CN117442774A - Injectable silicon-phosphorus-calcium-based dental paste with high osteogenesis activity and preparation method and application thereof - Google Patents
Injectable silicon-phosphorus-calcium-based dental paste with high osteogenesis activity and preparation method and application thereof Download PDFInfo
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- CN117442774A CN117442774A CN202311383181.6A CN202311383181A CN117442774A CN 117442774 A CN117442774 A CN 117442774A CN 202311383181 A CN202311383181 A CN 202311383181A CN 117442774 A CN117442774 A CN 117442774A
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- injectable
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- dental paste
- calcium
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- BXYHXVIURNMBJM-UHFFFAOYSA-N [P].[Si].[Ca] Chemical compound [P].[Si].[Ca] BXYHXVIURNMBJM-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 230000000694 effects Effects 0.000 title claims abstract description 16
- 230000011164 ossification Effects 0.000 title claims abstract description 10
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 239000000843 powder Substances 0.000 claims abstract description 71
- 239000000463 material Substances 0.000 claims abstract description 46
- 239000007790 solid phase Substances 0.000 claims abstract description 37
- 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 abstract description 32
- 239000007788 liquid Substances 0.000 claims abstract description 25
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims abstract description 23
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims abstract description 23
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims abstract description 23
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims abstract description 23
- 238000002156 mixing Methods 0.000 claims abstract description 15
- 238000011049 filling Methods 0.000 claims abstract description 10
- 239000007864 aqueous solution Substances 0.000 claims abstract description 5
- BCAARMUWIRURQS-UHFFFAOYSA-N dicalcium;oxocalcium;silicate Chemical compound [Ca+2].[Ca+2].[Ca]=O.[O-][Si]([O-])([O-])[O-] BCAARMUWIRURQS-UHFFFAOYSA-N 0.000 claims description 21
- 229910021534 tricalcium silicate Inorganic materials 0.000 claims description 21
- 235000019976 tricalcium silicate Nutrition 0.000 claims description 21
- 239000007791 liquid phase Substances 0.000 claims description 18
- 239000002245 particle Substances 0.000 claims description 17
- 230000002188 osteogenic effect Effects 0.000 claims description 16
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 239000000243 solution Substances 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 7
- 238000011065 in-situ storage Methods 0.000 abstract description 2
- 229910052588 hydroxylapatite Inorganic materials 0.000 abstract 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 abstract 1
- 230000000052 comparative effect Effects 0.000 description 15
- OSMSIOKMMFKNIL-UHFFFAOYSA-N calcium;silicon Chemical compound [Ca]=[Si] OSMSIOKMMFKNIL-UHFFFAOYSA-N 0.000 description 11
- 210000004262 dental pulp cavity Anatomy 0.000 description 10
- 239000008367 deionised water Substances 0.000 description 9
- 229910021641 deionized water Inorganic materials 0.000 description 9
- 238000002347 injection Methods 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 210000000988 bone and bone Anatomy 0.000 description 8
- 239000011575 calcium Substances 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 230000014509 gene expression Effects 0.000 description 8
- 229910052586 apatite Inorganic materials 0.000 description 7
- 229910052918 calcium silicate Inorganic materials 0.000 description 7
- 239000000378 calcium silicate Substances 0.000 description 7
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 7
- 238000004090 dissolution Methods 0.000 description 7
- VSIIXMUUUJUKCM-UHFFFAOYSA-D pentacalcium;fluoride;triphosphate Chemical compound [F-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O VSIIXMUUUJUKCM-UHFFFAOYSA-D 0.000 description 7
- 210000000963 osteoblast Anatomy 0.000 description 6
- 239000002002 slurry Substances 0.000 description 6
- 238000002791 soaking Methods 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- 238000005303 weighing Methods 0.000 description 6
- 239000001506 calcium phosphate Substances 0.000 description 5
- 229910000389 calcium phosphate Inorganic materials 0.000 description 5
- 235000011010 calcium phosphates Nutrition 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000002131 composite material Substances 0.000 description 5
- 210000003074 dental pulp Anatomy 0.000 description 5
- 239000012890 simulated body fluid Substances 0.000 description 5
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 4
- 230000033558 biomineral tissue development Effects 0.000 description 4
- 230000007547 defect Effects 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- CBOCVOKPQGJKKJ-UHFFFAOYSA-L Calcium formate Chemical compound [Ca+2].[O-]C=O.[O-]C=O CBOCVOKPQGJKKJ-UHFFFAOYSA-L 0.000 description 3
- 229920002752 Konjac Polymers 0.000 description 3
- 230000004888 barrier function Effects 0.000 description 3
- 230000000975 bioactive effect Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229940044172 calcium formate Drugs 0.000 description 3
- 235000019255 calcium formate Nutrition 0.000 description 3
- 239000004281 calcium formate Substances 0.000 description 3
- 208000019786 dental pulp disease Diseases 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000006703 hydration reaction Methods 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 238000004626 scanning electron microscopy Methods 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229920001661 Chitosan Polymers 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 108010087230 Sincalide Proteins 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000003462 bioceramic Substances 0.000 description 2
- 238000010609 cell counting kit-8 assay Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 230000036571 hydration Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000000252 konjac Substances 0.000 description 2
- 235000019823 konjac gum Nutrition 0.000 description 2
- 238000002386 leaching Methods 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 230000002787 reinforcement Effects 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 2
- 238000007711 solidification Methods 0.000 description 2
- 230000008023 solidification Effects 0.000 description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- 101150080498 ALP gene Proteins 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000024216 Periapical disease Diseases 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000002639 bone cement Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000005548 dental material Substances 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000002542 deteriorative effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 108010025899 gelatin film Proteins 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000001879 gelation Methods 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 235000010485 konjac Nutrition 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- GVALZJMUIHGIMD-UHFFFAOYSA-H magnesium phosphate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GVALZJMUIHGIMD-UHFFFAOYSA-H 0.000 description 1
- 239000004137 magnesium phosphate Substances 0.000 description 1
- 229910000157 magnesium phosphate Inorganic materials 0.000 description 1
- 229960002261 magnesium phosphate Drugs 0.000 description 1
- 235000010994 magnesium phosphates Nutrition 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229940111688 monobasic potassium phosphate Drugs 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 239000006259 organic additive Substances 0.000 description 1
- 230000002138 osteoinductive effect Effects 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 230000003239 periodontal effect Effects 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 235000019353 potassium silicate Nutrition 0.000 description 1
- 238000011085 pressure filtration Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000000250 revascularization Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- NTHWMYGWWRZVTN-UHFFFAOYSA-N sodium silicate Chemical compound [Na+].[Na+].[O-][Si]([O-])=O NTHWMYGWWRZVTN-UHFFFAOYSA-N 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 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
- A61L27/02—Inorganic materials
- A61L27/025—Other specific inorganic materials not covered by A61L27/04 - A61L27/12
-
- 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
- A61L27/14—Macromolecular materials
- A61L27/20—Polysaccharides
-
- 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
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
-
- 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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
-
- 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
- A61L2430/12—Materials or treatment for tissue regeneration for dental implants or prostheses
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Dental Preparations (AREA)
Abstract
The invention discloses an injectable silicon-phosphorus-calcium-based dental paste with high osteogenesis activity and a preparation method and application thereof, belonging to the field of biomedical materials. The dental paste is prepared by mixing solid phase powder and curing liquid; the solid phase powder at least comprises alpha-tricalcium phosphate; the solidifying liquid at least comprises an aqueous solution of hydroxypropyl methyl cellulose. The dental paste prepared by the invention is easy to inject, can be cured in situ by itself, has excellent anti-collapsibility and osteogenesis activity, can induce bone-like hydroxyapatite to deposit, and can be used for preparing dental filling repair materials.
Description
Technical Field
The invention belongs to the technical field of biomedical materials, and particularly relates to an injectable silicon-phosphorus-calcium-based dental paste with high osteogenesis activity, and a preparation method and application thereof.
Background
Dental pulp diseases and periapical diseases are common and multiple diseases of the oral cavity. According to the periapical lesion of the dental pulp of a patient, the clinical treatment method of the dental pulp disease mainly comprises pulp capping operation, pulp chamber bottom and root canal perforation repair, root canal treatment operation, root tip induction forming operation, root tip barrier operation, root canal filling, blood circulation reconstruction and the like. The factors determining the therapeutic effect of dental pulp diseases are numerous, and dental filling restoration materials are the most critical step. The silicon-calcium-based bioceramic paste is a material with better comprehensive performance in the field of dental pulp at present, and the mineral trioxide aggregate (MTA, mineral Trioxide Aggregate) is the first silicon-calcium-based bioceramic material entering clinical application, and has excellent bioactivity, biocompatibility, bone-like apatite mineralization capacity, sealing capacity, certain antibacterial performance and the like.
However, the MTA materials of the initial version have disadvantages such as poor operability, difficulty in injection, poor anti-collapsibility, insufficient curing properties, and susceptibility to discoloration of the tooth. Early MTA formulations had a strong gritty feel, were difficult to modulate, and were difficult to deliver into the long and narrow curved root canal. In addition, MTA slurries are prone to free particle collapse in aqueous environments, e.g., in revascularization, MTA slurries are often placed on blood clots to seal the root canal and induce dental pulp mineralization. However, the unset paste collapses upon contact with fresh blood clot, which can lead to micro-leakage of free paste particles and potential inflammatory reactions. The curing time of MTA is as long as about 4 hours, and the overlong curing time not only prolongs the treatment time and increases additional operation procedures, but also can improve the slurry collapse and displacement risks.
Researchers have accelerated the hydration of calcium silicate-based materials by doping with inorganic salts (e.g., calcium chloride and calcium carbonate, etc.) to shorten their cure time. In addition, by using organic gelling agents such as sodium alginate, chitosan, gelatin and the like, the anti-collapsibility and the operation characteristics of the silicon-calcium-based paste can be effectively improved, after the organic additive is introduced, an organic gel film can be formed on the surfaces of paste particles, the erosion of external moisture can be effectively resisted, the organic matters have good rheological property and gelling property, and the binding capacity and the flowability of the paste particles can be enhanced. However, the organic matters adhering to the surfaces of the paste particles inevitably hinder the hydration reaction of the calcium silicate-based material, thereby deteriorating the solidification performance thereof. At present, the field mainly uses an organic-inorganic composite strengthening strategy to solve the defects of the method.
CN202111263723.7 discloses an anti-collapsibility silicon-calcium-based root canal filling paste, a preparation method and application thereof, wherein the root canal filling paste takes a silicon-calcium-based compound and calcium formate as solid phases, and a konjac gum solution as a liquid phase, wherein the hydration acceleration effect of the calcium formate and the konjac gum binding effect effectively improve the anti-collapsibility and the solidification characteristic of the silicon-calcium-based material. However, calcium formate itself has no gelling property and cannot be cured by itself, and in addition, konjak gum can form a liquid phase with high viscosity at a lower concentration, and mixing and stirring of the solid phase and the liquid phase are difficult at a slightly higher concentration.
In addition, CN200710047442.1 discloses an in-situ self-curing bioactive material for filling human bone defect and a preparation method thereof, wherein the material takes calcium phosphate and tricalcium silicate as composite powder to prepare the bone repair material with self-curing property, although the solid phase powder of the material relates to calcium phosphate with self-curing gelation property, the calcium phosphate is a complex system with various curing properties, and the curing mechanism and curing behavior of different component combinations are greatly different. In addition, the material is not related to solving the problem of insufficient anti-collapsibility of the calcium silicate-based material.
CN103007340a discloses a self-curing composite bone repairing material for repairing hard tissue of human body and its application, said bone repairing material contains solid phase of tricalcium silicate and calcium phosphate bone cement, and several inorganic substances of monobasic potassium phosphate and magnesium oxide, and its liquid phase contains potassium citrate and chitosan. Although the bone repair material has a short curing time, because the material contains various gelling systems with curing characteristics such as a calcium silicate base, a calcium phosphate, a magnesium phosphate and the like, and the binding performance of organic matters in a liquid phase is insufficient, the material has poor collapsibility, injection performance and operation performance.
When used in root tip induction forming, root tip barrier, root canal filling and other treatments, the dental material with excellent osteogenesis inducing property is favorable for eliminating inflammation of periapical and periodontal membrane, stimulating cementation of root tip, promoting the continuous growth and development of root, and promoting regeneration of bone defect parts such as alveolar bone. For these reasons, there is a strong need in the art of dental pulp therapy to develop a calcium silicate-based bioactive paste material that has good solidifying properties, is injectable, is resistant to collapsibility, and has high osteogenic activity.
However, there has been no report so far on the synergistic use of α -tricalcium phosphate type self-curing material with hydroxypropyl methylcellulose to improve the handleability, collapsibility and osteogenic activity of the calcium silicate-based paste.
Disclosure of Invention
The invention aims to: the invention aims at overcoming the defects of the prior art and providing an injectable silicon-phosphorus-calcium-based dental paste with high osteogenic activity, and a preparation method and application thereof. The dental paste provided by the invention can solve the problems of insufficient operability, poor collapsibility and the like of the traditional silicon-calcium-based material, and can improve the osteoinductive capacity of the dental paste.
The technical scheme is as follows: the aim of the invention is achieved by the following technical scheme:
the invention provides an injectable silicon-phosphorus-calcium-based dental paste with high osteogenic activity, which is prepared by mixing solid phase powder and curing liquid; the solid phase powder at least comprises alpha-tricalcium phosphate; the solidifying liquid at least comprises an aqueous solution of hydroxypropyl methyl cellulose.
The invention uses the alpha-tricalcium phosphate self-curing paste to cooperate with the hydroxypropyl methylcellulose to form an organic-inorganic composite reinforcement body for the first time, improves the hardening dynamics of the silicon-calcium-based material through the alpha-tricalcium phosphate self-curing paste, accelerates the curing reaction of the paste, and simultaneously improves the operation performance and the collapsibility resistance of the silicon-calcium-based material through the hydroxypropyl methylcellulose to strengthen the cohesion among paste particles.
In a preferred embodiment of the present invention, the dental paste is prepared by mixing a curing liquid and a solid phase powder at a ratio of 0.4 to 0.65 g/g.
Preferably, the solid phase powder comprises tricalcium silicate and alpha tricalcium phosphate.
Further preferably, the tricalcium silicate has a powder particle size of 0.1 to 10 μm. Under the grain size range, the tricalcium silicate has good fineness and good blending operation characteristic.
Further, in the solid phase powder, the weight percentage of tricalcium silicate is 50-90%, the weight percentage of alpha-tricalcium phosphate is 10-50%, and the sum of the weight percentages is 100%.
Preferably, the solidifying liquid is an aqueous solution containing disodium hydrogen phosphate and hydroxypropyl methylcellulose.
Further, in the curing liquid, the weight percentage of disodium hydrogen phosphate is 1-5%, and the weight percentage of hydroxypropyl methylcellulose is 0.5-3%.
The invention also provides a preparation method of the injectable silicon-phosphorus-calcium-based dental paste, which comprises the following steps:
(1) Uniformly mixing tricalcium silicate powder and alpha-tricalcium phosphate powder to obtain solid phase powder;
(2) Adding hydroxypropyl methyl cellulose powder into water to be fully dissolved to obtain a uniform liquid phase, and then dissolving disodium hydrogen phosphate powder into the liquid phase to obtain a curing liquid;
(3) The obtained curing liquid and solid phase powder are uniformly mixed according to a proportion, and the injectable silicon-phosphorus-calcium-based dental paste with high osteogenesis activity is obtained.
The invention also provides application of the injectable silicon-phosphorus-calcium-based dental paste in preparing dental filling restoration materials. The injectable silicon-phosphorus-calcium-based dental paste provided by the invention can be applied to the dental pulp science treatment fields such as root tip barrier surgery, root tip filling, root tip induction forming surgery, root canal treatment, medullary canal covering surgery and the like.
The beneficial effects are that:
1. the invention uses the alpha-tricalcium phosphate self-curing paste to cooperate with the hydroxypropyl methylcellulose to form an organic-inorganic composite reinforcement body for the first time, improves the hardening dynamics of the silicon-calcium-based material through the alpha-tricalcium phosphate self-curing paste, accelerates the curing reaction of the paste, and simultaneously improves the operation performance and the collapsibility resistance of the silicon-calcium-based material through the hydroxypropyl methylcellulose to strengthen the cohesion among paste particles.
2. After the alpha-tricalcium phosphate self-curing system is introduced, the invention can effectively enhance the expression of the osteogenesis related genes of the calcium silicate-based material, and improve the paste biocompatibility and the bone promoting capacity.
3. The silicon-phosphorus-calcium-based bioactive paste has excellent bone-like apatite mineralization capability, can promote rapid deposition of apatite crystals, is tightly attached to a tooth body, and has excellent sealing performance. In addition, the paste has strong alkali forming ability and antibacterial property.
4. The invention can prepare the injectable dental paste material with adjustable flow property by reasonably proportioning the solid phase powder and the curing liquid, and can meet the use requirements of different clinical application.
Drawings
FIG. 1 is a graph showing the results of injection force of injectable SiP-Ca-based dental paste with high osteogenic activity prepared in accordance with the examples of the present invention;
FIG. 2 is an anti-collapsibility photograph of the injectable SiP-Ca-based dental pastes having high osteogenic activity prepared in comparative examples 1 and 2 and examples 1-3 according to the present invention;
FIG. 3 is an anti-collapsibility photograph of the injectable SiP-Ca-based dental pastes having high osteogenic activity prepared in examples 4-6 according to the present invention after shaking;
FIG. 4 is a graph showing the set time results of injectable SiP-Ca-based dental pastes with high osteogenic activity prepared in accordance with the examples of this invention;
FIG. 5 is a graph showing the results of the alkali forming ability of the injectable SiP-Ca-based dental paste with high osteogenic activity prepared in accordance with the examples of the present invention;
FIG. 6 shows the results of the cell activity of the injectable SiP-Ca-based dental paste with high osteogenic activity prepared in the example of the present invention;
FIG. 7 shows the ALP gene expression results on osteoblasts of the injectable SiP-Ca-based dental paste having high osteogenic activity prepared in the example of the present invention;
FIG. 8 shows the OPN gene expression results of injectable SiP-Ca-based dental paste with high osteogenic activity on osteoblasts prepared in accordance with the example of the present invention;
fig. 9 is an SEM photograph of the surface of the injectable silicon phosphorus calcium-based dental paste having high osteogenic activity prepared in example 1 according to the present invention after SBF soaking.
Detailed Description
The technical scheme of the present invention is described in detail below through specific examples, but the scope of the present invention is not limited to the examples.
The specific techniques or conditions are not identified in the examples and are described in the literature in this field or are carried out in accordance with the product specifications. The reagents or equipment used were conventional products available for purchase through regular channels, with no manufacturer noted.
The experimental methods in the following examples are conventional methods unless otherwise specified. The test materials used in the examples below, unless otherwise specified, are commercially available products, wherein tricalcium silicate powder and alpha-tricalcium phosphate powder are purchased from Kunshan advanced technology. The particle size of the tricalcium silicate powder is 0.1-10 mu m.
Example 1
Weighing 90% by weight of tricalcium silicate powder and 10% by weight of alpha-tricalcium phosphate powder, and uniformly mixing to obtain solid phase powder; 0.6g of hydroxypropyl methylcellulose is dissolved in 18.9g of deionized water, and after the dissolution is completed, 0.5g of disodium hydrogen phosphate powder is added and stirred sufficiently to form a uniform liquid phase.
And fully and uniformly stirring the curing liquid and the solid phase powder according to the proportion of 0.5g/g to prepare the dental paste material.
Example 2
Weighing 70% by weight of tricalcium silicate powder and 30% by weight of alpha-tricalcium phosphate powder, and uniformly mixing to obtain solid phase powder; 0.6g of hydroxypropyl methylcellulose is dissolved in 18.9g of deionized water, and after the dissolution is completed, 0.5g of disodium hydrogen phosphate powder is added and stirred sufficiently to form a uniform liquid phase.
And fully and uniformly stirring the curing liquid and the solid phase powder according to the proportion of 0.5g/g to prepare the dental paste material.
Example 3
Weighing 50% by weight of tricalcium silicate powder and 50% by weight of alpha-tricalcium phosphate powder, and uniformly mixing to obtain solid phase powder; 0.6g of hydroxypropyl methylcellulose is dissolved in 18.9g of deionized water, and after the dissolution is completed, 0.5g of disodium hydrogen phosphate powder is added and stirred sufficiently to form a uniform liquid phase.
And fully and uniformly stirring the curing liquid and the solid phase powder according to the proportion of 0.5g/g to prepare the dental paste material.
Example 4
Weighing 70% by weight of tricalcium silicate powder and 30% by weight of alpha-tricalcium phosphate powder, and uniformly mixing to obtain solid phase powder; 0.05g of hydroxypropyl methylcellulose is dissolved in 9.45g of deionized water, and after the dissolution is completed, 0.5g of disodium hydrogen phosphate powder is added and stirred sufficiently to form a uniform liquid phase.
And fully and uniformly stirring the curing liquid and the solid phase powder according to the proportion of 0.4g/g to prepare the dental paste material.
Example 5
Weighing 90% by weight of tricalcium silicate powder and 10% by weight of alpha-tricalcium phosphate powder, and uniformly mixing to obtain solid phase powder; 0.3g of hydroxypropyl methylcellulose is dissolved in 9.6g of deionized water, and after the dissolution is completed, 0.1g of disodium hydrogen phosphate powder is added and stirred sufficiently to form a uniform liquid phase.
And fully and uniformly stirring the curing liquid and the solid phase powder according to the proportion of 0.65g/g to prepare the dental paste material.
Example 6
Weighing 70% by weight of tricalcium silicate powder and 30% by weight of alpha-tricalcium phosphate powder, and uniformly mixing to obtain solid phase powder; 0.15g of hydroxypropyl methylcellulose is dissolved in 9.75g of deionized water, and after the dissolution is completed, 0.1g of disodium hydrogen phosphate powder is added and stirred sufficiently to form a uniform liquid phase.
And fully and uniformly stirring the curing liquid and the solid phase powder according to the proportion of 0.5g/g to prepare the dental paste material.
Comparative example 1
Single tricalcium silicate powder is used as solid phase powder, and deionized water is used as curing liquid;
and fully and uniformly stirring the curing liquid and the solid phase powder according to the proportion of 0.5g/g to prepare the dental paste material.
Comparative example 2
Single tricalcium silicate powder is used as solid phase powder, and deionized water is used as curing liquid; 0.6g of hydroxypropyl methylcellulose is dissolved in 18.9g of deionized water, and after the dissolution is completed, 0.5g of disodium hydrogen phosphate powder is added and stirred sufficiently to form a uniform liquid phase.
And fully and uniformly stirring the curing liquid and the solid phase powder according to the proportion of 0.5g/g to prepare the dental paste material.
The following performance characterization was performed for each example and comparative example:
injectability determination: the prepared paste material was loaded into a syringe, and then placed in a universal tester to determine the variation of its injection force and displacement, and the injectability, expressed as the weight of paste injected as a percentage of the total weight of the raw paste, was expressed by measuring the weight of the paste before and after injection.
The injection performance test of comparative examples 1-2 and examples 1-6 showed that the paste of comparative example 1 had a gritty feel, low inter-particle viscosity, difficulty in injection, and severe pressure filtration phenomenon, whereas the paste of comparative example 2 had an injectability of 93%, showing excellent injectability, and the results showed that the incorporation of hydroxypropyl methylcellulose in the paste slurry could improve injectability. As can be seen from fig. 1, the injection force required for the pastes of examples 1-3 is significantly reduced compared to comparative example 2, i.e., the pastes are easier to inject and have better injectability, which results indicate that the injectability can be enhanced after the incorporation of the α -tricalcium phosphate self-curing material into the paste. In addition, the pastes of examples 4, 5 and 6 were easy to inject, and had excellent injectability.
Determination of anti-collapsibility: the blended paste material was placed in a syringe, and injected into a water glass dish, and after shaking in a shaker for 10 minutes, the free collapse of the paste particles was observed.
As a result of the anti-collapse property test of comparative examples 1 to 2 and examples 1 to 6, as shown in FIG. 2, the paste of comparative example 1 was exposed to water to cause a particle release phenomenon, and after shaking for 10 minutes, the paste was not collapsed and the particles were scattered over the entire liquid surface. In contrast, in comparative example 2, no particle release phenomenon occurred before and after vibration of the paste, and excellent anti-collapse properties were exhibited. Similarly, the pastes of examples 1-3 maintained the original slurry shape after vibration, without particle collapse. From the above results, it is clear that hydroxypropyl methylcellulose and α -tricalcium phosphate effectively improve the anti-collapse ability of the paste material. In addition, as can be seen from fig. 3, the pastes of examples 4 to 6 all maintained the initial injection shape after vibration, and the particles in the slurry did not collapse and leak, showing excellent anti-collapse properties.
Curing time measurement: the freshly prepared paste material was placed into a mold, and then placed into an environment at 37 ℃ for curing, and the curing time of the paste was measured by a vicat.
The results of the tests conducted in examples 1 and 3 and comparative example 2, as shown in FIG. 4, show that the initial setting and final setting times of the paste in comparative example 2 are 79 and 190 minutes, respectively, and the initial setting and final setting times of the paste in example 1 are 64 and 182 minutes, respectively, and the paste setting time is shortened, and the results indicate that the introduction of 10% α -tricalcium phosphate into the paste can accelerate the hardening of the paste, and that the paste setting time is prolonged when the α -tricalcium phosphate content is further increased to 50%.
Alkaline formation ability test: placing the newly prepared paste material into a mold, curing at 37deg.C to obtain a cured product, soaking the sample in Tris-HCl solution (pH=7.4, 37deg.C) to obtain a ratio of surface area of the sample to volume of Tris-HCl solution of 0.1cm 2 /mL. After soaking for different time, the solution of the soaked sample is measured by a pH meterIs a pH value of (c).
As shown in FIG. 5, the test results of examples 1-3 show that after the sample is soaked for 1 day, tris-HCl solution can be alkaline, the pH is up to 8.97, when the soaking time is longer than 5 days, the pH of the Tris-HCl solution after all the samples are soaked exceeds 10, the strong alkaline forming capability is shown, and a certain sterilization effect can be shown in an environment with the pH being greater than 9.
Cell activity and osteogenic gene expression test: grinding the cured paste sample into fine powder, adding the powder into a DMEM (Hyclone, USA) cell culture medium for leaching, and centrifugally collecting supernatant to obtain a sample leaching solution for subsequent testing. The osteoblast (ATCC) is taken as an experimental cell, the cell activity of different pastes is evaluated by a cell Counting Kit (Counting Kit-8, CCK-8, beyotidme, china), firstly, the osteoblast is added into a DMEM culture medium containing the prepared dental paste extract for culture, then the CCK-8 reagent is added, the incubation is carried out at 37 ℃ in a dark place, and then the OD value at 450nm is measured by an enzyme-labeling instrument.
Cell viability (%) = sample group corrected OD value/control group corrected OD value x 100%.
And detecting the influence of different samples on the expression conditions of the osteogenic related genes ALP and OPN in the cells by using an RT-PCR test method. Osteoblasts were cultured in a medium containing the sample extract, then total RNA was extracted with an RNA kit (Omega, china), and the obtained RNA was converted into cDNA using a reverse transcription kit (Takara, japan). Finally, the expression of ALP and OPN osteogenesis-related genes was detected by quantitative real-time reverse transcription polymerase chain reaction (PCR apparatus, bio-Rad, USA), and the sequences of the synthesized primer genes were as shown in Table 1, with GAPDH as a reference.
PCR reaction procedure: 10. Mu.L of the reaction system contained PSYBR Premix Ex Taq II (2X) 5. Mu.L, 0.4. Mu.L each of the forward and reverse primers, 1. Mu.L of RT reaction solution (cDNA solution), dH 2 O (sterilized distilled water) 4.2. Mu.L was added to the eight-way tube. Samples were subjected to fluorescent quantitative PCR detection using a Bio-Rad CFX Manager system, with the following procedure set forth: 95 ℃,30s, 45 cycles are started, and each cycle condition is as follows: 95 ℃,5s,60 ℃ and 30s. GAPDH is used as an internal reference, and BioRad CFX Manager software is used for dividing experimental resultsAnd (5) separating.
Primer gene sequences synthesized in Table 1
The results of testing examples 1 and 3 and comparative example 2, in which the cell activity was increased to 171% in example 1, and the highest cell activity was exhibited, are shown in fig. 6, and examples 1 to 3 are all higher than comparative example 2, indicate that α -tricalcium phosphate can increase the activity of paste on osteoblasts. ALP and OPN gene expression is shown in FIGS. 7 and 8, wherein the paste extract solutions of examples 1-3 were effective in up-regulating ALP and OPN gene expression, showing excellent bone-promoting ability.
Induction of apatite mineralization test: after the paste was cured, the wafer samples were immersed in Simulated Body Fluid (SBF) and observed for apatite formation on the sample surfaces by Scanning Electron Microscopy (SEM).
SEM photographs of the surface of the paste of example 1 of the present invention after soaking SBF are shown in fig. 9, and after soaking SBF, dense spherical osteoid apatite is formed on the surface of the hardened paste, indicating that the paste has excellent ability to induce osteoid apatite formation.
As described above, although the present invention has been shown and described with reference to certain preferred embodiments, it is not to be construed as limiting the invention itself. Various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.
Claims (9)
1. An injectable silicon-phosphorus-calcium-based dental paste with high osteogenic activity, characterized in that the dental paste is prepared by mixing solid phase powder and curing liquid; the solid phase powder at least comprises alpha-tricalcium phosphate; the solidifying liquid at least comprises an aqueous solution of hydroxypropyl methyl cellulose.
2. The injectable calcium-phosphorus-silicon-based dental paste according to claim 1, wherein the dental paste is prepared by mixing a curing liquid and a solid phase powder at a ratio of 0.4 to 0.65 g/g.
3. The injectable silico-phosphocalcic dental paste of claim 1, wherein the solid phase powder comprises tricalcium silicate and alpha tricalcium phosphate.
4. An injectable silico-phosphocalcic dental paste according to claim 3, wherein the powder particle size of the tricalcium silicate is 0.1 to 10 μm.
5. An injectable silico-phosphocalcic dental paste according to claim 3, wherein the weight percentage of tricalcium silicate in the solid phase powder is 50-90%, the weight percentage of α -tricalcium phosphate is 10-50% and the sum of the two weight percentages is 100%.
6. The injectable calcium-phosphorus-silicon-based dental paste of claim 1 wherein the solidifying solution is an aqueous solution containing disodium hydrogen phosphate and hydroxypropyl methylcellulose.
7. The injectable calcium-phosphorus-silicon-based dental paste of claim 6, wherein the curing liquid comprises 1-5% by weight of disodium hydrogen phosphate and 0.5-3% by weight of hydroxypropyl methylcellulose.
8. A method of preparing an injectable silico-phosphocalcic dental paste according to any of claims 1 to 7, comprising the steps of:
(1) Uniformly mixing tricalcium silicate powder and alpha-tricalcium phosphate powder to obtain solid phase powder;
(2) Adding hydroxypropyl methyl cellulose powder into water to be fully dissolved to obtain a uniform liquid phase, and then dissolving disodium hydrogen phosphate powder into the liquid phase to obtain a curing liquid;
(3) The obtained curing liquid and solid phase powder are uniformly mixed according to a proportion, and the injectable silicon-phosphorus-calcium-based dental paste with high osteogenesis activity is obtained.
9. Use of an injectable silico-phosphocalcic dental paste according to any of claims 1 to 7 for the preparation of a dental filling restorative material.
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