CN107307926A - A kind of porous beta tricalcium phosphate drug sustained release system and preparation method thereof - Google Patents
A kind of porous beta tricalcium phosphate drug sustained release system and preparation method thereof Download PDFInfo
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- CN107307926A CN107307926A CN201710686757.4A CN201710686757A CN107307926A CN 107307926 A CN107307926 A CN 107307926A CN 201710686757 A CN201710686757 A CN 201710686757A CN 107307926 A CN107307926 A CN 107307926A
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- Prior art keywords
- tricalcium phosphate
- bata
- sustained release
- structure body
- release system
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- 239000003814 drug Substances 0.000 title claims abstract description 90
- 229940079593 drug Drugs 0.000 title claims abstract description 65
- 238000013268 sustained release Methods 0.000 title claims abstract description 58
- 239000012730 sustained-release form Substances 0.000 title claims abstract description 58
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 title claims abstract 5
- 239000000463 material Substances 0.000 claims abstract description 8
- 239000001506 calcium phosphate Substances 0.000 claims description 81
- 229940078499 tricalcium phosphate Drugs 0.000 claims description 81
- 229910000391 tricalcium phosphate Inorganic materials 0.000 claims description 81
- 229920003229 poly(methyl methacrylate) Polymers 0.000 claims description 50
- 239000004926 polymethyl methacrylate Substances 0.000 claims description 50
- 239000002002 slurry Substances 0.000 claims description 26
- 239000002245 particle Substances 0.000 claims description 19
- 239000000758 substrate Substances 0.000 claims description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 14
- 238000011049 filling Methods 0.000 claims description 14
- 238000005245 sintering Methods 0.000 claims description 14
- 238000001035 drying Methods 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 239000008367 deionised water Substances 0.000 claims description 6
- 229910021641 deionized water Inorganic materials 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 238000010792 warming Methods 0.000 claims description 6
- 238000013461 design Methods 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- 239000000853 adhesive Substances 0.000 claims description 4
- 230000001070 adhesive effect Effects 0.000 claims description 4
- 239000002270 dispersing agent Substances 0.000 claims description 4
- 239000011440 grout Substances 0.000 claims description 4
- 238000007654 immersion Methods 0.000 claims description 4
- 238000007493 shaping process Methods 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- 238000009834 vaporization Methods 0.000 claims description 4
- 230000008016 vaporization Effects 0.000 claims description 4
- 238000012423 maintenance Methods 0.000 claims description 2
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 210000000988 bone and bone Anatomy 0.000 abstract description 12
- 238000007599 discharging Methods 0.000 abstract description 6
- 230000007547 defect Effects 0.000 abstract description 5
- 208000015181 infectious disease Diseases 0.000 abstract description 3
- 230000008439 repair process Effects 0.000 abstract description 2
- 235000019731 tricalcium phosphate Nutrition 0.000 abstract description 2
- 210000001519 tissue Anatomy 0.000 abstract 1
- 239000010440 gypsum Substances 0.000 description 6
- 229910052602 gypsum Inorganic materials 0.000 description 6
- 239000011148 porous material Substances 0.000 description 5
- 230000009471 action Effects 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000003825 pressing Methods 0.000 description 4
- 230000006835 compression Effects 0.000 description 3
- 238000007906 compression Methods 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 239000003292 glue Substances 0.000 description 3
- 229920003023 plastic Polymers 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 238000000280 densification Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 208000002925 dental caries Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 230000000278 osteoconductive effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 1
- 229960001225 rifampicin Drugs 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000002407 tissue scaffold Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
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- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/28—Bones
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- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2/3094—Designing or manufacturing processes
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/02—Inorganic materials
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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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
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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
- A61L27/56—Porous materials, e.g. foams or sponges
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- A—HUMAN NECESSITIES
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- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
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- A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
- A61F2/30771—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth applied in original prostheses, e.g. holes or grooves
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- A—HUMAN NECESSITIES
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- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
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- A—HUMAN NECESSITIES
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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
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
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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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2210/00—Anatomical parts of the body
- A61M2210/02—Bones
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Animal Behavior & Ethology (AREA)
- Transplantation (AREA)
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- Vascular Medicine (AREA)
- Cardiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Anesthesiology (AREA)
- Dispersion Chemistry (AREA)
- Hematology (AREA)
- Inorganic Chemistry (AREA)
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Abstract
The invention discloses a kind of porous beta tricalcium phosphate drug sustained release system and preparation method thereof, the slow-released system includes：First structure body with loose structure, it is interior with open-topped cavity；The second structure with loose structure matched with the cavity size of first structure body, it is arranged in the cavity of first structure body；There is open-topped cavity, it is used to load medicine in second structure；The material of the first structure body and the second structure is β tricalcium phosphates；The aperture of the first structure body is more than the aperture of the second structure.The porous beta tricalcium phosphate drug sustained release system that the present invention is provided can improve the useful load and sustained release drugs of slow releasing pharmaceutical；Further, it is also possible to repair bone tissue discharging while medicine is acted, it is adaptable to vertebra, the treatment of sclerous tissues's defect such as long bone and infection.
Description
Technical field
The present invention relates to biomedicine field, and in particular to a kind of porous bata-tricalcium phosphate drug sustained release system and its preparation
Method.
Background technology
Traditional administering mode is mainly oral, injection etc., and fluctuating occurs in blood concentration, there is crest and trough, crest
Concentration has often exceeded suitable concentration and has caused toxic side effect, and trough then can not have treatment and make less than minimum treatment concentration
With.
Therefore, it is badly in need of building a kind of drug sustained release system at present, it can be with sustained release drugs, and being applicable needs long-term prescription
Patient, is not required to next step processing after, can effectively improve the doctor of patient from property.
Bone tissue infection is the problem of clinical orthopaedicses, and systemic administration is often difficult to reach valid density in diseased region, and
Bone tissue infection selects suitable tissue scaffold design combination antibiotic formation drug sustained release system often with bone tissue defect
It is current study hotspot.Bata-tricalcium phosphate is common bone renovating material, with good biocompatibility and osteoconductive,
Antibiotic-loaded can reach to the effect of localized sustained release medicine, reduction general toxicity and filling bone defects in bata-tricalcium phosphate
Really.
The content of the invention
It is slow to improve it is an object of the invention to provide a kind of porous bata-tricalcium phosphate drug sustained release system and preparation method thereof
The useful load and sustained release drugs of drug release thing, and repair bone tissue discharging while medicine is acted.
To reach above-mentioned purpose, the invention provides a kind of porous bata-tricalcium phosphate drug sustained release system, including：
First structure body with loose structure, it is interior with open-topped cavity；
The second structure with loose structure matched with the cavity size of first structure body, it is arranged on first structure
In the cavity of body；
There is open-topped cavity, it is used to load medicine in second structure；
The material of the first structure body and the second structure is bata-tricalcium phosphate；
The aperture of the first structure body is more than the aperture of the second structure.
Above-mentioned porous bata-tricalcium phosphate drug sustained release system, wherein, the aperture of the first structure body is 500-800 μ
m；The aperture of second structure is 10-100 μm.
Above-mentioned porous bata-tricalcium phosphate drug sustained release system, wherein, it is provided with the first structure body multiple vertical
Bata-tricalcium phosphate solid post, it is used for the intensity for improving the system.
Above-mentioned porous bata-tricalcium phosphate drug sustained release system, wherein, the shape of the first structure body and the second structure
Shape is cylinder.
Above-mentioned porous bata-tricalcium phosphate drug sustained release system, wherein, the wall thickness of the first structure body is more than the second knot
The wall thickness of structure body.
The thicker effect (plant densification rod) for primarily serving mechanical strength support of first structure body wall, implants simultaneously
Filling bone defects, and its 500-800 μm of aperture meet blood vessel and grow into requirement, beneficial to skeletonization osteoacusis, while there is certain control medicine
Thing release action；Second structure body aperture it is smaller it is main serve medicament slow release (aperture is too big, burst drug release substantially, do not have
The purpose of localized sustained medication), but its mechanics holding strength is not enough, and aperture is nor the optimum aperture scope of osteoacusis, not
Beneficial to skeletonization, thus need to set first structure body on the outside of it.
The porosity of first structure body is 70%, and the porosity of second structure in 10 μm of apertures is 10%-30%；100μ
The porosity of second structure in m apertures is 2%-6%, and aperture selection and porosity select medicine and medicine according to specific needs
Thing concentration, action time is adjusted.
Present invention also offers a kind of preparation method of above-mentioned porous bata-tricalcium phosphate drug sustained release system, comprising following
Step：
Step 1：The mould that design matches with the first structure body size；
Step 2：Pass through Mold Making polymethyl methacrylate (PolymethylMethacrylate, PMMA) support；
Step 3：Prepare bata-tricalcium phosphate slurries；
Step 4：Make first structure body：Bata-tricalcium phosphate slurries are poured into polymethyl methacrylate support, are in the milk
Obtained first structure body is dried after end；
Step 5：Make the second structure：The filling rod that size is less than first structure body cavity body is put into first structure body
In cavity, and the bata-tricalcium phosphate slurries that polymethyl methacrylate will be mixed with, pour into the cavity and filling rod of first structure body
Between, filling rod is taken out after grout curing and obtains the second structure；After being further dried, first structure body and the second structure
Slow-released system base substrate is integrally formed；
Step 6：The heating vaporization of slow-released system base substrate, removes the poly methyl methacrylate particle in idiosome, many to be formed
Hole bata-tricalcium phosphate drug sustained release system base substrate；
Step 7：Porous bata-tricalcium phosphate medicament slow release is obtained after porous bata-tricalcium phosphate drug sustained release system blank sintering
System.
The preparation method of above-mentioned porous bata-tricalcium phosphate drug sustained release system, wherein, the step 2 is specifically included：To
Poly methyl methacrylate particle is added in the mould and is compacted, addition aqueous acetone solution makes poly methyl methacrylate particle
Bonding, the fixed shaping of immersion, polymethyl methacrylate support is made after drying.
The preparation method of above-mentioned porous bata-tricalcium phosphate drug sustained release system, wherein, the step 3 is specifically included：Will
Bata-tricalcium phosphate grinds to form slurry after being mixed with deionized water, and obtains after adding dispersant, adhesive and surfactant, stirring
Bata-tricalcium phosphate slurries.
The preparation method of above-mentioned porous bata-tricalcium phosphate drug sustained release system, wherein, the step 6 is specifically included：It is right
Drug sustained release system base substrate is heated with 260 DEG C of temperature, and is maintained 5-12 hours.
The preparation method of above-mentioned porous bata-tricalcium phosphate drug sustained release system, wherein, the step 7 is specifically included：It is right
Porous bata-tricalcium phosphate drug sustained release system base substrate is sintered：First, it is warming up to from room temperature level with 300 DEG C/h speed
500 DEG C, maintain the temperature 2 hours；Then 1100 DEG C are warming up to 300 DEG C/h speed again, maintain the temperature 4 hours；Finally,
Blow-on obtains porous bata-tricalcium phosphate drug sustained release system when being cooled to 150 DEG C from 1100 DEG C of speed with 300 DEG C/h.
Relative to prior art, the invention has the advantages that：The porous bata-tricalcium phosphate medicament slow release system of the present invention
The cavity space of the second structure can improve greatly the useful load of slow releasing pharmaceutical in system；First structure body and the second structure are tool
There is the loose structure of different pore size, it is possible to achieve continuously discharge medicine；In addition, can be in release medicine using bata-tricalcium phosphate material
Bone tissue is repaired while thing is acted.
Brief description of the drawings
Fig. 1 is the structural representation of porous bata-tricalcium phosphate drug sustained release system of the invention；
Fig. 2 is the diagrammatic cross-section of porous bata-tricalcium phosphate drug sustained release system of the invention；
Fig. 3 is the base of inventive die, the assembling schematic diagram of central slightly rod and thin rod；
Fig. 4 is the outer sleeve schematic diagram of inventive die；
Fig. 5 presses compression mould schematic diagram for inventive die；
Fig. 6 for drug sustained release system of the present invention the second structure in 100 μm of apertures PMMA contents and daily drug release amount
Graph of a relation；
Fig. 7 for 10 μm of apertures in the second structure of drug sustained release system of the present invention PMMA contents and daily drug release amount
Graph of a relation.
Embodiment
Below in conjunction with accompanying drawing, by specific embodiment, the invention will be further described, and these embodiments are merely to illustrate
The present invention, is not limiting the scope of the invention.
As depicted in figs. 1 and 2, the invention provides a kind of porous bata-tricalcium phosphate drug sustained release system, including：
First structure body 1 with loose structure, it is interior with open-topped cavity, and the first structure body 1 is used to supply
Cell adhesion, creep, rise in value and insoluble drug release；
The second structure 2 with loose structure matched with the cavity size of first structure body 1, it is arranged on the first knot
In the cavity of structure body 1, second structure 2 is used for the rate of release for controlling medicine；
There is open-topped cavity, it is used to load medicine in second structure 2；
The material of the structure 2 of first structure body 1 and second is bata-tricalcium phosphate；
The aperture of the first structure body 1 is more than the aperture of the second structure 2.
The aperture of the first structure body 1 is 500-800 μm；The aperture of second structure 2 is 10-100 μm.
Multiple vertical bata-tricalcium phosphate solid posts 3 are provided with the first structure body 1, it is used to improve the system
Intensity；Preferably, 4 bata-tricalcium phosphate solid posts 3 in cross distribution are provided with.
The structure 2 of first structure body 1 and second is shaped as cylinder.
The wall thickness of the first structure body 1 is more than the wall thickness of the second structure 2.
The thicker effect (plant densification rod) for primarily serving mechanical strength support of first structure body wall, implants simultaneously
Filling bone defects, and its 500-800 μm of aperture meet blood vessel and grow into requirement, beneficial to skeletonization osteoacusis, while there is certain control medicine
Thing release action；Second structure body aperture it is smaller it is main serve medicament slow release (aperture is too big, burst drug release substantially, do not have
The purpose of localized sustained medication), but its mechanics holding strength is not enough, and aperture is nor the optimum aperture scope of osteoacusis, not
Beneficial to skeletonization, thus need to set first structure body on the outside of it.
The porosity of first structure body is 70%, and the porosity of second structure in 10 μm of apertures is 10%-30%；100μ
The porosity of second structure in m apertures is 2%-6%, and aperture selection and porosity select medicine and medicine according to specific needs
Thing concentration, action time is adjusted.
Present invention also offers a kind of preparation method of above-mentioned porous bata-tricalcium phosphate drug sustained release system, comprising following
Step：
Step 1：The mould that design matches with the size of first structure body 1；
Step 2：Pass through Mold Making polymethyl methacrylate support；
Step 3：Prepare bata-tricalcium phosphate slurries；
Step 4：Make first structure body 1：Bata-tricalcium phosphate slurries are poured into polymethyl methacrylate support, are in the milk
Obtained first structure body 1 is dried after end；
Step 5：Make the second structure 2：The filling rod of undersized is put into the cavity of first structure body 1, is used
Dropper, which is drawn, is mixed with the bata-tricalcium phosphate slurries of polymethyl methacrylate, instill first structure body 1 cavity and filling rod it
Between, filling rod is taken out after grout curing and obtains the second structure 2, after being further dried, the structure of first structure body 1 and second
2 are integrally formed slow-released system base substrate；
Step 6：Slow-released system base substrate heating vaporization, to remove the poly methyl methacrylate particle in idiosome；
Step 7：Slow-released system is obtained after the slow-released system blank sintering for removing poly methyl methacrylate particle.
The step 2 is specifically included：Poly methyl methacrylate particle is added into the mould and is compacted, acetone is added
The aqueous solution bonds poly methyl methacrylate particle, the fixed shaping of immersion, and polymethyl methacrylate support is made after drying.
The step 3 is specifically included：Grind to form slurry after bata-tricalcium phosphate is mixed with deionized water, and add dispersant,
Bata-tricalcium phosphate slurries are obtained after adhesive and surfactant, stirring.
The step 6 is specifically included：Slow-released system base substrate is placed in sintering tank, is then placed in draft glue discharging furnace, with 260 DEG C
High temperature maintain 5-12 hours.
The step 7 is specifically included：Porous bata-tricalcium phosphate drug sustained release system base substrate is placed in sintering tank, Ran Houfang
Enter sintering in sintering furnace：First, 500 DEG C are warming up to from room temperature level with 300 DEG C/h speed, maintain the temperature 2 hours；Then
1100 DEG C are warming up to 300 DEG C/h speed again, the temperature is maintained 4 hours；Finally, dropped from 1100 DEG C of speed with 300 DEG C/h
Temperature to blow-on at 150 DEG C obtains porous bata-tricalcium phosphate medicine.
In a specific embodiment of drug sustained release system preparation method of the present invention：
Step 1：As shown in Fig. 3, Fig. 4 and Fig. 5, the stainless steel mould that design matches with the size of first structure body 1,
It includes base 4, the thick rod 5 in center agreed with base 4, the thin rod 6 of four centrally located thick surroundings of rod 5, hollow outer cover
Cylinder 7, it is used to central thick rod and thin rod being inserted in it, and its height is higher than the height of the thick rod in center and thin rod, and by pressing mold
Tool 8, it, which is used to move up and down in the hollow cavity of outer sleeve 7, has carried out pressing operation.
Step 2：Make polymethyl methacrylate support：
First, regulation and control workplace temperature and mold temperature.Room temperature maintains 27 DEG C or so, 30 DEG C or so of mold temperature.Mould
The temperature of tool can pass through the maintenance that soaks in a tepid bath.
Secondly, it is 500-800 μm of PMMA particle to weigh 3.7g particle diameters using electronic balance, pours into stainless steel mould, connects
Compacting PMMA particles to exclude intergranular air, make PMMA even particle distributions.
Then, by 75% (w/w) acetone, (acetone is 75 with pure water mass ratio:25) it is rapidly injected in mould until note
It is full, note not making acetone excessively spilling, while using stopwatch timing, using and firmly pressing by compression mould 8 at 1 point and 10 seconds, press
Rotated after pressure, proper amount of acetone is then added again, maintained 20 seconds after pressing again.
Finally, take away by deionized water shower after compression mould 8, extract the mould of sleeve 7 and by mould together with organic of PMMA
In frame immersion deionized water, mold base 4 is removed, the thick rod 5 in center and the thin rod 6 of surrounding is extracted, if the thick rod 5 in center is not drawn out easily
When, it is necessary to encased with gauze, extracted by pliers, thin rod 6 directly can take out by pliers.There is machine support to put complete PMMA
In dry 12 hours in 50 DEG C of baking ovens.
Step 3：Prepare bata-tricalcium phosphate slurries：
The bata-tricalcium phosphate powder of 1300g100% purity is weighed, 580g deionized waters are measured, is put into grinding mill and mills 2
Hour.Slurries are poured into beaker after into slurry, appropriate dispersant, adhesive and surfactant is proportionally added into, stirring is put into
Stirring obtains bata-tricalcium phosphate slurries in 10 minutes in machine.
Step 4：Make first structure body 1：
1st step, the soft paper slip of strip that filled plastics film is wrapped up in PMMA support cavitys, its top exceeds PMMA supports
Surface；
2nd step, discharges the gypsum mold surrounded by four plasterboards on gypsum；Polished using fine sandpaper and file,
Smooth plasterboard and gypsum mold contact surface, is allowed to be in close contact；Gypsum mold can be clamped, fixed PMMA supports, it is ensured that
Enough slurries are fully infiltrated into PMMA supports, and reduce slurries loss；
3rd step, PMMA supports are placed in gypsum mold, fixed using rubber band；
4th step, the bata-tricalcium phosphate slurries fully mixed are injected in gypsum mold, PMMA cantilever tips need to be flooded, make
It is fully infiltrated into PMMA supports.Observation is noted in moisture absorption process, if exposing PMMA supports, needs to supplement β-phosphoric acid
DFP slurries.
5th step, after grouting terminates, the paper slip filled in cavity is taken out, and the gauze soaked with deionized water clears up support
Surface, file modification shaping, drying at room temperature is put into 50 DEG C of electric drying oven with forced convections after 20 minutes and dried 8 hours, obtains first
Structure 1.
Step 5：Make the second structure 2：
1st step, by before gained bata-tricalcium phosphate slurries equivalent divide equally, be separately added into 0wt%, 10wt%, 20wt%,
30wt% a diameter of 100 μm of PMMA powder or 0wt%, 10wt%, 20wt%, 30wt% a diameter of 10 μm of PMMA powder
End, is put into mixer and stirs 10 minutes, and standby porous beta to prepare the second structure 2 with different pore size and porosity-
Tricalcium phosphate drug sustained release system.
2nd step, takes out and the smaller plastics filling rod of diameter is put into dried first structure body 1, its cavity, use drop
Pipe draws a little above-mentioned bata-tricalcium phosphate slurries for being mixed with PMMA, instills in cavity, and plastics filling rod is taken out after grout curing,
Tunnel wall week is repaired using small file, the second structure 2 is obtained, thickness is about 0.6mm.Drying at room temperature is put into 50 DEG C after 20 minutes
Dried 8 hours in electric drying oven with forced convection, slow-released system base substrate is integrally formed in the structure 2 of first structure body 1 and second.
Step 6：The heating vaporization of slow-released system base substrate：
Bata-tricalcium phosphate drug sustained release system base substrate after drying and moulding is placed in sintering tank, is put into draft glue discharging furnace, with 260
DEG C high temperature maintained in draft glue discharging furnace 7 hours, can by ceramic idiosome PMMA particles vaporize remove.
Step 7：Slow-released system blank sintering：
After the completion of dumping, the bata-tricalcium phosphate drug sustained release system base substrate packet after dumping is placed in sintering tank, is put into
In sintering furnace, sintering stage includes heating up and two stages of cooling.Temperature rise period：First, from room temperature level with 300 DEG C/h speed
Rate heats up, and reaches 500 DEG C after 100 minutes, maintains this temperature 2 hours；Then heated up 2 hours, reached with 300 DEG C/h speed again
1100 DEG C, maintain this temperature 4 hours.Temperature-fall period：Cool 40 minutes 3 hours from 1100 DEG C of speed with 300 DEG C/h, drop to
Can blow-on at 150 DEG C.So far bata-tricalcium phosphate drug sustained release system sintering is finished.By the bata-tricalcium phosphate medicine after the completion of sintering
It is standby after thing slow-released system high-temperature sterilization.
As shown in Figure 6 and Figure 7, will there is different pore size and the second structure 2 of porosity prepared by above-described embodiment
Porous bata-tricalcium phosphate drug sustained release system load rifampin after, pass through silica gel plug closing opening side carry out closed, Yu Ti
Outer progress sustained release rate measure.PMMA content increase, then mean the increase of porosity, in the experiment in vitro of 4 weeks, with
The increase of porosity, drug releasing rate increase, and 10 μm of aperture set rates of release are more than 100 μm of aperture sets.In same hole
In the case of gap rate, the quantity and shared volume in 10 μm of aperture set holes are noticeably greater than 100 μm of aperture sets, are conducive to Medicated Permeation.
The aufbauprinciple of the loose structure of porous bata-tricalcium phosphate drug sustained release system provided by the present invention is：Lead to first
Cross pore forming particles PMMA and make PMMA porous supports, secondly pour into bata-tricalcium phosphate slurry in porous PMMA supports, then
Other materials in addition to bata-tricalcium phosphate including PMMA particles are steamed together by being heated at high temperature, both can obtain porous
Bata-tricalcium phosphate structure.And the aperture of porous bata-tricalcium phosphate structure is by the size controlling of the PMMA particles selected；It is many
The porosity of hole bata-tricalcium phosphate structure is controlled by the weight percent (wt%) of PMMA particles.
In summary, the cavity space of second structure greatly can be with porous bata-tricalcium phosphate drug sustained release system of the invention
Improve the useful load of slow releasing pharmaceutical；First structure body and the second structure are the loose structure with different pore size, it is possible to achieve
Continuous release medicine；In addition, repairing bone tissue while being acted using bata-tricalcium phosphate material discharging medicine.
Although present disclosure is discussed in detail by above preferred embodiment, but it should be appreciated that above-mentioned
Description is not considered as limitation of the present invention.After those skilled in the art have read the above, for the present invention's
A variety of modifications and substitutions all will be apparent.Therefore, protection scope of the present invention should be limited to the appended claims.
Claims (10)
1. a kind of porous bata-tricalcium phosphate drug sustained release system, it is characterised in that including：
First structure body with loose structure, it is interior with open-topped cavity；
The second structure with loose structure matched with the cavity size of first structure body, it is arranged on first structure body
In cavity；
There is open-topped cavity, it is used to load medicine in second structure；
The material of the first structure body and the second structure is bata-tricalcium phosphate；
The aperture of the first structure body is more than the aperture of the second structure.
2. porous bata-tricalcium phosphate drug sustained release system as claimed in claim 1, it is characterised in that the first structure body
Aperture is 500-800 μm；The aperture of second structure is 10-100 μm.
3. porous bata-tricalcium phosphate drug sustained release system as claimed in claim 1, it is characterised in that in the first structure body
Multiple vertical bata-tricalcium phosphate solid posts are provided with, it is used for the intensity for improving the system.
4. porous bata-tricalcium phosphate drug sustained release system as claimed in claim 1, it is characterised in that the first structure body and
Second structure is shaped as cylinder.
5. porous bata-tricalcium phosphate drug sustained release system as claimed in claim 1, it is characterised in that the first structure body
Wall thickness is more than the wall thickness of the second structure.
6. a kind of preparation method of the porous bata-tricalcium phosphate drug sustained release system in 1-5 such as claim as described in any one,
Characterized in that, comprising the steps of：
Step 1：The mould that design matches with the first structure body size；
Step 2：Pass through Mold Making polymethyl methacrylate support；
Step 3：Prepare bata-tricalcium phosphate slurries；
Step 4：Make first structure body：Bata-tricalcium phosphate slurries are poured into polymethyl methacrylate support, grouting terminates
Obtained first structure body is dried afterwards；
Step 5：Make the second structure：The filling rod that size is less than first structure body cavity body is put into the cavity of first structure body
It is interior, and the bata-tricalcium phosphate slurries that polymethyl methacrylate will be mixed with, pour between the cavity of first structure body and filling rod,
Filling rod is taken out after grout curing and obtains the second structure；After being further dried, first structure body and the second entire structure
Form slow-released system base substrate；
Step 6：Slow-released system base substrate heating vaporization, remove idiosome in poly methyl methacrylate particle, with formed porous beta-
Tricalcium phosphate drug sustained release system base substrate；
Step 7：Porous bata-tricalcium phosphate drug sustained release system is obtained after porous bata-tricalcium phosphate drug sustained release system blank sintering.
7. the preparation method of porous bata-tricalcium phosphate drug sustained release system as claimed in claim 6, it is characterised in that the step
Rapid 2 specifically include：Poly methyl methacrylate particle is added into the mould and is compacted, addition aqueous acetone solution makes poly- methyl
Methyl acrylate particle is bonded, the fixed shaping of immersion, and polymethyl methacrylate support is made after drying.
8. the preparation method of porous bata-tricalcium phosphate drug sustained release system as claimed in claim 6, it is characterised in that the step
Rapid 3 specifically include：Slurry is ground to form after bata-tricalcium phosphate is mixed with deionized water, and adds dispersant, adhesive and surface and is lived
Property agent, obtains bata-tricalcium phosphate slurries after stirring.
9. the preparation method of porous bata-tricalcium phosphate drug sustained release system as claimed in claim 6, it is characterised in that the step
Rapid 6 specifically include：Drug sustained release system base substrate is heated with 260 DEG C of temperature, and maintained 5-12 hours.
10. the preparation method of porous bata-tricalcium phosphate drug sustained release system as claimed in claim 6, it is characterised in that described
Step 7 is specifically included：Porous bata-tricalcium phosphate drug sustained release system base substrate is sintered：First, from room temperature level with 300
DEG C/h speed is warming up to 500 DEG C, maintains the temperature 2 hours；Then 1100 DEG C, maintenance are warming up to 300 DEG C/h speed again
The temperature 4 hours；Finally, blow-on obtains porous bata-tricalcium phosphate medicine when being cooled to 150 DEG C from 1100 DEG C of speed with 300 DEG C/h
Thing slow-released system.
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