Methods and compositions for stabilizing nanogels and dental compositions produced from nanogels
阅读说明：本技术 使纳米凝胶稳定的方法和组合物以及由纳米凝胶产生的牙科组合物 (Methods and compositions for stabilizing nanogels and dental compositions produced from nanogels ) 是由 金晓明 B·尤斯塔 C·舒弗勒 J·科里 T·泰积斯 K·纽豪斯 J·布伦内斯 吕辉 于 2019-08-29 设计创作，主要内容包括：本发明涉及使纳米凝胶稳定的方法和组合物,以及这种纳米凝胶在牙科组合物中用作添加剂的用途。(The present invention relates to methods and compositions for stabilizing nanogels, and the use of such nanogels as additives in dental compositions.)
1. A dental composition comprising a nanogel, the nanogel being formed by a method comprising the steps of:
(a) polymerizing a mixture comprising:
(i) at least one comonomer having one ethylenically unsaturated group,
(ii) at least one of a comonomer having two ethylenically unsaturated groups and at least one comonomer having at least three ethylenically unsaturated groups,
(iii) at least one chain transfer agent, and
(iv) an initiator;
to obtain a nanogel solution; and is
(b) Terminating the polymerization by reducing the reaction temperature and quenching the nanogel solution with a free radical scavenger.
2. The dental composition of claim 1, wherein the mixture further comprises a solvent.
3. The dental composition of claim 1 wherein the free radical scavenger is present in at least 0.1% by weight based on the total weight of the comonomers in the mixture.
4. The dental composition of claim 1, wherein the free radical scavenger in step (b) is: TEMPO, substituted TEMPO, a polychlorinated triphenylmethyl radical, phenalkenyl, cyclopentadienyl, other carbon-centered radicals, nitroxide radicals, di-t-alkyl imines, delocalized radicals containing hydrazino units, metal-coordinated phenoxy radicals, stable radicals containing thiazolyl units, or stable radicals with heavy elements in the p-region.
5. The dental composition of claim 4, wherein the free radical scavenger is TEMPO.
6. The dental composition of claim 1, wherein the comonomer having one ethylenically unsaturated group is selected from the group consisting of: (meth) acrylic acid C1-C12Alkyl esters, hydroxyalkyl (meth) acrylates, allyl ethers, aromatic (meth) acrylates, vinyl ethers, vinyl esters, vinyl amines, acrylamides, methacrylamides, hydroxyalkyl acrylamides, and hydroxyalkyl methacrylamides.
7. The dental composition of claim 1, wherein the comonomer having two ethylenically unsaturated groups comprises a compound having formula I:
X-R-Y
formula I
Wherein the content of the first and second substances,
x is a (meth) acryloyl or (meth) acrylamide moiety;
y is a (meth) acryloyl, methacrylamide, allyl, vinyl ether, vinyl ester, or vinylamine moiety;
r is a direct bond or an organic moiety;
wherein the organic moiety is unsubstituted or substituted C1-C18Alkylene, unsubstituted or substituted C3-C8Cycloalkylene, unsubstituted or substituted aralkylene, unsubstituted or substituted C1-C8Cycloalkylalkylene, unsubstituted or substituted C5-C18Arylene radical, or unsubstituted or substituted C3-C18A heteroarylene group; wherein each unsubstituted or substituted organic moiety may contain C1-C4Alkylene, 1 to 4 carbamate groups (-NH- (C ═ O) -O-or-O- (C ═ O) -NH-), 1 to 8 at least one of oxygen atoms or nitrogen atoms; wherein each substituted organic moiety is selected from the group consisting of alkyl, hydroxy, thiol, -COOM, -PO3M、-O-PO3M2or-SO3M, wherein M and M are independent of each other and are a hydrogen atom or a metal.
8. The dental composition of claim 1, wherein the comonomer having at least three ethylenically unsaturated groups is selected from the group consisting of: trimethylolpropane tri (meth) acrylate, pentaerythritol triacrylate, and pentaerythritol tetraacrylate, dipentaerythritol hexaacrylate, and N, N '-bisacryloyl-N, N' -bisallyl-1, 4-but-2-enediamine.
9. The dental composition of claim 1, wherein the comonomer comprises at least one comonomer having at least three ethylenically unsaturated groups present in a range of from 1 to 30 mole percent based on the total molar amount of comonomers in the mixture.
10. The dental composition of claim 1, wherein the comonomer having one ethylenically unsaturated group is present in a range of from 50 to 95 mole percent based on the total molar amount of comonomers in the mixture.
11. The dental composition of claim 1, wherein the comonomer having two ethylenically unsaturated groups is present in a range of from 5 to 50 mole percent based on the total molar amount of comonomer in the mixture.
12. The dental composition of claim 1, wherein the at least one chain transfer agent is RSH, wherein R is a linear or branched alkyl group having 3 to 20 carbon atoms.
13. The dental composition of claim 1, wherein the at least one chain transfer agent is present at a concentration of 5 to 50 mole percent based on the total moles of comonomer in the mixture.
14. The dental composition of claim 1, wherein the initiator is selected from at least one of an organic peroxide and an azo compound.
15. The dental composition of claim 14, wherein the initiator is selected from the group consisting of benzoyl peroxide, 2-azobis- (2-methylpropanenitrile), and 2, 2-azobis- (2-methylbutyronitrile).
16. The dental composition of claim 1 wherein the initiator is present at a concentration of 0.5 to 5.0% by weight based on the total weight of comonomers in the mixture.
17. The dental composition of claim 1, wherein the nanogel is soluble in at least one solvent selected from the group consisting of methyl ethyl ketone, acetone, and toluene.
18. The dental composition of claim 1, wherein the nanogel is present at a concentration of 5 to 40 weight percent based on the total weight of the composition.
19. The dental composition of claim 18, further comprising:
(i) at least one filler in a concentration of 5 to 95% by weight, based on the total weight of the composition,
(ii) at least one polymerization initiator in a concentration of 0.05 to 5% by weight, based on the total weight of the composition.
20. A nanogel formed by a method comprising the steps of:
(a) polymerizing a mixture comprising:
(i) at least one comonomer having one ethylenically unsaturated group,
(ii) at least one of a comonomer having two ethylenically unsaturated groups and at least one comonomer having at least three ethylenically unsaturated groups,
(iii) at least one chain transfer agent, and
(iv) an initiator;
to obtain a nanogel solution; and is
(b) Terminating the polymerization by reducing the reaction temperature and quenching the nanogel solution with a free radical scavenger;
wherein the nanogel is substantially free of macrogels.
21. The nanogel of claim 20 wherein said nanogel has a hydrodynamic radius of 2nm to 20 nm.
22. A method of using a nanogel as defined in claim 20 to prepare a dental composition, wherein said dental composition is a dental composite, a dental adhesive, a dental cement, a resin modified glass ionomer, a varnish, a sealant, a denture material, a composite block, and a composite ink for dental 3D printing.
23. A method of forming a nanogel, the method comprising:
(a) polymerizing a mixture comprising:
(i) at least one comonomer having one ethylenically unsaturated group,
(ii) at least one of a comonomer having two ethylenically unsaturated groups and at least one comonomer having at least three ethylenically unsaturated groups,
(iii) at least one chain transfer agent, wherein the chain transfer agent,
(iv) an initiator;
to obtain a nanogel solution; and is
(b) Terminating the polymerization by reducing the reaction temperature and quenching the nanogel solution with a free radical scavenger to form the nanogel.
24. The method of claim 23, wherein the free radical scavenger is present in a concentration such that the nanogel solution has thermal stability for 7 days of storage at 25 ℃.
25. The method of claim 23, wherein the mixture further comprises a solvent.
26. The method of claim 23, wherein the radical scavenger in step (b) is: TEMPO, substituted TEMPO, and the polychlorinated triphenylmethyl radicals, phenalkenyl radicals, cyclopentadienyl radicals, and other carbon-centered radicals, nitroxide radicals, di-t-alkyl imines, delocalized radicals containing hydrazino units, metal-coordinated phenoxy radicals, stable radicals containing thiazolyl units, or stable radicals having heavy elements in the p region.
27. The method of claim 26, wherein the radical scavenger is TEMPO.
28. The method of claim 23, wherein the thermal polymerization is conducted at a reaction temperature of 60 ℃ to 120 ℃.
29. The method of claim 23, wherein the terminating of the polymerization is carried out at a reaction temperature of-196 ℃ to 25 ℃.
30. The method of claim 24, wherein the radical scavenger is present in at least 0.1 weight percent based on the total weight of comonomer in the mixture.
31. The method of claim 24, wherein a free radical scavenger is added to the nanogel solution when 55-85% of the ethylenically unsaturated groups in the comonomer mixture have reacted to form the nanogel.
32. The method of claim 23, wherein the comonomer having one ethylenically unsaturated group is selected from the group consisting of: (meth) acrylic acid C1-C12Alkyl esters, hydroxyalkyl (meth) acrylates, allyl ethers, aromatic (meth) acrylates, vinyl ethers, vinyl esters, vinyl amines, acrylamides, methacrylamides, hydroxyalkyl acrylamides, and hydroxyalkyl methacrylamides.
33. The method of claim 23, wherein the comonomer having two ethylenically unsaturated groups comprises a compound having formula I:
X-R-Y
formula I
Wherein the content of the first and second substances,
x is a (meth) acryloyl or (meth) acrylamide moiety;
y is a (meth) acryloyl, methacrylamide, allyl, vinyl ether, vinyl ester, or vinylamine moiety;
r is a direct bond or an organic moiety;
wherein the organic moiety is unsubstituted or substituted C1-C18Alkylene, unsubstituted or substituted C3-C8Cycloalkylene, unsubstituted or substituted aralkylene, unsubstituted or substituted C1-C8Cycloalkylalkylene, unsubstituted or substituted C5-C18Arylene radical, or unsubstituted or substituted C3-C18A heteroarylene group; wherein each unsubstituted or substituted organic moiety may contain C1-C4Alkylene, 1 to 4 carbamate groups (-NH- (C ═ O) -O-or-O- (C ═ O) -NH-), 1 to 8 at least one of oxygen atoms or nitrogen atoms; wherein each substituted organic moiety is selected from the group consisting of alkyl, hydroxy, thiol, -COOM, -PO3M、-O-PO3M2or-SO3M, wherein M and M are independent of each other and are a hydrogen atom or a metal.
34. The method of claim 32, wherein the comonomer having one ethylenically unsaturated group is 2-phenoxyethyl (meth) acrylate or benzyl (meth) acrylate.
35. The method of claim 33, wherein the comonomer having two ethylenically unsaturated groups is selected from the group consisting of: 2,2' -bis [4- (3-methacryloyloxy-2-hydroxypropoxy) -phenyl ] propane (bis-GMA), tetraethylene glycol di (meth) acrylate (TEGDMA), and Urethane Dimethacrylate (UDMA).
36. The method of claim 23, wherein the comonomer having at least three ethylenically unsaturated groups is selected from the group consisting of: trimethylolpropane tri (meth) acrylate, pentaerythritol triacrylate, pentaerythritol tetraacrylate, and N, N '-bisacryloyl-N, N' -bisallyl-1, 4-but-2-enediamine.
37. The method of claim 23, wherein the comonomer having at least three ethylenically unsaturated groups is present in a range of from 1 to 30 mole percent based on the total moles of comonomer in the mixture.
38. The method of claim 23, wherein the comonomer having one ethylenically unsaturated group is present in the range of 50 to 95 mole percent based on the total moles of the comonomers in the mixture.
39. The method of claim 23, wherein the comonomer having two ethylenically unsaturated groups is present in a range of from 5 to 50 mole percent based on the total moles of the comonomer in the mixture.
40. The method of claim 23, wherein the initiator is present in a concentration of 0.5 to 5.0 weight ratio based on the total weight of the comonomers in the mixture.
41. The method of claim 23, wherein the at least one chain transfer agent is present at a concentration of 5 to 50 weight percent based on the total moles of comonomer in the mixture.
Technical Field
The present invention relates to methods and compositions for stabilizing nanogels, and the use of such nanogels as additives in dental compositions.
Background
Nanogels are highly branched discrete polymer particles. Nanogels have traditionally been synthesized by solution copolymerization of monomethacrylate/dimethacrylate monomers.
A major drawback of previous nanogel processes is that poor copolymerization of monomethacrylates and dimethacrylates will result in migration of the composition from the feed composition into the final nanogel. Overall low yields and high recoveries of monomethacrylate have been observed. Furthermore, there is a potential formation of macrogels during polymerization and after vacuum drying, which would jeopardize its redispersibility in the resin.
Chain transfer agents have been added to nanogel compositions to avoid large particle gelation. U.S. patent No. 9,138,383 discloses soluble nanogel polymers produced by polymerizing a monomer mixture comprising a monovinyl monomer, a divinyl monomer, a chain transfer agent, and an initiation-transfer-termination agent.
U.S. patent No. 9,845,415 discloses a water dispersible nanogel produced by a process comprising the steps of: (i) combining a monomer mixture comprising at least one monovinyl monomer, at least one divinyl monomer, a difunctional chain transfer agent, and an initiator; and (ii) polymerizing the mixture to form a water dispersible nanogel; wherein the at least one monovinyl monomer comprises polyethoxy (10) ethyl methacrylate (E10 HEMA).
Other challenges include effective removal of all by-products (unreacted monomethacrylate, residual dodecanethiol (DDT) and residual solvent) to ensure nanogel quality and performance.
Furthermore, polymerization shrinkage and failure shrinkage stresses remain major limitations of modern dental composites, and there is still a great need to lighten them to produce advanced composite restorations with improved material integrity and well-preserved bonds, especially for increasingly applied blocky restorations.
Nanogels can be readily dispersed in a matching monomer matrix as a pre-polymerized and polymerizable additive, which helps to reduce volume shrinkage due to the effective reduction of polymerizable double bonds. Furthermore, during polymerization, these monomer-swollen nanogel particles effectively act as "stress absorbers" during rapid photopolymerization and network development.
Disclosure of Invention
As discussed above, there is a great need to reduce the polymerization shrinkage and failure stress of dental composites to produce advanced composite restorations.
It is an object of the present invention to provide a nanogel produced by the method of the invention, which can be used as an additive in dental compositions to significantly reduce shrinkage stress and further enhance the mechanical properties of the cured product.
Furthermore, there is a continuing need to develop efficient methods of forming nanogels that will avoid the formation of large particle gels during the reaction to stabilize nanogel solutions. This will avoid large particle gelation during handling and allow the nanogels to be easily re-dispersed in the resin later on. This method will enable the removal of all by-products to achieve better quality of the nanogel.
The present invention provides methods and compositions for stabilizing nanogel compositions to achieve a robust manufacturing process without large particle gelation.
In a first aspect of the invention, there is provided a dental composition comprising a nanogel formed by a process comprising the steps of:
(a) polymerizing a mixture comprising:
(i) at least one comonomer having one ethylenically unsaturated group,
(ii) at least one of a comonomer having two ethylenically unsaturated groups and at least one comonomer having at least three ethylenically unsaturated groups,
(iii) at least one chain transfer agent, and
(iv) an initiator;
to obtain a nanogel solution; and is
(b) The polymerization was terminated by lowering the reaction temperature and quenching the nanogel solution with a free radical scavenger.
In one embodiment, provided is the use of a nanogel obtained by the method according to the invention for the preparation of a dental composition. The dental composition can be a dental composite, a dental adhesive, a dental cement, a resin modified glass ionomer, a varnish (vanish), a sealant, a denture material, a composite block, and a composite ink for dental 3D printing.
In another aspect of the invention, a method of forming a nanogel is provided. The method comprises the following steps:
(a) polymerizing a mixture comprising:
(i) at least one comonomer having one ethylenically unsaturated group,
(ii) at least one of a comonomer having two ethylenically unsaturated groups and at least one comonomer having at least three ethylenically unsaturated groups,
(iii) at least one chain transfer agent, and
(iv) an initiator;
to obtain a nanogel solution; and is
(b) The polymerization was terminated by lowering the reaction temperature and quenching the nanogel solution with a free radical scavenger.
In one embodiment of the method, the nanogel is substantially free of macrogels.
In another embodiment of the method, the nanogel has a hydrodynamic radius of 2nm to 20 nm.
In yet another embodiment of the method, the free radical scavenger is present in a concentration such that the nanogel solution has thermal stability for 7 days of storage at 25 ℃.
Overall, it was observed that nanogels contributed to delayed gelation and vitrification, which not only resulted in a slow stress expansion rate but also reduced the magnitude of the final shrinkage stress.
Benefits are not limited to dental composites: dental adhesives with nanogel additives also have the potential to achieve improved durability and material properties.
Brief Description of Drawings
FIG. 1 depicts a scheme for synthesizing a UDMA/POEMA nanogel.
FIG. 2 shows Methacrylate (MA) conversion in a TEMPO-stabilized nanogel process (ZZ 1-85 with TEMPO at 80 ℃ at 0.09% by weight of the total weight of monomers).
FIG. 3 depicts the general mechanism of side reactions in methacrylate-nitroxide systems.
FIG. 4 depicts possible side reactions of TEMPO-quenched nanogels at elevated temperatures.
FIG. 5 shows the effect of aging at room temperature on the UV spectrum of a TEMPO-stabilized UDMA/POEMA nanogel/ZZ 1-127B Methyl Ethyl Ketone (MEK) solution (TEMPO at 0.20% by weight based on the total weight of the monomers).
FIG. 6 shows the effect of heat aging on the UV spectrum of a MEK solution of TEMPO-stabilized nanogel/ZZ 1-99 with variable TEMPO (at 40 deg.C, A: 0%, B: 0.20%, C: 0.16%, D: 0.12%, weight ratio of total weight of monomers).
FIG. 7 depicts the UV spectrum of a heat-aged nanogel/MEK solution ZZ1-99B (at 40 ℃, AIBN 0.90%, TEMPO 0.20%, weight ratio of total weight of monomers).
FIG. 8 shows nanogels containing TMPTMA crosslinker13C NMR[DMSO-d6]Wherein the TMPTMA crosslinker has a characteristic peak at 7.02 ppm.
FIG. 9 depicts nanogels containing 15 mole% TMPTMA crosslinker in CDCl3In (1)13C-NMR, wherein the TMPTMA crosslinker has a characteristic peak at 7.50 ppm.
FIG. 10 shows nanogels containing 20 mole% TMPTMA crosslinker in CDCl3In (1)13C-NMR, wherein the TMPTMA crosslinker has a characteristic peak at 7.51 ppm.
FIG. 11 depicts nanogels containing 25 mole% TMPTMA crosslinker in CDCl3In (1)13C-NMR, wherein the TMPTMA crosslinker has a characteristic peak at 7.50 ppm.
FIG. 12 shows nanogels containing 30 mole% BAABE crosslinker and 70 mole% POEMA in CDCl3In (1)13C-NMR, wherein BAABE and POEMA have characteristic peaks at 118.11, 132.23 and 176.62 ppm.
Detailed Description
The above aspects and other aspects, features and advantages of the present invention are described below in connection with various embodiments with reference to the accompanying drawings.
Some terms used in the present invention are defined as follows:
unless otherwise specified, the term "alkyl" refers to a monovalent branched or unbranched saturated hydrocarbon chain having 1 to 18 carbon atoms. The term may be exemplified by groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, n-decyl, dodecyl, tetradecyl, and the like. The alkyl group may be further substituted with one or more substituents selected from the group consisting of alkenyl, alkoxy, and hydroxyl.
Unless otherwise specified, the term "alkylene" refers to a straight-chain saturated divalent hydrocarbon group having one to eighteen carbon atoms or a branched-chain saturated divalent hydrocarbon group having three to eighteen carbon atoms, such as methylene, ethylene, 2-dimethylethylene, propylene, 2-methylpropylene, butylene, and the like, preferably methylene, ethylene, or propylene.
The term "arylene" is a divalent moiety of "aryl". The term "aryl" refers to a C5-C18 membered aromatic, heterocyclic, fused aromatic, fused heterocyclic, bi-aromatic or bi-heterocyclic ring system. Broadly defined, "aryl" as used herein includes 5, 6, 7, 8, 9 and 10 membered monocyclic aromatic groups, which groups may include zero to four heteroatoms, such as benzene, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, triazole, pyrazole, pyridine, pyrazine, pyridazine, pyrimidine, and the like. Those "aryl" groups having heteroatoms in the ring structure may also be referred to as "heteroaryl" or "heterocyclic" or "heteroaromatic". The aromatic ring may be substituted at one or more ring positions with one or more substituents including, but not limited to: halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxy, alkoxy, amino (or quaternized amino), nitro, mercapto, imino, amido, phosphonate, phosphinate, carbonyl, carboxyl, silyl, ether, alkylthio, sulfonyl, sulfonamido, ketone, aldehyde, ester, heterocyclyl, aromatic or heteroaromatic moieties, -CF3-CN, and combinations thereof.
The term "aryl" also includes polycyclic ring systems having two or more cyclic rings in which two or more carbons are common to two adjoining rings (i.e., "fused rings"), wherein at least one of the rings is aromatic, e.g., the other cyclic ring(s) can be cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, and/or heterocycle. Examples of heterocyclic rings include, but are not limited to: benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzoxazolinyl, benzothiazolyl, benzotriazolyl, benzotetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazolinyl, carbazolyl, 4aH carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 2H,6H-1,5, 2-dithiazinyl, dihydrofuro [2,3b ] tetrahydrofuran, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolynyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isatinoyl, isobenzofuranyl, isochromanyl, isoindolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, methylenedioxyphenyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2, 3-oxadiazolyl, 1,2, 4-oxadiazolyl, 1,2, 5-oxadiazolyl, 1,3, 4-oxadiazolyl, oxazolidinyl, oxazolyl, oxindolyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, piperidonyl, 4-piperidonyl, piperonyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazole, pyridothiazole, pyridinyl, nitrophenyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, 2H-pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrazolyl, 6H-1,2, 5-thiadiazinyl, 1,2, 3-thiadiazolyl, 1,2, 4-thiadiazolyl, 1,2, 5-thiadiazolyl, 1,3, 4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl, and xanthenyl.
The term "aralkylene" is a divalent moiety of "aralkyl". The term "aralkyl" refers to a compound having the formula-Ra-a radical of an aryl radical, wherein RaIs an alkylene group as defined above, such as methylene, ethylene and the like. The aryl moiety is optionally substituted as described above for aryl.
The term "cycloalkylene" is a divalent moiety of "cycloalkyl". The term "cycloalkyl" refers to a monocyclic or polycyclic cycloalkyl group. Examples of monocyclic cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Examples of polycyclic cycloalkyl groups include, for example, adamantyl, norbornyl, decahydronaphthyl, 7-dimethyl-bicyclo [2.2.1]Heptylalkyl, tricyclo [5.2.1.02,6]Decyl groups and the like. Unless the specification expressly states otherwise, the term "cycloalkyl" is intended to include one or more substituents optionally substitutedMonocyclic or polycyclic cycloalkyl substituted with substituents selected from alkyl, halo, oxo, or alkylene chains.
The term "cycloalkylalkylene" refers to the group-Ra-cycloalkyl-, wherein R isaIs an alkylene group as defined above, such as methylene, ethylene and the like. C as used herein1-C8Cycloalkylalkylene is meant to be via C1-C8Alkylene-linked cycloalkyl groups.
The term "heteroarylene" is a divalent moiety of "heteroaryl".
In the context of the present invention, the term "(meth) acrylate" is intended to refer to both acrylates and the corresponding methacrylates.
In the context of the present invention, the term "(meth) acrylamide" is intended to include both acrylamide and methacrylamide.
The present invention provides methods and compositions for stabilizing nanogel compositions. The nanogels obtained by the process according to the invention are particularly useful for the preparation of dental compositions. The dental composition can be a dental composite, a dental adhesive, a dental cement, a resin modified glass ionomer, a paint, a sealant, a denture material, a composite block, or a composite ink for dental 3D printing.
The dental composition according to the invention comprises a nanogel as a component.
In one aspect of the present invention, there is provided a dental composition comprising a nanogel formed by a method comprising the steps of:
(a) polymerizing a mixture comprising:
(i) at least one comonomer having one ethylenically unsaturated group,
(ii) at least one of a comonomer having two ethylenically unsaturated groups and at least one comonomer having at least three ethylenically unsaturated groups,
(iii) at least one chain transfer agent, and
(iv) an initiator;
to obtain a nanogel solution; and is
(b) The polymerization was terminated by lowering the reaction temperature and quenching the nanogel solution with a free radical scavenger.
The expression "at least one of a comonomer having two ethylenically unsaturated groups and at least one comonomer having at least three ethylenically unsaturated groups" is to be understood as meaning both a comonomer having only two ethylenically unsaturated groups "," at least one comonomer having at least three ethylenically unsaturated groups ", or" a comonomer having two ethylenically unsaturated groups and at least one comonomer having at least three ethylenically unsaturated groups ".
In one embodiment of the dental composition, the nanogel may be present at a concentration of 5 to 40 weight percent, alternatively 10 to 30 weight percent, alternatively 10 to 25 weight percent, or any value, range, or subrange therebetween, based on the total weight of the composition, all based on the total weight of the composition.
In certain embodiments of the nanogels formed by the methods disclosed herein, the comonomer having one ethylenically unsaturated group is selected from the group consisting of: (meth) acrylic acid C1-C12Alkyl esters, hydroxyalkyl (meth) acrylates, allyl ethers, aromatic (meth) acrylates, vinyl ethers, vinyl esters, vinyl amines, acrylamides, methacrylamides, hydroxyalkyl acrylamides, and hydroxyalkyl methacrylamides.
(meth) acrylic acid C1-C12Examples of alkyl esters may include, but are not limited to: methyl (meth) acrylate, ethyl (meth) acrylate, isopropyl (meth) acrylate, propyl (meth) acrylate, isobutyl (meth) acrylate, hexyl (meth) acrylate, cyclohexyl (meth) acrylate, lauryl (meth) acrylate, and isobornyl (meth) acrylate.
Examples of hydroxyalkyl (meth) acrylates may include, but are not limited to: hydroxyethyl (meth) acrylate (HEMA), polyethoxyethyl methacrylate, hydroxypropyl methacrylate and hydroxybutyl methacrylate, 6-hydroxyhexyl (meth) acrylate, and 10-hydroxydecyl (meth) acrylate.
Examples of aromatic (meth) acrylates may include, but are not limited to: 2-phenoxyethyl (meth) acrylate, phenyl (meth) acrylate, benzoyl (meth) acrylate, benzyl (meth) acrylate, 2-phenylethyl (meth) acrylate, 3-phenylpropyl (meth) acrylate, 4-phenylbutyl (meth) acrylate, 4-methylphenyl (meth) acrylate, 4-methylbenzyl (meth) acrylate, and 2- (4-methoxyphenyl) ethyl methacrylate.
Examples of hydroxyalkyl acrylamides may include, but are not limited to: hydroxyethyl acrylamide, N-tris (hydroxymethyl) methyl) acrylamide, N- (hydroxymethyl) acrylamide, or a combination thereof.
Examples of hydroxyalkyl methacrylamides include N-methylol (meth) acrylamide, hydroxyethyl (meth) acrylamide, and N, N-bis- (2-hydroxyethyl) methacrylamide.
Examples of the vinyl ether may include ethyl vinyl ether, n-propyl vinyl ether, isopropyl vinyl ether, n-butyl vinyl ether, isobutyl vinyl ether, cyclohexyl vinyl ether, hydroxybutyl vinyl ether, cyclohexanedimethanol monovinyl ether, 2-ethylhexyl vinyl ether, dodecyl vinyl ether, and octadecyl vinyl ether.
Examples of vinyl esters may include, but are not limited to: vinyl acetate, vinyl propionate, vinyl butyrate, vinyl isobutyrate, vinyl caproate, vinyl stearate, vinyl neononanoate, vinyl neodecanoate, vinyl valerate, vinyl caproate, vinyl laurate, vinyl isovalerate, vinyl 2-ethylhexanoate, vinyl 2, 2-dimethyloctanoate, vinyl 2-methyl-2-propyl-valerate, vinyl 4-methyl-4-butylhexanoate, and vinyl neoate (neo acid).
Examples of the methacrylamide include (meth) acrylamide, N-methyl (meth) acrylamide, N-ethyl (meth) acrylamide, N-dimethyl (meth) acrylamide, N-diethyl (meth) acrylamide, N-methylethyl (meth) acrylamide, and N- (2-hydroxyethyl) methacrylamide.
Examples of acrylamides include, but are not limited to: n-butylacrylamide, diacetone acrylamide, N, N-dimethylacrylamide, N, N-dibenzylacrylamide, N-ethylacrylamide, N- (2-hydroxyethyl) acrylamide, and N-methyl-N- (2-hydroxyethyl) acrylamide.
In certain embodiments, the comonomer having one ethylenically unsaturated group may be present in an amount of 50 to 95 mole percent, alternatively 55 to 80 mole percent, alternatively 65 to 75 mole percent, or any value, range, or subrange therebetween, based on the total moles of comonomer in the mixture.
In certain embodiments of the nanogels formed by the methods disclosed herein, the comonomer having two ethylenically unsaturated groups comprises a compound having the formula I:
X-R-Y
formula I
Wherein the content of the first and second substances,
x is a (meth) acryloyl or (meth) acrylamide moiety;
y is a (meth) acryloyl, methacrylamide, allyl, vinyl ether, vinyl ester, or vinylamine moiety;
r is a direct bond or an organic moiety;
wherein the organic moiety is selected from the group consisting of: unsubstituted or substituted C1-C18Alkylene, unsubstituted or substituted C3-C8Cycloalkylene, unsubstituted or substituted aralkylene, unsubstituted or substituted C1-C8Cycloalkylalkylene, unsubstituted or substituted C5-C18Arylene group, and unsubstituted or substituted C3-C18A heteroarylene group; wherein the organic moiety may contain at least one of: c1-C4Alkylene, 1 to 7 carbonyl groups, 1 to 7 carboxyl groups (- (C ═ O) -O-or-O- (C ═ O) -), 1 to 7 amide groups (- (C ═ O) -NH-or- (NH- (C ═ O) -), 1 to 7 carbamate groups (-NH- (C ═ O) -O-or-O- (C ═ O) -NH-), and 1 to 14 heteroatoms selected from oxygen, nitrogen and sulfur, and wherein each substituted organic moiety may be selected from the group consisting of alkyl, hydroxyl, thiol, -COOM, -PO and3M、-O-PO3M2or-SO3M, wherein M and M are independent of each other and are a hydrogen atom or a metal.
In a particular embodiment, the organic moiety is unsubstituted or substituted C1-C18Alkylene, unsubstituted or substituted C3-C8Cycloalkylene, unsubstituted or substituted aralkylene, unsubstituted or substituted C1-C8Cycloalkylalkylene, unsubstituted or substituted C5-C18Arylene radical, or unsubstituted or substituted C3-C18A heteroarylene group; wherein each unsubstituted or substituted organic moiety may contain C1-C4Alkylene, 1 to 4 carbamate groups (-NH- (C ═ O) -O-or-O- (C ═ O) -NH-), 1 to 8 at least one of oxygen atoms or nitrogen atoms; wherein each substituted organic moiety may be selected from the group consisting of alkyl, hydroxy, thiol, -COOM, -PO3M、-O-PO3M2or-SO3M, wherein M and M are independent of each other and are a hydrogen atom or a metal.
With respect to organic moieties, the phrase "at least one of the organic moieties may contain.. means that groups that may be contained in the organic moieties are incorporated into the organic moieties by covalent bonds. For example, in UDMA, two carbamate groups (-NH- (C ═ O) -O-or-O- (C ═ O) -NH-) are incorporated into the organic moiety.
In one embodiment, the comonomer having two ethylenically unsaturated groups may be selected from the group consisting of: di (meth) acrylate, allyl (meth) acrylate, di (meth) acrylamide, (meth) acrylate (meth) acrylamide, vinyl (meth) acrylate, (meth) acrylate vinyl thioester, (meth) acrylate vinyl amide, vinyl ether (meth) acrylate, vinyl ester (meth) acrylate, vinyl amine (meth) acrylate, allyl (meth) acrylamide, (meth) acrylamide vinyl ester, (meth) acrylamide vinyl thioester, vinyl ether (meth) acrylamide and vinyl amine (meth) acrylamide.
Examples of comonomers having two ethylenically unsaturated groups may include, but are not limited to: ethylene glycol diacrylate, ethylene glycol dimethacrylate, diethylene glycol di (meth) acrylate, polyethylene glycol diacrylate (in which the number of repeating oxyethylene units is from 2 to 30), polyethylene glycol dimethacrylate (in which the number of repeating oxyethylene units is from 2 to 30, especially triethylene glycol dimethacrylate ("TEGDMA"), butanediol di (meth) acrylate, tetraethylene glycol di (meth) acrylate, neopentyl glycol diacrylate, neopentyl glycol dimethacrylate, 1, 6-hexanediol di (meth) acrylate, 1, 10-decanediol di (meth) acrylate, pentaerythritol di (meth) acrylate, 4,4,6,16 (or 4,6,6,16) -tetramethyl-10, 15-dioxo-11, 14-dioxa-2, 9-diazepan-16-enoic acid 2- [ (2-methyl-1-oxo-2-propen-1-yl) oxy ] ethyl ester (CAS No. 72869-86-4) (UDMA), N ' -ethylenebis (meth) acrylamide, N ' -propylenebis (meth) acrylamide, N ' -butylenebis (meth) acrylamide, N ' -pentamethylenebis (meth) acrylamide, N ' -hexamethylenebis (meth) acrylamide, dimethyleneether bisacrylamide, dimethyleneether dimethylacrylamide, methylenebisacrylamide, and methylenebismethacrylamide, compounds having the formula:
in certain embodiments, the comonomer having two ethylenically unsaturated groups may be present in an amount of from 5 to 50 mole percent, alternatively from 10 to 40 mole percent, alternatively from 20 to 30 mole percent, or any value, range, or subrange therebetween, based on the total moles of comonomer in the mixture.
In certain embodiments of the nanogels formed by the methods disclosed herein, the comonomer having at least three ethylenically unsaturated groups is selected from the group consisting of: trimethylolpropane tri (meth) acrylate, pentaerythritol triacrylate, and pentaerythritol tetraacrylate, dipentaerythritol hexaacrylate, and N, N '-bisacryloyl-N, N' -bisallyl-1, 4-but-2-enediamine (BAABE).
In certain embodiments, the comonomer having at least three ethylenically unsaturated groups may be present in an amount of 1 to 30 mole percent, alternatively 2 to 20 mole percent, alternatively 5 to 15 mole percent, or any value, range, or subrange therebetween, based on the total moles of comonomer in the mixture.
In certain embodiments of the nanogels formed by the methods disclosed herein, at least one chain transfer agent may be included.
Chain transfer agents may be used to provide shorter polymer chains, which retard macrogel formation. The chain transfer agent may be RSH, wherein R is a linear or branched alkyl group having 3 to 20 carbon atoms. Examples of the chain transfer agent may include propanethiol, butanethiol, hexanethiol, 1-dodecanethiol, mercaptoethanol, and combinations thereof.
The amount of the at least one chain transfer agent is present in a concentration of 5 to 50 mole percent, alternatively 10 to 40 mole percent, alternatively 20 to 30 mole percent, or any value, range, or subrange therebetween, based on the total molar amount of comonomers in the mixture.
In certain embodiments of the nanogels formed by the methods disclosed herein, an initiator may be included.
Thermal polymerization of the comonomer can be initiated by decomposition of the initiator. The initiator may be selected from at least one of an organic peroxide and an azo compound.
In certain embodiments, the initiator is selected from the group consisting of benzoyl peroxide, 2-azobis- (2-methylpropanenitrile), and 2, 2-azobis- (2-methylbutyronitrile). In a preferred embodiment, the initiator is azobis (isobutyronitrile).
The thermal initiator may be present at a concentration of 0.5 to 5.0 weight percent based on the total weight of the comonomers in the mixture. Alternatively 0.5 to 3.0 weight percent, alternatively 1.0 to 2.0 weight percent, or any value, range, or sub-range therebetween, based on the total weight of the comonomers in the mixture.
In certain embodiments of the nanogels formed by the methods disclosed herein, a free radical scavenger may be included.
A radical scavenger may be added at the end of a conventional radical polymerization to terminate the polymerization. This will eliminate all free radical species as inactive species within the resulting polymer. A stable nanogel system will be achieved to allow its subsequent exposure to heat and vacuum without causing any unwanted large particle gelation.
The free radical scavenger is present in an amount of at least 0.05% and at most 2.5% by weight, or the free radical scavenger may be present in an amount of at least 0.1% and at most 1.5% by weight, all based on the total weight of comonomers in the mixture. Alternatively, the free radical scavenger may be present in an amount of at least 0.1% by weight based on the total initiator used in the nanogel or from 10 to 50% by weight based on the total initiator used in the nanogel.
Examples of free radical scavengers may include, but are not limited to: TEMPO, substituted TEMPO, and polychlorinated triphenylmethyl radicals, phenalenyl radicals, cyclopentadienyl and other carbon-centered radicals, nitroxide radicals, di-t-alkyl imines, delocalized radicals containing hydrazine (hydrazyl) units, metal-coordinated phenoxy radicals, and stable radicals containing thiazolyl units, or stable radicals with heavy elements in the p-region.
TEMPO is 2,2,6, 6-tetramethylpiperidin-1-oxyl. Representative examples of TEMPO structures and substituted TEMPO are depicted below:
examples of the polychlorinated triphenylmethyl radicals may include the following:
phenalkenyl is a structure depicted as follows:
typical structures of cyclopentadienyl radicals include:
the di-tert-butyl imine oxide radical includes the structure of the formula:
the metal-coordinated phenoxy radical may comprise the structure depicted below:
in one embodiment of the nanogel formed by the method of the invention, the nanogel is substantially free of macrogels.
The nanogel formed by the process of the invention has a hydrodynamic radius of less than 50nm, alternatively the nanogel has a hydrodynamic radius of from 1nm to 50nm, more preferably from 2nm to 20 nm.
In one aspect of the present invention, there is provided a method of forming a nanogel, the method comprising the steps of:
(a) polymerizing a mixture comprising:
(i) at least one comonomer having one ethylenically unsaturated group,
(ii) at least one of a comonomer having two ethylenically unsaturated groups and at least one comonomer having at least three ethylenically unsaturated groups,
(iii) at least one chain transfer agent, and
(iv) an initiator;
to obtain a nanogel solution; and is
(b) The polymerization was terminated by lowering the reaction temperature and quenching the nanogel solution with a free radical scavenger.
Thermal polymerization can be carried out using any free radical polymerization method, such as solution, suspension, emulsion, and bulk polymerization methods.
In one embodiment of the method of forming a nanogel, a mixture of at least one of a comonomer having one ethylenically unsaturated group, a comonomer having two ethylenically unsaturated groups, and at least one comonomer having at least three ethylenically unsaturated groups, at least one chain transfer agent, and an initiator may be dissolved in a solvent.
Suitable solvents for use in the process of making nanogels herein are inert solvents. Examples of suitable solvents would be solvents in which the monomers are dissolved, such as dipolar aprotic solvents, such as methyl ethyl ketone or methyl isobutyl ketone; ketones such as acetone, 2-butanone or cyclohexanone; hydrocarbons such as toluene and xylene; ethers, such as dioxane or tetrahydrofuran. In one embodiment, the solvent is methyl ethyl ketone or methyl isobutyl ketone.
The amount of solvent may be such that it is present at a concentration that minimizes macrogel formation, which may be 2 to 10 times the total weight of the total comonomers.
In one embodiment of the method of forming a nanogel, the thermal polymerization can be conducted at a reaction temperature of 40 ℃ to 150 ℃, such as 60 ℃ to 120 ℃ or 75 ℃ to 105 ℃.
In one embodiment of the method of forming a nanogel, thermal polymerization can be terminated by lowering the reaction temperature and quenching the nanogel solution with a free radical scavenger.
In some embodiments where the thermal polymerization is terminated, the reaction temperature may be reduced by cooling the nanogel solution at a temperature of-196 ℃ to 25 ℃.
In some embodiments where the thermal polymerization is terminated, the nanogel solution can be quenched when a free radical scavenger is added to the nanogel solution when 55-85% of the ethylenically unsaturated groups in the comonomer mixture have reacted to form the nanogel. In one embodiment, the free radical scavenger is added to the nanogel solution when 75 to 80% of the ethylenically unsaturated groups in the comonomer mixture have reacted to form the nanogel.
In additional embodiments, the methods disclosed herein can further comprise precipitating the nanogel mixture with a non-polar solvent after quenching with the free radical scavenger. Alternatively, the nanogel mixture was dialyzed against the solvent using a regenerated cellulose membrane with a 10kDa molecular weight cut-off.
The non-polar solvent used to precipitate the nanogel mixture may be pentane, hexane, n-heptane, cyclohexane, octane, or petroleum ether.
The solvent used for dialysis of the nanogel mixture can be acetone, 2-butanone or isobutyl methyl ketone.
After precipitating or dialyzing the nanogel mixture, the solvent can be removed under vacuum to form a nanogel.
The nanogels formed by the process of the invention are redispersible in a suitable solvent to produce stable nanoparticle suspensions. For example, the nanogels can be readily re-dispersed in a solvent selected from the group consisting of acetone, toluene, or methyl ethyl ketone to provide a suitable suspension.
The dental compositions disclosed herein may contain a polymerizable resin, a polymerization initiator, and additional fillers.
Polymerizable resin
In one embodiment of the dental composition, the polymerizable resin may be present in an amount of about 1% to about 95% by weight of the dental composition.
The polymerizable resin may be selected from the group consisting of: acrylic acid esters, methacrylic acid esters, ethylenically unsaturated compounds, carboxyl group-containing unsaturated monomers,c of (meth) acrylic acid2-8Hydroxyalkyl esters, C of (meth) acrylic acid1-24Alkyl or cycloalkyl esters, C of (meth) acrylic acid2-18Alkoxyalkyl esters, olefin or diene compounds, mono/diesters, monoethers, adducts, TPH resins, SDR resins and/or BPA-free resins.
Examples of specific acrylate resins include, but are not limited to: methyl acrylate, ethyl acrylate, propyl acrylate, isopropyl acrylate, 2-hydroxyethyl acrylate, hydroxypropyl acrylate, tetrahydrofurfuryl acrylate, glycidyl acrylate, glycerol mono-and diacrylates, ethylene glycol diacrylate, polyethylene glycol diacrylate, neopentyl glycol diacrylate, trimethylolpropane triacrylate, mono-, di-, tri-and tetraacrylates of pentaerythritol and dipentaerythritol, 1, 3-butanediol diacrylate, 1, 4-butanediol diacrylate, 1, 6-hexanediol diacrylate, 2,2 '-bis [3 (4-phenoxy) -2-hydroxypropane-1-acrylate ] propane, 2,2' -bis (4-acryloyloxyphenyl) propane, 2,2 '-bis [4 (2-hydroxy-3-acryloyloxy-phenyl) propane, 2,2' -bis (4-acryloyloxyethoxyphenyl) propane, 2,2 '-bis (4-acryloyloxypropylphenyl) propane, 2,2' -bis (4-acryloyloxydiethoxyphenyl) propane, and dipentaerythritol pentaacrylate.
Examples of specific conventional methacrylate resins include, but are not limited to: methyl methacrylate, ethyl methacrylate, propyl methacrylate, isopropyl methacrylate, tetrahydrofurfuryl methacrylate, glycidyl methacrylate, diglycidyl methacrylate of bisphenol A (2, 2-bis [4- (2-hydroxy-3-methacryloxypropoxy) phenyl ] propane) (BisGMA), glycerol mono-and dimethacrylate, ethylene glycol dimethacrylate, polyethylene glycol dimethacrylate, triethylene glycol dimethacrylate (TEGDMA), neopentyl glycol dimethacrylate, trimethylolpropane trimethacrylate, mono-, di-, tri-and tetramethacrylates of pentaerythritol and dipentaerythritol, 1, 3-butanediol dimethacrylate, 1, 4-butanediol dimethacrylate, bis [2- (methacryloyloxy) ethyl ] phosphate (BisMEP), 1, 6-hexanediol dimethacrylate, 2,2 '-bis (4-methacryloxyphenyl) propane, 2,2' -bis [4 (2-hydroxy-3-methacryloxy-phenyl) ] propane, 2,2 '-bis (4-methacryloxyethoxyphenyl) propane, 2,2' -bis (4-methacryloxyprophenyl) propane, 2,2 '-bis (4-methacryloxydiethoxyphenyl) propane, and 2,2' -bis [3 (4-phenoxy) -2-hydroxypropane-1-methacrylate ] propane.
Examples of ethylenically unsaturated compounds include, but are not limited to: acrylates, methacrylates, hydroxy-functional acrylates, hydroxy-functional methacrylates, halogen-and hydroxy-containing methacrylates, and combinations thereof. Such radically polymerizable compounds include: n-, sec-or tert-butyl methacrylate, hexyl methacrylate, 2-ethylhexyl methacrylate, octyl methacrylate, decyl methacrylate, lauryl methacrylate, cyclohexyl methacrylate, stearyl methacrylate, allyl (meth) acrylate, glycerol tri (meth) acrylate, diethylene glycol di (meth) acrylate, triethylene glycol di (meth) acrylate, 1, 3-propylene glycol di (meth) acrylate, trimethylolpropane tri (meth) acrylate, 1,2, 4-butanetriol tri (meth) acrylate, 1, 4-cyclohexanediol di (meth) acrylate, pentaerythritol tetra (meth) acrylate, sorbitol hexa (meth) acrylate, tetrahydrofurfuryl (meth) acrylate, bis [1- (2-acryloyloxy) ] -p-ethoxyphenyl dimethyl methane, bis [1- (3-acryloyloxy-2-hydroxy) ] -p-propoxyphenyldimethylmethane, ethoxylated bisphenol a di (meth) acrylate, tris (meth) acrylate of tris (hydroxyethyl) isocyanurate; (meth) acrylamides (i.e., acrylamide and methacrylamide) such as (meth) acrylamide, methylenebis- (meth) acrylamide, and diacetone (meth) acrylamide; urethane (meth) acrylate, urethane-modified BisGMA resin, bis- (meth) acrylate of polyethylene glycol; and monomers containing chlorine, bromine, fluorine and hydroxyl groups, such as 3-chloro-2-hydroxypropyl (meth) acrylate.
Examples of the carboxyl group-containing unsaturated monomer include, but are not limited to, monomers such as acrylic acid, methacrylic acid, crotonic acid, itaconic acid, maleic acid, and fumaric acid.
C of (meth) acrylic acid2-8Examples of hydroxyalkyl esters include, but are not limited to, 2-hydroxyethyl (meth) acrylate, 2-hydroxypropyl (meth) acrylate, 3-hydroxypropyl (meth) acrylate, and hydroxybutyl (meth) acrylate.
C of (meth) acrylic acid2-18Examples of alkoxyalkyl esters include, but are not limited to, methoxybutyl methacrylate, methoxyethyl methacrylate, ethoxyethyl methacrylate, and ethoxybutyl methacrylate.
Olefin or diene compounds include, but are not limited to, ethylene, propylene, butylene, isobutylene, isoprene, chloropropene, fluoroolefins, and vinyl chloride.
Examples of the monoester may include a monoester between a polyether polyol (e.g., polyethylene glycol, polypropylene glycol or polytetramethylene glycol) and an unsaturated carboxylic acid (preferably methacrylic acid), a monoester or a diester between an unsaturated compound having an anhydride group (e.g., maleic anhydride or itaconic anhydride) and a diol (e.g., ethylene glycol, 1, 6-hexanediol or neopentyl glycol).
Examples of monoethers may include monoethers between polyether polyols (e.g., polyethylene glycol, polypropylene glycol, or polybutylene glycol) and hydroxyl-containing unsaturated monomers (e.g., 2-hydroxy methacrylate).
Examples of the adduct may include, but are not limited to, an adduct between an unsaturated carboxylic acid and a monoepoxy compound, an adduct between glycidyl (meth) acrylate (preferably glycidyl methacrylate) and a monobasic acid (e.g., acetic acid, propionic acid, p-tert-butyl benzoic acid, or fatty acid).
Initiator
Initiators are commonly used in chain growth polymerization, such as free radical polymerization, to initiate by thermal or light regulation.
Thermal polymerization initiators are compounds that generate free radicals or cations upon exposure to heat. For example, azo compounds such as 2,2' -azobis (isobutyronitrile) (AIBN) and organic peroxides such as Benzoyl Peroxide (BPO) are well known thermal radical initiators, and benzenesulfonates and alkyl sulfonium salts have been developed as thermal cationic initiators. Organic and inorganic compounds can be used to generate free radicals that initiate polymerization. Free radicals may be generated by thermal or ambient redox conditions. The decomposition rate of some initiators varies with pH and the presence of amines.
Additional free radical initiators may include organic photoinitiators. Suitable photoinitiators include form I and form II. They may be used independently or as a mixture of different photoinitiators plus additional coinitiators. Suitable photosensitizers may include monoketones and diketones (e.g., alpha diketones) that absorb some light in the range of about 300nm to about 800nm, such as about 400nm to about 500nm, such as camphorquinone, benzil, furiluoyl, 3,6, 6-tetramethylcyclohexanedione, phenanthrenequinone, and other cyclic alpha diketones. In embodiments, the initiator is camphorquinone. Examples of electron donor compounds include substituted amines, such as ethyl 4- (N, N-dimethylamino) benzoate as a promoter.
Other suitable photoinitiators for polymerizing free radical photopolymerizable compositions may include phosphine oxides, which typically have a functional wavelength range of about 380nm to about 1200 nm. In embodiments, phosphine oxide free radical initiators having a functional wavelength range of about 380nm to about 450nm are acyl and diacyl phosphine oxides.
Commercially available phosphine oxide photoinitiators capable of initiating free radicals when irradiated in the wavelength range of greater than about 380nm to about 450nm may include: 1-hydroxycyclohexyl phenyl ketone (IRGACURE 184), 2, 2-dimethoxy-1, 2-diphenylethan-1-one (IRGACURE651), bis (2,4, 6-trimethylbenzoyl) phenylphosphine oxide (IRGACURE 819), 1- [4- (2-hydroxyethoxy) phenyl ] -2-hydroxy-2-methyl-1-propan-1-one (IRGACURE 2959), 2-benzyl-2-dimethylamino-1- (4-morpholinophenyl) butanone (IRGACURE 369), 2-methyl-1- [4- (methylthio) phenyl ] -2-morpholinopropan-1-one (IRGACURE 907), and 2-hydroxy-2-methyl-1-phenylpropan-1-one (DAROCUR 1173), bis (2,4, 6-trimethylbenzoyl) phenylphosphine oxide (IRGACURE 819), bis (2, 6-dimethoxybenzoyl) - (2,4, 4-trimethylpentyl) phosphine oxide (CGI 403), a mixture of bis (2, 6-dimethoxybenzoyl) -2,4, 4-trimethylpentylphosphine oxide and 2-hydroxy-2-methyl-1-phenylpropan-1-one in a weight ratio of 25:75 (IRGACURE 1700), a mixture of bis (2,4, 6-trimethylbenzoyl) phenylphosphine oxide and 2-hydroxy-2-methyl-1-phenylpropan-1-one in a weight ratio of 1:1 (DAROCUR 4265), and ethyl 2,4, 6-trimethylbenzylphenylphosphonite (LUCIRIN LR 8893X).
In one embodiment of the dental composition, the initiator may be present in an amount of 0.05% to about 5% by weight of the dental composition.
Filler material
The dental compositions of the present invention may include a filler.
Examples of suitable filler particles include, but are not limited to: strontium silicate, strontium borosilicate, barium silicate, barium borosilicate, barium fluoroaluminium borosilicate glass, barium aluminoborosilicate, calcium silicate, calcium alumino sodium fluorophosphosilicate, lanthanum silicate, aluminum silicate, and combinations comprising at least one of the foregoing fillers. The filler particles may also comprise silicon nitride, titanium dioxide, fumed silica, colloidal silica, quartz, kaolin ceramic, calcium hydroxyapatite, zirconia, and mixtures thereof. Examples of fumed silicas include OX-50 from DeGussa AG (having an average particle size of 40 nm), Aerosil R-972 from DeGussa AG (having an average particle size of 16 nm), Aerosil 9200 from DeGussa AG (having an average particle size of 20 nm), other Aerosil fumed silicas can include Aerosil 90, Aerosil 150, Aerosil 200, Aerosil 300, Aerosil 380, Aerosil R711, Aerosil R7200, and Aerosil R8200; and Cab-O-Sil M5, Cab-O-Sil TS-720, Cab-O-Sil TS-610 from Cabot Corp.
The filler particles used in the compositions disclosed herein can be surface treated prior to blending with the organic compound. Surface treatments using silane coupling agents or other compounds are beneficial because they enable more uniform dispersion of the filler particles in the organic resin matrix and also improve physical and mechanical properties. Suitable silane coupling agents include 3-methacryloxypropyltrimethoxysilane, methacryloxyoctyltrimethoxysilane, styrylethyltrimethoxysilane, 3-mercaptopropyltrimethoxysilane, and mixtures thereof.
The filler particles may have a particle size of about 0.002 microns to about 25 microns. In one embodiment, the filler may comprise a micron-sized radiopaque filler, such as a mixture of barium aluminofluoroborosilicate glass (BAFG, having an average particle size of about 1 micron) and nanofiller particles, such as fumed silica, OX-50 (having an average particle size of about 40 nm), such as DeGussa AG. The concentration of the micro-sized glass particles may be from about 50% to about 75% by weight of the dental composition, and the nano-sized filler particles may be from about 1% to about 20% by weight of the dental composition.
Dental compositions of the present invention may include filler materials in an amount of about 5 to about 95 weight percent.
In the formulated composition, further additives may optionally be included: uv stabilizers, fluorescers, opacifiers, pigments, viscosity modifiers, defluorinating agents, polymerization inhibitors, and the like. Typical polymerization inhibitors for free radical systems may include hydroquinone Monomethyl Ether (MEHQ), Butylated Hydroxytoluene (BHT), Tertiary Butyl Hydroquinone (TBHQ), hydroquinone, phenol, butyl hydroxyaniline, and the like. The inhibitor acts as a free radical scavenger to capture free radicals in the composition and extend the shelf life stability of the composition. If present, the polymerization inhibitor may be present in an amount of about 0.001% to about 1.5% by weight of the dental composition, such as about 0.005% to about 1.1% by weight or about 0.01% to about 0.08% by weight of the dental composition. The composition may include one or more polymerization inhibitors.
The invention discussed herein is further illustrated by the nanogel compositions, dental compositions, described in the following examples, but these examples should not be construed as limiting the scope of the invention.
Example (b):
batch reaction (conventional thermal process):solution copolymerization of isobornyl methacrylate (IBMA) and Urethane Dimethacrylate (UDMA) (molar ratio 70/30) was carried out using 20 mol% Mercaptoethanol (ME) and 20 mol% 1-dodecanethiol (DDT) as chain transfer agents. Thermal polymerization used 1 wt% 2, 2-azobisisobutyronitrile in 2-butanone (MEK) or toluene at 75-80 deg.C.
Various laboratory batches of nanogels based on UDMA/IBMA (molar ratio 30:70) and/or UDMA/POEMA (molar ratio 30:70) were successfully reproduced, but consistently achieving lower yields of 50-70%, see the examples in table I. In addition, it was revealed that although the initially precipitated nanogel could be completely dissolved, a part of the macrogel could be formed together with the nanogel during the solvent removal process. The presence of such macrogels will negatively impact the yield and dissolution of any resulting nanogels in the formulated resin mixture.
Table I: effect of composition and solvent on yield and solubility of Nanogels Via batch Process
The low yields are attributed to poor copolymerization of monomethacrylates and dimethacrylates, e.g., POEMA with UDMA, although POEMA appears to have better copolymerization than IBMA. Thus, less POEMA was incorporated into the nanogel, and the actual composition of such nanogel would deviate from the 30/70 molar ratio feed composition of UDMA/POEMA, see table II, example 17.
Table II: resin composition and solvent effect on nanogel solubility for improved yield
For the hexane soluble fraction in the current nanogel process, UDMA/IBMA versus UDMA/POEMA, based on NMR analysis, the following were inferred:
(i) for UDMA/IBMA (30/70 in MEK): 44.5g (37.5% by weight) of hexane soluble liquid was collected as unreacted IBMA, IBMA oligomers and free DDT. There is very little UDMA.
(ii) For UDMA/POEMA (25/75 in MEK): 40.0g (33.5% by weight) of a hexane-soluble liquid was collected as POEG/POEG, unreacted POEMA, POEMA oligomers and free DDT. Very little UDMA was found and no crystalline residue.
(a) Based on1H NMR analysis assessed 12.8g (32%) as free DDT and 27.2g (68%) as free POEMA and/or POEMA oligomers;
(b) DDT was recovered at 12.8/13.6-94% by weight; POEMA was recovered at 27.2/56.8-47.9% by weight.
The final composition of this nanogel would therefore be 39/61 (mole ratio) UDMA/POEMA.
There is still the problem of insoluble fraction in the final nanogel after drying, which is attributed to the macrogel due to instability of the trapped free radicals in the nanogel. This problem needs to be addressed to facilitate the subsequent handling process and to ensure the quality of redispersion of the final nanogel in any formulated composition. Therefore, it is suggested to introduce a chemical quenching process into such reaction systems to stabilize the nanogel and avoid any large particle gelation during handling. The formed nanogel will also be able to be easily re-dispersed in the resin later on.
For this purpose, the stable free radical TEMPO should work well. For the general mechanism of controlled radical polymerization via Nitroxide Mediated Polymerization (NMP), the propagating radical should be properly terminated. A key aspect of NMP is that the reversibility will vary depending on the structural nature of the monomer and/or the nitroxide compound. For example, styrene can be further thermally cracked at high temperatures such as 110-120 ℃ to rejoin the free radical polymerization to develop a controlled free radical polymerization. However, unless specifically designed nitroxides are used, such reversible processes will not occur in any methacrylate system. More specifically, for methacrylates, TEMPO will not act as NMP, although it should quench methacrylate propagating radicals appropriately. Therefore, TEMPO should be an ideal candidate for stabilizing nanogels.
Preparation example 1:
the following raw materials were used:
solution copolymerization of 2-phenylethanediol methacrylate (POEMA) and Urethane Dimethacrylate (UDMA) (molar ratio 70/30, FIG. 1) was carried out using 30 mole% 1-dodecanethiol (DDT) as a chain transfer agent. 2, 2-Azobisisobutyronitrile (AIBN), 1% by weight in 200g of 2-butanone (MEK) at 75 to 80 ℃ was added. The methacrylate conversion was monitored by FTIR and the reaction solution was drained once the target conversion of 75-80% was reached. To this drained solution was added 0.20% by weight TEMPO to allow mixing at room temperature for 30min to form a nanogel mixture. The nanogel mixture was precipitated in 2000mL of hexane under vigorous agitation to produce a wet nanogel. The wet nanogel was isolated by decanting the hexane solution. The wet nanogel was further dried under reduced pressure for at least 12 hours. The dried nanogel was collected and the residue in the dry flask was completely soluble in acetone, which is a good indicator that an efficient TEMPO quenching process had taken place. In addition, such TEMPO-stabilized nanogels should be readily re-soluble in acetone or other resin blends.
As depicted in fig. 2, the overall methacrylate conversion increased steadily during normal free radical polymerization. The reaction solution was drained when the conversion reached 75% and no further increase in conversion was found in the drained and/or room temperature aged one day solution, which should indicate that TEMPO is very effective in permanently terminating the radical propagation.
For nanogel ZZ1-99(UDMA/POEMA (30/70 in MEK)), the same reaction system was divided into four sections, with different amounts of TEMPO added at 0% (ZZ1-99A), 0.20% (ZZ1-99B), 0.16% (ZZ1-99C) and 0.12% (ZZ1-99D) weight ratios. Then, post-polymerization heat aging was performed at 40 ℃ for several days (as depicted in fig. 6 and 7). The aged solution was monitored for physical appearance, discoloration, and solution viscosity. As depicted in table III and fig. 7, macrogels formed with the system without any TEMPO addition, and other systems looked good. However, it was also noted that for those systems with high concentrations of TEMPO, a higher viscosity was produced after further aging at 40 ℃. Surprisingly the least viscosity increase was found from the nanogel solution with the lowest TEMPO (ZZ1-99D, 0.12% TEMPO). The general mechanism of side reactions in the methacrylate-nitroxide system is shown in FIG. 3 (Macromol. Rapid Commun.2015, 36 (13): 1227-1247). Possible side reactions that can occur with nanogel/TEMPO solutions when aged at high temperatures (MEK system 40-80 ℃, and up to 100 ℃ for other solvents such as toluene) are shown in fig. 4.
Table III: effect of Heat aging on solution viscosity of TEMPO-stabilized Nanogels in MEK
For the hexane soluble fraction in TEMPO stabilized nanogel process, the following were observed:
(i) for UDMA/POEMA (25/75 in MEK): 40.0g (33.5% by weight) of a hexane-soluble liquid was collected as POEG/POEG, unreacted POEMA, POEMA oligomers and free DDT. There was little UDMA and no crystal residue.
(ii) For UDMA/POEMA (30/70, ZZ1-99B, ZZ1-99C, ZZ1-99D in MEK) andat room temperature TEMPO followed by aging at 40 ℃ for 15 days: 21.5g (18.9% by weight) of a hexane-soluble liquid was collected as POEG/POEG, unreacted POEMA, POEMA oligomers and free DDT. There was little UDMA but much crystal residue.
(iii) For UDMA/POEMA (30/70, ZZ1-127A in MEK) andTEMPO, unaged at room temperature: 31.0g (28% by weight) of hexane-soluble liquid was collected as POEG/POEG, unreacted POEMA, POEMA oligomers and free DDT. There was very little UDMA and no crystal residue.
(a) Based on1H NMR evaluation 14.5g (46.8%) free DDT, 13.1g (42.2%) free POEMA and 3.4g (11.0%) POEMA oligomer were present.
(b)14.5/19.1 ═ 76% by weight of DDT was recovered; POEMA was recovered in 35% by weight (13.1+ 3.4)/47.1.
(c) The final composition of this nanogel would therefore be 39/61 (mole ratio) UDMA/POEMA.
(iv) For UDMA/POEMA (30/70, ZZ1-127B in MEK) andTEMPO at RT and then aging at RT 7 Sky: 26.9g (27% by weight) of hexane-soluble liquid was collected as POEG/POEG, unreacted POEMA, POEMA oligomers and free DDT. There was little UDMA and little crystal residue.
(v) For UDMA/BZMA (30/70, ZZ1-130A in MEK) andTEMPO, unaged at room temperature: 38.8g (36% by weight) of hexane soluble liquid was collected as unreacted BZMA, BZMA oligomers and free DDT. There was little UDMA and no crystal residue.
(vi) For UDMA/BZMA (30/70, ZZ1-130B in MEK) andTEMPO at RT and then aging at RT 7 Sky: 33.2g (34% by weight) of hexane-soluble liquid was collected as unreacted BZMA, BZMA oligomers and free DDT. There was little UDMA and no crystal residue.
For nanogel ZZ1-127B (UDMA/POEMA (30/70 in MEK)), 0.20% by weight TEMPO was added. Then, post polymerization aging was performed at room temperature for several days (as depicted in fig. 5).
In addition, it should also be noted that the other consequences of TEMPO dosing at elevated temperatures or at room temperature and subsequent aging also at elevated temperatures can lead to further side reactions, which jeopardize the purpose of effectively stabilizing the nanogels.
Finally, as shown in table IV, a robust overall yield of about 77% was achieved for this TEMPO-stabilized UDMA/POEMA nanogel system. On the other hand, it was also found that the total yield of nanogels (about 66%) could not be improved by simply converting to monomethacrylates with high purity (99.5% BZMA).
Table IV: effect of TEMPO on the yield and solubility of nanogels via batch Process
For TEMPO-stabilized UDMA/POEMA/DDT/MEK nanogel processes, the following were observed:
(i) TEMPO quenching at elevated temperatures or further thermal aging at elevated temperatures can trigger TEMPO/methacrylate radical side reactions, which are responsible for the formation of floes in MEK solutions (TEMPO related side reactions). TEMPO quenching at ambient temperature is therefore recommended.
(ii) TEMPO in the range of 10-15% by weight based on AIBN used in the nanogel will be effective in chemically quenching nanogel propagating radicals. This will result in a stable nanogel free of large particle gelation that is easy to handle later. This is evident from the fact that fully soluble nanogels can be recovered from the post-vacuum drying process.
(iii) It is recommended that this chemical quenching should not be carried out at high temperatures (80 ℃). Alternatively, once the desired conversion (75%) was reached, the drained nanogel solution was quenched directly. Subsequent additional aging at room temperature will not have any negative effect on stability and will not produce crystalline by-products in the nanogel and nanogel residue.
Preparation example 2: nanogel containing 8 mol% of trivinyl crosslinker
306.8g (1.488 moles) of ethylene glycol phenyl ether methacrylate (POEMA), 55.2g (0.1632 moles) of trimethylolpropane trimethacrylate (TMPTMA), 180.0g (0.3825 moles) of bis- (2-methacryloylethyl) -N, N' -1, 9-nonene biscarbamate (UDMA), 5.4g (0.033 moles) of 2, 2-azobis- (2-methylpropionitrile) (AIBN) and 123.9g (0.612 moles) of dodecanethiol (DDT) were dissolved in 1084.0g of methyl isobutyl ketone (MIBK). The solution was then pumped through a Fluitec containment continuous flow reactor at a flow rate of 4mL/min at 100 ℃. The resulting product solution was then quenched by dropping into 0.54g of pre-dissolved 2,2,6, 6-tetramethyl-piperidin-1-oxyl (TEMPO) placed in an ice bath. The resulting crude product was then dialyzed against acetone using a regenerated cellulose membrane with a 10kDa molecular weight cut-off (MWCO) for 8 days. The purified product was then evaporated under reduced pressure and dried under vacuum.
Is then used13The product was analyzed by C-NMR. -CH at 7.02ppm3The peak (FIG. 8) is descriptive of the trifunctional crosslinker used and demonstratesSuccessful incorporation into nanogels was achieved.
Preparation examples 3,4, 5: nanogels containing 15, 20 or 25 mol% of trivinyl crosslinker
Ethylene glycol phenyl ether methacrylate (POEMA), trimethylolpropane trimethacrylate (TMPTMA), bis- (2-methacryloylethyl) -N, N' -1, 9-nonene biscarbamate (UDMA), 2-azobis- (2-methylpropanenitrile) (AIBN), and dodecanethiol (DDT) were dissolved in methyl isobutyl ketone (MIBK). The solution was then pumped through a Fluitec containment continuous flow reactor at a flow rate of 4mL/min at 100 ℃. The resulting crude product solution was then quenched by dropping into 0.1g of pre-dissolved 2,2,6, 6-tetramethyl-piperidin-1-oxyl (TEMPO) placed in an ice bath. The resulting crude product was then dialyzed against acetone using a regenerated cellulose membrane with a 10kDa molecular weight cut-off (MWCO) for 10 days. The purified product was then evaporated under reduced pressure and dried under vacuum.
Table V gives an overview of the amounts of reagents used for the synthesis of nanogels containing 15 mol%, 20 mol% or 25 mol% of trivinyl crosslinker.
Table V: demonstration of the amount of reagents used to synthesize nanogels containing 15, 20, or 25 mole% of trivinyl crosslinker
Is then used13C-NMR analysis of the nanogels. 7.50-7.51ppm CH3The peaks (fig. 9, 10, 11) are descriptive of the trifunctional crosslinker used and demonstrate the successful incorporation of TMPTMA into each nanogel.
Preparation example 6: nanogel containing 30 mole% of divinyl diallyl mono-alkenyl crosslinker
In a 250mL round bottom flask, 34.00g (0.165 mole) of ethylene glycol phenyl ether methacrylate (POEMA), 9.39g (0.071 mole) of N, N '-bisacryloyl-N, N' -bisallyl-1, 4-but-2-enediamine (BAABE), 0.53g (0.003 mole) of 2, 2-azobis- (2-methylpropionitrile) (AIBN), and 14.30g (0.071 mole) of dodecanethiol (DDT) were dissolved in 106.78mL of methyl isobutyl ketone (MIBK). The reaction was carried out at 80 ℃ for 110 min. The resulting crude product solution was then quenched by placing in a liquid nitrogen bath. The resulting crude product was then dialyzed against acetone using a regenerated cellulose membrane with a 10kDa molecular weight cut-off (MWCO) for 19 days. The purified product was then evaporated under reduced pressure and dried under vacuum.
Is then used13The product was analyzed by C-NMR. A representative BAABE peak has CH with acryloyl groups at 118.11ppm2-and 132.23ppm of allyl-CH- (FIG. 12). A representative POEMA peak is the aromatic carbon at 176.62 ppm. These peaks describe the composition of the pentafunctional crosslinker and POEMA used and demonstrate the successful incorporation of both into the nanogel.
Application example 1: TEMPO quenched nanogels incorporating 8 mol% TMPTMA in the feed composition were dispersed in ceram.x Universal resin at 10 wt% loading and compared to nanogels without TMPTMA (POEMA/UDMA only). As shown in table VI, the resin with nanogels containing 8 mol% TMPTMA also dispersed well in the ceram.x Universal resin, resulting in similar viscosity and refractive index. Furthermore, comparable flexural strength and flexural modulus were found compared to POEMA/UDMA nanogel alone and to the center. More importantly, a significant reduction in shrinkage stress was observed at only 10 wt% nanogel loading.
Table VI: properties of Ceram. x Universal resin dispersed with nanogels containing 8 mol% TMPTMA versus no TMPTMA
Application example 2: TEMPO quenched nanogels incorporating 15 mol%, 20 mol% or 25 mol% TMPTMA or 30 mol% BABBE in the feed composition were dispersed in a ceram. x Universal resin at 10 wt% loading. Properties of the ceram. x Universal resin dispersed with nanogels containing 15 mol%, 20 mol%, or 25 mol% TMPTMA, or 30 mol% BABBE are shown in table VII.
Table VII: properties of Ceram. x Universal resin dispersed with Nanogel containing 15 mol%, 20 mol% or 25 mol% TMPTMA or 30 mol% BAABE
Previous studies by the inventors have found that nanogel modified Prime & Bond NTs improve shear adhesion strength to dentin (SBS) after 5,000 and 10,000 thermal cycle periods. Furthermore, no significant change was observed for Prime & Bond NT after 6 months of water storage at 37 ℃, but for nanogel modified Prime & Bond NT, higher SBS for dentin and enamel was observed after 6 months of water storage at 37 ℃.
While the invention has been described with reference to one or more embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope thereof. Therefore, it is intended that the invention not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out this invention, but that the invention will include all embodiments falling within the scope of the appended claims. Moreover, all numbers expressing quantities of ingredients, and so forth used in the detailed description are to be understood as being indicative of the exact nature and approximate values explicitly identified.