CN101461962A - Composite bone material capable of being injected and preparation method thereof - Google Patents
Composite bone material capable of being injected and preparation method thereof Download PDFInfo
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- CN101461962A CN101461962A CNA2009100769380A CN200910076938A CN101461962A CN 101461962 A CN101461962 A CN 101461962A CN A2009100769380 A CNA2009100769380 A CN A2009100769380A CN 200910076938 A CN200910076938 A CN 200910076938A CN 101461962 A CN101461962 A CN 101461962A
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Abstract
The invention relates to an injectable composite bone material and a preparation method thereof, and belongs to the technical field of biomaterial. The injectable composite bone material is prepared from collagen stroma nanocrystal calcium phosphate and semi-hydrated calcium sulphate powder by mixing, while sterilized medical water is prepared from the injectable composite bone material according to a certain ratio of liquid to solid, so that the liquid phase and the solid phase can be mixed evenly to prepare the injectable composite bone material during use. The material and the method introduce semi-hydrated calcium sulphate into nanocrystal calcium phosphate/collagen composite material with a natural bone classification structure and characteristics to prepare an injectable bone repair material so as to realize performance complementation, not only can maintain the characteristics of the imitated natural bone structure, but also endow new injectable performance to the materials, thereby having wider application range.
Description
Technical field
The invention belongs to the biomaterial scientific domain, be specifically related to injectable compound bone material and preparation method thereof.
Background technology
Osteoporosis is one of major disease that threatens human health, and collapse of vertebra that is caused by osteoporosis and fracture etc. still lack effective Therapeutic Method at present, becomes medically to be badly in need of the difficult problem that solves.New less invasive techniques-percutaneous vertebral body is strengthened art and begins to be applied to clinical in recent years, its prevention spinal fracture, recovers the determined curative effect of vertebral height.The Injectable self-curable bone renovating material that this technology is used is a kind of original position osteanagenesis repair materials, it has adapted to the requirement that surgical technic is hindered by Wicresoft, little with tissue injury, do not destroy repair district's blood for, easy to operation, greatly alleviate advantage such as patient misery and extremely pay attention to.Wicresoft's formed in situ injectable bone repair materials is except that being used for the treatment of osteoporosis, and assisting of also can be used for fracturing fixed and the pulp cavity internal fixation, and aspects such as bone cyst and the reparation of bone tuberculosis postoperative have a extensive future, and are a kind of bio-medical materials of urgent clinical needs.
Biomaterial seminar of Tsing-Hua University is template with the tropocollagen molecule according to the nano compound stephanoporate material of bionical thinking design, the modulating intracellular calcium microcosmic salt deposits on the ordered arrangement collagen fibers, being self-assembled into the nanocrystalline calcium phosphate/collagen composite materials with nature bone hierarchy and characteristic, is a kind of bone induction material of biologically active.The brilliant calcium phosphate of Collagon base nanometer is a kind of good nanometer bone material, its porosity is greater than 70%, pore size is 300 ± 250 μ m (seeing Fig. 1 a, Fig. 1 b, Fig. 1 c), crystalline size is not more than 50 μ m, can keep the morphological characteristic finished behind the implant into body, cell can be entered in the bone material grow, its comprcssive strength is suitable with the human body spongy bone, is not less than 0.8Mpa.
But nanocrystalline calcium phosphate/collagen composite materials is a solid-state form, can't satisfy the demand of Wicresoft's original position operation, as with nanocrystalline calcium phosphate/collagen composite materials serving as basis preparation injectable bone repair materials, the feature that both can keep imitative nature bone structure, give material new injectable performance again, had wide applications more.
Summary of the invention
At the defective in the above-mentioned field, the present invention provides a kind of injectable compound bone material based on the brilliant calcium phosphate of Collagon base nanometer, both can keep the feature of imitative nature bone structure, has given material new injectable performance again, has wide applications more.
The preparation method of this injectable compound bone material is provided simultaneously.
The injectable compound bone material is mixed by brilliant calcium phosphate of Collagon base nanometer and half-H 2 O calcium sulphate powder.
The percentage by weight that the brilliant calcium phosphate of described Collagon base nanometer accounts for compound bone material is 2-25%.
Preferably: 5-20%.
Separate loading injectable compound bone material comprises injectable compound bone material and the medical aseptic water of distinguishing independent packaging, its solvent and solute weight ratio 0.4-1.0:1.
The preparation method of injectable compound bone material comprises the steps: the brilliant calcium phosphate powder of (1) preparation Collagon base nanometer, (2) preparation half-H 2 O calcium sulphate powder, and (3) get final product the powder of step 1 and step 2 by required mixed.
The preparation of the brilliant calcium phosphate powder of described Collagon base nanometer is adopted following step: A successively, is slowly dripped in the molten collagen solution of acid and contain PO
4 3-Solution, make in every gram collagen and contain 0.01～0.1mol PO
4 3-, stirring in the time of dropping, the concentration of described collagen solution is 5 * 10
-5～5 * 10
-3G/ml; B, slow dropping while stirring contain Ca
2+Aqueous solution, the Ca of adding
2+The mol ratio of the P that adds in the amount and the first step is 1～2:1, C, in solution, slowly drip NaOH solution while stirring, making pH value is 6-8, D, above-mentioned solution left standstill are removed supernatant, and centrifugalize goes out precipitation, use the deionized water washing and precipitating, again precipitate is put into the freezer dryer lyophilization, ground subsequently and make dry powder, be the brilliant calcium phosphate bone material powder of Collagon base nanometer.
Described acid is hydrochloric acid, nitric acid or acetic acid.
Following method is adopted in the preparation of described half-H 2 O calcium sulphate powder: the calcium sulphate dihydrate that takes by weighing certain mass, take by weighing sodium citrate and each portion of aluminum sulfate respectively as crystal modifier by 0.25% of calcium sulphate dihydrate quality, whole raw materials are added in the hydrothermal reaction kettle, press the calcium sulphate dihydrate mass ratio and add 5-6 water doubly, at reaction temperature 110-130 ℃, pressure 0.1-0.2MPa, reaction is 5-8 hour under mixing speed 200-500 rev/min the condition, filter then and obtain half-H 2 O calcium sulphate, 120 ℃ were dried by the fire 2-3 hours in baking oven, again in baking oven 90 ℃ spend the night, grind and to make dry powder, be the half-H 2 O calcium sulphate powder.
Half-H 2 O calcium sulphate (CaSO
41/2H
2O) as a kind of injectable artificial bone, wide material sources, preparation technology is simple, has good microporosity, biocompatibility and bone conduction activity, has entered clinical as product.But because its no bone-inducting active, degraded and absorbed speed is very fast, can not be complementary with new bone formation speed, has limited its further development and application.Brilliant calcium phosphate of Collagon base nanometer and CaSO
41/2H
2The O combination, be prepared into the syringeability bone material, after adding medical water allotment, become thickly, inject the bone injury repair place, in 10-30 minute, finish curing with supporting syringe, suitable and the human body spongy bone of its intensity, the combination of above-mentioned two kinds of materials can also improve the biological activity and the degradation rate of material, realizes performance complement, is expected to become more rational artificial bone.
The present invention introduces half-H 2 O calcium sulphate in having the nanocrystalline calcium phosphate/collagen composite materials of nature bone hierarchy and characteristic, preparation injectable bone repair materials, solidify in vivo, realize performance complement, the feature that both can keep imitative nature bone structure, give material new injectable performance again, had wide applications more.
Description of drawings
The longitudinal section electron microscope photo scanning of the brilliant calcium phosphate of Fig. 1 a Collagon base nanometer
The cross section electron microscope photo scanning of Fig. 1 b material
Fig. 1 c is that amplify the part of (Fig. 1 b), and arrow is indicated the nHA/RC granule that is dispersed in the framework
The stereoscan photograph of Fig. 2 half-H 2 O calcium sulphate,
The left side is the product of Britain hundred match companies, and the right is the half-H 2 O calcium sulphate that obtains in the preparation process of the present invention
Fig. 3 XRD infrared ray diffraction collection of illustrative plates
Above figure be the half-H 2 O calcium sulphate that obtains in the preparation process of the present invention, below figure be the product of Britain hundred match companies.
Fig. 4 contains the injectable bone scanning of materials electromicroscopic photograph of the brilliant calcium phosphate of 4% Collagon base nanometer
Fig. 5 contains the injectable bone scanning of materials electromicroscopic photograph of the brilliant calcium phosphate of 20% Collagon base nanometer
The specific embodiment
The invention will be further described below in conjunction with example.
Embodiment one
(1) 20g collagen colloidal sol is dissolved in the 300ml0.5M acetic acid solution, slowly drips 11ml 1mol/l Na
2HPO
4And 18.3ml1mol/lCaCl
2, use magnetic stirrer in the time of dropping; NaOH solution to the pH value that slowly drips 0.5ml 1mol/l then is 7; Left standstill solution 1 day, and removed supernatant, centrifugalize goes out precipitation, puts into the freezer dryer drying after cleaning three times repeatedly with deionized water, makes dry powder after the grinding.(seeing Fig. 1 a, Fig. 1 b, Fig. 1 c)
(2) take by weighing calcium sulphate dihydrate 100 grams, each 0.25 gram of sodium citrate and aluminum sulfate adds among the hydro-thermal reaction Fu, adds 567ml water again, 120 ℃ of reaction temperatures, pressure 0.15MPa, reaction is 6 hours under the condition that mixing speed is 400 rev/mins, filters then to obtain precipitation, 120 ℃ were dried by the fire 2-3 hours in baking oven, again in baking oven 90 ℃ spend the night, grind and to make dry powder, be the half-H 2 O calcium sulphate powder after testing.Fig. 2, Fig. 3 are that the half-H 2 O calcium sulphate and hundred that this experiment makes is matched product (the artificial bone repair materials industry authority) performance comparison of companies, by half-H 2 O calcium sulphate (CSH) the performance basically identical of above this product as can be seen with hundred match companies.
(3) the brilliant calcium phosphate powder of Collagon base nanometer and half-H 2 O calcium sulphate powder are mixed with 4/96 mass ratio, obtain the brilliant calcium phosphate content of Collagon base nanometer and be the brilliant calcium phosphate of Collagon base nanometer-half-H 2 O calcium sulphate mixed dust formulation 1 gram (see figure 4) of 4%, by liquid-solid ratio is 0.5 for powder is equipped with aseptic medical water 0.5 gram, obtains the brilliant calcium phosphate of injectable Collagon base nanometer-half-H 2 O calcium sulphate bone material.
Embodiment two
(1) 30g collagen colloidal sol is dissolved in the 300ml0.5M acetic acid solution, slowly drips 11ml 1mol/l Na
2HPO
4With 18.3ml 1mol/lCaCl
2, use magnetic stirrer in the time of dropping; NaOH solution to the pH value that slowly drips 0.5ml 1mol/l then is 7; Left standstill solution 5 days, and removed supernatant, centrifugalize goes out precipitation, puts into the freezer dryer drying after cleaning three times repeatedly with deionized water, makes dry powder after the grinding.
(2) take by weighing calcium sulphate dihydrate 200 grams, each 0.50 gram of sodium citrate and aluminum sulfate adds in the hydrothermal reaction kettle, adds 1134ml water again, 110 ℃ of reaction temperatures, pressure 0.1MPa, reaction is 5 hours under the condition that mixing speed is 200 rev/mins, filters then to obtain precipitation, 120 ℃ were dried by the fire 2-3 hours in baking oven, again in baking oven 90 ℃ spend the night, grind and to make dry powder, be the half-H 2 O calcium sulphate powder.
(3) the brilliant calcium phosphate powder of Collagon base nanometer and half-H 2 O calcium sulphate powder are mixed with 10/90 mass ratio, obtain the brilliant calcium phosphate content of Collagon base nanometer and be the brilliant calcium phosphate of Collagon base nanometer-half-H 2 O calcium sulphate mixed dust formulation 1 gram of 10%, by liquid-solid ratio is 0.6 for powder is equipped with aseptic medical water 0.6 gram, obtains the brilliant calcium phosphate of injectable Collagon base nanometer-half-H 2 O calcium sulphate bone material.
Embodiment three
(1) 8g collagen colloidal sol is dissolved in the 300ml0.1M salpeter solution, slowly drips 10ml 1mol/l (NH
4)
2HPO
4With 10ml 1mol/lCaCl
2, use magnetic stirrer in the time of dropping; NaOH solution to the pH value that slowly drips 0.5ml1mol/l then is 7; Left standstill solution 4 days, and removed supernatant, centrifugalize goes out precipitation, puts into the freezer dryer drying after cleaning three times repeatedly with deionized water, makes dry powder after the grinding.
(2) take by weighing calcium sulphate dihydrate 300 grams, each 0.75 gram of sodium citrate and aluminum sulfate adds in the hydrothermal reaction kettle, adds 1701ml water again, 130 ℃ of reaction temperatures, pressure 0.2MPa, reaction is 8 hours under the condition that mixing speed is 500 rev/mins, filters then to obtain precipitation, 120 ℃ were dried by the fire 2-3 hours in baking oven, again in baking oven 90 ℃ spend the night, grind and to make dry powder, be the half-H 2 O calcium sulphate powder.
(3) the brilliant calcium phosphate powder of Collagon base nanometer and half-H 2 O calcium sulphate powder are mixed with 20/80 mass ratio, obtain the brilliant calcium phosphate content of Collagon base nanometer and be the brilliant calcium phosphate of Collagon base nanometer-half-H 2 O calcium sulphate mixed dust formulation 1 gram (see figure 5) of 20%, by liquid-solid ratio is 0.8 for powder is equipped with aseptic medical water 0.8 gram, obtains the brilliant calcium phosphate of injectable Collagon base nanometer-half-H 2 O calcium sulphate bone material.
Claims (8)
1, injectable compound bone material is mixed by brilliant calcium phosphate of Collagon base nanometer and half-H 2 O calcium sulphate powder.
2, injectable compound bone material according to claim 1, the percentage by weight that the brilliant calcium phosphate of described Collagon base nanometer accounts for compound bone material is 2-25%.
3, injectable compound bone material according to claim 1, the percentage by weight that the brilliant calcium phosphate of described Collagon base nanometer accounts for compound bone material is 5-20%.
4, separate loading injectable compound bone material comprises arbitrary described injectable compound bone material of claim 1-3 and the medical aseptic water of distinguishing independent packaging, its solvent and solute weight ratio 0.4-1.0:1.
5, the preparation method of the arbitrary described injectable compound bone material of claim 1-3, comprise the steps: the brilliant calcium phosphate powder of (1) preparation Collagon base nanometer, (2) preparation half-H 2 O calcium sulphate powder, (3) get final product the powder of step 1 and step 2 by required mixed.
6, preparation method according to claim 5, the preparation of the brilliant calcium phosphate powder of described Collagon base nanometer adopt following step: A successively, slowly drip in the molten collagen solution of acid and contain PO
4 3-Solution, make in every gram collagen and contain 0.01～0.1molPO
4 3-, stirring in the time of dropping, the concentration of described collagen solution is 5 * 10-5～5 * 10-3g/ml; B, slow dropping while stirring contain Ca
2+Aqueous solution, the Ca of adding
2+The mol ratio of the P that adds in the amount and the first step is 1～2:1, C, in solution, slowly drip NaOH solution while stirring, making pH value is 6-8, D, above-mentioned solution left standstill are removed supernatant, and centrifugalize goes out precipitation, use the deionized water washing and precipitating, again precipitate is put into the freezer dryer lyophilization, ground subsequently and make dry powder, be the brilliant calcium phosphate bone material powder of Collagon base nanometer.
7, preparation method according to claim 6, described acid are hydrochloric acid, nitric acid or acetic acid.
8, preparation method according to claim 5, following method is adopted in the preparation of described half-H 2 O calcium sulphate powder: the calcium sulphate dihydrate that takes by weighing certain mass, take by weighing sodium citrate and each portion of aluminum sulfate respectively as crystal modifier by 0.25% of calcium sulphate dihydrate quality, whole raw materials are added in the hydrothermal reaction kettle, press the calcium sulphate dihydrate mass ratio and add 5--6 water doubly, at reaction temperature 110-130 ℃, pressure 0.1-0.2MPa, reaction is 5-8 hour under mixing speed 200-500 rev/min the condition, filter then and obtain half-H 2 O calcium sulphate, in baking oven 120 ℃ the baking 2-3 hours, again in baking oven 90 ℃ spend the night, grinding makes dry powder, is the half-H 2 O calcium sulphate powder.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102008748A (en) * | 2010-11-08 | 2011-04-13 | 胡钢锋 | Application of injectable degradable calcium sulfate and calcium phosphate material in repairing femoral head necrosis |
| CN102205150A (en) * | 2011-05-19 | 2011-10-05 | 清华大学 | Preparation method for anti-infectious nano collagen/ calcium phosphate bone repair material |
| CN102764455A (en) * | 2012-07-20 | 2012-11-07 | 清华大学 | Anti-infection mineralized collagen and calcium sulfate bone repair material and preparation method thereof |
| EP2524707A1 (en) * | 2011-05-16 | 2012-11-21 | Beijing Allgens Medical Science & Technology Co., Ltd. | Injectible, biocompatible synthetic bone growth composition |
| CN101816808B (en) * | 2010-02-05 | 2013-02-13 | 深圳兰度生物材料有限公司 | Injectable porous high-strength bone repair material |
| CN101816807B (en) * | 2010-02-05 | 2013-02-13 | 深圳兰度生物材料有限公司 | Bone repairing material for personalized treatment |
| 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 |
-
2009
- 2009-01-14 CN CNA2009100769380A patent/CN101461962A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN101816808B (en) * | 2010-02-05 | 2013-02-13 | 深圳兰度生物材料有限公司 | Injectable porous high-strength bone repair material |
| CN101816807B (en) * | 2010-02-05 | 2013-02-13 | 深圳兰度生物材料有限公司 | Bone repairing material for personalized treatment |
| CN102008748A (en) * | 2010-11-08 | 2011-04-13 | 胡钢锋 | Application of injectable degradable calcium sulfate and calcium phosphate material in repairing femoral head necrosis |
| CN102008748B (en) * | 2010-11-08 | 2013-07-31 | 胡钢锋 | Application of injectable degradable calcium sulfate and calcium phosphate material in repairing femoral head necrosis |
| EP2524707A1 (en) * | 2011-05-16 | 2012-11-21 | Beijing Allgens Medical Science & Technology Co., Ltd. | Injectible, biocompatible synthetic bone growth composition |
| CN102205150A (en) * | 2011-05-19 | 2011-10-05 | 清华大学 | Preparation method for anti-infectious nano collagen/ calcium phosphate bone repair material |
| CN102764455A (en) * | 2012-07-20 | 2012-11-07 | 清华大学 | Anti-infection mineralized collagen and calcium sulfate bone repair material and preparation method thereof |
| CN102764455B (en) * | 2012-07-20 | 2014-11-26 | 清华大学 | Anti-infection mineralized collagen and calcium sulfate bone repair material and preparation method thereof |
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Application publication date: 20090624 |