CN109395171A - A kind of bone renovating material of carrying medicament and preparation method thereof - Google Patents
A kind of bone renovating material of carrying medicament and preparation method thereof Download PDFInfo
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L27/46—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/402—Anaestetics, analgesics, e.g. lidocaine
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/41—Anti-inflammatory agents, e.g. NSAIDs
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
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- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
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Abstract
The present invention relates to a kind of bone renovating material of carrying medicament, comprising sodium alginate, chitosan, more minerals calcium phosphate microspheres, hyaluronic acid, pH adjusting agent, polysorbate20, carrying medicament polymer, can be used for improving bone density, bone cavity avoided to infect.
Description
Technical field
The invention belongs to field of medicaments, are related to bone renovating material, the preparation method of a kind of carrying medicament.
Background technique
Ideal bone tissue engineer cell epimatrix material generally requires good biocompatibility, good biology
Degradability has 3 D stereo porous structure, plasticity and certain mechanical strength, bone guided activity and easy sterilizability.At present
Bone renovating material be generally divided into three categories, mainly have natural macromolecular material, such as chitin and its derivative, collagen, fiber
Protein adhesive；Artificial synthesized macromolecule, such as polylactic acid, polycaprolactone, polylactide polyglycolic acid copolymer；Inorganic material, such as biology
Degradation class ceramics, hydroxyapatite, coral and cuttle bone.
To make filling material of bone both be able to satisfy the demand of mechanical strength, while also bioactivity with higher and performance one
Fixed local therapeutic effects, combined artificial bone renovating material are research emphasis in recent years all the time, and chitosan is as a kind of
Biological macromolecule material has stronger suction-operated, can be used as the carrier of growth factor, is conducive to the structure of cambium
Remodeling and building, therefore have huge application potential in terms of bone tissue engineer, it there is now many for chitosan-hydroxy-apatite
When the report of stone composite material shows that chitosan content is 30%, the compression strength highest of composite material, up to 120MPa or so
([J] material Leader, 2012,26 (15): 102-106)；Although current bone renovating material can meet bone tissue reparation and substitution
The requirement of material, but it is not able to satisfy the ability for continuing and stablizing release drug still.
Summary of the invention
The purpose of the present invention is to provide a kind of effects more preferably to carry medicine bone renovating material, and provides preparation method.This
The load medicine bone renovating material provided is invented while with good mechanical strength with biocompatibility, it can be according to organization internal inflammation
Disease situation, part discharge drug, achieve the effect that long-acting stable release.
In preferred embodiment of the invention scheme, the bone renovating material includes sodium alginate, chitosan, more minerals
Calcium phosphate microsphere, hyaluronic acid, polysorbate20, pH adjusting agent, carrying medicament polymer.
In the other preferred embodiment scheme of the present invention, the bone renovating material is by sodium alginate, chitosan, calcium phosphate
Porous microsphere, hyaluronic acid, pH adjusting agent, the polymer of carrying medicament, cell culture fluid, deionized water composition, each group
Divide and be calculated by mass percentage, sodium alginate content is 0.3~0.8%, and chitosan content is 0.1~0.5%, more mineral phosphors
Sour calcium porous microsphere content is 30~50%, hyaluronic acid contents are 0.1~1%, pH adjusting agent content is 0.01~0.05%,
Polysorbate20 content is 1~5%, and the polymer content of carrying medicament is 1~4%, cell culture liquid hold-up is 10~
20%, water content is 10~20%, and the sum of said components are 100%.
In preferred embodiment of the invention scheme, the polymer is selected from pH sensitive polymer.
In preferred embodiment of the invention scheme, the polymer is selected from the block copolymerization being made of polyethylene glycol and polyester
Object.
In preferred embodiment of the invention scheme, the mass ratio of the polyethylene glycol and polyester is selected from 1:1~1:3, preferably
1:1、1:1.5、1:2、1:3。
In preferred embodiment of the invention scheme, the polyester is selected from the one or two of lactide, glycolide；It is described poly-
Ethylene glycol is selected from the one or two of double hydroxyl polyethylene glycol, mono methoxy polyethylene glycol.
In preferred embodiment of the invention scheme, the molecular weight of the polyethylene glycol is selected from 1000~10000.
In preferred embodiment of the invention scheme, the pH adjusting agent is selected from sodium phosphate, sodium dihydrogen phosphate, sodium citrate.
In preferred embodiment of the invention scheme, more minerals calcium phosphate porous microsphere average grain diameters be selected from 1000~
2000nm, preferably 1500nm.
In currently preferred above-described embodiment scheme, the drug is selected from local anaesthesia drug, and the local anaesthesia drug is selected from cloth
Than cacaine, lidocaine, procaine, totokaine and Ropivacaine.
In currently preferred above-described embodiment scheme, the drug is selected from antibiotics, the Tri-Biocin
Object is selected from vancomycin, tetracycline, gentamicin, tobramycin, Ansai good fortune, cefotaxime, cefotaxime and cefadroxil.
In currently preferred above-described embodiment scheme, the drug is selected from Bone formation drug, the Bone formation medicine
Object is selected from parathyroid hormone or growth hormone.
In preferred embodiment of the invention scheme, the bone renovating material is prepared by following three step:
S1, bone renovating material is prepared；
S2, the polymer that carrying medicament is prepared；
S3, product and hyaluronic acid, pH adjusting agent, cell culture fluid by obtaining step 1 and step 2, deionization
Water, polysorbate20, which are further mixed with to obtain, carries medicine bone renovating material.
In preferred embodiment scheme of the present invention, the S1's method particularly includes:
(1) Sodium Polyacrylate or poly- asparagus fern is added at least two phosphoric acid cationic inorganic salt and inorganic salts containing silicate ion
The mixed solution that phosphoric acid na concn is 10% (w/v) is obtained in propylhomoserin sodium water solution, and temperature is maintained to exist in 30~50 DEG C and pH range
5.0~8.0；Solution containing at least two inorganic ions is added drop-wise in sodium phosphate mixed solution；It is maintained after being added dropwise molten
Liquid system temperature continuously stirs 10 minutes~3 hours ageing solid precipitatings；Solid precipitating, washing filtering, and vacuum is precipitated in filtering
It is dry, more minerals calcium phosphate microspheres are prepared.
(2) the appropriate sodium alginate of room temperature lower-weighing is dissolved in containing Ca2+、Sr2+Aqueous solution in, be sufficiently stirred, be prepared about
The Sodium Alginate Hydrogel Films of 50~100g/L.
(3) the appropriate Chitosan powder of room temperature lower-weighing is dissolved in acetic acid solution, is sufficiently stirred, and about 20~30g/ is prepared
The chitosan solution of L.
(4) by the more minerals calcium phosphate microspheres being prepared by (1), be added to the sodium alginate being prepared by (2)
In hydrogel, the chitosan solution being prepared by (3) is slowly dropped into again after mixing evenly, is stirred evenly, bone is prepared
Repair materials.
In the preferred example scheme of the present invention, the phosphoric acid cationic inorganic salt in (1) is selected from Na3PO4Or
K3PO4, the inorganic salts containing silicate ion are selected from Na2SiO3、CaSiO3、K2SiO3Or K3SiO3；The inorganic salts and polyacrylic acid
The molar ratio of sodium or poly (sodium aspartate) is selected from 1:7~1:15, preferably 1:12,1:10；
PH range further preferred 5.8~7.5；The inorganic ions is selected from Ca2+、Sr2+、Zn2+、Mg2+One kind or more
Kind；
In the further preferred example scheme of the present invention, the total mole number of inorganic ions and inorganic salts in (1)
The ratio between total mole number is 5:4~4:3.
In the further preferred example scheme of the present invention, washing filter solvents are selected from ionized water or anhydrous in (1)
Ethyl alcohol.
In preferred embodiment scheme of the present invention, the S2's method particularly includes:
A couple of days is mixed in the water phases such as polymer and pure water, physiological saline, hydrochloric acid salt buffer solution or cell culture fluid
(such as 3~6 days), spontaneous aquation forms micella in water；Or polymer and drug are codissolved in organic solvent, it is spin-dried for forming a film,
The aquations such as pure water, physiological saline, PBS or tissue culture medium are added, carrier micelle is formed.
In preferred embodiment scheme of the present invention, the S3's method particularly includes:
(1) appropriate hyaluronic acid powder is dissolved in deionized water, is sufficiently stirred, hyaluronic acid solution is prepared, added
Enter appropriate sodium citrate solution and adjust pH to 7~8, polysorbate20, the bone renovating material that step 1 is prepared, step is added
Rapid 2 carrier micelle, the cell culture fluids being prepared, deionized water are sufficiently stirred to obtain final load medicine bone renovating material.
In preferred embodiment of the invention scheme, discovery polysorbate20 can be dispersed in bone for carrier micelle
Key effect is played in repair materials, carrier micelle is made not assemble, not deposit, and guarantees the continuity and stability of drug release.
In preferred embodiment of the present invention scheme, polysorbate20 account for carry medicine bone renovating material mass ratio be selected from 1~
5%, preferably 1%.
In currently preferred above-described embodiment scheme, the load medicine bone renovating material is by drug administration by injection, preferably locally
Tissue injection, the local organization injection are selected from bone cavity.
In currently preferred above-described embodiment scheme, the bone renovating material and load medicine of the load medicine bone renovating material
The polymer of object is preferably being retained separately before application, ready-to-use by subsidiary medicinal solvent before use.
The beneficial effects of the present invention are:
Load medicine bone renovating material of the invention, manufacture craft is relatively easy, and each component ratio is suitable for answering for minimally invasive injection
With good mobility is suitable for the filling of fracture face and bone defect of different shapes gap；In addition Bone Defect Repari of the invention
Material introduces carrier micelle, and compared with traditional porous microsphere prepared by inorganic material carries medicine, drugloading rate is bigger, releases
Medicine is more stable；To sum up load medicine bone renovating material of the invention provides good for osteogenic cell migration, adherency, Proliferation, Differentiation
Microenvironment, while stable drug release feature can reduce local inflammation reaction, relieve pain, and improve patients ' life quality, have non-
Often high medical value.
Detailed description of the invention
In the description and claims of this application, unless otherwise stated, science used herein and skill
Art noun has the normally understood meaning of those skilled in the art institute.
Specific embodiment
The preparation of embodiment 1, bone renovating material
Reagent: hydrochloric acid, dehydrated alcohol, acetic acid, NaSiO3、Na3PO3, a water acetic acid calcium, SrCl2、ZnCl2、MgCl2Purchase
From Sinopharm Chemical Reagent Co., Ltd.；
(1) by NaSiO3And Na3PO3It is added in poly-aspartate sodium water solution for 1:12 in molar ratio, keeps sodium phosphate dense
Degree is 10% (w/v), and control mixed solution temperature maintains 37 DEG C, and salt acid for adjusting pH is added to 7.0, continuously stirs to be formed uniformly
Solution；Again by a water acetic acid calcium, SrCl2、ZnCl2、MgCl2Solution is added dropwise in sodium phosphate mixed solution, makes Ca2+、Sr2+、Zn2 +、Mg2+Total mole number and SiO3 2-、PO4 3-Total mole number ratio be 5:4, maintain solution temperature and continuously to stir after being added dropwise
It mixes and is allowed to be aged 30 minutes；Stop stirring and filtering precipitation precipitating；3 times are successively washed with deionized water and dehydrated alcohol, then
Filtering vacuum is dry, and more minerals calcium phosphate microspheres are prepared.
(2) room temperature lower-weighing 60g sodium alginate powder is dissolved in the Ca containing 500ppm2+With the Sr of 50ppm2+Aqueous solution in,
It is sufficiently stirred when being added, makes the hydrogel that concentration is 60g/L.
(3) room temperature lower-weighing 20g Chitosan powder, is dissolved in the acetic acid solution of 5g/L, is sufficiently stirred and makes concentration
For the chitosan solution of 20g/L.
(4) it weighs 5g step (1) and more minerals calcium phosphate microspheres is prepared, what addition 3.5mL step (2) was prepared
In Sodium Alginate Hydrogel Films, after stirring, the chitosan solution 2.0mL that step (3) is prepared is slowly dropped into
In hydrogel, stirs evenly and Injectable bone repair material about 15g is prepared.
The preparation of embodiment 2, carrier micelle
Reagent: stannous octoate, methylene chloride, ether are bought from Sinopharm Chemical Reagent Co., Ltd.；Double poly- second of hydroxyl
Glycol, EDCHCl, DMAP are bought from Aladdin reagent (Shanghai) Co., Ltd..
(1) be added double hydroxyl polyethylene glycol (2000) of 35g in three-necked flask, 130 DEG C vaccum dewatering 4~5 hours, it is logical
Enter nitrogen and be cooled to 60~70 DEG C, lactide 70g is added, 30mg stannous octoate (contains a small amount of toluene), and 100 DEG C vacuumize 30~50
Minute, it is passed through argon gas protection, 130~135 DEG C is warming up to and reacts 10~14 hours.Product is poured out while hot after completion of the reaction, it is cold
But product is dissolved in methylene chloride after；It is precipitated using ether, obtains BAB type block polymer；Go BAB type block polymerization
N-Boc- histidine 3.0g, 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride (EDCHCl) is added in object 15g
5.2g, 4- Dimethylaminopyrimidine (DMAP) 3.7g, methylene chloride 150mL react 48~54 hours under room temperature, rotate removing unit
Divide solvent, precipitated with ether, further washed with 80 DEG C of ether, remove remaining unreacted reactant and catalyst, is freeze-dried.
(2) 10mg vancomycin and triethylamine are codissolved in methanol/chloroform (volume ratio 1:1, similarly hereinafter), are slowly added dropwise
Contain in the methanol/chloroform solution that above-mentioned steps (1) prepare resulting polymers (5mg/mL) to 100mL, be spin-dried for forming a film, phosphorus is added
Phthalate buffer aquation is filtered with 0.8 μm of filter paper, and dialysis removes free vancomycin, can must contain the glue of vancomycin
Beam about 0.5g, its encapsulation rate is 95% or more after measured.
Embodiment 3, the preparation for carrying medicine bone renovating material
Reagent: polysorbate20, hyaluronic acid powder, sodium citrate are bought from the limited public affairs of Chinese medicines group chemical reagent
Department；Cell culture fluid is bought from Nanjing Dou Lai Bioisystech Co., Ltd.
0.05g hyaluronic acid powder is dissolved in 3mL deionized water, is sufficiently stirred, hyaluronic acid solution is prepared, is added
Enter sodium citrate buffer and adjust pH to 7.2~7.4,0.01g polysorbate20 is added, is allowed to be sufficiently mixed；To mixing
The Injectable bone repair material 5g that embodiment 1 is prepared is added in solution, then embodiment 2 is added into mixed solution and is prepared into
The carrier micelle 0.1g arrived is added cell culture fluid 2mL, adds aseptic deionized water and be settled to 10mL, mix well, and prepares
Obtaining injectable load medicine can repair materials 10mL.
Embodiment 4, carry medicine bone renovating material in osteoporosis model to marrow cavity of femur osteanagenesis efficiency test+
Experimental animal and biomaterial: 3 monthly age SD grade Healthy female rats, weight (240~270) g are purchased from University Of Suzhou
Experimental Animal Center, feeding environment temperature (22 ± 2) DEG C, relative humidity 50% ± 10%, room lighting based on natural lighting,
Well-ventilated, environment are quieter；Staphylococcus aureus (ATCC25923) is bought from the limited public affairs of the triumphant microorganism science and technology of Guangdong ring
Department.
Reference substance: reference substance 1 is prepared according to the method for embodiment 1, does not carry medicine；Reference substance 2 is according to CN101244275A reality
Apply the method preparation of the record of example 2.
Experimental method:
(1) modeling: 40 rats are divided into 5 groups, every group each 8, respectively Sham group, negative control group, test group (this
The load medicine bone renovating material that inventive embodiments 3 are prepared, vancomycin content are 0.2mg/mL), (injection of positive controls 1
Reference substance 1, does not carry medicine)；Positive controls 2 (injection reference substance 2, vancomycin content are 0.2mg/mL)；In above-mentioned each group,
Sham group does not extract ovary and only removes a small amount of adipose tissue at ovary, and negative control group, positive controls and each injection group carry out
Extract operation on ovary.It after each group rat completes corresponding surgical procedure, raises to after the 24th week, measures the bone of each group rat femur
Density, the mean bone density of discovery Sham group femur are 0.287 ± 0.006gcm-2, the average bone of the femur of each operation group is close
Degree is 0.243 ± 0.007gcm-2, two groups have significant difference (p < 0.05), prompt osteoporosis model modeling at
Function.
(2) Material injection: first to negative control group, test group, positive controls rat stock under sterile and anesthesia
The bone cavity injection of bone contains 1 × 107The staphylococcus aureus suspension of CFU/100 μ L bacterium amount, Sham group inject same amount of normal saline,
Then bone wax seals injection pin hole, sutures fur；Continue raising 2 days；Irradiation is carried out to each injection group material using gamma-rays to go out
Bacterium injects phase to the two back leg bone cavity of rat of test group, negative control group, positive controls under sterile and anesthesia respectively
Sterile sampling 1mL, Sham group and negative control group the injection same amount of normal saline answered, then bone wax seals injection pin hole, suture
Fur.Test group and Sham group, negative control group, positive controls are continued into raising 8 weeks, put to death each group rat, takes out and completes
Femur, measures the bone density of each group rat femur, and concrete condition is shown in Table 1.
Each group rat femur bone density changes after table 18 weeks
Data representation and statistical procedures:
Experimental data is expressed as average (Mean) ± standard deviation (S.D.).Statistics ratio is carried out using excel software t inspection
Compared with, " * * " indicate discovery negative control group compared with Sham group, bone density be decreased obviously (**P < 0.01), there is statistical significance,
In the case where intervening without correlation, bone density declines always for prompt；" ## " indicates test group compared with negative control group, and bone density has bright
It is aobvious to rise, and test group is compared to positive controls 2, the rising of the bone density of the femur of rat it is more significant (##p<
0.01vs#p<0.05)；Positive controls 1 are compared with negative control group without significant change.
Experimental result:
During the experiment, in negative control group and positive controls 1, rat each dead 1, there is general essence in other rats
Refreshing state difference, irritability, the situation of back leg inconvenient activity；2 rat general spirit situation of positive controls is poor, irritability, after
The situation of leg inconvenient activity；Other group of rat shows no obvious abnormalities.
In addition, shown according to statistical result, bone cavity memory in the case of infections, the load medicine that the present invention is prepared
Bone renovating material plays an important role to the skeletonization recovery of rat compared to the bone renovating material (reference substance 1) for not carrying medicine, can
Bone density is significantly improved, while avoiding the general infection excited by local infection；It is porous with the load medicine in currently available technology
Microballoon compares (reference substance 2), more obvious to the raising of rat femur density, while because drug release is stablized, more so that the later period is big
Osteogenic cell migration, adherency, Proliferation, Differentiation, accelerate the reparation of femur in mouse femur.
Claims (10)
1. a kind of load medicine bone renovating material, which is characterized in that the load medicine bone renovating material includes sodium alginate, chitosan, more
Minerals calcium phosphate microsphere, hyaluronic acid, pH adjusting agent, polysorbate20, the polymer of carrying medicament, cell culture fluid and
Water.
2. carrying medicine bone renovating material as described in claim 1, which is characterized in that the polymer is selected from by polyethylene glycol and gathers
The block copolymer of ester composition.
3. carrying medicine bone renovating material as claimed in claim 2, which is characterized in that the polyester is selected from lactide, glycolide
It is one or two kinds of；The polyethylene glycol is selected from the one or two of double hydroxyl polyethylene glycol, mono methoxy polyethylene glycol, described poly-
The molecular weight of ethylene glycol is selected from 1000~10000；The mass ratio of the polyethylene glycol and polyester be selected from 1:1~1:3, preferably 1:
1.5。
4. carrying medicine bone renovating material as claimed in claim 3, which is characterized in that more minerals calcium phosphate microspheres are averaged grain
Diameter is selected from 1000~2000nm, preferably 1500nm.
5. as claimed in claim 4 carry medicine bone renovating material, which is characterized in that the bone renovating material by sodium alginate,
Chitosan, calcium phosphate porous microballoon, hyaluronic acid, pH adjusting agent, the polymer of carrying medicament, cell culture fluid and water composition,
Each component is calculated by mass percentage:
Sodium alginate content: 0.3~0.8%；
Chitosan content: 0.1~0.5%；
More minerals calcium phosphate porous microsphere contents: 30~50%；
Hyaluronic acid contents: 0.1~1%；
PH adjusting agent content: 0.01~0.05%；
Polysorbate20 content: 1~5%；
The polymer content of carrying medicament: 1~4%；
Cell culture liquid hold-up: 10~20%；
Water content: 10~20%；
The sum of said components are 100%.
6. carrying medicine bone renovating material as described in claim 1, which is characterized in that the drug is selected from antibiotics or rush
Bon e formation drug, the antibiotics are selected from vancomycin, tetracycline, gentamicin, tobramycin, Ansai good fortune, cephalo
His pyridine, cefotaxime and cefadroxil, preferably vancomycin；The rush bone tissue formed drug be selected from parathyroid hormone or
Growth hormone.
7. a kind of prepare the method as described in claim 1 for carrying medicine bone renovating material, which comprises the following steps:
S1, bone renovating material is prepared；
S2, the polymer that carrying medicament is prepared；
S3, by by S1 and S2 acquisition product and hyaluronic acid, pH adjusting agent, cell culture fluid, water, polysorbate20 into
One step, which is mixed with to obtain, carries medicine bone renovating material.
8. a kind of preparation method for carrying medicine bone renovating material as claimed in claim 7, which is characterized in that the preparation method of the S1
Include:
(1) Sodium Polyacrylate or poly-aspartate is added at least two phosphoric acid cationic inorganic salt and inorganic salts containing silicate ion
In sodium water solution phosphoric acid na concn be 10% (w/v) mixed solution, maintain temperature 30~50 DEG C and pH range 5.0~
8.0, the solution containing at least two inorganic ions is added drop-wise in sodium phosphate mixed solution, maintains solution system after being added dropwise
Temperature continuously stirs 10 minutes~3 hours ageing solid precipitatings；Solid precipitating, washing filtering is precipitated in filtering, and is dried in vacuo,
More minerals calcium phosphate microspheres are prepared；
(2) sodium alginate is dissolved in containing Ca at room temperature2+、Sr2+Aqueous solution in, be sufficiently stirred, about 50~100g/L be prepared
Sodium Alginate Hydrogel Films；
(3) Chitosan powder is dissolved in acetic acid solution at room temperature, is sufficiently stirred, the chitosan of about 20~30g/L is prepared
Solution；
(4) by the more minerals calcium phosphate microspheres being prepared by (1), be added to the sodium alginate water-setting being prepared by (2)
In glue, the chitosan solution being prepared by (3) is slowly dropped into again after mixing evenly, is stirred evenly, Bone Defect Repari is prepared
Material.
9. a kind of preparation method for carrying medicine bone renovating material as claimed in claim 8, which is characterized in that phosphoric acid in (1)
Cationic inorganic salt is selected from Na3PO4Or K3PO4, the inorganic salts containing silicate ion are selected from Na2SiO3、CaSiO3、K2SiO3Or
K3SiO3；The molar ratio of the inorganic salts and Sodium Polyacrylate or poly (sodium aspartate) is selected from 1:7~1:15；The inorganic ions
Selected from Ca2+、Sr2+、Zn2+、Mg2+It is one or more.
10. a kind of preparation method for carrying medicine bone renovating material as described in any one of claim 7~8, which is characterized in that the S2
The preparation method of the polymer of carrying medicament, comprising:
A couple of days is mixed in the water phases such as polymer and pure water, physiological saline, hydrochloric acid salt buffer solution or cell culture fluid, in water
In spontaneous aquation form micella；Or polymer and drug are codissolved in organic solvent, it is spin-dried for forming a film, adds water, physiology salt
The aquations such as water, PBS or tissue culture medium form carrier micelle；
The preparation method of the S3 includes:
Appropriate hyaluronic acid powder is dissolved in deionized water, is sufficiently stirred, hyaluronic acid solution is prepared；Appropriate lemon is added
Lemon acid sodium solution adjusts pH to 7~8, and polysorbate20, the bone renovating material that S1 is prepared, the load that S2 is prepared is added
Medicine micella, cell culture fluid, water are sufficiently stirred to obtain final load medicine bone renovating material.
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