CN103041452A - Porous bone repair framework material of gelatin/nano bone-like apatite, and preparation method and application thereof - Google Patents
Porous bone repair framework material of gelatin/nano bone-like apatite, and preparation method and application thereof Download PDFInfo
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Abstract
The invention belongs to the field of biomedical materials, and particularly relates to a porous bone repair framework material of gelain/nano bone-like apatite, and a preparation method and an application thereof. The porous bone repair framework material with calcium phosphate and uniformly dispersed gelatin molecules is obtained by a step of homogeneous nucleation of calcium and phosphate ions induced by gelatin molecules in a gelatin solution, a subsequent step of growth of nano bone-like apatite crystals, and a final step of a freeze drying method. A molar ratio of Ca to P in the porous bone repair framework material of the nano bone-like apatite is 1-2.2, and a mass content ratio of the nano bone-like apatite to the gelatin is 1.2 : 1-1 : 33. The porous bone repair framework material has good biological compatibility and biodegradability and can endure some compression pressure. The toughness is increased with the content of the gelatin content increasing. The porous bone repair framework material can be used as filling materials for bones, teeth or plastic surgeries.
Description
Technical field
The invention belongs to biomedical materials field, particularly the porous bone of a kind of gelatin for preparing via the biomineralization principle/nano bone apatite is repaired frame material, and this porous bone is repaired preparation method and the application of frame material.
Background technology
Natural bone is the calcium microcosmic salt through the macromolecular nucleation of inducing of non-collagen, and through the complex biological mineralising system with fine grading structure that collagen macromole canonic generation forms.Non-collagen macromole is the protein macromolecule that is formed by 18 seed amino acid assembled arrangement, has the calcium of being conducive to microcosmic salt nucleation site on its strand, can effectively reduce the interface energy that calcium and phosphorus ions precipitates from solution.The collagen macromole also is the protein macromolecule that is formed by 18 seed amino acid assembled arrangement, but the collagen macromole is by two α 1 and left-handed the forming of α 2 chains, carboxyl on its strand and amino group mostly participated in the intramolecular chemical bond of collagen fiber and, only have outside the group of minority is exposed to, become the basic point of standard calcium microcosmic salt growth.
Gelatin is the product of collagen degradation, and it has not only kept collagen as the more peculiar advantages of biomaterial.Compare with collagen, the gelatin no antigen implants without immunological rejection; And low price, soluble in water, easily process; The construction unit of gelatin is Gly-Pro and hydroxyproline and lysine (Gly-Pro-Hyp-Hyl), is flexible ampholyte, is conducive to cytoadherence.So utilize gelatin as the template of calcium microcosmic salt nucleation and growth, simulation biomineralization system, preparation chemical analysis and the similar bone-repairing composite material of natural bone also are inevitable choices.
Chinese patent (application number 200810052418.1) discloses a kind of nano sheet-shaped hydroxyapatite and gelatin composite material and preparation method.The hydroxyapatite content of this material is up to more than 33%, and has laminar structuredly, and interlamellar spacing is 5.8～6.3nm, and the two reaches compound on the nanoscale to make hydroxyapatite and gelatin.But this material also is not compound on the molecule degree of calcium microcosmic salt and gelatin.
Chinese patent (application number 200410003454.0) discloses compound porous frame material of a kind of biomineralization fibroin/macromolecule and preparation method thereof.The method at first obtains the precipitate of fibroin and calcium microcosmic salt via the biomineralization principle, then further macromolecule is compound preferably with biocompatibility with this precipitate, the porous framework material that obtains has good biocompatibility and biological degradability, can be used in clinical repair.But this preparation method is still more loaded down with trivial details, can use some poisonous organic reagents during the dissolving macromolecule.
The people such as the Hae-Won Kim of Korea S utilize the biomineralization principle to synthesize gelatin and compound porous material (the Kim H-W of nanometer hydroxyapatite, Knowles JC, Kim H-E.Porous scaffolds of gelatin-hydroxyapatite nanocomposites obtained by biomimetic approach:Characterization and antibiotic drug release.Journal of Biomedical Materials Research Part B:Applied Biomaterials 2005; 74B (2): 686-698.).The highest 30wt% that accounted for of the ratio of the nanometer hydroxyapatite in this porous material, porosity reaches 89～92%, and pore size is at 0.5～1 μ m and 300～500 μ m.The author utilizes this porous material to coat the antibacterials tetracycline, has studied the release efficiency of tetracycline in this material, and the result shows that the tetracycline rate of release is controlled.It is 1.667 calcium microcosmic salt and the composite of gelatin that but the author has only studied Ca/P.
The present invention utilizes the biomineralization principle, directly prepares the finely dispersed porous bone of polycalcium microcosmic salt and gelatin molecule and repair frame material in gelatin solution.
Summary of the invention
One of purpose of the present invention is to provide the low porous bone that can be used for the gelatin that bone repairs/nano bone apatite of a kind of cost to repair frame material; The two reaches compound on the molecular scale to the invention enables nano bone apatite and gelatin, reaches the porous framework material of simulation natural bone tissue structure.
Two of purpose of the present invention is to provide a kind of preparation technology simple, and what can be fit to large-scale production is prepared the method that the porous bone of gelatin/nano bone apatite is repaired frame material via the biomineralization principle.
The application that three of purpose of the present invention is to provide the porous bone of gelatin/nano bone apatite to repair frame material.
The porous bone that can be used for the gelatin that bone repairs/nano bone apatite of the present invention is repaired frame material, be to utilize directly preparation gelatin and nano bone apatite composite porous from aqueous solution of biomineralization principle, this composite porous and natural bone has similar chemical composition; Wherein, the molar ratio of the Ca/P of nano bone apatite is 1～2.2, and nano bone apatite is 1.2: 1～1: 33 with the mass content ratio of gelatin.
Described porous bone is repaired can further contain a kind of in anti-inflammation drugs, antler polypeptide or the bone growth inducing factor in the frame material.
The porosity that described porous bone is repaired frame material is 35%～90%; The aperture that described porous bone is repaired frame material is 30～500 μ m.
Described gelatin is crosslinked gelatin or uncrosslinked gelatin.
Described crosslinked gelatin or uncrosslinked gelatin are selected from one or more in crosslinked or uncrosslinked osseocolla, crosslinked or uncrosslinked hide glue, the crosslinked or uncrosslinked fish glue.
The preparation method that the porous bone of the gelatin that can be used for the bone reparation of the present invention/nano bone apatite is repaired frame material may further comprise the steps:
1) gelatin particle is joined swelling in the deionized water and form gelatin solution (can be heated to the swelling of carrying out gelatin particle under 35 ℃～75 ℃ the condition), then in gelatin solution, add the phosphate solid, stirring is fully dissolved phosphate, obtains the solution of mix homogeneously; Wherein phosphatic addition is to calculate (mass ratio of preferably phosphate and gelatin particle is 1: 2～1: 20) that adds according to the mol ratio of the Ca/P of nano bone apatite and the mass ratio of nano bone apatite and gelatin particle; With the pH of alkali liquor regulator solution, make it reach the required pH condition of reaction (preferred pH is 5～11);
2) calcium salt is joined in the deionized water, stirring is fully dissolved calcium salt; The addition of calcium salt is that the mass ratio that calculates (preferred calcium salt and step 1) the described gelatin particle that adds according to the mass ratio of the mol ratio of the Ca/P of nano bone apatite and nano bone apatite and gelatin particle is 3: 2～1: 7); PH with the alkali liquor regulator solution reaches the required pH condition of reaction (preferred pH is 5～11);
3) be 20 ℃～75 ℃ and stir that (the preferred speed that stirs is under the condition of 100rpm～3000rpm) in temperature, with step 1) solution prepared dropwise is added drop-wise to step 2) in the solution prepared, in the dropping process, constantly with the pH of alkali liquor conditioned reaction system, keep reaction required pH condition (preferred pH is 5～11); Step 1) after the solution of preparing dropwises, obtains a milky liquid; Keep reaction system to be 20 ℃～75 ℃ and to stir that (the preferred speed that stirs is the mixture that ageing obtains nano bone apatite and gelatin under the condition of 100rpm～3000rpm), and this mixture is milky liquid (time of ageing can be 0 hour～7 days) in the required pH condition of reaction (preferred pH is 5～11), reaction temperature;
4) with step 3) after the nano bone apatite that obtains and the mixture of gelatin freezing (preferred temperature be-40 ℃～-196 ℃) drying, can obtain the porous bone reparation frame material that can be used for gelatin/nano-apatite that bone repairs of the present invention.
The porosity that described porous bone is repaired frame material is 35%～90%; The aperture that described porous bone is repaired frame material is 30～500 μ m.
In step 1) the solution of mix homogeneously in can further add a kind of in anti-inflammation drugs, antler polypeptide or the bone growth inducing factor.The consumption of anti-inflammation drugs, antler polypeptide or the bone growth inducing factor is 1 ‰～10% of gelatin particle quality.
Described anti-inflammation drugs can be gentamycin or vancomycin.
The described bone growth inducing factor can be selected from bone morphogenetic protein, transforming growth factor, fibroblast growth factor, insulin like growth factor, the growth hormone a kind of.
Described calcium salt is lime nitrate, calcium chloride or their mixture.
Described phosphate is selected from one or more the mixture in diammonium phosphate, dipotassium hydrogen phosphate, sodium hydrogen phosphate, Ammonium biphosphate, potassium dihydrogen phosphate, the sodium dihydrogen phosphate.
Described alkali liquor is the aqueous solution of potassium hydroxide, sodium hydroxide or ammonium hydroxide; The preferred concentration of solution is 0.1M～2M.
Described gelatin is crosslinked gelatin or uncrosslinked gelatin.With step 3) further add cross-linking agent before the nano bone apatite that obtains and the mixture lyophilization of gelatin and can obtain crosslinked gelatin.The mass concentration of cross-linking agent is 5 ‰～15%; The addition of cross-linking agent is the cross-linking agent that every gram gelatin particle preferably adds 30 μ l～1000 μ l.
Be used for the crosslinked described cross-linking agent of gelatin and be selected from least a of group that glutaraldehyde, dialdehyde glucose, genipin, glutamine transaminage etc. form.
Described crosslinked gelatin or uncrosslinked gelatin are selected from one or more in crosslinked or uncrosslinked osseocolla, crosslinked or uncrosslinked hide glue, the crosslinked or uncrosslinked fish glue.
The porous bone of the gelatin that can be used for the bone reparation of the present invention/nano bone apatite repair frame material can be used for bone, tooth, and the plastic surgery in packing material use.
It is in gelatin solution that the porous bone of the gelatin that can be used for the bone reparation of the present invention/nano bone apatite is repaired frame material, induce the homogeneous nucleation of calcium, phosphonium ion and the growth of follow-up nano bone phosphorite crystal thereof through gelatin molecule, the synthos and the finely dispersed porous bone reparation of gelatin molecule frame material that finally obtain through freeze-drying.This porous bone is repaired frame material and is had good biocompatibility and biological degradability, and can bear certain compression stress, and its toughness increases along with the increase of gelatine content, can be used as bone, and the packing material in tooth or the plastic operation uses.It is low that porous bone of the present invention is repaired the frame material cost, and preparation technology is simple, is suitable for industrialization production.
Description of drawings
Fig. 1. the porous bone of the gelatin that the embodiment of the invention 1 prepares/nano bone apatite is repaired the Electronic Speculum picture of frame material.
The specific embodiment
Embodiment 1
1) bone gelatin granule 10g is joined swelling in the 200ml deionized water, then be heated to 55 ℃ and form the bone gelatin solution, then add the diammonium phosphate ((NH of 9.2g in the bone gelatin solution
4)
2HPO
4) solid, stirring is fully dissolved it, obtains the solution of mix homogeneously; The pH that regulates bone gelatin solution with potassium hydroxide (KOH) aqueous solution reaches 5.0;
2) with 16.5g lime nitrate (Ca (NO
3)
24H
2O) join in the 200ml deionized water, stirring is fully dissolved lime nitrate; The pH that regulates mentioned solution with potassium hydroxide (KOH) aqueous solution reaches 5.0;
3) be that 37 ℃ and stir speed (S.S.) are under the condition of 100rpm in temperature, with step 1) solution prepared dropwise is added drop-wise to step 2) in the solution prepared, in the dropping process, constantly with the pH of potassium hydroxide (KOH) aqueous solution conditioned reaction system, make the pH of reaction system remain on 5.0 times and react; Step 1) after the solution of preparing dropwises, obtains a milky liquid; Keep that above-mentioned reaction system equals 5 at pH, reaction temperature is that 37 ℃ and stir speed (S.S.) are to proceed ageing 23 hours under the condition of 100rpm, obtains the mixture of nano bone apatite and bone gelatin, this mixture is milky liquid;
4) with step 3) the nano bone apatite that obtains and the mixture of bone gelatin are after temperature is carried out lyophilization under for-30 ℃, and the porous bone that obtains can be used for bone gelatin/nano-apatite that bone repairs is repaired frame material; The Electronic Speculum picture as shown in Figure 1.
The mass content ratio that this porous bone is repaired nano bone apatite and bone gelatin in frame material is 1.2: 1, nano bone apatite consist of calcium hydrogen phosphate, the molar ratio of the Ca/P of nano bone apatite is 1: 1.Its surface and the inner aperture structure that is UNICOM, porosity is 76%, the aperture is 100 μ m～500 μ m.Can be used for bone, tooth and orthopedic packing material use.
Embodiment 2
1) bone gelatin granule 200g is joined swelling in the 200ml deionized water, then be heated to 55 ℃ and form the bone gelatin solution, then add the diammonium phosphate ((NH of 5.3g in the bone gelatin solution
4)
2HPO
4) solid, stirring is fully dissolved it, obtains the solution of mix homogeneously; The pH that regulates bone gelatin solution with potassium hydroxide (KOH) aqueous solution reaches 11;
2) with the lime nitrate (Ca (NO of 20.8g
3)
24H
2O) join in the 200ml deionized water, stirring is fully dissolved lime nitrate; The pH that regulates mentioned solution with potassium hydroxide (KOH) aqueous solution reaches 11;
3) be that 37 ℃ and stir speed (S.S.) are under the condition of 3000rpm in temperature, with step 1) solution prepared dropwise is added drop-wise to step 2) in the solution prepared, in the dropping process, constantly with the pH of potassium hydroxide (KOH) aqueous solution conditioned reaction system, make the pH of reaction system remain on 11 times and react; Step 1) after the solution of preparing dropwises, obtains a milky liquid; Keep that above-mentioned reaction system equals 11 at pH, reaction temperature is that 37 ℃ and stir speed (S.S.) are to proceed ageing 23 hours under the condition of 3000rpm, obtains the mixture of nano bone apatite and bone gelatin, this mixture is milky liquid;
4) with step 3) the nano bone apatite that obtains and the mixture of bone gelatin temperature for-30 ℃ under after lyophilization, the porous bone that obtains can be used for bone gelatin/nano-apatite that bone repairs is repaired frame material.
The mass content ratio that this porous bone is repaired nano bone apatite and bone gelatin in frame material is 1: 33, nano bone apatite consist of the class hydroxyapatite, the molar ratio of the Ca/P of nano bone apatite is 2.2.Its surface and the inner aperture structure that is UNICOM, porosity is 90%, the aperture is 30 μ m～200 μ m.Can be used for bone, tooth and orthopedic packing material use.
Embodiment 3
1) isinglass granule 50g is joined swelling in the 200ml deionized water, then be heated to 55 ℃ and form the isinglass solution, then add the dipotassium hydrogen phosphate (K of 7.0g in the isinglass solution
2HPO
4) solid, stirring is fully dissolved it, then adds bone morphogenetic protein 2 5mg.With ammonium hydroxide ((NH
4) OH) pH of regulator solution, make it reach 10.10; Obtain the solution of mix homogeneously;
2) with the lime nitrate (Ca (NO of 14.2g
3)
24H
2O) join in the 200ml deionized water, stirring is fully dissolved lime nitrate; With ammonium hydroxide ((NH
4) OH) the aqueous solution pH that regulates mentioned solution reaches 10.10;
3) be that 37 ℃ and stir speed (S.S.) are under the condition of 400rpm, with step 1 in temperature) solution prepared dropwise is added drop-wise to step 2) in the solution prepared, in the dropping process constantly with ammonium hydroxide ((NH
4) OH) pH of aqueous solution conditioned reaction system, make the pH of reaction system remain on 10.10 times and react; Step 1) after the solution of preparing dropwises, obtains a milky liquid; Keep that above-mentioned reaction system equals 10.10 at pH, reaction temperature is that 37 ℃ and stir speed (S.S.) are to proceed ageing 23 hours under the condition of 400rpm, obtains the mixture of nano bone apatite and isinglass, this mixture is milky liquid;
4) with step 3) the nano bone apatite that obtains and the mixture of isinglass are after temperature is carried out lyophilization under for-20 ℃, and the porous bone that obtains can be used for isinglass/nano-apatite that bone repairs is repaired frame material.
The mass content ratio that this porous bone is repaired nano bone apatite and isinglass in frame material is 3: 25, nano bone apatite consist of the class hydroxyapatite, the molar ratio of the Ca/P of nano bone apatite is 1.5, contains bone morphogenetic protein.Its surface and the inner aperture structure that is UNICOM, porosity is 84%, the aperture is 70 μ m～400 μ m.Can be used for bone, tooth and orthopedic packing material use.Embodiment 4
1) bone gelatin granule 25g is joined swelling in the 200ml deionized water, then be heated to 55 ℃ and form the bone gelatin solution, then add the diammonium phosphate ((NH of 5.3g in the bone gelatin solution
4)
2HPO
4) solid, stirring is fully dissolved it, then adds anti-inflammation drugs vancomycin 25mg; With ammonium hydroxide ((NH
4) OH) the aqueous solution pH that regulates bone gelatin solution reaches 10.10;
2) with the calcium chloride Ca (Cl) of 6.7g
2Join in the 200ml deionized water, stirring is fully dissolved calcium chloride; With ammonium hydroxide ((NH
4) OH) the aqueous solution pH that regulates mentioned solution reaches 10.10;
3) be that 37 ℃ and stir speed (S.S.) are under the condition of 400rpm, with step 1 in temperature) solution prepared dropwise is added drop-wise to step 2) in the solution prepared, in the dropping process constantly with ammonium hydroxide ((NH
4) OH) pH of aqueous solution conditioned reaction system, make the pH of reaction system remain on 10.10 times and react; Step 1) after the solution of preparing dropwises, obtains a milky liquid; Keep that above-mentioned reaction system equals 10.10 at pH, reaction temperature is that 37 ℃ and stir speed (S.S.) are to proceed ageing 23 hours under the condition of 400rpm, obtains the mixture of nano bone apatite and bone gelatin, this mixture is milky liquid;
4) with step 3) the nano bone apatite that obtains and the mixture of bone gelatin are after temperature is carried out lyophilization under for-40 ℃, and the porous bone that obtains can be used for bone gelatin/nano-apatite that bone repairs is repaired frame material.
The mass content ratio that this porous bone is repaired nano bone apatite and bone gelatin in frame material is 6: 25, nano bone apatite consist of the class hydroxyapatite, the molar ratio of the Ca/P of nano bone apatite is 1.667, contains the anti-inflammation drugs vancomycin.Its surface and the inner aperture structure that is UNICOM, porosity is 62%, the aperture is 30 μ m～500 μ m.Can be used for bone, tooth and orthopedic packing material use.
Embodiment 5
1) hide glue granule 25g is joined swelling in the 200ml deionized water, then be heated to 55 ℃ and form the hide glue solution, then add the sodium hydrogen phosphate (Na of 5.7g in the hide glue solution
2HPO
4) solid, stirring is fully dissolved it, obtains the solution of mix homogeneously; The pH that regulates bone gelatin solution with potassium hydroxide (KOH) aqueous solution reaches 10.10;
2) with the calcium chloride CaCl of 6.7g
2Join in the 200ml deionized water, stirring is fully dissolved calcium chloride; The pH that regulates mentioned solution with potassium hydroxide (KOH) aqueous solution reaches 10.10;
3) be that 37 ℃ and stir speed (S.S.) are under the condition of 400rpm in temperature, with step 1) solution prepared dropwise is added drop-wise to step 2) in the solution prepared, in the dropping process, constantly with the pH of potassium hydroxide (KOH) aqueous solution conditioned reaction system, make the pH of reaction system remain on 10.10 times and react; Step 1) after the solution of preparing dropwises, obtains a milky liquid; Keep that above-mentioned reaction system equals 10.10 at pH, reaction temperature is that 37 ℃ and stir speed (S.S.) are to proceed ageing 23 hours under the condition of 400rpm, obtains the mixture of nano bone apatite and hide glue, this mixture is milky liquid;
4) to step 3) add 2.5ml 8 (v/v) % glutaraldehyde solution in the nano bone apatite that obtains and the mixture of hide glue, continued crosslinked 30 minutes;
5) with step 4) the nano bone apatite that obtains and crosslinked hide glue are after temperature is carried out lyophilization under for-40 ℃, and the porous bone that obtains can be used for hide glue/nano-apatite that bone repairs is repaired frame material.
The mass content ratio that this porous bone is repaired nano bone apatite and hide glue in frame material is 6: 25, nano bone apatite consist of the class hydroxyapatite, the molar ratio of the Ca/P of nano bone apatite is 1.667, hide glue is the hide glue behind the glutaraldehyde cross-linking.Its surface and the inner aperture structure that is UNICOM, porosity is 62%, the aperture is 30 μ m～500 μ m.Can be used for bone, tooth and orthopedic packing material use.
Claims (11)
1. the porous bone of the gelatin for the bone reparation/nano bone apatite is repaired frame material, and it is characterized in that: the molar ratio of the Ca/P of nano bone apatite is 1～2.2, and nano bone apatite is 1.2: 1～1: 33 with the mass content ratio of gelatin;
Described gelatin is crosslinked gelatin or uncrosslinked gelatin.
2. the porous bone of the gelatin of repairing for bone according to claim 1/nano bone apatite is repaired frame material, it is characterized in that: described porous bone is repaired and is contained a kind of in anti-inflammation drugs, antler polypeptide or the bone growth inducing factor in the frame material.
3. the porous bone of the gelatin for the bone reparation according to claim 2/nano bone apatite is repaired frame material, and it is characterized in that: described anti-inflammation drugs is gentamycin or vancomycin;
The described bone growth inducing factor is selected from bone morphogenetic protein, transforming growth factor, fibroblast growth factor, insulin like growth factor, the growth hormone a kind of.
4. the porous bone of the gelatin for the bone reparation according to claim 1 and 2/nano bone apatite is repaired frame material, it is characterized in that: the porosity that described porous bone is repaired frame material is 35%～90%, and the aperture is 30～500 μ m.
5. the porous bone of the gelatin of repairing for bone according to claim 1/nano bone apatite is repaired frame material, it is characterized in that: described crosslinked gelatin or uncrosslinked gelatin are selected from one or more in crosslinked or uncrosslinked osseocolla, crosslinked or uncrosslinked hide glue, the crosslinked or uncrosslinked fish glue.
One kind according to claim 1～5 the described gelatin of repairing for bone of any one/porous bone of nano bone apatite repair the preparation method of frame material, it is characterized in that, described method may further comprise the steps:
1) gelatin particle is joined swelling formation gelatin solution in the deionized water, then add the phosphate solid in gelatin solution, stir, obtain the solution of mix homogeneously, wherein the mass ratio of phosphate and gelatin particle is 1: 2～1: 20; PH with the alkali liquor regulator solution is 5～11;
2) calcium salt being joined in the deionized water, stirs, wherein calcium salt and step 1) mass ratio of described gelatin particle is 3: 2～1: 7; PH with the alkali liquor regulator solution is 5～11;
3) under temperature is 20 ℃～75 ℃ and stirring condition, with step 1) solution prepared dropwise is added drop-wise to step 2) in the solution prepared, constantly the pH with alkali liquor conditioned reaction system is 5～11 in the dropping process; Step 1) after the solution of preparing dropwised, ageing obtained the mixture of nano bone apatite and gelatin;
4) with step 3) after the nano bone apatite that obtains and the mixture lyophilization of gelatin, the porous bone that obtains described gelatin/nano-apatite of repairing for bone is repaired frame material;
Described gelatin is crosslinked gelatin or uncrosslinked gelatin;
Described crosslinked gelatin is with step 3) obtain after adding cross-linking agent before the nano bone apatite that obtains and the mixture lyophilization of gelatin.
7. preparation method according to claim 6 is characterized in that: step 1) add in the solution of described mix homogeneously a kind of in anti-inflammation drugs, antler polypeptide or the bone growth inducing factor arranged.
8. preparation method according to claim 7, it is characterized in that: the consumption of described anti-inflammation drugs, antler polypeptide or the bone growth inducing factor is 1 ‰～10% of gelatin particle quality;
Described anti-inflammation drugs is gentamycin or vancomycin;
The described bone growth inducing factor is selected from bone morphogenetic protein, transforming growth factor, fibroblast growth factor, insulin like growth factor, the growth hormone a kind of.
9. preparation method according to claim 6, it is characterized in that: described calcium salt is lime nitrate, calcium chloride or their mixture;
Described phosphate is selected from one or more the mixture in diammonium phosphate, dipotassium hydrogen phosphate, sodium hydrogen phosphate, Ammonium biphosphate, potassium dihydrogen phosphate, the sodium dihydrogen phosphate;
Described crosslinked gelatin or uncrosslinked gelatin are selected from one or more in crosslinked or uncrosslinked osseocolla, crosslinked or uncrosslinked hide glue, the crosslinked or uncrosslinked fish glue.
10. preparation method according to claim 6, it is characterized in that: described alkali liquor is the aqueous solution of potassium hydroxide, sodium hydroxide or ammonium hydroxide.
11. according to claim 1～5 application of the porous bone reparation frame material of the described gelatin for the bone reparation of any one/nano bone apatite, it is characterized in that: the porous bone of described gelatin for the bone reparation/nano bone apatite is repaired the packing material use that frame material is used for bone, tooth, reaches the plastic surgery.
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| CN115887776A (en) * | 2021-09-24 | 2023-04-04 | 中国科学院理化技术研究所 | Composite porous scaffold formed on basis of gelatin-induced magnesium phosphate deposition and preparation method and application thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01288269A (en) * | 1988-05-16 | 1989-11-20 | Tonen Corp | Composite molding |
| EP1380313A1 (en) * | 2002-07-11 | 2004-01-14 | MERCK PATENT GmbH | Method of preparing porous calcium phosphate morsels and granules via Gelatin processing |
| CN101444646A (en) * | 2007-11-27 | 2009-06-03 | 中国科学院理化技术研究所 | Gelatin/calcium phosphate composite porous microsphere for bone repair and preparation method and usage of the porous microsphere |
| CN101785878A (en) * | 2009-01-22 | 2010-07-28 | 中国科学院理化技术研究所 | Composite porous forming material for bone restoration, preparation method and application thereof |
-
2011
- 2011-10-13 CN CN2011103094878A patent/CN103041452A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01288269A (en) * | 1988-05-16 | 1989-11-20 | Tonen Corp | Composite molding |
| EP1380313A1 (en) * | 2002-07-11 | 2004-01-14 | MERCK PATENT GmbH | Method of preparing porous calcium phosphate morsels and granules via Gelatin processing |
| CN101444646A (en) * | 2007-11-27 | 2009-06-03 | 中国科学院理化技术研究所 | Gelatin/calcium phosphate composite porous microsphere for bone repair and preparation method and usage of the porous microsphere |
| CN101785878A (en) * | 2009-01-22 | 2010-07-28 | 中国科学院理化技术研究所 | Composite porous forming material for bone restoration, preparation method and application thereof |
Non-Patent Citations (3)
| Title |
|---|
| 《高分子学报》 20060228 滕淑华等 明胶中alpha组分含量对明胶P羟基磷灰石 第65-68页 6-11 , 第1期 * |
| 殷海荣等: "超声时间对羟基磷灰石P明胶复合材料生物学性能的影响", 《陶瓷》, no. 10, 31 December 2008 (2008-12-31), pages 16 - 19 * |
| 滕淑华等: "明胶中α组分含量对明胶P羟基磷灰石", 《高分子学报》, no. 1, 28 February 2006 (2006-02-28), pages 65 - 68 * |
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