CN112043862A - Magnesium slow-release bone cement with self-curing function and preparation method thereof - Google Patents
Magnesium slow-release bone cement with self-curing function and preparation method thereof Download PDFInfo
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- 239000002639 bone cement Substances 0.000 title claims abstract description 84
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 title claims abstract description 77
- 239000011777 magnesium Substances 0.000 title claims abstract description 75
- 229910052749 magnesium Inorganic materials 0.000 title claims abstract description 75
- 238000002360 preparation method Methods 0.000 title claims description 20
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims abstract description 60
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 59
- 239000000843 powder Substances 0.000 claims abstract description 58
- 239000001506 calcium phosphate Substances 0.000 claims abstract description 40
- 229910000389 calcium phosphate Inorganic materials 0.000 claims abstract description 40
- 235000011010 calcium phosphates Nutrition 0.000 claims abstract description 40
- 239000002994 raw material Substances 0.000 claims abstract description 31
- 238000002156 mixing Methods 0.000 claims abstract description 26
- 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 25
- 239000008367 deionised water Substances 0.000 claims abstract description 22
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 22
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims abstract description 21
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims abstract description 21
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 21
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 20
- 150000002681 magnesium compounds Chemical class 0.000 claims abstract description 19
- -1 calcium phosphate compound Chemical class 0.000 claims abstract description 16
- 239000000243 solution Substances 0.000 claims description 29
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
- 239000007864 aqueous solution Substances 0.000 claims description 24
- 238000005303 weighing Methods 0.000 claims description 21
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 16
- 238000003756 stirring Methods 0.000 claims description 16
- GBNXLQPMFAUCOI-UHFFFAOYSA-H tetracalcium;oxygen(2-);diphosphate Chemical compound [O-2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GBNXLQPMFAUCOI-UHFFFAOYSA-H 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 14
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 12
- 239000011575 calcium Substances 0.000 claims description 12
- 229910052791 calcium Inorganic materials 0.000 claims description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 10
- 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 claims description 9
- 239000004137 magnesium phosphate Substances 0.000 claims description 9
- 229910000157 magnesium phosphate Inorganic materials 0.000 claims description 9
- 229960002261 magnesium phosphate Drugs 0.000 claims description 9
- 235000010994 magnesium phosphates Nutrition 0.000 claims description 9
- MHJAJDCZWVHCPF-UHFFFAOYSA-L dimagnesium phosphate Chemical compound [Mg+2].OP([O-])([O-])=O MHJAJDCZWVHCPF-UHFFFAOYSA-L 0.000 claims description 8
- 229910000395 dimagnesium phosphate Inorganic materials 0.000 claims description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 8
- 239000004568 cement Substances 0.000 claims description 7
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 5
- 239000001095 magnesium carbonate Substances 0.000 claims description 5
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 5
- 229910012375 magnesium hydride Inorganic materials 0.000 claims description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 5
- 235000019341 magnesium sulphate Nutrition 0.000 claims description 5
- 239000003513 alkali Substances 0.000 claims description 4
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 3
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 3
- 230000015556 catabolic process Effects 0.000 abstract description 8
- 238000006731 degradation reaction Methods 0.000 abstract description 8
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 abstract description 6
- 229910001425 magnesium ion Inorganic materials 0.000 abstract description 6
- 239000003431 cross linking reagent Substances 0.000 abstract description 3
- 159000000003 magnesium salts Chemical class 0.000 abstract description 3
- 239000000395 magnesium oxide Substances 0.000 description 11
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 11
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 11
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 10
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 10
- 230000000694 effects Effects 0.000 description 9
- 210000000988 bone and bone Anatomy 0.000 description 6
- 238000013268 sustained release Methods 0.000 description 5
- 239000012730 sustained-release form Substances 0.000 description 5
- 239000002609 medium Substances 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- 150000002680 magnesium Chemical class 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000002195 synergetic effect Effects 0.000 description 3
- RLFWWDJHLFCNIJ-UHFFFAOYSA-N 4-aminoantipyrine Chemical compound CN1C(C)=C(N)C(=O)N1C1=CC=CC=C1 RLFWWDJHLFCNIJ-UHFFFAOYSA-N 0.000 description 2
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000001099 ammonium carbonate Substances 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- PKAHQJNJPDVTDP-UHFFFAOYSA-N methyl cyclopropanecarboxylate Chemical compound COC(=O)C1CC1 PKAHQJNJPDVTDP-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000011164 ossification Effects 0.000 description 2
- 230000009818 osteogenic differentiation Effects 0.000 description 2
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 235000012501 ammonium carbonate Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- TYJOJLOWRIQYQM-UHFFFAOYSA-L disodium;phenyl phosphate Chemical compound [Na+].[Na+].[O-]P([O-])(=O)OC1=CC=CC=C1 TYJOJLOWRIQYQM-UHFFFAOYSA-L 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 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 description 1
- 150000004059 quinone derivatives Chemical class 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Images
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/02—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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
- A61L2300/604—Biodegradation
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
Abstract
The invention discloses magnesium slow-release bone cement with a self-curing function, which is characterized by being prepared by mixing and curing water aqua and powder, wherein the powder comprises the following raw material components in percentage by mass: 60-95% of calcium phosphate compound and 5-40% of magnesium compound; the water agent comprises the following raw materials in percentage by mass: 10-30% of citric acid, 5-20% of polyvinylpyrrolidone and 40-84% of deionized water. The organic cross-linking agent and the specific magnesium salt are added simultaneously to serve as donors for slowly releasing magnesium ions, so that the slow release of the magnesium ions is realized, calcium phosphate bone cement disintegration caused by over-fast magnesium degradation in the prior art is avoided, and in addition, the magnesium-released bone cement obtained by the invention has better biocompatibility and certain bone-promoting capacity, and can well meet the clinical use requirements.
Description
Technical Field
The invention belongs to the technical field of medical bone cement, and particularly relates to magnesium slow-release bone cement with a self-curing function and a preparation method thereof.
Background
The calcium phosphate cement is expected to become an ideal bone filler for repairing bone defects because the calcium phosphate cement finally forms hydroxyapatite similar to natural bone components in vivo and has better biocompatibility; but the calcium phosphate cement has weak bone formation promoting capacity; after magnesium or magnesium oxide is added into calcium phosphate cement, the bone activity can be improved and promoted through the slow release of magnesium; however, because the degradation speed of magnesium or magnesium oxide is high, the slow release rate of magnesium is difficult to control, and the calcium phosphate bone cement containing magnesium or magnesium oxide can be rapidly disintegrated in the water environment; therefore, the development of bone cement with better performance is still one of the main subjects of the research and development personnel.
Disclosure of Invention
In view of the above, the present invention aims to provide a magnesium slow-release bone cement with a self-curing function, which solves the problems that the existing bone cement containing magnesium has a high degradation speed of magnesium and is difficult to control the slow-release speed of magnesium, so that calcium phosphate bone cement containing magnesium or magnesium oxide rapidly disintegrates in an environment with water and the bone cement has poor bone formation promoting ability.
The invention also aims to provide a preparation method of the magnesium slow-release bone cement with the self-curing function.
In order to achieve the purpose, the technical scheme of the invention is realized as follows: the magnesium slow-release bone cement with the self-curing function is prepared by mixing and curing a water agent and powder, wherein the powder comprises the following raw material components in percentage by mass: 60-95% of calcium phosphate compound and 5-40% of magnesium compound; the water agent comprises the following raw materials in percentage by mass: 10-30% of citric acid, 5-20% of polyvinylpyrrolidone and 40-84% of deionized water.
Preferably, the ratio of the mass of the powder to the volume of the aqueous solution is 0.1-1 ml of aqueous solution added to 1-2 g of powder.
Preferably, the calcium phosphate compound is at least one of tetracalcium phosphate, calcium phosphate, and calcium hydrogen phosphate.
Preferably, the magnesium compound is at least one of magnesium sulfate, magnesium phosphate, magnesium hydrogen phosphate, magnesium hydride and magnesium carbonate.
The second technical scheme of the invention is realized as follows: a preparation method of magnesium slow-release bone cement with a self-curing function is realized by the following steps:
s1, respectively weighing the following raw material components in percentage by mass: 60-95% of calcium phosphate compound and 5-40% of magnesium compound, and fully mixing the weighed calcium phosphate compound and magnesium compound to obtain powder for later use;
s2, respectively weighing the following raw material components in percentage by mass: 10-30% of citric acid, 5-20% of polyvinylpyrrolidone and 40-84% of deionized water, and fully mixing the weighed citric acid, polyvinylpyrrolidone and magnesium compound to obtain a clear aqueous solution to obtain an aqueous solution for later use;
and S3, adding 0.1-1 ml of water aqua into every 1-2 g of powder according to the mass-volume ratio of the powder obtained in the S1 to the water aqua obtained in the S2, mixing, stirring into a viscous state, standing and curing to obtain the magnesium slow-release bone cement.
Preferably, in S1, the calcium phosphate compound is at least one of tetracalcium phosphate, calcium phosphate, and calcium hydrogen phosphate.
Preferably, in S1, the magnesium compound is at least one of magnesium sulfate, magnesium phosphate, magnesium hydrogen phosphate, magnesium hydride, and magnesium carbonate.
Preferably, in S2, after obtaining the clear aqueous solution, the method further includes: and adjusting the pH value of the clarified aqueous solution to 3-7.4 by using an alkali solution.
Preferably, the alkali solution is a sodium bicarbonate solution or a sodium hydroxide solution.
Preferably, in the S3, the temperature of the standing solidification is 4-37 ℃. .
Compared with the prior art, the invention has the beneficial effects that: the organic cross-linking agent and the specific magnesium salt are added simultaneously to serve as donors for slowly releasing magnesium ions, so that the slow release of the magnesium ions is realized, calcium phosphate bone cement disintegration caused by over-fast magnesium degradation in the prior art is avoided, and in addition, the magnesium-released bone cement obtained by the invention has better biocompatibility and certain bone-promoting capacity, and can well meet the clinical use requirements.
According to the preparation method, the proportional relation among the raw materials forming the powder, the proportional relation among the raw materials forming the aqua, the proportional relation when the powder and the aqua are mixed and cured and the pH value of the aqua is controlled to be 3-7.4 are controlled at the same time, and the synergistic effect among the substances is utilized, so that a series of magnesium slow-release bone cements with slow magnesium degradation speed are obtained, and the problems that calcium phosphate bone cement containing magnesium or magnesium oxide is rapidly disintegrated in a water environment and the bone cement has poor bone promoting capability are effectively avoided; in addition, the method has simple process and easy operation, and the prepared product is widely popularized and used.
Drawings
FIG. 1 is a bar graph comparing the biocompatibility test of the magnesium slow-release bone cement obtained in example 1 of the present invention with that of a conventional calcium phosphate bone cement containing magnesium oxide;
FIG. 2 is a graph comparing the magnesium-sustained release bone cement obtained in example 1 of the present invention with a conventional calcium phosphate bone cement containing magnesium oxide after the anti-disintegration capability test in water;
FIG. 3 is a graph showing the comparison between the alkaline phosphatase activity in the magnesium-extended bone cement obtained in example 1 of the present invention and the alkaline phosphatase activity in the conventional bone cement.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
In the following examples, the raw materials used in the preparation of the magnesium-containing slow-release bone cement can be obtained by direct purchase or by the prior art.
When the carbonate solution is prepared in the following embodiments, the solute used is a salt capable of ionizing carbonate ions in water, and may be, for example, ammonium bicarbonate, ammonium carbonate, sodium bicarbonate, or the like;
the embodiment of the invention provides magnesium slow-release bone cement with a self-curing function, which is prepared by mixing and curing powder and water agent according to the mass-volume ratio of 0.1-1 ml of water agent added into every 1-2 g of powder, wherein the powder comprises the following raw material components in percentage by mass: 60-95% of calcium phosphate compound and 5-40% of magnesium compound; the water agent comprises the following raw materials in percentage by mass: 10-30% of citric acid, 5-20% of polyvinylpyrrolidone and 40-84% of deionized water.
Wherein the calcium phosphate compound is at least one of tetracalcium phosphate, calcium phosphate and calcium hydrophosphate; the magnesium compound is at least one of magnesium sulfate, magnesium phosphate, magnesium hydrogen phosphate, magnesium hydride and magnesium carbonate.
The embodiment of the invention also provides a preparation method of the magnesium slow-release bone cement with the self-curing function, which is realized by the following steps:
s1, respectively weighing the following raw material components in percentage by mass: 60-95% of calcium phosphate compound and 5-40% of magnesium compound, and fully mixing the weighed calcium phosphate compound and magnesium compound to obtain powder for later use;
s2, respectively weighing the following raw material components in percentage by mass: 10-30% of citric acid, 5-20% of polyvinylpyrrolidone and 40-84% of deionized water, fully mixing the weighed citric acid, polyvinylpyrrolidone and magnesium compound to obtain a clear aqueous solution, and adjusting the pH value of the clear aqueous solution to 3-7.4 by using a sodium bicarbonate solution or a sodium hydroxide solution to obtain a water aqua for later use;
and S3, adding 0.1-1 ml of water aqua into every 1-2 g of powder according to the mass-volume ratio of the powder obtained in the step S1 to the water aqua obtained in the step S2, mixing, stirring into a viscous state, and standing and curing at room temperature or 37 ℃ to obtain the magnesium slow-release bone cement.
After the scheme is adopted, aiming at the magnesium-releasing bone cement: by simultaneously adding the organic cross-linking agent and the specific magnesium salt, the calcium phosphate bone cement is prevented from disintegrating due to too fast magnesium degradation while realizing the slow release of magnesium ions, and in addition, the magnesium-released bone cement obtained by the invention has better biocompatibility and certain bone-promoting capacity, and can well meet the clinical use requirement.
The preparation method of the magnesium-releasing slow bone cement comprises the following steps: by simultaneously controlling the proportional relation among raw materials forming the powder, the proportional relation among raw materials forming the aqua, the proportional relation when the powder and the aqua are mixed and cured and controlling the pH value of the aqua to be 3-7.4, a series of magnesium slow-release bone cements with slow magnesium degradation speed are obtained by utilizing the synergistic effect among the substances, so that the problems that the calcium phosphate bone cement containing magnesium or magnesium oxide is quickly disintegrated in a water environment and the bone cement has poor bone-promoting capacity are effectively avoided; in addition, the method has simple process and easy operation, and the prepared product is widely popularized and used.
The following are specific examples
Example 1
The magnesium slow-release bone cement with the self-curing function provided in this embodiment 1 is prepared from powder and aqueous agent according to a mass-to-volume ratio of 1 g: 0.5ml of the powder is prepared by mixing and solidifying, and the powder comprises the following raw material components in percentage by mass: 2.86g of tetracalcium phosphate, 0.8g of calcium hydrophosphate and 0.34g of magnesium phosphate; the water agent comprises the following raw materials in percentage by mass: 1g of citric acid, 1g of polyvinylpyrrolidone and 8ml of deionized water.
The magnesium slow-release bone cement with the self-curing function provided by the embodiment 1 is realized by the following steps:
s1, preparation of powder: sequentially weighing 2.92g of tetracalcium phosphate, 1.08g of calcium hydrophosphate and 0.1g of magnesium phosphate, and fully and uniformly stirring to obtain powder;
s2, preparation of an aqueous solution: weighing 8ml of deionized water, weighing 1g of citric acid and 1g of polyvinylpyrrolidone, adding into the deionized water, stirring until the solution is clear, and adjusting the pH value to 5.0 by using a sodium bicarbonate solution or a sodium hydroxide solution to obtain an aqueous solution;
s3, mixing the powder obtained in the step S1 with the water aqua obtained in the step S2 according to the mass-to-volume ratio of 1 g: 0.5ml of the magnesium slow-release bone cement is mixed and stirred into a sticky state, and is kept stand and solidified at room temperature or 37 ℃ to obtain the magnesium slow-release bone cement.
Example 2
The magnesium slow-release bone cement with the self-curing function provided in this embodiment 2 is prepared from powder and aqueous agent according to a mass-to-volume ratio of 1 g: 0.55ml of powder is prepared by mixing and solidifying, and the powder comprises the following raw materials in percentage by mass: 2.86g of tetracalcium phosphate, 0.8g of calcium hydrophosphate and 0.3g of magnesium hydrophosphate; the water agent comprises the following raw materials in percentage by mass: 1.5g of citric acid, 0.8g of polyvinylpyrrolidone and 7.7ml of deionized water.
The magnesium slow-release bone cement with the self-curing function provided by the embodiment 2 is realized by the following steps:
s1, preparation of powder: sequentially weighing 2.86g of tetracalcium phosphate, 0.8g of calcium hydrophosphate and 0.3g of magnesium hydrogen phosphate, and fully and uniformly stirring to obtain powder;
s2, preparation of an aqueous solution: weighing 7.7ml of deionized water, weighing 1.5g of citric acid and 0.8g of polyvinylpyrrolidone, adding into the deionized water, stirring until the solution is clear, and adjusting the pH value to 3.0 by using a sodium bicarbonate solution or a sodium hydroxide solution to obtain a water aqua;
s3, mixing the powder obtained in the step S1 with the water aqua obtained in the step S2 according to the mass-to-volume ratio of 1 g: mixing at a ratio of 0.55ml, stirring to form a viscous state, and standing and curing at room temperature or 37 ℃ to obtain the magnesium slow-release bone cement.
Example 3
The magnesium slow-release bone cement with the self-curing function provided in this embodiment 3 is prepared from powder and aqueous agent according to a mass-to-volume ratio of 1 g: 1ml of the powder is prepared by mixing and solidifying, and the powder comprises the following raw material components in percentage by mass: 2.86g of tetracalcium phosphate, 0.8g of calcium hydrophosphate and 0.3g of magnesium hydrophosphate; the water agent comprises the following raw materials in percentage by mass: 1.5g of citric acid, 0.8g of polyvinylpyrrolidone and 7.7ml of deionized water.
The magnesium slow-release bone cement with the self-curing function provided by the embodiment 3 is realized through the following steps:
s1, preparation of powder: sequentially weighing 2.86g of tetracalcium phosphate, 0.8g of calcium hydrophosphate and 0.3g of magnesium hydrogen phosphate, and fully and uniformly stirring to obtain powder;
s2, preparation of an aqueous solution: weighing 7.7ml of deionized water, weighing 1.5g of citric acid and 0.8g of polyvinylpyrrolidone, adding into the deionized water, stirring until the solution is clear, and adjusting the pH value to 6.0 by using a sodium bicarbonate solution or a sodium hydroxide solution to obtain a water aqua;
s3, mixing the powder obtained in the step S1 with the water aqua obtained in the step S2 according to the mass-to-volume ratio of 1 g: mixing the materials in a proportion of 1ml, stirring the mixture into a viscous state, and standing and curing the viscous state at room temperature or 37 ℃ to obtain the magnesium slow-release bone cement.
Example 4
In the magnesium slow-release bone cement with the self-curing function provided in this embodiment 4, the powder and the aqueous agent are mixed according to a mass-to-volume ratio of 1.5 g: 1ml of the powder is prepared by mixing and solidifying, and the powder comprises the following raw material components in percentage by mass: 2.86g of tetracalcium phosphate, 0.8g of calcium hydrophosphate and 0.3g of magnesium hydrophosphate; the water agent comprises the following raw materials in percentage by mass: 1.5g of citric acid, 0.8g of polyvinylpyrrolidone and 7.7ml of deionized water.
The magnesium slow-release bone cement with the self-curing function provided by the embodiment 4 is realized by the following steps:
s1, preparation of powder: sequentially weighing 2.86g of tetracalcium phosphate, 0.8g of calcium hydrophosphate and 0.3g of magnesium hydrogen phosphate, and fully and uniformly stirring to obtain powder;
s2, preparation of an aqueous solution: weighing 7.7ml of deionized water, weighing 1.5g of citric acid and 0.8g of polyvinylpyrrolidone, adding into the deionized water, stirring until the solution is clear, and adjusting the pH value to 7.4 by using a sodium bicarbonate solution or a sodium hydroxide solution to obtain a water aqua;
s3, mixing the powder obtained in the step S1 with the water aqua obtained in the step S2 according to the mass-to-volume ratio of 1 g: mixing the materials in a proportion of 1ml, stirring the mixture into a viscous state, and standing and curing the viscous state at room temperature or 37 ℃ to obtain the magnesium slow-release bone cement.
Example 5
In the magnesium slow-release bone cement with the self-curing function provided in this embodiment 5, the powder and the aqueous agent are mixed according to a mass-to-volume ratio of 2 g: 0.5ml of the powder is prepared by mixing and solidifying, and the powder comprises the following raw material components in percentage by mass: 2.92g of tetracalcium phosphate, 1.08g of calcium hydrophosphate and 0.1g of magnesium phosphate; the water agent comprises the following raw materials in percentage by mass: 1g of citric acid, 1g of polyvinylpyrrolidone and 8ml of deionized water.
The magnesium slow-release bone cement with the self-curing function provided in this embodiment 5 is implemented by the following steps:
s1, preparation of powder: sequentially weighing 2.92g of tetracalcium phosphate, 1.08g of calcium hydrophosphate and 0.1g of magnesium phosphate, and fully and uniformly stirring to obtain powder;
s2, preparation of an aqueous solution: weighing 8ml of deionized water, weighing 1g of citric acid and 1g of polyvinylpyrrolidone, adding into the deionized water, stirring until the solution is clear, and adjusting the pH value to 5.0 by using a sodium bicarbonate solution or a sodium hydroxide solution to obtain an aqueous solution;
s3, mixing the powder obtained in the step S1 with the water aqua obtained in the step S2 according to the mass-to-volume ratio of 2 g: 0.5ml of the magnesium slow-release bone cement is mixed and stirred into a sticky state, and is kept stand and solidified at room temperature or 37 ℃ to obtain the magnesium slow-release bone cement.
Thus, MCPC in fig. 1 represents the magnesium slow-release bone cement obtained in the embodiment of the present invention, and Ctrl represents the existing calcium phosphate bone cement; in FIG. 2, MgO-CPC represents the existing calcium phosphate cement containing magnesium oxide.
As can be seen from FIG. 1, the biocompatibility of the magnesium-sustained release bone cement obtained in example 1 of the present invention is superior to that of the existing magnesium oxide-containing calcium phosphate bone cement after the 3 rd day of culture;
as can be seen from FIG. 2, the anti-disintegration capability of the magnesium sustained-release bone cement obtained in example 1 of the present invention in water is superior to that of the conventional Ctrl bone cement.
In addition, in order to verify how the alkaline phosphatase activity in the magnesium sustained-release bone cement obtained by the present invention is, the alkaline phosphatase activity test was performed on the magnesium sustained-release bone cement (MCPC), the osteogenic differentiation medium (Positive-Ctrl), the calcium phosphate bone cement (CPC) and the common medium (Negative-Ctrl) obtained in example 1 of the present invention by comparing the existing osteogenic differentiation medium (Positive-Ctrl), calcium phosphate bone cement (CPC) and common medium (Negative-Ctrl),
the specific method for detecting the activity of the alkaline phosphatase comprises the following steps: culturing human mesenchymal stem cells by using the differentiation culture medium containing the leaching liquor of the experimental group materials, when culturing for 3 rd, 7 th and 14 th days, cracking the cells, extracting cell lysate as a detection sample of alkaline phosphatase, sequentially adding a sample to be detected, buffer solution and matrix solution into a 96-hole microporous plate according to the requirements of an alkaline phosphatase detection kit, incubating for 15 minutes at 37 ℃, and adding color developing solution for color development. The alkaline phosphatase decomposes disodium phenylphosphate to generate free phenol and phosphoric acid, the phenol reacts with 4-aminoantipyrine in alkaline solution to generate red quinone derivatives through potassium ferricyanide oxidation, and the enzyme activity can be determined according to the red color. Measuring the value by using an enzyme-labeling instrument, and calculating; the specific test results are shown in fig. 3:
as can be seen from FIG. 3, the alkaline phosphatase activity value in the magnesium-extended bone cement obtained according to the present invention increased with the number of days tested, while the alkaline phosphatase activity value in the conventional bone cement decreased with the increase of the number of days tested.
In conclusion, by simultaneously adding polyvinylpyrrolidone and a specific magnesium compound into the original bone cement system, the obtained magnesium slow-release bone cement realizes slow release of magnesium ions, and simultaneously avoids calcium phosphate bone cement disintegration caused by too fast magnesium degradation in the prior art.
In addition, when the magnesium slow-release bone cement is prepared, the proportional relation among the raw materials forming the powder, the proportional relation among the raw materials forming the aqueous solution, the proportional relation when the powder and the aqueous solution are mixed and cured and the pH value of the aqueous solution is controlled to be 3-7.4, and the synergistic effect among the substances is utilized, so that a series of magnesium slow-degradation-speed magnesium slow-release bone cements are obtained, and the problems that the calcium phosphate bone cement containing magnesium or magnesium oxide is rapidly disintegrated in the water environment and the bone cement has poor bone promoting capability are effectively avoided; in addition, the method has simple process and easy operation, and the prepared product is widely popularized and used.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are included in the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.
Claims (10)
1. The magnesium slow-release bone cement with the self-curing function is characterized by being prepared by mixing and curing a water agent and a powder agent, wherein the powder agent comprises the following raw material components in percentage by mass: 60-95% of calcium phosphate compound and 5-40% of magnesium compound; the water agent comprises the following raw materials in percentage by mass: 10-30% of citric acid, 5-20% of polyvinylpyrrolidone and 40-84% of deionized water.
2. The magnesium slow-release bone cement with the self-curing function according to claim 1, wherein the ratio of the mass of the powder to the volume of the aqueous solution is 0.1-1 ml of the aqueous solution added to 1-2 g of the powder.
3. The magnesium slow-release bone cement with the self-curing function according to claim 2, wherein the calcium phosphate compound is at least one of tetracalcium phosphate, calcium phosphate and calcium hydrophosphate.
4. The magnesium slow-release bone cement with the self-curing function according to claim 2 or 3, wherein the magnesium compound is at least one of magnesium sulfate, magnesium phosphate, magnesium hydrogen phosphate, magnesium hydride and magnesium carbonate.
5. A preparation method of magnesium slow-release bone cement with a self-curing function is characterized by comprising the following steps:
s1, respectively weighing the following raw material components in percentage by mass: 60-95% of calcium phosphate compound and 5-40% of magnesium compound, and fully mixing the weighed calcium phosphate compound and magnesium compound to obtain powder for later use;
s2, respectively weighing the following raw material components in percentage by mass: 10-30% of citric acid, 5-20% of polyvinylpyrrolidone and 40-84% of deionized water, and fully mixing the weighed citric acid, polyvinylpyrrolidone and magnesium compound to obtain a clear aqueous solution to obtain an aqueous solution for later use;
and S3, adding 0.1-1 ml of water aqua into every 1-2 g of powder according to the mass-volume ratio of the powder obtained in the S1 to the water aqua obtained in the S2, mixing, stirring into a viscous state, standing and curing to obtain the magnesium slow-release bone cement.
6. The method for preparing a magnesium cement having a self-curing function as claimed in claim 5, wherein in the step S1, the calcium phosphate compound is at least one of tetracalcium phosphate, calcium phosphate and calcium hydrogen phosphate.
7. The method for preparing magnesium cement with slow release of self-curing function as claimed in claim 6, wherein in S1, the magnesium compound is at least one of magnesium sulfate, magnesium phosphate, magnesium hydrogen phosphate, magnesium hydride and magnesium carbonate.
8. The method for preparing magnesium slow-release bone cement with self-curing function according to claim 7, wherein after obtaining the clear aqueous solution in S2, the method further comprises: and adjusting the pH value of the clarified aqueous solution to 3-7.4 by using an alkali solution.
9. The method for preparing magnesium slow-release bone cement with self-curing function according to claim 8, wherein the alkali solution is sodium bicarbonate solution or sodium hydroxide solution.
10. The method for preparing magnesium slow-release bone cement with self-curing function according to any one of claims 5 to 9, wherein the temperature of the standing curing in S3 is 4-37 ℃.
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