CN108434518A - Traditional Chinese medicine monomer sequence is sustained preparation method of the skeletonization at blood vessel calcium phosphorus timbering material - Google Patents
Traditional Chinese medicine monomer sequence is sustained preparation method of the skeletonization at blood vessel calcium phosphorus timbering material Download PDFInfo
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- CN108434518A CN108434518A CN201810513292.7A CN201810513292A CN108434518A CN 108434518 A CN108434518 A CN 108434518A CN 201810513292 A CN201810513292 A CN 201810513292A CN 108434518 A CN108434518 A CN 108434518A
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- Prior art keywords
- calcium phosphorus
- skeletonization
- blood vessel
- timbering material
- solution
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- 239000000463 material Substances 0.000 title claims abstract description 64
- MWKXCSMICWVRGW-UHFFFAOYSA-N calcium;phosphane Chemical compound P.[Ca] MWKXCSMICWVRGW-UHFFFAOYSA-N 0.000 title claims abstract description 56
- 239000000178 monomer Substances 0.000 title claims abstract description 30
- 210000004204 blood vessel Anatomy 0.000 title claims abstract description 26
- 239000003814 drug Substances 0.000 title claims abstract description 26
- 230000002459 sustained effect Effects 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 210000000988 bone and bone Anatomy 0.000 claims abstract description 47
- 239000011248 coating agent Substances 0.000 claims abstract description 28
- 238000000576 coating method Methods 0.000 claims abstract description 28
- 239000013078 crystal Substances 0.000 claims abstract description 20
- 239000002253 acid Substances 0.000 claims abstract description 12
- 229930189092 Notoginsenoside Natural products 0.000 claims abstract description 10
- 238000013268 sustained release Methods 0.000 claims abstract description 10
- 239000012730 sustained-release form Substances 0.000 claims abstract description 10
- 239000004615 ingredient Substances 0.000 claims abstract description 8
- 239000000243 solution Substances 0.000 claims description 54
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 claims description 27
- 229910021642 ultra pure water Inorganic materials 0.000 claims description 27
- 239000012498 ultrapure water Substances 0.000 claims description 27
- 230000007547 defect Effects 0.000 claims description 20
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 17
- 210000004369 blood Anatomy 0.000 claims description 14
- 239000008280 blood Substances 0.000 claims description 14
- 230000001954 sterilising effect Effects 0.000 claims description 14
- 229910000397 disodium phosphate Inorganic materials 0.000 claims description 13
- 238000003756 stirring Methods 0.000 claims description 13
- 210000000130 stem cell Anatomy 0.000 claims description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 11
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 10
- 239000007983 Tris buffer Substances 0.000 claims description 10
- 239000001110 calcium chloride Substances 0.000 claims description 10
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 10
- 239000001506 calcium phosphate Substances 0.000 claims description 10
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 10
- 235000011010 calcium phosphates Nutrition 0.000 claims description 10
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 10
- 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 claims description 10
- 238000001291 vacuum drying Methods 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 9
- 238000001556 precipitation Methods 0.000 claims description 9
- 235000011148 calcium chloride Nutrition 0.000 claims description 8
- 230000015556 catabolic process Effects 0.000 claims description 8
- 238000006731 degradation reaction Methods 0.000 claims description 8
- 235000019800 disodium phosphate Nutrition 0.000 claims description 8
- 238000002604 ultrasonography Methods 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 6
- 235000016709 nutrition Nutrition 0.000 claims description 6
- 230000002792 vascular Effects 0.000 claims description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 5
- 238000004140 cleaning Methods 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 238000012544 monitoring process Methods 0.000 claims description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 5
- 230000006698 induction Effects 0.000 claims description 4
- 230000001939 inductive effect Effects 0.000 claims description 4
- 230000035479 physiological effects, processes and functions Effects 0.000 claims description 4
- 239000006228 supernatant Substances 0.000 claims description 4
- 206010057249 Phagocytosis Diseases 0.000 claims description 3
- 230000017531 blood circulation Effects 0.000 claims description 3
- 210000002540 macrophage Anatomy 0.000 claims description 3
- 230000008782 phagocytosis Effects 0.000 claims description 3
- 239000002994 raw material Substances 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 2
- 101100127672 Arabidopsis thaliana LAZY2 gene Proteins 0.000 claims 2
- 101100516503 Danio rerio neurog1 gene Proteins 0.000 claims 2
- 101100364400 Mus musculus Rtn4r gene Proteins 0.000 claims 2
- 101100516512 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) NGR1 gene Proteins 0.000 claims 2
- 230000001934 delay Effects 0.000 claims 1
- 239000011664 nicotinic acid Substances 0.000 abstract description 4
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 239000007853 buffer solution Substances 0.000 abstract description 2
- 239000002131 composite material Substances 0.000 abstract description 2
- 239000002159 nanocrystal Substances 0.000 abstract 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 13
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 13
- 230000000694 effects Effects 0.000 description 12
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 6
- 230000011164 ossification Effects 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 239000007788 liquid Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical class [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 3
- YMIFCOGYMQTQBP-UHFFFAOYSA-L calcium;dichloride;hydrate Chemical class O.[Cl-].[Cl-].[Ca+2] YMIFCOGYMQTQBP-UHFFFAOYSA-L 0.000 description 3
- 238000013270 controlled release Methods 0.000 description 3
- 238000005304 joining Methods 0.000 description 3
- 235000011147 magnesium chloride Nutrition 0.000 description 3
- 238000003760 magnetic stirring Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000003643 water by type Substances 0.000 description 3
- 208000006386 Bone Resorption Diseases 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- ZQBZAOZWBKABNC-UHFFFAOYSA-N [P].[Ca] Chemical compound [P].[Ca] ZQBZAOZWBKABNC-UHFFFAOYSA-N 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 230000024279 bone resorption Effects 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- 238000003501 co-culture Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- FYFFGSSZFBZTAH-UHFFFAOYSA-N methylaminomethanetriol Chemical compound CNC(O)(O)O FYFFGSSZFBZTAH-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 230000035764 nutrition Effects 0.000 description 2
- 210000002997 osteoclast Anatomy 0.000 description 2
- 230000002642 osteogeneic effect Effects 0.000 description 2
- 230000002188 osteogenic effect Effects 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 1
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 210000002449 bone cell Anatomy 0.000 description 1
- 229940112869 bone morphogenetic protein Drugs 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000002316 cosmetic surgery Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000006624 extrinsic pathway Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 230000004072 osteoblast differentiation Effects 0.000 description 1
- 230000002138 osteoinductive effect Effects 0.000 description 1
- 150000007965 phenolic acids Chemical class 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
Classifications
-
- 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
- A61L27/02—Inorganic materials
- A61L27/12—Phosphorus-containing materials, e.g. apatite
-
- 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
- A61L27/28—Materials for coating prostheses
-
- 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
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- 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
- A61L27/50—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
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/21—Acids
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
-
- 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
- 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
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
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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
- 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
- A61L2300/604—Biodegradation
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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
- A61L2300/606—Coatings
- A61L2300/608—Coatings having two or more layers
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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
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/02—Methods for coating medical devices
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- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/08—Coatings comprising two or more layers
-
- 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
- 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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- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Dermatology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Transplantation (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
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- Inorganic Chemistry (AREA)
- Materials For Medical Uses (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to traditional Chinese medicine monomer sequence sustained release skeletonization into the preparation method of blood vessel calcium phosphorus timbering material, including step：1) prepared by calcium phosphorus crystal holer；2) it is sustained skeletonization coating；3) sustained release is at blood vessel coating；4) functional particulate is repeated into 25 cycles, spare after crystal lyophilized, all operations carry out in gnotobasis；According to the different clinical calcium phosphorus holders for needing to prepare required size and shape.The beneficial effects of the invention are as follows：With the micro-nano microdeposit technology of low temperature, order cycle carries traditional Chinese medicine monomer ingredient tanshin polyphenolic acid B and notoginsenoside R, and structure can facilitate composite bionic calcium phosphorus timbering material of the bone at blood vessel simultaneously；The micro-nano microdeposit technology of low temperature is the bionic coating prepared using the micro-nano microdeposit technology of low temperature, and the micro-nano crystal of calcium phosphorus is formed in buffer system, which can condense into the holder with some strength at normal temperatures.
Description
Technical field
The present invention relates to a kind of traditional Chinese medicine monomer sequences to be sustained skeletonization into the preparation method of blood vessel calcium phosphorus timbering material, can be made into
It is widely used in the calcium phosphorus timbering material of the reconstruction operation of plastic surgery, orthopaedic trauma and tooth-planting, belongs to Medical treatment device
Tool technical field.
Background technology
The reparation of long segment bone defect caused by wound, tumour, inflammation etc. be the most difficult problems that face of clinician it
One.Long bone defect reparation difficulty is big, and mainly since bone defect position blood supply is poor, new vessels grow into difficulty, and nutrition cannot
It supplies in time and then influences skeletonization effect.Currently, promoting vascularization Engineering Bone mainly by combining microsurgical technique, but the party
Method mainly provides blood fortune by extrinsic pathway for graft, and effect is difficult to meet clinical needs.The combined growth factor is (such as
VEGF, BMP) can induce new vessels formed, but growth factor price and dosage it is higher caused by some side effects limit
Its application clinically is made.
The degradability of ideal bone renovating bracket material should be consistent with new bone formation speed, synkaingenesis blood vessel can and
When required nutrient and stem cell etc. in its osteogenetic process be provided, therefore it is to repair large segmental bone defect that skeletonization is gone forward side by side at blood vessel
It is crucial.There is traditional Chinese medicine monomer tanshin polyphenolic acid B (SALB) good angiogenesis, notoginsenoside R (NGR1) to have good skeletonization
Activity, traditional Chinese medicine monomer definite ingredients are cheap, thus clinically using can significantly reduce clinical treatment cost, mitigate patient
Financial burden, the bone filler clinically used now mostly come from foreign countries, and expensive and skeletonization effect is undesirable, inhale
Receipts slowly are clinically not easy to heal, and extend the clinical effect time.
Invention content
The purpose of the present invention is overcoming deficiency in the prior art, a kind of traditional Chinese medicine monomer sequence is provided and is sustained skeletonization into blood vessel
The preparation method of calcium phosphorus timbering material.
Traditional Chinese medicine monomer sequence is sustained skeletonization into the preparation method of blood vessel calcium phosphorus timbering material, includes the following steps：
1) prepared by calcium phosphorus crystal holer：
1.1) 40.1-42.5g NaCL, 0.8-1.2g KCL, 1.2-1.5g CaCL are taken22H2O, 0.8-1.2g
MgCL26H2Above-mentioned 4 parts of materials are dissolved in ultra-pure water and are stirred simultaneously, the 1mM of 15-20 milliliters of a concentration of 1mM is added by O
HCL, PH are reduced to 1.8-2, this is solution one；
1.2) 0.3-0.4g Na are taken2HPO42H2O is dissolved in ultra-pure water, this is solution two, and solution two is poured into solution one
In；
1.3) it takes 4.5-5.5g sodium bicarbonates to be poured slowly into solution one, while the 1mM HCL monitoring solution PHs of 1mM is added dropwise
Value is allowed to remain between 5.8-6.2；
1.4) ultra-pure water is ultimately joined, temperature control monitors pH value 12-14 hours simultaneously in 36.5-37.5 degree；
1.5) precipitation generates, and removes supernatant, and precipitation is resuspended with ultra-pure water, is centrifuged on centrifuge, the above cleaning step weight
It is 4-5 times multiple；
1.6) sterilizing filter vacuum filter is used, the calcium phosphate obtained in filter is collected in former, baking is put in
Case, calcium phosphate timbering material is at milky after timbering material drying；
2) it is sustained skeletonization coating：
2.1) calcium phosphorus crystal holer is respectively put into the over-saturation calcium phosphorus solution containing sterile NGR1, matches and is：7-9g
HCl；0.33-0.4g Na2HPO4·2H2O；0.5-0.7g CaCl2·2H2O；5-7g；Trishydroxymethylaminomethane TRIS
Base is added 35-45 milliliters of 1M HCL and adjusts pH value 7.35-7.45；
2.2) sterilizing filter filters this supersaturated solution, stirs 36-48 hours, is cooled to room temperature, and collects timbering material
5-10 seconds ultrasonic, ultrapure water forms NGR1- calcium phosphorus holders after vacuum drying；
3) sustained release is at blood vessel coating：
3.1) NGR1- calcium phosphorus holders are respectively put into the over-saturation calcium phosphorus solution containing sterile SalB, match and is：7-9g
HCl；0.33-0.4g Na2HPO4·2H2O；0.5-0.7g CaCl2·2H2O；5-7g trishydroxymethylaminomethanes TRIS
Base is added 35-45 milliliters of 1M HCL and adjusts pH value 7.35-7.45；
3.2) sterilizing filter filters this supersaturated solution, stirs 36-48 hours, is cooled to room temperature, and collects timbering material
5-10 seconds ultrasonic, ultrapure water forms SalB-NGR1- calcium phosphorus holders after vacuum drying；
4) above-mentioned functional particulate is repeated into 2-5 cycle, it is crystal lyophilized spare afterwards, all operation in gnotobasis into
Row；According to the different clinical calcium phosphorus holders for needing to prepare required size and shape.
This traditional Chinese medicine monomer sequence is sustained skeletonization into the application method of blood vessel calcium phosphorus timbering material, includes the following steps：
1) when timbering material being filled into bone defect position, the coating of the macrophage phagocytosis material surface in blood, together
When be sustained out tanshin polyphenolic acid B and calcium phosphorus composition, tanshin polyphenolic acid B activates the stem cell in blood, rapid induction at blood vessel generation, in bone
Defect point forms vascular system, and blood circulation is to supply nutritional ingredient and raw material at bone defect；
2) coating continues to be sustained notoginsenoside R while degradation, the stem cell that efficient inducing blood tape loop comes at
Bone cell differentiation, and using the calcium phosphorus composition of degradation, it is mineralized into area of new bone in defect point, the structures such as area of new bone bone trabecula can compare
Physiology bone structure.
The beneficial effects of the invention are as follows:With the micro-nano microdeposit technology of low temperature, it is red that order cycle carries traditional Chinese medicine monomer ingredient
Phenolic acid B and notoginsenoside R, structure can facilitate composite bionic calcium phosphorus timbering material of the bone at blood vessel simultaneously.Low temperature is micro-nano micro- heavy
Product technology is the bionic coating prepared using the micro-nano microdeposit technology of low temperature, and calcium phosphorus micro nanocrystalline is formed in buffer system
Body, the crystal can condense into the holder with some strength at normal temperatures.The holder can realize orderly carry traditional Chinese medicine monomer at
Point, it is sintered to form that technology is different from traditional holder, low temperature microdeposit technology can preferably keep the activity of traditional Chinese medicine monomer.In shape
At CYCLIC LOADING notoginsenoside R and tanshin polyphenolic acid B while controlled-release coating, the traditional Chinese medicine monomer structure of petal-shaped cycle interaction is formed,
It is sustained tanshin polyphenolic acid B while calcium phosphor coating dissolves, new vessels is promoted to be formed, while blood fortune brings stem cell and osteogenetic process
The necessary factor and nutrient.Calcium phosphor coating further dissolves sustained release notoginsenoside R, preferably can ship the dry of source using blood
Cell efficiently induces stem cell to osteoblast conversion, and promotes the formation of skeletonization mineralising and area of new bone.Clinically make in recent years
It is Bone Morphogenetic Protein BMP, but it is expensive, such as excessive Osteogenesis spur (lacking into vascular) of side effect is excessive
Activation osteoclast causes bone resorption etc. and influences its clinical application.Traditional Chinese medicine monomer sequence sustained release can solve this problem,
There is tanshin polyphenolic acid B good angiogenesis to provide area of new bone energy and stem cell source, notoginsenoside R be traditional Chinese medicine by with
It is with a history of thousands of years in treatment bone defect, it is almost without side-effects, it can not only continue skeletonization but also bone resorption can be prevented
Equal side effects.The local sustained release of this timbering material can be such that completion skeletonization occurs at the sequence of blood vessel, obtain best osteogenic induction
Effect, the area of new bone formed can compare normal bone structure, and for the compound traditional Chinese medicine monomer of timbering material derived from China, source is wide in addition
General, cheap, the clinical bone renovating bracket material of this high osteoinductive of low cost is that the urgent of large segmental bone defect is repaired in China
It needs.
Description of the drawings
Fig. 1 is building-up process schematic diagram；
Fig. 2 is scanning electron microscope (SEM) photograph (SEM), it is seen that coralliform traditional Chinese medicine monomer layer；
It is (left that Fig. 3 is into vessel graph：Control group.It is right：Material group)；
Fig. 4 is that skeletonization mineralising figure is (left：Control group.It is right：Material group)；
Fig. 5 is internal heterotopic Osteogenesis MicroCT figures, shows area of new bone pattern；
Fig. 6 is scanning electron microscope (SEM) photograph (SEM), it is seen that more uniform coralliform traditional Chinese medicine monomer layer；
It is (left that Fig. 7 is into vessel graph：Control group.It is right：Material group)；
Fig. 8 is that skeletonization mineralising figure is (left：Control group.It is right：Material group)；
Fig. 9 is internal heterotopic Osteogenesis MicroCT figures, shows area of new bone pattern.
Specific implementation mode
The present invention is described further with reference to embodiment.The explanation of following embodiments is merely used to help understand this
Invention.It should be pointed out that for those skilled in the art, without departing from the principle of the present invention, also
Can be with several improvements and modifications are made to the present invention, these improvement and modification also fall into the protection domain of the claims in the present invention
It is interior.
The present invention is divided into calcium phosphorus crystal and controlled-release coating, in vivo under the action of osteoclast, in controlled-release coating
Calcium phosphorus releases traditional Chinese medicine monomer tanshin polyphenolic acid B while degradation, acts at bone defect and promotes into the generation of blood vessel first, newborn
After vascularization by blood stem cell and nutritional ingredient take at bone defect.Next step calcium phosphor coating continues to degrade, sustained release
Go out notoginsenoside R, can efficiently the stem cell in inducing blood break up to skeletonization direction, and using the calcium phosphorus of degradation as former
Material, micro constitutent and the factor in blood provide nutrition, finally efficiently complete the physiology reparation of entire bone defect.
The technical solution adopted in the present invention is：Traditional Chinese medicine monomer sequence is sustained preparation of the skeletonization at blood vessel calcium phosphorus timbering material
Method, characterization step are as follows：
It is prepared by calcium phosphorus crystal holer：Operation carries out in aseptic superclean bench.40.1-42.5g sodium chloride (NaCL) is taken,
0.8-1.2g potassium chloride (KCL), 1.2-1.5g calcium chloride hydrates (CaCL22H2O), 0.8-1.2g hydrated magnesium chlorides
(MgCL26H2O), above-mentioned 4 parts of materials are dissolved in ultra-pure water (MillQ water) simultaneously and stirred, 15-20 milliliters of addition is dense
Degree is the hydrogen chloride (1mM HCL) of 1mM, and PH is reduced to 1.8-2, this is solution one.Take 0.3-0.4g hypophosphite monohydrate disodium hydrogens
(Na2HPO42H2O it) is dissolved in 5 milliliters of ultra-pure waters (MillQ water), this is solution two, and solution two is poured into solution one.It takes
4.5-5.5g sodium bicarbonates are poured slowly into solution one, while hydrogen chloride (1mM HCL) the monitoring solution pH value that 1mM is added dropwise is allowed to
It remains between 5.8-6.2.Ultimately joining ultra-pure water makes total amount of liquid at 1000 milliliters, the rotating speed on magnetic stirring apparatus
(260r/min), temperature control monitor pH value 12-14 hours simultaneously in 36.5-37.5 degree.Precipitation generates, and removes supernatant, sinks
Shallow lake is resuspended 5 minutes with ultra-pure water, and 5000r/min is centrifuged 5 minutes on centrifuge, and the above cleaning step repeats 4-5 times, micro- with 0.22
The sterilizing filter vacuum filter of rice, the calcium phosphate obtained in filter is collected in former (with the diameter independently made
For 5mm circle formers), it is put in 37 degree of baking ovens 12 hours, calcium phosphate timbering material is at milky after timbering material drying.
It is sustained skeletonization coating：Calcium phosphorus crystal holer is respectively put into containing sterile 1mg, 10mg, 100mg, the NGR1 of 1g is (single
Body definite ingredients are commercially available) 1000ml over-saturation calcium phosphorus solutions in (7-9g HCl；0.33-0.4g Na2HPO4·2H2O；
0.5-0.7g CaCl2·2H2O；35-45 milliliters of 1M HCL are added in 5-7g trishydroxymethylaminomethane TRIS base [Sigma]
Adjust pH value 7.35-7.45.0.2 μm of sterilizing filter filters this supersaturated solution) 37 DEG C of rotating speeds of constant temperature be 50 revs/min stirring
It 36-48 hours, is cooled to room temperature, collects timbering material ultrasound 5-10 seconds, ultrapure water forms NGR1- calcium after vacuum drying
Phosphorus holder.
It is sustained into blood vessel coating：NGR1- calcium phosphorus holders are respectively put into containing sterile 0.1mg, 1mg, 10mg, 100mg's
(7-9g HCl in the 1000ml over-saturation calcium phosphorus solutions of SalB (monomer component is clearly commercially available)；0.33-0.4g Na2HPO4·
2H2O；0.5-0.7g CaCl2·2H2O；5-7g trishydroxymethylaminomethane TRIS base [Sigma] are added 35-45 milliliters
1M HCL adjust pH value 7.35-7.45.0.2 μm of sterilizing filter filters this supersaturated solution) 37 DEG C of rotating speeds of constant temperature be 50 revs/min
Stirring 36-48 hours, is cooled to room temperature, and collects timbering material ultrasound 5-10 seconds, and ultrapure water is formed after vacuum drying
SalB-NGR1- calcium phosphorus holders.
Above-mentioned functional particulate is repeated into 2-5 cycle, spare after crystal lyophilized, all operations carry out in gnotobasis
(building-up process schematic diagram 1).It can be according to the different clinical calcium phosphorus holders for needing to prepare required size and shape.
When timbering material is filled into bone defect position, the coating of the macrophage phagocytosis material surface in blood, simultaneously
It is sustained out tanshin polyphenolic acid B and calcium phosphorus composition, tanshin polyphenolic acid B activates the stem cell in blood, rapid induction to be lacked in bone at the generation of blood vessel
Vascular system is formed at damage, blood circulation is to supply nutritional ingredient and raw material at bone defect.Coating continues to be sustained while degradation
Notoginsenoside R, the stem cell to osteoblast differentiation that efficient inducing blood tape loop comes, and the calcium phosphorus composition of degradation is utilized,
It is mineralized into area of new bone in defect point, the structures such as area of new bone bone trabecula can compare physiological bone structure.
Embodiment one：
It is prepared by calcium phosphorus crystal holer：Operation carries out in aseptic superclean bench.Take 42g sodium chloride (NaCL), 1g chlorinations
Potassium (KCL), 1.4g calcium chloride hydrates (CaCL22H2O), 1g hydrated magnesium chlorides (MgCL26H2O), above-mentioned 4 parts of materials is molten simultaneously
Solution (MillQ water) and stirs in ultra-pure water, and the hydrogen chloride (1mM HCL) of 18 milliliters of a concentration of 1mM is added, and PH is reduced to 2,
This is solution one.Take 0.35g hypophosphite monohydrate disodium hydrogens (Na2HPO42H2O it) is dissolved in 5 milliliters of ultra-pure waters (MillQ water), this
For solution two, solution two is poured into solution one.It takes 5g sodium bicarbonates to be poured slowly into solution one, while the chlorination of 1mM is added dropwise
Hydrogen (1mM HCL) monitoring solution pH value is allowed to remain at 6.Ultimately joining ultra-pure water makes total amount of liquid at 1000 milliliters,
Rotating speed (260r/min) on magnetic stirring apparatus, temperature control monitor pH value 14 hours simultaneously at 37 degree.Precipitation generates, in removal
Clear liquid, precipitation are resuspended 5 minutes with ultra-pure water, and 5000r/min is centrifuged 5 minutes on centrifuge, and the above cleaning step is repeated 5 times, and are used
0.22 micron of sterilizing filter vacuum filter, the calcium phosphate obtained in filter is collected in former (independently to make
Diameter 5mm circle formers for), be put in 37 degree of baking ovens 12 hours, calcium phosphate timbering material is at breast after timbering material drying
White.
It is sustained skeletonization coating：Calcium phosphorus crystal holer is respectively put into the NGR1 containing sterile 100mg, and (monomer component clearly may be used
Purchase) 1000ml over-saturation calcium phosphorus solutions in (8g HCl；0.38g Na2HPO4·2H2O；0.6g CaCl2·2H2O；6g tri-
Hydroxymethyl aminomethane TRIS base [Sigma] are added 40 milliliters of 1M HCL and adjust pH value 7.4.0.2 μm of sterilizing filter mistake
Filter this supersaturated solution) 37 DEG C of rotating speeds of constant temperature are 50 revs/min and stir 48 hours, be cooled to room temperature, collect timbering material ultrasound 5
Second, ultrapure water forms NGR1- calcium phosphorus holders after vacuum drying.
It is sustained into blood vessel coating：NGR1- calcium phosphorus holders are respectively put into the SalB containing sterile 10mg, and (monomer component is clear
It is commercially available) 1000ml over-saturation calcium phosphorus solutions in (8g HCl；0.38g Na2HPO4·2H2O；0.6g CaCl2·2H2O；6g
Trishydroxymethylaminomethane TRIS base [Sigma] are added 40 milliliters of 1M HCL and adjust pH value 7.4.0.2 μm of sterilizing filter
Filtering this supersaturated solution) 37 DEG C of rotating speeds of constant temperature are 50 revs/min and stir 48 hours, be cooled to room temperature, collect timbering material ultrasound 5
Second, ultrapure water forms SalB-NGR1- calcium phosphorus holders after vacuum drying.
Above-mentioned functional particulate is repeated into four cycles, spare after crystal lyophilized, all operations carry out in gnotobasis.
Visible rack surface is uniformly distributed coralloid traditional Chinese medicine monomer coating (Fig. 2) under one scanning electron microscope of embodiment.By this
Calcium phosphorus timbering material is sustained in huve cell-material co-cultivation and mescenchymal stem cell-material co-culture system
It was found that this material skeletonization is good at the more single calcium phosphorus timbering material of vascular effects and has notable difference (Fig. 3,4).For in animal body
Induced osteogenesis experiment finds that the osteogenic materials of Clinical practice are substantially better than at bone amount, and skeletonization effect is more notable after six weeks, and
MicroCT has found that the bone trabecula distance of area of new bone is closer, and structure is closer to normal bone structure (Fig. 5).
Embodiment two：
It is prepared by calcium phosphorus crystal holer：Operation carries out in aseptic superclean bench.Take 40g sodium chloride (NaCL), 0.8g chlorine
Change potassium (KCL), 1.2g calcium chloride hydrates (CaCL22H2O), 0.8g hydrated magnesium chlorides (MgCL26H2O), above-mentioned 4 parts of materials is same
When be dissolved in ultra-pure water (MillQ water) and stir, be added 16 milliliters of a concentration of 1mM hydrogen chloride (1mM HCL), PH drop
It is 1.8, this is solution one.Take 0.3g hypophosphite monohydrate disodium hydrogens (Na2HPO42H2O) it is dissolved in 5 milliliters of ultra-pure waters (MillQ water)
In, this is solution two, and solution two is poured into solution one.It takes 4.5g sodium bicarbonates to be poured slowly into solution one, while 1mM is added dropwise
Hydrogen chloride (1mM HCL) monitoring solution pH value be allowed to remain at 5.8.Ultimately joining ultra-pure water makes total amount of liquid exist
1000 milliliters, rotating speed (260r/min) on magnetic stirring apparatus, temperature control monitors pH value 12 hours simultaneously at 36.5 degree.Precipitation
It generates, removes supernatant, precipitation is resuspended 5 minutes with ultra-pure water, and 5000r/min is centrifuged 5 minutes on centrifuge, the above cleaning step
It is repeated 5 times, with 0.22 micron of sterilizing filter vacuum filter, the calcium phosphate obtained in filter is collected in former
(by taking the diameter 5mm circle formers independently made as an example), is put in 37 degree of baking ovens 12 hours, calcium phosphate branch after timbering material drying
Frame material is at milky.
It is sustained skeletonization coating：Calcium phosphorus crystal holer is respectively put into the NGR1 containing sterile 1mg, and (monomer component is clearly commercially available
Buy) 1000ml over-saturation calcium phosphorus solutions in (7g HCl；0.34g Na2HPO4·2H2O；0.55g CaCl2·2H2O；5g tri-
Hydroxymethyl aminomethane TRIS base [Sigma] are added 38 milliliters of 1M HCL and adjust pH value 7.35.0.2 μm of sterilizing filter mistake
Filter this supersaturated solution) 37 DEG C of rotating speeds of constant temperature are 50 revs/min and stir 48 hours, be cooled to room temperature, collect timbering material ultrasound 5
Second, ultrapure water forms NGR1- calcium phosphorus holders after vacuum drying.
It is sustained into blood vessel coating：NGR1- calcium phosphorus holders are respectively put into the SalB containing sterile 0.1mg, and (monomer component is bright
It is really commercially available) 1000ml over-saturation calcium phosphorus solutions in (7g HCl；0.34g Na2HPO4·2H2O；0.55g CaCl2·
2H2O；5g trishydroxymethylaminomethane TRIS base [Sigma] are added 38 milliliters of 1M HCL and adjust pH value 7.35.0.2 μm of nothing
Bacterium filter filters this supersaturated solution) 37 DEG C of rotating speeds of constant temperature be 50 revs/min stir 48 hours, be cooled to room temperature, collect holder
Material ultrasound 5 seconds, ultrapure water form SalB-NGR1- calcium phosphorus holders after vacuum drying.
Above-mentioned functional particulate is repeated into two cycles, spare after crystal lyophilized, all operations carry out in gnotobasis.
The visible coralloid traditional Chinese medicine monomer coating (Fig. 6) of rack surface more uniform distribution under two scanning electron microscope of embodiment.It will
This sustained release calcium phosphorus timbering material is co-cultured for huve cell-material and mescenchymal stem cell-material co-culture system
Middle discovery, this material skeletonization are preferable (Fig. 7,8) at vascular effects.For in animal body induced osteogenesis experiment find, at bone amount compared with
More, skeletonization effect is more notable after six weeks, and MicroCT has found that the trabecular bone structure of area of new bone is similar to physiology bone structure (Fig. 9).
Claims (3)
1. a kind of traditional Chinese medicine monomer sequence sustained release skeletonization is at the preparation method of blood vessel calcium phosphorus timbering material, it is characterised in that：Including such as
Lower step：
1) prepared by calcium phosphorus crystal holer：
1.1) 40.1-42.5g NaCL, 0.8-1.2g KCL, 1.2-1.5g CaCL are taken22H2O, 0.8-1.2g MgCL26H2O, will
Above-mentioned 4 parts of materials are dissolved in ultra-pure water and stir simultaneously, and the 1mM HCL of 15-20 milliliters of a concentration of 1mM are added, and PH is reduced to
1.8-2, this is solution one；
1.2) 0.3-0.4g Na are taken2HPO42H2O is dissolved in ultra-pure water, this is solution two, and solution two is poured into solution one；
1.3) 4.5-5.5g sodium bicarbonates are taken to be poured slowly into solution one, while the 1mM HCL monitoring solution pH values that 1mM is added dropwise make
Remain between 5.8-6.2；
1.4) ultra-pure water is ultimately joined, temperature control monitors pH value 12-14 hours simultaneously in 36.5-37.5 degree；
1.5) precipitation generates, and removes supernatant, and precipitation is resuspended with ultra-pure water, is centrifuged on centrifuge, and the above cleaning step repeats 4-5
It is secondary；
1.6) sterilizing filter vacuum filter is used, the calcium phosphate obtained in filter is collected in former, baking oven is put in, is propped up
Calcium phosphate timbering material is at milky after frame material drying；
2) it is sustained skeletonization coating：
2.1) calcium phosphorus crystal holer is respectively put into the over-saturation calcium phosphorus solution containing sterile NGR1, matches and is：7-9g HCl；
0.33-0.4g Na2HPO4·2H2O；0.5-0.7g CaCl2·2H2O；5-7g；Trishydroxymethylaminomethane TRIS base,
35-45 milliliters of 1M HCL are added and adjust pH value 7.35-7.45；
2.2) sterilizing filter filters this supersaturated solution, stirs 36-48 hours, is cooled to room temperature, and collects timbering material ultrasound
5-10 seconds, ultrapure water formed NGR1- calcium phosphorus holders after vacuum drying；
3) sustained release is at blood vessel coating：
3.1) NGR1- calcium phosphorus holders are respectively put into the over-saturation calcium phosphorus solution containing sterile SalB, match and is：7-9g HCl；
0.33-0.4g Na2HPO4·2H2O；0.5-0.7g CaCl2·2H2O；5-7g trishydroxymethylaminomethane TRIS base, add
Enter 35-45 milliliters of 1M HCL and adjusts pH value 7.35-7.45；
3.2) sterilizing filter filters this supersaturated solution, stirs 36-48 hours, is cooled to room temperature, and collects timbering material ultrasound
5-10 seconds, ultrapure water formed SalB-NGR1- calcium phosphorus holders after vacuum drying；
4) above-mentioned functional particulate is repeated into 2-5 cycle, spare after crystal lyophilized, all operations carry out in gnotobasis；
According to the different clinical calcium phosphorus holders for needing to prepare required size and shape.
2. traditional Chinese medicine monomer sequence according to claim 1 is sustained preparation method of the skeletonization at blood vessel calcium phosphorus timbering material,
It is characterized in that：Calcium phosphorus crystal holer is respectively put into containing sterile 1mg, 10mg, 100mg in step 2.1), the NGR1's of 1g
In 1000ml over-saturation calcium phosphorus solutions；NGR1- calcium phosphorus holders are respectively put into containing sterile 0.1mg, 1mg in step 3.1),
In the 1000ml over-saturation calcium phosphorus solutions of the SalB of 10mg, 100mg.
3. traditional Chinese medicine monomer sequence according to claim 1 is sustained application method of the skeletonization at blood vessel calcium phosphorus timbering material,
It is characterized in that：Include the following steps：
1) when timbering material being filled into bone defect position, the coating of the macrophage phagocytosis material surface in blood delays simultaneously
Disengage tanshin polyphenolic acid B and calcium phosphorus composition, tanshin polyphenolic acid B activates the stem cell in blood, rapid induction at blood vessel generation, in bone defect
Place forms vascular system, and blood circulation is to supply nutritional ingredient and raw material at bone defect；
2) coating continues to be sustained notoginsenoside R while degradation, and the stem cell that efficient inducing blood tape loop comes is thin to skeletonization
Born of the same parents break up, and using the calcium phosphorus composition of degradation, and area of new bone is mineralized into defect point, and the structures such as area of new bone bone trabecula can compare physiology
Bone structure.
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| 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 |
| WO2023178938A1 (en) * | 2022-03-23 | 2023-09-28 | 苏州卓欣雅科技有限公司 | 3d-printed degradable intravascular stent loaded with salvianolic acid b |
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Inventor after: Liu Yi Inventor after: Lin Zhen Inventor after: Wang Jing Inventor after: Du Jiang Inventor before: Lin Zhen Inventor before: Liu Yi Inventor before: Wang Jing Inventor before: Du Jiang |
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Effective date of registration: 20200103 Address after: 311217 Room 301, block B, Chuang Chuang, Xinzhong street, Xinjie street, Xiaoshan, Hangzhou, Zhejiang. Applicant after: HANGZHOU HUIBO TECHNOLOGY Co.,Ltd. Address before: 510632 Whampoa West Road, Guangdong, Guangzhou, No. 601, No. Applicant before: Lin Zhen |
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Inventor after: Lin Zhen Inventor after: Liu Yi Inventor after: Wang Jing Inventor after: Du Jiang Inventor before: Liu Yi Inventor before: Lin Zhen Inventor before: Wang Jing Inventor before: Du Jiang |
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Denomination of invention: Preparation method of calcium phosphate scaffold material for sustained release osteogenesis and vascularization of traditional Chinese medicine monomer sequence Effective date of registration: 20221030 Granted publication date: 20200207 Pledgee: Zhejiang Xiaoshan Rural Commercial Bank Co.,Ltd. Development Zone sub branch Pledgor: HANGZHOU HUIBO TECHNOLOGY Co.,Ltd. Registration number: Y2022330002852 |