JPH0251884B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention provides compositions advantageously suitable for dental restoration applications,
In particular, it relates to such compositions which have good stability on standing under various conditions over long periods of time. Polymerization catalysts, such as free radical polymerization initiators,
and U.S. Patent No. 3066112 granted to Bowen.
BIS-
Methacrylate-type monomers, such as the bisphenol A-glycidyl methacrylate reaction product called GMA, provide valuable substrates for a variety of dental restoration procedures, such as fillings, hole and fissure sealants, etc. be done. Generally, such compositions are used in accordance with the prescribed order, and contact thereof with the polymerization catalyst activator in the presence of the polymerizable monomer occurs only during actual use by the dentist. The materials are selected and dosed to ensure fairly rapid polymerization upon such contact to produce a solid mass polymer in the oral cavity. For ease of handling and processing, such a composition can be provided to the dentist in the form of various viscous pastes that allow it to be homogeneously blended with minimal effort. As described in the prior art, the above can be accomplished by providing physically separate filler-containing compositions, each containing monomer/catalyst, monomer/activator, etc. Such compositions that are commercially available are packaged separately. Despite the precautions taken by the manufacturer, it is in practice that undesirable polymerization of the monomer composition upon standing can occur quite rapidly and to a disruptive extent prior to the time of contact of the composition with the active agent composition. will be discovered. Although various inhibitors can be included in the monomer composition to prevent foreign free radicals from reacting with the composition that may induce polymerization, such undesired polymerization is noteworthy. Polymers formed from such destabilized monomer compositions necessarily have poor structural integrity, color, etc. Furthermore, it is quite possible that the affected monomers become completely unsuitable for dental applications due to hardening of the monomer composition (a corollary of premature polymerization). Therefore, economic efficiency may be impaired. To avoid this problem of premature polymerization,
It is common dentist practice to refrigerate the components of polymer-forming compositions until use. Various methods have been provided in the past to alleviate the above problems. For example, it has been found that the use of special free radical catalysts, such as those with good thermal stability, can effectively retard some of the destabilization of the monomer. However, such methods suffer from thermal effects in all cases. That is, it is based on the assumption that the free radical generation reaction of the catalyst is promoted or initiated at high temperatures. Furthermore, this method has a rather narrow selection range of catalysts. Other techniques have proposed using significantly larger amounts of fillers, such as silica, to achieve sufficient storage stability. However, inorganic fillers of the type commonly used in said compositions may significantly retard the curing or polymerization of the methacrylate monomers, as pointed out in said publication. This is apparently due to the use of silane couplings, which serve the purpose of restoring, at least in part, the curability or polymerizability of the monomers. The effectiveness of measures for suppressing undesired premature polymerization of monomers should be significantly amplified at the time of monomer/catalyst activator contact, at which point a fairly rapid and efficient polymerization is unavoidable. The most important thing is not to. Although what has been described above is only an example of the technology related to the present invention, effective implementation of the repair method is difficult;
It is clear that this requires a careful and precise balancing of a number of factors that may themselves be self-contained or may themselves create other problems. With the present invention, the stability problems of the monomers described above are addressed for use in the formulation of the monomer compositions, rather than any interaction that may occur between the materials used as synergistic ingredients in the compositions. It was discovered that this phenomenon is caused in principle by the properties of the monomers used. The present invention shows that mixing methacrylate monomers, especially those of the BIS-GMA type that are commonly available commercially, with catalysts, especially peroxide, hydroperoxide type catalysts, reduces the lifetime and that when the mixture is not mixed with catalyst, This is based on the surprising discovery that polymers frequently polymerize under storage conditions prior to use, rendering the product unsealable for remedial purposes. Such pseudoreactivity is exhibited even under mild ambient conditions (eg, conditions during normal storage). For example, in laboratory tests using commercially available BIS-GMA as monomer and adding catalyst to it, but not treating it with the method of the present invention,
The polymer is obtained after just one day at room temperature. whether this instability is due to contaminants;
There is still no answer as to where the pollutants come from. It is probably introduced at some point during the preparation and/or processing of the methacrylate monomer and/or precursor. In particular, it is known that it is difficult to purify bisphenol A type methacrylate monomer by distillation because it has a high boiling point. Therefore, the possibility that this monomer is contaminated with high-boiling substances cannot be excluded. Whatever the reason, what is known so far is that methacrylate monomers can be used with ion exchange materials,
Treatment with sulfonic acid type cation exchange resins, especially in the acid form, significantly reduces the polymerization tendency of the monomers, especially when mixed with catalysts, and this is especially noticeable when the catalysts are of the free radical peroxide type. As mentioned earlier, the instability problem is BIS−
This is particularly serious in the case of monomer compositions containing GMA. Surprisingly, this BIS-GMA polymerizes after only one day at room temperature in the presence of the thermostable catalyst cumene hydroperoxide (e.g. 2% on monomer basis). On the contrary, commercially available methyl methacrylate containing a polymerization inhibitor containing 1 to 2% benzoyl peroxide polymerizes within a few days after being left at 25°C; As expected, it exhibits very high stability in the presence of peroxides. Assuming a half-life of 10 hours, the temperature is preferably about 73°C when benzoyl peroxide is used, and 160°C and 170°C for cumene hydroperoxide and t-butyl hydroperoxide, respectively.
BIS-GMA is therefore somewhat unusual in that it polymerizes fairly quickly even with the use of thermally stable catalyst materials. The above explanation has been made to point out the significance of the fact that each pollutant may have different properties and that each pollutant has different effects on different catalyst materials. .
When BIS-GMA is used as the only or major monomer, prolonged contact of the monomer with the catalyst prior to treatment should be avoided, but for other monomers, such as methyl methacrylate, this requirement may be avoided. It's not that strict. In the former case, the treatment with the ion exchange resin is preferably carried out before the monomer and the catalyst come into contact. Sulfonic acid type cation exchange resins are well known and commercially available in many forms. Particularly preferred in the present invention are sulfonated, cross-linked polystyrene resins, one example of which is a beaded one is DOWEX50W-X8 [1.9 meq/ml, H ⁺ type (wet weight basis) to 5.1 meq/ml (dry weight basis). )] is commercially available under the trade name. In addition, suitable sulfonic acid cation exchange resins
DOWEX50W−X2, DOWEX50W−X4 and
POWEX50W-X10 (Dow Chemical Co.), Amberlite IR120 and Amberlite 15 (Rohm & Haas), and Fisher Chem. Co. Lexin 101(H).
The last Lexin 101(H) is 4.6meq/ml (dry basis)
It has the characteristic value. Cation exchange resins are most effectively used to treat the monomers before catalyzing them (ie, used as pretreatment agents). According to this method, contaminants removable by cation exchange treatment, including those of a cationic nature, are at least substantially removed from the monomer, ie, physically extracted from the monomer. Impurities present in commercially available cation exchange resins can be removed by washing with acetone and drying in an oven, after which the resin is contacted with a methacrylate monomer. This contact can be made in the usual manner. For example, ion exchange beads (e.g. 16-200 mesh, preferably 20
-50 mesh) to the methacrylate monomer solution, stir the mixture for the required time, and filter the beads. This contact continues until the contaminants are at least substantially removed. Whether the contaminant has been at least substantially removed is determined by storage stability testing. For example, in laboratory tests, 8 parts of cation exchange resin and BIS-
In the case of a mixed solution consisting of 52 parts of the GMA-containing monomer composition, a monomer product substantially free of contaminants was obtained after being left under stirring for 24 hours. As an alternative method of removing contaminants from the monomer, passing the monomer through a column of a suitable ion exchange resin in a known manner satisfies the purpose. Methacrylate monomer materials suitable for use in the present invention are well known to those skilled in the art. Generally preferred materials include monomers having a central portion containing at least one aromatic ring and at least two terminal acrylic groups. As a monomer of this type, BIS
-GMA is particularly preferred and in preferred embodiments accounts for at least about 50% by weight of the total monomer composition. BIS, commercially available from Freeman chem (Co.) under the trade name NUPOL
-GMA is also an example of a substance that can be suitably used in the present invention. Methacrylate monomers particularly suitable for use in the present invention have the general formula: Here M is methacryloyloxy, that is, CH ₂ =
C(CH ₃ )COO ^- ; M' is methacrylyloxy or hydroxyl; A is methylene; alkylene having 1 to 3 carbon atoms such as propylene and isopropylene, hydroxymethylene, and 2-hydroxypropylene Hydroxyalkylene having 1 to 3 carbon atoms or acetoxyalkylene having 3 to 5 carbon atoms in the alkylene group, such as 2-acetoxypropylene, 3-acetoxymethylene, etc.; n is 1 to 4, preferably 1 or 2; m is 2 or 3 and p is 1
or 2, where the sum of m and p is 4; R is hydrogen, methyl, ethyl or ethyl or -A
-M (where A and M are as described above);
Ar is phenylene, e.g. O-phenylene, m
-phenylene or p-phenylene, alkyl-substituted phenylene, such as tolylene or 5-phenylene
B is a cycloaliphatic group having 6 to 10 carbon atoms, such as t-butyl-m-phenylene or 1,3-cyclohexylene;

[Formula] Here, R ₄ and R ₅ each independently represent hydrogen, alkyl, e.g., C ₁ to _{C 4}
or substituted alkyl; and R′ is ethylene;
Alkylene having 2 to 12 carbon atoms such as dodecylene or -R ² (-O-R ² )-OR ² - where R is 2 to 3 carbon atoms such as ethylene, propylene or isopropylene. and R ³ is propylene, and X is 0 to 5;
Tolylene, methylene-bis-phenylene or alkylene having 2 to 12 carbon atoms. Monomers having the above formula are well known and commonly commercially available. Alternatively, they can be synthesized using conventional synthetic methods, for example diphenolic acid, phloroglucinol or bisphenols and glycidyl methacrylate with various tertiary amines and/or
or by reacting in the presence of phosphine or by reacting methacrylic acid with an epoxide-containing compound such as diglycidyl ether of bisphenol. Many of these monomers combine the appropriate alcohol with methacrylic acid,
It is also produced by reaction with methacrylic chloride or methacrylic anhydride. Monomers having these formulas are illustrated below; Monomers having the formula, and are preferred in the present invention. Among these monomers, the formula
and are particularly preferred, and the monomers are more often used in mixtures of monomers, and. Other methacrylate monomers suitable for use in the practice of this invention have the following general formula (where M and Ar are as previously described); (MR ⁴ OAr) ₂ C(CH ₃ ) ₂ ; R ⁴ is Propylene; (MR ⁵ OAr) ₂ and (MR ⁵ O) ₂ Ar; R ⁵ is 2-
Hydroxy-propylene; MAR ⁶ M, where R ⁶
is hydroxycyclopentyl or hydroxycyclohexyl and A is 2-hydroxyethylene; and M ₂ R ⁸ , where R ⁸ is Generally, these monomers are commercially available or can be easily prepared. Detailed manufacturing methods for these monomers are available in U.S. Patent Nos. 3066112; 3721644; 3730947;
3770811 and 3774305. Tertiary eutectic mixtures suitable for use in the present invention are disclosed in U.S. Pat.
Listed in 3539526. All of the aforementioned patents are fully incorporated herein by reference. It is to be understood that mixtures of two or more suitable methacrylate monomers also fall within the scope of the invention. In fact, depending on the choice of monomers, mixtures may be desired to optimize the properties of the dentifrice composition. Thus, it is desirable that the monomer or monomer mixture have a viscosity of about 100 to about 10,000 poise as measured on a Bruckfield viscometer at room temperature at 20 rpm. The more viscous mass is easier to handle at high temperatures. As mentioned above, preferred mixtures contain at least about 50 wt% BIS-GMA. Preferred aliphatic dimethacrylate monomers (also referred to as diluent monomers) and the aforementioned
Monomers particularly suitable for use in the BIS-GMA mixture are: meheximethylene dimethacrylate (HMDMA), triethylene glycol dimethacrylate (TEGDMA) and polyethylene glycol dimethacrylate (PEGDMA).
In a highly preferred embodiment, the monomer composition comprises
Consisting of a 1:1 mixture of BIS-GMA, this system has excellent stability at room temperature and elevated temperature (37°C). Free radical generating catalysts useful in the present invention typically activate to initiate polymerization of the aforementioned monomers and, in the case of filler-containing systems, at least about 25,000 to
30000psi and preferably at least about 35000~
Solid MAS with excellent compressive strength of 40000psi
It is an organic compound that generates free radicals that can form polymers. Preferred compounds are organic peroxides and hydroperoxides, of which benzoyl peroxide, cumene hydroperoxide and t-butyl hydroperoxide are particularly preferred. The catalyst usually comprises about 5 to 5%, preferably 1 to 4% by weight of total monomers.
%, and most preferably 1-3%. A particular advantage of the present invention is that large amounts of catalyst can be used within the given range without adversely affecting stability. A further advantage of the present invention is that it can be stored without the need for fillers and is therefore an optional ingredient in the compositions of the present invention. Thus,
Good stability of the monomer composition is obtained regardless of the presence or absence of such compounds. In use, the amount of filler can vary up to about 40% of the weight of the monomer. However, in view of the polymerization (curing) retarding effect of the filler, it is desirable to limit the amount of filler to less than 100%, preferably less than about 80%, of the weight of the total composition. The inorganic particulate fillers used in the compositions of the invention include quartz glass, quartz, crystalline silica, amorphous silica, soda glass beads, barium glass and other radiopaque glasses, glass rods, ceramic oxides. , including synthetic inorganics such as silicate glass and beta-eucryptite (LiAlSiO ₄ ),
The latter has a negative expansion coefficient. It is also possible to use finely divided materials and powdered hydroxylapatite; materials that react with silane coupling agents are also preferred. A small amount of color material is included to match the composition to the various shades of teeth. Suitable color materials include iron oxide black, cadmium yellow and orange, fluorescent zinc oxide, titanium dioxide, etc. Filler particles are generally less than about 50 microns in diameter and preferably less than 30 microns in diameter. Unfilled compositions are particularly useful when the dental composition is used as a coating, a restoration margin sealant, or an adhesive. As mentioned above, coupling agents, and indeed any agents used herein, are particularly beneficial with the use of silica fillers, as they suppress filler effects and thus restore an approximate equivalent amount of polymerizability. This is because they tend to at least partially hinder the polymerization that occurs. The beneficial effects of coupling agents, which are silane compounds, are most evident with respect to the compressive strength that characterizes the final dental polymer. A silane coupling agent is a material containing at least one polymerizable double bond that reacts with a methacrylate monomer. Examples of suitable coupling agents are gamma-methacryloxypropyltrimethoxysilane, vinyltrichlorosilane, tris(2-methoxyethoxy)silane, tris(acetoxy)
Vinylsilane, 1-N-(vinylbenzylaminoethyl)aminopropyl trimethoxylane-3.
The first specified material is preferred for use with methacrylate monomers. Because they are similar in double bond reactivity. Coupling agents may simply be added into monomer compositions containing fillers, e.g.
It is not a requirement that the prehydrolysis reaction according to the acid/alkali hydrolysis method described in 3066112 can be used in such an operation. Therefore, the filler (usually quartz) will dry approximately 0.5
It can be first slurried with an aqueous solution of the coupling agent at a concentration such that ~2% by weight of the coupling agent is precipitated or reacted with the filler and then mixed with the monomer composition. Obviously, this latter operation results in reaction with the filler and/or
or lead to a many-fold increase in the amount of silane bound to the filler. However, the strength properties of the dental polymers prepared with the compositions of this invention are good and consistent no matter what procedure is used. The form of dental polymers in the oral cavity is the active agent-containing composition of the present invention, which is usually supplied as a material of paste-like consistency, which may be enriched with fillers of the type described above. This can be done by mixing with. Suitable activators include, but are not limited to, substituted thioureas (e.g. acetylthiourea), N,N-dimethyl-para-toluidine and para-toluenesulfuric acid, as is well known. isn't it.
Polymerization and concomitant hardening occur rapidly, but over a sufficient period of time to allow the dentist to quickly treat the desired area with the composition. The resulting polymer has good strength, especially compressive strength, and shows no appreciable tendency to flaking, flaking or other failure. The polymers are completely non-toxic and show no tendency to produce low molecular weight substances or other substances that may cause medullary irritation and are therefore in all major respects less susceptible to the effects of fluids present in the oral cavity. It is recognized that it is inactive against. Polymerizable dental compositions prepared and formulated as described herein are stable for many months at room temperature and exhibit no signs of premature polymerization. Furthermore, good stability also appears to be exhibited at elevated temperatures, with certain preferred compositions exhibiting good long-term stability at temperatures on the order of 37°C. It is understood that the above-mentioned problem of impurity contamination varies in degree depending on the type of methacrylate monomer used and the catalyst material.
Thus, in certain instances, improved stability may be obtained through the combination of low-fouling or conversely high-fouling monomers with relatively stable catalyst materials. The importance of the catalyst in this respect is not at all diminished. However, to the extent that contamination contributes to catalyst dissociation reactions and associated free radical generation, the aforementioned treatments and compositions formulated thereby provide the aforementioned stability improvements. It is not always possible to know what type of substance exhibits such a function, since in many, if not most cases, the substances capable of exerting such an effect on the catalyst cannot be precisely chemically identified. However, such materials may still be present in the methacrylate monomer due to the manufacturing or other processing steps of the methacrylate monomer. In particular, BIS-SMA is
This is a more dramatic example of a commercially available material that the inventor has discovered to contain such a destabilizing contaminant. Purification of monomers, including monomers that have been or have been in contact with a catalyst, produces significant amounts of free radicals, i.e., amounts sufficient to initiate polymerization at a rate that forms significant polymers in a relatively short period of time. should be carried out before free radicals are generated. Here, "short time" means a period of time shorter than what would normally be considered to be associated with inventory. In most cases, the polymerizable composition will be used by a dentist within a few weeks of purchase. As far as the compositions of this invention are concerned, monomer destabilization will not be a problem since the compositions of this invention will last significantly longer than a dentist's storage or inventory period under normally expected storage conditions. This is because it is stable over a long period of time. Furthermore, given that the polymerizable composition will often be refrigerated prior to use by the dentist, even longer storage periods may be appropriate. Furthermore, it will be clear that the mixing of monomers and catalyst by the manufacturer will occur according to a schedule and necessarily close to the time prior to sale. However, inevitably, given a sufficiently long storage time and/or high temperature atmosphere, gel formation in the monomer composition will occur. Therefore, even if the free radical concentration is low, gelation will occur over time. As used herein, "prior to the formation of free radicals" or "prior to the formation of a significant amount of free radicals" shall have meanings consistent with, and should be understood with full reference to, the foregoing. It is. Therefore, treating the preformed mixture of catalyst and monomer in accordance with one aspect of the invention prior to the formation of significant free radicals ensures that the free radicals present at the time of the treatment are removed within said required storage time. It only means that it is not sufficient to cause gelation of the monomer composition. The stability of commercially available BIS-GMA and methyl methacrylate (MMA) in the presence of organic peroxide and hydroperoxide catalysts is compared as follows. MMA (Rohm & Haas, hydroquinone methyl ether) in various proportions
MEHQ (containing 10 ppm) was mixed with the catalyst to make 2% each of benzoyl peroxide (BP), cumene hydroperoxide (CHP) and t-butyl hydroperoxide (TBH) solutions.
These solutions were left at room temperature (20-25°C). BIS-GMA (manufactured by Freeman Chemical Co., trademark "NUPOL") was mixed with each of the above catalysts to similarly prepare 2% solutions, and these were left at 20 to 25°C. The results obtained are shown in the table below.

[Table] In section (a), it shows that gelation did not occur 9 days after the end of the experiment. Surprisingly, it is found that BIS-GMA makes a more stable mixture with the less thermally stable catalyst, BP, compared to either TBH or CHP. As mentioned above, both TBH or CHP are recommended to be used at significantly higher temperatures than BP and are therefore more susceptible to polymerization than BP when TBH or CHP is dissolved in the monomer. would be expected to provide high stability. The data for MMA are more in line with conventional expectations, confirming the rather anomalous stability profile of BIS-GMA in the presence of free radical catalysts. Gel time indicates the date when gel formation was first observed. The following examples are included for illustrative purposes and the invention is not limited thereto. All "parts" and "%" are by weight. Example 1 BIS-GMA (“NUPOL” 46-4005, manufacturing batch No. 124793) and hexamethylene dimethacrylate (HMDMA; manufactured by Sartomer Chemicals, lot)
No.PB844) was washed with acetone and dried in an oven.
8 parts of DOWEX50W-X8 ion exchange resin beads (1.9MEQ/ml, H ⁺ form) were added. The mixture was stirred for 24 hours and then passed through a sintered glass filter to remove the beads. To this monomer solution, 0.026 parts of inhibitor was added to replace the inhibitor thought to have been lost during the ion exchange treatment.
MEHQ was added. A portion of the monomer solution thus treated was used to prepare solutions containing 2% BP and 4% BP, respectively.
A solution containing CHP was made. After being left at room temperature for 6 months,
These solutions showed no polymer formation. The experiment was terminated at that point. The stability for the BIS-GMA composition is compared to the 2 day gelation time of BIS-GMA for the 2% CHP solution in the table.
Significantly improved. In this example, BIS-GMA/
The greatly improved stability obtained for the HMDMA monomer solution is an even more surprising result when considering the high concentration of CHP (4%). Example 2 First, to 25 parts of the monomer composition obtained by the ion exchange treatment of Example 1, 5 parts were added on a monomer basis.
% of silane coupling agent was added followed by 75 parts of amorphous silica. This composition is stable at room temperature for over a year with no observed gel formation. Example 3 The aged composition obtained in Example 2 was mixed with the same amount of a composition of similar composition but without CHP and 2% acetylthiourea was added. Rapid and complete curing occurred. Other monomer compositions that were tested in the same manner as in each of the above examples and obtained similar stabilizing effects are as follows (the numbers in brackets are "parts"). BIS-GMA (71) + HMDMA (29) BIS-GMA (71) + PEGDMA (29) * BIS-GMA (50) + TEGDMA (50) * * BIS-GMA (71) + TEGDMA (29) * Polyethylene glycol dimethitaacrylate * *Trimethylene glycol dimethacrylate

Claims (1)

[Scope of Claims] 1. Comprising at least one methacrylate monomer having 2 to 4 polymerizable olefin-type double bonds and a free radical-releasing polymerization catalyst capable of initiating polymerization of the monomer when activated. , the catalyst is present in an amount sufficient to achieve a predetermined polymerization rate and/or degree of polymerization, and the monomer is treated with a sulfonic acid type cation exchange resin in free acid form prior to contact with the catalyst. A polymerizable dental restorative material composition stabilized against premature activation by a catalytic component, comprising: 2. The composition of claim 1, wherein at least about 50% by weight of said methacrylate monomer has at least one aromatic ring in its central portion. 3. At least about 50% by weight of the methacrylate monomer is the reaction product of bisphenol A and glycidyl methacrylate.
Compositions as described in Section. 4. The composition of claim 3 comprising up to about 50% by weight hexamethylene dimethacrylate. 5. The composition of claim 4, wherein said monomer comprises an approximately 1:1 mixture of the reaction product of bisphenol A and glycidyl methacrylate and hexamethylene dimethacrylate. 6 Approximately 400% by weight based on the weight of the monomer
2. A composition according to claim 1, comprising a granular inorganic filler. 7. The composition according to claim 6, wherein the filler is a quartz material. 8. The composition according to claim 7, wherein the filler is silica. 9. The composition of claim 8 comprising up to 5% by weight of said monomer of a coupling agent silane. 10 About 0.5 to 5 based on the weight of the monomer
% of a free radical catalyst selected from the group consisting of benzoyl peroxide, cumene hydroperoxide, t-butyl hydroperoxide, p-methane hydroperoxide, diisopropylbenzene hydroperoxide. thing.