Microcapsule and preparation method thereof, self-repairing resin and preparation method thereof, and dental prosthesis

Abstract

The invention provides a microcapsule and a preparation method thereof, self-repairing resin and a preparation method thereof, and a dental prosthesis. The microcapsule is prepared from the following raw materials: a polymer matrix, an active substance, a plasticizer, a dispersing agent and metacrylic acid esters, wherein the active substance contains bone morphogenetic protein; the self-repairing resin comprises the microcapsule; the dental restoration comprises the microcapsule and / or self-repairing resin. According to the invention, the problem that the dental resin material has micro-cracks and wear in the long-term service process is solved.

Description

Technical Field

[0001] The invention relates to the field of dental resins, and in particular to a microcapsule and a preparation method thereof, a self-repairing resin and a preparation method thereof, and a dental restoration. Background Art

[0002] Dental resin materials have shown good aesthetics and operability in clinical applications, but the decline of their mechanical properties is an inevitable problem in long-term use. Microcracks and wear will gradually accumulate, resulting in the decline of material performance, which may eventually require repair or replacement. In addition, traditional resin materials have limited resistance to chemical and physical attacks in the oral environment and are susceptible to acid and alkali corrosion and bacterial invasion.

[0003] Therefore, how to solve the above-mentioned problem of cracking of dental resin materials needs to be studied urgently. Summary of the invention

[0004] The purpose of the present invention is to provide a microcapsule and a preparation method thereof, a self-repairing resin and a preparation method thereof, and a dental restoration, so as to solve the problem that microcracks and wear will occur in dental resin materials during long-term service.

[0005] To achieve the above object, the present invention provides the following technical solutions:

[0006] A microcapsule, wherein the raw materials of the microcapsule include:

[0007] A polymer matrix, an active substance, a plasticizer, a dispersant, and methacrylates, wherein the active substance comprises a bone morphogenetic protein.

[0008] In some embodiments of the present invention, the polymer matrix is ​​30 to 60 parts by weight, the active substance is 5 to 40 parts by weight, the plasticizer is 1 to 10 parts by weight, the dispersant is 1 to 10 parts by weight, and the methacrylate is 1 to 10 parts by weight;

[0009] Preferably, the polymer matrix is ​​20 to 40 parts by weight, the active substance is 15 to 40 parts by weight, the plasticizer is 3 to 7 parts by weight, the dispersant is 3 to 7 parts by weight, and the methacrylate is 3 to 7 parts by weight.

[0010] In some embodiments of the present invention, the polymer matrix is ​​at least one selected from natural polymers, semi-synthetic polymers, and synthetic polymers;

[0011] Preferably, the natural polymer is at least one selected from gelatin, gum arabic, chitosan, and alginate;

[0012] Preferably, the semi-synthetic polymer is at least one selected from methyl cellulose, ethyl cellulose, carboxymethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, and hydroxypropyl cellulose;

[0013] Preferably, the synthetic polymer is at least one selected from polylactic acid-co-glycolic acid, polylactic acid, poly-α-hydroxycarboxylic acid, polyacrylate, polyethylene glycol, and polymethacrylate;

[0014] More preferably, the polylactic acid-glycolic acid copolymer comprises 40 to 75 wt.% of units derived from lactic acid and 25 to 60 wt.% of units derived from glycolic acid;

[0015] More preferably, the glass transition temperature of the polylactic acid-glycolic acid copolymer is 40-60°C.

[0016] In some embodiments of the present invention, the active substance further comprises a biomolecule other than bone morphogenetic protein;

[0017] Preferably, the biomolecule is at least one selected from a polypeptide and a protein;

[0018] Preferably, the bone morphogenetic protein is 10 to 20 parts by weight, preferably 10 to 15 parts by weight;

[0019] Preferably, the biomolecules other than bone morphogenetic protein, more preferably polypeptides and proteins, are in an amount of 1 to 10 parts by weight, preferably 5 parts by weight.

[0020] In some embodiments of the present invention, the plasticizer is selected from at least one of phthalate plasticizers, epoxy plasticizers, polymer plasticizers, acrylate plasticizers, phosphate esters, triethanolamine, and dioctyl adipate;

[0021] Preferably, the phthalate plasticizer is selected from at least one of dibutyl phthalate and (2-ethylhexyl) phthalate;

[0022] Preferably, the epoxy plasticizer is epoxidized soybean oil;

[0023] Preferably, the polymer plasticizer is a polyester plasticizer, and the polyester plasticizer is selected from at least one of poly(hexanediol adipate), poly(butylene adipate), poly(ethylene adipate), poly(furfuryl furandicarboxylate), poly(hexanediol furandicarboxylate), poly(hexanediol terephthalate), polyethylene terephthalate, and poly(butylene terephthalate);

[0024] Preferably, the phosphate ester is selected from at least one of tricresyl phosphate and trioctyl phosphate;

[0025] Preferably, the acrylic ester plasticizer is 1,6-hexanediol diacrylate.

[0026] In some embodiments of the present invention, the dispersant is at least one of polyvinyl pyrrolidone, sodium dodecyl sulfonate, sodium benzene sulfonate, polyacrylamide, sodium polystyrene sulfonate, and dibasic acid esters;

[0027] Preferably, the dibasic acid ester is at least one of dioctyl sebacate and diisodecyl adipate;

[0028] Preferably, the molecular weight of the polyvinyl pyrrolidone is less than 40,000. More preferably, the polyvinyl pyrrolidone is at least one of K10, K15, and K30, and more preferably K15.

[0029] In some embodiments of the present invention, the methacrylate is selected from C1-C8 alkyl methacrylate, C1-C8 hydroxy alkyl methacrylate, preferably selected from at least one of hydroxyethyl methacrylate, modified hydroxyethyl methacrylate, methyl methacrylate, ethyl methacrylate, propyl methacrylate, and hydroxypropyl methacrylate.

[0030] In order to achieve the above object, the present invention also provides the following technical solutions:

[0031] A method for preparing the above-mentioned microcapsules, the method is any one selected from the group consisting of emulsion polymerization, solvent evaporation, and spray drying.

[0032] In some embodiments of the present invention, the emulsion polymerization method comprises the following steps:

[0033] S1, providing a polymer matrix, an active substance, a plasticizer, a dispersant and methacrylates;

[0034] S2, mixing the active substance and water;

[0035] S3, adding a dispersant to the mixture obtained in step S2 to emulsify the mixture to obtain an emulsion;

[0036] S4, mixing the polymer matrix, methacrylate, plasticizer and the emulsion obtained in step S3 to cause a polymerization reaction;

[0037] S5, drying the product obtained in step S4;

[0038] S6, crushing and sieving the dried product obtained in step S5 to obtain the microcapsules.

[0039] In some embodiments of the present invention, in step S2, the mixing is performed in an emulsification container. Preferably, the emulsification container is an emulsification pot.

[0040] Preferably, the mixing is performed by stirring, wherein the stirring speed is 400 to 600 rpm and the stirring time is 10 to 20 min;

[0041] And / or, in step S3, the emulsification conditions are: temperature of 30-50° C., stirring speed of 1500-2500 rpm, and stirring time of 0.5-2 h;

[0042] And / or, in step S4, the polymerization reaction conditions are: temperature of 30-50° C., stirring speed of 1500-2500 rpm, and stirring time of 0.5-2 h;

[0043] And / or, in step S5, the drying conditions are: temperature of 50-70° C., and drying time of 4-8 h;

[0044] And / or, in step S6, the screening process is performed using a sieve, and the mesh size of the sieve is any one of 50 mesh, 100 mesh or 150 mesh.

[0045] In order to achieve the above object, the present invention also provides the following technical solutions:

[0046] A self-repairing resin, the raw materials of the self-repairing resin comprising:

[0047] Acrylic monomer, initiator, inorganic filler, auxiliary agent and the above microcapsule or microcapsule obtained by the above method;

[0048] Preferably, the initiator is a mixture of a free radical photoinitiator and a cationic photoinitiator.

[0049] In some embodiments of the present invention, the acrylic monomer is 15 to 50 parts by weight, the initiator is 0.1 to 10 parts by weight, the inorganic filler is 20 to 70 parts by weight, and the microcapsule is 10 to 40 parts by weight;

[0050] Preferably, the acrylic monomer is 15 to 30 parts by weight, the initiator is 0.2 to 4 parts by weight, the inorganic filler is 30 to 70 parts by weight, and the microcapsule is 15 to 30 parts by weight.

[0051] In some embodiments of the present invention, the acrylic monomer is selected from any one of bisphenol A propylene glycol dimethacrylate, triethylene glycol dimethacrylate, methyl methacrylate, hydroxyethyl methacrylate, urethane dimethacrylate, ethoxylated bisphenol A propylene glycol dimethacrylate, polyethylene glycol acrylate, ethylene glycol dimethacrylate, methyl α-cyanoacrylate, butyl α-cyanoacrylate, and decyl α-cyanoacrylate, or a combination of two or more thereof.

[0052] In some embodiments of the present invention, the photoinitiator includes at least one of a free radical photoinitiator and a cationic photoinitiator;

[0053] Preferably, the free radical photoinitiator is selected from at least one of camphorquinone, TPO, phenylbis(2,4,6-trimethylbenzoic acid)phosphine oxide, phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide, and benzophenone;

[0054] Preferably, the cationic photoinitiator is selected from at least one of diazonium salts, diaryl iodonium salts, triaryl sulfonium salts, alkyl sulfonium salts, iron arene salts, sulfonyloxy ketones, and triaryl siloxane ethers;

[0055] Preferably, the photoinitiator comprises a free radical photoinitiator and a cationic photoinitiator;

[0056] More preferably, the photoinitiator is a mixture of camphorquinone and diaryliodonium salt;

[0057] More preferably, the diaryliodonium salt is diphenyliodonium hexafluorophosphate.

[0058] In some embodiments of the present invention, the inorganic filler is at least one of calcium silicate particles, quartz powder, barium glass powder, lanthanum glass powder, borosilicate glass powder, silicon oxide-zirconium oxide composite powder, silicon oxide-ytterbium oxide composite powder, silicon dioxide powder, zirconium oxide powder, and titanium oxide powder;

[0059] Preferably, the particle size of the inorganic filler is 0.3 to 1.5 μm, preferably 0.5 to 1 μm;

[0060] Preferably, the inorganic filler is barium glass powder;

[0061] Preferably, the barium content in the barium glass powder is 20 to 50 wt.%, preferably 30 to 40 wt.%;

[0062] Preferably, the lanthanum metal content in the lanthanum glass powder is about 10 to 50 wt.%, preferably 20 to 40 wt.%;

[0063] Preferably, the content of zirconium in the silicon oxide-zirconium oxide composite powder is 20 to 40 wt.%;

[0064] Preferably, the ytterbium content in the silicon oxide-ytterbium oxide composite powder is 10 to 40 wt.%.

[0065] In some embodiments of the present invention, the auxiliary agent is selected from at least one of a fluorescent agent, an indicator, an inhibitor, an accelerator, a viscosity modifier, a wetting agent, an antioxidant, a surfactant, a stabilizer, and a diluent;

[0066] Preferably, the fluorescent agent is at least one of resazurin and Bengal tiger red;

[0067] Preferably, the inhibitor is butylated hydroxytoluene;

[0068] Preferably, the antioxidant is sun-fast yellow;

[0069] Preferably, the auxiliary agent is 0 to 0.5 parts by weight, more preferably 0.2 to 0.5 parts by weight.

[0070] In order to achieve the above object, the present invention also provides the following technical solutions:

[0071] A method for preparing the above self-healing resin, the method comprising the following steps:

[0072] A1, providing acrylic monomers, initiators, inorganic fillers, additives and the above-mentioned microcapsules or microcapsules obtained by the above-mentioned method;

[0073] A2, mixing the acrylic monomer, microcapsules and initiator;

[0074] A3, mixing the mixture obtained in step A2 with the inorganic filler;

[0075] A4, stirring the mixture obtained in step A3 under vacuum conditions to obtain the self-healing resin.

[0076] In some embodiments of the present invention, in step A2, the mixing is carried out under heating conditions by stirring with a double planetary stirrer, wherein the heating temperature is 30 to 50° C., the stirring speed is 10 to 30 rpm, and the stirring time is 0.5 to 2 h;

[0077] And / or, in the step A3, the mixing is carried out by stirring with a double planetary stirrer under heating conditions, wherein the heating temperature is 50 to 70° C., the stirring speed is 10 to 30 rpm, and the stirring time is 0.5 to 2 h;

[0078] And / or, in step A4, the vacuum degree is -0.1 to (-0.01) MPa, the stirring speed is 5 to 20 rpm, the stirring temperature is 50 to 70° C., and the stirring time is 0.5 to 2 h.

[0079] In order to achieve the above object, the present invention also provides the following technical solutions:

[0080] A dental restoration, wherein the dental restoration is any one of an inlay, an onlay, a crown, a bridge, a molar / anterior veneer, and an implant superstructure;

[0081] The dental restoration is made using the microcapsules, or the microcapsules obtained by the method, or the self-repairing resin, or the self-repairing resin obtained by the method.

[0082] Further areas of applicability will become apparent from the description provided herein.

[0083] The description and specific examples in this summary are intended for purposes of illustration only and are not intended to limit the scope of the present invention.

[0084] Compared with the prior art, the technical solution provided by the present invention has the following beneficial effects:

[0085] The present invention provides a microcapsule and a preparation method thereof, a self-repairing resin and a preparation method thereof, and a dental restoration, so as to solve the problem that microcracks and wear may occur in dental resin materials during long-term service.

[0086] The core innovation of the dental resin material involved in the present invention lies in its unique self-repairing function. This resin can release pre-packaged restorative agents through built-in microcapsule components when it is mechanically damaged, thereby achieving self-repair; the microcapsules contain one or more monomers, and when cracks appear on the surface of the resin, the microcapsules rupture, and the released contents will rapidly polymerize, fill the cracks and restore the integrity of the material; it is worth noting that the above-mentioned restorative agent refers to bone morphogenetic protein BMP.

[0087] Compared with existing dental resin materials, the self-healing resin of this patent has the following advantages:

[0088] 1. Higher mechanical strength: Due to the existence of self-repair mechanism, the resin material can quickly restore its mechanical properties after being damaged, thereby extending its service life;

[0089] 2. Better durability: Self-healing resins can resist wear and tear from daily use and chemical erosion in the oral environment;

[0090] 3. Simplified maintenance process: Traditional restorative materials may require regular maintenance and repair, while self-healing resins reduce this need, providing convenience for patients and dentists;

[0091] 4. Cost-effectiveness: Although the initial cost of self-healing resins may be slightly higher, their longer service life and reduced maintenance requirements can ultimately reduce overall costs.

[0092] In order to achieve the self-repair function, this patent adopts a special microcapsule design, which allows the microcapsule to rupture and release the repair agent when it is subjected to specific stimuli, such as temperature changes or mechanical stress. In addition, molecules that can promote dynamic bonding are added to the resin. These molecules can quickly reorganize after the microcapsule ruptures, further enhancing the repair effect; it is worth noting that dynamic bonding refers to HEMA, which is a relatively hydrophilic molecule that can ensure good affinity and compatibility between BMP, tooth body and water, and strengthen the bonding between material interfaces. BRIEF DESCRIPTION OF THE DRAWINGS

[0093] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings required for use in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some implementation plans of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without paying any creative work.

[0094] Figure 1 A flowchart of a method for preparing microcapsules provided in one embodiment of the present invention;

[0095] Figure 2 A flowchart of a method for preparing a self-healing resin provided in another embodiment of the present invention. DETAILED DESCRIPTION

[0096] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments in the present invention, all other embodiments obtained by those skilled in the art without creative work belong to the scope of protection of the present invention. It should be understood that the specific embodiments described herein are only used to illustrate and explain the present invention, and are not used to limit the present invention.

[0097] Any specific numerical value disclosed herein (including the endpoint of the numerical range) is not limited to the exact value of the numerical value, but should be understood to also cover values ​​close to the exact value, such as all possible numerical values ​​within the range of ±5% of the exact value. In addition, for the disclosed numerical range, the endpoint values ​​of the range, the endpoint values ​​and the specific point values ​​in the range, and the specific point values ​​can be arbitrarily combined to obtain one or more new numerical ranges, and these new numerical ranges should also be regarded as specifically disclosed herein.

[0098] The terms of the present invention are only intended to describe specific exemplary embodiments and are not intended to be limiting. Unless the context clearly indicates otherwise, the singular forms "one", "a kind of" and "the" as used in the present invention may be intended to also include plural forms. The terms "comprise", "include", "contain" and "have" are inclusive, thus illustrating the presence of the features, elements, compositions, steps, integers, operations and / or components, but do not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components and / or their collections. Although the open term "comprising" should be understood as a non-limiting term for describing and claiming the various embodiments described in the present invention, in some aspects, the term is alternatively understood as a more restrictive and limited term, such as "consisting of..." or "consisting essentially of..." Thus, for any given embodiment of a narration composition, material, component, element, feature, integer, operation and / or process step, the present invention also particularly includes an embodiment consisting of or essentially consisting of such a composition, material, component, element, feature, integer, operation and / or process step. In the case of “consisting of,” alternative embodiments exclude any additional compositions, materials, components, elements, features, integers, operations and / or process steps, while in the case of “consisting essentially of,” any additional compositions, materials, components, elements, features, integers, operations and / or process steps that materially affect the basic and novel characteristics are excluded from such embodiments, but any compositions, materials, components, elements, features, integers, operations and / or process steps that do not materially affect the basic and novel characteristics may be included in the embodiments.

[0099] Any method steps, processes, and operations described herein should not be construed as necessarily requiring their performance in the particular order discussed or illustrated, unless expressly identified as a certain order of performance. It should also be understood that additional or alternative steps may be used unless otherwise stated.

[0100] In the present invention, except for the contents explicitly described, any matters or items not mentioned are directly applicable to those known in the art without any change. Moreover, any embodiment described in the present invention can be freely combined with one or more other embodiments described in the present invention, and the technical solutions or technical ideas formed thereby are regarded as part of the original disclosure or original record of the present invention, and should not be regarded as new contents that have not been disclosed or anticipated by the present invention, unless a person skilled in the art considers that the combination is obviously unreasonable.

[0101] Unless otherwise specified, the terms used herein have the same meaning as commonly understood by those skilled in the art. If a term is defined herein and its definition is different from the commonly understood meaning in the art, the definition herein shall prevail.

[0102] Unless otherwise stated, when % is mentioned herein, it means wt. %.

[0103] It is worth noting that, among the various organic substances mentioned in the specification of the present invention, at least some of the English abbreviations or aliases are as follows for reference by those skilled in the art: bisphenol A propylene glycol dimethacrylate (BisGMA), triethylene glycol dimethacrylate (TEGDMA), methyl methacrylate (MMA), hydroxyethyl methacrylate (HEMA), urethane dimethacrylate (UDMA), ethoxylated bisphenol A propylene glycol dimethacrylate (BisEMA), polyethylene glycol dimethacrylate (PEGDMA), ethylene glycol dimethacrylate (EGDMA), phenyl bis(2,4,6-trimethylbenzoic acid) phosphine oxide (Irgacure 369, other trade names, codes), phenyl bis(2,4,6-trimethylbenzoyl) phosphine oxide (819 photoinitiator), benzophenone (BP).

[0104] The "TPO" described in the present specification refers to (2,4,6-trimethylbenzoyl)diphenylphosphine oxide, and its CAS number is 75980-60-8 and its EINECS number is 278-355-8.

[0105] First aspect

[0106] A microcapsule, the raw materials of which include: a polymer matrix, an active substance, a plasticizer, a dispersant, and methacrylates, wherein the active substance contains bone morphogenetic protein.

[0107] In some embodiments of the present invention, the polymer matrix is ​​30 to 60 parts by weight, the active substance is 5 to 40 parts by weight, the plasticizer is 1 to 10 parts by weight, the dispersant is 1 to 10 parts by weight, and the methacrylate is 1 to 10 parts by weight.

[0108] In some embodiments of the present invention, the polymer matrix is ​​20 to 40 parts by weight, the active substance is 15 to 40 parts by weight, the plasticizer is 3 to 7 parts by weight, the dispersant is 3 to 7 parts by weight, and the methacrylate is 3 to 7 parts by weight.

[0109] In some embodiments of the present invention, the polymer matrix is ​​at least one of a natural polymer, a semi-synthetic polymer, and a synthetic polymer.

[0110] In some embodiments of the present invention, the natural polymer is at least one of gelatin, gum arabic, chitosan, and alginate. These four substances are natural polymers that have the characteristics of good hydrophilicity, good biocombination, and good dispersibility. These natural polymers are commonly used colloid materials for medical devices.

[0111] In some embodiments of the present invention, the semi-synthetic polymer is at least one of methyl cellulose, ethyl cellulose, carboxymethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, and hydroxypropyl cellulose.

[0112] In some embodiments of the present invention, the synthetic polymer is at least one of polylactic acid-glycolic acid copolymer, polylactic acid, poly-α-hydroxycarboxylic acid, polyacrylate, polyethylene glycol, and polymethacrylate. The polymer has good solubility and can be dissolved in a variety of common solvents. In addition, the above polymer has excellent biocompatibility. These polymers are prepared by chemical modification using natural cellulose or synthetic cellulose as raw materials. Its characteristics are that it can play a good auxiliary role in dispersion and has good solubility in aqueous solution to form a gel. The main function of these substances is to provide a good dispersion interface, but what is different from the above polymers is their viscosity, stable flow state, and relatively concentrated molecular weight.

[0113] In some embodiments of the present invention, the polylactic acid-glycolic acid copolymer comprises 40-75wt.% of units derived from lactic acid and 25-60wt.% of units derived from glycolic acid. Exemplarily, the mass fraction of the units based on lactic acid in the polylactic acid-glycolic acid copolymer can be any one of 45wt.%, 50wt.%, 55wt.%, 60wt.%, 65wt.% or 70wt.%, or a range consisting of any two values, and the mass fraction of the units based on glycolic acid in the polylactic acid-glycolic acid copolymer can be any one of 30wt.%, 35wt.%, 40wt.%, 45wt.%, 50wt.% or 55wt.%, or a range consisting of any two values.

[0114] In some embodiments of the present invention, the glass transition temperature of the polylactic acid-glycolic acid copolymer is 40 to 60°C. Exemplarily, the glass transition temperature can be any one of 45°C, 50°C or 55°C or a range consisting of any two values. The glass transition temperature of 40 to 60°C is mainly to control the molecules to be fully swollen and dissolved during the processing, and to fully fuse with BMP and other substances in the process.

[0115] In some embodiments of the present invention, the active substance comprises bone morphogenetic proteins (BMPs). Bone morphogenetic protein-2 (BMP-2) is a member of the transforming growth factor-β (TGF-β) superfamily.

[0116] It is worth mentioning that bone morphogenetic protein 2 (BMP-2) is a pleiotropic ligand protein belonging to the TNF-β family. BMP-2 forms BMP / TGF-β signaling and participates in vascular and valvular homeostasis, which is a key process in embryonic development. BMP-2 / TGF-β signaling can be terminated by inhibitory SMADs, including SMAD6 and SMAD7, which are activated and induced by BMP signaling and shut down BMP signaling through multiple mechanisms. BMP-2 is widely present in different animals, and the sequence in humans is similar to that in rats (91.86%) and mice (92.13%). BMPs contribute significantly to the pathophysiology of atherosclerosis, pulmonary vascular disease, and vascular and valvular calcification. BMP-2 binds to different receptors, such as type I receptors (ALK-2 / -3 / -6) and type II receptors (BMPR2, ACVR2A), to regulate various calcification types. BMP-2 promotes mononuclear cell infiltration and inflammation in atherosclerotic legionella. It is associated with increased plaque formation through proinflammatory and proatherogenic effects, promotion of oxidative stress, endothelial dysfunction, and osteogenic differentiation. BMP-2 is overexpressed by myofibroblasts and preosteoblasts in the ossified areas of human calcified valves in densely infiltrated areas of B and T lymphocytes and is a link between atherosclerotic vascular calcification and normal bone formation mechanisms. BMP-2 induces angiogenesis, endothelial cell (EC) proliferation and migration. BMP-2 also enhances the expression of the osteoblast and chondrocyte master transcriptional regulator RUNX2 to promote mineralization of cultured human coronary artery smooth muscle cells in a manner that is dependent on oxidative stress and endoplasmic reticulum (ER) stress.

[0117] In some embodiments of the present invention, preferably, the bone morphogenetic protein is 10-20 parts by weight, preferably 10-15 parts by weight.

[0118] In some embodiments of the present invention, the active substance further comprises other biomolecules in addition to bone morphogenetic protein. The biomolecule is at least one selected from polypeptides and proteins. Preferably, the biomolecules in addition to bone morphogenetic protein, more preferably polypeptides and proteins, are 1 to 10 parts by weight, preferably 5 parts by weight.

[0119] In some embodiments of the present invention, the molecular weight of any one of the polypeptides and proteins is 500 to 50,000 Daltons; illustratively, it can be any one of 1,000 Daltons, 2,000 Daltons, 5,000 Daltons, 10,000 Daltons, 20,000 Daltons or 35,000 Daltons, or a range consisting of any two of the values.

[0120] In some embodiments of the present invention, the plasticizer is selected from at least one of phthalate plasticizers, epoxy plasticizers, polymer plasticizers, acrylate plasticizers, phosphate esters, triethanolamine, and dioctyl adipate.

[0121] In some embodiments of the present invention, the phthalate plasticizer is selected from at least one of dibutyl phthalate and (2-ethylhexyl) phthalate.

[0122] In some embodiments of the present invention, the epoxy plasticizer is epoxidized soybean oil.

[0123] In some embodiments of the present invention, the polymer plasticizer is a polyester plasticizer, and the polyester plasticizer is selected from at least one of poly(hexanediol adipate), poly(butylene adipate), poly(ethylene adipate), poly(furfuryl furandicarboxylate), poly(hexanediol furandicarboxylate), poly(hexanediol terephthalate), polyethylene terephthalate, and poly(butylene terephthalate);

[0124] Preferably, the phosphate ester is selected from at least one of tricresyl phosphate and trioctyl phosphate.

[0125] In some embodiments of the present invention, the acrylic ester plasticizer is 1,6-hexanediol diacrylate.

[0126] In some embodiments of the present invention, the dispersant is at least one of polyvinyl pyrrolidone, sodium dodecyl sulfonate, sodium benzene sulfonate, polyacrylamide, sodium polystyrene sulfonate, and dibasic acid esters.

[0127] In some embodiments of the present invention, the dibasic acid ester is at least one of dioctyl sebacate and diisodecyl adipate.

[0128] In some embodiments of the present invention, the molecular weight of the polyvinyl pyrrolidone is less than 40,000, for example, 10,000 or 20,000; more preferably, the polyvinyl pyrrolidone is at least one of K10, K15, and K30, more preferably K15.

[0129] In some embodiments of the present invention, the methacrylate is selected from C1-C8 alkyl methacrylate, preferably C1-C4 alkyl methacrylate, hydroxy C1-C8 alkyl methacrylate, preferably hydroxy C1-C4 alkyl methacrylate, and more preferably at least one selected from hydroxyethyl methacrylate, a modified form of hydroxyethyl methacrylate, methyl methacrylate, ethyl methacrylate, propyl methacrylate, and hydroxypropyl methacrylate.

[0130] Second aspect

[0131] A method for preparing the above-mentioned microcapsules, the method is any one selected from emulsion polymerization, solvent evaporation method, and spray drying method, that is, the above-mentioned microcapsules can be prepared by any one of emulsion polymerization, solvent evaporation method, and spray drying method.

[0132] See also Figure 1 In some embodiments of the present invention, the emulsion polymerization method comprises the following steps:

[0133] S1, providing a polymer matrix, an active substance, a plasticizer, a dispersant and methacrylates;

[0134] S2, mixing the active substance and water;

[0135] S3, adding a dispersant to the mixture obtained in step S2 to emulsify the mixture to obtain an emulsion;

[0136] S4, mixing the polymer matrix, methacrylate, plasticizer and the emulsion obtained in step S3 to cause a polymerization reaction;

[0137] S5, drying the product obtained in step S4;

[0138] S6, crushing and sieving the dried product obtained in step S5 to obtain the microcapsules.

[0139] In some embodiments of the present invention, in step S2, the mixing is performed in an emulsification container, preferably, the emulsification container is an emulsification pot;

[0140] Preferably, the mixing is performed by stirring, wherein the stirring speed is 400-600 rpm, and the stirring time is 10-20 min. Exemplarily, the stirring speed can be any one of 450 rpm, 500 rpm, or 550 rpm, or a range consisting of any two values, and the stirring time is any one of 12 min, 15 min, or 17 min, or a range consisting of any two values.

[0141] In some embodiments of the present invention, in step S3, the emulsification conditions are: temperature of 30-50°C, stirring speed of 1500-2500 rpm, stirring time of 0.5-2h. Exemplarily, the heating temperature is any one of 35°C, 40°C or 45°C or a range consisting of any two values, the stirring speed is 2000 rpm or 2200 rpm, and the stirring time is any one of 1h, 1.5h or 1.6h or a range consisting of any two values.

[0142] In some embodiments of the present invention, in step S4, the conditions of the polymerization reaction are: temperature of 30-50°C, stirring speed of 1500-2500rpm, stirring time of 0.5-2h. Exemplarily, the reaction temperature is any one of 35°C, 40°C or 45°C or a range consisting of any two values, the stirring speed is any one of 1800rpm, 2000rpm or 2300rpm or a range consisting of any two values, and the stirring time is 1h or 1.5h.

[0143] In some embodiments of the present invention, in step S5, the drying conditions are: a temperature of 50 to 70°C, and a drying time of 4 to 8 hours. Exemplarily, the drying temperature is any one of 55°C, 60°C, or 65°C, or a range consisting of any two values, and the drying time is any one of 5h, 6h, or 7h, or a range consisting of any two values.

[0144] In some embodiments of the present invention, in step S6, a sieve is used for the sieving process, and the mesh size of the sieve is any one of 50 mesh, 100 mesh or 150 mesh.

[0145] The selection of process parameters mainly takes into account the characteristics of the raw materials. The maximum temperature is selected not to exceed 70°C to prevent the polymer chain from being tempered. The general processing temperature is selected between 40 and 60°C, mainly considering the solubility and processing difficulty of the preparation process.

[0146] In terms of processing conditions, the preparation of microspheres requires emulsification, and basically a quick and short-time emulsification is used in order to protect the integrity of the polymer structure. The conditions of the emulsification process are not harsh and a general emulsification process is used.

[0147] The drying process uses low-temperature and long-term heat drying to prevent high temperature from damaging the molecules.

[0148] The third aspect

[0149] A self-repairing resin, whose raw materials include: acrylic monomers, initiators, inorganic fillers, additives and the above-mentioned microcapsules or microcapsules obtained by the above-mentioned method; preferably, the initiator is a mixture of a free radical photoinitiator and a cationic photoinitiator.

[0150] In some embodiments of the present invention, the acrylic monomer is 15 to 50 parts by weight, the initiator is 0.1 to 10 parts by weight, the inorganic filler is 20 to 70 parts by weight, and the microcapsule is 10 to 40 parts by weight. In a preferred embodiment, the total weight of the raw materials of the self-healing resin is 100 parts by weight. Preferably, the total weight of the acrylic monomer, initiator, inorganic filler, auxiliary agent and microcapsule is 100 parts by weight.

[0151] In some embodiments of the present invention, the acrylic monomer is 15 to 30 parts by weight, the initiator is 0.2 to 4 parts by weight, the inorganic filler is 30 to 70 parts by weight, and the microcapsule is 15 to 30 parts by weight.

[0152] In some embodiments of the present invention, the acrylic monomer is any one selected from bisphenol A propylene glycol dimethacrylate, triethylene glycol dimethacrylate, methyl methacrylate, hydroxyethyl methacrylate, urethane dimethacrylate, ethoxylated bisphenol A propylene glycol dimethacrylate, polyethylene glycol acrylate, ethylene glycol dimethacrylate, methyl α-cyanoacrylate, butyl α-cyanoacrylate, and decyl α-cyanoacrylate, or a combination of two or more thereof.

[0153] In some embodiments of the present invention, the free radical photoinitiator is selected from at least one of camphorquinone, TPO, phenylbis(2,4,6-trimethylbenzoic acid)phosphine oxide, phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide, and benzophenone.

[0154] In some embodiments of the present invention, the cationic photoinitiator is at least one of a diazonium salt, a diaryl iodonium salt, a triaryl sulfonium salt, an alkyl sulfonium salt, an iron arene salt, a sulfonyloxy ketone, and a triaryl siloxane ether.

[0155] In some embodiments of the present invention, the photoinitiator is a mixture of camphorquinone and diaryliodonium salt.

[0156] In some embodiments of the present invention, the diaryliodonium salt is diphenyliodonium hexafluorophosphate.

[0157] In some embodiments of the present invention, the inorganic filler is at least one selected from calcium silicate particles, quartz powder, barium glass powder, lanthanum glass powder, borosilicate glass powder, silicon oxide-zirconium oxide composite powder, silicon oxide-ytterbium oxide composite powder, silicon dioxide powder, zirconium oxide powder, and titanium oxide powder.

[0158] Preferably, the inorganic filler is nano powder;

[0159] Preferably, the particle size of the inorganic filler is 0.3 to 1.5 μm, preferably 0.5 to 1 μm;

[0160] In some embodiments of the present invention, the inorganic filler is barium glass powder.

[0161] In some embodiments of the present invention, the barium content in the barium glass powder is 20 to 50 wt.%, preferably 30 to 40 wt.%.

[0162] In some embodiments of the present invention, the particle size of the barium glass powder is 0.3-1.5 μm, preferably 0.5-1 μm.

[0163] In some embodiments of the present invention, the lanthanum metal content in the lanthanum glass powder is about 10 to 50 wt.%, preferably 20 to 40 wt.%.

[0164] In some embodiments of the present invention, the particle size of the lanthanum glass powder is 0.3 to 1.5 μm, preferably 0.5 to 1 μm.

[0165] In some embodiments of the present invention, the content of zirconium in the silicon oxide-zirconium oxide composite powder is 20-40 wt.%, and the particle size is 0.3-1.5 μm, preferably 0.5-1 μm.

[0166] In some embodiments of the present invention, the ytterbium content in the silicon oxide-ytterbium oxide composite powder is 10-40 wt.%, and the particle size is 0.3-1.5 μm, preferably 0.5-1 μm.

[0167] In some embodiments of the present invention, the particle size of the nano-silicon dioxide powder is 0.3-1.5 μm, preferably 0.5-1 μm.

[0168] In some embodiments of the present invention, the particle size of the nano zirconium oxide powder is 0.3 to 1.5 μm, preferably 0.5 to 1 μm.

[0169] In some embodiments of the present invention, the particle size of the nano titanium oxide powder is 0.3-1.5 μm, preferably 0.5-1 μm.

[0170] In some embodiments of the present invention, the auxiliary agent is selected from at least one of a fluorescent agent, an indicator, an inhibitor, an accelerator, a viscosity modifier, a wetting agent, an antioxidant, a surfactant, a stabilizer, and a diluent.

[0171] In some embodiments of the present invention, the fluorescent agent is selected from at least one of resazurin and Bengal tiger red.

[0172] In some embodiments of the present invention, the inhibitor is butylated hydroxytoluene.

[0173] In some embodiments of the present invention, the antioxidant is sun-fast yellow.

[0174] In some embodiments of the present invention, the auxiliary agent is 0 to 0.5 parts by weight, more preferably 0.2 to 0.5 parts by weight.

[0175] It is worth noting that in some embodiments of the present invention, a resin monomer combination is used to ensure the stability of the resin reaction, and the initiator system uses two initiators, free radical and cationic, which are beneficial for reducing the increase in resin shrinkage and contact with the tooth and promoting tooth healing and regeneration.

[0176] The fourth aspect

[0177] See also Figure 2 , a method for preparing the above self-healing resin, the method comprising the following steps:

[0178] A1, providing acrylic monomers, initiators, inorganic fillers, additives and the above-mentioned microcapsules or microcapsules obtained by the above-mentioned method;

[0179] A2, mixing the acrylic monomer, microcapsules and initiator;

[0180] A3, mixing the mixture obtained in step A2 with the inorganic filler;

[0181] A4, stirring the mixture obtained in step A3 under vacuum conditions to obtain the self-healing resin.

[0182] In some embodiments of the present invention, in step A2, the mixing is carried out under heating conditions by stirring with a double planetary stirrer, wherein the heating temperature is 50-70°C, the stirring speed is 10-30rpm, and the stirring time is 0.5-2h. Exemplarily, the heating temperature is any one of 55°C, 60°C, and 65°C or a range between any two values, the stirring speed is any one of 15rpm, 20rpm, and 25rpm or a range between any two values, and the stirring time is any one of 1h, 1.2h, or 1.6h or a range between any two values.

[0183] In some embodiments of the present invention, in step A3, the mixing is carried out under heating conditions by stirring with a double planetary stirrer, wherein the heating temperature is 50-70°C, the stirring speed is 10-30rpm, and the stirring time is 0.5-2h. Exemplarily, the heating temperature is any one of 55°C, 60°C, and 65°C or a range between any two values, the stirring speed is any one of 15rpm, 20rpm, or 25rpm or a range between any two values, and the stirring time is any one of 1h, 1.3h, or 1.6h or a range between any two values.

[0184] In some embodiments of the present invention, in step A4, the vacuum degree is -0.1 to (-0.01) MPa, the stirring speed is 5 to 20 rpm, the stirring temperature is 50 to 70°C, and the stirring time is 0.5 to 2 hours. Exemplarily, the vacuum degree is any one of -0.08 MPa, -0.05 MPa or -0.03 MPa or a range between any two values, the stirring speed is any one of 10 rpm, 12 rpm, 16 rpm or a range between any two values, and the stirring speed is any one of 55°C, 60°C, 65°C or a range between any two values.

[0185] Fifth Aspect

[0186] A dental restoration, a specific example of which can be any one of an inlay, an onlay, a crown, a bridge, a molar / anterior veneer, and an implant superstructure; the dental restoration is made of the above-mentioned microcapsules, or the microcapsules obtained by the above-mentioned method, or the above-mentioned self-repairing resin, or the self-repairing resin obtained by the above-mentioned method.

[0187] In some embodiments of the present invention, the self-healing resin provided by the present invention can be filled into a carious cavity and cured by ultraviolet irradiation to form the dental restoration; it can be understood that the specific process parameters of this operation, such as the wavelength of ultraviolet rays, irradiation power and duration, are common knowledge in the art and are not enumerated here.

[0188] The present invention provides a microcapsule and a preparation method thereof, a self-repairing resin and a preparation method thereof, and a dental restoration, which solve the problem of microcracks and wear of dental resin materials during long-term service.

[0189] The core innovation of the dental resin material involved in the present invention lies in its unique self-repairing function. This resin can release pre-packaged repair agents through built-in microcapsule components when it is mechanically damaged, thereby achieving self-repair; the microcapsules contain one or more monomers and catalysts. When cracks appear on the resin surface, the microcapsules rupture, and the released contents will quickly polymerize, fill the cracks and restore the integrity of the material.

[0190] Compared with existing dental resin materials, the self-healing resin of this patent has the following advantages:

[0191] 1. Higher mechanical strength: Due to the existence of self-repair mechanism, the resin material can quickly restore its mechanical properties after being damaged, thereby extending its service life;

[0192] 2. Better durability: Self-healing resins can resist wear and tear from daily use and chemical erosion in the oral environment;

[0193] 3. Simplified maintenance process: Traditional restorative materials may require regular maintenance and repair, while self-healing resins reduce this need, providing convenience for patients and dentists;

[0194] 4. Cost-effectiveness: Although the initial cost of self-healing resins may be slightly higher, their longer service life and reduced maintenance requirements can ultimately reduce overall costs.

[0195] In order to achieve the self-healing function, this patent uses a special microcapsule design that allows the microcapsules to rupture and release the repair agent when subjected to specific stimuli, such as temperature changes or mechanical stress. In addition, molecules that promote dynamic bonding are added to the resin, which can quickly reorganize after the microcapsules rupture, further enhancing the repair effect.

[0196] Example 1

[0197] This embodiment includes two processes, one is the preparation of microcapsules, and the other is the preparation of self-healing resin.

[0198] The preparation process of the microcapsules is as follows:

[0199] S1, preparing raw materials: providing 40 parts by weight of polylactic acid-co-glycolic acid, 8 parts by weight of bone morphogenetic protein, 8 parts by weight of a mixture of polypeptides and proteins, 4 parts by weight of di(2-ethylhexyl)phthalate, 4 parts by weight of polyvinyl pyrrolidone, and 4 parts by weight of hydroxyethyl methacrylate, wherein the mass ratio of the polypeptide to the protein in the mixture of polypeptides and proteins is 1:1, the molecular weight of the polypeptide is 1000-20000, and the molecular weight of the protein is 1000-20000;

[0200] S2, preparing the emulsion: pouring the bone morphogenetic protein, water, and the mixture of peptides and proteins into an emulsifying pot, and stirring at a stirring speed of 500 rpm for 15 min;

[0201] S3, heating: heating the emulsion obtained in step S2 to 40°C, and emulsifying the emulsion at a stirring speed of 1500 rpm for 1 hour. The emulsification process here refers to the dispersion process of the polymer matrix, and the polypeptide and protein have a certain auxiliary effect;

[0202] S4, microcapsule polymerization: polylactic acid-co-glycolic acid, di(2-ethylhexyl) phthalate, polyvinyl pyrrolidone, hydroxyethyl methacrylate and the emulsion obtained in step S3 were mixed, and emulsified at 40° C. with a stirring speed of 2000 rpm for 1 h;

[0203] S5, drying: using a blower, drying the emulsion obtained in step S4 at a drying temperature of 60° C. for 6 hours;

[0204] S6, sieving: the dried product obtained in step S5 is crushed and sieved with a 100-mesh sieve to obtain the microcapsules.

[0205] The microcapsules prepared by the above process are used in the preparation process of the following self-healing resin:

[0206] A1: preparing raw materials: providing 20 parts by weight of bisphenol A propylene glycol dimethacrylate, 10 parts by weight of urethane dimethacrylate, 6 parts by weight of triethylene glycol dimethacrylate, 17 parts by weight of the microcapsule, 0.4 parts by weight of camphorquinone, 0.2 parts by weight of diphenyliodonium hexafluorophosphate, 30 parts by weight of barium glass powder, and 15 parts by weight of nano-silicon dioxide, wherein the barium content of the barium glass powder is 25wt.%, and the particle size is 0.8μm, and the particle size of the nano-silicon dioxide is 0.8μm;

[0207] A2, stirring and mixing: mix the bisphenol A propylene glycol dimethacrylate, triethylene glycol dimethacrylate, urethane dimethacrylate, the microcapsule, camphorquinone, and diphenyliodonium hexafluorophosphate in step A1, and stir with a double planetary stirrer at 60° C. and a stirring speed of 20 rpm for 1 hour;

[0208] A3, powder mixing: the mixture in step A2 is mixed with barium glass powder and nano-silicon dioxide, and stirred with a double planetary stirrer at 60°C and a stirring speed of 20 rpm for 3 h;

[0209] A4, vacuuming: Stir the product obtained in step A3 for 1 h under the conditions of vacuum degree of -0.1 MPa, temperature of 60°C and stirring speed of 10 rpm.

[0210] Example 2

[0211] This embodiment includes two processes, one is the preparation of microcapsules, and the other is the preparation of self-healing resin.

[0212] The preparation process of the microcapsules is as follows:

[0213] S1, preparing raw materials: providing 36 parts by weight of polylactic acid-co-glycolic acid, 8 parts by weight of bone morphogenetic protein, 6 parts by weight of a mixture of polypeptides and proteins, 4 parts by weight of di(2-ethylhexyl) phthalate, 4 parts by weight of polyvinyl pyrrolidone, and 4 parts by weight of hydroxyethyl methacrylate, wherein the mass ratio of the polypeptide to the protein in the mixture of polypeptides and proteins is 1:1, the molecular weight of the polypeptide is 1000-20000, and the molecular weight of the protein is 1000-20000;

[0214] S2, preparing the emulsion: pouring the bone morphogenetic protein, water, and the mixture of peptides and proteins into an emulsifying pot, and stirring at a stirring speed of 500 rpm for 15 min;

[0215] S3, heating: heating the emulsion obtained in step S2 to 40°C, and emulsifying at a stirring speed of 1500 rpm for 1 hour;

[0216] S4, microcapsule polymerization: polylactic acid-co-glycolic acid, di(2-ethylhexyl) phthalate, polyvinyl pyrrolidone, hydroxyethyl methacrylate and the emulsion obtained in step S3 were mixed, and emulsified at 40° C. with a stirring speed of 2000 rpm for 1 h;

[0217] S5, drying: using a blower, drying the emulsion obtained in step S4 at a drying temperature of 60° C. for 6 hours;

[0218] S6, sieving: the dried product obtained in step S5 is crushed and sieved with a 100-mesh sieve to obtain the microcapsules.

[0219] The microcapsules prepared by the above process are used in the preparation process of the following self-healing resin:

[0220] A1: preparing raw materials: providing 10 parts by weight of bisphenol A propylene glycol dimethacrylate, 10 parts by weight of dimethacrylate urethane, 8 parts by weight of dimethacrylate triethylene glycol, 15.5 parts by weight of the microcapsule, 0.2 parts by weight of camphorquinone, 0.2 parts by weight of diphenyliodonium hexafluorophosphate, 30 parts of strontium glass powder, and 10 parts of nano zirconium dioxide, wherein the strontium element content in the strontium glass powder is 30wt.%, and the particle size is 0.8μm, and the particle size of the nano zirconium dioxide is 0.8μm;

[0221] A2, stirring and mixing: mix the bisphenol A propylene glycol dimethacrylate, triethylene glycol dimethacrylate, urethane dimethacrylate, the microcapsule, camphorquinone, and diphenyliodonium hexafluorophosphate in step A1, and stir with a double planetary stirrer at 60° C. and a stirring speed of 20 rpm for 1 hour;

[0222] A3, powder mixing: the mixture in step A2 is mixed with strontium glass powder and nano-silicon dioxide, and stirred with a double planetary stirrer at 60°C and a stirring speed of 20 rpm for 3 h;

[0223] A4, vacuuming: Stir the product obtained in step A3 for 1 h under the conditions of vacuum degree of -0.1 MPa, temperature of 60°C and stirring speed of 10 rpm.

[0224] Example 3

[0225] This embodiment includes two processes, one is the preparation of microcapsules, and the other is the preparation of self-healing resin.

[0226] The preparation process of the microcapsules is as follows:

[0227] S1, preparing raw materials: providing 50 parts by weight of polylactic acid-co-glycolic acid, 12 parts by weight of bone morphogenetic protein, 24 parts by weight of a mixture of polypeptides and proteins, 4 parts by weight of di(2-ethylhexyl)phthalate, 4 parts by weight of polyvinyl pyrrolidone, and 4 parts by weight of hydroxyethyl methacrylate, wherein the mass ratio of the polypeptide to the protein in the mixture of polypeptides and proteins is 1:1, the molecular weight of the polypeptide is 1000-20000, and the molecular weight of the protein is 1000-20000;

[0228] S2, preparing the emulsion: pouring the bone morphogenetic protein, water, and the mixture of peptides and proteins into an emulsifying pot, and stirring at a stirring speed of 400 rpm for 10 min;

[0229] S3, heating: heating the emulsion obtained in step S2 to 30°C, and emulsifying at a stirring speed of 1500 rpm for 0.5 h;

[0230] S4, microcapsule polymerization: polylactic acid-co-glycolic acid, di(2-ethylhexyl) phthalate, polyvinyl pyrrolidone, hydroxyethyl methacrylate and the emulsion obtained in step S3 were mixed, and emulsified at 30° C. with a stirring speed of 1500 rpm for 1 h;

[0231] S5, drying: using a blower, drying the emulsion obtained in step S4 at a drying temperature of 60° C. for 6 hours;

[0232] S6, sieving: the dried product obtained in step S5 is crushed and sieved with a 100-mesh sieve to obtain the microcapsules.

[0233] The microcapsules prepared by the above process are used in the preparation process of the following self-healing resin:

[0234] A1: preparing raw materials: providing 10 parts by weight of bisphenol A propylene glycol dimethacrylate, 20 parts by weight of dimethacrylate urethane, 4 parts by weight of dimethacrylate triethylene glycol, 24.5 parts by weight of the microcapsule, 0.5 parts by weight of TPO, 20 parts by weight of barium glass powder, 10 parts by weight of strontium glass powder, 15 parts by weight of nano silicon dioxide, 3 parts by weight of nano zirconium dioxide, and 7 parts by weight of silicon oxide zirconium oxide composite powder, wherein the barium content of the barium glass powder is 25wt.%, the strontium content of the strontium glass powder is 25wt.% and the particle size is 0.8μm, and the particle size of the nano silicon dioxide is 0.8μm;

[0235] A2, stirring and mixing: the bisphenol A propylene glycol dimethacrylate, triethylene glycol dimethacrylate, urethane dimethacrylate, the microcapsules and TPO in step A1 are stirred by a double planetary stirrer at 60° C. and a stirring speed of 20 rpm for 1 hour;

[0236] A3, powder mixing: the mixture in step A2 is mixed with barium glass powder, strontium glass powder, nano-silicon dioxide, and silicon oxide zirconium oxide composite powder, and stirred with a double planetary stirrer at 60° C. and a stirring speed of 20 rpm for 3 h;

[0237] A4, vacuuming: Stir the product obtained in step A3 for 1 h under the conditions of vacuum degree of -0.1 MPa, temperature of 60°C and stirring speed of 10 rpm.

[0238] Example 4

[0239] This embodiment includes two processes, one is the preparation of microcapsules, and the other is the preparation of self-healing resin.

[0240] The preparation process of the microcapsules is as follows:

[0241] S1, preparing raw materials: providing 24 parts by weight of polylactic acid-co-glycolic acid, 8 parts by weight of bone morphogenetic protein, 28 parts by weight of a mixture of polypeptides and proteins, 6 parts by weight of di(2-ethylhexyl)phthalate, 6 parts by weight of polyvinyl pyrrolidone, and 6 parts by weight of hydroxyethyl methacrylate, wherein the mass ratio of the polypeptide to the protein in the mixture of polypeptides and proteins is 1:1, the molecular weight of the polypeptide is 1000-20000, and the molecular weight of the protein is 1000-20000;

[0242] S2, preparing the emulsion: pouring the bone morphogenetic protein, water, and the mixture of peptides and proteins into an emulsifying pot, and stirring at a stirring speed of 600 rpm for 20 min;

[0243] S3, heating: heating the emulsion obtained in step S2 to 50°C, and emulsifying at a stirring speed of 2500 rpm for 2 hours;

[0244] S4, microcapsule polymerization: polylactic acid-co-glycolic acid, di(2-ethylhexyl) phthalate, polyvinyl pyrrolidone, hydroxyethyl methacrylate and the emulsion obtained in step S3 were mixed, and emulsified at 50° C. with a stirring speed of 2500 rpm for 1 h;

[0245] S5, drying: using a blower, drying the emulsion obtained in step S4 at a drying temperature of 60° C. for 6 hours;

[0246] S6, sieving: the dried product obtained in step S5 is crushed and sieved with a 100-mesh sieve to obtain the microcapsules.

[0247] The microcapsules prepared by the above process are used in the preparation process of the following self-healing resin:

[0248] A1: preparing raw materials: providing 20 parts by weight of bisphenol A propylene glycol dimethacrylate, 20 parts by weight of dimethacrylate urethane, 4 parts by weight of dimethacrylate triethylene glycol, 19.5 parts by weight of the microcapsule, 0.3 parts by weight of camphorquinone, 20 parts by weight of barium glass powder, and 20 parts by weight of nano-silicon dioxide, wherein the barium content of the barium glass powder is 25wt.%, and the particle size is 0.8μm, and the particle size of the nano-silicon dioxide is 0.8μm;

[0249] A2, stirring and mixing: the bisphenol A propylene glycol dimethacrylate, triethylene glycol dimethacrylate, urethane dimethacrylate, the microcapsules, and camphorquinone in step A1 are stirred with a double planetary stirrer at 60° C. and a stirring speed of 20 rpm for 1 hour;

[0250] A3, powder mixing: the mixture in step A2 is mixed with barium glass powder and nano-silicon dioxide, and stirred with a double planetary stirrer at 60°C and a stirring speed of 20 rpm for 3 h;

[0251] A4, vacuuming: Stir the product obtained in step A3 for 1 h under the conditions of vacuum degree of -0.1 MPa, temperature of 60°C and stirring speed of 10 rpm.

[0252] Comparative Example 1

[0253] This embodiment includes two processes, one is the preparation of microcapsules, and the other is the preparation of self-healing resin.

[0254] The preparation process of the microcapsules is as follows:

[0255] S1, prepare raw materials: provide 60 parts by weight of polylactic acid-glycolic acid copolymer, 2 parts by weight of di(2-ethylhexyl) phthalate, and 6 parts by weight of hydroxyethyl methacrylate,

[0256] S2, microcapsule polymerization: poly(lactic acid-co-glycolic acid), di(2-ethylhexyl) phthalate, and hydroxyethyl methacrylate were mixed and emulsified at 40°C with a stirring speed of 2000 rpm for 1 h;

[0257] S3, drying: using a blower, drying the emulsion obtained in step S2 at a drying temperature of 60° C. for 6 hours;

[0258] S4, sieving: the dried product obtained in step S3 is crushed and sieved with a 100-mesh sieve to obtain the microcapsules.

[0259] The microcapsules prepared by the above process are used in the preparation process of the following self-healing resin:

[0260] A1: preparing raw materials: providing 14 parts by weight of bisphenol A propylene glycol dimethacrylate, 10 parts by weight of urethane dimethacrylate, 6 parts by weight of triethylene glycol dimethacrylate, 17 parts by weight of the microcapsule, 0.2 parts by weight of camphorquinone, 30 parts by weight of barium glass powder, and 15 parts by weight of nano-silicon dioxide, wherein the barium content of the barium glass powder is 25wt.%, and the particle size is 0.8μm, and the particle size of the nano-silicon dioxide is 0.8μm;

[0261] A2, stirring and mixing: the bisphenol A propylene glycol dimethacrylate, triethylene glycol dimethacrylate, urethane dimethacrylate, the microcapsules, and camphorquinone in step A1 are stirred with a double planetary stirrer at 60° C. and a stirring speed of 20 rpm for 1 hour;

[0262] A3, powder mixing: the mixture in step A2 is mixed with barium glass powder and nano-silicon dioxide, and stirred with a double planetary stirrer at 60°C and a stirring speed of 20 rpm for 3 h;

[0263] A4, vacuuming: Stir the product obtained in step A3 for 1 h under the conditions of vacuum degree of -0.1 MPa, temperature of 60°C and stirring speed of 10 rpm.

[0264] Comparative Example 2

[0265] This embodiment includes two processes, one is the preparation of microcapsules, and the other is the preparation of self-healing resin.

[0266] The preparation process of the microcapsules is as follows:

[0267] S1, preparing raw materials: providing 60 parts by weight of polylactic acid-co-glycolic acid, 20 parts by weight of a mixture of polypeptides and proteins, 4 parts by weight of di(2-ethylhexyl)phthalate, and 4 parts by weight of hydroxyethyl methacrylate, wherein in the mixture of polypeptides and proteins, the mass ratio of polypeptides to proteins is 1:1, the molecular weight of the polypeptides is 1000-20000, and the molecular weight of the proteins is 1000-20000;

[0268] S2, prepare the emulsion: pour water and the mixture of peptides and proteins into the emulsifier and stir at a stirring speed of 500 rpm for 15 min;

[0269] S3, heating: heating the emulsion obtained in step S2 to 40°C, and emulsifying at a stirring speed of 1500 rpm for 1 hour;

[0270] S4, microcapsule polymerization: polylactic acid-co-glycolic acid, di(2-ethylhexyl) phthalate, hydroxyethyl methacrylate and the emulsion obtained in step S3 were mixed, and emulsified at 40° C. with a stirring speed of 2000 rpm for 1 h;

[0271] S5, drying: using a blower, drying the emulsion obtained in step S4 at a drying temperature of 60° C. for 6 hours;

[0272] S6, sieving: the dried product obtained in step S5 is crushed and sieved with a 100-mesh sieve to obtain the microcapsules.

[0273] The microcapsules prepared by the above process are used in the preparation process of the following self-healing resin:

[0274] A1: preparing raw materials: providing 10 parts by weight of bisphenol A glycerol dimethacrylate, 10 parts by weight of urethane dimethacrylate, 4 parts by weight of triethylene glycol dimethacrylate, 22 parts by weight of the microcapsule, 0.2 parts by weight of camphorquinone, 0.1 parts by weight of diphenyliodonium hexafluorophosphate, 20 parts by weight of barium glass powder, 10 parts by weight of strontium glass powder, 5 parts by weight of nano-silicon dioxide, and 5 parts by weight of silicon oxide zirconium oxide composite powder, wherein the barium content of the barium glass powder is 25wt.%, the strontium content of the strontium glass powder is 30wt%, and the particle size is 0.8μm, and the particle size of the nano-silicon dioxide and silicon oxide zirconium oxide composite powder is 0.8μm;

[0275] A2, stirring and mixing: mix the bisphenol A propylene glycol dimethacrylate, triethylene glycol dimethacrylate, urethane dimethacrylate, the microcapsule, camphorquinone, and diphenyliodonium hexafluorophosphate in step A1, and stir with a double planetary stirrer at 60° C. and a stirring speed of 20 rpm for 1 hour;

[0276] A3, powder mixing: the mixture in step A2 is mixed with barium glass powder and nano-silicon dioxide, and stirred with a double planetary stirrer at 60°C and a stirring speed of 20 rpm for 3 h;

[0277] A4, vacuuming: Stir the product obtained in step A3 for 1 h under the conditions of vacuum degree of -0.1 MPa, temperature of 60°C and stirring speed of 10 rpm.

[0278] The raw materials and amounts of Examples 1 to 4 and Comparative Examples 1 to 2 are summarized in Table 1 below.

[0279] Table 1 Raw materials and dosage of Examples 1 to 4 and Comparative Examples 1 to 2

[0280]

[0281]

[0282] Test Case

[0283] This test example involves the performance testing of the particle size, resin shrinkage, crack healing state, shrinkage and mechanical properties of the microcapsules of the present invention:

[0284] (1) Microcapsule particle size: Particle size was measured using a laser particle size analyzer.

[0285] Table 2 Particle size of microcapsules obtained in each example

[0286] Example 1 Example 2 Example 3 Example 4 Particle size (D50) 135μm 162μm 287μm 519μm

[0287] (2) The test method for mechanical properties is as follows: Flexural strength is tested according to the method specified in 7.11 of YY 1042-2011, and the results meet the requirements of 2.4;

[0288] The compression performance is determined in accordance with GB / T 1041-2008 for the determination of compression performance of plastics. The size of the sample is a cylinder with a diameter of 4 mm and a height of 6-10 mm. The shrinkage rate is the volume change after 14 days of reaction.

[0289] Table 3 Performance parameters of dental restorations made from self-repairing resins obtained in various embodiments and comparative examples

[0290]

[0291] (4) Healing status of tooth cracks: Measure calcium production at the bone crack site, test Ca production at the crack before and after repair, and use an energy spectrometer to measure calcium production.

[0292] Table 4 Ca generation in the cracks of dental restorations made of self-repairing resins obtained in various embodiments and comparative examples

[0293]

[0294] The above is only a specific implementation of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can easily think of changes or substitutions within the technical scope disclosed by the present invention, which should be covered within the protection scope of the present invention. Therefore, the protection scope of the present invention shall be based on the protection scope of the claims. In addition, the specification uses specific examples to illustrate the principles and implementation methods of the present invention. The description of the above embodiments is only used to help understand the method of the present invention and its core idea. The content of this specification should not be understood as a limitation on the present invention.

Claims

1. A microcapsule, It is characterized in that The raw materials of the microcapsules include: A polymer matrix, an active substance, a plasticizer, a dispersant, and methacrylates, wherein the active substance comprises a bone morphogenetic protein.

2. The microcapsule according to claim 1, It is characterized in that The polymer matrix is ​​30 to 60 parts by weight, the active substance is 5 to 40 parts by weight, the plasticizer is 1 to 10 parts by weight, the dispersant is 1 to 10 parts by weight, and the methacrylate is 1 to 10 parts by weight; Preferably, the polymer matrix is ​​20 to 40 parts by weight, the active substance is 15 to 40 parts by weight, the plasticizer is 3 to 7 parts by weight, the dispersant is 3 to 7 parts by weight, and the methacrylate is 3 to 7 parts by weight.

3. The microcapsule according to claim 1, It is characterized in that The polymer matrix is ​​selected from at least one of natural polymers, semi-synthetic polymers and synthetic polymers; Preferably, the natural polymer is selected from at least one of gelatin, gum arabic, chitosan and alginate; Preferably, the semi-synthetic polymer is selected from at least one of methyl cellulose, ethyl cellulose, carboxymethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose and hydroxypropyl cellulose; Preferably, the synthetic polymer is selected from at least one of polylactic acid-co-glycolic acid, polylactic acid, poly-α-hydroxycarboxylic acid, polyacrylate, polyethylene glycol, and polymethacrylate; More preferably, the polylactic acid-co-glycolic acid comprises 40 to 75 wt.% of units derived from lactic acid and 25 to 60 wt.% of units derived from glycolic acid; More preferably, the glass transition temperature of the polylactic acid-glycolic acid copolymer is 40-60°C.

4. The microcapsule according to claim 1, It is characterized in that The active substance further comprises biomolecules other than bone morphogenetic protein; preferably, the biomolecule is at least one selected from polypeptides and proteins; Preferably, the bone morphogenetic protein is 10 to 20 parts by weight, preferably 10 to 15 parts by weight; Preferably, the biomolecules other than bone morphogenetic protein, more preferably polypeptides and proteins, are in an amount of 1 to 10 parts by weight, preferably 5 parts by weight.

5. The microcapsule according to claim 1, It is characterized in that The plasticizer is selected from at least one of phthalate plasticizers, epoxy plasticizers, polymer plasticizers, acrylate plasticizers, phosphate esters, triethanolamine, and dioctyl adipate; Preferably, the phthalate plasticizer is selected from at least one of dibutyl phthalate and (2-ethylhexyl) phthalate; Preferably, the epoxy plasticizer is epoxidized soybean oil; Preferably, the polymer plasticizer is a polyester plasticizer, and the polyester plasticizer is selected from at least one of poly(hexanediol adipate), poly(butylene adipate), poly(ethylene adipate), poly(furfuryl furandicarboxylate), poly(hexanediol furandicarboxylate), poly(hexanediol terephthalate), polyethylene terephthalate, and poly(butylene terephthalate); Preferably, the phosphate ester is selected from at least one of tricresyl phosphate and trioctyl phosphate; Preferably, the acrylic ester plasticizer is 1,6-hexanediol diacrylate.

6. The microcapsule according to claim 1, It is characterized in that The dispersant is at least one of polyvinyl pyrrolidone, sodium dodecyl sulfonate, sodium benzene sulfonate, polyacrylamide, sodium polystyrene sulfonate, and dibasic acid esters; Preferably, the dibasic acid ester is at least one of dioctyl sebacate and diisodecyl adipate; Preferably, the molecular weight of the polyvinyl pyrrolidone is less than 40,000. More preferably, the polyvinyl pyrrolidone is at least one of K10, K15, and K30, and more preferably K15.

7. The microcapsule according to claim 1, It is characterized in that The methacrylates are selected from methacrylic acid C 1 -C 8 Alkyl ester, methacrylate hydroxy C 1 -C 8 The alkyl ester is preferably at least one selected from the group consisting of hydroxyethyl methacrylate, a modified product of hydroxyethyl methacrylate, methyl methacrylate, ethyl methacrylate, propyl methacrylate, and hydroxypropyl methacrylate.

8. A method for preparing the microcapsules according to any one of claims 1 to 7, It is characterized in that The method is selected from any one of emulsion polymerization, solvent evaporation and spray drying.

9. The method according to claim 8, It is characterized in that The emulsion polymerization method comprises the following steps: S1, providing a polymer matrix, an active substance, a plasticizer, a dispersant and methacrylates; S2, mixing the active substance and water; S3, adding a dispersant to the mixture obtained in step S2 to emulsify the mixture to obtain an emulsion; S4, mixing the polymer matrix, methacrylate, plasticizer and the emulsion obtained in step S3 to cause a polymerization reaction; S5, drying the product obtained in step S4; S6, crushing and sieving the dried product obtained in step S5 to obtain the microcapsules.

10. The method according to claim 9, It is characterized in that In step S2, the mixing is performed in an emulsification container. Preferably, the emulsification container is an emulsification pot. Preferably, the mixing is performed by stirring, wherein the stirring speed is 400 to 600 rpm and the stirring time is 10 to 20 min; And / or, in step S3, the emulsification conditions are: temperature of 30-50° C., stirring speed of 1500-2500 rpm, and stirring time of 0.5-2 h; And / or, in step S4, the polymerization reaction conditions are: temperature of 30-50° C., stirring speed of 1500-2500 rpm, and stirring time of 0.5-2 h; And / or, in step S5, the drying conditions are: temperature of 50-70° C., and drying time of 4-8 h; And / or, in step S6, the screening process is performed using a sieve, and the mesh size of the sieve is any one of 50 mesh, 100 mesh or 150 mesh.

11. A self-healing resin, It is characterized in that The raw materials of the self-healing resin include: Acrylic monomer, initiator, inorganic filler, auxiliary agent and microcapsule as claimed in any one of claims 1 to 7 or microcapsule obtained by the method as claimed in any one of claims 8 to 10; Preferably, the initiator is a mixture of a free radical photoinitiator and a cationic photoinitiator.

12. The self-healing resin according to claim 11, It is characterized in that The acrylic monomer is 15 to 50 parts by weight, the initiator is 0.1 to 10 parts by weight, the inorganic filler is 20 to 70 parts by weight, and the microcapsule is 10 to 40 parts by weight; Preferably, the acrylic monomer is 15 to 30 parts by weight, the initiator is 0.2 to 4 parts by weight, the inorganic filler is 30 to 70 parts by weight, and the microcapsule is 15 to 30 parts by weight.

13. The self-healing resin according to claim 11, It is characterized in that The acrylic monomer is selected from any one of bisphenol A propylene glycol dimethacrylate, triethylene glycol dimethacrylate, methyl methacrylate, hydroxyethyl methacrylate, urethane dimethacrylate, ethoxylated bisphenol A propylene glycol dimethacrylate, polyethylene glycol acrylate, ethylene glycol dimethacrylate, methyl α-cyanoacrylate, butyl α-cyanoacrylate, and decyl α-cyanoacrylate, or a combination of two or more thereof.

14. The self-healing resin according to claim 11, It is characterized in that The photoinitiator includes at least one of a free radical photoinitiator and a cationic photoinitiator; Preferably, the free radical photoinitiator is selected from at least one of camphorquinone, TPO, phenylbis(2,4,6-trimethylbenzoic acid)phosphine oxide, phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide, and benzophenone; Preferably, the cationic photoinitiator is selected from at least one of diazonium salts, diaryl iodonium salts, triaryl sulfonium salts, alkyl sulfonium salts, iron arene salts, sulfonyloxy ketones, and triaryl siloxane ethers; Preferably, the photoinitiator comprises a free radical photoinitiator and a cationic photoinitiator; More preferably, the photoinitiator is a mixture of camphorquinone and diaryliodonium salt; More preferably, the diaryliodonium salt is diphenyliodonium hexafluorophosphate.

15. The self-healing resin according to claim 11, It is characterized in that The inorganic filler is at least one selected from calcium silicate particles, quartz powder, barium glass powder, lanthanum glass powder, borosilicate glass powder, silicon oxide-zirconium oxide composite powder, silicon oxide-ytterbium oxide composite powder, silicon dioxide powder, zirconium oxide powder, and titanium oxide powder; Preferably, the inorganic filler is barium glass powder; Preferably, the inorganic filler is nano powder; Preferably, the particle size of the inorganic filler is 0.3 to 1.5 μm, preferably 0.5 to 1 μm; Preferably, the barium content in the barium glass powder is 20 to 50 wt.%, preferably 30 to 40 wt.%; Preferably, the lanthanum metal content in the lanthanum glass powder is about 10-50wt.%, preferably 20-40wt.%, Preferably, the content of zirconium in the silicon oxide-zirconium oxide composite powder is 20 to 40 wt.%; Preferably, the ytterbium content in the silicon oxide-ytterbium oxide composite powder is 10 to 40 wt.%.

16. The self-healing resin according to claim 11, It is characterized in that The auxiliary agent is selected from at least one of a fluorescent agent, an indicator, an inhibitor, an accelerator, a viscosity modifier, a wetting agent, an antioxidant, a surfactant, a stabilizer, and a diluent; Preferably, the fluorescent agent is at least one of resazurin and Bengal tiger red; Preferably, the inhibitor is butylated hydroxytoluene; Preferably, the antioxidant is sun-fast yellow; Preferably, the auxiliary agent is 0 to 0.5 parts by weight, more preferably 0.2 to 0.5 parts by weight.

17. A method for preparing the self-healing resin according to any one of claims 11 to 16, It is characterized in that The method comprises the following steps: A1, providing an acrylic monomer, an initiator, an inorganic filler, an auxiliary agent, and a microcapsule according to any one of claims 1 to 7 or a microcapsule obtained by the method according to any one of claims 8 to 10; A2, mixing the acrylic monomer, microcapsules and initiator; A3, mixing the mixture obtained in step A2 with the inorganic filler; A4, stirring the mixture obtained in step A3 under vacuum conditions to obtain the self-healing resin.

18. The method according to claim 17, It is characterized in that In the step A2, the mixing is carried out by stirring with a double planetary stirrer under heating conditions, wherein the heating temperature is 30 to 50° C., the stirring speed is 10 to 30 rpm, and the stirring time is 0.5 to 2 h; And / or, in the step A3, the mixing is carried out by stirring with a double planetary stirrer under heating conditions, wherein the heating temperature is 50 to 70° C., the stirring speed is 10 to 30 rpm, and the stirring time is 0.5 to 2 h; And / or, in step A4, the vacuum degree is -0.1 to (-0.01) MPa, the stirring speed is 5 to 20 rpm, the stirring temperature is 50 to 70° C., and the stirring time is 0.5 to 2 h.

19. A dental restoration, It is characterized in that The dental restoration is any one of an inlay, an onlay, a crown, a bridge, a molar / anterior veneer, and an implant superstructure; The dental restoration is made using the microcapsules according to any one of claims 1 to 7, or the microcapsules obtained by the method according to any one of claims 8 to 10, or the self-healing resin according to any one of claims 11 to 16, or the self-healing resin obtained by the method according to any one of claims 17 to 18.

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