WO2017047886A1 - Catechol derivative-based adhesive composition and production method therefor - Google Patents

Abstract

The present invention relates to a catechol derivative-based adhesive composition and a production method therefor, and more specifically, to a catechol derivative-based adhesive composition comprising a hydroxyl protecting group and various functional groups, and a production method therefor. The adhesive composition, according to the present invention, is produced so as to be based on a catechol derivative compound and to comprise a hydroxyl protecting group and various functional groups, and thus has excellent biocompatibility, is economical and exhibits excellent adhesive strength even in a wet condition, and thus has the effect of being capable of being used as a dental or surgical adhesive.

Description

Adhesive composition based on catechol derivatives and preparation method thereof

The present invention relates to an adhesive composition based on a catechol derivative and a method for preparing the same, and more particularly, to an adhesive composition based on a catechol derivative and a preparation method including a hydroxyl protecting group and various functional groups.

Various restorative materials are used in connection with the treatment of dental caries and the aesthetic function of the oral cavity. Mainly, composite resins, metal alloys, ceramics, ceramics, glass, and the like are used. Since these materials are not adhesive to hemorrhoids, compositions for adhering restorative materials to teeth are being developed.

In general, tooth adhesion is largely divided into enamel and dentin adhesion. Enamel is a very hard tissue consisting of 95% mineral, 1% organic and 4% moisture. Enamel adhesion generally dissolves hydroxyapatite crystals by acid corrosion to expose enmel rods to the surface, and micromechanically bonds as the adhesive penetrates and hardens. Teeth dentin is composed of 70% mineral, 20% organic, 10% moisture. Compared with enamel, it is characterized by a lot of organic and moisture. Early dentin adhesives were hydrophobic and did not penetrate the smear layer of dentin well. This resulted in very low adhesive strength. To solve this problem, we began to add hydrophilic monomers such as 2-hydroxy methacrylate (HEMA), which allowed the adhesive to penetrate the dentin layer and tolerate in wet environments. . However, HEMA has a disadvantage of low strength after polymerization.

Mussels that adhere to the surface of rocks and the like produce and secrete an adhesion protein, which contains 3,4-dihydroxyphenyl-L-alanine (DOPA), most of which has catechol functional groups. DOPA is a derivative of tyrosine, one of the amino acids in living organisms, and a precursor of dopamine and norepinephrine, which are signaling agents. DOPA is a material that plays a key role in the adhesion protein of mussels, which are marine organisms. For this reason, adhesives containing DOPA can be considered suitable for use as dental adhesives. However, even though the adhesion ability of DOPA itself is excellent, it is easily oxidized to dopaquinone in the air, and the hydroxyl group is changed to a carboxyl group, which causes DOPA to lose its coordination with metal. In addition, when oxidized, there is a disadvantage that can react with other materials to cause an undesired cross-linking reaction may lower the adhesion ability. In order to eliminate these side reactions, the catechol derivatives must be reacted in the absence of oxygen, but the production cost is relatively high. To develop and commercialize adhesives utilizing DOPA, DOPA can be prevented from being oxidized. Developing mechanisms is essential.

In the search for an adhesive composition, the inventors have found that an adhesive composition based on a catechol derivative including a hydroxyl protecting group and various functional groups is excellent in biocompatibility, economical, and shows excellent adhesive strength even under wet conditions. The present invention has been completed.

Accordingly, the present invention is to provide an adhesive composition and a method of manufacturing the same.

In addition, the present invention is to provide a bone adhesive, comprising the adhesive composition.

In addition, the present invention is to provide a dental adhesive, comprising the adhesive composition.

In addition, the present invention is to provide an implant kit comprising the dental adhesive.

In order to achieve the above object,

The present invention

It provides an adhesive composition comprising a compound of formula (1).

[Formula 1]

In Chemical Formula 1,

P is a hydroxyl protecting group,

L1 or L2 are each independently hydrogen, hydroxyl group, C ₁ to C ₂₀ carboxyl group, C ₁ to C ₁₀ linear or branched alkyl group, C ₁ to C ₁₀ alkoxy group, acrylate group, methacrylate And pentanerythritol tetrakis (3-mercaptopropionate, PETMP).

In addition, the present invention comprises the step of photopolymerizing a mixture of the compound of Formula 1, the methacrylate monomer, a photoinitiator, an aromatic tertiary amine having an electron withdrawing group, an organic solvent, and a filler; comprising, preparing an adhesive composition Provide a method.

The present invention also provides a bone adhesive, comprising the adhesive composition.

The present invention also provides a dental adhesive comprising the adhesive composition.

The present invention also provides an implant kit comprising the dental adhesive.

The adhesive composition according to the present invention is prepared by including a hydroxyl protecting group and various functional groups based on the catechol derivative compound, thereby providing excellent biocompatibility, economical efficiency, and excellent adhesion strength even under wet conditions. There is an effect that can be used as the adhesive for the.

1 is a view showing a scanning electron microscope (Scanning Electron Microscopy, SEM) image of the dental root canal filling sealer of (a) Examples 3-5 and (b) Comparative Example 3.

Hereinafter, the present invention will be described in detail.

The present invention provides an adhesive composition comprising the compound of formula (1).

[Formula 1]

In Chemical Formula 1,

P is a hydroxyl protecting group,

L1 or L2 are each independently hydrogen, hydroxyl group, C ₁ to C ₂₀ carboxyl group, C ₁ to C ₁₀ linear or branched alkyl group, C ₁ to C ₁₀ alkoxy group, acrylate group, methacrylate And pentanerythritol tetrakis (3-mercaptopropionate, PETMP).

P denotes a hydroxyl protecting group and "hydroxyl protecting group" means a functional group that protects the hydroxyl group from undesirable reactions during the synthetic procedure. The hydroxyl protecting group may be silyl ether, methyl ether, C ₁ -C ₆ alkyl ether, tetrahydropyranyl or -SiR ₁ R ₂ R _3, etc., but is preferably -SiR ₁ R ₂ R ₃ . Specifically, examples of the hydroxyl protecting group include methyl, ethyl, propyl, t-butyl, isopropyl, methoxymethyl (MOM), methylthiomethyl, t-butylthiomethyl, (phenyldimethylsilyl) methoxymethyl, benzyl Oxymethyl, p-ethoxybenzyloxymethyl, (4-methoxyphenoxy) methyl, guoacolmethyl, t-butoxymethyl, 4-pentenyloxymethyl, siloxymethyl, 2-methoxyethoxymethyl , 2,2,2-trichloroethoxymethyl, bis (2-chloro-ethoxy) methyl and 2- (trimethylsilyl) -ethoxymethyl), 1-ethoxyethyl, 1- (2, chloroethoxy ) Ethyl, 1-methyl-1-methoxyethyl, 1-methyl-1-benzyloxyethyl, 1-methyl-1-benzyloxy-2-fluoroethyl, 2,2,2-trichloroethyl, 2- Trimethylsilethyl, 2- (phenylselenyl) ethyl, allyl, p-chlorophenyl, p-methoxyphenyl, 2,4-dinitrophenyl, benzyl, p-methoxybenzyl, 3,4-dimethoxybenzyl, o-nitrobenzyl, p-nitrobenzyl, p-halobenzyl, 2,6-dichlorobenzyl, p-cyanobenzyl, etc. And, examples of the -SiR ₁ R ₂ R ₃ is trimethylsilyl, triethylsilyl, tri-isopropyl silyl, dimethyl-isopropyl silyl, diethyl isopropyl silyl, dimethyl silyl teksil, tert- butyldimethylsilyl, di -tert- Butylmethylsilyl, tert-butyldiphenylsilyl, tribenzylsilyl, tri-p-xylylsilyl, triphenylsilyl, diphenylmethylsilyl, tert-butyl (methoxy) diphenylsilyl and the like. The silylation step can be performed according to standard methodologies known to those skilled in the art.

The compound of Formula 1 is preferably a catechol derivative based compound.

The catechol derivative is a compound containing a dihydroxy group, and can be coordinated with the metal. Specifically, eugenol, dopa (3,4-dihydroxyphenylalanine (DOPA), dopa quinone (Dopa o-quinone), topa (2,4,5-trihydroxyphenylalanine (TOPA), or topa quinone (Topa quinone) And the like.

 In the catechol derivative compound, the compound of Formula 1 is substituted with a hydroxyl group to the hydroxyl protecting group to solve the disadvantage of oxidative stability of catechol, and various crosslinking agents to increase the compatibility with other monomers and oligomers It is preferably a compound based on substituted catechol derivatives.

Specifically, the compound of Formula 1 may be a catechol derivative compound protected with -SiR ₁ R ₂ R ₃ represented by the following Formula 2, Formula 3, Formula 4, Formula 5 or Formula 6.

[Formula 2]

[Formula 3]

[Formula 4]

[Formula 5]

[Formula 6]

In Formula 2, Formula 3, Formula 4, Formula 5 or Formula 6,

R 1, R 2 or R 3 are each independently hydrogen, a C ₁ to C ₁₀ straight or branched alkyl group, C ₁ to C ₁₀ alkoxy, C ₆ to C ₁₀ aryl group and C ₆ to C ₁₀ heteroaryl group It is any one selected from the group consisting of.

Compound of Formula 2 may be prepared as in Scheme 1 below.

Scheme 1

In Scheme 1, eugenol and HSiR ₁ R ₂ R ₃ compounds are reacted under tris pentafluorophenyl borane (TPFPB) to silyl-protected catechol (SPC) The compound of Formula 2 may be prepared by preparing a compound and reacting the SPC with pentaneerythritol tetrakis (3-mercaptopropionate) (PETMP). In addition, since the PETMP includes four thiol groups, SPC may bind to 1-4.

In addition, the compound of Formula 3 or Formula 4 may be prepared as in Scheme 2 below.

Scheme 2

In Scheme 2, SPC and peroxoic acid are reacted under dichloromethane (DCM) to prepare the compound of Formula 3, and the compound of Formula 3 is reacted with methacrylic acid (methacrylic acid) of Formula 4 Compounds can be prepared.

In addition, the compound of Formula 5 (SPC Acid) may be prepared as in Scheme 3 below.

Scheme 3

In Scheme 3, 3,4-dihydroxyphenylacetic acid (3,4-Dihydroxyphenylacetic acid) or homovanillic acid (Homovanillic acid) and HSiR ₁ R ₂ R ₃ compound tris pentafluorophenyl borane (tris Reaction under pentafluorophenyl borane (TPFPB) can be used to prepare silyl-protected catecholic acid (SPC acid) compounds.

In addition, the compound of Chemical Formula 6 may be prepared as in Scheme 4 below.

Scheme 4

In Scheme 4, the compound of Chemical Formula 6 may be prepared by sequentially esterifying the SPC acid, 1,10-decanediol (1, 10-decandiol), and methacrylic acid (Methacrylic acid). In addition, 3,4-dihydroxyphenylacetic acid (3,4-Dihydroxyphenylacetic acid) or homovanillic acid (Homovanillic acid) to 1,10-decanediol (1, 10-decandiol), methacrylic acid ( Methacrylic acid) was sequentially esterified and the HSiR ₁ R ₂ R ₃ compound was added under tris pentafluorophenyl borane (TPFPB) as in Scheme 3 above to attach the hydroxyl protecting group of catechol. Reaction may yield a compound of Formula 6.

The compound of Formula 1 is preferably included in 1 to 20% by weight relative to the total weight of the adhesive composition.

The adhesive composition may further include a methacrylate-based polymer monomer, a photoinitiator, an aromatic tertiary amine having an electron withdrawing group, an organic solvent, and a filler.

The methacrylate-based polymer monomer may include a hydrophobic methacrylate functional group, low volatility and polymerization shrinkage, fast curing, moderate molecular weight, and high stability monomer. Specifically, 2,2-bis- (4- (2-hydroxy-3-methacryloyloxypropoxy) phenyl) propane (Bis-GMA), triethylene glycol dimethacrylate (TEGDMA), ethylene Glycol Dimethacrylate (EGDMA), Ethoxylate Bisphenol A Dimethacrylate (Bis-EMA), Urethane Dimethacrylate (UDMA), Anhydrous 4-methacryloxyethyltrimeric (4-META), Di Pentaerythritol pentaacrylate monophosphate (PENTA), biphenyl dimethacrylate (BPDM), glycerol phosphate dimethacrylate (GPDM), propylene glycol dimethacrylate (PGDMA) and the like.

In addition, the methacrylate-based polymer monomer may be a polymer monomer having low viscosity and excellent hydrophilicity. Specifically, 2-hydroxyethyl methacrylate, 3-hydroxypropyl methacrylate, 2-hydroxypropyl methacrylate, 3-hydroxypropyl methacrylate, 1,3-dihydroxypropyl methacrylate Latex, 2,3-dihydroxypropyl methacrylate, 2-trimethylammoniumethyl methacrylate, polyethylene glycol dimethacrylate and the like.

The content of the methacrylate monomer is not particularly limited, but is preferably 10 to 99% by weight, more preferably 10 to 90% by weight based on the total weight of the composition. If the content of the monomer is 10% by weight or less, it is difficult to form the desired polymer and not easy to be mixed with the filler. On the contrary, if the content of the monomer is 99% by weight or more, it is not preferable because of lack of workability due to an increase in viscosity.

The initiator of the polymerization reaction may function in various ways, such as a cation formation mechanism, an anion formation mechanism, a radical formation mechanism, and the like, depending on the type of catalyst used in the polymerization reaction, and a double radical formation mechanism is most commonly used. According to these polymerization mechanisms, the polymerization reaction may be performed by a photopolymerization reaction, a chemical polymerization reaction, or the like, but is not limited thereto.

The photopolymerization reaction is carried out by a photoinitiator which is activated by visible or ultraviolet (UV) light to initiate the polymerization of the monomer, the photoinitiator is camphorquinone, benzyl, 2,3-pentanedione, benzyldimethylketal, benzyl diethyl Ketal, 2-chlorothioxanthone, 2,4-diethylthioxanthone, 2,4,6-trimethylbenzoyldiphenylphosphine oxide, bis (2,4,6-trimethylbenzolyl) phenylphosphine oxide, Dibenzoylphenylphosphine oxide, bis (2,6-dimethoxybenzoyl) phenylphosphine oxide, tris (2,4-dimethinbenzoyl) phosphine oxide, tris (2-methoxybenzoyl) phosphine oxide, 2, 6-dimethoxybenzoyldiphenylphosphine oxide, 2,6-dichlorobenzoyldiphenylphosphine oxide, 2,3,5,6-tetramethylbenzoyldiphenylphosphine oxide, benzoyl-bis (2,6-dimethylphenyl ) Phosphonate, 2,4,6-trimethylbenzoylethoxyphenylphosphine oxide, 3,3'-carbonylbis (7-die No No) coumarin, 3- (4-methoxybenzoyl) and the like coumarin, 3-thenoyl coumarin.

The chemical polymerization reaction is carried out by a peroxide compound, such as benzoyl peroxide (BPO), used together with an aromatic tertiary amine promoter having an electron withdrawing group to form radicals by heat to initiate polymerization.

Moreover, as an aromatic tertiary amine which has the said electron attracting group, 4-N, N- dimethylamino benzoate ethyl, 4-N, N- dimethylamino benzoate, 4-N, N- dimethylamino benzoic acid propyl, 4-N , N-dimethylaminobenzoic acid 2-butoxyethyl, 4-N, N-dimethylaminobenzoic acid 2- (methacryloyloxy) ethyl, 4-N, N-dimethylaminobenzophenone and the like can be used.

The organic solvent may be methanol, ethanol, 1-propanol, isopropyl alcohol, acetone, methyl ethyl ketone, 1,2-dimethoxyethane, 1,2-diethoxyethane, tetrahydrofuran, but is not limited thereto. It is not.

The filler may be an inorganic filler, an organic filler, a stabilizer, or the like.

The inorganic filler may be amorphous synthetic silica, crystalline natural silica, barium aluminum silicate, kaolin, talc, strontium aluminum silicate, and the like, and other acid reactive fillers, nano zirconia fillers, and the like, but is not limited thereto. In general, since the inorganic filler is hydrophilic, the compatibility with the hydrophobic polymerization monomer is inferior, and thus the affinity with the polymerization monomer can be enhanced by including a binder component or by surface treating the inorganic filler with a silane coupling agent.

The organic filler is synthesized in the form of a powder after synthesis of a monomer constituting the matrix after polymerization or monomers compatible with the dental restorative composition by bulk polymerization, emulsion polymerization, suspension polymerization, etc., the average particle diameter of 0.001 to 1 ㎛ What was granulated can be used. In some cases, an inorganic or organic filler may not be added, but instead the mechanical strength may be increased by increasing the curing molecular weight of the monomer.

The stabilizer may preferably be a phenolic or phosphate stabilizer.

In addition, the adhesive composition may further include a known compound such as polymerization inhibitor, antioxidant, colorant, fluorine additive.

In addition, the present invention comprises the step of photopolymerizing a mixture of the compound of Formula 1, methacrylate-based monomer, photoinitiator, aromatic tertiary amine having an electron withdrawing group, an organic solvent, and filler; It provides a manufacturing method.

The photopolymerization is preferably performed for 1 to 24 hours under visible light or UV irradiation.

The present invention also provides a bone adhesive, comprising the adhesive composition.

The bone adhesive can maintain the adhesion even in the presence of water, it can be used for adhesion in water.

The present invention also provides a dental adhesive comprising the adhesive composition.

The dental adhesive may adhere to one or more substrates selected from the group consisting of biomaterials, plastics, glass, metals, and polymer synthetic resins, and may be used for bonding or fixing the substrates.

The dental adhesive can be used in various formulations, for example in the form of liquid, cement, primer or root canal filling sealer.

The dental adhesive may be for the prevention or treatment of periodontal disease.

The present invention also provides an implant kit comprising the dental adhesive.

Dental adhesives according to the present invention not only have excellent biocompatibility, but also exhibit excellent adhesive strength in teeth and various restorations.

Hereinafter, preferred examples are provided to aid in understanding the present invention. However, the following examples are merely provided to more easily understand the present invention, and the contents of the present invention are not limited by the examples.

Example 1. Preparation of Functionalized Catechol Derivatives

1-1. Preparation of Siylated Catechol Derivatives (SPCs)

Eugenol, 1,10-decanediol, methacrylic acid, 3,4-dihydroxyphenylacetic acid (3,4-) Dihydroxyphenylacetic acid, Homovanillic acid, 1,3-dicyclohexylcarbodiimide, and 4-dimethylaminopyridine are sigma-Aldrich Triethylsilane and tris (pentafluorophenyl) Borane (TPFPB) are purchased from Alfa Aesar, and dichloromethane is purchased from JUNSEI. It was.

First, 1 g eugenol and 1.56 g triethylsilane were mixed at room temperature and then stirred for 5 minutes. Thereafter, 18.7 mg of tris (pentafluorophenyl) borane as a reaction catalyst was added to the mixture to react the mixture. After completion of the reaction, the product was dissolved in 10 ml of dichloromethane solvent and filtered through a syringe filter containing neutral alumina particles to remove the remaining tris (pentafluorophenyl) borane after the reaction. protected catechol, SPC).

1-2. Preparation of Epoxy Silylated Catechol Derivatives

10 g of the silylated catechol derivative (SPC) and 8.75 g of 3-chlorobenzoperoxoic acid prepared in Example 1-1 were mixed in a dichloromethane solvent at 0 ° C., and then 18 hours. Reacted for a while. Thereafter, the dichloromethane present in the reaction mixture was volatilized, the reaction mixture was extracted with ethyl acetate, washed twice with saturated sodium bisulfite solution, washed twice with saturated sodium bicarbonate solution, and then ethyl acetate Volatilized. Thereafter, the first separated reaction mixture was subjected to column chromatography using silica / nucleic acid: ethyl acetate (90:10) to separate the pure material to obtain an epoxy silylated catechol derivative as a product.

The ¹ H NMR measurement results of the product are shown below.

¹ H NMR (CDCl ₃ ) 0.74 (q, 12H, -Si-CH ₂ CH ₃ ) 0.98 (t, 18H, -Si-CH ₂ CH ₃ ) 2.52 (q, 1H, -CH ₂ CH-O-CH ₂ ) 2.69 (q, 1H, -CH ₂ CH-O-CH ₂ ) 2.78 (t, 1H, -CH ₂ CH-O-CH ₂ ) 2.81 (q, 1H, -CH ₂ CH-O-CH ₂ ) 3.11 (m, 1H, -CH ₂ CH-O-CH ₂ ) 6.69 (d, 1H, Ar-H) 6.64 (q, 1H, Ar-H) 6.77 (d, 1H, Ar-H).

1-3. Preparation of methacrylate silylated catechol derivatives (Methacrylated SPC)

5 g of the epoxy silylated catechol derivative prepared in Example 1-2, 1.75 g of methacrylic acid (methacrylic acid) and the catalyst tetraethylammonium bromide (4-tetraethylammonium bromide) at 90 ℃ 4-methoxyphenol (4 -Methoxyphenol) was mixed and reacted for 4 hours. Thereafter, the reaction mixture was extracted with ethyl acetate, washed twice with saturated sodium bicarbonate solution, and then ethyl acetate was evaporated. Thereafter, the first separated reaction mixture was subjected to column chromatography using silica / nucleic acid: ethyl acetate (90:10) to separate a pure substance, thereby obtaining a methacrylate silylated catechol derivative (Methacrylated SPC) as a product. Obtained.

The ¹ H NMR measurement results of the product are shown below.

1 H NMR (CDCl ₃ ) 0.74 (q, 12H, -Si-CH ₂ CH ₃ ) 0.98 (t, 18H, -Si-CH ₂ CH ₃ ) 1.95 (d, 3H, -CH ₂ -C (CH ₃ ) = CH ₂ ) 2.20 (d, 1H, -CH ₂ CH (OH) CH ₂ OOC-) 2.72 (m, 2H, -CH ₂ CH (OH) CH ₂ OOC-) 4.10 (q, 1H, -CH (OH) CH ₂ OOC-) 4.22 (q, 1H, -CH (OH) CH ₂ OOC-) 5.58 (d, 1H, -CH ₂ C (CH ₃ ) = CH ₂ ) 6.13 (d, 1H, -CH ₂ C ( CH ₃ ) = CH ₂ ) 6.69 (d, 1H, Ar-H) 6.64 (q, 1H, Ar-H) 6.77 (d, 1H, Ar-H).

1-4. Preparation of PETMP-SPC

The silylated catechol derivatives (SPC) and pentane erythritol tetrakis (3-mercaptopropionate) prepared in Example 1-1 (pentaerythritol tetrakis (3-mercaptopropionate), PETMP) were prepared using dimethoxy-2-phenylaceto. PETMP-SPC was obtained by reaction under a phenone (dimethoxy-2-phenylacetophenon) catalyst in an equivalent ratio of 1: 1: 0.05.

1-5. Preparation of 10-Chain Methacrylate SPC

First, 5.04 g 3,4-dihydroxyphenylacetic acid (3,4-Dihydroxyphenylacetic acid) and 6.98 g triethylsilane were mixed at room temperature, and then stirred for 5 minutes. Thereafter, 61.4 mg of tris (pentafluorophenyl) borane as a reaction catalyst was added to the mixture and reacted. After completion of the reaction, the product was dissolved in 20 ml of dichloromethane solvent and filtered through a syringe filter containing neutral alumina particles to remove the remaining tris (pentafluorophenyl) borane after the reaction. protected catecholic acid, SPC acid). And 3.97g SPC acid and 1.74g 1,10-decanediol (1, 10-decandiol) was mixed and esterified (Esterification) for 12 hours at 140 ℃. The reaction mixture was then subjected to column chromatography using silica / nucleic acid: ethyl acetate (90:10) to separate the pure material to obtain a primary product, which obtained 2.76 g of primary product and 0.86 g of methacrylic acid ( Methacrylic acid) was mixed at 0 ° C. and esterified by using 1,3-dicyclohexylcarbodiimide and 4-dimethylaminopyridine as catalysts at room temperature for 12 hours. (Esterification). The product was washed three times with 100 ml of distilled water, dissolved in DCM and filtered with MgSO ₄ . 10-Chain methacrylated SPC can be prepared by removing the solvent using a vacuum oven.

Example 2. Preparation of Adhesive Composition

Bisphenol A glycidylmethacrylate (40% by weight), methacryloyloxy-decyl-dihydrogen-phosphate (methacryloyloxi-decyl-dihydrogen-phosphate, 10-MDP) 10% by weight, Example 1 10% by weight of methacrylate-SPC, and 36.5% by weight of ethanol, followed by 1% by weight of photoinitiator Camphorquinone and co-initiator 2-butoxyethyl-4-dimethylaminobenzoate, And 2.5% by weight of the mixture to prepare a dental adhesive composition.

Example 3. Preparation of dental adhesive

3-1. Preparation of Liquid Dental Adhesives 1

A liquid dental adhesive 1 having a composition of Table 1 was prepared, including methacrylate-SPC (or PETMP-SPC) according to Example 1.

Table 1

Liquid dental glue 1
ingredient	Content ( wt% )
ethanol	35
water	2.3
2,2-bis- (4- (2-hydroxy-3-methacryloyloxypropoxy) phenyl) propane (Bis-GMA)	44
2-hydroxyethyl methacrylate (HEMA)	10
Methacrylate-SPC (or PETMP-SPC)	7
Campoquinone (CQ)	One
4-N, N-dimethylaminobenzoic acid 2-butoxyethyl	0.7
sum	100

3-2. Preparation of Liquid Dental Adhesives 2

In Example 3-1, the content of methacrylate-SPC (or PETMP-SPC) was reduced to 5 wt%, and methacryloyloxy-decyl-dihydrogen-phosphate (methacryloyloxi-decyl-dihydrogen-phosphate, A liquid dental adhesive 2 was prepared in the same manner as in Example 3-1, except that 2% by weight of 10-MDP) was added.

3-3. Preparation of Cement-type Dental Adhesives 1

Cement-type dental adhesive 1, including the composition of Table 2 (first paste) and Table 3 (second paste) including PETMP-SPC according to Example 1 was prepared.

TABLE 2

Cement Type Dental Adhesive-First Paste
ingredient	Content (% by weight)
2,2-bis- (4- (2-hydroxy-3-methacryloyloxypropoxy) phenyl) propane (Bis-GMA)	30
Triethylene Glycol Dimethacrylate (TEGDMA)	10
Benzenesulphonic acid sodium salt	One
Campoquinone (CQ)	0.7
N, N-bis (2-hydroxyethyl) -p-toluidine (DHEPT)	0.3
Calcium Alumino-Pluorosiliconite Glass	57
Amorphous synthetic silica	One
sum	100

TABLE 3

Cement Type Dental Adhesive-Second Paste
ingredient	Content (% by weight)
2,2-bis- (4- (2-hydroxy-3-methacryloyloxypropoxy) phenyl) propane (Bis-GMA)	5
PETMP-SPC	15
2-hydrooxyethyl methacrylate (HEMA)	15
Benzoyl peroxide (BPO)	0.5
Butyl hydroxytoluene (BHT)	0.5
Barium Aluminosilicate	63
Amorphous synthetic silica	One
sum	100

3-4. Preparation of Cement-type Dental Adhesives 2

In Table 3 of Example 3-3, the content of PETMP-SPC was reduced to 10% by weight, and that of methacryloyloxy-decyl-dihydrogen-phosphate (methacryloyloxi-decyl-dihydrogen-phosphate, 10-MDP) Cement-type dental adhesive 2 was prepared in the same manner as in Example 3-3, except that the content was added by 5% by weight.

3-5. Preparation of dental root canal sealer 1

The dental root canal filling sealer 1 including the composition of Table 4 (first paste) and Table 5 (second paste) including PETMP-SPC according to Example 1 was prepared.

Table 4

Dental Root Canal Filling Sealer-First Paste
ingredient	Content (% by weight)
Bisphenol-A Epoxy Resin	46.7
PETMP-SPC	15
Calcium tungstate	30
Zirconium oxide	7.9
Amorphous synthetic silica	0.3
Iron oxide pigments	0.1
sum	100

Table 5

Dental Cement Manufacturing-Second Paste
ingredient	Content (% by weight)
Dibenzyldiamine	11.3
Aminoadamantane	5.2
Tricyclodecane-diamine	0.6
Calcium tungstate	64.7
Zirconium oxide	16.2
Amorphous synthetic silica	2
sum	100

3-6. Dental Root canal filling Sealer  2, manufacturing

In Table 4 of Example 3-5, the content of PETMP-SPC was reduced to 10% by weight, and of methacryloyloxy-decyl-dihydrogen-phosphate (methacryloyloxi-decyl-dihydrogen-phosphate, 10-MDP) A dental sealer for dental root canal filling was prepared in the same manner as in Example 3-5, except that the content was added by 5% by weight.

Comparative Example 1. Preparation of Liquid Dental Adhesive

A liquid dental adhesive was prepared in the same manner as in Example 3-1, except that 4-META was contained in 7 wt% instead of methacrylate-SPC (or PETMP-SPC) in Example 3-1.

Comparative Example 2. Preparation of Cement Type Dental Adhesive

Cement-type dental adhesive was prepared in the same manner as in Example 3-3, except that 15 wt% of 4-META was substituted for PETMP-SPC in Table 3 of Example 3-3.

Comparative Example 3. Preparation of Dental Root Canal Filler Sealer

In Example 4 of Table 3-5, except for containing 15% by weight of 4-META instead of PETMP-SPC, a dental root canal filling sealer was prepared in the same manner as in Example 3-5.

Experimental Example 1. Measurement of adhesive strength

Adhesive strength to the dental adhesive according to Examples 3-1 to 3-4 and Comparative Examples 1 to 2 were measured. First, the tooth was polished so that the dentin layer of the tooth was exposed, and the surface of the tooth was corroded by acid treatment with 35% phosphate gel for 10 seconds. Thereafter, after removing the moisture on the surface of the tooth, a dental adhesive was applied to a certain amount of teeth, and then the restorative was lifted to photopolymerize to prepare a test piece. The prepared test piece was placed in distilled water and stored at 35 ° C. for 24 hours, and then the adhesive strength was measured by moving the crosshead at a speed of 0.8 mm / min using a universal testing machine. Its adhesive strength measurement results are shown in Table 6.

Table 6

	Adhesive strength (MPa)
Example 3-1	18.34
Example 3-2	20.30
Example 3-3	10.59
Example 3-4	11.32
Comparative Example 1	6.21
Comparative Example 2	3.85

As shown in Table 6, as a result of evaluation of the adhesive strength, the dental adhesive according to Examples 3-1 to 3-4 including the methacrylate-SPC (or PETMP-SPC) of the present invention is 4-META. It can be seen that more excellent adhesive strength compared to the adhesive according to Comparative Examples 1 to 2 included. In addition, in the case of the liquid adhesive of Example 3-2 and the cemented adhesive of Examples 3-4, as the methacryloyloxy-decyl-dihydrogen-phosphate (10-MDP) was added, further improved adhesion Strength is shown.

The scanning electron microscope (Scanning Electron Microscopy, SEM) image of the adhesion to the tooth surface using the dental root canal filling sealer of (a) Examples 3-5 and (b) Comparative Example 3 is shown in FIG.

As shown in Figure 1, it can be seen that the dental root canal filling sealer according to Example 3-5 shows an excellent adhesive strength compared to the sealer according to Comparative Example 3.

Claims (19)

1. Adhesive composition comprising a compound of formula (1).

   [Formula 1]

   

   In Chemical Formula 1,

   P is a hydroxyl protecting group,

   L1 or L2 are each independently hydrogen, hydroxyl group, C ₁ to C ₂₀ carboxyl group, C ₁ to C ₁₀ linear or branched alkyl group, C ₁ to C ₁₀ alkoxy group, acrylate group, methacrylate And pentanerythritol tetrakis (3-mercaptopropionate, PETMP).
2. The method of claim 1,

   The compound of Formula 1 is a compound represented by the following formula (2), (3), (4), (5) or (6).

   [Formula 2]

   

   [Formula 3]

   

   [Formula 4]

   

   [Formula 5]

   

   [Formula 6]

   

   In Formula 2, Formula 3, Formula 4, Formula 5 or Formula 6,

   R 1, R 2 or R 3 are each independently hydrogen, a C ₁ to C ₁₀ straight or branched alkyl group, C ₁ to C ₁₀ alkoxy, C ₆ to C ₁₀ aryl group and C ₆ to C ₁₀ heteroaryl group It is any one selected from the group consisting of.
3. The method of claim 1,

   The compound of Formula 1 is characterized in that contained in 1 to 20% by weight relative to the total weight of the adhesive composition, the adhesive composition.
4. The method of claim 1,

   The adhesive composition further comprises an methacrylate-based polymer monomer, a photoinitiator, an aromatic tertiary amine having an electron withdrawing group, an organic solvent, and a filler.
5. The method of claim 4, wherein

   The methacrylate-based polymerization monomer is 2,2-bis- (4- (2-hydroxy-3-methacryloyloxypropoxy) phenyl) propane (Bis-GMA), triethylene glycol dimethacrylate ( TEGDMA), ethylene glycol dimethacrylate (EGDMA), ethoxylate bisphenol A dimethacrylate (Bis-EMA), urethane dimethacrylate (UDMA), anhydrous 4-methacryloxyethyltrimeric (4- META), dipentaerythritol pentaacrylate monophosphate (PENTA), biphenyl dimethacrylate (BPDM), and glycerol phosphate dimethacrylate (GPDM), propylene glycol dimethacrylate (PGDMA) Adhesive composition, characterized in that at least one hydrophobic monomer selected from the group.
6. The method of claim 4, wherein

   The methacrylate-based polymer monomer is 2-hydroxyethyl methacrylate, 3-hydroxypropyl methacrylate, 2-hydroxypropyl methacrylate, 3-hydroxypropyl methacrylate, 1,3-dihydrate Adhesion, characterized in that at least one hydrophilic monomer selected from the group consisting of oxypropyl methacrylate, 2,3-dihydroxypropyl methacrylate, 2-trimethylammonium ethyl methacrylate, polyethylene glycol dimethacrylate Sex composition.
7. The method of claim 4, wherein

   The methacrylate monomer is characterized in that it comprises 10 to 99% by weight relative to the total weight of the composition, adhesive composition.
8. The method of claim 4, wherein

   The photoinitiator is camphorquinone, benzyl, 2,3-pentanedione, benzyldimethyl ketal, benzyl diethyl ketal, 2-chlorothioxanto, 2,4-diethyl thioxanthone, 2,4,6-trimethylbenzoyldi Phenylphosphine oxide, bis (2,4,6-trimethylbenzolyl) phenylphosphine oxide, dibenzoylphenylphosphine oxide, bis (2,6-dimethoxybenzoyl) phenylphosphine oxide, tris (2,4- Dimethinbenzoyl) phosphine oxide, tris (2-methoxybenzoyl) phosphine oxide, 2,6-dimethoxybenzoyldiphenylphosphine oxide, 2,6-dichlorobenzoyldiphenylphosphine oxide, 2,3,5 , 6-tetramethylbenzoyldiphenylphosphine oxide, benzoyl-bis (2,6-dimethylphenyl) phosphonate, 2,4,6-trimethylbenzoylethoxyphenylphosphine oxide, 3,3'-carbonylbis At least one member selected from the group consisting of (7-diethylanino) coumarin, 3- (4-methoxybenzoyl) coumarin, and 3-tenoylcoumarin. That is, the adhesive composition.
9. The method of claim 4, wherein

   The aromatic tertiary amine having the electron withdrawing group is 4-N, N-dimethylaminobenzoate ethyl, 4-N, N-dimethylaminobenzoate, 4-N, N-dimethylaminobenzoic acid propyl, 4-N, N- Dimethylaminobenzoic acid 2-butoxyethyl, 4-N, N-dimethylaminobenzoic acid 2- (methacryloyloxy) ethyl, and 4-N, N-dimethylaminobenzophenone It is made, the adhesive composition.
10. The method of claim 4, wherein

    The organic solvent is one or more selected from the group consisting of methanol, ethanol, 1-propanol, isopropyl alcohol, acetone, methyl ethyl ketone, 1,2-dimethoxyethane, 1,2-diethoxyethane, and tetrahydrofuran It is characterized in that, the adhesive composition.
11. The method of claim 4, wherein

    Wherein the filler is at least one inorganic filler selected from the group consisting of amorphous synthetic silica, crystalline natural silica, barium aluminum silicate, kaolin, talc, and strontium aluminum silicate.
12. Photopolymerizing a mixture of a compound of Formula 1, a methacrylate-based polymer monomer, a photoinitiator, an aromatic tertiary amine having an electron withdrawing group, an organic solvent, and a filler;

    [Formula 1]

    

    In Chemical Formula 1,

    P is a hydroxyl protecting group,

    L1 or L2 are each independently hydrogen, hydroxyl group, C ₁ to C ₂₀ carboxyl group, C ₁ to C ₁₀ linear or branched alkyl group, C ₁ to C ₁₀ alkoxy group, acrylate group, methacrylate Group, and pentanerythritol tetrakis (3-mercaptopropionate) (PETMP).
13. The method of claim 12,

    The photopolymerization is characterized in that it is carried out for 1 to 24 hours under visible light or UV irradiation, method of producing an adhesive composition.
14. A bone adhesive comprising the adhesive composition of claim 1.
15. The method of claim 14,

    The bone adhesive is characterized in that the adhesive for water, bone adhesive
16. Dental adhesive comprising the adhesive composition of claim 1.
17. The method of claim 16,

    The dental adhesive is a dental adhesive, characterized in that the formulation of the liquid type, cement type, primer or root canal filling sealer.
18. The method of claim 16,

    The dental adhesive is a dental adhesive, characterized in that for the prevention or treatment of periodontal disease.
19. An implant kit comprising the dental adhesive of claim 16.

Images