CN101417149B - Degradable biological composite material of phosphate containing calcium and preparation method thereof - Google Patents
Degradable biological composite material of phosphate containing calcium and preparation method thereof Download PDFInfo
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- CN101417149B CN101417149B CN2008100463421A CN200810046342A CN101417149B CN 101417149 B CN101417149 B CN 101417149B CN 2008100463421 A CN2008100463421 A CN 2008100463421A CN 200810046342 A CN200810046342 A CN 200810046342A CN 101417149 B CN101417149 B CN 101417149B
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Abstract
The invention provides a degradable bioactivity composite containing calcium phosphate and a preparation method thereof. The composite consists of calcium phosphate and a multiple amino acid polymer; wherein, the weight percentage of inorganic composition is not more than 50 percent and the residual substance is the multiple amino acid polymer which is formed by the polymerization of caprolactam and at least 5 other amino acids; wherein, the molar ratio of the caprolactam in the polymer is 40-90 percent and the respective molar ratio of other single amino acid is not less than 0.5 percent. During preparation, the caprolactam is mixed with all amino acids and dehydration is carried out under the protection of inert gases and stirring, and pre-polymerization composition reaction and polymerization reaction are respectively carried out at the temperature of 210-250DEG C, thus obtaining the composite. The indexes of the prepared material such as mechanic performance, degradation period and the like can be adjusted and controlled according to the use requirements.
Description
Technical field
The present invention relates to degradable biological medical composite material of a kind of calcareous phosphate component and preparation method thereof.
Background technology
Existing at present report and/or the biological activity medical composite material that contains calcareous phosphate inorganic constituents that uses comprise two types of degradable and non-degradables.Degradable composition is just like Ca (H
2PO
4)
2(MCP), Ca
2P
2O
7(CPP), CaHPO
42H
2O (DCP), Ca
3(PO
4)
2(TCP) etc.; Nondegradable composition can include like Ca
10(PO
4)
6(HO)
2(HA), Ca
10(PO
4)
6O (OXA) and CaOCa
3(PO
4)
2(TTCP) etc.Because it has good biological activity and biocompatibility, be widely used in bone reparation and bone and rebuild the field.Tricalcium phosphate (TCP) particularly as wherein because of its calcium/phosphorus ratio in forming is 1.5 and degradable, has good biology performance; Can transmitting tissue grow; Promptly have bone conductibility, behind the moulding material implanting to human body, can form synostosis (being biological activity) with body tissue in a short time.The existence form of TCP has β-type and two kinds of crystal phase structures of α-type.Wherein β-TCP is the low temperature phase, and stable existence is below room temperature to 1120 ℃; α-TCP then is the high temperature phase, and stable existence in 1120 ℃～1470 ℃ scopes can meta exist under anhydrous room temperature.Tricalcium phosphate (TCP) has and the different biological property of hydroxyapatite (HA), and the main distinction is that biodegradation can take place TPC, and implanting can be by bio-absorbable.In general, the degradation rate of α-TCP is greater than β-TCP, and changes the apatite phase into through hydrolysis easily.α-TCP good than β-TCP aspect biocompatibility, also more better aspect biological activity than HA.Though calcareous phosphate has good biological activity, its intensity is low, and fragility is big, the easy fracture.Many at present with the coating form appearance, can't be used for the reparation of bearing position.
In order to obtain ideal hard tissue repair and reconstruction biomaterials, the composite of polymer/inorganic salt is by extensive studies and application.This type composite has the toughness and the calcareous phosphatic biological activity of polymer concurrently, can use in the force part, thereby reach the purpose of repair and reconstruction.This type composite also can be divided into two types of non-degradable and degradables.For example, polyethylene kind and polyamide-based composite that main at present research and the inert polymer composite of using are filled with HA, its shortcoming is that the dispersibility of HA in polymer is relatively poor, and form and composition and osseous tissue gap are bigger, and use is restricted.The degradable composite material that another kind of research is more is the composite of polylactic acid series and HA and TCP.Polylactic acid generally can be degraded and absorbed less than six months in vivo fully, and degradation speed is difficult to accurate control, and catabolite has inflammation and stimulation to body tissue, so its material The Nomenclature Composition and Structure of Complexes performance all need be improved.
Research is thought; The reconstruction of ideal sclerous tissues, reparation and molding material, what need is the composite of controlled degradation, its mechanical property can progressively reduce with the repair and reconstruction of tissue; And the degraded composition progressively is absorbed metabolism and tissue is not produced side effect such as stimulation, inflammation; After tissue reconstruction was accomplished, material was degraded basically and absorbs, and formed bone and advanced the collaborative processes that material moves back.Employed above-mentioned polymer/inorganic salt composite still can not satisfy this instructions for use at present, and it is necessary therefore studying and can being adapted to biological activity bionic biomaterial internal milieu, that have excellent mechanical property, controllable degradation speed.
Summary of the invention
Given this; The present invention will provide the degradable biological medical composite material of the calcareous phosphate component of a kind of new model; Make it become biomechanical property and the good biological activity and the compatibility that can not only have with from body bone coupling; And have good and bionic biomedical and an organizational project composite controllable degradation speed, to satisfy medical science and use needs in hard tissue repair and the reconstruction field clinically.On this basis, the present invention also will provide the method for preparing of the degradable biological medical composite material of said this calcareous phosphate component.
The degradable biological composite material of the said calcareous phosphate component of the present invention; Form by calcareous phosphate component and polynary amino acid polymer; Wherein the weight of calcareous phosphate component is the 5wt%～50wt% of composite gross weight; Wherein the content with 30～40wt% is good; All the other are by caprolactam and at least 5 kinds of polynary amino acid polymer compositions that other aminoacid is polymerized; Wherein the molar ratio of caprolactam is 40%～90% in the component of polymer, and all the other are other aminoacid of the amino acid whose molar ratio of each single kind >=0.5%, and said other aminoacid is selected from glycine, alanine, leucine, isoleucine, valine, threonine, serine, phenylalanine, tyrosine, tryptophan, proline, hydroxyproline, lysine and arginine.The above-mentioned CaHPO that said calcareous phosphate component can adopt existing at present report and/or use
42H
2O (DCP), Ca
3(PO
4)
2(TCP), Ca
10(PO
4)
6(HO)
2(HA) etc. can under the intravital humoral effect of people, discharge calcium, phosphonium ion, help promoting the composition of bone growth and healing.
For making above-mentioned composite satisfy biological activity and biocompatibility requirement to greatest extent; Said other aminoacid in first amino acid polymer composition in the above-mentioned composition; To adopt acceptable natural alkalescence of human body and/or neutral amino acid as far as possible is good, the natural amino acid of forms such as corresponding L-tyrosine, L-phenylalanine, L-lysine, L-proline in said each seed amino acid.
The test demonstration, under the prerequisite that guarantees material property, said polynary amino acid polymer composition in the above-mentioned composite of the present invention; Generally adopt by caprolactam and 5 kinds of said other amino acid whose composition forms; Can obtain satisfied effect, and can simplify composition, reduce cost.
In composite of the present invention, for making said calcareous phosphate component better dispersibility is arranged, in order to giving full play to its biological effect, therefore said calcareous phosphate component being that the form of nano_scale particle is good.For this reason, used calcareous phosphate component can adopt the corresponding inorganic salt slurry form by above-mentioned existing report and/or use.
For guaranteeing and improve its biocompatibility and effect that the calcium in the said calcareous phosphate component/phosphorus mol ratio is ideal with the scope that is adopted as (1～2)/1.
Test shows; The above-mentioned composite that can be used for tissue repair or tissue engineering bracket of the present invention; Its degradation property and mechanical property can be by regulating caprolactam and other amino acid whose kind, ratio and/or polymerization process; Molecular weight through changing polymer is controlled and is regulated, and can also control and regulate through adjusting calcareous phosphatic kind and content, thereby can obtain meeting the mechanical property of instructions for use and/or the composite of degradation speed.Testing result shows; The comprcssive strength of the above-mentioned composite of the present invention can be in 40～150Mpa scope inner control and adjustment; Bending strength can be in 30～120Mpa scope inner control and adjustment; Tensile strength can be in 30～140Mpa scope inner control and adjustment, and elastic modelling quantity can be in 0.5～10Gpa scope inner control and adjustment; In simulated body fluid, soaking the degradation speed in 12 weeks can be in 5%～100% scope inner control and adjustment, and the bone that these performances can adapt to well and satisfy under the different situations is repaired needs.
When the above-mentioned degradable biological composite material of the present invention prepares; For guaranteeing the wherein nanoscale state of inorganic salt composition; Can adopt said calcareous phosphate inorganic salt composition slurry (moisture content generally can greater than 95%) is mixed mutually with caprolactam and 5 kinds of other aminoacid ingredients of said ratio at least; Inert gas shielding with fully stir under behind 80 ℃～200 ℃ moisture that fully removes in the material; Carry out the prepolymerization compound reaction in 210 ℃～220 ℃, carry out polyreaction in 230 ℃～250 ℃ then, obtain said composite.With above-mentioned, and is good with the calcareous phosphate component of adopting meter level to said calcareous phosphate component as raw material; The range of choice of said other aminoacid ingredient except that caprolactam is also with above-mentioned.Generally speaking, said other aminoacid can adopt 5 kinds in selection glycine, alanine, leucine, isoleucine, valine, threonine, serine, phenylalanine, tyrosine, tryptophan, proline, hydroxyproline, lysine and the arginine can reach comparatively ideal effect.
To used calcareous phosphate component, be good all to adopt mode through reacting current preparation.For example; A kind of mode that can reference is to be raw material with calcium/phosphorus mol ratio for the lime nitrate and the sodium phosphate (or other corresponding soluble component) of (1～2)/1; Regulate pH with what select to be easy to remove noresidue like compositions such as sodium carbonate or sodium bicarbonate, fully precipitate and wash the calcareous phosphate component slurry of resulting nanoscale afterwards.
Prepolymerization reaction and polyreaction in the above-mentioned preparation process can be accomplished in the scope at 0.5～5 hour respectively generally speaking, and the yield of composite products generally can reach more than 90%.In the preparation process, the change that increases according to reaction mass viscosity in the course of reaction, and/or situation such as darken, and/or combine different modes such as said response time, can realize control to each step polyreaction process.
After said calcareous phosphate has adopted slurry form in the above-mentioned preparation process; Owing to kept the microgranule of its nanoscale state effectively; Can have the activity of bigger surface area and Geng Gao than micro-size particles; Therefore can make the inorganic salt composition be evenly distributed in very much high molecular polymer mutually in, have good organic/inorganic interface, thereby improve the performance of product material better.
In the above-mentioned preparation process of the present invention, adopt caprolactam as main polymer monomer.Because this monomeric fusing point lower (79 ℃), at first fusion after being heated, remaining aminoacid can dissolve in the caprolactam of molten state and forms uniform molten mass with the rising of temperature gradually, and this is that ten minutes is favourable to the polymer that forms even molecular weight distribution.
Because composite of the present invention does not add any other raw material in the preparation process, do not produce outer any other small-molecule substance that dewaters yet, this will be highly advantageous to and guarantee the biocompatibility of the material that obtains.And another important feature of this method for preparing is simple, and control is with low cost easily, especially uses nano level inorganic salt slurry, and performance of composites is greatly improved.
Inorganic salt composition in the above-mentioned composite of the present invention is verified and at the material with good biological safety that uses, and degradable is calcium ion and corresponding phosphate anion under humoral effect; Aminoacid in the polymer moieties also is the acceptable composition of human body, thereby can have excellent biomechanical property and the biological activity and the compatibility, helps organizing the interaction with cell and storeroom.Product after the degraded is near neutral oligopeptide or aminoacid micromolecule, or is that carbon dioxide and water are discharged through metabolic degradation further, and safety is very high.Zoopery is the result show: this material non-toxic, non-stimulated, nothing allergy, no any untoward reaction between material and the tissue.Behind this polymer bone-renovation material implantable bioartificial body, under the effect of body tissue, can progressively degrade, can use, reach the purpose of repair and reconstruction in the force part according to the degradation speed cycle of design in advance.Thereby be a kind of have controllable degradation speed, with from the biomechanical property of body bone coupling and the bionic biomedical and the tissue engineering material of the good biological activity and the compatibility, improved existing deficiency of present similar repair materials and problem.
The specific embodiment below in conjunction with embodiment is done further to specify to foregoing of the present invention again.But should this be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following instance.Do not breaking away under the above-mentioned technological thought situation of the present invention, various replacements or change according to ordinary skill knowledge and customary means are made all should comprise within the scope of the invention.
The specific embodiment
Embodiment 1
With 70.845g Ca (NO
3)
24H
2O is dissolved in the 300ml deionized water, fully after the dissolving, through the uncovered beaker of the 100ml that packs into after No. 4 glass hourglass buckets filtrations; With 76.04g Na
3PO
412H
2O is dissolved in the 200ml deionized water, after treating to dissolve fully, filters with No. 4 glass hourglass buckets, puts into separatory funnel.In stirring at room with under with sodium bicarbonate adjusting and maintenance pH6.9～7.1 conditions, sodium radio-phosphate,P-32 solution is dropped in the calcium nitrate solution, added in 20 minutes.Be heated to 80 ℃ and kept 2 hours, the natural cooling sealing, leave standstill 48 hours after, remove clear liquid, deionized water wash 6 times, nanoscale calcium phosphate slurry, content is 3.75wt%, the Ca/P mol ratio is 1.51, and is subsequent use.
Add above-mentioned calcium phosphate slurry 1000g and caprolactam 45.2g, glycine 0.75g, leucine 1.31g in the three-necked bottle; Phenylalanine 2.475g, lysine 1.46g, proline are 2.875g; Serine is 1.051g, alanine 1.782g, and nitrogen protection is stirred down and is warming up to 80 ℃; Caprolactam melts, and stirring down, continuation slowly was warming up to 200 ℃ of constant temperature 1 hour.Be warming up to 220 ℃ and carry out the prepolymerization compound reaction after 2 hours, be warming up to 230 ℃ again and carried out polyreaction 2 hours, cool to room temperature gets light yellow composite product 87g.The testing result of gained composite product: the content of calcium phosphate in composite is 40%; Comprcssive strength is 120Mpa, and tensile strength is 100Mpa, bending strength 90Mpa, elastic modelling quantity 4.5Gpa; Weight-loss ratio in simulated body fluid behind the immersion 12w is 62%.
Embodiment 2
The preparation of nano-calcium phosphate slurry is with embodiment 1.
Add nano-calcium phosphate slurry 1000g and the caprolactam 45.2g that presses the preparation of embodiment 1 the same manner, glycine 0.75g, leucine 1.31g in the three-necked bottle; Phenylalanine 2.475g, lysine 1.46g, proline are 2.875g; Serine is 1.051g, alanine 1.782g, and nitrogen protection is stirred down and is warming up to 70 ℃; Caprolactam melts, and continues to stir to be warming up to 200 ℃ and constant temperature 1 hour.Be warming up to 220 ℃ and carry out prepolymerization reaction 0.5 hour, be warming up to 230 ℃ again and carried out polyreaction 1 hour, cool to room temperature gets light yellow composite product 88.5g.The testing result of gained composite product: the calcium phosphate content in the composite is 40%; Comprcssive strength is 102Mpa, and tensile strength is 95Mpa, bending strength 74Mpa, elastic modelling quantity 2.5Gpa; Weight-loss ratio in simulated body fluid behind the immersion 12w is 85%.
Embodiment 3
The preparation of nano-calcium phosphate slurry is with embodiment 1.
Add nano-calcium phosphate slurry 1000g and the caprolactam 45.2g that presses the preparation of embodiment 1 the same manner, glycine 0.75g, leucine 1.31g in the three-necked bottle; Phenylalanine 2.475g, lysine 1.46g, proline are 2.875g; Serine is 1.051g, alanine 1.782g, and nitrogen protection is stirred down and is warming up to 70 ℃; Caprolactam melts, and continues to stir to be warming up to 200 ℃ and constant temperature 1 hour.Be warming up to 220 ℃ and carry out prepolymerization reaction 5 hours, be warming up to 230 ℃ again and carried out polyreaction 4.5 hours, cool to room temperature gets light yellow composite product 85g.The testing result of gained composite product: the calcium phosphate content in the composite is 40%; Comprcssive strength is 143Mpa, and tensile strength is 131Mpa, bending strength 115Mpa, elastic modelling quantity 8.5Gpa; Weight-loss ratio in simulated body fluid behind the immersion 12w is 23%.
The foregoing description 1～3 shows, prepares the prepolymerization/polymerization reaction time in the process through changing the present invention, can realize the purpose that the correlated performance of products therefrom material is adjusted.
Embodiment 4
Add nano-calcium phosphate slurry 370g and the caprolactam 7.91g that presses the preparation of embodiment 1 the same manner, glycine 0.75g, leucine 1.31g in the three-necked bottle; Phenylalanine 2.475g, lysine 1.46g, proline are 2.875g; Serine is 1.051g, and alanine 1.782g is warming up to 80 ℃ under nitrogen protection and the stirring; Caprolactam melts, and continues to stir slowly to be warming up to 200 ℃ and constant temperature 1 hour.Be warming up to 220 ℃ and carry out the prepolymerization compound reaction after 0.5 hour, be warming up to 230 ℃ again and carried out polyreaction 1 hour, cool to room temperature gets light yellow composite product 30.5g.The testing result of gained composite product: the calcium phosphate content in the composite is 40%; Comprcssive strength is 35Mpa, and tensile strength is 31Mpa, bending strength 19Mpa, elastic modelling quantity 1.1Gpa; Weightlessness 100% behind the immersion 12w in simulated body fluid.
Embodiment 5
Add nano-calcium phosphate slurry 2050g and the caprolactam 101.7g that presses the preparation of embodiment 1 the same manner, glycine 0.75g, leucine 1.31g in the three-necked bottle; Phenylalanine 2.475g, lysine 1.46g, proline are 2.875g; Serine is 1.051g, and alanine 1.782g is warming up to 80 ℃ under nitrogen protection and the stirring; Caprolactam melts, and continues to stir slowly to be warming up to 200 ℃ and constant temperature 1 hour.Be warming up to 220 ℃ and carry out the prepolymerization compound reaction after 0.5 hour, be warming up to 230 ℃ again and carried out polyreaction 1 hour, cool to room temperature gets light yellow composite product 180g.The testing result of gained composite product: the calcium phosphate content in the composite is 40%; Comprcssive strength is 121Mpa, and tensile strength is 107Mpa, bending strength 91Mpa, elastic modelling quantity 4.6Gpa; Weightlessness 61% behind the immersion 12w in simulated body fluid.
The foregoing description 2,4 and 5 shows, through changing and adjust the ratio of different aminoacids raw material, also can reach the purpose that changes as required and adjust gained composite correlated performance.
Embodiment 6
Add nano-calcium phosphate slurry 85g and the caprolactam 45.2g that presses the preparation of embodiment 1 the same manner, glycine 0.75g, leucine 1.31g in the three-necked bottle; Phenylalanine 2.475g, lysine 1.46g, proline are 2.875g; Serine is 1.051g, alanine 1.782g, and nitrogen protection and stirring are warming up to 80 ℃; Caprolactam melts, and continues to stir slowly to be warming up to 200 ℃ and constant temperature 1 hour.Be warming up to 220 ℃ and carried out the prepolymerization compound reaction 0.5 hour, continue to be warming up to 230 ℃ again and carried out polyreaction 1 hour, cool to room temperature gets light yellow composite product 97.5g.The testing result of gained composite product: the calcium phosphate content in the composite is 5%; Comprcssive strength is 85Mpa, and tensile strength is 81Mpa, bending strength 62Mpa, elastic modelling quantity 2.8Gpa; Weightlessness 63% behind the immersion 12w in simulated body fluid.
Embodiment 7
Add nano-calcium phosphate slurry 400g and the caprolactam 45.2g that presses the preparation of embodiment 1 the same manner, glycine 0.75g, leucine 1.31g in the three-necked bottle; Phenylalanine 2.475g, lysine 1.46g, proline are 2.875g; Serine is 1.051g, alanine 1.782g, and nitrogen protection and stirring are warming up to 80 ℃; Caprolactam melts, and continues to stir slowly to be warming up to 200 ℃ and constant temperature 1 hour.Be warming up to 220 ℃ and carried out the prepolymerization compound reaction 0.5 hour, continue to be warming up to 230 ℃ again and carried out polyreaction 1 hour, cool to room temperature gets light yellow composite product 97.5g.The testing result of gained composite product: the calcium phosphate content in the composite is 20%; Comprcssive strength is 97Mpa, and tensile strength is 86Mpa, bending strength 75Mpa, elastic modelling quantity 3.8Gpa; Weightlessness 72% behind the immersion 12w in simulated body fluid.
The foregoing description 2,6 and 7 result reality change and adjustment inorganic salt components in proportions, can realize the purpose that the correlated performance of composite is adjusted equally.
Embodiment 8
Ca (NO with 23.615g
3)
24H
2The Na of O and 38.02g
3PO
412H
2O is dissolved in the 100ml deionized water respectively and with after No. 4 glass hourglass buckets filtrations, is under 5.0～6.5 conditions sodium radio-phosphate,P-32 solution to be added dropwise in the calcium nitrate solution in stirring at room with using sodium bicarbonate to regulate and keep pH value, adds in 10 minutes.Dropwise post-heating to 80 ℃ maintenance 2 hours, natural cooling, sealing and standing was removed clear liquid after 48 hours, and deionized water centrifuge washing 6 times gets nanoscale calcium hydrogen phosphate slurry 50g, and calcium hydrogen phosphate content is 4.2wt%, and the Ca/P mol ratio is 1.05.
Add above-mentioned calcium hydrogen phosphate slurry 485g and caprolactam 45.2g in the three-necked bottle, glycine 0.75g, alanine 3.56g, phenylalanine 2.475g, lysine 1.46g, proline are 2.875g.Under nitrogen protection, stir and to be warming up to 80 ℃, caprolactam melts, and continues to stir slowly to be warming up to 200 ℃ and constant temperature 1 hour.Be warming up to 220 ℃ then and carried out the prepolymerization compound reaction 5 hours, be warming up to 250 ℃ again and carried out polyreaction 5 hours, cool to room temperature gets light yellow composite product 69.5g.The testing result of gained composite product: the calcium phosphate content in the composite is 25%; Comprcssive strength is 120Mpa, and tensile strength is 109Mpa, bending strength 101Mpa, elastic modelling quantity 6.9Gpa; After in simulated body fluid, soaking 12w, weightless 26%.
Embodiment 9
Ca (NO with 118.1g
3)
2.4H
2The Na of O and 114.06g
3PO
412H
2O is dissolved in the 300ml deionized water respectively and with after No. 4 glass hourglass buckets filtrations, is under 7.0～7.3 conditions in stirring at room with using sodium bicarbonate to regulate and keep pH value, and sodium radio-phosphate,P-32 solution is dropped in the calcium nitrate solution, added in 20 minutes.Dropwise, be heated to 80 ℃ and kept 2 hours, the natural cooling sealing was placed 48 hours.Remove clear liquid, deionized water centrifuge washing 6 times gets nano-grade hydroxy apatite slurry 300g, hydroxyapatite content 4.5wt%, and the Ca/P mol ratio is 1.65.
Add above-mentioned calcareous phosphate slurry and the caprolactam 45.2g of 745g, glycine 0.75g, alanine 3.56g in the three-necked bottle; Phenylalanine 2.475g; Lysine 1.46g, proline are 2.875g, are warming up to 80 ℃ under nitrogen protection and the stirring; Caprolactam melts, and continues to stir slowly to be warming up to 200 ℃ and constant temperature 1 hour.Be warming up to 220 ℃ and carry out the prepolymerization compound reaction after 5 hours, be warming up to 240 ℃ again and carried out polyreaction 5 hours, cool to room temperature gets light yellow composite product 84.5g.The testing result of gained composite product: the calcareous phosphate content in the composite is 36%; Comprcssive strength is 150Mpa, and tensile strength is 138Mpa, bending strength 115Mpa, elastic modelling quantity 8.6Gpa; After in simulated body fluid, soaking 12w, weightless 11%.
Embodiment 10
The nanometer hydroxyapatite slurry preparation method is with example 9
Add above-mentioned calcareous phosphate slurry and the caprolactam 45.2g of 745g, glycine 0.75g, serine 2.11g in the three-necked bottle; Arginase 12 .61g, threonine 1.19g, lysine 1.46g; Hydroxyproline is 3.28g, and tyrosine 1.81g is warming up to 80 ℃ under nitrogen protection and the stirring; Caprolactam melts, and continues to stir slowly to be warming up to 200 ℃ and constant temperature 1 hour.Be warming up to 220 ℃ and carry out the prepolymerization compound reaction after 5 hours, be warming up to 240 ℃ again and carried out polyreaction 5 hours, cool to room temperature gets light yellow composite product 86.5g.The testing result of gained composite product: the calcareous phosphate content in the composite is 34%; Comprcssive strength is 120Mpa, and tensile strength is 108Mpa, bending strength 102Mpa, elastic modelling quantity 6.6Gpa; After in simulated body fluid, soaking 12w, weightless 17%.
Embodiment 11
The calcium hydrogen phosphate slurry preparation method is with example 8
Add above-mentioned inorganic salt slurry and the caprolactam 45.2g of 100g, glycine 1.5g, tryptophan 0.75g in the three-necked bottle; Valine 1.76g, isoleucine 1.31g, lysine 2.92g; Hydroxyproline is 1.97g, and tyrosine 1.81g is warming up to 80 ℃ under nitrogen protection and the stirring; Caprolactam melts, and continues to stir slowly to be warming up to 200 ℃ and constant temperature 1 hour.Be warming up to 220 ℃ and carry out the prepolymerization compound reaction after 5 hours, be warming up to 240 ℃ again and carried out polyreaction 5 hours, cool to room temperature gets light yellow composite product 86.5g.The testing result of gained composite product: the calcareous phosphate content in the composite is 30%; Comprcssive strength is 123Mpa, and tensile strength is 105Mpa, bending strength 99Mpa, elastic modelling quantity 7.6Gpa; After in simulated body fluid, soaking 12w, weightless 37%.
Comparative Examples 1
Ca (NO with 118.1g
3)
24H
2The Na of O and 114.06g
3PO
412H
2O is dissolved in the 300ml deionized water respectively and with after No. 4 glass hourglass buckets filtrations, is under 7.0～7.3 conditions sodium radio-phosphate,P-32 solution to be dropped in the calcium nitrate solution in stirring at room with using sodium bicarbonate to regulate and keep pH value, adds in 20 minutes.Dropwise, be heated to 80 ℃ and kept 2 hours, the natural cooling sealing was placed 48 hours.Remove clear liquid, deionized water centrifuge washing 6 times gets calcium phosphate slurry 300g, and calcium phosphate is 33.5wt%.Oven dry.Product is a white powder, is white inorganic salt particle behind the sintering, and is crisp, hard, and behind the immersion 12w, weightlessness 2% is difficult to degraded in simulated body fluid.
Comparative Examples 2
Add caprolactam 26g in the three-necked bottle, glycine 6g, alanine 26.7g, phenylalanine 24.75g, lysine 2.92, proline divides 5.75g, and stirring slowly is warming up to 200 ℃ and kept 1 hour under the nitrogen protection.Be warming up to 220 ℃ and carry out the prepolymerization compound reaction after 1 hour, be warming up to 230 ℃ again and carried out polyreaction 1.5 hours, cool to room temperature gets brownish red polymeric articles 93.8g; Fusing point is 120 ℃.The testing result of products obtained therefrom: comprcssive strength is 30Mpa, and tensile strength is 45Mpa, bending strength 40Mpa, elastic modelling quantity 1.1Gpa; After in simulated body fluid, soaking 12w, weightless 95%.Because of it does not contain calcareous phosphate component, and the molar ratio of caprolactam is lower, so product is soft, mechanical strength is lower.
Claims (9)
1. the degradable biological composite material of calcareous phosphate component; It is characterized in that forming by calcareous phosphate component and polynary amino acid polymer; Wherein calcareous phosphate component is 5～50wt% of gross weight; All the other are by caprolactam and at least 5 kinds of polynary amino acid polymer compositions that other aminoacid is polymerized; Wherein the molar ratio of caprolactam is 40%～90% in the component of polymer; All the other are other aminoacid of the amino acid whose molar ratio of each single kind >=0.5%, and said other aminoacid is selected from glycine, alanine, leucine, isoleucine, valine, threonine, serine, phenylalanine, tyrosine, tryptophan, proline, hydroxyproline, lysine and arginine.
2. the degradable biological composite material of calcareous phosphate component as claimed in claim 1 is characterized in that other aminoacid in the said polynary amino acid polymer composition is acceptable natural alkalescence of human body and/or neutral amino acid.
3. the degradable biological composite material of calcareous phosphate component as claimed in claim 1 is characterized in that said polynary amino acid polymer composition is made up of caprolactam and 5 kinds of other aminoacid.
4. the degradable biological composite material of calcareous phosphate component as claimed in claim 1 is characterized in that said calcareous phosphate component is a nano_scale particle.
5. the degradable biological composite material of calcareous phosphate component as claimed in claim 1, the content that it is characterized in that said calcareous phosphate component is 30～40wt% of gross weight.
6. like the degradable biological composite material of the described calcareous phosphate component of one of claim 1 to 5, it is characterized in that the calcium/phosphorus mol ratio in the said calcareous phosphate component is (1～2)/1.
7. the method for preparing the degradable biological composite material of the said calcareous phosphate component of claim 1; It is characterized in that said calcareous phosphate component slurry is mixed with caprolactam and 5 kinds of other aminoacid ingredients of said ratio at least; Inert gas shielding with fully stir under behind 80 ℃～200 ℃ moisture that fully removes in the material; Carry out the prepolymerization compound reaction in 210 ℃～220 ℃; And then carry out polyreaction in 230 ℃～250 ℃, and obtaining said composite, prepolymerization compound reaction and polymerization reaction time are 0.5～5 hour respectively.
8. method for preparing as claimed in claim 7 is characterized in that said other aminoacid ingredient is acceptable natural alkalescence of human body and/or neutral amino acid.
9. method for preparing as claimed in claim 7 is characterized in that said other aminoacid is 5 kinds that are selected from glycine, alanine, leucine, isoleucine, valine, threonine, serine, phenylalanine, tyrosine, tryptophan, proline, hydroxyproline, lysine and the arginine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008100463421A CN101417149B (en) | 2008-10-22 | 2008-10-22 | Degradable biological composite material of phosphate containing calcium and preparation method thereof |
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| CN101698117B (en) * | 2009-10-27 | 2012-11-07 | 张为鹏 | Bone-repairing composite material and method for preparing the same |
| CN107841149B (en) * | 2016-09-29 | 2020-10-23 | 四川大学 | Preparation method of hydrophilic polyphosphate amino acid copolymer composite material |
| CN106823010A (en) * | 2016-12-28 | 2017-06-13 | 四川国纳科技有限公司 | The purposes of bioabsorbable polyphosphate amino acid copolymer material |
| CN112546296B (en) * | 2020-12-14 | 2022-04-22 | 中鼎凯瑞科技成都有限公司 | Composite bone repair material with light display effect and self-positioning function and preparation method thereof |
| CN113181430A (en) * | 2021-04-12 | 2021-07-30 | 北京冬曦既驾科技咨询有限公司 | Medical ceramic slurry for additive manufacturing and medical article prepared from medical ceramic slurry |
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| WO2001051027A2 (en) * | 2000-01-11 | 2001-07-19 | Intralytix, Inc. | Polymer blends as biodegradable matrices for preparing biocomposites |
| CN1958082A (en) * | 2006-09-14 | 2007-05-09 | 清华大学 | Mineralized polypeptide material in use for repairing bones, and preparation method |
| WO2007067561A2 (en) * | 2005-12-06 | 2007-06-14 | Etex Corporation | Porous calcium phosphate bone material |
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| WO2001051027A2 (en) * | 2000-01-11 | 2001-07-19 | Intralytix, Inc. | Polymer blends as biodegradable matrices for preparing biocomposites |
| WO2007067561A2 (en) * | 2005-12-06 | 2007-06-14 | Etex Corporation | Porous calcium phosphate bone material |
| CN1958082A (en) * | 2006-09-14 | 2007-05-09 | 清华大学 | Mineralized polypeptide material in use for repairing bones, and preparation method |
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