CN103948966B - The preparation method of retinoic acid hydroxylapatite bionic compound and this bionical complex - Google Patents
The preparation method of retinoic acid hydroxylapatite bionic compound and this bionical complex Download PDFInfo
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Abstract
The present invention relates to a kind of preparation method and this bionical complex of retinoic acid hydroxylapatite bionic compound.The preparation method that the object of this invention is to provide a kind of retinoic acid hydroxylapatite bionic compound and the retinoic acid hydroxylapatite bionic compound utilizing the method obtained, this bionical complex skeletonization is utilized in clinical practice, not only cost is low, skeletonization is effective, and can effectively avoid the complication such as ectopic osteogenesis and postoperative swelling.Technical scheme of the present invention is: a, prepare bionical layer kernel; B, in the coated one functional layer of bionical layer core surface; C, in step b products therefrom surface a coated one functional layer again.The present invention is mainly applicable to technical field of medical instruments.
Description
Technical field
The preparation method that the present invention relates to a kind of retinoic acid hydroxylapatite bionic compound and the retinoic acid hydroxylapatite bionic compound utilizing the method obtained, can be made into the hydroxyapatite biomimetic material of reconstruction operation being widely used in plastic surgery, orthopaedic trauma and tooth-planting.Belong to technical field of medical instruments.
Background technology
The bone does not connect that Cranial defect causes and delayed union are difficult problems for puzzlement clinical treatment.Although autologous bone transplanting is the goldstandard of repairing bone defect, be the critical defect that it is difficult to overcome for district's complication.Desirable tissue engineered bone should possess: the biocompatibility that (1) is good and biodegradation absorbability; (2) suitable three-dimensional microstructures; (3) three-dimensional geometry form is easily processed to form; (4) suitable surface physicochemical property; (5) certain mechanical strength can support physiological stress.Because all-trans-retinoic acid (ATRA) is clinical conventional medicament, cheap, thus use clinically and can significantly reduce clinical treatment cost, alleviate patient economy burden, the bone filler used clinically now mainly comes from abroad, expensive and skeletonization effect is undesirable, absorb and slowly not easily heal clinically, the prolongation clinical effect time.
In addition, the osteogenic materials of present clinical middle use needs to strengthen using dosage to make up absorbed bone filler in osteogenetic process, this not only adds medical treatment cost, also can make bone filling position swelling, cause the postoperative long-term swelling of patient, the art district form shortcoming such as unsightly.
Summary of the invention
The technical problem to be solved in the present invention is: the retinoic acid hydroxylapatite bionic compound providing a kind of preparation method of retinoic acid hydroxylapatite bionic compound for above-mentioned Problems existing and utilize the method obtained, this bionical complex skeletonization is utilized in clinical practice, not only cost is low, skeletonization is effective, and can effectively avoid the complication such as ectopic osteogenesis and postoperative swelling.
The technical solution adopted in the present invention is: the preparation method of retinoic acid hydroxylapatite bionic compound, it is characterized in that step is as follows:
A, get 6.5-8 gram of hydrogen chloride, 2-3 gram calcium chloride hydrate, 38-41 gram sodium chloride, 1-2 gram disodium-hydrogen, 39-40 gram pH value be the TRIS buffer of 7.4, add 1L ultra-pure water, adjust ph to 6.25, magnetic stirring apparatus keeps temperature 37 degree and with the rotating speed Keep agitation 24 hours of 50r/min, after generating precipitation, filter with the Filter Vacuum of 0.22 micron, and carry out degerming to the solid matter obtained after filtration;
B, with ultra-pure water, step a gained material to be cleaned, put it in shaper after filtering compression in vacuum environment, form certain solid shape, vacuum drying is after 2 hours, grind it with sterilizing metal bar, then the metal net shaped sieve of mistake obtains the bionical layer inner core particles that diameter is less than 0.22 micron;
C, get 1-1.5 gram of hydrogen chloride, 0.3-0.7 gram calcium chloride hydrate, 26-28 gram sodium chloride, 0.3-0.5 gram disodium-hydrogen, 38-40 gram pH value be the TRIS buffer of 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 1-3 microgram sterilizing, 37 degree of waters bath with thermostatic control, after dissolving completely, bionical for step b gained layer kernel is put into wherein, magnetic stirring apparatus maintains the rotating speed Keep agitation 24 hours of 50 revs/min, ultrasonic disperse 30-50 minute, logical nitrogen, oxygen in removing system, is cooled to room temperature after magnetic agitation reaction terminates;
D, by after step c gained mixed liquor vacuum draw, carry out normal pressure or vacuum drying, obtain the bionical layer kernel that Surface coating has functional layer;
E, get 1-1.5 gram of hydrogen chloride, 0.3-0.7 gram calcium chloride hydrate, 26-28 gram sodium chloride, 0.3-0.5 gram disodium-hydrogen, 38-40 gram pH value be the TRIS buffer of 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 1-3 microgram sterilizing, 37 degree of waters bath with thermostatic control, after dissolving completely, the bionical layer kernel being coated with functional layer is put into wherein, magnetic stirring apparatus maintains the rotating speed Keep agitation 24 hours of 50 revs/min, ultrasonic disperse 30-50 minute, logical nitrogen, oxygen in removing system, is cooled to room temperature after magnetic agitation reaction terminates;
F, by after step e gained mixed liquor vacuum draw, carry out normal pressure or vacuum drying.
It also comprises step g: repeat step e, f several times successively, obtain the bionical complex that the functional layer number of plies is different.
The diameter of described retinoic acid hydroxylapatite bionic compound is less than 0.5mm.
The preparation method of retinoic acid hydroxylapatite bionic compound, is characterized in that step is as follows:
A, get 7.3 grams of hydrogen chloride, 2.58 grams of calcium chloride hydrate, 39.78 grams of sodium chloride, 1.42 grams of disodium-hydrogens, 39.4 grams of pH value are the TRIS buffer of 7.4, add 1L ultra-pure water, adjust ph to 6.25, magnetic stirring apparatus keeps temperature 37 degree and with the rotating speed Keep agitation 24 hours of 50r/min, after generating precipitation, filter with the Filter Vacuum of 0.22 micron, and carry out degerming to the solid matter obtained after filtration;
B, with ultra-pure water, step a gained material to be cleaned, put it in shaper after filtering compression in vacuum environment, form certain solid shape, vacuum drying is after 2 hours, grind it with sterilizing metal bar, then the metal net shaped sieve of mistake obtains the bionical layer inner core particles that diameter is less than 0.22 micron;
C, get 1.26 grams of hydrogen chloride, 0.516 gram of calcium chloride hydrate, 27.2 grams of sodium chloride, 0.4 gram of disodium-hydrogen, 39.4 grams of pH value are the TRIS buffer of 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 1-3 microgram sterilizing, 37 degree of waters bath with thermostatic control, after dissolving completely, bionical for step b gained layer kernel is put into wherein, magnetic stirring apparatus maintains the rotating speed Keep agitation 24 hours of 50 revs/min, ultrasonic disperse 40 minutes, logical nitrogen, oxygen in removing system, is cooled to room temperature after magnetic agitation reaction terminates;
D, by after step c gained mixed liquor vacuum draw, vacuum drying 18-48 hour, obtains the bionical layer kernel that Surface coating has functional layer;
E, get 1.26 grams of hydrogen chloride, 0.516 gram of calcium chloride hydrate, 27.2 grams of sodium chloride, 0.4 gram of disodium-hydrogen, 39.4 grams of pH value are the TRIS buffer of 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 1-3 microgram sterilizing, 37 degree of waters bath with thermostatic control, after dissolving completely, the bionical layer kernel being coated with functional layer is put into wherein, magnetic stirring apparatus maintains the rotating speed Keep agitation 24 hours of 50 revs/min, ultrasonic disperse 40 minutes, logical nitrogen, oxygen in removing system, is cooled to room temperature after magnetic agitation reaction terminates;
F, by after step e gained mixed liquor vacuum draw, vacuum drying 18-48 hour.
It also comprises step g: repeat step e, f several times successively, obtain the bionical complex that the functional layer number of plies is different.
Dryly in described steps d and step f carry out under freezing vacuum condition, drying time is 24-28 hour.
The diameter of described retinoic acid hydroxylapatite bionic compound is less than 0.5mm.
Adopt the retinoic acid hydroxylapatite bionic compound that described preparation method obtains, it is characterized in that: it comprises the bionical layer kernel as timbering material, and be wrapped in this bionical layer kernel outer, absorbed when skeletonization the functional layer simultaneously discharging retinoic acid, described functional layer is spongy.
The number of plies of described functional layer be two-layer or two-layer more than.
The diameter of described retinoic acid hydroxylapatite bionic compound is less than 0.5mm.
The invention has the beneficial effects as follows: ATRA is embedded in wherein by the present invention in the process forming hydroxyapatite, form the latticed structure of class, act on slow releasing ATRA in the process of hydroxyapatite in osteoclast, reach maximum skeletonization effect.Recent research finds, the bone meal used clinically can cause ectopic osteogenesis (formation such as normal portions hyperosteogeny), bone formation is excessive and new born bone tissue disorderly, this is the puzzlement of a lot of clinician, ATRA hydroxylapatite bionic compound can well address this problem, not only can continue skeletonization but also can ectopic osteogenesis be prevented, osteogenic materials is made to maintain low dosage slow releasing ATRA at corresponding position, local slow release mode can obtain the induced osteogenesis effect of its best, finally reaches maximum skeletonization effect.
The retinoic acid hydroxylapatite bionic compound that the present invention obtains is by bionical layer kernel, and the functional layer composition be wrapped in outside this bionical layer kernel, during skeletonization, calcium phosphate in functional layer discharges all-trans-retinoic acid while degraded, act in organism and promote osteoblastic ossification, what osteoblast utilized calcium phosphate to degrade calcareously sets up new bone as raw material, enclose bionical layer kernel after new bone formation and be filled in Cranial defect place, bionical layer kernel will be present in Cranial defect place as timbering material, thus complete the reparation of whole Cranial defect, well avoid the complication such as swelling after clinic operation, and skeletonization successful is better than clinical bone filler.
Detailed description of the invention
Embodiment 1: the present embodiment preparation process is as follows:
A, get 7.3 grams of hydrogen chloride (HCL), 2.58 grams of calcium chloride hydrate (CaCL
2h
2o), 39.78 grams of sodium chloride (NaCL), 1.42 grams of disodium-hydrogen (Na
2hPO
4), 39.4 grams of pH value are the TRIS buffer of 7.4, add 1L ultra-pure water, adjust ph to 6.25, magnetic stirring apparatus keeps temperature 37 degree and with the rotating speed Keep agitation 24 hours of 50r/min, after generating precipitation, filter with the Filter Vacuum of 0.22 micron, and it is degerming to carry out High Temperature High Pressure to the solid matter obtained after filtering;
B, with ultra-pure water, step a gained material to be cleaned, put it in shaper after filtering compression in vacuum environment, form certain solid shape (cylindrical or strip), be convenient to drying; Vacuum drying, after 2 hours, grinds it with sterilizing metal bar, then with metal net shaped sieve removing bulk solid, obtains the bionical layer inner core particles that diameter is less than 0.22 micron;
C, get 1.26 grams of hydrogen chloride (HCL), 0.516 gram of calcium chloride hydrate (CaCL
2h
2o), 27.2 grams of sodium chloride (NaCL), 0.4 gram of disodium-hydrogen (Na
2hPO
4), 39.4 grams of pH value are the TRIS buffer of 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 2 microgram sterilizings, 37 degree of waters bath with thermostatic control, put into wherein by bionical for step b gained layer kernel after dissolving completely, and magnetic stirring apparatus maintains the rotating speed Keep agitation 24 hours of 50 revs/min, ultrasonic disperse 40 minutes, logical nitrogen, the oxygen in removing system, is cooled to room temperature after magnetic agitation reaction terminates;
D, by after step c gained mixed liquor vacuum draw, vacuum drying 18-48 hour, obtains the bionical layer kernel that Surface coating has functional layer;
E, get 1.26 grams of hydrogen chloride (HCL), 0.516 gram of calcium chloride hydrate (CaCL
2h
2o), 27.2 grams of sodium chloride (NaCL), 0.4 gram of disodium-hydrogen (Na
2hPO
4), 39.4 grams of pH value are the TRIS buffer of 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 2 microgram sterilizings, 37 degree of waters bath with thermostatic control, put into wherein by the bionical layer kernel being coated with functional layer after dissolving completely, and magnetic stirring apparatus maintains the rotating speed Keep agitation 24 hours of 50 revs/min, ultrasonic disperse 40 minutes, logical nitrogen, the oxygen in removing system, is cooled to room temperature after magnetic agitation reaction terminates;
F, by after step e gained mixed liquor vacuum draw, vacuum drying 18-48 hour.
Embodiment 2: the present embodiment preparation process is as follows:
A, get 7.3 grams of hydrogen chloride (HCL), 2.58 grams of calcium chloride hydrate (CaCL
2h
2o), 39.78 grams of sodium chloride (NaCL), 1.42 grams of disodium-hydrogen (Na
2hPO
4), 39.4 grams of pH value are the TRIS buffer of 7.4, add 1L ultra-pure water, adjust ph to 6.25, magnetic stirring apparatus keeps temperature 37 degree and with the rotating speed Keep agitation 24 hours of 50r/min, after generating precipitation, filter with the Filter Vacuum of 0.22 micron, and it is degerming to carry out High Temperature High Pressure to the solid matter obtained after filtering;
B, with ultra-pure water, step a gained material to be cleaned, put it in shaper after filtering compression in vacuum environment, form certain solid shape (cylindrical or strip), be convenient to drying; Vacuum drying, after 2 hours, grinds it with sterilizing metal bar, then with metal net shaped sieve removing bulk solid, obtains the bionical layer inner core particles that diameter is less than 0.22 micron;
C, get 1.26 grams of hydrogen chloride (HCL), 0.516 gram of calcium chloride hydrate (CaCL
2h
2o), 27.2 grams of sodium chloride (NaCL), 0.4 gram of disodium-hydrogen (Na
2hPO
4), 39.4 grams of pH value are the TRIS buffer of 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 2 microgram sterilizings, 37 degree of waters bath with thermostatic control, put into wherein by bionical for step b gained layer kernel after dissolving completely, and magnetic stirring apparatus maintains the rotating speed Keep agitation 24 hours of 50 revs/min, ultrasonic disperse 40 minutes, logical nitrogen, the oxygen in removing system, is cooled to room temperature after magnetic agitation reaction terminates;
D, by after step c gained mixed liquor vacuum draw, lyophilisation 24-28 hour, obtains the bionical layer kernel that Surface coating has functional layer;
E, get 1.26 grams of hydrogen chloride (HCL), 0.516 gram of calcium chloride hydrate (CaCL
2h
2o), 27.2 grams of sodium chloride (NaCL), 0.4 gram of disodium-hydrogen (Na
2hPO
4), 39.4 grams of pH value are the TRIS buffer of 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 2 microgram sterilizings, 37 degree of waters bath with thermostatic control, put into wherein by the bionical layer kernel being coated with functional layer after dissolving completely, and magnetic stirring apparatus maintains the rotating speed Keep agitation 24 hours of 50 revs/min, ultrasonic disperse 40 minutes, logical nitrogen, the oxygen in removing system, is cooled to room temperature after magnetic agitation reaction terminates;
F, by after step e gained mixed liquor vacuum draw, lyophilisation 24-28 hour.
Embodiment 3: the present embodiment preparation process is as follows:
A, get 6.5 grams of hydrogen chloride (HCL), 2 grams of calcium chloride hydrate (CaCL
2h
2o), 38 grams of sodium chloride (NaCL), 1 gram of disodium-hydrogen (Na
2hPO
4), 39 grams of pH value are the TRIS buffer of 7.4, add 1L ultra-pure water, adjust ph to 6.25, magnetic stirring apparatus keeps temperature 37 degree and with the rotating speed Keep agitation 24 hours of 50r/min, after generating precipitation, filter with the Filter Vacuum of 0.22 micron, and it is degerming to carry out High Temperature High Pressure to the solid matter obtained after filtering;
B, with ultra-pure water, step a gained material to be cleaned, put it in shaper after filtering compression in vacuum environment, form certain solid shape (cylindrical or strip), be convenient to drying; Vacuum drying, after 2 hours, grinds it with sterilizing metal bar, then with metal net shaped sieve removing bulk solid, obtains the bionical layer inner core particles that diameter is less than 0.22 micron;
C, get 1 gram of hydrogen chloride (HCL), 0.3 gram of calcium chloride hydrate (CaCL
2h
2o), 26 grams of sodium chloride (NaCL), 0.3 gram of disodium-hydrogen (Na
2hPO
4), 38 grams of pH value are the TRIS buffer of 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 1 microgram sterilizing, 37 degree of waters bath with thermostatic control, put into wherein by bionical for step b gained layer kernel after dissolving completely, and magnetic stirring apparatus maintains the rotating speed Keep agitation 24 hours of 50 revs/min, ultrasonic disperse 30 minutes, logical nitrogen, the oxygen in removing system, is cooled to room temperature after magnetic agitation reaction terminates;
D, by after step c gained mixed liquor vacuum draw, carry out normal pressure or vacuum drying, obtain the bionical layer kernel that Surface coating has functional layer;
E, get 1 gram of hydrogen chloride (HCL), 0.3 gram of calcium chloride hydrate (CaCL
2h
2o), 26 grams of sodium chloride (NaCL), 0.3 gram of disodium-hydrogen (Na
2hPO
4), 38 grams of pH value are the TRIS buffer of 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 1 microgram sterilizing, 37 degree of waters bath with thermostatic control, put into wherein by the bionical layer kernel being coated with functional layer after dissolving completely, and magnetic stirring apparatus maintains the rotating speed Keep agitation 24 hours of 50 revs/min, ultrasonic disperse 30 minutes, logical nitrogen, the oxygen in removing system, is cooled to room temperature after magnetic agitation reaction terminates;
F, by after step e gained mixed liquor vacuum draw, carry out normal pressure or vacuum drying.
Embodiment 4: the present embodiment preparation process is as follows:
A, get 8 grams of hydrogen chloride (HCL), 3 grams of calcium chloride hydrate (CaCL
2h
2o), 41 grams of sodium chloride (NaCL), 2 grams of disodium-hydrogen (Na
2hPO
4), 40 grams of pH value are the TRIS buffer of 7.4, add 1L ultra-pure water, adjust ph to 6.25, magnetic stirring apparatus keeps temperature 37 degree and with the rotating speed Keep agitation 24 hours of 50r/min, after generating precipitation, filter with the Filter Vacuum of 0.22 micron, and it is degerming to carry out High Temperature High Pressure to the solid matter obtained after filtering;
B, with ultra-pure water, step a gained material to be cleaned, put it in shaper after filtering compression in vacuum environment, form certain solid shape (cylindrical or strip), be convenient to drying; Vacuum drying, after 2 hours, grinds it with sterilizing metal bar, then with metal net shaped sieve removing bulk solid, obtains the bionical layer inner core particles that diameter is less than 0.22 micron;
C, get 1.5 grams of hydrogen chloride (HCL), 0.7 gram of calcium chloride hydrate (CaCL
2h
2o), 28 grams of sodium chloride (NaCL), 0.5 gram of disodium-hydrogen (Na
2hPO
4), 40 grams of pH value are the TRIS buffer of 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 3 microgram sterilizings, 37 degree of waters bath with thermostatic control, put into wherein by bionical for step b gained layer kernel after dissolving completely, and magnetic stirring apparatus maintains the rotating speed Keep agitation 24 hours of 50 revs/min, ultrasonic disperse 50 minutes, logical nitrogen, the oxygen in removing system, is cooled to room temperature after magnetic agitation reaction terminates;
D, by after step c gained mixed liquor vacuum draw, carry out constant pressure and dry, obtain the bionical layer kernel that Surface coating has functional layer;
E, get 1.5 grams of hydrogen chloride (HCL), 0.7 gram of calcium chloride hydrate (CaCL
2h
2o), 28 grams of sodium chloride (NaCL), 0.5 gram of disodium-hydrogen (Na
2hPO
4), 40 grams of pH value are the TRIS buffer of 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 3 microgram sterilizings, 37 degree of waters bath with thermostatic control, put into wherein by the bionical layer kernel being coated with functional layer after dissolving completely, and magnetic stirring apparatus maintains the rotating speed Keep agitation 24 hours of 50 revs/min, ultrasonic disperse 50 minutes, logical nitrogen, the oxygen in removing system, is cooled to room temperature after magnetic agitation reaction terminates;
F, by after step e gained mixed liquor vacuum draw, carry out constant pressure and dry.
The various embodiments described above, can repeat step e, f several times (3-4 time) as required successively, and to obtain the different bionical complex of the functional layer number of plies, general diameter is preferably less than 0.5mm.
The retinoic acid hydroxylapatite bionic compound size utilizing the various embodiments described above obtained is even, it comprises the bionical layer kernel as timbering material, and be wrapped in this bionical layer kernel outer, in spongiform functional layer, wherein the number of plies of functional layer be two-layer or two-layer more than.Human osteoblast's process is the coefficient process of osteoblast and osteoclast, first be that functional layer material absorbs by osteoclast, then osteoblast utilizes the new bone of calcareous formation of material degradation, enclose bionical layer kernel after new bone formation and be filled in Cranial defect place, bionical layer kernel will be present in Cranial defect place as timbering material, under the effect of bionical layer kernel and functional layer, finally complete the reparation of whole Cranial defect.The spongy functional layer of this material ectomesoderm acts on osteoblast at the absorbed all-trans-retinoic acid that discharges simultaneously, is conducive to osteoblast and forms new bone.
In clinical trial, retinoic acid hydroxylapatite bionic compound the present invention obtained is used for finding in skeletonization-osteoclast co-culture system, and skeletonization effect more single hydroxyapatite material is obvious; For finding in animal large area Cranial defect model, surrounding becomes bone amount to be obviously better than the osteogenic materials of Clinical practice, after eight weeks, skeletonization effect is more remarkable, and hard tissue slicing finds the bone trabecula close together of area of new bone, and its structure is closer to the normal bone structure around Cranial defect.
Claims (10)
1. a preparation method for retinoic acid hydroxylapatite bionic compound, is characterized in that step is as follows:
A, get 6.5-8 gram of hydrogen chloride, 2-3 gram calcium chloride hydrate, 38-41 gram sodium chloride, 1-2 gram disodium-hydrogen, 39-40 gram pH value be the TRIS buffer of 7.4, add 1L ultra-pure water, adjust ph to 6.25, magnetic stirring apparatus keeps temperature 37 degree and with the rotating speed Keep agitation 24 hours of 50r/min, after generating precipitation, filter with the Filter Vacuum of 0.22 micron, and carry out degerming to the solid matter obtained after filtration;
B, with ultra-pure water, step a gained material to be cleaned, put it in shaper after filtering compression in vacuum environment, form certain solid shape, vacuum drying is after 2 hours, grind it with sterilizing metal bar, then the metal net shaped sieve of mistake obtains the bionical layer inner core particles that diameter is less than 0.22 micron;
C, get 1-1.5 gram of hydrogen chloride, 0.3-0.7 gram calcium chloride hydrate, 26-28 gram sodium chloride, 0.3-0.5 gram disodium-hydrogen, 38-40 gram pH value be the TRIS buffer of 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 1-3 microgram sterilizing, 37 degree of waters bath with thermostatic control, after dissolving completely, bionical for step b gained layer kernel is put into wherein, magnetic stirring apparatus maintains the rotating speed Keep agitation 24 hours of 50 revs/min, ultrasonic disperse 30-50 minute, logical nitrogen, oxygen in removing system, is cooled to room temperature after magnetic agitation reaction terminates;
D, by after step c gained mixed liquor vacuum draw, carry out normal pressure or vacuum drying, obtain the bionical layer kernel that Surface coating has functional layer;
E, get 1-1.5 gram of hydrogen chloride, 0.3-0.7 gram calcium chloride hydrate, 26-28 gram sodium chloride, 0.3-0.5 gram disodium-hydrogen, 38-40 gram pH value be the TRIS buffer of 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 1-3 microgram sterilizing, 37 degree of waters bath with thermostatic control, after dissolving completely, the bionical layer kernel being coated with functional layer is put into wherein, magnetic stirring apparatus maintains the rotating speed Keep agitation 24 hours of 50 revs/min, ultrasonic disperse 30-50 minute, logical nitrogen, oxygen in removing system, is cooled to room temperature after magnetic agitation reaction terminates;
F, by after step e gained mixed liquor vacuum draw, carry out normal pressure or vacuum drying.
2. the preparation method of retinoic acid hydroxylapatite bionic compound according to claim 1, is characterized in that it also comprises step g: repeat step e, f several times successively, obtain the bionical complex that the functional layer number of plies is different.
3. the preparation method of retinoic acid hydroxylapatite bionic compound according to claim 1 and 2, is characterized in that: the diameter of described retinoic acid hydroxylapatite bionic compound is less than 0.5mm.
4. a preparation method for retinoic acid hydroxylapatite bionic compound, is characterized in that step is as follows:
A, get 7.3 grams of hydrogen chloride, 2.58 grams of calcium chloride hydrate, 39.78 grams of sodium chloride, 1.42 grams of disodium-hydrogens, 39.4 grams of pH value are the TRIS buffer of 7.4, add 1L ultra-pure water, adjust ph to 6.25, magnetic stirring apparatus keeps temperature 37 degree and with the rotating speed Keep agitation 24 hours of 50r/min, after generating precipitation, filter with the Filter Vacuum of 0.22 micron, and carry out degerming to the solid matter obtained after filtration;
B, with ultra-pure water, step a gained material to be cleaned, put it in shaper after filtering compression in vacuum environment, form certain solid shape, vacuum drying is after 2 hours, grind it with sterilizing metal bar, then the metal net shaped sieve of mistake obtains the bionical layer inner core particles that diameter is less than 0.22 micron;
C, get 1.26 grams of hydrogen chloride, 0.516 gram of calcium chloride hydrate, 27.2 grams of sodium chloride, 0.4 gram of disodium-hydrogen, 39.4 grams of pH value are the TRIS buffer of 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 1-3 microgram sterilizing, 37 degree of waters bath with thermostatic control, after dissolving completely, bionical for step b gained layer kernel is put into wherein, magnetic stirring apparatus maintains the rotating speed Keep agitation 24 hours of 50 revs/min, ultrasonic disperse 40 minutes, logical nitrogen, oxygen in removing system, is cooled to room temperature after magnetic agitation reaction terminates;
D, by after step c gained mixed liquor vacuum draw, vacuum drying 18-48 hour, obtains the bionical layer kernel that Surface coating has functional layer;
E, get 1.26 grams of hydrogen chloride, 0.516 gram of calcium chloride hydrate, 27.2 grams of sodium chloride, 0.4 gram of disodium-hydrogen, 39.4 grams of pH value are the TRIS buffer of 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 1-3 microgram sterilizing, 37 degree of waters bath with thermostatic control, after dissolving completely, the bionical layer kernel being coated with functional layer is put into wherein, magnetic stirring apparatus maintains the rotating speed Keep agitation 24 hours of 50 revs/min, ultrasonic disperse 40 minutes, logical nitrogen, oxygen in removing system, is cooled to room temperature after magnetic agitation reaction terminates;
F, by after step e gained mixed liquor vacuum draw, vacuum drying 18-48 hour.
5. the preparation method of retinoic acid hydroxylapatite bionic compound according to claim 4, is characterized in that it also comprises step g: repeat step e, f several times successively, obtain the bionical complex that the functional layer number of plies is different.
6. the preparation method of the retinoic acid hydroxylapatite bionic compound according to claim 4 or 5, is characterized in that: dryly in described steps d and step f carry out under freezing vacuum condition, and drying time is 24-28 hour.
7. the preparation method of the retinoic acid hydroxylapatite bionic compound according to claim 4 or 5, is characterized in that: the diameter of described retinoic acid hydroxylapatite bionic compound is less than 0.5mm.
8. the retinoic acid hydroxylapatite bionic compound adopting preparation method described in claim 1 or 4 to obtain, it is characterized in that: it comprises the bionical layer kernel as timbering material, and be wrapped in this bionical layer kernel outer, absorbed when skeletonization the functional layer simultaneously discharging retinoic acid, described functional layer is spongy.
9. retinoic acid hydroxylapatite bionic compound according to claim 8, is characterized in that: the number of plies of described functional layer be two-layer or two-layer more than.
10. retinoic acid hydroxylapatite bionic compound according to claim 8, is characterized in that: the diameter of described retinoic acid hydroxylapatite bionic compound is less than 0.5mm.
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| CN108434518B (en) * | 2018-05-25 | 2020-02-07 | 杭州彗搏科技有限公司 | Preparation method of traditional Chinese medicine monomer sequence slow-release osteogenic blood vessel calcium-phosphorus stent material |
| CN115382016B (en) * | 2021-05-19 | 2023-06-23 | 北京荷月顺畅生物科技有限公司 | Bionic bone material for resisting cancer, medicinal composition containing bionic bone material and preparation method of medicinal composition |
| CN115382010B (en) * | 2021-05-19 | 2023-06-06 | 北京荷月顺畅生物科技有限公司 | Bionic bone material and preparation method thereof |
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