (HPLC) measurement PBS
Meter release content, the result of drug release are as shown in Figure 9.
From fig. 9, it can be seen that the release of drug is very fast at the initial stage of immersion, and after impregnating 5 hours, the initial load of drug release
The 23% of medicine total amount, total volume is 37% after 10 hours.Then, drug release rate is gradually reduced.Pharmaceutical release time is held
Continue up to 400 hours, after impregnating 400 hours, the total volume of drug is 85%.Therefore, composite bone cement can also be carried as drug
Body, drug release rate is moderate, meets clinical requirement, thus promoting it to reach be more good effect in terms of Bone Defect Repari
Fruit.
The present invention is described in detail above, its object is to allow the personage for being familiar with this field technology that can understand this
The content of invention is simultaneously implemented, and it is not intended to limit the scope of the present invention, all Spirit Essence institutes according to the present invention
The equivalent change or modification of work, should be covered by the scope of protection of the present invention.
Claims (23)
1. the composition that one kind can form composite bone cement, wherein the composition includes to form polymethyl acrylate bone
Composition and tuna fishbone dust/hyaluronate microspheres of cement；With the gross weight of the composition for forming composite bone cement
Amount is 100% meter comprising tuna fishbone dust/hyaluronate microspheres that mass fraction is 8%~60%；
Tuna fishbone dust/the hyaluronate microspheres be prepared with hyaluronic acid as raw material using tuna fishbone dust it is micro-
Ball, wherein by the total weight of tuna fishbone dust and hyaluronic acid be 100% in terms of, the mass fraction of the tuna fishbone dust
It is 30%~70%, the mass fraction of the hyaluronic acid is 30%~70%；
The partial size of the bone meal tuna fishbone dust/hyaluronate microspheres is 30 μm~500 μm.
2. the composition according to claim 1 for forming composite bone cement, wherein with the combination of the composite bone cement
The total weight of object is 100% meter, and the composition for forming polymethyl acrylate bone cement includes that mass fraction is 6.4%
~59.625% polymethyl methacrylate powder；The polymerization initiator that mass fraction is 0.2%~3%；Mass fraction is
The polymeric activator that 24.25%~59.94% methyl methacrylate and mass fraction are 0.025%~1.8%.
3. the composition according to claim 2 for forming composite bone cement, wherein the polymethyl methacrylate powder
The partial size of body is 40 μm~80 μm.
4. the composition according to claim 2 for forming composite bone cement, wherein the polymerization initiator includes peroxide
Change dibenzoyl；The polymerization activator includes N, N- dimethyl-p-toluidine.
5. the composition according to claim 1 or 2 for forming composite bone cement, wherein the tuna fishbone dust/thoroughly
Bright matter acid microballoon is prepared as follows to obtain:
(a) aqueous solution containing the tuna fishbone dust and the hyaluronic acid is formed；
(b) step (a) obtained aqueous solution is spray-dried in 100~150 DEG C of temperature ranges, the tuna is made
Fishbone dust/hyaluronate microspheres.
6. the composition according to claim 5 for forming composite bone cement, wherein by adjust solution concentration and/
Or the size of microballoon described in the size Control of nozzle.
7. the composition that one kind can form composite bone cement, wherein the composition includes solid phase pulvis and solidify liquid；With solid phase powder
The sum of agent and solidify liquid weight are 100% meter, and the mass fraction of the solid phase pulvis is 40%~75%, the matter of the solidify liquid
Measuring score is 25%~60%；
It is in terms of 100% by the weight of the solid phase pulvis comprising the tuna fishbone dust that mass fraction is 20%~80%/thoroughly
Bright matter acid microballoon；
Tuna fishbone dust/the hyaluronate microspheres be prepared with hyaluronic acid as raw material using tuna fishbone dust it is micro-
Ball, wherein by the total weight of tuna fishbone dust and hyaluronic acid be 100% in terms of, the mass fraction of the tuna fishbone dust
It is 30%~70%, the mass fraction of the hyaluronic acid is 30%~70%.
8. the composition according to claim 7 for forming composite bone cement, wherein the tuna fishbone dust/transparent
The partial size of matter acid microballoon is 30 μm~500 μm.
9. the composition according to claim 7 for forming composite bone cement, wherein the solid phase pulvis further includes medicine
Object.
10. the composition according to claim 9 for forming composite bone cement, wherein the drug includes antibiolics
Powder.
11. the composition according to claim 10 for forming composite bone cement, wherein the antibiotic medicinal powder includes sulphur
Sour gentamicin or rifampin medicinal powder.
12. the composition according to claim 11 for forming composite bone cement, wherein solid phase pulvis described in every 1g loads
The drug of 2~300mg.
13. the composition according to claim 7 for forming composite bone cement, wherein with the weight of the solid phase pulvis
For 100% meter, further include mass fraction be 16%~79.5% polymethyl methacrylate powder and mass fraction be
0.5%~4% polymerization initiator.
14. the composition according to claim 13 for forming composite bone cement, wherein the polymethyl methacrylate
The partial size of powder is 40 μm~80 μm.
15. the composition according to claim 14 for forming composite bone cement, wherein the polymerization initiator included
Aoxidize dibenzoyl.
16. forming the composition of composite bone cement according to claim 7 or 13, wherein with the weight of the solidify liquid
Amount is 100% meter comprising the methyl methacrylate and mass fraction that mass fraction is 97%~99.9% be 0.1%~
3% polymerization activator.
17. the composition according to claim 16 for forming composite bone cement, wherein the polymerization activator includes N,
N- dimethyl-p-toluidine.
18. forming the composition of composite bone cement according to claim 7 or 13, wherein the tuna fishbone dust/
Hyaluronate microspheres are prepared as follows to obtain:
(a) aqueous solution containing the tuna fishbone dust and the hyaluronic acid is formed；
(b) step (a) obtained aqueous solution is spray-dried in 100~150 DEG C of temperature ranges, the tuna is made
Fishbone dust/hyaluronate microspheres.
19. the composition according to claim 18 for forming composite bone cement, wherein by the concentration for adjusting solution
And/or the size of microballoon described in the size Control of nozzle.
20. a kind of composite bone cement slurry is formed described in claim 1 described in the composition of composite bone cement
The composition and tuna fishbone dust/hyaluronate microspheres are mixed for forming polymethyl acrylate bone cement can
The composite bone cement slurry of injection；Or
It is the Composite Bone water that the described in any item compositions for forming composite bone cement of claim 2-6 are made to injectable
Slurry body；Wherein, the tuna fishbone dust/hyaluronate microspheres, the polymethyl methacrylate powder and the polymerization
Initiator is added in the form of pulvis, and the methyl methacrylate and the polymeric activator are added in the form of liquor；
Or
It is to mix the solid phase pulvis in composition described in any one of claim 7~19 with the solidify liquid,
Form the composite bone cement slurry of injectable.
21. a kind of composite bone cement is that composite bone cement slurry described in claim 20 is solidified 5~25min to obtain
's.
22. appointing in the composition according to any one of claims 1 to 6 for forming composite bone cement or claim 7~19
Formed described in one composite bone cement composition or claim 20 described in composite bone cement slurry or right want
Composite bone cement described in 21 is asked to prepare the application in bone renovating material.
23. application according to claim 22, wherein the bone renovating material include bone tissue packing material and/or
Timbering material.
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| CN108273131B (en) * | 2018-03-19 | 2021-07-27 | 深圳市中科海世御生物科技有限公司 | Composite bone cement, preparation method and application thereof, and bone repair material |
| US20220111115A1 (en) * | 2018-07-30 | 2022-04-14 | Agency For Science, Technology And Research | A bone cement composition |
| CN109847100B (en) * | 2019-04-09 | 2020-06-16 | 浙江科惠医疗器械股份有限公司 | Bone cement with biological activity and preparation method thereof |
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| CN102210887A (en) * | 2010-04-01 | 2011-10-12 | 英属维京群岛商冠亚股份有限公司 | Bioactive orthopaedic implant constituent |
| CN102462863A (en) * | 2010-11-10 | 2012-05-23 | 姜文学 | Polyvinylpyrrolidone composite material used for bone defect restoration, its preparation method and its application method |
| CN104841016A (en) * | 2014-12-19 | 2015-08-19 | 中国科学院深圳先进技术研究院 | Tuna fishbone meal material, preparation method and application thereof |
| CN104922731A (en) * | 2015-06-01 | 2015-09-23 | 深圳市中科海世御生物科技有限公司 | Compound bone cement precursor as well as preparation method and application of strontium borate bioglass/polymethyl methacrylate compound bone cement |
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