CN116370715B - Shapable porous biological composite bone filling material containing statin drugs and preparation method thereof - Google Patents
Shapable porous biological composite bone filling material containing statin drugs and preparation method thereof Download PDFInfo
- Publication number
- CN116370715B CN116370715B CN202310521156.3A CN202310521156A CN116370715B CN 116370715 B CN116370715 B CN 116370715B CN 202310521156 A CN202310521156 A CN 202310521156A CN 116370715 B CN116370715 B CN 116370715B
- Authority
- CN
- China
- Prior art keywords
- statin
- powder
- calcium sulfate
- collagen gel
- anhydrous calcium
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 210000000988 bone and bone Anatomy 0.000 title claims abstract description 70
- 239000000463 material Substances 0.000 title claims abstract description 58
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 title claims abstract description 37
- 238000011049 filling Methods 0.000 title claims abstract description 23
- 239000002131 composite material Substances 0.000 title claims abstract description 21
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 239000003814 drug Substances 0.000 title abstract description 12
- 229940079593 drug Drugs 0.000 title abstract description 8
- 239000000843 powder Substances 0.000 claims abstract description 40
- 229940095564 anhydrous calcium sulfate Drugs 0.000 claims abstract description 34
- 229920001184 polypeptide Polymers 0.000 claims abstract description 31
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 31
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 31
- 239000000512 collagen gel Substances 0.000 claims abstract description 29
- 238000002156 mixing Methods 0.000 claims abstract description 14
- 239000011812 mixed powder Substances 0.000 claims abstract description 12
- 238000003756 stirring Methods 0.000 claims abstract description 8
- 239000000203 mixture Substances 0.000 claims abstract description 6
- 238000005303 weighing Methods 0.000 claims abstract description 5
- 235000015110 jellies Nutrition 0.000 claims abstract description 4
- 239000008274 jelly Substances 0.000 claims abstract description 4
- 238000003825 pressing Methods 0.000 claims abstract description 4
- 239000007787 solid Substances 0.000 claims abstract description 4
- FJLGEFLZQAZZCD-MCBHFWOFSA-N (3R,5S)-fluvastatin Chemical compound C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 FJLGEFLZQAZZCD-MCBHFWOFSA-N 0.000 claims description 25
- 229960003765 fluvastatin Drugs 0.000 claims description 25
- 238000000034 method Methods 0.000 claims description 16
- 239000000945 filler Substances 0.000 claims description 6
- 239000011173 biocomposite Substances 0.000 claims description 3
- 238000003860 storage Methods 0.000 claims description 3
- 229960000672 rosuvastatin Drugs 0.000 claims description 2
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 claims description 2
- 241000283690 Bos taurus Species 0.000 claims 1
- 241000282887 Suidae Species 0.000 claims 1
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 51
- 230000007547 defect Effects 0.000 description 19
- 230000008569 process Effects 0.000 description 9
- 229940095672 calcium sulfate Drugs 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- 230000011164 ossification Effects 0.000 description 6
- 238000007711 solidification Methods 0.000 description 6
- 230000008023 solidification Effects 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 208000027418 Wounds and injury Diseases 0.000 description 5
- 239000012620 biological material Substances 0.000 description 5
- 230000015556 catabolic process Effects 0.000 description 5
- 238000006731 degradation reaction Methods 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 210000004872 soft tissue Anatomy 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 4
- 230000010478 bone regeneration Effects 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000001976 improved effect Effects 0.000 description 4
- 208000014674 injury Diseases 0.000 description 4
- 210000000963 osteoblast Anatomy 0.000 description 4
- 108010035532 Collagen Proteins 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 229920001436 collagen Polymers 0.000 description 3
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 210000000214 mouth Anatomy 0.000 description 3
- 230000002188 osteogenic effect Effects 0.000 description 3
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 3
- 239000004926 polymethyl methacrylate Substances 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 description 2
- 208000020084 Bone disease Diseases 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- ZQBZAOZWBKABNC-UHFFFAOYSA-N [P].[Ca] Chemical compound [P].[Ca] ZQBZAOZWBKABNC-UHFFFAOYSA-N 0.000 description 2
- 230000000735 allogeneic effect Effects 0.000 description 2
- 108010045569 atelocollagen Proteins 0.000 description 2
- 230000003416 augmentation Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000000316 bone substitute Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000009193 crawling Effects 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 230000000399 orthopedic effect Effects 0.000 description 2
- 230000002138 osteoinductive effect Effects 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 230000001360 synchronised effect Effects 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 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 description 2
- KJTLQQUUPVSXIM-ZCFIWIBFSA-M (R)-mevalonate Chemical compound OCC[C@](O)(C)CC([O-])=O KJTLQQUUPVSXIM-ZCFIWIBFSA-M 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 108010049931 Bone Morphogenetic Protein 2 Proteins 0.000 description 1
- 208000006386 Bone Resorption Diseases 0.000 description 1
- 102100024506 Bone morphogenetic protein 2 Human genes 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- KJTLQQUUPVSXIM-UHFFFAOYSA-N DL-mevalonic acid Natural products OCCC(O)(C)CC(O)=O KJTLQQUUPVSXIM-UHFFFAOYSA-N 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000020550 Joint related disease Diseases 0.000 description 1
- 206010031252 Osteomyelitis Diseases 0.000 description 1
- 208000008312 Tooth Loss Diseases 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
- 206010047700 Vomiting Diseases 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229940088623 biologically active substance Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000002639 bone cement Substances 0.000 description 1
- 210000002805 bone matrix Anatomy 0.000 description 1
- 230000024279 bone resorption Effects 0.000 description 1
- 230000037118 bone strength Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 239000004568 cement Substances 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000037319 collagen production Effects 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 230000008094 contradictory effect Effects 0.000 description 1
- 238000002316 cosmetic surgery Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000000887 face Anatomy 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000005541 medical transmission Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 238000002324 minimally invasive surgery Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 230000004072 osteoblast differentiation Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000009323 psychological health Effects 0.000 description 1
- 238000002278 reconstructive surgery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000008673 vomiting Effects 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
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L27/446—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with other specific inorganic fillers other than those covered by A61L27/443 or A61L27/46
-
- 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
- A61L27/52—Hydrogels or hydrocolloids
-
- 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
- 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
-
- 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
- A61L2300/204—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
-
- 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
- A61L2300/422—Anti-atherosclerotic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- General Health & Medical Sciences (AREA)
- Dermatology (AREA)
- Veterinary Medicine (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Dispersion Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Materials Engineering (AREA)
- Composite Materials (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Materials For Medical Uses (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention relates to the technical field of bone filling materials, in particular to a mouldable porous biological composite bone filling material containing statin drugs and a preparation method thereof. The preparation method comprises the following steps: (1) The anhydrous calcium sulfate powder and the statin powder are weighed according to a proportion, then the anhydrous calcium sulfate powder and the statin powder are mixed and placed on a mixing plate, and after being mixed repeatedly by a cutter adjusting level at normal temperature, the mixture is mixed repeatedly up and down; wherein, the weight ratio of the anhydrous calcium sulfate powder to the statin powder is 1: 0.005-0.01; (2) Rapidly weighing the end-removed polypeptide collagen gel in proportion at normal temperature, wherein the end-removed polypeptide collagen gel is in a solid jelly shape; the weight ratio of the terminal-removed polypeptide collagen gel to the anhydrous calcium sulfate and statin mixed powder is 1: 2-2: 1, a step of; (3) Placing the weighed end-removed polypeptide collagen gel on a stirring plate, and repeatedly pressing and stirring by a knife at normal temperature to obtain the mouldable porous biological composite bone filling material containing statin drugs.
Description
Technical Field
The invention relates to the technical field of bone filling materials, in particular to a shapable porous biological composite bone filling material and a preparation method thereof.
Background
Bone tissue is one of the most widely distributed and common organs of the human body, and loss of function is one of the main causes of the reduction of quality of life. Currently, massive bone resorption and defects due to severe trauma, infection, bone tumor and other factors are increasingly becoming a significant challenge for clinicians. As the aging population becomes more and more severe, the incidence of bone diseases (e.g., osteoporosis, osteoarthritis, and osteomyelitis) and trauma related injuries caused by primary tumor resection and orthopedic surgery (e.g., total joint replacement and implant fixation) increases, which results in an increasing demand for bone filling and repair materials.
At present, the most main method for treating bone defect is autologous or allogeneic bone grafting, but the problems of lack of a donor, great surgical traumatism, high cost, limitation of the shape of the bone defect part and the like are caused, and great difficulties are brought to patients and clinicians. About 200 tens of thousands of bone grafting procedures for the spine, pelvic and other trunk bones are internationally available each year, however, about 50% of implants, whether autogenous or allograft, are faced with failure for a variety of reasons. High incidence of bone and joint related diseases such as osteoporosis, arthritis, obesity, diabetes, cancer, etc., causes damage to bone tissue, and ultimately affects the health and function of human bones. Therefore, how to reduce the success rate of surgery for patients with bone defects, reduce the economic burden of patients, and improve the life quality of patients is an urgent problem to be solved.
The damage to the patient caused by the oral bone defect is also obvious. Firstly, the teeth of the patient are lost, so that the vomiting, the unclear pronunciation, the soft tissue defect and the eating of the patient are influenced, the appearance of the patient is possibly changed, and finally the psychological and mental burden of the patient is caused. Missing teeth can seriously affect the function and beauty of chewing and auxiliary pronunciation of a patient, and can also affect the health of the oral and jaw system and the psychological health of the patient. Tooth loss has been shown to be a risk factor for obesity, diabetes, cardiovascular disease, part of the tumor types and Alzheimer's disease.
Autologous bone grafting (the grafting of tissue from one location to another in the same patient's body) is the most successful treatment of bone defects, and is also the gold standard. It faces many limitations such as: poor availability of harvested tissue, chronic donor site pain, morbidity and complications, and the like. Moreover, significant injury and pain can occur during additional complex procedures, while bone removal can lead to donor site morbidity. Allogeneic bone (tissue is transplanted from a patient with different genotypes to another patient) and xenograft (tissue is transplanted from a donor of another species) are also one of the more widely used alternative materials in clinic at present, but the application prospect is limited to a certain extent due to the disadvantages of immune-mediated rejection, risk of infectious disease transmission, inability to meet the treatment of massive bone defects and the like.
For the above reasons, the discovery of synthetic materials has opened a new era in the field of bone graft medicine. Such biomaterials are receiving increasing attention for their excellent biocompatibility, absorbability, bone conductivity, plasticity, etc., including polymethyl methacrylate (PMMA), calcium Phosphate Cement (CPC), calcium sulfate (CAS), etc. Especially, the calcium-phosphorus artificial bone biological material can be injected into bone defect positions with various geometric shapes for in-situ shaping and curing due to the advantages of good biocompatibility, in-situ curing, injectability and the like, thereby greatly improving the success rate of the bone defect treatment in clinic. However, with the clinical application and the deep research, problems such as: PMMA has the defects of high polymerization temperature, poor biocompatibility, nondegradability and the like; CPC has the disadvantages of long bone formation time, poor mechanical properties and the like. On the other hand, the material is mostly used for plastic surgery, orthopaedics and the like, and the injectable bone biological material has little application in the oral cavity.
Injectable calcium phosphate and calcium sulfate bone substitutes are the most common calcium-phosphorus biomaterials. The composite material is degraded while providing space and guiding support for the growth of blood vessels and osteoblasts, namely the degradation and absorption process is synchronous with the crawling replacement process of bones, and the bone substitute absorption time is consistent with the clinical healing time of fracture. Especially because of its injectability, it is especially convenient for the treatment of bone defects in the oral cavity. The method is simple to operate, and the risk of infection is reduced by transmucosal injection or minimally invasive fenestration injection, so that the physical and psychological burden of a patient is further reduced.
Calcium sulfate (CAS) has potential for minimally invasive surgery in surgical reconstructive surgery in stomatology, orthopedics, etc., due to its biocompatibility and bone conduction characteristics, and its low price and injectability. Moreover, because it is stiffer and more supportive than CPC, it has become a clinically common replacement for bone defects. CAS has been used as a bone defect filling repair material for centuries, but the purity of CAS is not high due to limitations of the manufacturing process of early CAS, resulting in poor clinical use. However, with the continued development of technology, CAS has been made to exist in an ultra-high purity crystal structure. Studies have shown that CAS has good histocompatibility, does not produce inflammation and irritation to surrounding tissues, and more importantly, CAS has a degradation time of 1-4 months in vivo, which is consistent with the formation time of new bone, which also creates favorable conditions for regeneration of new bone. On the other hand, studies have shown that the CAS osteogenesis mechanism includes two aspects: CAS fills the bone defect, restores bone appearance, prevents soft tissue ingrowth, and provides space and conductive scaffolding for vascular and osteoblast ingrowth while degrading. The CAS degradation and absorption process is synchronous with the crawling replacement process of the bone, and finally continuous bone tissues are formed in the bone grafting area; CAS has osteoinductive activity by locally forming a slightly acidic environment during the degradation and absorption process of CAS, causing the release of osteogenic factors by local decalcification and bone matrix. The CAS forms a high-calcium environment locally during in-vivo degradation, provides a calcium source for new bone formation, and simultaneously can promote osteoblast proliferation and differentiation. Therefore, CAS is an osteogenic material that has bone conductivity, osteoinductive properties, and osteogenic action, is nontoxic, has no immunogenicity, and can be completely biodegraded in a short time.
However, there are also studies showing that CAS has a disadvantage in that it is cured at a high rate to inhibit bone regeneration. Therefore, in order to greatly exploit the advantages of CAS, there is a need to develop a novel composite material that combines other materials.
Statins play a role in stimulating bone regeneration via the mevalonate pathway, they inhibit 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and thereby affect growth factors in osteoblasts, for example: up-regulating BMP-2 and VEGF expression. Research shows that the statin medicine can promote bone healing, form New Bone (NB), strengthen bone strength, increase bone volume, etc. In addition, it has been found that statins promote bone formation around implants when injected systemically or locally. But the effect of statins can only be maintained for 5 days when used alone without an effective Drug Delivery System (DDS). There is also a need for a better drug release material that allows for the stable release of a biologically active substance in vivo over a prolonged period of time.
CN106390192a discloses a biological bone cement, which consists of powder and liquid, wherein the weight percentage of the powder is: 0.1-50% of calcium sulfate; 0.01-10% of hydrophilic biological material; 0.1-50% of acrylic resin; 1.0-30% of developer; initiator 0.001-5%; the liquid comprises the following components in percentage by weight: 10-99% of acrylic monomer; 0.01-5% of promoter; 0-1% of antioxidant. However, the calcium sulfate in the material is not a main material and is only used as an additive; the fracture strength is too high, the application range is that the bone of the body is used, and the bone can not be used for the jawbone of the oral cavity. Moreover, the release temperature of the material during the reaction is at least 48 ℃, and if the material is placed at the bone defect during the reaction, the cell death around the wound is easy to cause; in addition, it has a long curing time.
The atelopeptide collagen has high moisturizing ability and excellent biocompatibility, and is often used as a tissue engineering scaffold for culturing cells. On the other hand, atelocollagen has a positive effect of guiding tissue regeneration, and it can promote osteoblast differentiation and type I collagen production, thereby playing a role in inducing bone regeneration. Thus, the inventors' research team utilized these features to improve and enhance CAS performance using atelocollagen as a solvent to mix with CAS.
In "Injectable Porous Bioresorbable Composite Containing Fluvastatin for Bone Augmentation"(ACS Biomater.Sci.Eng.2019,5,5422-5429), the research team in which the inventors participated adopts calcium sulfate, liquid end-removed polypeptide collagen and fluvastatin, but the test experiment is that the sample is placed at 37 ℃ for 7 days and then is tested. The product has long hardening time, and soft tissue pressure can deform the material during suturing, so that the material treatment effect is reduced, and the possibility of use during operation is reduced.
Therefore, how to improve the above materials is one of the technical problems to be solved in the art.
Disclosure of Invention
Aiming at the problems, the invention aims to provide a mouldable porous biological composite bone filling material containing statin drugs and a preparation method thereof.
In order to solve the technical problems, the application provides the following technical scheme:
a preparation method of a statin-containing shapeable porous biological composite bone filling material comprises the following steps:
(1) The anhydrous calcium sulfate powder and the statin powder are weighed according to a proportion, then the anhydrous calcium sulfate powder and the statin powder are mixed and placed on a mixing plate, and after being mixed repeatedly by a cutter adjusting level at normal temperature, the mixture is mixed repeatedly up and down; wherein, the weight ratio of the anhydrous calcium sulfate powder to the statin powder is 1: 0.005-0.01;
(2) Rapidly weighing the end-removed polypeptide collagen gel in proportion at normal temperature, wherein the end-removed polypeptide collagen gel is in a solid jelly shape; the weight ratio of the terminal-removed polypeptide collagen gel to the anhydrous calcium sulfate and statin mixed powder is 1: 2-2: 1, a step of;
(3) Placing the weighed end-removed polypeptide collagen gel on a stirring plate, and repeatedly pressing and stirring by a knife at normal temperature to obtain the mouldable porous biological composite bone filling material containing statin drugs.
In the step (1), the horizontal repeated mixing is carried out for 20-30s by using a cutter at a speed of 1-3 times/s, and then the vertical repeated mixing is carried out for 20-30s.
Wherein in the step (3), the cutter is repeatedly pressed and stirred for 25-90s at the speed of 0.5-1 times/s.
Wherein the purity of the anhydrous calcium sulfate powder is more than or equal to 99.99 percent.
Wherein the purity of the statin powder is more than or equal to 98 percent.
Wherein, the origin of the polypeptide collagen gel with the end removed is cow or pig, the purity is more than 99 percent, and the fat content is less than 1 percent; the molecular weight is 270-300KD, and the storage temperature is 2-8deg.C.
Wherein the temperature at normal temperature is 18-37 ℃.
Wherein the statin comprises fluvastatin or rosuvastatin.
Compared with the prior art, the statin drug-containing shapable porous biological composite bone filling material and the preparation method thereof have at least the following beneficial effects:
The statin medicine-containing shapable porous biological composite bone filling material can reach the compressive strength of 20Mpa in 1 hour (the actual solidification time is less than 30 minutes, and the test is completed in 30 minutes after solidification), can be hardened (with a certain supporting property) in a very short time when being applied to clinical treatment and placed at a bone defect, so that the soft tissue pressure can not deform the material when being sutured, the material treatment effect is improved, and the possibility of using the material during operation is greatly improved.
The prolonged operation time and the curing speed of the material are relatively contradictory properties, and the material of the invention well solves the contradiction. The material increases the operation time in the process of filling the bone defect part, and shortens the self-curing time after the filling operation is finished.
The statin medicine-containing shapable porous biological composite bone filling material has the characteristics of shapable property, absorbability, porous carrying property, prolonged operation time, shortened material curing speed, improved bone formation level and the like, and can play a role in guiding bone regeneration well.
The following describes the statin-containing plastic porous biological composite bone filling material and the preparation method thereof with reference to the accompanying drawings.
Drawings
FIG. 1 is a photograph showing the process of formulating a statin-containing moldable porous biocomposite bone filler material; wherein A: schematic diagram before material mixing; b: schematic of the gel of the polypeptide collagen with the end removed before mixing; c: schematic of the morphology of the mixed materials; d: material filling to a circular glass mold schematic;
FIG. 2 is a photograph showing the temperature of the process of compounding a statin-containing moldable porous biocomposite bone filler material; wherein A: measuring the temperature at the beginning of material mixing; b: measuring the highest temperature in the mixing process of materials; c: measuring the temperature when the material is not solidified; d: measuring the temperature of the solidified material; e: measuring the temperature after the material is solidified for 1 hour;
FIG. 3 is a photograph of a compressive strength test;
FIG. 4 is a statistical graph of the experimental results of examples 1-10.
Detailed Description
Example 1
Referring to fig. 1-2, a method for preparing a fluvastatin-containing shapable porous biological composite bone filler material comprises the following steps:
(1) The anhydrous calcium sulfate powder and the fluvastatin powder are weighed according to the proportion, then the anhydrous calcium sulfate powder and the fluvastatin powder are mixed and placed on a mixing plate, a stainless steel knife is used for mixing for 20-30s at the speed of 1-3 times per second at the normal temperature (18-37 ℃), and then the mixture is mixed up and down repeatedly for 20-30s. Wherein, the weight ratio of the anhydrous calcium sulfate powder (the purity is more than or equal to 99.99%) to the fluvastatin powder (the purity is more than or equal to 98%) is 1:0.005;
(2) Rapidly weighing the end-removed polypeptide collagen gel in proportion at normal temperature (18-37 ℃), wherein the end-removed polypeptide collagen gel is in a solid jelly shape; the weight ratio of the terminal polypeptide collagen gel to the anhydrous calcium sulfate and fluvastatin mixed powder is 1:1, a step of;
(3) Placing the weighed end-removed polypeptide collagen gel on a stirring plate, repeatedly pressing and stirring at a speed of 0.5-1 time/s for 25-90s by using a stainless steel knife at normal temperature to obtain the fluvastatin-containing mouldable porous biological composite bone filling material, namely filling the bone defect part.
Wherein the source of the polypeptide collagen gel is cow or pig, the purity is more than 99%, the fat content is less than 1%, the molecular weight is 270-300KD, and the storage temperature is 2-8deg.C.
Example 2
Compared with example 1, the difference is that: the weight ratio of the terminal-removed polypeptide collagen gel to the anhydrous calcium sulfate and fluvastatin mixed powder is 3:2.
Example 3
Compared with example 1, the difference is that: the weight ratio of the terminal-removed polypeptide collagen gel to the anhydrous calcium sulfate and fluvastatin mixed powder is 2:1.
Example 4
Compared with example 1, the difference is that: the weight ratio of the terminal-removed polypeptide collagen gel to the anhydrous calcium sulfate and fluvastatin mixed powder is 2:3.
Example 5
Compared with example 1, the difference is that: the weight ratio of the terminal-removed polypeptide collagen gel to the anhydrous calcium sulfate and fluvastatin mixed powder is 1:2.
Example 6
Compared with example 1, the difference is that: the weight ratio of the anhydrous calcium sulfate powder (the purity is more than or equal to 99.99%) to the fluvastatin powder (the purity is more than or equal to 98%) is 1:0.01.
Example 7
Compared with example 1, the difference is that: the weight ratio of the anhydrous calcium sulfate powder (the purity is more than or equal to 99.99%) to the fluvastatin powder (the purity is more than or equal to 98%) is 1:0.01; the weight ratio of the terminal-removed polypeptide collagen gel to the anhydrous calcium sulfate and fluvastatin mixed powder is 3:2.
Example 8
Compared with example 1, the difference is that: the weight ratio of the anhydrous calcium sulfate powder (the purity is more than or equal to 99.99%) to the fluvastatin powder (the purity is more than or equal to 98%) is 1:0.01; the weight ratio of the terminal-removed polypeptide collagen gel to the anhydrous calcium sulfate and fluvastatin mixed powder is 2:1.
Example 9
Compared with example 1, the difference is that: the weight ratio of the anhydrous calcium sulfate powder (the purity is more than or equal to 99.99%) to the fluvastatin powder (the purity is more than or equal to 98%) is 1:0.01; the weight ratio of the terminal-removed polypeptide collagen gel to the anhydrous calcium sulfate and fluvastatin mixed powder is 2:3.
Example 10
Compared with example 1, the difference is that: the weight ratio of the anhydrous calcium sulfate powder (the purity is more than or equal to 99.99%) to the fluvastatin powder (the purity is more than or equal to 98%) is 1:0.01; the weight ratio of the terminal-removed polypeptide collagen gel to the anhydrous calcium sulfate and fluvastatin mixed powder is 1:2.
The shapeable time, setting time, average temperature, maximum temperature, compressive strength (measurement completed within 30 minutes after setting) and new bone formation rate of examples 1 to 10 were tested, the compressive strength test is shown in fig. 3, and the results are shown in fig. 4 and table 1.
TABLE 1
Note that: CAS: anhydrous calcium sulfate; FS: fluvastatin; ACG: an end-removed polypeptide collagen gel.
Compared with the product in "Injectable Porous Bioresorbable Composite Containing Fluvastatin for Bone Augmentation"(ACS Biomater.Sci.Eng.2019,5,5422-5429) of the inventor, the solidification time of the product prepared by the invention is greatly shortened, and other indexes are improved to different degrees.
Anhydrous calcium sulfate was identified in 2019: the optimal result is 3:2, but the setting time still needs 34 minutes, and researches show that the setting time is most suitable in clinical treatment. Other proportions, although short in setting time, have poor physical properties and cannot be used. In oral clinical treatment, the operation time should not be too long, so the setting time of the material should not be too long. If the bone filler material is used to suture the wound before it is not coagulated, the material is easily deformed by external conditions such as soft tissue, resulting in an unsatisfactory therapeutic effect. In the experiment of the invention, the solidification time is greatly shortened under the condition that the performance precursors of other aspects of the material are not influenced, and in the optimal scheme (the proportion of 1:1 of the embodiment 1), the solidification time is shortened to about 11 minutes. The mechanism of analysis is roughly: the gel is susceptible to cations and the gel strength increases with increasing cation concentration over a range. When the gel contacts Ca 2+, ca 2+ induces a good uniform network structure, and Ca 2+ can reduce repulsive force among macromolecules in the gel, so that the interior of the gel is kinked and wound to form the network structure, and anhydrous calcium sulfate particles are better wrapped, so that the two react faster and more uniformly, and the two react mutually to improve the material performance.
In addition, in order to achieve the desired effect, the in vitro experiments in 2019 publication were performed after the materials were synthesized and left to stand at 37℃for 7 days (see, e.g., 2.3.1, 2.3.2, and 2.4, respectively, for example, 2.3.1, for "7 days in a 37℃vacuum oven", 2.3.2, respectively, for mechanical properties (i.e., compressive strength) for "cylindrical test specimen made as described above", and 2.2, for "mold was placed in a 37℃vacuum oven", for which the solidification conditions were more stringent and complicated than the present invention.
The above examples are only illustrative of the preferred embodiments of the present invention and are not intended to limit the scope of the present invention, and various modifications and improvements made by those skilled in the art to the technical solution of the present invention should fall within the scope of protection defined by the claims of the present invention without departing from the spirit of the present invention.
Claims (3)
1. The preparation method of the statin-containing shapeable porous biological composite bone filling material is characterized by comprising the following steps:
(1) Weighing anhydrous calcium sulfate powder and statin powder according to a proportion, mixing the anhydrous calcium sulfate powder and the statin powder, placing the mixture on a mixing plate, mixing the mixture horizontally and repeatedly at a speed of 1-3 times/s at normal temperature for 20-30s, and mixing the mixture vertically and repeatedly for 20-30s; wherein, the weight ratio of the anhydrous calcium sulfate powder to the statin powder is 1: 0.005-0.01; the statin comprises fluvastatin or rosuvastatin; the purity of the anhydrous calcium sulfate powder is more than or equal to 99.99 percent; the purity of the statin powder is more than or equal to 98%;
(2) Rapidly weighing the end-removed polypeptide collagen gel in proportion at normal temperature, wherein the end-removed polypeptide collagen gel is in a solid jelly shape; the weight ratio of the terminal-removed polypeptide collagen gel to the anhydrous calcium sulfate and statin mixed powder is 1: 2-2: 1, a step of; the source of the terminal-removed polypeptide collagen gel is cattle or pigs, the purity is more than 99%, and the fat content is less than 1%; the molecular weight of the polypeptide collagen gel with the end removed is 270-300KD, and the storage temperature is 2-8 ℃;
(3) Placing the weighed end-removed polypeptide collagen gel on a stirring plate, repeatedly pressing and stirring at a speed of 0.5-1 time/s for 25-90s by a knife at normal temperature to obtain the statin-containing mouldable porous biological composite bone filling material; the setting time of the material is less than 30 minutes.
2. The method for preparing the statin-containing shapable porous biological composite bone filler material according to claim 1, wherein the method comprises the following steps: the temperature at the normal temperature is 18-37 ℃.
3. The moldable porous biocomposite bone filler material containing statin prepared by the preparation method of claim 1 or 2.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310521156.3A CN116370715B (en) | 2023-05-10 | 2023-05-10 | Shapable porous biological composite bone filling material containing statin drugs and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310521156.3A CN116370715B (en) | 2023-05-10 | 2023-05-10 | Shapable porous biological composite bone filling material containing statin drugs and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN116370715A CN116370715A (en) | 2023-07-04 |
| CN116370715B true CN116370715B (en) | 2024-05-17 |
Family
ID=86965869
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310521156.3A Active CN116370715B (en) | 2023-05-10 | 2023-05-10 | Shapable porous biological composite bone filling material containing statin drugs and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116370715B (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5273964A (en) * | 1985-03-20 | 1993-12-28 | Lemons J E | Inorganic and organic composition for treatment of bone lesions |
| KR20130141846A (en) * | 2012-06-18 | 2013-12-27 | 주식회사 본셀바이오텍 | Composition comprising atelocollagen-coated bone powder for reproduction of bone and method for preparing the same |
| WO2019048697A1 (en) * | 2017-09-11 | 2019-03-14 | Bone Support Ab | Macro- and microporous composite cryogel biomaterial for use in bone regeneration |
| CN113384746A (en) * | 2021-07-21 | 2021-09-14 | 中国人民解放军总医院 | Bone cement composite material and preparation method thereof |
| CN115109069A (en) * | 2022-07-07 | 2022-09-27 | 首都医科大学 | Stereospecific synthesis method of acetyldihydroartemisinin and application of acetyldihydroartemisinin in resisting atherosclerosis |
| CN115177785A (en) * | 2022-06-16 | 2022-10-14 | 贵阳福尔康医疗器材有限公司 | Bone defect repair material and preparation method and application thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020072804A1 (en) * | 2000-09-20 | 2002-06-13 | Donda Russell S. | Combination biological-non-biological material prosthetic implant and method |
| AU2003237185A1 (en) * | 2002-05-07 | 2003-11-11 | The Research Foundation Of State University Of New York | A method to rapidly prepare and screen formulations and compositions containing same |
| US9107983B2 (en) * | 2010-10-27 | 2015-08-18 | Warsaw Orthopedic, Inc. | Osteoconductive matrices comprising statins |
| WO2015031882A1 (en) * | 2013-09-02 | 2015-03-05 | Muffin Incorporated | Products comprising an extracellular matrix tissue material and osteogenic protein |
-
2023
- 2023-05-10 CN CN202310521156.3A patent/CN116370715B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5273964A (en) * | 1985-03-20 | 1993-12-28 | Lemons J E | Inorganic and organic composition for treatment of bone lesions |
| KR20130141846A (en) * | 2012-06-18 | 2013-12-27 | 주식회사 본셀바이오텍 | Composition comprising atelocollagen-coated bone powder for reproduction of bone and method for preparing the same |
| WO2019048697A1 (en) * | 2017-09-11 | 2019-03-14 | Bone Support Ab | Macro- and microporous composite cryogel biomaterial for use in bone regeneration |
| CN113384746A (en) * | 2021-07-21 | 2021-09-14 | 中国人民解放军总医院 | Bone cement composite material and preparation method thereof |
| CN115177785A (en) * | 2022-06-16 | 2022-10-14 | 贵阳福尔康医疗器材有限公司 | Bone defect repair material and preparation method and application thereof |
| CN115109069A (en) * | 2022-07-07 | 2022-09-27 | 首都医科大学 | Stereospecific synthesis method of acetyldihydroartemisinin and application of acetyldihydroartemisinin in resisting atherosclerosis |
Non-Patent Citations (3)
| Title |
|---|
| effect of pore size in bone regeneration using polydopamine laced hydroxyapatite collagen calcium silicate scaffolds fabricated by 3d mould printing technology;dong joon lee et al;《orthod craniofac res》;20190510;全文 * |
| Injectable Porous Bioresorbable Composite Containing Fluvastatin for Bone Augmentation;tianren zhou et al;《ACS biomaterials science and engineering》;摘要、介绍和第2.2-2.3小节 * |
| 辛伐他汀组织工程骨材料的制备及性能研究;梁军;曹红彬;辛景义;;天津医药;20120815(08);全文 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN116370715A (en) | 2023-07-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6139578A (en) | Preparation of cell seeded ceramic compositions | |
| JP6851377B2 (en) | Bioactive polymer for bone regeneration | |
| CN1414868A (en) | Bioactive and osteoprorotic bone cement | |
| JP5319524B2 (en) | Use of gelatin and a cross-linking agent to produce a cross-linking therapeutic composition | |
| US8231909B2 (en) | Injectable composite material suitable for use as a bone substitute | |
| JP4002299B2 (en) | Improved hydrogel for tissue treatment | |
| CN112023120A (en) | Injectable pre-filled bone repair particle and preparation method and application thereof | |
| Saitoh et al. | Effect of polylactic acid on osteoinduction of demineralized bone: preliminary study of the usefulness of polylactic acid as a carrier of bone morphogenetic protein | |
| AU2007200685B2 (en) | Granulate-Matrix | |
| CN111973797B (en) | Non-invasive implantation high-viscosity adhesive material for orthopedics department and preparation method and application thereof | |
| Mansouri et al. | The role of cuttlebone and cuttlebone derived hydroxyapatite with platelet rich plasma on tibial bone defect healing in rabbit: An experimental study | |
| CN116370715B (en) | Shapable porous biological composite bone filling material containing statin drugs and preparation method thereof | |
| JP3860417B2 (en) | Transplant prosthesis with long-term stability | |
| RU2009134037A (en) | FORMABLE, BIOODEGRADABLE MATERIAL | |
| JPWO2004105825A1 (en) | Biomaterial for bone formation, formulation for injection containing the material, kit for preparing the material, and bone formation method using them | |
| CN112933294A (en) | Plastic bone cement regeneration and repair material | |
| Gut et al. | In vitro and in vivo (rabbit, guinea pig, mouse) properties of a novel resorbable polymer and allogenic bone composite for guided bone regeneration and orthopedic implants | |
| CN116354632B (en) | Magnesium phosphate bone cement for providing microenvironment for promoting bone regeneration and preparation method thereof | |
| MX2014012728A (en) | Self-hardening bioactive cement compositions with partially deacetylated chitin as bone graft substitutes. | |
| Ezz et al. | Histological assessment of injectable macro-porous calcium phosphate cement (CPC) versus autogenous bone graft on healing of osseous defect (experimental animal study) | |
| CN115006609A (en) | Degradable material suitable for pre-operation preparation of fracture internal fixation and preparation method and application thereof | |
| CN116251235A (en) | Porous bone guiding/inducing self-solidifying calcium phosphate composite material and preparation method thereof | |
| CN114209879A (en) | Composite bone cement material and preparation method thereof | |
| Giacomin et al. | Socket Preservation using Human Recombinant Growth Hormone Associated with Bio-Oss® Biomaterial with the Purpose of Improving Healing and Reducing Treatment Time-A Case Report | |
| CN118286522A (en) | Absorbable internal fixation material for fracture repair and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |