阅读说明：本技术 一种用于骨修复生物磷酸钙陶瓷浆料及其制备方法 (Biological calcium phosphate ceramic slurry for bone repair and preparation method thereof ) 是由 刘玮玮 卢秉恒 王晶 王磊 王静 于 2020-06-30 设计创作，主要内容包括：本发明公开了一种用于骨修复生物磷酸钙陶瓷浆料及其制备方法。该陶瓷浆料具有高固含量、低粘度、高分散性,解决现有出现二次团聚导致陶瓷浆料分散不均的问题,其组成成分按照重量百分比划分,由56～88％磷酸钙盐、2～4％亲水性表面活性剂、8～35％活性稀释剂、0～8％低聚物、0.2～4％分散剂、0.1～4％光引发剂、0.1～2％流平助剂、0.1～2％消泡助剂以及0.04～0.4％抗氧化剂组成。(The invention discloses a biological calcium phosphate ceramic slurry for bone repair and a preparation method thereof. The ceramic slurry has high solid content, low viscosity and high dispersibility, solves the problem of uneven dispersion of the ceramic slurry caused by secondary agglomeration in the prior art, and comprises the following components in percentage by weight, 56-88% of calcium phosphate salt, 2-4% of hydrophilic surfactant, 8-35% of active diluent, 0-8% of oligomer, 0.2-4% of dispersing agent, 0.1-4% of photoinitiator, 0.1-2% of leveling assistant, 0.1-2% of defoaming assistant and 0.04-0.4% of antioxidant.)

1. The biological calcium phosphate ceramic slurry for bone repair is characterized by comprising, by weight, 56-88% of calcium phosphate, 2-4% of a hydrophilic surfactant, 8-35% of a reactive diluent, 0-8% of an oligomer, 0.2-4% of a dispersant, 0.1-4% of a photoinitiator, 0.1-2% of a leveling aid, 0.1-2% of a defoaming aid and 0.04-0.4% of an antioxidant.

2. The calcium phosphate bio-ceramic slurry for bone repair according to claim 1, wherein: the calcium phosphate ceramic slurry is composed of 75% of calcium phosphate salt, 3% of hydrophilic surfactant, 11% of reactive diluent, 1% of oligomer, 4% of dispersing agent, 3% of photoinitiator, 1.5% of leveling aid, 1% of defoaming aid and 0.5% of antioxidant.

3. The biological calcium phosphate ceramic slurry for bone repair according to claim 1 or 2, characterized in that: the calcium phosphate salt is hydroxyapatite or amorphous calcium phosphate or calcium hydrophosphate monohydrate or calcium hydrophosphate dihydrate or anhydrous calcium hydrophosphate or octacalcium phosphate.

4. The biological calcium phosphate ceramic slurry for bone repair according to claim 1 or 2, characterized in that: the hydrophilic surfactant is linear alkyl sodium sulfonate or fatty acid methyl ester sodium sulfonate or alpha-alkenyl sodium sulfonate or fatty alcohol polyoxyethylene ether sodium sulfate or N-methylaminocarboxylic acid sodium.

5. The biological calcium phosphate ceramic slurry for bone repair according to claim 1 or 2, characterized in that: the active diluent is one or more of 1, 6-hexanediol diacrylate, trimethylolpropane triacrylate, tripropylene glycol diacrylate, polyethylene glycol (200) diacrylate, polyethylene glycol (400) diacrylate, polyethylene glycol (600) diacrylate, dipropylene glycol diacrylate and neopentyl glycol diacrylate.

6. The biological calcium phosphate ceramic slurry for bone repair according to claim 1 or 2, characterized in that: the oligomer is epoxy acrylic resin, polyurethane acrylic resin or polyester acrylate.

7. The biological calcium phosphate ceramic slurry for bone repair according to claim 1 or 2, characterized in that: the dispersing agent is one or a combination of more of German Bick BYK-110, sodium polyphosphate, ammonium polyacrylate, sodium polyacrylate, triethylhexylphosphoric acid, sodium lauryl sulfate, fatty acid polyglycol ester and sodium hexametaphosphate;

the photoinitiator is one or a combination of more of benzoin dimethyl ether, isopropyl thioxanthone, benzophenone, triphenyl hexafluoroantimonate, diphenyl- (2,4, 6-trimethyl benzoyl) oxyphosphorus, phenyl bis (2,4, 6-trimethyl benzoyl) phosphine oxide and 1-hydroxycyclohexyl phenyl ketone;

the antioxidant is 6-tertiary butyl-4-methylphenol, bis (3, 5-tertiary butyl-4-hydroxyphenyl) thioether or tetra (beta- (3, 5-tertiary butyl-4-hydroxyphenyl) propionic acid) pentaerythritol ester;

the leveling auxiliary agent is German bike BYK-358N, German bike BYK-333, polyether modified polydimethylsiloxane (AKN-1131) or polyether modified silicone oil (AKN-114);

the defoaming auxiliary agent is German BYK-A530, German BYK-065 or German BYK-088.

8. A method for preparing the biological calcium phosphate ceramic slurry for bone repair according to claim 1, which comprises the following steps:

step 1: preparation of surface-modified calcium phosphate salts

Step 1.1: respectively dissolving soluble calcium salt and soluble phosphate into deionized water to obtain a calcium salt solution and a phosphate solution;

step 1.2: adding a hydrophilic surfactant into a calcium salt solution, slowly dripping a phosphate solution into the solution after completely dissolving, firstly stirring at a constant temperature, then standing, and finally carrying out vacuum filtration, cleaning, drying and grinding to obtain surface-modified calcium phosphate powder;

step 2: preparation of premix

Sequentially adding the reactive diluent, the oligomer, the leveling aid, the defoaming aid, the photoinitiator and the antioxidant into a water bath kettle at a constant temperature, and mixing and stirring; wherein, the adding process is to add the latter component after the former component is completely dissolved to obtain the premixed solution;

and step 3: preparation of calcium phosphate ceramic slurry

Adding the surface-modified calcium phosphate powder obtained in the step 1 into the premixed liquid in batches, adding a part of dispersing agent after adding a part of calcium phosphate powder, and then fully performing ultrasonic stirring until all the calcium phosphate powder is added, and then putting the mixture into a light-tight tank filled with a zirconium oxide grinding ball for ball milling and defoaming treatment to prepare the biological calcium phosphate ceramic slurry for bone repair.

9. The method for preparing a calcium phosphate bio-ceramic slurry for bone repair according to claim 8, wherein: the molar ratio of the soluble calcium salt to the soluble phosphate in the step 1.1 is 0.5-1.67: 1.

10. the method for preparing a calcium phosphate bio-ceramic slurry for bone repair according to claim 8, wherein: the constant temperature in the step 1.2 is 37-60 ℃; the stirring speed is 300-600 r/min; standing for 4-24 h; the drying mode is freeze drying or drying by adopting a blast drying oven at 37-80 ℃;

the constant temperature in the step 2 is 37-60 ℃; the ultrasonic stirring time in the step 3 is 4-6 h; the ball milling treatment time is 1-3 h.

Technical Field

The invention belongs to the field of biological ceramics, and designs biological calcium phosphate ceramic slurry for bone repair and a preparation method thereof.

Background

Calcium phosphate ceramics belong to bioactive ceramic materials, generally show that after being implanted into a body, a hydroxyl carbonate apatite layer is formed on the surface and is connected with human bones, and the calcium phosphate ceramics are reported as early as the twentieth century and the seventies and are rapidly applied to clinic. The traditional calcium phosphate ceramic bone implant forming methods include dry pressing, wet pressing, extrusion forming, injection forming, direct solidification forming and the like, and the methods cannot meet clinical personalized requirements, such as: complex appearance, precise pore connectivity, porosity and the like.

The 3D printing technology can be used for rapid and high-precision forming, DICOM data of a human body are obtained through computed tomography, a three-dimensional entity is constructed in a layer-by-layer overlapping mode, and personalized design can be achieved. At present, the ceramic material 3D printing technology mainly comprises three-dimensional light curing molding (SLA) and Digital Light Processing (DLP), and has high printing precision and considerable post-processing mechanical strength.

In an SLA or DLP forming mode, the preparation of slurry is a core technology, high solid content and low viscosity (the more uniform dispersion, the higher the solid content at the same viscosity) are both required to be met, and the dispersibility of ceramic particles plays an important role in the performance of printed parts. The ceramic particles form a uniformly dispersed and stable system in the polymer solution, which depends on the acting force between the particles, and the system is stable when the repulsion between the particles is greater than the attraction, and the agglomeration is easily generated between the particles when the repulsion is less than the attraction. In order to ensure that the ceramic particles form a stable system in the polymer solution. The current research mainly focuses on the surface of ceramic particles, and the ceramic slurry with high dispersibility, high solid content and low viscosity is prepared by increasing the surface repulsion force among the particles so as to meet the requirement of a high-precision photocuring forming mode.

Chinese patent CN108706969A provides a water-based biological ceramic light-cured slurry and a preparation method and application thereof, the patent solves the problem of stability of the water-based biological ceramic light-cured slurry and improves the sedimentation amount of the slurry;

chinese patent CN108658607A provides a novel ceramic slurry, a ceramic prepared from the novel ceramic slurry and an application of the novel ceramic slurry, and the novel ceramic slurry and the ceramic prepared from the novel ceramic slurry are prepared by mixing ceramic powder and a dispersing agent to obtain modified ceramic powder, so that the problems of low solid content and high viscosity in the printing process of the ceramic slurry are solved;

the document [ Zhen Wang, Chunzhen Huang, et al.. Development of a Novel aqueous Hydroxypate Suspension for Stereolithography Applied to BoneTissue engineering, International,2018 ] describes the modification of the surface of hydroxyapatite particles with ammonium polyacrylate salts to obtain hydroxyapatite slurry with a solids content of 52 vol.%.

However, in all of the above three methods, the fusion property between the ceramic powder and the polymer resin is improved by surface modification of the formed ceramic powder again, and the solid content and dispersibility of the slurry are improved, but the above methods ignore a problem: the surface modification method mainly comprises ball milling, drying and grinding, so that the ceramic powder has high dispersibility and high specific surface area from the factory, secondary agglomeration can occur after modification treatment, and the dispersion uniformity of the ceramic powder in resin is reduced.

Disclosure of Invention

In order to solve the defects and shortcomings of the prior art, the biological calcium phosphate ceramic slurry for bone repair and the preparation method thereof are provided. The invention aims to synthesize a surface-modified calcium phosphate material by adopting an in-situ method, and the surface-modified calcium phosphate material is used as a raw material, so that the prepared ceramic slurry has high solid content, low viscosity and high dispersibility, and the problem of nonuniform dispersion of the ceramic slurry caused by secondary agglomeration in the prior art is solved.

The specific technical scheme of the invention is as follows:

the invention provides a biological calcium phosphate ceramic slurry for bone repair, which is characterized by comprising, by weight, 8-35% of a reactive diluent, 0-8% of an oligomer, 0.2-4% of a dispersant, 0.1-4% of a photoinitiator, 0.1-2% of a leveling aid, 0.1-2% of a defoaming aid, 0.04-0.4% of an antioxidant, 56-88% of a calcium phosphate salt and 2-4% of a hydrophilic surfactant.

Further, the calcium phosphate ceramic slurry is composed of 75% of calcium phosphate salt, 3% of hydrophilic surfactant, 11% of reactive diluent, 1% of oligomer, 4% of dispersant, 3% of photoinitiator, 1.5% of leveling aid, 1% of defoaming aid and 0.5% of antioxidant.

Preferably, the calcium phosphate salt is hydroxyapatite or amorphous calcium phosphate or calcium hydrogen phosphate monohydrate or calcium hydrogen phosphate dihydrate or anhydrous calcium hydrogen phosphate or octacalcium phosphate.

Preferably, the hydrophilic surfactant is linear alkyl sodium sulfonate or fatty acid methyl ester sodium sulfonate or alpha-alkenyl sodium sulfonate or fatty alcohol polyoxyethylene ether sodium sulfate or sodium N-methylamide carboxylate. The hydrophilic surfactants can be hydrolyzed in water, the hydrolyzed anions can be electrostatically adsorbed with calcium ions and then combined with phosphate ions to form modified calcium phosphate, and the surfactants can be fused with polymer resin, so that the dispersibility of the powder is improved.

Preferably, the reactive diluent is one or more of 1, 6-hexanediol diacrylate, trimethylolpropane triacrylate, tripropylene glycol diacrylate, polyethylene glycol (200) diacrylate, polyethylene glycol (400) diacrylate, polyethylene glycol (600) diacrylate, dipropylene glycol diacrylate, and neopentyl glycol diacrylate; the active diluents have photosensitive characteristics, and are polymerized under the excitation of a photoinitiator, so that the photocuring forming effect is achieved;

preferably, the oligomer is epoxy acrylic resin, polyurethane acrylic resin or polyester acrylate; the oligomers have photosensitive characteristics, can be added as auxiliary materials, and improve the curing time and the cured strength of the reactive diluent.

Preferably, the dispersant is one or more of German Bick BYK-110, sodium polyphosphate, ammonium polyacrylate, sodium polyacrylate, triethylhexylphosphoric acid, sodium lauryl sulfate, fatty acid polyglycol ester and sodium hexametaphosphate; the dispersing agent has the capability of reducing the surface energy of powder, and has higher dispersibility for calcium phosphate ceramic.

Preferably, the photoinitiator is one or more of benzoin dimethyl ether, isopropyl thioxanthone, benzophenone, triphenyl hexafluoroantimonate, diphenyl- (2,4, 6-trimethyl benzoyl) oxyphosphorus, phenyl bis (2,4, 6-trimethyl benzoyl) phosphine oxide and 1-hydroxycyclohexyl phenyl ketone; the photoinitiator is polymerized with the oligomer in the ultraviolet spectrum range to achieve the effect of photocuring and forming;

preferably, the antioxidant is 6-tertiary butyl-4-methylphenol, bis (3, 5-tertiary butyl-4-hydroxyphenyl) sulfide or tetra (beta- (3, 5-tertiary butyl-4-hydroxyphenyl) propionic acid) pentaerythritol ester; the antioxidants are phenolic compounds with space obstruction, can delay or inhibit the performance change of the active diluent and the oligomer, and prolong the service life;

preferably, the leveling assistant is German Bick BYK-358N, German Bick BYK-333, polyether modified polydimethylsiloxane or polyether modified silicone oil; the leveling auxiliary agents can reduce the surface tension of the material and have a wetting effect;

preferably, the defoaming assistant is Germany BYK-A530, Germany BYK-065 or Germany BYK-088; the defoaming auxiliaries all contain a defoaming polymer to eliminate bubbles in the slurry;

in addition, the invention also provides a method for preparing the calcium phosphate ceramic slurry, which comprises the following specific implementation steps:

step 1: preparation of surface-modified calcium phosphate salts

Step 1.1: respectively dissolving soluble calcium salt and soluble phosphate into deionized water to obtain a calcium salt solution and a phosphate solution;

step 1.2: adding a hydrophilic surfactant into a calcium salt solution, slowly dripping a phosphate solution into the solution after completely dissolving, firstly stirring at a constant temperature, then standing, and finally carrying out vacuum filtration, cleaning, drying and grinding to obtain surface-modified calcium phosphate powder;

step 2: preparation of premix

Sequentially adding the reactive diluent, the oligomer, the leveling aid, the defoaming aid, the photoinitiator and the antioxidant into a water bath kettle at a constant temperature, and mixing and stirring; wherein, the adding process is to add the latter component after the former component is completely dissolved to obtain the premixed solution;

and step 3: preparation of calcium phosphate ceramic slurry

Adding the surface-modified calcium phosphate powder obtained in the step 1 into the premixed liquid in batches, adding a part of dispersing agent after adding a part of calcium phosphate powder, and then fully performing ultrasonic stirring until all the calcium phosphate powder is added, and then putting the mixture into a light-tight tank filled with a zirconium oxide grinding ball for ball milling and defoaming treatment to prepare the biological calcium phosphate ceramic slurry for bone repair.

Preferably, the molar ratio of the soluble calcium salt to the soluble phosphate in the step 1.1 is 0.5-1.67: 1.

preferably, the constant temperature in the step 1.2 is 37-60 ℃; the stirring speed is 300-600 r/min; standing for 4-24 h; the drying mode is freeze drying or drying by adopting a blast drying oven at 37-80 ℃;

preferably, the constant temperature in the step 2 is 37-60 ℃;

preferably, the ultrasonic stirring time in the step 3 is 4-6 h; the ball milling treatment time is 1-3 h.

The soluble calcium salt in the step A is calcium nitrate, calcium chloride or calcium bicarbonate;

compared with the prior art, the invention has the following beneficial effects:

1. the invention takes the hydrophilic surfactant as the template, the calcium phosphate prepared by the in-situ synthesis method has higher dispersity and simple process, and avoids the generation of secondary agglomeration compared with the method of carrying out surface modification on the formed ceramic powder.

2. According to the invention, the calcium phosphate salt synthesized in the step 1 is used as a raw material to prepare the polymer photocuring ceramic slurry, which is beneficial to dispersion of ceramic particles in a polymer, improves the fusibility of the particles and a polymer solution, and achieves the purposes of high solid content and low viscosity.

3. The antioxidant added into the premix in step 2 of the invention can interrupt the autoxidation reaction chain of the polymer by decomposing hydroperoxide, thereby inhibiting or relieving the change of the performance of the polymer and prolonging the storage time of the slurry.

Detailed Description

The calcium phosphate ceramic slurry for bone repair provided by the present invention will be further described in detail with reference to the following specific examples.