CN106474542A - A kind of injectable bone substitution material and its preparation method and application - Google Patents
A kind of injectable bone substitution material and its preparation method and application Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/20—Polysaccharides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/02—Inorganic materials
- A61L27/025—Other specific inorganic materials not covered by A61L27/04 - A61L27/12
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
Abstract
The invention provides a kind of injectable bone substitution material, described material is a kind of paste being made up of calcium sulfate and hyaluronate sodium or cross-linking hyaluronic acid sodium；Described calcium sulfate is calcium sulphate dihydrate；In described paste, calcium sulphate dihydrate and hyaluronate sodium or cross-linking hyaluronic acid sodium weight are than for 200 270:1.Present invention also offers the preparation method and application of described injectable bone substitution material.The injectable bone substitution material that the present invention provides, raw material composition is few, low cost, makes simple, easy to use.In addition, the bone alternate material that the present invention provides is that a kind of paste has syringeability, there are higher viscosity and anti-collapsibility ability, workable, but also there is good ossification, in clinical bone injury reparation, there is vast application prospect.
Description
Technical field
The present invention relates to bio-medical material technology and biomedical engineering field are and in particular to a kind of injectable bone substitutes
Material and its preparation method and application.
Background technology
Because the Cranial defect that wound, disease and regression lead to is a kind of common orthopaedics problem.Autologous bone, allograph bone and conjunction
Bone alternate material is become to be frequently with three class materials in Bone Defect Repari operation.Autologous bone no rejects and has good repairing effect, but from
The filling of body bone needs to gather from healthy bone group, haves the shortcomings that damage, Bone mineral change.Particularly when needing to carry out big section bone
During filling, it is difficult to collect the autologous bone of suitable size and shape.Then there is rejection and the risk of infection in allograph bone.
Calcium sulfate is in nature with calcium sulphate dihydrate (CaSO4·2H2O presented in), referred to as Gypsum Fibrosum, it is slightly soluble in
Water.Gypsum Fibrosum is transparent or semitransparent tabular or fibrous crystal, and property is crisp, 128 DEG C of mistake 1.5H2O, 163 DEG C lose 2H2O.Work
In industry, Gypsum Fibrosum is heated to 150 DEG C and is dehydrated into Gypsum Fibrosum preparata CaSO4·0.5H2O (or bassanite), adds water and is converted into CaSO4·
2H2O.Can be used for plaster bandage accordingly, make plaster model, chalk, artware, construction material.
Calcium sulfate as a kind of traditional bone renovating material, with its good biocompatibility, syringeability, bone conductibility
Have a good application prospect Deng in terms of Bone Defect Repari, the MIIG bone cement of Wright company of U.S. development and production, not only clinical
Curative effect and biological property are more definite, stable, and provide a kind of effective way for minimally-invasive treatment Cranial defect；But, sulfur
It is shorter, the shortcomings of being degraded and lack bone-inducting active by absorption quickly that sour calcium bone cement there is also the injectable time simultaneously.
Hyaluronic acid (Hyaluronic acid, or hyaluronate, HA) obtains extensively should in medical domain
With including viscoelasticity operation, arthritis treatment, preventing the increase of postoperative tissue adhesion, medicament slow release and soft tissue (as skin
The application of skin, urinary system and reconstruction) etc..Hyaluronic acid injection liquid (the A Er that Japanese Seikagaku Kogyo Co. Ltd. produces
Control) have been widely used for the intra-articular injection treatment of osteoarthritis.But because natural HA is easy to degrade in vivo, it is difficult
Retain, limit the performance of its curative effect.Especially in recent years the aspect such as Film with Preventing Adhesion and Soft-tissue operation application it is desirable to HA
In human body planted agent, there is suitable retention time, sometimes even require longer-term persistence in vivo.Thus excite researcher to sky
So interest of the structure of modification work of HA, and substantial amounts of research has been carried out to its derivant.The HA derivant changing structure remains HA
Good biocompatibility, and have more preferable rheologic behavio(u)r is nontoxic to human body, have no stimulation.The way of structure of modification
One of footpath is to carry out crosslinking using cross-linking agent to the group of hyaluronic acid, can obtain respectively being shaped as powder in different substrate
The water-fast product of end, thin film or coating.
Because homogenous material is limited to material performance itself, composite becomes the study hotspot of current bone-grafting material.Reason
The bone-grafting material thought should have following characteristic：There is biological degradability and biocompatibility, no or low immunogenicity；There is bone conduction
Property and osteoinductive；Mechanical resistance；Can be used as the carrier of the cytokine profiles such as bone morphogenetic protein(BMP).Therefore, meet above-mentioned plant
A kind of NEW TYPE OF COMPOSITE bone-grafting material of bone material characteristic is urgently developed.
Content of the invention
An object of the present invention is to provide a kind of injectable bone substitution material degraded it is intended to solve sulphuric acid calcium absorption
Hurry up, lack bone-inducting active the problems such as.
The second object of the present invention is to provide a kind of preparation method of injectable bone substitution material.
The third object of the present invention is to provide a kind of application in bone injury reparation for injectable bone substitution material.
For achieving the above object, present invention firstly provides a kind of injectable bone substitution material, described material is by calcium sulfate
A kind of paste made with hyaluronate sodium or cross-linking hyaluronic acid sodium；Described calcium sulfate is calcium sulphate dihydrate；Described paste
In thing, calcium sulphate dihydrate and hyaluronate sodium or cross-linking hyaluronic acid sodium weight are than for 200-270:1.
Preferably, in described paste calcium sulphate dihydrate and hyaluronate sodium or cross-linking hyaluronic acid sodium weight than for 223:
1.
Preferably, described hyaluronate sodium is aqueous solution of sodium hyaluronate, and described cross-linking hyaluronic acid sodium is cross-linked transparent
Matter acid sodium aqueous solution；Described aqueous solution of sodium hyaluronate or cross-linking hyaluronic acid sodium aqueous solution mass concentration are 0.08%-
0.12%.
Preferably, described aqueous solution of sodium hyaluronate or cross-linking hyaluronic acid sodium aqueous solution mass concentration are 0.1%.
Preferably, described cross-linking hyaluronic acid sodium is to react generation, described cross-linking agent by hyaluronate sodium and cross-linking agent
Including one or more of cinnamic acid, formaldehyde, dimethylol urea, dihydroxymethyl ethyl carbamide, polyisocyanate or vinyl sulfone.
Preferably, described cross-linking agent is cinnamic acid.
Cross-linking hyaluronic acid sodium of the present invention can be with oneself preparation it is also possible to buy on the market.
Further, the present invention provides a kind of preparation method of injectable bone substitution material, and methods described is by anhydrous sulfur
The injectable bone substitution material paste that sour calcium is proportionally mixed to prepare with hyaluronate sodium or cross-linking hyaluronic acid sodium solution,
In described paste, calcium sulphate dihydrate and hyaluronate sodium or cross-linking hyaluronic acid sodium weight are than for 200-270:1, the method
Preparation condition is room temperature, normal pressure, and humidity is 40%-70%.
As in a preferred embodiment, comprise the following steps that：
By the hyaluronate sodium of dead plaster and 0.1% mass concentration or cross-linking hyaluronic acid sodium solution according to weight
For 2:1 ratio mixing, room temperature, humidity 40%-70%, 1 normal atmosphere, mechanically fully mix, mixed
In thing, the weight of calcium sulphate dihydrate and hyaluronate sodium is than for 223:1.
Further, the invention provides described bone alternate material promote osteoblastic propagation and differentiation in should
With.
The bone alternate material of present invention preparation has promotion preosteoblast through osteoblastic proliferation and Analytical Chemical Experiment checking
Propagation and the effect of differentiation.
Further, present invention also offers application in preparing bone repairing support for the described injectable bone substitution material.
Preferably, described bone repairing support can be obtained with hyaluronate sodium or cross-linking hyaluronic acid sodium by calcium sulfate, also may be used
To add other compositions；Described bone repairing support can be used as the carrier of the cytokine profiles such as bone morphogenetic protein(BMP)；Described
Bone morphogenetic protein(BMP) includes：BMP-1、BMP-2、BMP-3、BMP-7、BMP-14.
Further, present invention also offers described injectable bone substitution material bone injury reparation in application.
Beneficial effects of the present invention are as follows：
The bone alternate material studied at present and apply contains calcium sulfate and the product category of hyaluronate sodium is various, and becomes
Part is complicated, usually contains three or more composition.But up to the present, such material does not have any one and has significantly
Advantage is simultaneously applied to clinic.
Technical scheme mixes only with calcium sulfate and hyaluronate sodium (or cross-linking hyaluronic acid sodium), its advantage
As follows：
1. the bone alternate material making of the present invention is simple and practical, and surgeon can be in operating room field fabrication.Only need
Prepare commercially available Related product and aseptic stainless steel.This can realize easily in operating room.
2., although the bone alternate material raw material composition of the present invention is few, all sent out by cell in vitro and internal heterotopic Osteogenesis
Existing, compared with existing bone alternate material calcium sulfate, the bone alternate material of the present invention has more preferable biocompatibility, more preferably
Promote preosteoblast propagation and break up, thus promoting the effect of internal skeletonization.
3. the bone alternate material of the present invention is due to having syringeability, thus can be used for Minimally Invasive Surgery, as bone cyst
Inject after puncture.Bone alternate material better than current solid-state.
In a word, the injectable bone substitution material that the present invention provides, raw material composition is few, low cost, makes simple, user
Just.In addition, the bone alternate material that the present invention provides is that a kind of paste has syringeability, there are higher viscosity and anti-collapsibility energy
Power, workable, but also there is good ossification, in clinical bone injury reparation, there is vast application prospect.
Brief description
Calcium sulfate chemical composition and crystal structure after Fig. 1 XRD analysis calcium sulfate and cross-linking hyaluronic acid sodium mixing；
Stability observing in phosphate buffer PBS for the tri- kinds of materials of Fig. 2；
The impact to cytoactive for the tri- kinds of materials of Fig. 3；
The impact of three kinds of material cell proliferation of Fig. 4 variable concentrations；
The impact to cell Osteoblast Differentiation for Fig. 5 material；
The impact to cell skeletonization for Fig. 6 x-ray analysis injectable bone substitution material；
Fig. 7 Micro-CT analyzes the impact to cell skeletonization for the injectable bone substitution material.
Specific embodiment
Hereinafter implement for the present invention is described, but be not limited to the scope of the present invention.If not specializing, in embodiment
The conventional meanses that technological means used are well known to those skilled in the art.
Dead plaster is mixed by the present invention with the aqueous solution of sodium hyaluronate of aqueous solution of sodium hyaluronate or crosslinking, is obtained
Injectable bone substitution material paste.Described paste has higher viscosity and anti-collapsibility ability, workable.In vitro
Experiment in show, described injectable bone substitution material has the biocompatibility of height, and before being obviously promoted mice, skeletonization is thin
Born of the same parents' propagation and differentiation.Experiment confirms that described injectable bone substitution material is compared with simple calcium sulfate material in vivo, has more
Strong osteogenic ability.
Experiment material used by the present invention is as follows：
Dead plaster (ALDRICH, article No. 255696)；
Cross-linking hyaluronic acid sodium (Seikagaku corporation Japan, ProductName Gel-One)；
Hyaluronate sodium (make profits moral bio tech ltd in Nanjing, CAS 9067-32-7)；
MC3T3-E1 cell strain：(Chinese Academy of Medical Sciences's cell centre provides it is also possible to market is bought).
Instrument used by the present invention is as follows：
Micro-CT (SkyScan1272, BRUKER)；
XRD (XRD6100, Japanese Shimadzu).
Prepared by embodiment 1 bone alternate material
The sodium hyaluronate solution of anhydrous slufuric acid calcium powder and 0.1% mass concentration is compared 2 according to weight:1 ratio
Mixing, room temperature, humidity 40%-70%, 1 normal atmosphere, mechanically fully mix, two in thus obtained mixture
The weight ratio about 223 of H 2 O calcium sulphate and hyaluronate sodium:1.The existing good syringeability of paste of gained, can maintain again
Certain form and do not run off.
With method, cross-linking hyaluronic acid sodium is substituted hyaluronate sodium, same ratio mixes gained paste with calcium sulphate powders
For the second experimental mixture.
With calcium sulfate and phosphate buffered saline(PBS) (PBS) according to 2:1 weight is comparison than mixing gained pastel.
By whether changing calcium sulfate with after X-ray diffraction laboratory observation calcium sulfate and the mixing of cross-linking hyaluronic acid sodium solution
Chemical composition and crystal structure.
The stability of above-mentioned three kinds of materials is observed, observing time, point was 0 hour, 12 hours, 24 hours, 3 days and 7
My god.Sample is placed in 37 DEG C of cell incubators.
Result shows, X-ray diffraction experiment display calcium sulfate and hyaluronate sodium mixing material and calcium sulphate dihydrate have had
Exactly the same diffracting spectrum.The position at the peak that calcium sulfate and hyaluronate sodium mixing material are obtained and calcium sulphate dihydrate place peak
Match with intensity, illustrate that calcium sulfate mixes chemical composition and the crystal structure not changing calcium sulphate dihydrate with hyaluronate sodium,
As shown in figure 1, top curve is calcium sulphate dihydrate, lower curve is calcium sulfate and cross-linking hyaluronic acid sodium mixture.Calcium sulfate
With hyaluronate sodium mixing group compared with calcium sulfate and cross-linking hyaluronic acid sodium mixing group, the cream that cross-linking hyaluronic acid sodium is combined into
Shape thing viscosity is higher, and mastic form is more stable, is more convenient for operating.The stability of two groups of materials is superior to simple calcium sulfate group, such as
Shown in Fig. 2.
Prepared by embodiment 2 bone alternate material
According to the preparation method of embodiment 1, will be molten with the hyaluronate sodium of 0.1% mass concentration for anhydrous slufuric acid calcium powder
Liquid is according to weight than for 1.8:1 ratio mixing, the weight of calcium sulphate dihydrate and hyaluronate sodium in thus obtained mixture
Ratio about 200:1.
With method, crosslinked hyaluronate sodium is mixed gained paste for the second experiment with same ratio with calcium sulphate powders
Mixture.
Prepared by embodiment 3 bone alternate material
The sodium hyaluronate solution of anhydrous slufuric acid calcium powder and 0.1% mass concentration is compared 2.4 according to weight:1 ratio
Example mixing, the weight ratio about 270 of calcium sulphate dihydrate and hyaluronate sodium in thus obtained mixture:1.
With method, crosslinked hyaluronate sodium is mixed gained paste for the second experiment with same ratio with calcium sulphate powders
Mixture.
Make in the test of mixture and find, calcium sulphate powders are molten with the hyaluronate sodium of sodium hyaluronate solution or crosslinking
Liquid weight is than less than 1.8:1, then it is not easy to because gained mixture is excessive rarefied operate and maintains shape, weight ratio is more than
2.4:1 mixture is excessively sticky and reduces syringeability, and weight is than for 2:Mixture existing good syringeability when 1, and
Can maintain relatively stable in a liquid.The weight ratio being scaled the hyaluronate sodium of calcium sulfate and hyaluronate sodium or crosslinking is
200-270:1, wherein 223:When 1, syringeability and stability equalize the most.
Calcium sulfate that the advantage of inventive mixture is can to obtain using market, hyaluronate sodium, cross-linked transparent matter
Sour sodium product, is simply mixed and can be used by doctor in operating room.In a preferred embodiment of the invention by hyaluronate sodium
Or the mass concentration 0.1% of cross-linking hyaluronic acid sodium is fixing, thus adjustment calcium sulfate and sodium hyaluronate solution or cross-linked transparent
The weight of matter acid sodium solution is than the weight ratio of i.e. adjustable calcium sulfate and hyaluronate sodium or cross-linking hyaluronic acid sodium.
Embodiment 4 compatibility tests
Experiment packet：Blank control group (blank), simple calcium sulfate group (CA), hyaluronate sodium and calcium sulfate group (CA-
HA), cross-linking hyaluronic acid sodium and calcium sulfate group (CA-HAC).
The method specifying according to ISO10993-12, the method is specially：By 1 gram of calcium sulfate, hyaluronate sodium and sulphuric acid
Calcium, cross-linking hyaluronic acid sodium and calcium sulfate, three groups of materials are soaked in the liquid of 10mL respectively, and immersion liquid is using containing volume ratio
Cell culture fluid α-MEM (Gibco company) for 10% hyclone, 50U/mL penicillin and 50U/mL streptomycin.
Use α-MEM culture medium, simple sulfur acid extract, hyaluronate sodium and calcium sulfate lixiviating solution, cross-linked transparent matter respectively
Sour sodium and calcium sulfate lixiviating solution are in 37 DEG C of 5%CO2Skeletonization MC3T3-E1 cell strain before culture mice in incubator, propagation of taking the logarithm
Phase cell is configured to 1 × 104/ mL single cell suspension is inoculated in 96 orifice plates, every hole 100 μ L, and every group sets 6 multiple holes.Treat that cell pastes
After wall, add CCK-8 reagent, detect respectively 6 hours, 12 hours, the cell quantity of 24 hours, at microplate reader detection 450nm
Absorbance.
Result as shown in figure 3, only simple calcium sulfate group cytoactive is relatively low, remaining two groups and blank control group (cell
Culture fluid) compare zero difference, hyaluronate sodium and calcium sulfate group (CA-HA) and cross-linking hyaluronic acid sodium and calcium sulfate group are described
(CA-HAC) biocompatibility is superior to simple calcium sulfate group.
The rush hyperplasia effect of embodiment 5 material
With ordinary culture medium and 25%, 50%, 75%, 100% concentration, (lixiviating solution in embodiment 4 is defined as respectively
100% concentration, such as diluting one times with culture medium is then 50% concentration) simple calcium sulfate, hyaluronate sodium and calcium sulfate, crosslinked
MC3T3-E1 cell cultivated respectively by three kinds of lixiviating solution of hyaluronate sodium and calcium sulfate, is examined with CCK-8 test kit at the 1st, 3,5 day
Survey cell quantity, represented with the absorbance that microplate reader measures at 450nm.
Result as shown in figure 4,1,2,3 representing the 1st day, the 3rd day and the 5th day respectively in abscissa, when concentration is 25% He
When 50%, compared with the matched group of simple cell culture fluid, three kinds of lixiviating solution play the role of significantly to promote cell proliferation (p<
0.0001).When concentration is 75% concentration and 100% concentration, three kinds of lixiviating solution no difference of science of statistics compared with matched group.
The rush cell Osteoblast Differentiation effect of embodiment 6 material
50% concentration using simple calcium sulfate, hyaluronate sodium and calcium sulfate, cross-linking hyaluronic acid sodium and calcium sulfate
Three kinds of lixiviating solution carry out differentiation culture to MC3T3-E1 cell respectively, take culture fluid measurement to become in 1d, 7d, 14d and 21d respectively
Bone division guideline albumen alkali phosphatase (ALP), the concentration of collagen protein 1 (COL1) and osteocalcin (OCN).
Result is as shown in figure 5, calcium sulfate and hyaluronate sodium or two kinds of mixing materials of cross-linking hyaluronic acid sodium are in 14d
During with 21d, alkali phosphatase (ALP) concentration is all remarkably higher than blank group and simple calcium sulfate group (P<0.0001), simple sulfur
Sour calcium group and blank group zero difference；Collagen protein 1 (COL1) concentration is above blank control group, and calcium sulfate group at the 14th day was higher than
Blank control group, in the 21st day and blank control group zero difference；Osteocalcin (OCN) is above blank control group and simple sulphuric acid
Calcium group (p<0.0001), simple calcium sulfate group and blank control group zero difference.
The internal ossification of embodiment 7 material
Using new zealand white rabbit condyle of femur Cranial defect model, White Rabbit is derived from Beijing Union Medical College Animal Lab.,
Condyle of femur Cranial defect model is reference《Giavaresi G, Fini M, Salvage J, et al.Bone regeneration
potential of a soybean-based filler：experimental study in a rabbit cancellous
Bone defects.J Mater Sci Mater Med, 2010,21 (2)：615-626.》The method of document oneself preparation.
It is injected separately into pure calcium sulfate, hyaluronate sodium and calcium sulfate, cross-linking hyaluronic acid sodium and calcium sulfate, at the 6th week and the 12nd week
Dead animal, takes specimen to observe x-ray and Micro-CT performance.
In x-ray analysis result (as shown in Figure 6) and the Micro-CT analysis knot of the 6th week and the 12nd week after 3 kinds of materials of implantation
Really (as shown in Figure 7), all show that the skeletonization effect of two kinds of composites is better than simple calcium sulfate group, cross-linking hyaluronic acid sodium and sulfur
The ossification of sour calcium group (CA-HAC) is better than hyaluronate sodium and calcium sulfate group (CA-HA).
Although, above the present invention is described in detail with a general description of the specific embodiments,
On the basis of the present invention, it can be made some modifications or improvements, this will be apparent to those skilled in the art.Cause
This, these modifications or improvements without departing from theon the basis of the spirit of the present invention, belong to the scope of protection of present invention.
Claims (10)
1. a kind of injectable bone substitution material it is characterised in that described bone alternate material be by calcium sulfate and hyaluronate sodium or
A kind of paste that cross-linking hyaluronic acid sodium is made；Described calcium sulfate is calcium sulphate dihydrate；Calcium sulphate dihydrate in described paste
With hyaluronate sodium or cross-linking hyaluronic acid sodium weight than for 200-270:1.
2. bone alternate material as claimed in claim 1 is it is characterised in that calcium sulphate dihydrate and hyaluronate sodium in described paste
Or cross-linking hyaluronic acid sodium weight is than for 223:1.
3. bone alternate material as claimed in claim 1 or 2 is it is characterised in that described hyaluronate sodium is that hyaluronate sodium is water-soluble
Liquid, described cross-linking hyaluronic acid sodium is cross-linking hyaluronic acid sodium aqueous solution；Described aqueous solution of sodium hyaluronate or cross-linked transparent matter
Acid sodium aqueous solution mass concentration is 0.08%-0.12%.
4. bone alternate material as claimed in claim 3 is it is characterised in that described aqueous solution of sodium hyaluronate or cross-linked-hyaluronic acid
Sodium water solution mass concentration is 0.1%.
5. bone alternate material as claimed in claim 1 or 2 is it is characterised in that described cross-linking hyaluronic acid sodium is by hyaluronic acid
Sodium and cross-linking agent react and produce, and described cross-linking agent includes cinnamic acid, formaldehyde, dimethylol urea, dihydroxymethyl ethyl carbamide, poly- different
One or more of cyanate or vinyl sulfone.
6. bone alternate material as claimed in claim 5 is it is characterised in that described cross-linking agent is cinnamic acid.
7. a kind of preparation method of injectable bone substitution material it is characterised in that methods described be by dead plaster with transparent
Matter acid sodium or the injectable bone substitution material paste that is proportionally mixed to prepare of cross-linking hyaluronic acid sodium solution, described paste
Middle calcium sulphate dihydrate and hyaluronate sodium or cross-linking hyaluronic acid sodium weight are than for 200-270:1, the preparation condition of the method is
Room temperature, normal pressure, humidity are 40%-70%.
8. application in promoting osteoblastic propagation and differentiation for the bone alternate material described in any one of claim 1 to 6.
9. application in preparing bone repairing support for the bone alternate material described in any one of claim 1 to 6.
10. application in bone injury reparation for the bone alternate material described in any one of claim 1 to 6.
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