CN104027849A - Soy isoflavone supported biological composite material porous scaffold and preparation - Google Patents
Soy isoflavone supported biological composite material porous scaffold and preparation Download PDFInfo
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Abstract
The invention provides a soy isoflavone supported biological composite material porous scaffold and preparation. According to the porous scaffold, a nano calcium-deficient apatite-poly-amino acid copolymer composite material porous scaffold is used as a carrier, soy isoflavone is mixed in the carrier material, particularly, plant sourced 5,4',7-genistein is used as a growth factor component, wherein the mass ratio of the growth factor and the composite material is (1-10):100. When the porous scaffold is prepared, the components and a calcium sulphate dihydrate component foaming agent which is 5-15 percent by mass of the composite material are mixed, and are subjected to injection molding in an injection manner. Experiment results indicate that the cell proliferation degree of the porous scaffold to MG-63 is remarkably superior to that of a scaffold without supporting of soy isoflavone, the porous scaffold has significant difference and has an excellent prospect in serving as a scaffold material with excellent osteogenesis promoting performance.
Description
Technical field
The present invention relates to a kind of degradable nanometer calcium deficiency apatite/polynary amino acid copolymer composite porous support, particularly in timbering material, be mixed with soybean isoflavone can promote as somatomedin composition osteocyte propagation and skeletonization nanometer calcium deficiency apatite/polynary amino acid copolymer composite porous support and prepare.
Background technology
Bone does not connect is complication common in fractures process.The at present main method of clinical treatment, be replant into bone-grafting material by removing after fibrous tissue etc., fixing and the modus operandis such as fracture end pressurization are carried out in changing.Conventionally the bone-grafting material of using in operation, comprises autologous bone, allograph bone, artificial bone.Autologous bone has induced activity and support effect concurrently, can play induced osteogenesis support, osteoblastic effect is provided, and skeletonization effect is best, and can not cause immunoreation and pathophoresis, but its source is limited, and can cause patient's secondary injury, and may cause the complication of getting bone region.Allograph bone is also one of to select, but it is slow to have bone conductibility skeletonization, and has graft-rejection and the shortcoming that leads to the failure, has the danger of infectious diseases such as propagating hepatitis and acquired immune deficiency syndrome (AIDS), also involves ethical issues simultaneously, and therefore its application is also restricted.
Along with the development of the subject such as biomaterial, organizational project, existing kinds of artificial bone alternate material appearance, because artificial bone can be mass, wide material sources, can finally reduce the cost of bone defect healing, therefore artificial bone is the focus and emphasis of research for bone does not connect treatment all the time.But use merely artificial bone to the damaged treatment of this class of bone does not connect difficult healing bone, current effect is unsatisfactory.
Accordingly, utilizing the special regulating and controlling effect of skeletal growth factor to cell/tissue, build the compound rest of the compound promotion skeletal growth factor of artificial bone for bone does not connect reparation, has been one of the research forward position focus in this field at present.Molecular biology research shows, promotes osteogenesis composition can activate some gene in osteoblast as bone formation generation protein factor (BMP), thus promote that osteoblast cell adsorbs/sticks, propagation with break up etc.; Carrier material can be osteogenesis corresponding Calcium and phosphorous component is provided, and the therefore synergism of the two can be realized the good reparation of bone does not connect.At present, the compound BMP of artificial bone has been for repairing one of common method of bone does not connect.Current research shows, though BMP can induce bone mesenchymal cell to be divided into the tissues such as bone, cartilage, tendon and nerve, there is powerful ossification, can promote osseous tissue Fast Growth and reach the object of reparation, but the extraction difficulty of BMP is expensive, be difficult to be widely used, and BMP is when bone defect area stimulates skeletonization, also stimulated the hypertrophy of osteoclast, and the hypertrophy of osteoclast is early than osteoblast; In addition, it lacks good carrier material, use separately the requirement that is difficult to meet long-term sustained release, and its clinical trial result shows and is weaker than zoopery at present, and the kind of BMP, source, using dosage etc. all can have a significant impact to osteogenic induction activity.
In recent years studies have found that, extract from the soybean isoflavone (SI) of plant and have with chemical constitution like human body estrogens and similar functions and be called as phytoestrogen, can effectively prevent and treat for want of estrogen and the disease of the osteoporosis, cancer aspect and the cardiovascular aspect that cause of postmenopausal women.The report such as Fanti and Picherit by after excision rat ovary through skin injection and the soybean isoflavone of feeding, observing its result on the impact of skeletal system growth promoter shows, the cancellated bone density of femur backbone, metaphysis and distal femoral of experimental group animal of injection soybean isoflavone is apparently higher than matched group, and can effectively suppress bone-loss.
With regard to regard to the use of soybean isoflavone, generally adopt percutaneous injection and the oral two kinds of modes of feeding at present.But these two kinds of modes all need, by the metabolic system of body, ingredient is transported to fracture site, therefore can cause the medication amount deficiency of fracture site, effectively sustained release.Common solution is to carry out slow release after adopting drug sustained release system medicine carrying, reaches and continues and steady concentration administration, directly acts on the object of diseased region.For example, current medicine carrying mode conventional in the osseous tissue renovating materials such as support, normally makes medicine isoreactivity composition be adsorbed on the surface of timbering material by immersion.This method makes active component larger in the support initial stage burst size that implants, and the release of scaffold degradation stage non-activity composition, rate of release is extremely inhomogeneous, can not reach the degradable front long-acting of support in the object of focus.
Summary of the invention
For these reasons, the present invention will provide one can at the uniform velocity discharge for a long time somatomedin, effectively promote bone does not connect defect repair, somatomedin/composite porous support that reparation speed that bone is damaged is mated with the degradation speed of material, specifically the Biocomposite material porous support of a kind of year soybean isoflavone, to meet the needs of clinical bone defect repair.On this basis, the present invention also will provide a kind of preparation method to this porous support.
The Biocomposite material porous support of soybean isoflavone is carried in the present invention, with nanometer calcium deficiency apatite-polynary amino acid copolymer composite (nano calcium deficient hydroxyapatite-multi (amino acid) copolymer, n-CDHA-MAC) porous support (porous n-CDHA-MAC scaffold, PCMS) as carrier, it is characterized in that being mixed with soybean isoflavone as somatomedin composition in described carrier material, the mass ratio of somatomedin and composite is 1 ~ 10
:100.
Result of the test shows, the soybean isoflavone that contains this proportion in this composite porous support is as somatomedin, can produce effective promotion osteocyte propagation and differentiation, it is the active effect of alkali phosphatase, and can be according to the degradation speed of actual this composite porous support that uses, concrete content of selecting definite soybean isoflavone as somatomedin within the scope of this.For example, in the time that used timbering material has lower degradation speed, can suitably improve the load ratio of contained this somatomedin in support.
In the above-mentioned porous material of the present invention as described this nanometer calcium deficiency apatite-polynary amino acid copolymer composite of carrier, at Li h, Gong M, Yang AP, et al. Degradable biocomposite of nano calcium deficient hydroxyapatite/multi-(amino acid) copolymer. International Journal of Nanomedicine. 2012,7:1287-1295) etc. had the product of report in document.Wherein, the chemical formula of described nanometer calcium-deficient apatite is Ca
10 X(HPO
4) X (PO
4)
6 X(OH)
2 X, 0≤x<1 wherein, Ca/P is between 1.50-1.67, and its crystal structure is imperfect, and composition more close to osteolith, therefore has degradation speed fast, the feature that biological activity is high with structure.And common and the existing many research reports of osseous tissue renovating material the chemical formula of stoichiometric chemistry hydroxyapatite be Ca
10(PO
4)
6(OH)
2, Ca/P=1.67, its dissolubility is little, and the palliating degradation degree in human body is relatively low, is stored in for a long time and in body, is unfavorable for bone tissue restoration.
Research is at present found, can be used as the soybean isoflavone that somatomedin uses in the above-mentioned porous support of the present invention, can be divided into 9 kinds of glucosides and 3 kinds of sequestered isoflavone, wherein preferably 5 of plant origin, 4 ', 7-trihydroxy-isoflavone compound (Ge), molecular formula is C
15h
10o
5, molecular weight 270,298 DEG C of fusing points, have good stability.Because of structure and the estrogenic structure of human body of Ge compound the most approaching, after intracellular estrogen receptor (ER) combination, can cause ER conformation to be overturn, thereby and transcribe in conjunction with activated gene from the chromatin in the upper different startups of DNA region, to target organs performance full agonist, the effect of partial agonist or pure antagonist, in osteogenetic process, can promote the secretion of bdgf insulin-like growth factor-i (IGF-1), accelerate Oesteoblast growth, and suppress osteoclast and breed, realize the accurate control of cell growth, therefore Ge has better biological activity.
In above-mentioned porous support, generally, the mass ratio of the nanometer calcium deficiency apatite in described composite, can be with reference to the many similar composite porous modes that has been reported and/or use including aforementioned documents, be chosen as 10 ~ 50%, all the other are polynary amino acid copolymer.Experimental result shows, the height of apatite content in composite, to the release of the present invention's somatomedin described in load and/or somatomedin in this composite, all affects without obvious.
Polynary amino acid copolymer in above-mentioned porous support composition, particularly in the organic and inorganic type bone reparation/alternative composite material that contains hydroxyapatite constituents as the polynary amino acid copolymer of organic material component, comprising that publication number is the applicant's such as CN101385869A, CN101417149A early stage patent documentation, particularly in aforesaid document, all having fully and introduce.Wherein, this polynary amino acid copolymer by 6-aminocaprolc acid as main chain, as copolymerization units, polymerization becomes the polymer that a class degradation speed can be regulated by the molecular weight of polymer, copolymerization natural amino acid unit kind etc. with the necessary natural amino acid of human body.Its remarkable advantage is, the catabolite of this polynary amino acid copolymer is amino acid monomer or oligomer, to human body avirulence, and do not affect the pH value of implant site surrounding.
As aforementioned documents is introduced, as the carrier of the above-mentioned porous support of the present invention, it can be as said in aforementioned documents, and the porosity of described porous support carrier generally can be 65 ~ 95%, and better scope may be selected to be 80-95%.Experiment demonstration, porosity remains within the scope of this, is all conducive to Growth of Cells and sticks, and particularly in better porosity preferable range, is conducive to Growth of Cells most and sticks.。
The preparation of the Biocomposite material porous support of above-mentioned year soybean isoflavone of the present invention, one of method that can adopt, by the nanometer calcium deficiency apatite of described ratio-polynary amino acid copolymer composite and somatomedin composition, and be calcium sulphate dihydrate (the Calcium Sulphate of described composite quality 5-15%, CS) after the foaming agent of composition mixes, in injection moulding mode, 150 ~ 180 DEG C of injection temperatures, injection pressure 50 ~ 70MPa, injection speed 80 ~ 95%, under the condition that mold temperature is 50 ~ 70 DEG C, injection mo(u)lding is described porous support product.Wherein, more preferably condition when injection mo(u)lding is, injection temperature is 175 DEG C, and injection pressure is 70MPa, and injection speed is 80%, the temperature 60 C of mould.Due to 298 DEG C of the fusing points of the Ge as somatomedin, excellent heat stability, therefore described injection temperature is lower than its melt temperature, thereby can keep its physical and chemical performance, with and growth promotion performance all can be not destroyed, particularly ensure the pore structure of the porous material that forms.
The nanometer calcium deficiency apatite-polynary amino acid copolymer composite of one of wherein said raw material, can adopt the mode of aforementioned documents to prepare.For example, its basic preparation process, can be first by selected amino acid monomer in proportion and appropriate water add reaction vessel and be uniformly mixed, for example, after heating (160 DEG C) dehydration, aminoacid melting is treated in intensification (for example 210 DEG C), then adds the nanometer calcium deficiency apatite proceed step by step reaction (for example first react after 0.5-2 hour, continue to be warming up to 220 DEG C of reaction 0.5-1 hour) of described ratio, cooling, obtain described nanometer calcium deficiency apatite-polynary amino acid copolymer composite.For avoiding oxidation, polyreaction can be carried out and complete in the inert gas shielding environment such as nitrogen.
The foaming agent of the calcium sulfate constituents described in the above-mentioned preparation method of the present invention, adopts calcium sulphate dihydrate.
Under above-mentioned operation condition of injection, described raw mixture can be molten condition and can directly injection molding molding in mould in injection machine.Putting before this, for making described nanometer calcium deficiency apatite-polynary amino acid copolymer composite in raw material can be with other for pulverous raw material can faster and better mix uniformly effect, further can preferably first described nanometer calcium deficiency apatite-polynary amino acid copolymer composite be broken into after the granule that particle diameter is 3 ~ 5mm, then mix with all the other compositions.
In the above-mentioned preparation method of the present invention, by control and adjustment etc. to described foaming agent consumption, can also change the porosity in timbering material, thereby obtain having the porous support of different degradation rates, make somatomedin wherein there is different release efficiencies to reach, to adapt to and to meet different use needs.For example, suitably increase the usage ratio of described foaming agent, can obtain having the more support product of high porosity, the support that porosity is high can have higher degradation speed, thereby can discharge fast described somatomedin.
Experimental result shows, the soybean isoflavone that the present invention adopts is as somatomedin, particularly Ge, with and usage ratio, can make the remarkable Promote cell's growth of concentration of the bioactie agent that porous support discharges in degradation process; In cell cultivation process, the cell increment degree of porous support of the present invention, significantly be greater than the not similar porous support (PCMS) of this somatomedin of load, and have significant difference, show that porous support of the present invention has the good prospect as excellent osteogenesis performance timbering material.Be loaded among whole timbering material body with hybrid mode and adopt injection moulding mode will there is bioactive somatomedin, the somatomedin shape that can substantially be evenly distributed in support, its release at bone implant site can progressively be carried out along with the degraded of support, thereby can make to promote the growth factor release speed of bone defect healing and body bone tissue independently to repair speeds match, be conducive to the quick reparation that bone is damaged.And the raw material of porous support of the present invention is easy to get, also without immunological diseases risk, preparation method is simple and easy to do, and can realize and producing in enormous quantities and processing, can be orthopaedic disease, particularly to the treatment of bone does not connect provide a class new with valuable bone impairment renovation material.
Below in conjunction with the detailed description of the invention of accompanying drawing illustrated embodiment form, foregoing of the present invention is described in further detail again.But this should be interpreted as to the scope of the above-mentioned theme of the present invention only limits to following example.Without departing from the idea case in the present invention described above, various replacements or the change made according to ordinary skill knowledge and customary means, all should comprise within the scope of the invention.
Brief description of the drawings
Fig. 1 is in the embodiment of the present invention 1 and 2 and not carry somatomedin reference substance porous support product (PCMS) upper, detects the contrast of the compound cultivation MG-63 cell cell proliferation situation of 1,3,5,7 days with MTT.
Detailed description of the invention
embodiment 1
Be nanometer calcium deficiency apatite-polynary amino acid copolymer composite (n-CDHA-MAC) granule that 3 ~ 5mm and apatite content are 40wt% by particle diameter, with 5 of foaming agent calcium sulphate dihydrate (CS) and plant origin, 4 ', the 7-trihydroxy-isoflavone compound growth factor (Ge), according to n-CDHA/MAC:CS:Ge=90:10:1(quality) mix homogeneously, 175 DEG C of injection temperatures, injection pressure 70Mpa, injection speed 80%, 60 DEG C of mold temperatures, single mode injection volume is under the condition of 40mm, obtain being loaded with the composite porous support Ge-PCMS(product 1 of the present invention of somatomedin Ge), porosity is 81%.In phosphate buffer, carry out Ge release test, the Ge amount that this routine product discharged in 1 one weeks is about 0.0001g.The PCMS that does not carry Ge somatomedin preparing with same Yang Fangfa in contrast, cultivates discovery afterwards in 1,3,5,7 days by support and the compound cultivation of MG-63 cell, and the cell proliferation degree of this routine product 1 is greater than PCMS, and there were significant differences with PCMS.Cell proliferation OD value as shown in Figure 1.
embodiment 2
Be nanometer calcium deficiency apatite-polynary amino acid copolymer composite material granular, foaming agent CS and the Ge that 3 ~ 5mm and apatite content are 40wt% by particle diameter, according to n-CDHA/MAC:CS:Ge=90:10:5(quality) mix homogeneously, under the condition that is 40mm at 175 DEG C of injection temperatures, injection pressure 70Mpa, injection speed 80%, 60 DEG C of mold temperatures, single mode injection volume, obtain composite porous support Ge-PCMS(product 2 of the present invention), porosity is 80.4%.In phosphate buffer, carry out Ge release test, this routine 2 one weeks interior Ge amount that discharge of product is about 0.0004g.With PCMS in contrast, support and the compound cultivation of MG-63 cell are found for 1,3,5,7 days afterwards, the cell proliferation degree of this routine product 2 is greater than PCMS, and there were significant differences with PCMS.Cell proliferation OD value as shown in Figure 1.Fig. 1 result is clear to be shown, the present invention is loaded with the support product of somatomedin Ge, the Effect of promoting growth of MG-63 cell is all significantly better than not carrying to the contrast PCMS support of Ge.
In Fig. 1, the sample of numbering 1-Ge-PCMS is the product 1 of embodiment 1, and the sample of numbering 5-Ge-PCMS is the product 2 of embodiment 2.
embodiment 3
Be nanometer calcium deficiency apatite-polynary amino acid copolymer composite material granular, foaming agent CS and the Ge that 3 ~ 5mm and apatite content are 40wt% by particle diameter, by n-CDHA/MAC
:cS
:ge=90
:10
:10(quality) mix homogeneously, under the condition that is 40mm at 175 DEG C of injection temperatures, injection pressure 70Mpa, injection speed 80%, 60 DEG C of mold temperatures, single mode injection volume, obtain composite porous support Ge-PCMS(product 3 of the present invention), porosity is 81.7%.In phosphate buffer, carry out Ge release test, this routine 3 one weeks interior Ge amount that discharge of product is about 0.001g.With PCMS in contrast, support and the compound cultivation of MG-63 cell are found, cell proliferation degree is greater than PCMS, and there were significant differences with PCMS.
embodiment 4
Be nanometer calcium deficiency apatite/polynary amino acid copolymer composite material granular, foaming agent CS and the Ge that 3 ~ 5mm and apatite content are 40wt% by particle diameter, by n-CDHA/MAC
:cS
:ge=90
:10
:15(quality) mix homogeneously, under the condition that is 40mm at 175 DEG C of injection temperatures, injection pressure 70Mpa, injection speed 80%, 60 DEG C of mold temperatures, single mode injection volume, obtain porous support Ge-PCMS(product 4 of the present invention), porosity is 80.4%.In phosphate buffer, carry out drug release test, this routine 4 one weeks interior Ge amount that discharge of product is about 0.0015g.With product 3 samples of PCMS and embodiment 3 in contrast, support and the compound cultivation of MG-63 cell are found, cell proliferation degree and PCMS are suitable, but significantly lower than product 3.
embodiment 5
Be nanometer calcium deficiency apatite/polynary amino acid copolymer composite material granular, foaming agent CS and the Ge that 3 ~ 5mm and apatite content are 40wt% by particle diameter, by n-CDHA/MAC
:cS
:ge=90
:10
:0.5(quality) mix homogeneously, under the condition that is 40mm at 175 DEG C of injection temperatures, injection pressure 70Mpa, injection speed 80%, 60 DEG C of mold temperatures, single mode injection volume, obtain porous support Ge-PCMS(product 5 of the present invention), porosity is 81.9%.In phosphate buffer, carry out Ge release test, the Ge amount that this routine product discharged in 5 one weeks is about 0.00005g.With PCMS and product 1 sample in contrast, support and the compound cultivation of MG-63 cell are found, cell proliferation degree and PCMS are suitable, and without significant difference, compared with product 1, cell proliferation degree significantly reduces with PCMS.
embodiment 6
Be nanometer calcium deficiency apatite/polynary amino acid copolymer composite material granular, foaming agent calcium sulfate CS and the Ge that 3 ~ 5mm and apatite content are 40wt% by particle diameter, according to n-CDHA/MAC
:cS
:ge=85
:15
:5(mass ratio) ratio mix homogeneously, under the condition that is 40mm at 175 DEG C of injection temperatures, injection pressure 60Mpa, injection speed 90%, 60 DEG C of mold temperatures, single mode injection volume, obtain composite porous support Ge-PCMS(product 6 of the present invention), porosity is 95%.In phosphate buffer, carry out Ge release test, the Ge amount that this routine product discharged in 6 one weeks is about 0.0007g.With PCMS and product 3 samples in contrast, support and the compound cultivation of MG-63 cell are found, cell proliferation degree is greater than PCMS, and there were significant differences with PCMS.
embodiment 7
Be nanometer calcium deficiency apatite/polynary amino acid copolymer composite material granular, foaming agent calcium sulfate CS and the Ge that 3 ~ 5mm and apatite content are 40wt% by particle diameter, according to n-CDHA/MAC
:cS
:ge=95
:5
:5(mass ratio) ratio mix homogeneously, under the condition that is 40mm at 175 DEG C of injection temperatures, injection pressure 60Mpa, injection speed 90%, 60 DEG C of mold temperatures, single mode injection volume, obtain composite porous support Ge-PCMS(product 7 of the present invention), porosity is 65%.In phosphate buffer, carry out Ge release test, the Ge amount that this routine product discharged in 7 one weeks is about 0.0002g.With PCMS sample in contrast, support and the compound cultivation of MG-63 cell are found, cell proliferation degree is greater than PCMS, and there were significant differences with PCMS.
embodiment 8
Be nanometer calcium deficiency apatite/polynary amino acid copolymer composite material granular, foaming agent calcium sulfate CS and the Ge that 3 ~ 5mm and apatite content are 10wt% by particle diameter, according to n-CDHA/MAC
:cS
:ge=90
:10
:5(mass ratio) ratio mix homogeneously, under the condition that is 40mm at 175 DEG C of injection temperatures, injection pressure 60Mpa, injection speed 90%, 60 DEG C of mold temperatures, single mode injection volume, obtain composite porous support Ge-PCMS(product 8 of the present invention), porosity is 81.6%.In phosphate buffer, carry out Ge release test, the Ge amount that this routine product discharged in 8 one weeks is about 0.0005g.With PCMS sample in contrast, support and the compound cultivation of MG-63 cell are found, cell proliferation degree is greater than PCMS, and there were significant differences with PCMS.
The present invention that the various embodiments described above obtain is loaded with the composite porous support Ge-PCMS product of Ge, with the comparing result that the on cell proliferation degree of not carrying somatomedin support product affects, as shown in table 1.
Claims (8)
1. the Biocomposite material porous support of year soybean isoflavone, using nanometer calcium deficiency apatite-polynary amino acid copolymer composite porous support as carrier, it is characterized in that being mixed with soybean isoflavone as somatomedin composition in described carrier material, the mass ratio of somatomedin and composite is 1 ~ 10
:100.
2. porous support as claimed in claim 1, is characterized in that the described soybean isoflavone as somatomedin composition, for 5,4 of plant origin ', 7-trihydroxy-isoflavone.
3. the porous support as described in right 1 requirement, is characterized in that isoflavone is evenly distributed in support, but not is adsorbed on rack surface.
4. the porous support described in claim 1 or 2, is characterized in that the mass ratio of the nanometer calcium deficiency apatite in described composite is 10 ~ 50%, and all the other are polynary amino acid copolymer.
5. the porous support described in claim 1 or 2, the porosity that it is characterized in that described porous support carrier is 65 ~ 95%.
6. porous support claimed in claim 5, the porosity that it is characterized in that described porous support carrier is 80-95%.
7. the preparation method of the described Biocomposite material porous support that carries soybean isoflavone of one of claim 1 to 6, it is characterized in that the nanometer calcium deficiency apatite of described ratio-polynary amino acid copolymer composite and somatomedin composition, and after being the foaming agent mixing of calcium sulphate dihydrate constituents of described composite quality 5-15%, in injection moulding mode, 150 ~ 180 DEG C of injection temperatures, injection pressure 50 ~ 70MPa, injection speed 80 ~ 95%, under the condition that mold temperature is 50 ~ 70 DEG C, injection mo(u)lding is described porous support product.
8. preparation method as claimed in claim 7, the injection temperature that it is characterized in that described material injection mo(u)lding is 175 DEG C, and injection pressure is 70MPa, and injection speed is 80%, and the temperature of mould is 60 DEG C.
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|---|---|---|---|
| CN201410303875.9A CN104027849B (en) | 2014-06-30 | 2014-06-30 | Carry Biocomposite material porous support and the preparation of soybean isoflavone |
| CN201510152991.XA CN104771786B (en) | 2014-06-30 | 2014-06-30 | Carry plant growth factor 4,5 ', the preparation method of the Biocomposite material porous support of 7 trihydroxy-isoflavones |
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|---|---|---|---|
| CN201410303875.9A CN104027849B (en) | 2014-06-30 | 2014-06-30 | Carry Biocomposite material porous support and the preparation of soybean isoflavone |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104324415A (en) * | 2014-11-04 | 2015-02-04 | 四川国纳科技有限公司 | Multi(amino acid) polymer-hydroxyapatite bone repair material, supporting implant and preparation method thereof |
| CN106267375A (en) * | 2016-08-31 | 2017-01-04 | 禹宝庆 | A kind of 3 D-printing of soybean isoflavone that carries is containing strontium mesoporous bioglass support and preparation method thereof |
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| CN104771786B (en) * | 2014-06-30 | 2017-12-22 | 四川大学 | Carry plant growth factor 4,5 ', the preparation method of the Biocomposite material porous support of 7 trihydroxy-isoflavones |
| CN110801531A (en) * | 2018-05-25 | 2020-02-18 | 四川大学华西医院 | Bone repair scaffold material and preparation method and application thereof |
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| CN106267375B (en) * | 2016-08-31 | 2019-09-20 | 上海浩渤医疗科技有限公司 | A kind of 3 D-printing bracket of mesoporous bioglass containing strontium and preparation method thereof carrying isoflavones |
Also Published As
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| CN104027849B (en) | 2016-02-10 |
| CN104771786A (en) | 2015-07-15 |
| CN104771786B (en) | 2017-12-22 |
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