CN1446588A - Glass based nano hydroxyapatite biologic cement and its preparation method - Google Patents

Glass based nano hydroxyapatite biologic cement and its preparation method Download PDF

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CN1446588A
CN1446588A CN 03115107 CN03115107A CN1446588A CN 1446588 A CN1446588 A CN 1446588A CN 03115107 CN03115107 CN 03115107 CN 03115107 A CN03115107 A CN 03115107A CN 1446588 A CN1446588 A CN 1446588A
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glass
proportioning
hydroxyapatite
binding agent
bone
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CN1315538C (en
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黄文旵
王德平
周萘
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Tongji University
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Tongji University
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Abstract

A self-solidifying bioactive bone adhesive (also named as biologic cement) for repairing bone and adhering natural bone with artificial bone is prepared from phosphate glass phase for biocompatibility and bioactivity, hydroxy phosphorite nanocrystals, and mixing liquid through proportionally mixing. It can induce the generation and growth of new bone, and suppress the growth of cancer cells. Its advantage is high compression strength.

Description

Glass-base nanometer hydroxylapatite biology cement and preparation method thereof
Technical field
This invention relates to a kind of biologically active, and the bone bonding agent of solidification forming has higher mechanical strength voluntarily, and cancerous cell is had inhibitory action.
Background technology
Human organ and often organize because of inflammation, injured, aging, tumor or congenital malformation etc. cause and damage or damaged is lost original function.In order to substitute, repair or rebuild these organs and tissue, some artificial bones of being made by alloy, macromolecular material, bioceramic, artificial joint like surging clouds rise.But these biomaterials when surgical operation, are difficult to immediately be processed into according to the shape of defect the member of to be repaired or alternate organ and tissue, have limited these Application of Biomaterial.Polymethyl methacrylate (PMMA) bone cement commonly used clinically, the block of molding definite shape, filling bone cavity or fixing artificial joint.But owing to after the PMMA degradation in vivo becomes monomer, great toxicity is arranged.Because when using the PMMA bone cement, polymerization produces a large amount of heats, slough causes the replacement joint later stage loosening, seriously influences therapeutic effect again.Developed from the solidity calcium-phosphate cement by Japan in the eighties, part has solved the defective of organic polymer bone cement.Also having occurred corresponding commodity at home appears on the market.But its intensity is low, and is unsatisfactory.In May, 1998, United States Patent (USP) has appearred: USP4.735.625 (Bone cement renforcement and method), in June, 2000, United States Patent (USP) has appearred: USP6.075.067 (Cement for medical use, method for producing the cement and use of thecement), U.S. Pat P6.479.565 (Bioactive ceramic cement) has appearred in November, 2002.In these patents, all introduced high-molecular organic material, though beneficial to improving intensity, and some macromolecular material also possesses biological degradability, the too late inorganic matter of their biological activity.Inducing and conducting aspect the osteogenesis not as good as hydroxyapatite.At home, the Chinese patent 92105781 (inorganic-bone cement with biological active fibre) of in July, 1992 application; Chinese patent 00,102,993 three patents such as (biphase bone cement of tricalcium phosphate/oxyhydrogen-base apatite and manufacture methods thereof) of the Chinese patent 98110645 (porous calcium phosphate bone cement that contains pore former) of in February, 1998 application and in May, 2000 application, intensity to existing bone cement all can not produce bigger raising, and is especially all powerless on rupture strength.
Summary of the invention
The object of the present invention is to provide a kind ofly to have height biological activity and higher mechanical strength, and can discharge calcium ion, cancerous cell is had inhibiting bone binding agent, also claim biological cement.
The bone binding agent that the present invention proposes is a kind of multi-phase composites, by the phosphate glass of the biologically active and the hydraulicity hydroxyapatite crystal of filling nano-scale (see figure 1) that powder is formed mutually between granule and granule mutually, both mass ratioes of front and back are 60: 40-90: 10.
Above-mentioned complex is through cooperating with distiller liquor, and formation has close-burning biological cement.
Among the present invention, main body is a phosphate glass, and its set of dispense is as follows than (by quality):
P 2O 5： 10-35％，
SiO 2And/or Al 2O 315-50%,
CaO and/or MgO; 20-40%,
F -And/or R 2O:0-10%,
The gross mass of each component satisfies 100%, and wherein R is an alkali metal ion, for example can be Na, K etc., F -Be metal fluoride; The particle size of phosphate glass is 2～45 μ m.
Among the present invention, the set of dispense of hydroxyapatite crystal is as follows than (by quality):
Hydroxyapatite Ca 10(PO 4) 6(OH) 2: 80-100%,
Various aquation apatite Ca 10(PO 4) 6X 2YH 2O:20-0%,
Wherein X is F -Or/and HCO 3 -, or/and NH 2 -Deng anion radical, Y=1-10, the equivalent size of crystal grain are 10～90nm.In addition, this crystalline granule-morphology is spherical, perhaps is needle-like.Pattern is a spheroid, can increase crystalline unsaturated bond, can have more calcium ion drop wash rice to go out, improve the function of anticancer, pattern is acicular, is positioned at the block gap of aquation glass particle, can strengthen the interlacing degree of hydroxyapatite crystal, improve the intensity of bone binding agent.
Among the present invention, the set of dispense of employed distiller liquor is as follows than (by weight):
(NH 4) 2HPO 4?90-100％，
NH 4H 2PO 4?10-0％，
Its pH is 7.0-8.5.
Among the present invention, as follows with the proportioning of distiller liquor as the multi-phase composites of bone binding agent: every 10g solid powder cooperates the furnishing slurry with the 2-8ml distiller liquor.This slurry can be frozen into hard solid within 2-15 minute.
The preparation method of above-mentioned bone binding agent is as follows:
Press the component proportioning preparation batching of phosphate glass, it is placed in the platinum crucible, founds into glass melt; Again with the glass melt quenching between two copper coins, obtain water white glass flake; The glass flake pulverizing is ground to form required particle size, standby;
With Ca (NO 3) 24H 2The alcoholic solution of O and (NH 4) 2HPO 4Aqueous solution be the mixed of 1.6-.17 by the ratio of Ca/P, add the surfactant ethanolamine, be that 5-25 ℃, pH are stirring reaction under the condition of 9.8-11.2 in temperature, produce precipitate, promptly obtain nanometer hydroxyapatite.Wherein, when surfactant was excessive, the hydroxyapatite that obtains was spherical pattern, when surfactant more after a little while, the hydroxyl phosphoric acid lime stone that obtains is the needle-like pattern;
Above-mentioned phosphate glass granule is become multi-phase composites with the nanometer hydroxyapatite powder by the proportioning hybrid modulation.
At last, during use, with distiller liquor (as (NH 4) 2HPO 4With NH 4H 2PO 4Mixed solution) at room temperature mix with multi-phase composites by proportioning, through hydration reaction, the close-burning slurry of tool.Slurry retrogradation gradually, hardening form ammonium calcium phosphate hydras, through the explanation reaction of physiology simulated solution, on particulate surface, form the hydroxyapatite of nascent state gradually again.It has bigger activity, to the formation of new bone and grown inducing action and conduction.
Because the nano-hydroxy phosphoric acid calcium in the multi-phase composites has bigger specific surface, can separate out calcium ion by drop, the growth of cancerous cell there is certain inhibitory action, the Ca ion dissolution rate in the time of 37 ℃ in the human body life simulated solution is 5 * 10 -8-4 * 10 -7G/g (every gram sample dissolution rate).In addition, intergranular nanometer hydroxyapatite has also remedied formed hole between granule, has improved biological cement intensity.The highest compressive resistance after 7 days can reach 95MPa, and high breaking strength can reach 36MPa.Therefore, compare with existing product, glass-base nanometer hydroxylapatite biology cement involved in the present invention has more biological activity, and higher mechanical strength is arranged, but also has the effect of certain anticancer growth.
Description of drawings
Fig. 1: the multi-phase composites sketch of glass-base nanometer hydroxyapatite.Wherein: (A) contain the multi-phase composites of spherical nanometer hydroxyapatite, (B) contain the multi-phase composites of acicular nanometer hydroxyapatite.
Fig. 2: the hydration process sketch of the multi-phase composites of glass-base nanometer hydroxyapatite.
Number in the figure: 1 is the phosphate glass granule, and 2 is spherical nanometer hydroxyapatite, and 3 is the acicular nanometer hydroxyapatite.
The specific embodiment
Further introduce the present invention below by embodiment.
Embodiment 1:
Get analytically pure raw materials of Ca HPO respectively 42H 2O, Al (OH) 3, SiO 2, CaCO 3, MgCO 3And CaF 2, proportional by quality group is P 2O 512, Al 2O 35, SiO 240, MgO 5, and CaO 36, CaF 22 are mixed with glass batch, place platinum crucible, 1450～1550 ℃ found 4～6 hours after, the melt quenching between two copper coins, is obtained water white glass flake, and it pulverize is ground, its particle size is that the fine powder of 5 μ m is standby.Other gets analytical reagent Ca (NO 3) 24H 2O 19.7g is dissolved in 95% alcoholic solution of 200ml, and gets analytical reagent (NH 4) 2HPO 47.0g, be dissolved in the deionized water of 200ml, two liquid are mixed, and add 8 ethanolamine and make surperficial activator, use NH 4OH solution adjusts to 10 to the pH of mixed solution; Stir after 4 hours, it is precipitated static 12 hours, the sucking filtration after drying obtains globular nanometer hydroxyapatite, and its average-size is 45nm.Get analytical reagent (NH again 4) 2HPO 450g, NH 4H 2PO 42.5g after mixing, be dissolved in the deionized water of 100ml, be prepared into distiller liquor, its pH value is adjusted into 7.8.Take out 10g solid (8g glass fine powder, 2g nanometer hydroxyapatite) powder at last, fully mix, add distiller liquor 3.5ml, evenly reconcile into slurry, slurry is fashioned into 1cm * 1cm * 1cm cuboid sample and 4mm * 4mm * 60mm bar-shaped sample.Maintenance is 7 days under 100% relative humidity, and recording compressive resistance then is 87MPa, rupture strength 32MPa, cuboid sample in the 100ml normal saline, under 37 ℃ of conditions, Ca ++The amount of separating out is 1.2 * 10 in ionic first day -7G/g (dissolution rate of every gram sample).
Embodiment 2:
Get analytically pure raw materials of Ca HPO respectively 42H 2O, Al (OH) 3, SiO 2, CaCO 3, MgCO 3And CaF 2, proportional by quality group is P 2O 512, Al 2O 35, SiO 240, MgO 5, and CaO 36, CaF 22 are mixed with glass batch, place platinum crucible, 1450～1550 ℃ found 4～6 hours after, the melt quenching between two copper coins, is obtained water white glass flake, and it pulverize is ground, its particle size is that the fine powder of 5 μ m is standby.Other gets analytical reagent Ca (NO 3) 24H 2O 16.8g is dissolved in 95% alcoholic solution of 200ml, gets analytical reagent (NH 4) 2HPO 45.6g, be dissolved in the deionized water of 200ml, two liquid are mixed, and add 5 ethanolamine and make surperficial activator, use NH 4OH solution is adjusted into pH=10.5 with the acidity of mixed solution; Stirred 2 hours, it is precipitated static 12 hours, the sucking filtration after drying, the acquisition average diameter is 12nm, length is the acicular nanometer hydroxyapatite of 65nm.Get analytical reagent (NH again 4) 2HPO 450g, NH 4H 2PO 42.5g after mixing, be dissolved in the deionized water of 100ml, be prepared into distiller liquor, its pH value is adjusted into 7.8.Get the above-mentioned glass fine powder of 8g at last, the above-mentioned acicular nanometer hydroxyapatite of 2g fully mixes, in blended process, drip the 3.5ml distiller liquor, the uniform slurry of furnishing fashions into 1cm * 1cm * 1cm cuboid sample and 4mm * 4mm * 60mm bar-shaped sample with slurry, maintenance 7 days under 100% humidity respectively, recording compressive resistance then is 95MPa, rupture strength 36MPa, and cuboid sample is in the 100ml normal saline, under 37 ℃ of conditions, Ca ++The amount of separating out is 7.4 * 10 in ionic first day -8G/g (dissolution rate of every gram sample).
Embodiment 3:
Get analytically pure raw materials of Ca HPO respectively 42H 2O, SiO 2, CaCO 3And CaF 2, proportional by quality group is P 2O 520, SiO 237, CaO 42, CaF 21 is mixed with glass batch, places platinum crucible, 1450～1550 ℃ found 4～6 hours after, the melt quenching between two copper coins, is obtained water white glass flake.Particle size is pulverized, ground to form to glass is that the fine powder of 10 μ m is standby.Other gets analytical reagent Ca (NO 3) 24H 2O 19.7g is dissolved in 95% alcoholic solution of 200ml, gets analytical reagent (NH 4) 2HPO 47.0g, be dissolved in the deionized water of 200ml, two liquid are mixed, and add 8 ethanolamine as surfactant, use NH 4OH solution is adjusted to pH=10.0 with the acidity of mixing material; Stir after 4 hours, it is precipitated static 12 hours, the sucking filtration after drying obtains spherical nanometer hydroxyapatite, and its average diameter is 55nm.Get analytical reagent (NH again 4) 2HPO 450g, NH 4H 2PO 42.5g after mixing, be dissolved in the deionized water of 100ml, be prepared into distiller liquor, its acidity is adjusted into pH=7.8.Get the above-mentioned glass fine powder of 8g at last, the above-mentioned spherical nanometer hydroxyapatite of 2g fully mixes, in blended process, drip the 3.5ml distiller liquor, the uniform slurry of furnishing fashions into 1cm * 1cm * 1cm cuboid sample and 4mm * 4mm * 60mm bar-shaped sample with slurry, maintenance 7 days under 100% humidity respectively, recording compressive resistance then is 79MPa, rupture strength 27MPa, and cuboid sample is in the 100ml normal saline, under 37 ℃ of conditions, Ca ++The amount of separating out is 2.2 * 10 in ionic first day -7G/g (dissolution rate of every gram sample).
Embodiment 4:
Get analytical pure raw materials of Ca HPO respectively 42H 2O, SiO 2, CaCO 3And CaF 2, proportional by quality group is P 2O 520, SiO 237, CaO 42, CaF 21, be mixed with glass batch, place platinum crucible, 1450～1550 ℃ found 4～6 hours after, the melt quenching between two copper coins, is obtained water white glass flake.Particle size is pulverized, ground to form to glass is that the fine powder of 10 μ m is standby.Other gets analytical reagent Ca (NO 3) 24H 2O 16.8g is dissolved in 95% alcoholic solution of 200ml; Get analytical reagent (NH 4) 2HPO 45.6g, be dissolved in the deionized water of 200ml, two liquid are mixed, and add 5 ethanolamine as surfactant, use NH 4OH solution is adjusted to pH=10.5 with the acidity of mixing material; Stir after 4 hours, it is precipitated static 12 hours, the sucking filtration after drying, obtaining average diameter is the acicular nanometer hydroxyapatite of 75nm for 18nm length.Get analytical reagent (NH again 4) 2HPO 450g, NH 4H 2PO 42.5g after mixing, be dissolved in the deionized water of 100ml, be prepared into distiller liquor, its pH value adjusts to 7.8.Get the above-mentioned glass fine powder of 8g at last, the above-mentioned acicular nanometer hydroxyapatite of 2g fully mixes, in blended process, drip the 3.5ml distiller liquor, the uniform slurry of furnishing fashions into 1cm * 1cm * 1cm cuboid sample and 4mm * 4mm * 60mm strip sample with slurry, maintenance 7 days under 100% humidity respectively, the compressive resistance that records cuboid sample then is 91MPa, the rupture strength 33MPa of cuboid sample, and cuboid sample is in the 100ml normal saline, under 37 ℃ of conditions, Ca ++The amount of separating out is 8.9 * 10 in ionic first day -8G/g (dissolution rate of every gram sample).

Claims (7)

1. bone binding agent, it is characterized in that being a kind of multi-phase composites, hydroxyapatite crystal powder by filling nano-scale between the phosphate glass granule of the biologically active and the hydraulicity and granule is formed, and both mass ratioes of front and back are 60: 40-90: 10.
2. bone binding agent according to claim 1 is characterized in that every 10g multi-phase composites cooperates with the 2-8ml distiller liquor, forms to have close-burning biological cement.
3. bone binding agent according to claim 1 is characterized in that the component of main body phosphate glass is as follows by the proportioning of quality:
P 2O 5： 10-35％，
SiO 2And/or Al 2O 315-50%,
CaO and/or MgO; 20-40%,
F -And/or R 2O:0-10%,
The gross mass of each component satisfies 100%, and wherein R is an alkali metal ion, F -Be metal fluoride; The particle size of phosphate glass is 2～45 μ m.
4. bone binding agent according to claim 1 is characterized in that the component of hydroxyapatite crystal is as follows by the proportioning of quality:
Hydroxyapatite Ca 10(PO 4) 6(OH) 2: 80-100%,
Various aquation apatite Ca 10(PO 4) 6X 2YH 2O:20-0%,
Wherein X is F -Or/and HCO 3 -, or/and NH 2 -Anion radical, Y=1-10, the equivalent size of crystal grain are 10～90nm.
5. bone binding agent according to claim 2 is characterized in that the hydroxyapatite crystal component is as follows by the proportioning of quality:
(NH 4) 2HPO 4 90-100％，
NH 4H 2PO 4 10-0％，
Its pH is 7.0-8.5.
6. preparation method as the described bone binding agent of claim 1-5, it is characterized in that concrete steps are as follows: the component proportioning by phosphate glass prepares batch, and it is placed in the platinum crucible, founds into glass melt; Again with the glass melt quenching between two copper coins, obtain water white glass flake; The glass flake pulverizing is ground to form required particle size, standby;
With Ca (NO 3) 24H 2The alcoholic solution of O and (NH 4) 2HPO 4Aqueous solution be the mixed of 1.6-.17 by the ratio of Ca/P, add the surfactant ethanolamine, be that 5-25 ℃, pH are stirring reaction under the condition of 9.8-11.2 in temperature, produce precipitate, promptly obtain nanometer hydroxyapatite;
Above-mentioned phosphate glass granule is become multi-phase composites with nanometer hydroxyapatite powder art by the proportioning hybrid modulation.
7. preparation method according to claim 6 is characterized in that distiller liquor (NH 4) 2HPO 4With NH 4H 2PO 4Mixed liquor at room temperature mix by proportioning and multi-phase composites, through hydration reaction, must have close-burning slurry.
CNB031151078A 2003-01-23 2003-01-23 Glass based nano hydroxyapatite biologic cement and its preparation method Expired - Fee Related CN1315538C (en)

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JPS63102762A (en) * 1986-10-20 1988-05-07 丸野　重雄 Living body compatible composite and its production
CN1031040C (en) * 1989-11-16 1996-02-21 齐齐哈尔轻工学院 Bioactive coating-titanium alloy artificial bone, artificial joint and preparation method

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