CN103948966A - Method for preparing retinoic hydroxyapatite bionic compound, and bionic compound - Google Patents
Method for preparing retinoic hydroxyapatite bionic compound, and bionic compound Download PDFInfo
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Abstract
The invention relates to a method for preparing a retinoic hydroxyapatite bionic compound and the bionic compound. By virtue of the method for preparing the retinoic hydroxyapatite bionic compound and the retinoic hydroxyapatite bionic compound prepared by utilizing the method, a bone is formed by utilizing the bionic compound in the clinical application, the cost is low, the effect of bone formation is good, and ectopic bone formation, postoperative swelling and other complications can be effectively avoided. The technical scheme adopted by the invention is as follows: the preparation method comprises the following steps: a, preparing a core of a bionic layer; b, coating the surface of the core of the bionic layer with a functional layer; c, coating the surface of the product obtained in the step with one more functional layer. The bionic compound is mainly applied to the technical field of medical appliances.
Description
Technical field
The bionical complex of retinoic acid hydroxyapatite that the present invention relates to the preparation method of the bionical complex of a kind of retinoic acid hydroxyapatite and utilize the method to make, can be made into the hydroxyapatite biomimetic material of the reconstruction operation that is widely used in plastic surgery, orthopaedic trauma and tooth-planting.Belong to technical field of medical instruments.
Background technology
The damaged bone does not connect causing of bone and delayed union are difficult problems for puzzlement clinical treatment.Although autologous bone transplanting is the goldstandard of repairing bone defect, for district's complication, be its critical defect that is difficult to overcome.Desirable tissue engineered bone should possess: the biocompatibility that (1) is good and biodegradation absorbability; (2) suitable three-dimensional microcosmic structure; (3) be easily processed to form three-dimensional geometry form; (4) suitable surface physicochemical property; (5) certain mechanical strength can be supported physiological stress.Because all-trans-retinoic acid (ATRA) is clinical conventional medicament, cheap, thereby use and can significantly reduce clinical treatment cost clinically, alleviate patient economy burden, the bone filler using clinically now mainly comes from abroad, expensive and skeletonization effect is undesirable, absorb and be slowly difficult for clinically healing, extend the clinical effect time.
In addition, the osteogenic materials of clinical middle use now need to strengthen using dosage to make up absorbed bone filler in osteogenetic process, and this has not only increased medical treatment cost, also can make bone filling position swelling, cause the postoperative long-term swelling of patient, the shortcoming such as art district form is not attractive in appearance.
Summary of the invention
The technical problem to be solved in the present invention is: the bionical complex of retinoic acid hydroxyapatite that the preparation method of the bionical complex of a kind of retinoic acid hydroxyapatite is provided and utilizes the method to make for the problem of above-mentioned existence, in clinical practice, utilize this bionical complex skeletonization, 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 the bionical complex of retinoic acid hydroxyapatite, is characterized in that step is as follows:
A, get the TRIS buffer that 6.5-8 gram of hydrogen chloride, 2-3 gram hydration calcium chloride, 38-41 gram sodium chloride, 1-2 gram disodium-hydrogen, 39-40 gram pH value are 7.4, add 1L ultra-pure water, regulate pH value to 6.25, on magnetic stirring apparatus, keep temperature 37 degree and continue to stir 24 hours with the rotating speed of 50r/min, generate after precipitation, with the filter vacuum filtration of 0.22 micron, and the solid matter obtaining after filtering is carried out to degerming;
B, with ultra-pure water, step a gained material is cleaned, after filtering compression in vacuum environment, put it in shaper, form certain solid shape, after vacuum drying 2 hours, with sterilizing metal bar, it is ground, then cross metal net shaped sieve and obtain the bionical layer inner core particles that diameter is less than 0.22 micron;
C, get the TRIS buffer that 1-1.5 gram of hydrogen chloride, 0.3-0.7 gram hydration calcium chloride, 26-28 gram sodium chloride, 0.3-0.5 gram disodium-hydrogen, 38-40 gram pH value are 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 1-3 microgram sterilizing, 37 degree waters bath with thermostatic control, after dissolving completely, the bionical layer of step b gained kernel put into wherein, magnetic stirring apparatus maintains lasting the stirring 24 hours of rotating speed of 50 revs/min, ultrasonic dispersion 30-50 minute, logical nitrogen, remove the oxygen in system, after magnetic agitation reaction finishes, be cooled to room temperature;
D, by after step c gained mixed liquor vacuum draw, carry out normal pressure or vacuum drying, obtain the bionical layer kernel that surface is coated with functional layer;
E, get the TRIS buffer that 1-1.5 gram of hydrogen chloride, 0.3-0.7 gram hydration calcium chloride, 26-28 gram sodium chloride, 0.3-0.5 gram disodium-hydrogen, 38-40 gram pH value are 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 1-3 microgram sterilizing, 37 degree waters bath with thermostatic control, after dissolving completely, the bionical layer kernel that is coated with functional layer put into wherein, magnetic stirring apparatus maintains lasting the stirring 24 hours of rotating speed of 50 revs/min, ultrasonic dispersion 30-50 minute, logical nitrogen, remove the oxygen in system, after magnetic agitation reaction finishes, be cooled to room temperature;
F, by after step e gained mixed liquor vacuum draw, carry out normal pressure or vacuum drying.
It also comprises step g: repeating step e, f several times successively, obtain the bionical complex that the functional layer number of plies is different.
The diameter of the bionical complex of described retinoic acid hydroxyapatite is less than 0.5mm.
The preparation method of the bionical complex of retinoic acid hydroxyapatite, is characterized in that step is as follows:
A, get 7.3 grams of hydrogen chloride, 2.58 grams of hydration calcium chloride, 39.78 grams of sodium chloride, 1.42 grams of disodium-hydrogens, 39.4 grams of TRIS buffer that pH value is 7.4, add 1L ultra-pure water, regulate pH value to 6.25, on magnetic stirring apparatus, keep temperature 37 degree and continue to stir 24 hours with the rotating speed of 50r/min, generate after precipitation, with the filter vacuum filtration of 0.22 micron, and the solid matter obtaining after filtering is carried out to degerming;
B, with ultra-pure water, step a gained material is cleaned, after filtering compression in vacuum environment, put it in shaper, form certain solid shape, after vacuum drying 2 hours, with sterilizing metal bar, it is ground, then cross metal net shaped sieve and obtain 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 hydration calcium chloride, 27.2 grams of sodium chloride, 0.4 gram of disodium-hydrogen, 39.4 grams of TRIS buffer that pH value is 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 1-3 microgram sterilizing, 37 degree waters bath with thermostatic control, after dissolving completely, the bionical layer of step b gained kernel put into wherein, magnetic stirring apparatus maintains lasting the stirring 24 hours of rotating speed of 50 revs/min, ultrasonic dispersion 40 minutes, logical nitrogen, remove the oxygen in system, after magnetic agitation reaction finishes, be cooled to room temperature;
D, by after step c gained mixed liquor vacuum draw, vacuum drying 18-48 hour, obtains the bionical layer kernel that surface is coated with functional layer;
E, get 1.26 grams of hydrogen chloride, 0.516 gram of hydration calcium chloride, 27.2 grams of sodium chloride, 0.4 gram of disodium-hydrogen, 39.4 grams of TRIS buffer that pH value is 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 1-3 microgram sterilizing, 37 degree waters bath with thermostatic control, after dissolving completely, the bionical layer kernel that is coated with functional layer put into wherein, magnetic stirring apparatus maintains lasting the stirring 24 hours of rotating speed of 50 revs/min, ultrasonic dispersion 40 minutes, logical nitrogen, remove the oxygen in system, after magnetic agitation reaction finishes, be cooled to room temperature;
F, by after step e gained mixed liquor vacuum draw, vacuum drying 18-48 hour.
It also comprises step g: repeating step e, f several times successively, obtain the bionical complex that the functional layer number of plies is different.
In described steps d and step f, be dried under freezing vacuum condition and carry out, be 24-28 hour drying time.
The diameter of the bionical complex of described retinoic acid hydroxyapatite is less than 0.5mm.
The bionical complex of retinoic acid hydroxyapatite that adopts described preparation method 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, when skeletonization, be absorbed the functional layer that simultaneously discharges 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 the bionical complex of described retinoic acid hydroxyapatite is less than 0.5mm.
The invention has the beneficial effects as follows: the present invention is embedded in ATRA wherein in forming the process of hydroxyapatite, form the latticed structure of class, in osteoclast acts on the process of hydroxyapatite, slowly discharge ATRA, reach maximum skeletonization effect.Recently research is found, the bone meal using clinically can cause ectopic osteogenesis formation such as () normal position hyperosteogenys, bone formation is excessive and new born bone tissue disorderly, this is a lot of clinicians' puzzlement, the bionical complex of ATRA hydroxyapatite can well address this problem, not only can continue skeletonization but also can prevent ectopic osteogenesis, make osteogenic materials maintain low dosage at corresponding position and slowly discharge ATRA, local slow release mode can obtain its best induced osteogenesis effect, finally reaches maximum skeletonization effect.
The bionical complex of retinoic acid hydroxyapatite that the present invention obtains is by bionical layer kernel, and the functional layer being wrapped in outside this bionical layer kernel forms, during skeletonization, calcium phosphate in functional layer discharges all-trans-retinoic acid in degraded, act on the osteoblastic ossification of promotion in organism, osteoblast utilizes the calcareous of calcium phosphate degraded to set up new bone as raw material, after new bone formation, surrounded the filling of bionical layer kernel in the damaged place of bone, bionical layer kernel will be present in the damaged place of bone as timbering material, thereby complete the reparation that whole bone is damaged, well avoided the complication such as swelling after clinic operation, and skeletonization successful is better than clinical bone filler.
The specific embodiment
Embodiment 1: the present embodiment preparation process is as follows:
A, get 7.3 grams of hydrogen chloride (HCL), 2.58 grams of hydration calcium chloride (CaCL
2h
2o), 39.78 grams of sodium chloride (NaCL), 1.42 grams of disodium-hydrogen (Na
2hPO
4), 39.4 grams of TRIS buffer that pH value is 7.4, add 1L ultra-pure water, regulate pH value to 6.25, on magnetic stirring apparatus, keep temperature 37 degree and continue to stir 24 hours with the rotating speed of 50r/min, generate after precipitation, with the filter vacuum filtration of 0.22 micron, and the solid matter obtaining after filtering is carried out to High Temperature High Pressure degerming;
B, with ultra-pure water, step a gained material is cleaned, put it in shaper after filtering compression in vacuum environment, form certain solid shape (cylindrical or strip), be convenient to be dried; After vacuum drying 2 hours, with sterilizing metal bar, it is ground, then with metal net shaped sieve, remove bulk solid, obtain 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 hydration calcium chloride (CaCL
2h
2o), 27.2 grams of sodium chloride (NaCL), 0.4 gram of disodium-hydrogen (Na
2hPO
4), 39.4 grams of TRIS buffer that pH value is 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 2 microgram sterilizings, 37 degree waters bath with thermostatic control, put into the bionical layer of step b gained kernel wherein after dissolving completely, and magnetic stirring apparatus maintains lasting the stirring 24 hours of rotating speed of 50 revs/min, ultrasonic dispersion 40 minutes, logical nitrogen, removes the oxygen in system, after magnetic agitation reaction finishes, is cooled to room temperature;
D, by after step c gained mixed liquor vacuum draw, vacuum drying 18-48 hour, obtains the bionical layer kernel that surface is coated with functional layer;
E, get 1.26 grams of hydrogen chloride (HCL), 0.516 gram of hydration calcium chloride (CaCL
2h
2o), 27.2 grams of sodium chloride (NaCL), 0.4 gram of disodium-hydrogen (Na
2hPO
4), 39.4 grams of TRIS buffer that pH value is 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 2 microgram sterilizings, 37 degree waters bath with thermostatic control, put into the bionical layer kernel that is coated with functional layer wherein after dissolving completely, and magnetic stirring apparatus maintains lasting the stirring 24 hours of rotating speed of 50 revs/min, ultrasonic dispersion 40 minutes, logical nitrogen, removes the oxygen in system, after magnetic agitation reaction finishes, is cooled to room temperature;
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 hydration calcium chloride (CaCL
2h
2o), 39.78 grams of sodium chloride (NaCL), 1.42 grams of disodium-hydrogen (Na
2hPO
4), 39.4 grams of TRIS buffer that pH value is 7.4, add 1L ultra-pure water, regulate pH value to 6.25, on magnetic stirring apparatus, keep temperature 37 degree and continue to stir 24 hours with the rotating speed of 50r/min, generate after precipitation, with the filter vacuum filtration of 0.22 micron, and the solid matter obtaining after filtering is carried out to High Temperature High Pressure degerming;
B, with ultra-pure water, step a gained material is cleaned, put it in shaper after filtering compression in vacuum environment, form certain solid shape (cylindrical or strip), be convenient to be dried; After vacuum drying 2 hours, with sterilizing metal bar, it is ground, then with metal net shaped sieve, remove bulk solid, obtain 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 hydration calcium chloride (CaCL
2h
2o), 27.2 grams of sodium chloride (NaCL), 0.4 gram of disodium-hydrogen (Na
2hPO
4), 39.4 grams of TRIS buffer that pH value is 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 2 microgram sterilizings, 37 degree waters bath with thermostatic control, put into the bionical layer of step b gained kernel wherein after dissolving completely, and magnetic stirring apparatus maintains lasting the stirring 24 hours of rotating speed of 50 revs/min, ultrasonic dispersion 40 minutes, logical nitrogen, removes the oxygen in system, after magnetic agitation reaction finishes, is cooled to room temperature;
D, by after step c gained mixed liquor vacuum draw, lyophilisation 24-28 hour, obtains the bionical layer kernel that surface is coated with functional layer;
E, get 1.26 grams of hydrogen chloride (HCL), 0.516 gram of hydration calcium chloride (CaCL
2h
2o), 27.2 grams of sodium chloride (NaCL), 0.4 gram of disodium-hydrogen (Na
2hPO
4), 39.4 grams of TRIS buffer that pH value is 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 2 microgram sterilizings, 37 degree waters bath with thermostatic control, put into the bionical layer kernel that is coated with functional layer wherein after dissolving completely, and magnetic stirring apparatus maintains lasting the stirring 24 hours of rotating speed of 50 revs/min, ultrasonic dispersion 40 minutes, logical nitrogen, removes the oxygen in system, after magnetic agitation reaction finishes, is cooled to room temperature;
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 hydration calcium chloride (CaCL
2h
2o), 38 grams of sodium chloride (NaCL), 1 gram of disodium-hydrogen (Na
2hPO
4), 39 grams of TRIS buffer that pH value is 7.4, add 1L ultra-pure water, regulate pH value to 6.25, on magnetic stirring apparatus, keep temperature 37 degree and continue to stir 24 hours with the rotating speed of 50r/min, generate after precipitation, with the filter vacuum filtration of 0.22 micron, and the solid matter obtaining after filtering is carried out to High Temperature High Pressure degerming;
B, with ultra-pure water, step a gained material is cleaned, put it in shaper after filtering compression in vacuum environment, form certain solid shape (cylindrical or strip), be convenient to be dried; After vacuum drying 2 hours, with sterilizing metal bar, it is ground, then with metal net shaped sieve, remove bulk solid, obtain 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 hydration calcium chloride (CaCL
2h
2o), 26 grams of sodium chloride (NaCL), 0.3 gram of disodium-hydrogen (Na
2hPO
4), 38 grams of TRIS buffer that pH value is 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 1 microgram sterilizing, 37 degree waters bath with thermostatic control, put into the bionical layer of step b gained kernel wherein after dissolving completely, and magnetic stirring apparatus maintains lasting the stirring 24 hours of rotating speed of 50 revs/min, ultrasonic dispersion 30 minutes, logical nitrogen, removes the oxygen in system, after magnetic agitation reaction finishes, is cooled to room temperature;
D, by after step c gained mixed liquor vacuum draw, carry out normal pressure or vacuum drying, obtain the bionical layer kernel that surface is coated with functional layer;
E, get 1 gram of hydrogen chloride (HCL), 0.3 gram of hydration calcium chloride (CaCL
2h
2o), 26 grams of sodium chloride (NaCL), 0.3 gram of disodium-hydrogen (Na
2hPO
4), 38 grams of TRIS buffer that pH value is 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 1 microgram sterilizing, 37 degree waters bath with thermostatic control, put into the bionical layer kernel that is coated with functional layer wherein after dissolving completely, and magnetic stirring apparatus maintains lasting the stirring 24 hours of rotating speed of 50 revs/min, ultrasonic dispersion 30 minutes, logical nitrogen, removes the oxygen in system, after magnetic agitation reaction finishes, is cooled to room temperature;
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 hydration calcium chloride (CaCL
2h
2o), 41 grams of sodium chloride (NaCL), 2 grams of disodium-hydrogen (Na
2hPO
4), 40 grams of TRIS buffer that pH value is 7.4, add 1L ultra-pure water, regulate pH value to 6.25, on magnetic stirring apparatus, keep temperature 37 degree and continue to stir 24 hours with the rotating speed of 50r/min, generate after precipitation, with the filter vacuum filtration of 0.22 micron, and the solid matter obtaining after filtering is carried out to High Temperature High Pressure degerming;
B, with ultra-pure water, step a gained material is cleaned, put it in shaper after filtering compression in vacuum environment, form certain solid shape (cylindrical or strip), be convenient to be dried; After vacuum drying 2 hours, with sterilizing metal bar, it is ground, then with metal net shaped sieve, remove bulk solid, obtain 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 hydration calcium chloride (CaCL
2h
2o), 28 grams of sodium chloride (NaCL), 0.5 gram of disodium-hydrogen (Na
2hPO
4), 40 grams of TRIS buffer that pH value is 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 3 microgram sterilizings, 37 degree waters bath with thermostatic control, put into the bionical layer of step b gained kernel wherein after dissolving completely, and magnetic stirring apparatus maintains lasting the stirring 24 hours of rotating speed of 50 revs/min, ultrasonic dispersion 50 minutes, logical nitrogen, removes the oxygen in system, after magnetic agitation reaction finishes, is cooled to room temperature;
D, by after step c gained mixed liquor vacuum draw, carry out constant pressure and dry, obtain the bionical layer kernel that surface is coated with functional layer;
E, get 1.5 grams of hydrogen chloride (HCL), 0.7 gram of hydration calcium chloride (CaCL
2h
2o), 28 grams of sodium chloride (NaCL), 0.5 gram of disodium-hydrogen (Na
2hPO
4), 40 grams of TRIS buffer that pH value is 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 3 microgram sterilizings, 37 degree waters bath with thermostatic control, put into the bionical layer kernel that is coated with functional layer wherein after dissolving completely, and magnetic stirring apparatus maintains lasting the stirring 24 hours of rotating speed of 50 revs/min, ultrasonic dispersion 50 minutes, logical nitrogen, removes the oxygen in system, after magnetic agitation reaction finishes, is cooled to room temperature;
F, by after step e gained mixed liquor vacuum draw, carry out constant pressure and dry.
The various embodiments described above, can be as required repeating step e, f several times (3-4 time) successively, to obtain the bionical complex that the functional layer number of plies is different, general diameter is preferably less than 0.5mm.
The bionical complex size of retinoic acid hydroxyapatite of utilizing the various embodiments described above to make evenly, it comprises the bionical layer kernel as timbering material, and be wrapped in this bionical layer kernel outer, be spongiform functional layer, wherein the number of plies of functional layer be two-layer or two-layer more than.Human body osteogenetic process is the coefficient process of osteoblast and osteoclast, first be that osteoclast absorbs functional layer material, then osteoblast utilizes the new bone of calcareous formation of material degradation, after new bone formation, surrounded the filling of bionical layer kernel in the damaged place of bone, bionical layer kernel will be present in the damaged place of bone as timbering material, finally under the effect of bionical layer kernel and functional layer, complete the reparation that whole bone is damaged.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, the bionical complex of retinoic acid hydroxyapatite that the present invention is obtained finds for skeletonization-osteoclast co-culture system, and skeletonization effect more single hydroxyapatite material is obvious; For animal large area bone defect model, find, surrounding skeletonization amount is obviously better than the osteogenic materials of clinical use, after eight weeks, skeletonization effect is more remarkable, and sclerous tissues's section is found the bone trabecula close together of area of new bone, the normal bone structure around its structure is damaged closer to bone.
Claims (10)
1. a preparation method for the bionical complex of retinoic acid hydroxyapatite, is characterized in that step is as follows:
A, get the TRIS buffer that 6.5-8 gram of hydrogen chloride, 2-3 gram hydration calcium chloride, 38-41 gram sodium chloride, 1-2 gram disodium-hydrogen, 39-40 gram pH value are 7.4, add 1L ultra-pure water, regulate pH value to 6.25, on magnetic stirring apparatus, keep temperature 37 degree and continue to stir 24 hours with the rotating speed of 50r/min, generate after precipitation, with the filter vacuum filtration of 0.22 micron, and the solid matter obtaining after filtering is carried out to degerming;
B, with ultra-pure water, step a gained material is cleaned, after filtering compression in vacuum environment, put it in shaper, form certain solid shape, after vacuum drying 2 hours, with sterilizing metal bar, it is ground, then cross metal net shaped sieve and obtain the bionical layer inner core particles that diameter is less than 0.22 micron;
C, get the TRIS buffer that 1-1.5 gram of hydrogen chloride, 0.3-0.7 gram hydration calcium chloride, 26-28 gram sodium chloride, 0.3-0.5 gram disodium-hydrogen, 38-40 gram pH value are 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 1-3 microgram sterilizing, 37 degree waters bath with thermostatic control, after dissolving completely, the bionical layer of step b gained kernel put into wherein, magnetic stirring apparatus maintains lasting the stirring 24 hours of rotating speed of 50 revs/min, ultrasonic dispersion 30-50 minute, logical nitrogen, remove the oxygen in system, after magnetic agitation reaction finishes, be cooled to room temperature;
D, by after step c gained mixed liquor vacuum draw, carry out normal pressure or vacuum drying, obtain the bionical layer kernel that surface is coated with functional layer;
E, get the TRIS buffer that 1-1.5 gram of hydrogen chloride, 0.3-0.7 gram hydration calcium chloride, 26-28 gram sodium chloride, 0.3-0.5 gram disodium-hydrogen, 38-40 gram pH value are 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 1-3 microgram sterilizing, 37 degree waters bath with thermostatic control, after dissolving completely, the bionical layer kernel that is coated with functional layer put into wherein, magnetic stirring apparatus maintains lasting the stirring 24 hours of rotating speed of 50 revs/min, ultrasonic dispersion 30-50 minute, logical nitrogen, remove the oxygen in system, after magnetic agitation reaction finishes, be cooled to room temperature;
F, by after step e gained mixed liquor vacuum draw, carry out normal pressure or vacuum drying.
2. the preparation method of the bionical complex of retinoic acid hydroxyapatite according to claim 1, is characterized in that it also comprises step g: repeating step e, f several times successively, obtain the bionical complex that the functional layer number of plies is different.
3. the preparation method of the bionical complex of retinoic acid hydroxyapatite according to claim 1 and 2, is characterized in that: the diameter of the bionical complex of described retinoic acid hydroxyapatite is less than 0.5mm.
4. a preparation method for the bionical complex of retinoic acid hydroxyapatite, is characterized in that step is as follows:
A, get 7.3 grams of hydrogen chloride, 2.58 grams of hydration calcium chloride, 39.78 grams of sodium chloride, 1.42 grams of disodium-hydrogens, 39.4 grams of TRIS buffer that pH value is 7.4, add 1L ultra-pure water, regulate pH value to 6.25, on magnetic stirring apparatus, keep temperature 37 degree and continue to stir 24 hours with the rotating speed of 50r/min, generate after precipitation, with the filter vacuum filtration of 0.22 micron, and the solid matter obtaining after filtering is carried out to degerming;
B, with ultra-pure water, step a gained material is cleaned, after filtering compression in vacuum environment, put it in shaper, form certain solid shape, after vacuum drying 2 hours, with sterilizing metal bar, it is ground, then cross metal net shaped sieve and obtain 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 hydration calcium chloride, 27.2 grams of sodium chloride, 0.4 gram of disodium-hydrogen, 39.4 grams of TRIS buffer that pH value is 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 1-3 microgram sterilizing, 37 degree waters bath with thermostatic control, after dissolving completely, the bionical layer of step b gained kernel put into wherein, magnetic stirring apparatus maintains lasting the stirring 24 hours of rotating speed of 50 revs/min, ultrasonic dispersion 40 minutes, logical nitrogen, remove the oxygen in system, after magnetic agitation reaction finishes, be cooled to room temperature;
D, by after step c gained mixed liquor vacuum draw, vacuum drying 18-48 hour, obtains the bionical layer kernel that surface is coated with functional layer;
E, get 1.26 grams of hydrogen chloride, 0.516 gram of hydration calcium chloride, 27.2 grams of sodium chloride, 0.4 gram of disodium-hydrogen, 39.4 grams of TRIS buffer that pH value is 7.4, total amount is adjusted to 20 milliliters, and add the retinoic acid of 1-3 microgram sterilizing, 37 degree waters bath with thermostatic control, after dissolving completely, the bionical layer kernel that is coated with functional layer put into wherein, magnetic stirring apparatus maintains lasting the stirring 24 hours of rotating speed of 50 revs/min, ultrasonic dispersion 40 minutes, logical nitrogen, remove the oxygen in system, after magnetic agitation reaction finishes, be cooled to room temperature;
F, by after step e gained mixed liquor vacuum draw, vacuum drying 18-48 hour.
5. the preparation method of the bionical complex of retinoic acid hydroxyapatite according to claim 4, is characterized in that it also comprises step g: repeating step e, f several times successively, obtain the bionical complex that the functional layer number of plies is different.
6. according to the preparation method of the bionical complex of retinoic acid hydroxyapatite described in claim 4 or 5, it is characterized in that: in described steps d and step f, be dried under freezing vacuum condition and carry out, be 24-28 hour drying time.
7. according to the preparation method of the bionical complex of retinoic acid hydroxyapatite described in claim 4 or 5, it is characterized in that: the diameter of the bionical complex of described retinoic acid hydroxyapatite is less than 0.5mm.
8. one kind adopts the bionical complex of retinoic acid hydroxyapatite that preparation method obtains described in claim 1 or 4, it is characterized in that: it comprises the bionical layer kernel as timbering material, and be wrapped in this bionical layer kernel outer, when skeletonization, be absorbed the functional layer that simultaneously discharges retinoic acid, described functional layer is spongy.
9. the bionical complex of retinoic acid hydroxyapatite 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. the bionical complex of retinoic acid hydroxyapatite according to claim 8, is characterized in that: the diameter of the bionical complex of described retinoic acid hydroxyapatite is less than 0.5mm.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106745364A (en) * | 2016-11-30 | 2017-05-31 | 江苏永冠给排水设备有限公司 | A kind of Implant hydroxyapatite filter grain based on planting method fluorine removal water process and preparation method thereof |
| CN108434518A (en) * | 2018-05-25 | 2018-08-24 | 林振 | Traditional Chinese medicine monomer sequence is sustained preparation method of the skeletonization at blood vessel calcium phosphorus timbering material |
| CN115382016A (en) * | 2021-05-19 | 2022-11-25 | 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 |
| CN115382010A (en) * | 2021-05-19 | 2022-11-25 | 北京荷月顺畅生物科技有限公司 | Bionic bone material and preparation method thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002040645A2 (en) * | 2000-11-14 | 2002-05-23 | Rosemarie Daig | Cell constructs which can be obtained from mesenschymal stem cells and cells derivable therefrom and the use thereof |
| CN101007187A (en) * | 2007-01-26 | 2007-08-01 | 复旦大学附属华山医院 | Preparation method of composite drug-eluting stent and its drug coated layer |
| US20070190102A1 (en) * | 2000-06-30 | 2007-08-16 | Ping Luo | Method of preparing hydroxyapatite based drug delivery implant for infection and cancer treatment |
| US20100015068A1 (en) * | 2006-07-06 | 2010-01-21 | Massachusetts Institute Of Technology | Methods and Compositions For Altering Biological Surfaces |
| CN103656754A (en) * | 2013-11-25 | 2014-03-26 | 西南交通大学 | Preparation method for drug-carrying multi-layer tissue engineering micro-nano structure bracket |
-
2014
- 2014-05-07 CN CN201410190728.5A patent/CN103948966B/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070190102A1 (en) * | 2000-06-30 | 2007-08-16 | Ping Luo | Method of preparing hydroxyapatite based drug delivery implant for infection and cancer treatment |
| WO2002040645A2 (en) * | 2000-11-14 | 2002-05-23 | Rosemarie Daig | Cell constructs which can be obtained from mesenschymal stem cells and cells derivable therefrom and the use thereof |
| US20100015068A1 (en) * | 2006-07-06 | 2010-01-21 | Massachusetts Institute Of Technology | Methods and Compositions For Altering Biological Surfaces |
| CN101007187A (en) * | 2007-01-26 | 2007-08-01 | 复旦大学附属华山医院 | Preparation method of composite drug-eluting stent and its drug coated layer |
| CN103656754A (en) * | 2013-11-25 | 2014-03-26 | 西南交通大学 | Preparation method for drug-carrying multi-layer tissue engineering micro-nano structure bracket |
Non-Patent Citations (5)
| Title |
|---|
| DARIO PUPPI等: ""Poly(lactic-co-glycolic acid) electrospun fibrous meshes for the controlled release of retinoic acid"", 《ACTA BIOMATERIALIA》, vol. 6, no. 4, 14 August 2009 (2009-08-14), pages 1258 - 1268, XP026921445, DOI: 10.1016/j.actbio.2009.08.015 * |
| TIE LIU等: ""Deproteinized bovine bone functionalized with the slow delivery of BMP-2 for the repair of critical-sized bone defects in sheep"", 《BONE》, vol. 56, no. 1, 1 June 2013 (2013-06-01), pages 110 - 118, XP028675377, DOI: 10.1016/j.bone.2013.05.017 * |
| 支会英等: ""维甲酸对骨发生及骨改建的调控作用"", 《国外医学•创伤与外科基本问题分册》 * |
| 支会英等: ""维甲酸对骨发生及骨改建的调控作用"", 《国外医学•创伤与外科基本问题分册》, vol. 21, no. 1, 29 February 2000 (2000-02-29), pages 9 - 12 * |
| 王林红等: ""全反式维甲酸与骨形态发生蛋白的联合成骨作用研究进展"", 《口腔生物医学》, vol. 3, no. 4, 31 December 2012 (2012-12-31), pages 208 - 211 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106745364A (en) * | 2016-11-30 | 2017-05-31 | 江苏永冠给排水设备有限公司 | A kind of Implant hydroxyapatite filter grain based on planting method fluorine removal water process and preparation method thereof |
| CN108434518A (en) * | 2018-05-25 | 2018-08-24 | 林振 | Traditional Chinese medicine monomer sequence is sustained preparation method of the skeletonization at blood vessel calcium phosphorus timbering material |
| CN115382016A (en) * | 2021-05-19 | 2022-11-25 | 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 |
| CN115382010A (en) * | 2021-05-19 | 2022-11-25 | 北京荷月顺畅生物科技有限公司 | Bionic bone material and preparation method thereof |
| 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 |
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