CN101020079B - Modified artificial bone of coral with controllable degradation rate and its preparation process - Google Patents
Modified artificial bone of coral with controllable degradation rate and its preparation process Download PDFInfo
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- CN101020079B CN101020079B CN 200710027134 CN200710027134A CN101020079B CN 101020079 B CN101020079 B CN 101020079B CN 200710027134 CN200710027134 CN 200710027134 CN 200710027134 A CN200710027134 A CN 200710027134A CN 101020079 B CN101020079 B CN 101020079B
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- coral
- artificial bone
- calcium carbonate
- hydroxyapatite
- modified artificial
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Abstract
The modified artificial coral bone with controllable degradation rate is prepared with natural coral with 3D structure as the substrate and through hydrothermal chemical reaction. The modified artificial coral bone consists of calcium carbonate in 30-70 wt% and hydroxyapatite. The preparation process of the modified artificial coral bone includes the following steps: 1.rgtg the temperature and pressure inside high pressure kettle and making natural coral change chemically to obtain the mixture of calcium carbonate and hydroxyapatite; and 2. controlling the time of chemical reaction to controlthe content of calcium carbonate and hydroxyapatite in the artificial bone. The present invention has controlled hydroxyapatite degrading rate for the implanted artificial bone to maintain in body for 1-2 years without permanent retention in body.
Description
Technical field
The present invention relates to a kind of modified artificial bone of coral with controllable degradation rate and preparation method thereof, relate to specifically the different degradation rate artificial bone of different parts requirement packing material, be adapted at the application in bone wound surgery and the plastic and reconstructive surgery.Belong to biomedical materials field.
Background technology
Natural coral commonly used, its main component is aragonite, chemical constituent is calcium carbonate, because it has the three-dimensional porous structure similar to skeleton, once is applied to the damaged filling of clinical bone, can play bone guided effect.And the composition of its calcium is the essential element of skeleton, and catabolite is free from side effects, and presentation is good biocompatibility.But, because the effect of the carbonic anhydrase in the human body makes the Corallium Japonicum Kishinouye of filling just degradable when skeleton does not heal, so cause that bone is damaged again, affect bone healing.Research afterwards finds that in autoclave, Corallium Japonicum Kishinouye and ammonium di-hydrogen phosphate under suitable temperature, pressure, can obtain keeping Corallium Japonicum Kishinouye micro structure pure ha, i.e. coral hydroxyapatite through " hydro-thermal reaction ".The inorganic constituents of this product and skeleton is identical, and through zoopery and clinical verification, coral hydroxyapatite is gradually by Europe and north america approval, the biological safety of coral hydroxyapatite and biological activity are through for many years checking, generally approved, namely based on good biocompatibility and the body internal stability of this product, the finer and close hydroxyapatite product of Corallium Japonicum Kishinouye is developed to artificial bone, is widely used in now clinical as commodity.
Yet in the clinical course of using coral hydroxyapatite, people find again, although this product can well merge hard degradation with people's bone.There is external scholar to find, the coral hydroxyapatite in 6 years of implant into body, still remain intact, degradation rate is less than 10% or lower, the coral hydroxyapatite that is prior art can not be degraded, can retain in the long-term body after implanting, its anti-biological aging characteristic is very poor, and this is an obvious defective.Therefore, the coral hydroxyapatite of prior art is not desirable artificial bone.
Desirable artificial bone should be to have good biological safety and biological activity, and has good anti-biological aging effect.Best anti-biological aging is exactly to be absorbed fully by body and utilizes and not residual.Be when bone healing, to be degraded after in the artificial bone implant into body and to be absorbed, can not retain in the human body for a long time.
Summary of the invention
First purpose of the present invention is the shortcoming that retains in can long-term body after being difficult to degrade, implant for the coral hydroxyapatite artificial bone that overcomes prior art, and a kind of modified artificial bone of coral with controllable degradation rate is provided.
Second purpose of the present invention is for a kind of preparation method of modified artificial bone of coral with controllable degradation rate is provided.
First purpose of the present invention can reach by taking following measure:
Modified artificial bone of coral with controllable degradation rate, its construction features is: take the natural coral of three-dimensional porous structure as matrix, make through hydrothermal chemical reaction, made modified artificial bone of coral keeps the microcellular structure of former natural coral, modified artificial bone of coral mainly is made of calcium carbonate and coral hydroxyapatite, and wherein the weight percentage of calcium carbonate is 30%～70%.
First purpose of the present invention can also reach by taking following measure:
One embodiment of the present invention are: the main component of described natural coral is carbon, oxygen, calcium and phosphorus, and wherein the content of carbon is 1%～40%, and the content of oxygen is 1%～30%, and the content of calcium is 1%～50%, and the content of phosphorus is 1%～50%.
One embodiment of the present invention are: its porosity of described natural coral is 10～90%, and the aperture is 100～500um.
Second purpose of the present invention can reach by taking following measure:
The preparation method of foregoing modified artificial bone of coral with controllable degradation rate is characterized in:
1) natural coral of three-dimensional porous structure is put into autoclave, adjusting temperature in the autoclave and be 210～240 ℃, pressure is 35～55Kpa, make natural coral under described temperature, pressure condition, carry out chemical reaction, must be to calcium carbonate and hydroxyapatite mixture behind the chemical reaction; Described chemical equation is 5CaCO3+3 (NH4) 2HPO4 → Ca
5(PO
4)
3OH+6NH
3+ 4H
2O+5CO
2
2) by the calcium carbonate in the time control artificial bone of control chemical reaction and the percentage composition of coral hydroxyapatite; The chemical time of control is by equation Y=a+b * e
-cxDetermine that wherein Y is calcium carbonate content, x is the response time, and a, b are constant, its span a=0.110～0.116, b=0.80～0.90.
The present invention has following outstanding beneficial effect:
1, the present invention is by the control response time, can rationally control reaction depth, the calcium carbonate of control product and the ratio of hydroxyapatite, keeping Corallium Japonicum Kishinouye or the safety of coral hydroxyapatite good biological and bioactive while, reaching the purpose of control modified artificial bone of coral degradation in vivo speed.Therefore, the present invention can be according to need, by the time of control chemical reaction, the percentage composition of calcium carbonate in the control modifying artificial bone, thereby the degradation rate of control modified artificial bone of coral, the time that the artificial bone of implantation was kept 1 year to 2 years in vivo, can prevent that on the one hand the people's bone worker who fills from degrade before bone healing, preventing that secondary from fracturing, and can prevent that on the other hand artificial bone forever is deposited in the human body.
2, the present invention is that the inventor utilizes oneself design and the equipment of processing, through effort for many years, obtain through " hydro-thermal reaction " furtheing investigate the chemical kinetics of this reaction, and having obtained kinetics equation under the prerequisite of the technique of coral hydroxyapatite and method having grasped Corallium Japonicum Kishinouye.Process in conjunction with the degradation kinetics analysis of product in limit liquid and buffered environment, has obtained the controlled modified artificial bone of coral of vivo degradation speed to the chemical analysis of the modification Corallium Japonicum Kishinouye of the differential responses degree of depth.
The specific embodiment
Specific embodiment 1:
Take the natural coral of three-dimensional porous structure as matrix, make through hydrothermal chemical reaction, made modified artificial bone of coral keeps the microcellular structure of former natural coral, modified artificial bone of coral mainly is made of calcium carbonate and coral hydroxyapatite, and wherein the weight percentage of calcium carbonate is 30%～70%.
In the present embodiment: the main component of described natural coral is carbon, oxygen, calcium and phosphorus, and wherein the content of carbon is 1%～40%, and the content of oxygen is 1%～30%, and the content of calcium is 1%～50%, and the content of phosphorus is 1%～50%.Its porosity of described natural coral is 10～90%, and the aperture is 100～500um.
The preparation method of present embodiment comprises the steps:
1) natural coral of three-dimensional porous structure is put into autoclave, adjusting temperature in the autoclave and be 210～240 ℃, pressure is 35～55Kpa, make natural coral under described temperature, pressure condition, carry out chemical reaction, must be to calcium carbonate and hydroxyapatite mixture behind the chemical reaction; Described chemical equation is 5CaCO3+3 (NH4) 2HPO4 → Ca
5(PO
4)
3OH+6NH
3+ 4H
2O+5CO
2
2) by the calcium carbonate in the time control artificial bone of control chemical reaction and the percentage composition of coral hydroxyapatite; The chemical time of control is by equation Y=a+b * e
-cxDetermine that wherein Y is calcium carbonate content, x is the response time, and a, b are constant, its span a=0.110～0.116, b=0.80～0.90.
From the preparation process of present embodiment as can be known, chemical principle of the present invention is:
5CaCO3+3(NH4)2HPO4→Ca
5(PO
4)
3OH+6NH
3+4H
2O+5CO
2
Reaction condition is: 210～240 ℃, pressure is 35～55KPa, and the reactant in this reaction and product obtain being calcium carbonate and hydroxyapatite mixture after cleaning.Therefore, the control response time, controlled reaction depth, the two ratio of the end product that obtains is different, and the product that obtains all can have different manifestations with external degraded in vivo.Be the chemical kinetics equation formula, we utilize the origin of statistical software, adopt decline exponent pattern (Y=a+b * e
-cx) it is carried out Function Fitting, can get analog function and be:
Y=0.112+0.85 * e
-0.0776xVariance is: R
2=0.9700
Wherein Y is calcium carbonate content, and X is the response time, for example, under this reaction condition, control is 10.34 hours in the response time, can obtain calcium carbonate: the product of hydroxyapatite=1: 1, the control response time is 3.5 hours, can obtain calcium carbonate: hydroxyapatite=2: 1 products.
In the present embodiment, the degraded equation of modified artificial bone of coral in external simulated solution is:
Y=0.0295 * X
-0.2146Variance: R
2=0.918
Wherein Y is calcium carbonate content, and X is degradation time.The vivo degradation rule of modified artificial bone of coral is approximate with external degraded.
Below by experiment in vitro check natural coral, the degradation characteristic of modified artificial bone of coral of the present invention and pure coral hydroxyapatite: respectively with natural coral, (calcium carbonate: calcium phosphate was respectively 2: 1 modified artificial bone of coral, 1: 1,1: 2,) and each 1g of standard powder of pure coral hydroxyapatite, put into experiment in vitro limit liquid 20ml, (ph value=3 ± 0.2), in 37 ℃ of shaking baths 120 hours, several samples are dried respectively, measure loss amount, obtaining the result analyzes, the loss amount of modified artificial bone of coral and presents rule and changes between natural coral and pure coral hydroxyapatite.
Experimental data is:
0.24 0.23 0.19 0.19 0.20 0.183 0.174 0.170
Degradation amount
5 6 9 5 1 9 1 7
10.3
Response time (h) 1 3.38 5.36 7.64 13.65 17.9 24
4
Specific embodiment 2:
Respectively with natural coral, modified artificial bone of coral (calcium carbonate: calcium phosphate be respectively 2: 1,1: 1,1: 2) pure coral hydroxyapatite standard powder 1g, put into experiment in vitro simulated body fluid liquid 20ml, (ph value=7.4 ± 0.2), in 37 ℃ of shaking baths 30 days, several samples are dried respectively, measure loss amount, obtain the result and analyze, the loss amount of modified artificial bone of coral and presents rule and changes between natural coral and pure coral hydroxyapatite.
Test data:
0.03 0.02 0.02 0.02 0.01 0.01 0.01 0.01 0.01 0.01
Degradation amount
19 19 13 15 83 98 76 73 71 45
Response time
10.3 13.6
1 3 3.38 5.36 6 7.64 17.9 24
(h)
4 5
Specific embodiment 3
Respectively with natural coral, modified artificial bone of coral (calcium carbonate: calcium phosphate be respectively 2: 1,1: 1,1: 2) pure coral hydroxyapatite rule particle 1g, put into the defective region of experimental dog humerus bone defect model, take out gross specimen after 12 weeks, measure the x-ray density of defective region and the Corallium Japonicum Kishinouye composition residual quantity in specimen district, obtaining the result analyzes, the x-ray density of modified artificial bone of coral and Corallium Japonicum Kishinouye composition residual quantity and present rule and change between natural coral and pure coral hydroxyapatite.The degradation time of above-mentioned material is followed successively by: 6 weeks, 30 weeks, 60 weeks, 80 weeks and 80 week degradeds 5%.
Claims (3)
1. the preparation method of modified artificial bone of coral with controllable degradation rate is characterized in that:
1) take the natural coral of three-dimensional porous structure as matrix, make through hydrothermal chemical reaction, made modified artificial bone of coral keeps the microcellular structure of former natural coral, modified artificial bone of coral mainly is made of calcium carbonate and coral hydroxyapatite, and wherein the weight percentage of calcium carbonate is 30%～70%;
2) natural coral of three-dimensional porous structure is put into autoclave, adjusting temperature in the autoclave and be 210～240 ℃, pressure is 35～55Kpa, make natural coral under described temperature, pressure condition, carry out chemical reaction, must be to calcium carbonate and hydroxyapatite mixture behind the chemical reaction; Described chemical equation is 5CaCO
3+ 3 (NH
4)
2HPO
4→ Ca
5(PO
4)
3OH+6NH
3+ 4H
2O+5CO
2
3) by controlling the time of chemical reaction, the percentage composition of calcium carbonate and coral hydroxyapatite in the control artificial bone, thereby the degradation rate of control modified artificial bone of coral; The chemical time of control is by equation
Y=a+b * e -cx Determine that wherein Y is calcium carbonate content, x is the response time, and a, b are constant, its span a=0.112, b=0.85, and the span of c is 0.0776.
2. the preparation method of modified artificial bone of coral with controllable degradation rate according to claim 1, it is characterized in that: the main component of described natural coral is carbon, oxygen, calcium and phosphorus, wherein the content of carbon is 1%～40%, the content of oxygen is 1%～30%, the content of calcium is 1 %～50%, and the content of phosphorus is 1%～50%.
3. the preparation method of modified artificial bone of coral with controllable degradation rate according to claim 1, it is characterized in that: its porosity of described natural coral is 10～90%, the aperture is 100～500 μ m.
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| CN106730003A (en) * | 2016-12-11 | 2017-05-31 | 戴琪 | A kind of preparation method for luring bone development type bone cement |
| CN107823712A (en) * | 2017-12-13 | 2018-03-23 | 华中科技大学 | A kind of method for preparing imitative artificial bone of coral with cuttlebone and products thereof |
| CN110025406A (en) * | 2019-04-17 | 2019-07-19 | 上海黑焰医疗科技有限公司 | A kind of preparation method of 3D printing bone defect filler |
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|---|---|---|---|---|
| CN1528468A (en) * | 2003-10-16 | 2004-09-15 | 上海惠谷生物技术开发有限公司 | Porous calcium carbonate-hydroxyapatite gradient material and preparing method thereof |
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Granted publication date: 20131016 Termination date: 20140313 |