JPS6340831B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to an adhesive for human body rigid coarse textiles containing a pyrophosphate derivative and/or a polymer produced from the derivative. The adhesive of the present invention has excellent affinity with hard tissues such as bones and teeth, and exhibits remarkable effects particularly in dental treatment. Therefore, in the following explanation, the dental adhesive will be mainly described, but these explanations are not intended to limit the scope of application of the adhesive of the present invention. In dental treatment, various types of cements have been the mainstream filling material for partially missing teeth.
BACKGROUND ART Recently, heat-curable or photo-curable resin compositions with excellent strength, aesthetics, operability, etc. have been attracting attention. When filling the defect with these fillers,
Adhesiveness to the tooth structure is one of the important points, and if the adhesiveness is insufficient, the filling may fall off after filling, or the margin sealing properties may be insufficient, allowing saliva etc. to enter and form deep parts. It may also induce secondary caries. Furthermore, when attaching orthodontic bands and the like, the adhesion between the bands and the tooth structure is a problem. For this reason, various adhesives including cyanoacrylate adhesives have been developed, but these are not necessarily satisfactory in terms of their affinity for teeth. Recently, as research on this point has progressed, in order to satisfy the adhesion to teeth,
It has become clear that it must satisfy both affinity for enamel and affinity for dentin. The present inventors have conducted research to develop an adhesive having such characteristics, particularly an adhesive having good affinity for enamel and dentin, and have completed the present invention. That is, the adhesive of the present invention has a functional group having a polymerizable double bond in the molecule and An adhesive for human hard tissue containing a polymerizable monomer having a group represented by the following and/or a polymer in which at least the polymerizable monomer is one of the components. The above-mentioned pyrophosphate group linkers are occupied by four identical or different phosphate groups. The polymerizable functional group exists in one or more of the four phosphoric acid ester groups, and the type thereof is not particularly limited in the present invention, but a typical example is a double bond such as a vinyl group. A group containing is shown. Phosphate ester groups are derived from various unsaturated or saturated hydrocarbons or chain or cyclic compounds such as N, S, O, etc., in addition to groups having polymerizable functional groups, and the number and bond of these substituents Depending on the position, the polymerizable monomers can be classified into the following five types. That is, (1) the monomer has the general formula [Formula R ¹ is alkenyl, acryloyloxy,
means (lower) alkyl or aryl having one or more of methacryloyloxy, R ¹
(lower) alkyl in is hydroxy and/
Alternatively, it may be substituted with halogen. R ² means alkyl or aryl, and the aryl in R ² may be substituted with (lower) alkyl, (lower) alkoxy or halogen. still
R ² may be the same or different. ] Adhesive represented by (2) the monomer has the general formula [In the formula, R ¹ and R ² are the same as in (1) above, and R ¹ and R ²
may be the same or different from each other. ] Adhesive represented by (3) the monomer has the general formula [In the formula, R ¹ and R ² are the same as in (1) above, and R ¹ and R ²
may be the same or different from each other. ] Adhesive represented by (4) the monomer has the general formula [In the formula, R ¹ and R ² are the same as in (1) above, and R ¹ may be the same or different. ] Adhesive represented by (5) the monomer has the general formula [In the formula, R ¹ is the same as in (1) above, and R ¹ may be the same or different. ] Examples include adhesives shown below. The compounds represented by the above general formulas () to () are produced according to the following reaction formula. Reactions are divided into two types: reaction A when the target compound is symmetric, and reaction B when the target compound is asymmetric. The reaction mechanism will be shown below, with reaction A using a symmetrical pyrophosphate derivative (2) as the target compound, and reaction B using an asymmetric pyrophosphate derivative (2) as the target compound. [In the formula, R ¹ and R ² are the same as above. In reaction A, R ¹ and R ² are each the same, and in reaction B, R ² may be the same or different. Moreover, X means halogen. ]. In addition, when producing the target compound () () (), in the above reaction A or reaction B, R ¹ ,
It goes without saying that it is necessary to use starting materials corresponding to compounds () and () in which the number of R ² and the combination of bonding positions are changed. A more detailed explanation of the groups represented by R ¹ and R ² in the above general formula is as follows. R ¹ means (lower) alkyl or aryl having one or more of alkenyl, acryloyloxy or methacryloyloxy, such as allyl, acryloyloxy (lower) alkyl,
In addition to groups having one polymerizable functional group such as methacryloyloxy (lower) alkyl, etc., groups having two or more polymerizable functional groups such as diacryloyloxy (lower) alkyl, trimethacryloyloxy (lower) alkyl, etc. The vinyl group contained therein imparts polymerizability to the target compounds () to (). Examples of the (lower) alkyl in R ¹ include alkyl having 1 to 6 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, tertiary butyl, pentyl, and hexyl. Alkyl may be substituted with one or more hydroxy or halogen (eg, fluorine, chlorine, bromine, iodine, etc.). Examples of aryl include phenyl, xylyl, tolyl, biphenyl, anthryl, and phenanthryl. R ² means alkyl or aryl, and such alkyl may be not only the (lower) alkyl shown above but also a hydrocarbon having a larger number of carbon atoms. Further, examples of aryl include aryl as exemplified in R ¹ , and the aryl is
(Lower) alkyl as exemplified as (lower) alkyl in R ¹ , (lower) alkoxy [for example, alkoxy such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, tertiary butoxy, bentoxy, hexyloxy] and R ¹ It may be substituted with halogen, etc. as exemplified in the explanation of. Next, the above-mentioned process for producing target compounds () to () will be explained. Regarding reaction A, that is, the reaction when the target compound is a symmetrical pyrophosphoric acid ester compound: Under anhydrous conditions and at room temperature, a phosphoric acid compound ( ) (2 mol) having two substituents is added with dicyclohexylcarbodiimide (DCC) or the like in a solvent. React the dehydration condensation agent. The solvent is preferably one having selective solubility such as acetonitrile. The reaction is a dehydration condensation reaction in which one molecule of water is eliminated from two molecules of the compound (), and after the reaction is completed, operations such as purification are added to synthesize a symmetrical pyrophosphoric acid ester compound (). When DCC is used, DCC to which hydrogen and oxygen are added during the reaction becomes a urea derivative.
The derivatives are fractionated during purification of the target compound (). Next, regarding reaction B, that is, the reaction when the target compound is an asymmetric pyrophosphoric acid ester compound: A phosphoric acid compound ( ) ( ) (1 mol) with a substituent and a phosphoryl chloride ( ) (1 mol) in a solvent under anhydrous and low temperature conditions. ) in the presence of a dehydrohalogenating agent such as pyridine to form a crude compound ().
is obtained. The reaction temperature is preferably as low as about 0°C. Examples of the solvent include solvents that do not adversely affect the reaction, such as methylene chloride and chloroform. The reaction is a dehydrohalogenation condensation reaction in which one molecule of hydrogen halide is eliminated from one molecule of compound () and one molecule of compound (). After the reaction is completed, an asymmetric pyrophosphate ester compound () is synthesized by performing operations such as purification. The starting material () in the above reaction is orthophosphoric acid 2
1 in which the hydrogens of two hydroxyl groups are replaced with hydrocarbons, etc.
It is a basic phosphoric acid, and the following are exemplified. etc. On the other hand, compound () is a monohalide of phosphoric acid, in which the orthophosphoric acid bond is occupied by one halogen and two phosphoric acid ester groups. Examples of compounds in which the halogen is chlorine include those exemplified above as compound () in which the hydroxyl group is replaced with chlorine, and the following are also exemplified. The target compounds () to (), etc. can be produced in various ways by selecting the starting compounds (), () in possible combinations from the compound group shown above. The target substance () [(')] thus obtained is a polymerizable monomer, and is polymerized by the vinyl group in ^R1 . When using the above compound as an adhesive, it is necessary to mix it with a hardening agent (benzoyl peroxide, etc.) and a reaction accelerator (amines) to form an adhesive composition that can be used between a commercially available filler or crown and a missing tooth. An example is a method of intervening and curing. In addition, when forming the above composition, the above compound is considered to be a monomer for polymerization reaction, and the method includes a method of applying the monomer to the affected area and then curing it, and a method of polymerizing a different type of polymer with the monomer. By mixing the monomers,
A method in which the mixture is applied to the affected area and then cured; the monomers are polymerized with each other or with other polymerizable monomers, and the same or different monomers as above are mixed with the polymer, and the mixture is applied to the affected area. There is a way to harden it later. In addition, when using the above-mentioned compound, it is possible to use various combinations of adhesive components (the remainder after removing the curing agent, reaction accelerator, etc. from the composition).
Examples of the combinations are as follows. First, the combination unit is A: a compound of the present invention, monomer B: a homopolymer obtained from compound A, C: a copolymer of two or more monomer compounds A included in the present invention, or one or more monomer compounds A of the present invention and one species. Copolymer D with other polymerizable monomers mentioned above: Other polymerizable monomer E: Homopolymer F obtained from polymerizable monomer D: Copolymer obtained from polymerizable monomer D. When A is used alone When A is used in combination with one or more selected from the group consisting of B, C, D, E, and F Must include B and/or C and D, and Examples include use of combinations that optionally include E and/or F. The application of such an adhesive is not limited to teeth as described above, but can be used for adhesion to all hard tissues of the human body. Next, we will explain the characteristics of the adhesive of the present invention. For example, the dental filling material mentioned above has the following properties:
Adhesive properties are required to withstand long-term use after application. That is, if these are insufficient, the filling or crown may be damaged or fall out of the tooth cavity, necessitating retreatment. The adhesive of the present invention has excellent tensile, bending, and compressive strengths and elastic modulus after polymerization, so it exhibits excellent durability against various stresses received in the oral cavity, and has excellent abrasion resistance and hardness. Because of its excellent properties, the filling surface will not be damaged or worn away. Furthermore, since it absorbs less water and has a lower coefficient of thermal expansion, it exhibits stable durability even under the temperature and humidity conditions in the oral cavity. In addition to the above-mentioned physical properties, it also exhibits excellent adhesion properties, and has good affinity with the tooth structure, so the main component compound chemically bonds with the tooth structure, resulting in excellent adhesion at the joint surface and It has good edge sealing properties, as evidenced in Table 1. Furthermore, since the curing time of this monomer is short, there is little burden on patients. Furthermore, since the gelation time is appropriate and the workability during kneading is not impaired, there is no need to incorporate a low-molecular reactive diluent, and there is also the advantage that there is little irritation to the dental pulp. As described above, the composition of the present invention not only has high utility value as a dental adhesive, but also exhibits good properties as an adhesive for other hard tissues of the human body, and can be applied to a wide range of fields. Next, production examples and examples of the present invention will be shown. Production Example 1 Di-(2-methacryloyloxyethyl)phosphoric acid (2 mol) and dicyclohexylcarbodiimide (1 mol) were reacted in anhydrous acetonitrile at room temperature. After the reaction was completed, the urea derivative crystals were separated and the solvent was removed under reduced pressure. The residue was distilled off and the following pyrophosphoric acid ester compound was synthesized. IR: ν _nax , cm ^-1 2950, 1720, 1630, 1365, 1160, 980 NMR (CDCl ₃ ): δ 6.10 (bs, 1H×4, vinyl proton) 5.55 (m, 1H×4, vinyl proton) 4.30 ( m, 4H x 4, -CH ₂ CH ₂ -) 1.90 (d, 3H x 4, vinyl CH ₃ ) Production example 2 Di-(2-methacryloyloxyisopropyl)
Phosphoric acid (2 mol) and dicyclohexylcarbodiimide (1 mol) were reacted in the same manner as in Production Example 1,
The following pyrophosphoric acid ester compound was obtained. IR: ν _nax , cm ^-1 2950, 1720, 1630, 1375, 1160, 1000 NMR (CDCl ₃ ): δ 6.10 (bs, 1H×4, vinyl proton) 5.55 (m, 1H×4, vinyl proton) 4.85 ( m, 1H x 4, -CH ₂ CH CH ₃ ) 4.15 (m, 2H x 4, - CH ₂ CHCH ₃ ) 1.90 (d, 3H x 4, vinyl CH ₃ ) 1.30 (m, 3H x 4, -CH ₂ CH CH ₃ ) Production Example 3 Di-(2-acryloyloxyethyl)phosphoric acid (2 mol) and dicyclohexylcarbodiimide (1 mol) were reacted in the same manner as in Production Example 1 to obtain the following pyrophosphoric acid ester compound. IR: ν _nax , cm ^-1 2900, 1720, 1630, 1365, 1160, 970 NMR (CDCl ₃ ): δ 6.35 (m, 3H x 4, vinyl protons) 4.25 (m, 4H x 4, -CH ₂ CH ₂ -) Production Example 4 Di-(2-chloro-3-methacryloyloxypropyl)phosphoric acid (2 mol) and dicyclohexylcarbodiimide (1 mol) were reacted in the same manner as in Production Example 1 to obtain the following pyrophosphoric acid ester compound. Ta. IR: ν _nax , cm ^-1 2950, 1720, 1630, 1370, 1160, 1000, 760 NMR (CDCl ₃ ): δ 6.10 (bs, 1H×4, vinyl proton) 5.50 (m, 1H×4, vinyl proton) 4.20 (m, 4H x 4, - CH ₂ CH (Cl) CH ₂ ) 3.65 (m, 1H x 4, - CH ₂ CH (Cl) CH ₂ ) 1.90 (d, 3H x 4, vinyl CH ₃ ) Production example 5 Diallyl phosphoric acid (2 mol) and dicyclohexylcarbodiimide (1 mol) were reacted in the same manner as in Production Example 1 to obtain the following pyrophosphoric acid ester compound. IR: ν _nax , cm ^-1 2900, 1630, 1365, 1160, 980 NMR (CDCl ₃ ): δ 5.60 (m, 2H×4, vinyl protons) 4.10 (bs, 1H×4, vinyl protons) 3.50 (t, 2H×4, -CH ₂ -) Production Example 6 (2-methacryloyloxyethyl)(phenyl)phosphoric acid (2 mol) and dicyclohexylcarbodiimide (1 mol) were reacted in the same manner as in Production Example 1 to produce the following pyrophosphoric acid. An ester compound was obtained. IR: ν _nax , cm ^-1 2900, 1720, 1630, 1600, 1365, 1160, 980 NMR (CDCl ₃ ): δ 7.35 (s, 5H×2, arom.Protons) 6.10 (bs.1H×2, vinyl proton ) 5.55 (m, 1H x 2, vinyl proton) 4.25 (m.4H x 2, -CH ₂ CH ₂ -) 1.90 (d.3H x 2, vinyl CH ₃ ) Production example 7 (2-methacryloyloxyisopropyl)
(1-chlorophenyl)phosphoric acid (2 moles) and dicyclohexylcarbodiimide (1 mole) were reacted in the same manner as in Production Example 1 to obtain the following pyrophosphoric acid ester compound. IR: ν _nax , cm ^-1 2950, 1720, 1630, 1600, 1370, 1160, 980 NMR (CDCl ₃ ): δ 7.20 (m.4H×2, aroma.protons) 6.10 (bs.1H×2, vinyl proton ) 5.55 (m.1H×2, vinyl proton) 4.85 (m.1H×2,

【formula】) 4.15 (m.2H×2,

[Formula]) 1.90 (d.3H×2, vinyl CH ₃ ) 1.30 (m.3H×2,

[Formula]) Production Example 8 (Allyl)(4-tert-butylphenyl)phosphoric acid (2 mol) and dicyclohexylcarbodiimide (1 mol) were reacted in the same manner as in Production Example 1,
The following pyrophosphoric acid ester compound was obtained. IR: ν _nax , cm ^-1 2950, 1630, 1600, 1365, 1160, 980 NMR (CDCl ₃ ): δ 6.95 (ABq.4H×2, arom protons) 5.62 (m.2H×2, vinyl protons) 4.10 ( bs.1H×2, vinyl proton) 3.50 (t.2H×2, −CH ₂ −) 1.25 (s.9H×2, tert-butyl) Production example 9 (2-acryloyloxyethyl) (naphthyl)
Phosphoric acid (2 moles) and dicyclohexylcarbodiimide (1 mole) were reacted in the same manner as in Production Example 1 to obtain the following pyrophosphoric acid ester compound. IR: ν _nax , cm ^-1 2900, 1720, 1630, 1600, 1365, 1160, 980 NMR (CDCl ₃ ): δ 7.80-7.05 (m.7H×2, aroma.protons) 6.35 (m.3H×2, vinyl protons) 4.25 (m.4H×2, -CH ₂ CH ₂ -) Production example 10 Production example of (2-methacryloyloxyethyl) (7-methoxynaphthyl) phosphoric acid (2 mol) and dicyclohexylcarbodiimide (1 mol) The reaction was carried out in the same manner as in 1 to obtain the following pyrophosphoric acid ester compound. IR: ν _nax , cm ^-1 2950, 1720, 1630, 1600, 1365, 1160, 980 NMR (CDCl ₃ ): δ 7.70 to 6.70 (m.6H×2, arom.protons) 6.10 (bs.1H×2, vinyl proton) 5.55 (m.1H×2, vinyl proton) 4.25 (m.4H×2, −CH ₂ CH ₂ −) 3.90 (s.3H×2, −OCH ₃ ) 1.90 (d.3H×2, vinyl CH ₃ ) Production Example 11 (2-chloro-3-methacryloyloxypropyl)(2-methylphenyl)phosphoric acid (2 mol) and dicyclohexylcarbodiimide (1 mol) were reacted in the same manner as in Production Example 1 to produce the following pyrophosphoric acid ester. The compound was obtained. IR: ν _nax , cm ^-1 2950, 1720, 1630, 1600, 1370, 1160, 1000,
760 NMR (CDCl ₃ ): δ 6.85 (m.4H×2, arom.protons) 6.10 (bs.1H×2, vinyl proton) 5.55 (m.1H×2, vinyl proton) 3.65 (m.1H×2, -CH ₂ CH (Cl) CH ₂ -) 4.20 (m.4H x 2, -CH 2 CH (Cl) CH ₂ -) 2.20 (s.3H x ₂ , -CH ₃ ) 1.90 (d.3H ×2, vinyl CH ₃ ) Production example 12 Di-(2-hydroxy-3-methacryloyloxypropyl) phosphoric acid (1 mol) and (2-methacryloyloxyethyl)(phenyl)phosphoryl chloride (1 mol), pyridine (0.5 mol) and reacted at 0°C in anhydrous methylene chloride. After washing the reaction product with water and drying with sodium sulfate,
The solvent was distilled off under reduced pressure to synthesize the following pyrophosphoric acid ester compound. IR: ν _nax , cm ^-1 3400, 1720, 1635, 1600, 1365, 980 Production example 13 (2-methacryloyloxypropyl) (phenyl) phosphoric acid (1 mol), diethylphosphoryl chloride (1 mol) and pyridine (0.5 mol) ) was reacted in the same manner as in Production Example 12 to obtain the following pyrophosphoric acid ester compound. IR: νmax, cm ^-1 2900, 1720, 1635, 1600, 1365, 1160, 980 Example 1 The pyrophosphate compound obtained in Production Example 1 was used to bond a sample with properties similar to tooth substance, and the bond strength was determined. was measured. In measuring the adhesive strength, the following composition was prepared. As agent A, benzoyl peroxide (1 part by weight) was added to the pyrophosphoric acid ester compound (100 parts by weight) obtained in Production Example 1 and thoroughly mixed to obtain a uniform dispersion. Next, as agent B, p-toluenesulfinic acid (5 parts by weight) was added to ethyl alcohol (100 parts by weight) to obtain a homogeneous solution. Agent A and B
The agents were mixed in equal amounts and kneaded, and the adhesion to enamel and dentin was examined, and the results shown in Table 1 were obtained. As a comparative example, a conventionally widely used bis-GMA bonding agent (commercially available) was used. The method for measuring adhesive strength (sample preparation method) is as follows. Flatten fresh bovine tooth enamel (sample),
After finishing buffing with #600 emery paper, immerse in water at 37±1℃. In a measurement room maintained at 23±1℃ and relative humidity: 50±10%, immediately before testing, the sample is etched with a 38% phosphoric acid solution for 1 minute, washed with water, and then dried with ventilation. One drop of Agent A and Agent B were added onto the sample surface, kneaded, and applied thinly with a piece of sponge or a cotton ball. After about 10 seconds, pump out 2~
Spray for 3 seconds to evaporate volatile components. A stainless steel frame is provided on the coating surface, and a kneaded product of a commercially available composite filler material Adapt (manufactured by J&J Company, USA) is filled and hardened. After immersion in water at 37°C for 24 hours, adhesive strength was measured using an autograph. The adhesive area of the sample was set to a circle with a diameter of 6 mm, and the number of pieces measured was 5. On the other hand, the adhesive strength on dentin was measured as follows. Ivory 10-12mm in diameter and 6-12mm in height
Cut into cylindrical shapes, polish the surface with #600 emery paper, and leave to dry at 37±1°C for one week. The adhesive strength is measured in the same manner as in the case of bovine tooth enamel using a sample that has been immersed in water at 37±1° C. for 1 hour before the test. In the case of dentin, no etching treatment is performed. Examples 2 to 4 In the same manner as in Example 1, using the pyrophosphate ester compounds obtained in Production Examples 6, 12, and 13, the adhesive strength of each was measured, and the values shown in Table 1 were obtained. The case of Production Example 6 was defined as Example 2, the case of Production Example 12 as Example 3, and the case of Production Example 13 as Example 4. Example 5 In measuring adhesive strength, the following distribution composition was prepared. As agent A, the pyrophosphate compound obtained in Production Example 6 (70 parts by weight) and benzoyl peroxide (2 parts by weight) were added to the fine polymer powder (30 parts by weight) of the pyrophosphate compound obtained in Production Example 1. was added and thoroughly mixed to obtain a uniform dispersion. Next, as agent B, P-toluenesulfinic acid (5 parts by weight) was added to ethyl alcohol (100 parts by weight) to obtain a homogeneous solution. Table 1 shows the results of examining the adhesion to enamel and ivory by mixing equal amounts of Part A and Part B in the same manner as in the above Example.

[Table] * The adapter base material was destroyed.

Claims (1)

[Claims] 1. A functional group having a polymerizable double bond in the molecule; An adhesive for hard tissues of the human body, characterized in that it contains a pyrophosphate derivative monomer having a group represented by the following and/or a polymer obtained by polymerizing at least the derivative monomer as one of the polymerizable monomers. 2 In claim 1, the pyrophosphate ester derivative has the general formula [In the formula, R ¹ is alkenyl, acryloyloxy,
It means (lower) alkyl or aryl having one or more methacryloyloxys, where the (lower) alkyl in R ¹ may be substituted with hydroxy and/or halogen. R ² means alkyl or aryl, and the aryl is (lower)
It may be substituted with alkyl, (lower) alkoxy and/or halogen. Note that R ² may be the same or different.] An adhesive for human hard tissue. 3 In claim 1, the pyrophosphate ester derivative has the general formula [In the formula, R ¹ and R ² are the same as in claim 2, and R ¹ and R ² may be the same or different from each other.] . 4 In claim 1, the pyrophosphate ester derivative has the general formula [In the formula, R ¹ and R ² are the same as in claim 2, and R ¹ and R ² may be the same or different from each other.] . 5 In claim 1, the pyrophosphate ester derivative has the general formula [In the formula, R ¹ and R ² are the same as in claim 2, and R ¹ may be the same or different from each other.] An adhesive for human hard tissue. 6 In claim 1, the pyrophosphate ester derivative has the general formula [In the formula, R ¹ is the same as in claim 2,
R ¹ may be the same or different.] An adhesive for human hard tissue.