CN100536936C - New-type of inorganic bone grafting material and its preparation and use - Google Patents
New-type of inorganic bone grafting material and its preparation and use Download PDFInfo
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- CN100536936C CN100536936C CNB2007100639034A CN200710063903A CN100536936C CN 100536936 C CN100536936 C CN 100536936C CN B2007100639034 A CNB2007100639034 A CN B2007100639034A CN 200710063903 A CN200710063903 A CN 200710063903A CN 100536936 C CN100536936 C CN 100536936C
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Abstract
The present invention is one kind of new inorganic bone grafting material and belongs to the field of medical material. The inorganic bone grafting material consists of beta-tricalcium phosphate grain in 20-80 wt% and alpha-calcium sulfate semihydrate powder in 20-80 wt%, and the alpha-calcium sulfate semihydrate powder form layered structure in the surface and/or pores of beta-tricalcium phosphate grain. Both beta-tricalcium phosphate and alpha-calcium sulfate semihydrate have excellent biocompatibility and excellent in vivo degrading performance, and the composite artificial bone grain may be used in repairing bone defect of different shapes. The composite artificial bone grain has wide material source, convenient use, excellent performance, simple preparation process, low cost and other advantages.
Description
Technical field
The present invention relates to a kind of new-type of inorganic bone grafting material, Preparation Method And The Use, be specifically related to a kind ofly in the surgery medical operating, be used for substituting and repair the damaged absorbable combined artificial inorganic-bone cement of self-curing, the Preparation Method And The Use of osseous tissue, belong to field of medical materials.
Background technology
Skeleton is made up of inorganic constituents and organic principle two parts, and wherein inorganic constituents accounts for the 60-70% of dry weight, and main component is hydroxyapatite (Ca
10(PO
4)
65H
2O) and a small amount of sodium salt, magnesium salt etc., organic principle mainly is a type i collagen.About 25-50nm * the 40nm of the size of hydroxyapatite crystal * 200-350nm, crystal major axis (c axle) direction is consistent with the direction of type i collagen fiber, constitute the porous structure material that micropore is interconnected, among health adult's body skeleton is in dynamic equilibrium, the skeleton that osteoclast absorbs is replaced gradually by the new bone that osteoblast forms, about per 10 years skeleton update alls one time in the human body.Mechanical support is one of major physiological function of skeleton, but the bone that causes owing to reasons such as wound, infection, tumor, operations is damaged and need the operation of bone grafting very common, there are every year 6.2 hundred ten thousand example fracture to take place in the U.S., wherein there is 5-10% fracture delayed union or disunion can occur, 800,000 routine spinal fusion surgeries are arranged every year.The purpose of these disease treatments is to recover the seriality and the mechanical strength of skeleton, promotes new bone formation and recovers its physiological function by local bone grafting.The bone-grafting material of present clinical use comprises from body bone, homogeneous allogenic bone, bone morphogenetic protein (BMP), decalcified bone matrix (DBM), artificial bone etc., can be divided into the organic material with natural components and the inorganic material two big classes of synthetic.From the body bone is present ideal bone-grafting material, but because the source is limited, complication such as pain, infection appear easily for the district, it is reported that the incidence rate of complication can reach 30%, this makes people begin to seek other even more ideal bone grafting substitution material, cause the development of various novel bone-grafting materials and the quick growth of the market demand, 2005 are only U.S. bone-grafting material market just reaches 1,074 hundred million dollars, and annual with near 20% speed increase.
All there is certain shortcoming and defect in the various bone-grafting materials of present clinical use.Though homogeneous allogenic bone can keep certain osteogenic activity, it is limited to originate, and domestic price 400-800 unit/gram exists immunological rejection and pathophorous potential danger simultaneously, and the scope of application is restricted.DBM, BMP etc. derive from allograph bone, xenogenesis bone or obtain by expression of gene protein, and it is active but lack conduction osteogenic activity and mechanical strength to have a bone induced osteogenesis, and price is extremely expensive, can only use among a small circle clinically at present.Inorganic material mainly comprises calcium phosphate and calcium sulfate two big classes, has conduction osteogenic activity and mechanical strength, but does not have the induced osteogenesis activity.Though various bone-grafting materials differ from one another, remain the standard that various bone-grafting materials make every effort to reach from the body bone.Differ from one another as ideal bone-grafting material, but remain the standard that various bone-grafting materials make every effort to reach from the body bone.Should possess following performance as ideal bone-grafting material: (1) osteogenic activity; (2) excellent biological compatibility; (3) biodegradable; (4) can provide the support structure ability; (5) storage and easy to use clinically; (6) cost performance height.Use the difference at position according to bone-grafting material, in the above performance one or a part may be even more important, for example fill the damaged bone-grafting material of metaphysis bone and require to have certain mechanical strength, avoid articular cartilage face to subside, and when the treatment bone does not connect, just need have the bone-grafting material of osteogenic activity.Along with the understanding to body internal skeleton defect repair process and bone-grafting material structure, chemical characteristic and biological characteristics is more and more, more and more have the ability preparation or select suitable material to imitate characteristic from the body bone of people, development meets the even more ideal bone-grafting material of certain needs.
The source is abundant because the type of inorganic bone grafting material of synthetic has, storage and easy to use, excellent biological compatibility and avoid pathophorous advantage, in recent years research in this respect day by day increases, and the artificial bone of particularly various calcium phosphate and calcium sulfate material preparation becomes the research focus.Commercial abroad at present artificial type of inorganic bone grafting material has ChronOS
TM(bata-tricalcium phosphate), Pro-Osteon (porous Corallium Japonicum Kishinouye heat conversion hydroxyapatite), Norian SRS (calcium-phosphate cement), NovaBone (bio-vitric), Bio-OSS (cattle takes off organic bone meal), Osteoset (calcium sulfate) etc., these artificial type of inorganic bone grafting material respectively have characteristics, but abroad the artificial type of inorganic bone grafting material price of these high technology contents and high added value is extremely expensive, and the area of most of at home medical expense control strictnesses is used and is very restricted.Therefore seeking and developing the even more ideal artificial type of inorganic bone grafting material with independent intellectual property right is the important topic in biomaterial for medical purpose field in recent years.
It is popular that the calcium phosphate artificial bone uses, mainly be because of the mineral facies of its composition near bone, has excellent biological compatibility, thereby it synthesizes and application was attracted attention with regard to behaving since the sixties in last century, main by wet heating, dry process and Hydrothermal Preparation hydroxy apatite powder, make the high density hydroxyapatite through high-temperature calcination again, its compressive strength reaches 490.3-882.6MPa, bending strength reaches 196.1Mpa, is used for the reparation of bone and tooth and obtains certain effect.But the higher and dissolubility of this material degree of crystallinity is lower, and Mohs' hardness reaches 5, and elastic modelling quantity is the twice of bone, plastotype difficulty and be difficult to degraded in vivo.Porous hydroxyapatite is a kind of improved bone-grafting material with conduction osteogenic activity, derive through thermal chemical reaction by the calcium carbonate in the Corallium Japonicum Kishinouye and to form and have a hydroxyapatite crystal structure, with the porous space structure of human spongy bone similar, new bone can be grown in this hydroxyapatite rapidly.Only limit to non-heavy burden or have the bone under the strong fixedly protection damaged but use, in the hole of material, its mechanical strength promptly can be improved significantly in case new bone is grown into, but long-term in vivo clinical observation is found can not degrade substantially.The main deficiency of sintering or block calcium phosphate artificial bone is moulding difficulty and operation inconvenience, cause the appearance of various calcium-phosphate cements, the carbonatoapatite cement of Constanz development in 1996 is described as the revolutionary character progress of bone defect repair, this material is made up of dry powder and consolidation liquid two parts, during use the two accent is mixed pasty state, the bone that can repair arbitrary shape is damaged, and in-situ solidifying also has certain mechanical strength, forms a kind of carbonatoapatite (Ca
8.8(HPO
4)
0.7(PO
4)
4.5(CO
3)
0.7(OH)
1.3), chemical composition and crystal structure are similar to the mineral facies of normal bone tissues, obtain certain effect in disease treatments such as Colles fracture, intertrochanteric fracture, fracture of the tibial plateau, spinal fracture.But this material degradation in vivo speed is slower, and final only some is absorbed reconstruction.
The similar of bata-tricalcium phosphate biologic bracket material with microcellular structure is in normal spongy bone, and porosity reaches 90%, 75% pore diameter between the 100-1000 micron, and all the other pore diameters of 24% are at the 1-100 micron.Big hole allows osseous tissue to grow into, and the effect of performance biological support though little hole can not make bone grow into, can significantly improve the mobile and diffusion of liquid in the bone matrix, improves the metabolism of cell in the substrate.Because the composition characteristic of this pore structure and itself, the absorption rate after implanting approach normal bone healing speed, and new bone formation was just arranged in 3 weeks, absorb 86% when absorbing for 76%, 12 week during 6 weeks, when 52 weeks, have only 2% residual.Can not early loading but this polyporous materials repairing bone defect lacks mechanical strength, there are moulding difficulty and awkward shortcoming.
Calcium sulfate is commonly called as Gypsum Fibrosum, and name is from northern village, Paris because Gypsum Fibrosum Preparatum (half-H 2 O calcium sulphate) has the self-curing performance, promptly had as far back as 1794 the document record use the plaster fixation fracture limbs (Eton, MedicalCommentaries).And early start appears at 1892 with the Gypsum Fibrosum treatment bone damaged report that implants, and Dreesmann adopts pasty state calcium sulfate to mix 5% carbolic acid and fills the damaged patient of 8 routine bones, and wherein 6 routine patients obtain bony union.But the result difference of calcium sulfate clinical practice is very big, main cause is because the size of employed calcium sulfate is different with crystal structure, infiltration rate is too fast in vivo after causing filling bone damaged, before new bone formation, promptly absorbed fully, causing the bone defect to form cavity or clogged by soft tissue.Crystal structure by a series of special process control half-H 2 O calcium sulphates, form the alpha type crystal structure of neat and consistent, having dissolving was used for clinical by the FDA approval in 1996 with the relative calcium sulfate of medical grade slowly of absorption (Osteoset), tablet and powder (4.8 * the 3.3mm that comprises two kinds of specifications, 3 * 2.5mm), it is damaged to be mainly used in the various pardon bones of filling, but must keep the integrity of its tablet and powder, otherwise can influence its infiltration rate and bone defect repair effect.But its frangible characteristic and shortage mechanical strength limit it in clinical extensive use, need further improve to improve its effect clinically on mechanics and biology performance.
Because the shortcoming of single type of inorganic bone grafting material, many in recent years researchs are devoted to several type of inorganic bone grafting material are combined with each other, and bring into play advantage separately and remedy mutual shortcoming, to prepare even more ideal combined artificial bone renovating material.
Summary of the invention
First technical problem that the present invention will solve is: but the self-curing that a kind of in-situ solidifying is provided and has certain mechanical strength can absorb the composite inorganic bone-grafting material.
Another technical problem that the present invention will solve is: provide a kind of simple, the cycle short and the method for the above-mentioned composite inorganic bone-grafting material of preparation with low cost.
To achieve these goals, the present invention adopts following technical scheme:
A kind of new-type of inorganic bone grafting material, by mass percent is that bata-tricalcium phosphate granule and the mass percent of 20%-80% is that 80%-20% α-half-H 2 O calcium sulphate powder body is formed, and α-half-H 2 O calcium sulphate powder body is in bata-tricalcium phosphate particle surface and/or the inner layer structure that forms of its hole.Two kinds of compositions all can form in above-mentioned quality percentage scope and be applicable to that clinical type of inorganic bone grafting material, the content of the two depend on the predetermined degradation speed of bone material, and the content of α-half-H 2 O calcium sulphate is high more, and degradation speed is fast more.
The particulate diameter of described bata-tricalcium phosphate is 0.2-10mm, preferred 2-5mm.The particulate diameter of bata-tricalcium phosphate depends on the bone grafting position, and the granule of the big more needs in space, bone grafting position is big more.
New-type of inorganic bone grafting material can solidify than after mixing voluntarily with distilled water, blood or the normal saline liquid-solid with 0.2-0.6ml/g.
Principle of the present invention is: α type half-H 2 O calcium sulphate and β tricalcium phosphate are close with body bone tissue constituent, has the favorable tissue compatibility, α-half-H 2 O calcium sulphate has certain mechanical strength after having self-curing performance and curing, but degradation speed seems too fast with respect to the osseous tissue speed of growing into, before freshman bone tissue grows into, the α type half-H 2 O calcium sulphate major part of implanting is absorbed by autologous tissue, is unfavorable for growing into of self osseous tissue.And the bata-tricalcium phosphate granule with microcellular structure has ideal microcellular structure, but lack mechanical strength and self-curing performance, use and moulding difficulty, and β tricalcium phosphate degradation in vivo speed is slow excessively, influence growing into of freshman bone tissue, be unfavorable for equally being substituted by self osseous tissue.The present invention is with the compound cmposite artificial bone that becomes of above-mentioned two kinds of materials, utilize the speed of the different adjustment degraded of two kinds of component ratios, thereby make it to be complementary with self the osseous tissue speed of growing into, cmposite artificial bone is substituted by self osseous tissue gradually, utilize the solidified voluntarily characteristics of α type half-H 2 O calcium sulphate original position simultaneously, with α type half-H 2 O calcium sulphate is that binding agent is prepared into granular combined artificial osseous granules, is convenient to store and use.
The preparation method of new-type of inorganic bone grafting material comprises:
(1) preparation has the bata-tricalcium phosphate granule of microcellular structure:
(2) preparation α-half-H 2 O calcium sulphate powder body;
(3) the preparation mass percent is that bata-tricalcium phosphate granule and the mass percent of 20%-80% are 80%-20% α-half-H 2 O calcium sulphate powder body, forms α-half-H 2 O calcium sulphate powder layer in bata-tricalcium phosphate particle surface and/or space.
Described (1) preparation has the bata-tricalcium phosphate granule of microcellular structure, be to adopt xenogenesis or allosome spongy bone directly to calcine, getting healthy spongy bone calcines in high temperature furnace after sloughing organic principle, following 3 hours of 800 ℃ of conditions, 10 ℃/minute of heating rates, the forging bone piece is soaked in the (NH that concentration is 1M after taking out
4)
2HPO
4In the solution 24 hours, remove unnecessary liquid, 50 ℃ of oven dry 4 days are put in once more in the high-temperature calcination stove and calcine, following 1 hour of 1100 ℃ of conditions, 5 ℃/minute of heating rates, slowly cooling, rinsed with deionized water 2 times, 50 ℃ of oven dry 4 days.Prepared forging bone is pulverized to having the granule of microcellular structure.
Described (1) preparation has the bata-tricalcium phosphate granule of microcellular structure, the calcium hydrogen phosphate that also can adopt 2 parts by weight under 800 ℃ of conditions 3 hours, change calcium pyrophosphate into, calcium carbonate with 1 parts by weight mixes the back tabletting then, 1100 ℃ of condition slowly coolings after following 1 hour, make the bata-tricalcium phosphate powder body after the pulverizing, adopt the microporous foam technology to make bata-tricalcium phosphate granule with microcellular structure.
Described (2) preparation α-half-H 2 O calcium sulphate powder body, be to be that raw material is positioned in the airtight autoclave that steam pressure is 0.13Mpa with the analytical pure calcium sulphate dihydrate, the per minute that heats up gradually heats up 5 ℃, be heated to 123 ℃, heated at constant temperature 7h takes out dry 4-5h in the electric heating aeration cabinet that is placed on 120 ℃ then, adopt airflow milling to pulverize the gained material, mean diameter is smaller or equal to 5 μ m, can solidify after running into aqueous solution, and cured strength should be more than 80MPa.
Described (3) preparation mass percent is that bata-tricalcium phosphate granule and the mass percent of 20%-80% is 80%-20% α-half-H 2 O calcium sulphate powder body, in bata-tricalcium phosphate particle surface and/or space, form α-half-H 2 O calcium sulphate powder layer, be that to stir with dehydrated alcohol and α-half-H 2 O calcium sulphate be pasty state, adopt spraying method directly at bata-tricalcium phosphate particle surface spraying α-half-H 2 O calcium sulphate; Perhaps the bata-tricalcium phosphate granule is inserted in the above-mentioned pasty mixture and stir, make α-half-H 2 O calcium sulphate powder body be attached on bata-tricalcium phosphate granule particle surface and/or its hole inside; 37 ℃ of removal dehydrated alcohol that volatilize naturally.
Described (3) preparation mass percent is that bata-tricalcium phosphate granule and the mass percent of 20%-80% is 80%-20% α-half-H 2 O calcium sulphate powder body, forming α-half-H 2 O calcium sulphate powder layer in bata-tricalcium phosphate particle surface and/or space, is to adopt plasma method directly to spray α-half-H 2 O calcium sulphate powder body to be fixed in bata-tricalcium phosphate particle surface and/or the space.
It all is good carriers that antibiotic and DBM (decalcified bone matrix), BMP (bone morphogenetic protein) etc. have the material of bone-inducting active that a large amount of document proof α type half-H 2 O calcium sulphate and β tricalcium phosphate have been arranged, therefore, thus cmposite artificial bone also can be used as carrier that compound above-mentioned material is expanded its purposes.For example, in raw material, add repairing bone defects such as DBM, BMP with bone-inducting active, or composite antibiotic, the open complicated war wound of chemotherapeutics treatment, a variety of causes osteomyelitis or the bone tumor that cause.
The method of the compound again DBM of cmposite artificial bone, BMP, antibiotic or chemotherapeutics, be that DBM, BMP, antibiotic or chemotherapeutics are mixed with α-half-H 2 O calcium sulphate powder body, together spraying is fixed on the bata-tricalcium phosphate particle surface then, perhaps directly adds DBM, BMP, antibiotic or chemotherapeutics in cmposite artificial bone.For guaranteeing pharmaceutically active, adopt lyophilization to remove ethanol usually.
Advantage of the present invention is: the present invention is based on good biocompatibility of α-half-H 2 O calcium sulphate and bata-tricalcium phosphate and vivo degradation performance, employing has the bata-tricalcium phosphate particle surface spraying doses α-half-H 2 O calcium sulphate powder body of microcellular structure, the combined artificial osseous granules that preparation has the self-curing performance, thereby the bone of repairing arbitrary shape is damaged, the mechanical strength of in-situ solidifying and fast quick-recovery skeleton.Along with the quick degraded of calcium sulfate, the bata-tricalcium phosphate granule with microcellular structure provides comparatively ideal support for new bone growth, and can be gradually by the area of new bone creeping substitution in vivo.By studying its degradation in vivo and skeletonization mechanism, regulate α-half-H 2 O calcium sulphate spraying dosage and bata-tricalcium phosphate particle diameter and content size, make its degradation speed that implants consistent, thereby reach the effect of better bone defect repair and bone-graft fusion with bone formation rate on every side.This cmposite artificial bone wide material sources store and easy to use, can make a large amount of bones damaged and need the patient of bone grafting operation to obtain treating fast and effectively.Cmposite artificial bone function admirable provided by the invention, preparation technology is simple, use, manufacturing cycle weak point and with low cost.
The invention will be further described below in conjunction with the specific embodiment, and embodiments of the present invention are not limited to this, every according to principle perhaps in disclosed by the invention, any this area of enforcement be equal to replacement, all belong to protection scope of the present invention.
Description of drawings
Fig. 1 combined artificial osseous granules apparent structure figure.
Fig. 2 cmposite artificial bone Electronic Speculum structure chart.
Fig. 3 cmposite artificial bone solidifies rear surface figure.
Fig. 4 cmposite artificial bone X-ray diffraction collection of illustrative plates.
Fig. 5 a implants 1 day X-ray figure of repairing bone defect postoperative on the rabbit condyle of femur.
Fig. 5 b implants repairing bone defect postoperative 12 all X-ray figure on the rabbit condyle of femur.
Fig. 6 a implants repairing bone defect postoperative 4 all outside drawings on the rabbit condyle of femur.
Fig. 6 b implants repairing bone defect postoperative 12 all outside drawings on the rabbit condyle of femur.
The specific embodiment
Embodiment 1:
1. preparation has the bata-tricalcium phosphate granule of microcellular structure: get healthy bovine cancellous bone and pulverize to diameter is the 2-3mm granule, rinse the back well and calcined 3 hours in 800 ℃ of high temperature furnaces, be soaked in (the NH that concentration is 1M after the taking-up
4)
2HPO
4In the solution 24 hours, 50 ℃ of oven dry 4 days were put in 1100 ℃ of high-temperature calcination stoves calcining 1 hour once more, 5 ℃/minute of heating rates, and slowly cooling, rinsed with deionized water 2 times, 50 ℃ of oven dry 4 days, the preparation Main Ingredients and Appearance is the granule of bata-tricalcium phosphate.This granule has removed organic composition.Particulate diameter is 4mm.
2. preparation α-half-H 2 O calcium sulphate powder body: it is that the airtight autoclave of 0.13Mpa is heated to 123 ℃ that the analytical pure calcium sulphate dihydrate is placed steam pressure, heated at constant temperature 7h, take out dry 4-5h in the electric heating aeration cabinet that is placed on 120 ℃ then, adopt airflow milling to pulverize the gained material and be α-sulfate hemihydrate powder body of diameter 5 μ m.
3. bata-tricalcium phosphate and α-half-H 2 O calcium sulphate are pressed the ratio of weight and number preparation of 1:1, in bata-tricalcium phosphate particle surface and/or space, form α-half-H 2 O calcium sulphate powder layer: with 5g α-sulfate hemihydrate powder body and 10ml dehydrated alcohol mixing, add 5g bata-tricalcium phosphate granule then, fully mixing is placed in 37 ℃ of baking boxs dehydrated alcohol is volatilized gradually, can make compound bone grafting granule (Fig. 1).
Embodiment 2:
1. preparation has the bata-tricalcium phosphate granule of microcellular structure: get healthy bovine cancellous bone and pulverize to diameter is the 2-3mm granule, rinse the back well and calcined 3 hours in 800 ℃ of high temperature furnaces, be soaked in (the NH that concentration is 1M after the taking-up
4)
2HPO
4In the solution 24 hours, 50 ℃ of oven dry 4 days were put in 1100 ℃ of high-temperature calcination stoves calcining 1 hour once more, 5 ℃/minute of heating rates, and slowly cooling, rinsed with deionized water 2 times, 50 ℃ of oven dry 4 days, the preparation Main Ingredients and Appearance is the granule of bata-tricalcium phosphate.This granule has removed organic composition.Particulate diameter is 10mm.
2. preparation α-half-H 2 O calcium sulphate powder body: it is that the airtight autoclave of 0.13Mpa is heated to 123 ℃ that the analytical pure calcium sulphate dihydrate is placed steam pressure, heated at constant temperature 7h, take out dry 4-5h in the electric heating aeration cabinet that is placed on 120 ℃ then, adopt airflow milling to pulverize the gained material and be α-sulfate hemihydrate powder body of diameter 5 μ m.
3. bata-tricalcium phosphate and α-half-H 2 O calcium sulphate are pressed the ratio of weight and number preparation of 2:8, in bata-tricalcium phosphate particle surface and/or space, form α-half-H 2 O calcium sulphate powder layer: with 8g α-sulfate hemihydrate powder body and 10ml dehydrated alcohol mixing, be sprayed directly into then in 2g bata-tricalcium phosphate particle surface and its hole, place 37 ℃ of baking boxs that dehydrated alcohol is volatilized gradually, can make compound bone grafting granule.
Embodiment 3:
1. preparation has the bata-tricalcium phosphate granule of microcellular structure: the calcium hydrogen phosphate of 2 weight portions under 800 ℃ of conditions 3 hours, change calcium pyrophosphate into, calcium carbonate with 1 weight portion mixes the back tabletting then, 1100 ℃ of condition slowly coolings after following 1 hour, make the bata-tricalcium phosphate powder body after the pulverizing, adopt microporous foam technology (conventional method) to make bata-tricalcium phosphate granule with microcellular structure.Particulate diameter is 0.2mm.
2. preparation α-half-H 2 O calcium sulphate powder body: it is that the airtight autoclave of 0.13Mpa is heated to 123 ℃ that the analytical pure calcium sulphate dihydrate is placed steam pressure, heated at constant temperature 7h, take out dry 4-5h in the electric heating aeration cabinet that is placed on 120 ℃ then, adopt airflow milling to pulverize the gained material and be α-sulfate hemihydrate powder body of diameter 5 μ m.
3. bata-tricalcium phosphate and α-half-H 2 O calcium sulphate are pressed the ratio of weight and number preparation of 8:2, in bata-tricalcium phosphate particle surface and/or space, form α-half-H 2 O calcium sulphate powder layer: with 2g α-sulfate hemihydrate powder body and 10ml dehydrated alcohol mixing, adopt plasma spraying method to spray in 8g bata-tricalcium phosphate particle surface and the hole thereof then, fully mixing is placed in 37 ℃ of baking boxs dehydrated alcohol is volatilized gradually, can make compound bone grafting granule.
Embodiment 4:
The compound bone grafting granule of embodiment 1 preparation adopted sem observation to see to have the organic spongy bone particle surface of taking off of microcellular structure covering α-half-H 2 O calcium sulphate powder body (Fig. 2).This cmposite artificial bone runs into aqueous solution can be cured as the agglomerate (Fig. 3) with certain mechanical strength, adopt biomechanics testing machine (MTS 858 Mini.Bionix 2 after solidifying 1h, USA) test compression intensity, 5 Time Compression intensity are between 10-15MPa.Combined artificial osseous granules X-ray diffraction collection of illustrative plates can be seen the crest (Fig. 4) that has bata-tricalcium phosphate and α-sulfate hemihydrate simultaneously.
Embodiment 5:
The combined artificial osseous granules that embodiment 1 is made is packed after according to suitable weight packing, is used for the repairing bone defect animal model after can adopting the Co60 sterilization.Adopt rabbit to make the damaged animal model of diameter 5mm bone on the condyle of femur, adopt compound bone grafting granule repairing bone defect, 1 day X line of postoperative can be seen the complete filling bone of bone-grafting material, and damaged (Fig. 5 a).Postoperative 4 week is put to death rabbit, cut open condyle of femur can see compound bone-grafting material be filled in bone damaged in, combine closely with bone interface, inflammatory reaction and fibrous tissue generation are not seen in the interface, and (Fig. 6 a).Postoperative 12 all X lines can be seen the bone-grafting material major part and degrade, and put to death rabbit and cut condyle of femur open, can see compound bone-grafting material major part and degrade, by area of new bone creeping substitution (Fig. 6 b).
Claims (9)
1. type of inorganic bone grafting material, by mass percent is that bata-tricalcium phosphate granule and the mass percent by microcellular structure of 20%-80% is that 80%-20% α-half-H 2 O calcium sulphate powder body is formed, and α-half-H 2 O calcium sulphate powder body is in bata-tricalcium phosphate particle surface that microcellular structure is arranged and/or the inner layer structure that forms of its hole.
2. a kind of type of inorganic bone grafting material according to claim 1 is characterized in that: the particulate diameter of described bata-tricalcium phosphate is 0.2-10mm.
3. the preparation method of the described type of inorganic bone grafting material of claim 1 comprises:
(1) preparation has the bata-tricalcium phosphate granule of microcellular structure;
(2) preparation α-half-H 2 O calcium sulphate powder body;
(3) the preparation mass percent is that bata-tricalcium phosphate granule and the mass percent of 20%-80% are 80%-20% α-half-H 2 O calcium sulphate powder body, forms α-half-H 2 O calcium sulphate powder layer in bata-tricalcium phosphate particle surface and/or hole.
4. the preparation method of type of inorganic bone grafting material according to claim 3, it is characterized in that: described (1) preparation has the bata-tricalcium phosphate granule of microcellular structure, be that the pulverizing of employing xenogenesis or allosome spongy bone is the 2-3mm granule for diameter, directly calcining, getting healthy spongy bone calcines in high temperature furnace after sloughing organic principle, following 3 hours of 800 ℃ of conditions, 10 ℃/minute of heating rates, the forging bone piece is soaked in the (NH that concentration is 1M after taking out
4)
2HPO
4In the solution 24 hours, remove unnecessary liquid, 50 ℃ of oven dry 4 days are put in once more in the high-temperature calcination stove and calcine, following 1 hour of 1100 ℃ of conditions, 5 ℃/minute of heating rates, slowly cooling, rinsed with deionized water 2 times, 50 ℃ of oven dry 4 days.
5. the preparation method of type of inorganic bone grafting material according to claim 3, it is characterized in that: described (1) preparation has the bata-tricalcium phosphate granule of microcellular structure, it is the calcium hydrogen phosphate under 800 ℃ of conditions 3 hours that adopts 2 parts by weight, change calcium pyrophosphate into, calcium carbonate with 1 parts by weight mixes the back tabletting then, the bata-tricalcium phosphate powder body is made in 1100 ℃ of condition slowly coolings after following 1 hour after the pulverizing, adopt the microporous foam technology to make the bata-tricalcium phosphate granule with microcellular structure.
6. the preparation method of type of inorganic bone grafting material according to claim 3, it is characterized in that: described (2) preparation α-half-H 2 O calcium sulphate powder body, be to be that raw material is positioned in the airtight autoclave that steam pressure is 0.13Mpa with the analytical pure calcium sulphate dihydrate, the per minute that heats up gradually heats up 5 ℃, be heated to 123 ℃, heated at constant temperature 7h takes out dry 4-5h in the electric heating aeration cabinet that is placed on 120 ℃ then, the gained material is pulverized, and mean diameter is smaller or equal to 5 μ m.
7. the preparation method of type of inorganic bone grafting material according to claim 3, it is characterized in that: described (3) preparation mass percent is that bata-tricalcium phosphate granule and the mass percent of 20%-80% is 80%-20% α-half-H 2 O calcium sulphate powder body, in bata-tricalcium phosphate particle surface and/or hole, form α-half-H 2 O calcium sulphate powder layer, be that to stir with dehydrated alcohol and α-half-H 2 O calcium sulphate be pasty state, adopt spraying method directly at bata-tricalcium phosphate particle surface spraying α-half-H 2 O calcium sulphate; Perhaps the bata-tricalcium phosphate granule is inserted in the above-mentioned pasty mixture and stir, make α-half-H 2 O calcium sulphate powder body be attached on bata-tricalcium phosphate particle surface and/or its hole inside; 37 ℃ of removal dehydrated alcohol that volatilize naturally.
8. the preparation method of type of inorganic bone grafting material according to claim 3, it is characterized in that: described (3) preparation mass percent is that bata-tricalcium phosphate granule and the mass percent of 20%-80% is 80%-20% α-half-H 2 O calcium sulphate powder body, forming α-half-H 2 O calcium sulphate powder layer in bata-tricalcium phosphate particle surface and/or hole, is to adopt plasma method directly to spray α-half-H 2 O calcium sulphate powder body to be fixed on the bata-tricalcium phosphate particle surface.
9. the method for the compound DBM of the described type of inorganic bone grafting material of claim 1, BMP, antibiotic or chemotherapeutics, it is characterized in that: DBM, BMP, antibiotic or chemotherapeutics are mixed with α-half-H 2 O calcium sulphate powder body, together spraying is fixed on the bata-tricalcium phosphate particle surface then, perhaps directly adds DBM, BMP, antibiotic or chemotherapeutics in type of inorganic bone grafting material.
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| EP2331151B1 (en) * | 2008-08-27 | 2012-07-11 | Noraker | Bone substitute containing porous bio-glass and calcium sulphate |
| CN101596330B (en) * | 2009-07-09 | 2013-04-10 | 毛克亚 | Alpha-calcium sulfate hemihydrates/beta-tertiary calcium phosphate porous granular-type composite artificial bones and preparation method thereof |
| CN102085389B (en) * | 2011-01-14 | 2013-10-16 | 北京大清生物技术有限公司 | Preparation method of injectable bone repair material |
| CN102626526A (en) * | 2012-04-20 | 2012-08-08 | 无锡圆容生物医药股份有限公司 | Novel active absorbable bone cement material |
| TWI651103B (en) | 2013-12-13 | 2019-02-21 | 萊特醫技股份有限公司 | Multiphase bone graft replacement material |
| CN105107023A (en) * | 2015-07-01 | 2015-12-02 | 李亚屏 | Degradable porous composite scaffold material for bone transplantation |
| WO2018209579A1 (en) * | 2017-05-17 | 2018-11-22 | 高雄医学大学 | Composite scaffold containing drug |
| CN110236710A (en) * | 2018-03-09 | 2019-09-17 | 中日友好医院 | A method of promote bone-grafting material to promote postoperative skeletonization outside Dental implantion maxillary sinus |
| CN108525004B (en) * | 2018-05-09 | 2020-11-17 | 湖北民族学院 | Alpha-hemihydrate gypsum/hydroxyapatite composite microsphere and preparation method thereof |
| CN109793922A (en) * | 2019-03-01 | 2019-05-24 | 昆明理工大学 | A kind of calcium sulphate dihydrate/monetite Core-shell structure material and preparation method thereof |
| CN109821066A (en) * | 2019-03-04 | 2019-05-31 | 昆明理工大学 | A kind of preparation method of gelatin/dicalcium phosphate dihydrate/calcium sulphate dihydrate porous support |
| CN110251723A (en) * | 2019-08-01 | 2019-09-20 | 陶合体科技(苏州)有限责任公司 | A kind of porous composite ceramics and preparation method thereof being able to guide osteanagenesis |
| CN110282998A (en) * | 2019-08-01 | 2019-09-27 | 陶合体科技(苏州)有限责任公司 | Calcium phosphate porous ceramics and preparation method thereof based on calcium sulfate salt cladding |
| CN112479737B (en) * | 2020-12-09 | 2022-04-22 | 南京航空航天大学 | Controllable porous biological ceramic support and preparation method and application thereof |
| CN114404654B (en) * | 2022-01-28 | 2022-11-01 | 河南科技大学 | High-strength magnetic bone cement and preparation method thereof |
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