JP5127375B2 - Dental adhesive composition - Google Patents

Description

  The present invention relates to a dental adhesive composition for realizing an excellent adhesive force and adhesion durability between a restoration material and a tooth quality in the restoration of a tooth in the field of dentistry and the like.

  For the restoration of teeth damaged by caries or the like, a filling material called a composite resin is mainly used. This composite resin is generally used after being filled into a cavity of a tooth and then cured by polymerization. However, since this material does not have adhesiveness to the tooth itself, a dental adhesive is used in combination. This adhesive material is required to have an adhesive strength sufficient to overcome internal stress generated when the composite resin is cured, that is, tensile stress generated at the interface between the composite resin and the tooth. Otherwise, there is a possibility of not only dropping off due to long-term use in a harsh oral environment but also creating a gap at the interface between the composite resin and the tooth, from which bacteria may invade and adversely affect the dental pulp Because.

  Dental hard tissue consists of enamel and dentin, and clinically requires adhesion to both. Conventionally, for the purpose of improving adhesiveness, a method of pretreating a tooth surface prior to application of an adhesive has been used. As such a pretreatment material, an acid aqueous solution for decalcifying the tooth surface is generally used, and an acid aqueous solution such as phosphoric acid has been used. In the case of enamel, the adhesion mechanism with the treated surface is a macro mechanical fit in which the adhesive penetrates and hardens to the rough surface by decalcification of the acid aqueous solution, whereas in the case of dentin Is said to be a micro mechanical fitting in which the adhesive penetrates into the fine voids of the sponge-like collagen fibers exposed on the tooth surface after decalcification and hardens. However, the penetration into collagen fibers is not as easy as the enamel surface, and a penetration promoter called a primer is generally used after treatment with an acid aqueous solution. That is, this method is a three-step system that requires two stages of pretreatment before applying a dental adhesive to obtain good adhesion strength to both enamel and dentin. There was a problem of being complicated.

  In recent years, a two-step system (Patent Document 1) in which this pretreatment operation is simplified to one stage has been proposed, and further, a one-step system (Patent Document 2) that does not require pretreatment and adheres to a tooth using only an adhesive. Proposed.

  A polymerizable monomer having an acidic group is used for the pretreatment material of the two-step system and the adhesive material of the one-step system in order to decalcify the tooth. However, such acidic group-containing polymerizable monomers generally have low mechanical strength and poor water resistance, and therefore have a stable adhesive force for a long period of time under severe conditions such as in the mouth containing a lot of moisture. It was not always enough to maintain.

  On the other hand, although the adhesive composition (patent documents 3 and 4) using the high molecular compound which has an acidic group is also proposed, it cannot be said that adhesive force and adhesion durability are enough.

JP-A-06-009327 Japanese Patent Laid-Open No. 10-236912 Japanese Patent Laid-Open No. 05-246817 Japanese Patent Laid-Open No. 06-279226

  An object of this invention is to provide the dental adhesive composition which has the outstanding adhesive force and adhesive durability regarding the adhesion | attachment with the tooth substance of a dental restoration.

  The present inventors have intensively studied to solve the above problems. As a result, the use of alginic acid and / or alginate and water together with a strongly acidic group-containing polymerizable monomer for pretreatment materials and adhesives provides excellent adhesive strength and adhesion durability to the tooth. As a result, the present invention has been completed.

  That is, the present invention is a dental adhesive composition characterized by containing (A) alginic acid and / or alginate, (B) a strongly acidic group-containing polymerizable monomer, and (C) water. .

  The dental adhesive composition can be used as a dental pretreatment material. In this case, the dental adhesive composition is particularly excellent in the decalcification power of the tooth and the penetrating power into the tooth, and particularly excellent in the tooth quality. It has adhesive strength and durability.

  The dental adhesive composition can also be used as a dental adhesive. In this case, (A) alginic acid and / or alginate, (B) a strongly acidic group-containing polymerizable monomer, (C ) By adding (D) a photopolymerization initiator to water, a material exhibiting particularly excellent adhesive force and adhesion durability to a tooth can be obtained without pretreatment. Moreover, even if it pre-processes, the said adhesive force and adhesion durability are exhibited more favorably.

  The dental adhesive composition of the present invention can obtain higher adhesive strength and superior adhesion durability compared to conventional dental adhesives. By using the dental adhesive composition of the present invention as a pretreatment material or an adhesive for the treatment of caries, the invasion of caries bacteria from the adhesive interface between the dentine and the restorative material is suppressed, and the caries recur. Is prevented.

  The dental adhesive composition of the present invention comprises (A) alginic acid and / or alginate, and (B) a strongly acidic group-containing polymerizable monomer, and is used for teeth such as enamel and dentin. Excellent adhesion and durability for quality. The reason for this is that, in the presence of water, chemistry such as hydrogen bonding between calcium ions in the tooth structure decalcified by the strongly acidic group-containing polymerizable monomer and the carboxyl groups and hydroxyl groups of alginic acid and / or alginate. This is presumed to be due to the formation of an adhesive layer having excellent water resistance at the adhesion interface because of the strong interaction.

  Hereinafter, each of these components will be described.

  The (A) alginic acid used in the dental adhesive composition of the present invention is a linear polyuronic acid, and each uronic acid unit has a carboxyl group and a hydroxyl group. As described above, in the present invention, it is necessary to use a polymer compound having both a carboxyl group and a hydroxyl group in the molecular chain in order to have excellent adhesion to the tooth and adhesion durability.

Uronic acid has two types of structures, D-mannuronic acid and its epimer L-guluronic acid, but alginic acid used in the adhesive composition of the present invention has D-mannuronic acid (hereinafter referred to as M and M) in the molecule. A molar ratio of (abbreviated) to L-guluronic acid (hereinafter abbreviated as G) of M / G = 2.0 or less is preferable because the chemical interaction with calcium ions becomes stronger.
The alginates used in the adhesive composition of the present invention are the above-mentioned alkali metal salts and ammonium salts of alginic acid such as sodium and potassium. Among them, sodium and potassium salts have high adhesive strength equivalent to alginic acid. Is preferable.

  The molecular weight of alginic acid and / or alginate used in the adhesive composition of the present invention is preferably in the range of 5,000 to 200,000, more preferably 7,000 to 150,000. The range of 10,000 to 100,000 is most preferable. If the molecular weight is too small, the water resistance tends to be lowered even if it interacts with calcium ions. If the molecular weight is too large, the viscosity tends to be high and the handleability tends to be poor.

  Although the compounding quantity of alginic acid and / or alginate in the dental adhesive composition of this invention is not specifically limited, It is preferable that it is 0.01-20 mass% in the whole composition. More preferably, it is 0.1-20 mass%, Most preferably, it is 0.3-15 mass%.

  The (B) strongly acidic group-containing polymerizable monomer used in the dental adhesive composition of the present invention is a polymerizable monomer having at least one polymerizable unsaturated group and at least one strong acid group in one molecule. Any known compound can be used as long as it is a monomer. The strong acid group means an acid dissociation constant (pKa) of 3.0 or less. Specific examples include a phosphoric acid group and a sulfonic acid group. The number of such strong acid groups in the molecule is generally 1 to 4, and 1 to 2 is particularly preferable. The polymerizable unsaturated group is a derivative group of a (meth) acryloyl group such as a (meth) acryloyl group, a (meth) acryloyloxy group, a (meth) acryloylamino group, a (meth) acryloylthio group; a vinyl group: Examples include allyl group; styryl group and the like.

  Specific examples of strongly acidic group-containing polymerizable monomers include 2- (meth) acryloyloxyethyl dihydrogen phosphate, bis (2- (meth) acryloyloxyethyl) hydrogen phosphate, 2- (meta ) Acrylyloxyethyl phenyl hydrogen phosphate, 10- (meth) acryloyloxydecyl dihydrogen phosphate, 6- (meth) acryloyloxyhexyl dihydrogen phosphate, 2- (meth) acryloyloxyethyl 2-bromoethyl hydro Polymerizable monomers having a phosphate group in the molecule such as gen phosphate (also referred to as polymerizable acidic phosphate ester), and acid anhydrides and acid halides thereof; vinylphosphonic acid, p-vinylbenzenephosphone In the molecule such as acid Polymerizable monomer having a phosphono group; polymerizable monomer having a sulfonic acid group in the molecule such as 2- (meth) acrylamide-2-methylpropanesulfonic acid, p-vinylbenzenesulfonic acid and vinylsulfonic acid The body is illustrated.

  These strongly acidic group-containing polymerizable monomers may be used alone or in combination of a plurality of types.

  Among the above strongly acidic group-containing polymerizable monomers, a polymerizable acidic phosphate is particularly preferable because of its excellent adhesiveness to teeth. Moreover, it is preferable that it is a derivative group of a (meth) acryloyl group as a polymerizable unsaturated group at the point with the favorable polymerizability at the time of light irradiation.

  Although the compounding quantity of the strongly acidic group containing polymeric monomer in the dental adhesive composition of this invention is not specifically limited, It is preferable that it is 1-80 mass% in all the compositions. More preferably, it is 3-70 mass%, Most preferably, it is 7-55 mass%.

  The (C) water used in the dental adhesive composition of the present invention is a component added to effectively exert the decalcification action of the tooth together with the (B) strong acidic group-containing polymerizable monomer. The (C) water is preferably substantially free of impurities harmful to storage stability, biocompatibility and adhesion, and examples include deionized water and distilled water. The blending amount of (C) water in the adhesive of the present invention is not particularly limited and may be appropriately set. However, when the pretreatment material is used, it is within 60% by mass in the total composition. Is preferable, more preferably 5 to 55% by mass, and particularly preferably 20 to 55% by mass. Moreover, when it is set as an adhesive material, it is preferable within 30 mass% in all compositions, More preferably, it is 3-20 mass%, Most preferably, it is 7-20 mass parts.

  Examples of the (D) photopolymerization initiator used in the dental adhesive of the present invention include diacetyl, acetylbenzoyl, benzyl, 2,3-pentadione, 2,3-octadione, 4,4′-dimethoxybenzyl, 4,4. Α-diketones such as' -oxybenzyl, camphorquinone, 9,10-phenanthrenequinone, acenaphthenequinone, benzoin alkyl ethers such as benzoin methyl ether, benzoin ethyl ether, benzoin propyl ether, 2,4-di Thioxanthone derivatives such as ethoxythioxanthone, 2-chlorothioxanthone, methylthioxanthone, benzophenone derivatives such as benzophenone, p, p'-dimethylaminobenzophenone, p, p'-methoxybenzophenone, 2,4,6-trimethyl Benzoyldiphenylphos Acylphosphine oxide derivatives such as zinc oxide, bis (2,6-dimethoxybenzoyl) -2,4,4-trimethylpentylphosphine oxide, bis (2,4,6-trimethylbenzoyl) phenylphosphine oxide, and aryl borate compounds / Dye / photoacid generator system. Among these, an α-diketone photopolymerization initiator, an acylphosphine oxide photopolymerization initiator, and a photopolymerization initiator composed of a combination of an aryl borate compound / dye / photoacid generator are particularly preferable. is there.

  As the α-diketone, camphorquinone and benzyl are preferable. As the acylphosphine oxide, 2,4,6-trimethylbenzoyldiphenylphosphine oxide, bis (2,6-dimethoxybenzoyl) -2,4,4- Trimethylpentylphosphine oxide and bis (2,4,6-trimethylbenzoyl) phenylphosphine oxide are preferable. Although these α-diketones and acyl phosphine oxides alone exhibit photopolymerization activity, they can be used in combination with amine compounds such as ethyl 4-dimethylaminobenzoate, lauryl 4-dimethylaminobenzoate, and dimethylaminoethyl methacrylate. It is preferable because higher activity can be obtained.

  As the photopolymerization initiator of the aryl borate compound / dye / photoacid generator system, those described in JP-A-9-3109 and the like are preferably used. More specifically, tetraphenylboron An aryl borate compound such as a sodium salt is used as a dye, and a coumarin dye such as 3,3′-carbonylbis (7-diethylamino) coumarin or 3,3′-carbonylbis (4-cyano-7-diethylaminocoumarin) is used as a light. As the acid generator, those using a halomethyl group-substituted s-triazine derivative such as 2,4,6-tris (trichloromethyl) -s-triazine or a diphenyliodonium salt compound can be particularly preferably used.

  These photopolymerization initiators can be blended not only alone but also in combination of a plurality of types as required. These blending amounts are not particularly limited as long as they are effective amounts that do not hinder the effects of the present invention, and may be appropriately determined according to the use and purpose of the curable composition to be adjusted. It is 0.001-20 mass parts by making the sum total of a component into 100 mass parts. Specifically, in the case of α-diketone or acylphosphine oxide, the total polymerizable monomer component is 0.01 to 20 parts by mass, more preferably 0.1 to 10 parts by mass, based on 100 parts by mass. Further, 0.01 to 20 parts by mass of an amine compound may be added as necessary. In the case of an aryl borate compound / dye / photoacid generator system, the total of all polymerizable monomer components is 100 parts by mass, the dye is 0.001 to 1 part by mass, and the photoacid generator is 0.01 to What is necessary is just to be 10 mass parts.

  In the pretreatment material of the present invention, the above-described components (A) to (C) are usually expressed, and in the adhesive material, the effects (A) to (D) are usually expressed. As long as the effect of the above is not impaired, other components known as a compounding component of the dental adhesive composition as necessary, for example, a polymerizable monomer having no acidic group, a water-soluble organic solvent, an ultraviolet absorber, A polymerization inhibitor, a polymerization inhibitor, a dye, a pigment and the like may be blended.

  As the polymerizable monomer having no acidic group, a known monomer that can be used in the dental field can be used without limitation. Specifically, methyl (meth) acrylate, ethyl (meth) acrylate, isopropyl (meth) acrylate, butyl (meth) acrylate, 2-hydroxyethyl (meth) acrylate, 3-hydroxypropyl (meth) acrylate, glyceryl mono (Meth) acrylate, polyethylene glycol mono (meth) acrylate, ethylene glycol di (meth) acrylate, diethylene glycol di (meth) acrylate, triethylene glycol di (meth) acrylate, nonaethylene glycol di (meth) acrylate, propylene glycol di ( (Meth) acrylate, dipropylene glycol di (meth) acrylate, 2,2′-bis [4- (meth) acryloyloxyethoxyphenyl] propane, 2,2′-bis [ -(Meth) acryloyloxyethoxyethoxyphenyl] propane, 2,2'-bis {4- [3- (meth) acryloyloxy-2-hydroxypropoxy] phenyl} propane, 1,4-butanediol di (meth) acrylate 1,6-hexanediol di (meth) acrylate, 1,9-nonanediol di (meth) acrylate, trimethylolpropane tri (meth) acrylate, neopentyl glycol di (meth) acrylate, urethane (meth) acrylate, epoxy (Meth) acrylate etc. are mentioned.

  The blending amount of the polymerizable monomer having no acidic group is preferably within 75% by mass, more preferably within 65% by mass in the total composition.

  As the water-soluble organic solvent, known organic solvents can be used without any limitation as long as they exhibit water-solubility. The term “water-soluble” as used herein means that the solubility in water at 20 ° C. is 20 g / 100 ml or more. Specific examples of such water-soluble organic solvents include methanol, ethanol, propanol, isopropyl alcohol, acetone, methyl ethyl ketone, and the like. A plurality of these organic solvents can be mixed and used as necessary. In view of harmfulness to living organisms, ethanol, propanol or acetone is preferable.

  The blending amount of the water-soluble organic solvent is preferably within 75% by mass, more preferably within 65% by mass in the total composition.

  In addition, for example, when a plurality of kinds of optional components such as a polymerizable monomer having no acidic group and a water-soluble organic solvent are added, the total amount is 75% by mass in the total composition. Is preferable, and more preferably within 65% by mass.

  The method for producing the dental adhesive composition of the present invention is not particularly limited, and may be performed in accordance with a known method for producing a dental adhesive composition, and generally under an inert light such as red light. In addition, all components to be blended may be weighed and mixed well until a uniform solution is obtained.

  The method of using the dental adhesive composition of the present invention may also follow a known method of using the dental adhesive composition. For example, in the case of a pretreatment material, an adherend from which a carious portion has been removed, etc. The pretreatment material of the present invention is applied to the tooth structure to be used, and after leaving for about 5 to 60 seconds, the volatile components may be volatilized by lightly blowing compressed air or the like. In the case of dental adhesives, the adhesive material of the present invention is applied to the tooth structure that becomes an adherend from which the carious portion has been removed, and after leaving for about 5 to 60 seconds, it is volatile by lightly blowing compressed air or the like. The components may be volatilized and then polymerized and cured by irradiation with visible light using a dental irradiator.

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples. The compounds used in Examples and Comparative Examples and their abbreviations are shown in (1), and the pretreatment material and adhesive enamel and dentin bond strength measuring method of the present invention are shown in (2).
(1) Abbreviation and structure (A) component: alginic acid, alginate A-1; M / G ratio = 0.6, molecular weight 50,000
A-2; M / G ratio = 1.3, molecular weight 50,000
A-3; M / G ratio = 2.2, molecular weight 50,000
A-4; M / G ratio = 2.6, molecular weight 50,000
A-5; M / G ratio = 1.3, molecular weight 200,000
A-6; M / G ratio = 1.3, molecular weight 50,000, sodium salt,
A-7; M / G ratio = 1.3, molecular weight 50,000, potassium salt (B) component; strongly acidic group-containing polymerizable monomer PM; 2-methacryloyloxyethyl dihydrogen phosphate and bis (2- (Methacryloyloxyethyl) hydrogen phosphate mixture MDP; 10-methacryloyloxydecyl dihydrogen phosphate MAMS; 2-methacrylamide-2-methylpropanesulfonic acid (D) component; photopolymerization initiator CQ; camphorquinone DMBE; N, N-dimethyl p-ethyl benzoate TPO; 2,4,6-trimethylbenzoyldiphenylphosphine oxide and other components P-1; polymethacrylic acid, molecular weight 100,000
P-2: Cellulose
UDMA; 1,6-bis (methacrylethyloxycarbonylamino) trimethyloxane HEMA; 2-hydroxyethyl methacrylate EtOH; ethyl alcohol MA; methacrylic acid (2) enamel and dentin bond strength measurement method (2-1) When the adhesive composition of the invention is used as a pretreatment material The bovine front teeth are removed within 24 hours after slaughter, and the enamel and dentin planes are parallel to the labial surface with # 600 emery paper under water flow. I carved out. Next, air is blown onto these surfaces for about 10 seconds to dry, and then a double-sided tape with a hole having a diameter of 3 mm is fixed to the flat surface, followed by paraffin wax having a hole with a thickness of 0.5 mm and a diameter of 8 mm. A simulated cavity was formed by fixing to the same center on the circular hole. The pretreatment material of the present invention was applied into the simulated cavity and left for 20 seconds, and then dried by blowing compressed air for about 10 seconds. Next, a dental adhesive (Tokuso Mac Bond II Bonding Agent, manufactured by Tokuyama Dental Co., Ltd.) was applied to the simulated cavity and irradiated with a visible light irradiator (Power Light, manufactured by Tokuyama Dental Co., Ltd.) for 10 seconds. Cured. Further, a dental composite resin (Palfique Estelite Σ, manufactured by Tokuyama Dental Co., Ltd.) was filled thereon, and irradiated with a visible light irradiator for 30 seconds to prepare an adhesion test piece.

After immersing the above-mentioned adhesion test piece in 37 ° C. water for 24 hours, using a tensile tester (Autograph, manufactured by Shimadzu Corp.), it is pulled at a crosshead speed of 2 mm / min, and the tensile bond strength between the tooth and the composite resin is measured. did. Four tensile bond strengths per test were measured by the above method, and the average value was taken as the initial bond strength. Moreover, the adhesion test piece produced similarly was immersed in water at 4 ° C. and 60 ° C. for 1 minute alternately in a thermal shock tester, and after 3000 times, the tensile adhesive strength was measured in the same manner as described above. The value was defined as the adhesive strength after durability.
(2-2) When the adhesive composition of the present invention is used as an adhesive material The bovine front teeth are removed within 24 hours after slaughter, and enamel so that it is parallel to the lip surface with # 600 emery paper in the water. The texture and dentin plane were cut out. Next, air is blown onto these surfaces for about 10 seconds to dry, and then a double-sided tape with a hole having a diameter of 3 mm is fixed to the flat surface, followed by paraffin wax having a hole with a thickness of 0.5 mm and a diameter of 8 mm. A simulated cavity was formed by fixing to the same center on the circular hole. The adhesive of the present invention was applied in the simulated cavity and left for 20 seconds, and then dried by blowing compressed air for about 10 seconds. Next, the adhesive was cured by irradiating with a visible light irradiator (Power Light, manufactured by Tokuyama Dental Co., Ltd.) for 10 seconds. Further, a dental composite resin (Palfique Estelite Σ, manufactured by Tokuyama Dental Co., Ltd.) was filled thereon, and irradiated with a visible light irradiator for 30 seconds to prepare an adhesion test piece.

  After immersing the above-mentioned adhesion test piece in 37 ° C. water for 24 hours, using a tensile tester (Autograph, manufactured by Shimadzu Corp.), it is pulled at a crosshead speed of 2 mm / min, and the tensile bond strength between the tooth and the composite resin is measured. did. Four tensile bond strengths per test were measured by the above method, and the average value was taken as the initial bond strength. Moreover, the adhesion test piece produced similarly was immersed in water at 4 ° C. and 60 ° C. for 1 minute alternately in a thermal shock tester, and after 3000 times, the tensile adhesive strength was measured in the same manner as described above. The value was defined as the adhesive strength after durability.

Example 1
(A) 0.5 g of A-1 (alginic acid, M / G = 0.6) as component, 4.5 g of PM as component (B), 5 g of water as component (C), weighed and mixed An inventive pretreatment material was prepared. Using this pretreatment material, enamel and dentin bond strengths were measured according to the method of (2-1). Table 1 shows the composition of the pretreatment material and Table 2 shows the initial and post-durability adhesion strengths for enamel and dentin.

Examples 2 to 13 and Comparative Examples 1 to 6
According to the method of Example 1, pretreatment materials having different compositions were prepared. Table 1 shows the composition of the pretreatment material, and Table 2 shows the measurement results of the adhesive strength.

  In Examples 1 to 13, each component was blended so as to satisfy the constitution shown in the present invention. In any case, high adhesive strength was obtained after the initial stage and after the durability.

  On the other hand, in Comparative Examples 1-3, since the alginic acid which is (A) component or alginate is not mix | blended, although the initial adhesive strength is high, the adhesive strength after durability is falling. Comparative Examples 2 and 3 are examples of blending a polymer compound having a carboxyl group but not having a hydroxyl group, or a polymer compound having a hydroxyl group but not having a carboxyl group, It was not obtained. This shows that alginic acid and / or alginic acid having both a carboxyl group and a hydroxyl group in the molecule are essential for obtaining good adhesion durability. Since the strong acidic group containing polymerizable monomer which is (B) component is not mix | blended with the comparative examples 4 and 5, initial stage adhesive strength and adhesive durability are falling. Furthermore, since the comparative example 6 does not contain water as the component (C), the initial adhesive strength and the adhesive durability are lowered.

Example 14
(A) 1 g A-1 (alginic acid, M / G = 0.6) as component, 4 g PM and 4 g MAMS as component (B), 1 g water as component (C) and 0 as component (D) 0.05 g CQ and 0.05 g DMBE were weighed and mixed to prepare the adhesive of the present invention. Using the adhesive, enamel and dentin bond strength was measured according to the method of (2-2). The composition of the adhesive is shown in Table 3, and the initial and post-durability adhesive strengths for enamel and dentin are shown in Table 4.

Examples 15-29, Comparative Examples 7-12
Adhesives having different compositions were prepared according to the method of Example 14. The composition of the adhesive is shown in Table 3, and the measurement results of the adhesive strength are shown in Table 4.

  In Examples 14 to 29, each component was blended so as to satisfy the constitution shown in the present invention. In any case, high adhesive strength was obtained after the initial stage and after durability.

  On the other hand, in Comparative Examples 7-9, since the alginic acid which is (A) component or alginate is not mix | blended, although the initial adhesive strength is high, the adhesive strength after durability is falling. Since the strong acidic group containing polymerizable monomer which is (B) component is not mix | blended with the comparative examples 10 and 11, initial stage adhesive strength and adhesive durability are falling. Furthermore, since the comparative example 12 does not contain water as the component (C), the initial adhesive strength and the adhesive durability are lowered.

Claims (3)

A dental adhesive composition comprising (A) alginic acid and / or alginate, (B) a strongly acidic group-containing polymerizable monomer, and (C) water. A dental pretreatment material comprising the dental adhesive composition according to claim 1. The dental adhesive comprising the dental adhesive composition according to claim 1, further comprising (D) a photopolymerization initiator.