JP5552812B2 - Monofluorophosphorylated polymer compound - Google Patents

Description

  The present invention relates to a monofluorophosphorylated polymer compound.

  Conventionally, the use of a dentifrice containing a fluorine compound has been recommended as a daily self-care action for the purpose of preventing dental caries, which is one of the diseases of the oral cavity. Fluorine compound caries prevention mechanism is to restore the initial carious site by remineralization and restore it to the original healthy tooth quality.

  In order to further exhibit the effects of these fluorine compounds, a technique for gradually releasing fluorine in the oral cavity has been demanded. As such a technique, a technique of adding a fluoride of a cationic polymer compound to enhance a caries prevention effect (for example, Patent Document 1: Japanese Patent Laid-Open No. 3-5417), specific to a fluorine compound and cationized cellulose The technique (for example, patent document 2: Unexamined-Japanese-Patent No. 2001-163743) which improves the intraoral retention property of a fluorine compound, the feeling of use of a dentifrice, and stability is mix | blended by mix | blending this fragrance | flavor component. However, these technologies have insufficient sustained release properties. In addition, when blended in an aqueous preparation such as toothpaste, it has been required to have stability against hydrolysis from the viewpoint of inhibiting decomposition due to moisture.

Japanese Patent Laid-Open No. 3-5417 JP 2001-163743 A

  The present invention has been made in view of the above circumstances, and has a large amount of fluorine in the molecule. By applying it in the oral cavity, the fluorine can be released gradually in the oral cavity, and the monofluorophosphorus is excellent in hydrolysis stability. An object is to provide an oxidized polymer compound.

  As a result of intensive studies to achieve the above object, the present inventors obtained (A) monofluorophosphorylated (A) polymer or (B) polysaccharide containing an acrylamide derivative having a hydroxyl group as a structural unit. By applying the obtained polymer compound to the oral cavity, fluorine is released and sustainedly released by the enzyme reaction of the enzyme present in the oral cavity, and is stable against hydrolysis of the side chain of the polymer compound. In addition, it has been found that there is adhesion to the oral cavity, and fluorine can be retained by this adhesion, and the present invention has been made.

Accordingly, the present invention provides the following monofluorophosphorylated polymer compound.
[1]. A polymer having a weight average molecular weight of 1,000 to 1,000,000, wherein part or all of the hydrogen atoms of the hydroxyl group in the polymer compound selected from the group consisting of the following (A) and (B) is substituted with a monofluorophosphate group Monofluorophosphorylated polymer compound.
(A) (Co) polymer (B) polysaccharide containing an acrylamide derivative having a hydroxyl group as a constituent unit
[2]. The acrylamide derivatives having a hydroxyl group of (A) are N- (2-hydroxyethyl) (meth) acrylamide, N- (hydroxymethyl) (meth) acrylamide, N- (polyethylene glycol) (meth) acrylamide and N- [ The monofluorophosphorylated polymer compound according to [1], which is an acrylamide derivative selected from tris (hydroxymethyl) methyl] acrylamide.
[3]. The monofluorophosphorylated polymer according to [1] or [2], wherein (A) is a copolymer containing an acrylamide derivative having a hydroxyl group and a cationic monomer and / or a hydrophobic nonionic monomer as constituent units. Compound.
[4]. The monofluorophosphorylated polymer according to [3], wherein the monofluorophosphorylated polymer compound is a copolymer containing a monomer having a monofluorophosphate group and a cationic monomer and / or a hydrophobic nonionic monomer as constituent units. High molecular compound.
[5]. Cationic monomers are selected N, N-dimethyl (meth) acrylamide, N, N-dimethylaminopropyl (meth) acrylamide), a (meth) acrylic acid N, N-dimethylamino ethyl Le及 beauty these ammonium quaternary compound a monomer [3] or [4] Symbol mounting monofluorophosphate oxide polymer.
[6]. Hydrophobic nonionic monomers include methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, butyl (meth) acrylate, pentyl (meth) acrylate, hexyl (meth) acrylate, ( [3] to [ 5 ] which is a monomer selected from 2-ethylhexyl ( meth) acrylate, octyl (meth) acrylate, stearyl (meth) acrylate, cyclohexyl (meth) acrylate, benzyl (meth) acrylate and styrene The monofluorophosphorylated polymer compound according to any one of the above.
[7]. Said (B) is hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, methyl cellulose, ethyl cellulose, cellulose scan or hydroxypropyl starch [1] monofluorophosphate oxide polymer compound according.

  According to the monofluorophosphorylated polymer compound of the present invention, it has a large amount of fluorine in the molecule, and can be released / slowly released in the oral cavity by being applied to the oral cavity, and also has stability against hydrolysis. Can be planned.

2 is a ¹ H-NMR spectrum chart of an N- (2-hydroxyethyl) acrylamide polymer obtained in Preparation Example 1. FIG. 2 is a ¹ H-NMR spectrum chart of the polymer compound obtained in Example 1. FIG.

（式中、Ｍは水素原子、アルカリ金属、アンモニウム、モノエタノールアミン、ジエタノールアミン、トリエタノールアミン又はトリエチルアミンを示す。）
で表されるモノフルオロリン酸基で置換され、これを分子中に有する高分子化合物をいう。上記（Ａ）（共）重合体及び（Ｂ）の多糖類をモノフルオロリン酸化することによって得ることができる。このように、共有結合を介してモノフルオロリン酸基を有するため、例えば、単に高分子化合物とモノフルオロリン酸とが、イオン結合で結合していると、容易にモノフルオロリン酸イオンが容易に脱離してしまい、フッ素イオンの徐放性効果が不十分となる。In the monofluorophosphorylated polymer compound of the present invention, a part or all of the hydrogen atoms of the hydroxyl group in the (co) polymer or (B) polysaccharide containing (A) an acrylamide derivative having a hydroxyl group as a structural unit, A monofluorophosphate group is substituted with a monofluorophosphate group, and a monofluorophosphate group is introduced into (A) (co) polymer or (B) polysaccharide and monofluorophosphorylated. Monofluorophosphoric acid may be any of acid type, neutralized type, and partially neutralized type. Specifically, the following formula (1)

(In the formula, M represents a hydrogen atom, an alkali metal, ammonium, monoethanolamine, diethanolamine, triethanolamine or triethylamine.)
The high molecular compound which is substituted by the monofluorophosphate group represented by this, and has this in a molecule | numerator. The (A) (co) polymer and the polysaccharide (B) can be obtained by monofluorophosphorylation. Thus, since it has a monofluorophosphate group via a covalent bond, for example, when a polymer compound and monofluorophosphate are simply bonded by an ionic bond, the monofluorophosphate ion can be easily formed. The effect of sustained release of fluorine ions becomes insufficient.

(A) A (co) polymer containing a hydroxyl group-containing acrylamide derivative as a constituent unit As a hydroxyl group-containing acrylamide derivative, a molecule having a vinyl group, -C (= O) -NH- group, and a hydroxyl group in the molecule If it is, it will not specifically limit, It can use individually by 1 type or in combination of 2 or more types. Specifically, N- (2-hydroxyethyl) (meth) acrylamide, N- (hydroxymethyl) (meth) acrylamide, N- (polyethylene glycol) (meth) acrylamide, N- (2,2-dimethoxy-1 -Hydroxyethyl) (meth) acrylamide, N- (2-hydroxypropyl) (meth) acrylamide, N- [tris (hydroxymethyl) methyl] (meth) acrylamide, N, N'-dihydroxyethylene-bis (meth) acrylamide Etc. Here, as N- (polyethylene glycol) (meth) acrylamide, N- (diethylene glycol) (meth) acrylamide, N- (triethylene glycol) (meth) acrylamide, N- (tetraethylene glycol) (meth) acrylamide, and the like Is mentioned.

（式中、Ｒ¹は水素原子又はメチル基、Ｒ²は炭素数１〜６の２価炭化水素基、ポリエチレンオキサイド基（エチレンオキサイド基の繰り返し数：１〜５）、ポリプロピレンオキサイド基（プロピレンオキサイド基の繰り返し数：１〜５）、ポリエチレンオキサイド基（エチレンオキサイド基の繰り返し数：１〜５）及びポリプロピレンオキサイド基（プロピレンオキサイド基の繰り返し数：１〜５）を含むポリアルキレンオキサイド又はジメトキシエチル基である。）As the acrylamide derivative having a hydroxyl group, those represented by the following general formula (2) are preferable.

(Wherein R ¹ is a hydrogen atom or a methyl group, R ² is a divalent hydrocarbon group having 1 to 6 carbon atoms, a polyethylene oxide group (the number of repeating ethylene oxide groups: 1 to 5), a polypropylene oxide group (propylene oxide) Group repeating number: 1 to 5), polyalkylene oxide or dimethoxyethyl group including polyethylene oxide group (ethylene oxide group repeating number: 1 to 5) and polypropylene oxide group (propylene oxide group repeating number: 1 to 5) .)

  As what is represented by the said General formula (2), N- (2-hydroxyethyl) (meth) acrylamide, N- (hydroxymethyl) (meth) acrylamide, N- (polyethylene glycol) (meth) acrylamide, N -(2,2-dimethoxy-1-hydroxyethyl) (meth) acrylamide, N- (2-hydroxypropyl) (meth) acrylamide, N- (diethylene glycol) (meth) acrylamide, N- (triethylene glycol) (meta And N- (polyethylene glycol) (meth) acrylamide such as N- (tetraethylene glycol) (meth) acrylamide.

  Preferred examples include N- [tris (hydroxymethyl) methyl] (meth) acrylamide, N, N′-dihydroxyethylene-bis (meth) acrylamide) methyl] (meth) acrylamide, N, N′-dihydroxyethylene. -Bis (meth) acrylamide etc. are mentioned.

  Among preferred examples, N- (2-hydroxyethyl) (meth) acrylamide, N- (hydroxymethyl) (meth) acrylamide, N- (diethylene glycol) (meth) acrylamide and N- [tris (hydroxymethyl) methyl] acrylamide Are particularly preferred, and N- (2-hydroxyethyl) (meth) acrylamide is most preferred. In the present invention, “(meth) acrylic acid” represents one or both of acrylic acid and methacrylic acid, and “(meth) acrylamide” represents one or both of acrylamide and methacrylamide.

  The ratio of the acrylamide derivative having a hydroxyl group to the constituent unit composed of all monomers of the (co) polymer containing the acrylamide derivative having a hydroxyl group as a constituent unit is appropriately selected depending on the ratio of the constituent unit having a desired monofluorophosphate structure. However, 5 mass% or more is preferable, More preferably, it is 10-90 mass%, More preferably, it is 35-50 mass%. The upper limit is appropriately selected according to the proportion of structural units other than this monomer.

  Any monomer other than the acrylamide derivative having a hydroxyl group can be used. Examples thereof include ionic monomers for improving the adsorptivity to mucous membranes, hydrophilic (water-soluble) nonionic monomers for improving water solubility, and hydrophobic nonionic monomers for improving retention. The (A) acrylamide derivative having a hydroxyl group is excluded.

  Examples of the ionic monomer include a cationic monomer, an anionic monomer, and an amphoteric monomer. Examples of the cationic monomer include N, N-dimethylaminoethyl (meth) acrylamide, N, N-dimethylaminopropyl (meth) acrylamide, N, N-diethylaminopropyl (meth) acrylamide, and dialkylaminoalkyl (meth) acrylamide. Dialkylaminoalkyl (meth) acrylamide (dialkyl (1 to 3 carbon atoms) aminoalkyl (1 to 3 carbon atoms) (meth) acrylamide, (meth) acrylic acid N, N-dimethylaminoethyl, (meth) acrylic acid N, N-diethylaminoethyl, (meth) acrylic acid N, N-dipropylaminoethyl and the like (meth) acrylic acid dialkylaminoalkyl ((meth) acrylic acid dialkyl (carbon number 1 to 3) aminoalkyl (carbon number 1 to 3) ), N, N-dimethyl (meth) acrylic N, N-dimethylaminopropyl (meth) acrylamide, or an ammonium quaternized compound thereof, etc. Specific examples of the ammonium quaternized compound include trimethyl ammonium chloride, ethyl dimethyl chloride, and the like. Among these, dialkylaminoalkyl (meth) acrylamide, dialkylaminoalkyl (meth) acrylate, and ammonium quaternized products thereof are preferable, dialkylaminoalkyl (meth) acrylamide and ammonium quaternized products thereof are more preferable, N, N-dimethylaminopropylacrylamide methyl chloride is more preferred.

  As an anionic monomer, monomers having a phosphoric acid group such as acid phosphooxyethyl (meth) acrylate, 3-chloro-2-acid phosphooxypropyl (meth) acrylate, acid phosphooxypolyoxyethylene glycol mono (meth) acrylate , Monomers having a carboxylic acid group such as (meth) acrylic acid and maleic acid, and monomers having a sulfonic acid group such as 2-acrylamido-2-methylpropanesulfonic acid.

  Examples of amphoteric monomers include monomers having a phosphate group such as 3-dimethyl ((meth) acryloyloxyethyl) ammonium ethane phosphate, monomers having a carboxylic acid group such as 3-dimethyl (methacryloyloxyethyl) ammonium ethanecarboxylate, 3 -Monomers having a sulfonic acid group such as dimethyl (methacryloyloxyethyl) ammonium propane sulfonate.

  The lower limit of the ratio of the structural unit composed of ionic monomers to the structural unit composed of all monomers of the monofluorophosphorylated polymer compound may be 0% by mass, and the upper limit may be 50% by mass. Preferably it is 0.5-30 mass%, More preferably, it is 1-20 mass%. If it exceeds 50 mass%, the fluorine content may be lowered.

  Examples of the hydrophilic nonionic monomer include methoxypolyethylene glycol (meth) acrylate (p = 2 to 50; EO (ethylene oxide) addition mole number is 2 to 50). 0 mass% may be sufficient as the minimum of the ratio of the structural unit which consists of a water-soluble monomer with respect to the structural unit which consists of all the monomers of a monofluoro phosphorylated polymer compound, 0.5-50 mass% is preferable, More preferably, it is 1-30. % By mass. If it exceeds 50 mass%, the fluorine content may be lowered.

  Hydrophobic nonionic monomers include methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, butyl (meth) acrylate, pentyl (meth) acrylate, hexyl (meth) acrylate, Examples include 2-ethylhexyl (meth) acrylate, lauryl (meth) acrylate, octyl (meth) acrylate, stearyl (meth) acrylate, cyclohexyl (meth) acrylate, benzyl (meth) acrylate, and styrene. Among these, hexyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, lauryl (meth) acrylate, octyl (meth) acrylate, stearyl (meth) acrylate, and the like are preferable, lauryl (meth) acrylate, Stearyl (meth) acrylate is more preferred. However, the hydrophobic nonionic monomer is preferably copolymerized at a ratio that does not impair the water solubility of the polymer compound having a monofluorophosphate structure. 0 mass% may be sufficient as the minimum of the ratio of the structural unit which consists of a hydrophobic nonionic monomer with respect to the structural unit which consists of all the monomers of a monofluoro phosphopolymer compound, 0.05-50 mass% is preferable, More preferably, it is 0. It is 1-40 mass%, and 5-40 mass% is further more preferable. If it exceeds 50% by mass, the fluorine introduction rate and solubility may be lowered.

(B) Polysaccharide A polysaccharide is a polymer compound having a hydroxyl group, specifically, starch, hydroxymethyl starch, hydroxyethyl starch, hydroxypropyl starch, glycogen, inulin, lichenin, hemicellulose, amylopectin, heparin, heparitin sulfate. , Chondroitin sulfate, hyaluronic acid, keratosulfuric acid, chitin, chitosan, agar, carrageenan, alginic acid, fur celeran, locust bean gum, galactomannan, guar gum, syrup gum, tamarind gum, gum arabic, tragacanth gum, caraya gum, pectin, arabinogalactan, xanthan gum , Gellan gum, pullulan, dextran, cellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose Examples include roulose, carboxymethylcellulose, methylcellulose, ethylcellulose, and cationized cellulose. Among these, starch, hydroxymethyl starch, hydroxyethyl starch, hydroxypropyl starch, hydroxy starch, chondroitin sulfate, hyaluronic acid, chitin, chitosan, carrageenan, alginic acid, guar gum, tamarind gum, xanthan gum, dextran, cellulose, hydroxyethyl cellulose, hydroxy Propylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, methylcellulose, ethylcellulose, cationized cellulose are preferred, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, methylcellulose, ethylcellulose, cellulose, cationizedcellulose, hydroxystarch or hydroxypropyl Npun more preferably, hydroxypropyl cellulose, hydroxyethyl cellulose, more preferably cationized cellulose. Hydroxypropyl cellulose may have a low degree of substitution. In view of fluorine retention, cationized cellulose is particularly preferable. Among these, the thing of 0.1-2.5 mass% of cationization degrees is preferable, and the thing of 0.4-2.0 mass% is more preferable. The degree of cationization in the present invention means the ratio (mass%) of nitrogen atoms per glucose ring unit of the cationized cellulose component.

The monofluorophosphorylated polymer compound can be prepared by the following steps.
(I) Prepare (A) (co) polymer or (B) polysaccharide before monofluorophosphorylation.
(Ii) Monofluorophosphorylation of (A) (co) polymer or (B) polysaccharide of (i).
In this case, it is preferable in that the monofluorophosphorylated polymer compound can be easily separated from other low-molecular coexisting substances with a dialysis membrane.

  (I) Preparation of (A) (co) polymer or (B) polysaccharide before monofluorophosphorylation may be performed using a commercially available product, and (A) (co) polymer is an acrylamide having a hydroxyl group. You may (co) polymerize a derivative or the acrylamide derivative which has a hydroxyl group, and the monomer containing the said monomer other than this.

  The polymerization method for polymerizing the monomer is not particularly limited, and a solution polymerization method, an emulsion polymerization method, a suspension polymerization method, a solid phase polymerization method and the like are used. When polymerized by a solution polymerization method, examples of the solvent include water, lower alcohols such as methanol, ethanol and isopropyl alcohol, aromatic, aliphatic or heterocyclic compounds such as benzene, toluene, xylene, cyclohexane, hexane and tetrahydrofuran, Various organic solvents such as ethyl acetate, acetone, and methyl ethyl ketone can be used. The polymerization concentration is not particularly limited, but it is usually preferable to polymerize the monomer at a total concentration of 10 to 50% by mass in the solvent. The copolymerization may be random copolymerization or block copolymerization.

  Examples of the polymerization initiator used in the monomer polymerization include persulfates such as ammonium persulfate, sodium persulfate and potassium persulfate, peroxides such as benzoyl peroxide and lauryl peroxide, cumene hydroperoxide, hydroperoxide. Hydroperoxides such as azo compounds such as azobisisobutyronitrile. The concentration of the polymerization initiator is usually preferably from 0.1 to 10 mol% based on the total amount of monomers used. Further, a chain transfer agent such as alkyl mercaptan, a polymerization accelerator such as a Lewis acid compound, and a pH adjuster such as phosphoric acid, citric acid, tartaric acid, and lactic acid may be used to regulate the molecular weight. The polymerization temperature is appropriately determined depending on the solvent used and the polymerization initiator, but is usually room temperature (25 ° C.) to 150 ° C. The polymerization time is 1 to 10 hours. The molecular weight of the polymer compound of the present invention can be controlled by adjusting the polymerization conditions such as the amount of initiator used, the type of polymerization solvent, and the monomer concentration during polymerization. In the case where a monomer having a monofluorophosphoric acid structure via a covalent bond is polymerized, it can be obtained by the same polymerization method.

(Ii) Monofluorophosphorylation of (A) (co) polymer or (B) polysaccharide of (i).
The method for monofluorophosphorylating (A) (co) polymer or (B) polysaccharide is not particularly limited, but (A) (co) polymer or (B) polysaccharide and difluorophosphoric acid or its The method of making it react with a salt is mentioned. In the method of polymerizing a monomer having a monofluorophosphoric acid structure, the monofluorophosphoric acid may be hydrolyzed and eliminated during the polymerization reaction. Therefore, in order to increase the amount of monofluorophosphoric acid introduced, A method of reacting (A) (co) polymer or (B) polysaccharide with difluorophosphoric acid or a salt thereof is preferred.

  By reacting the (A) (co) polymer or (B) polysaccharide with difluorophosphoric acid or a salt thereof, the hydrogen atom of the hydroxyl group in the (A) (co) polymer or (B) polysaccharide is reacted. Part or all of them are substituted with the monofluorophosphate group, and the monofluorophosphate group is introduced into the (A) (co) polymer or (B) polysaccharide and monofluorophosphorylated.

  When the (A) (co) polymer or (B) polysaccharide is reacted with difluorophosphoric acid or a salt thereof, it is desirable to remove a proton donating solvent such as water and ethanol from the polymer compound. When it is not sufficiently removed, difluorophosphoric acid is hydrolyzed and cannot effectively react with the polymer compound. Examples of the method for removing the proton donating solvent include removal by leaving it under reduced pressure or under vacuum, removal using a drying agent such as silica gel and molecular sieve, and a dehydrating agent. In addition, from the viewpoint of reaction uniformity and operational safety, when the (A) (co) polymer or (B) polysaccharide is dissolved in various aprotic solvents, it is preferably dissolved and reacted. . Examples of the aprotic solvent include ethers such as diethyl ether, tetrahydrofuran and 1,4-dioxane, esters such as ethyl acetate, dimethyl sulfoxide, acetonitrile and acetone. Among these, diethyl ether, tetrahydrofuran and 1,4 -Ethers such as dioxane, esters such as ethyl acetate, dimethyl sulfoxide and acetonitrile are preferred. Moreover, it is desirable to remove proton-donating solvents such as water and ethanol mixed in the aprotic solvent.

  Reaction of (A) (co) polymer or (B) polysaccharide with difluorophosphoric acid or a salt thereof is carried out in order to prevent mixing of proton donating solvents such as water and ethanol from the outside, such as nitrogen or argon It is preferable to carry out in an inert atmosphere. Further, since the reaction between the hydroxyl group and difluorophosphoric acid is exothermic, the reaction temperature is −20 to 50 ° C., preferably −10 to 40 ° C., and either or both of difluorophosphoric acid and the polymer compound solution are gradually added. It is preferable to mix while dropping. The proportion of difluorophosphoric acid in the reaction solution obtained by mixing the polymer compound solution and (B) difluorophosphoric acid or a salt thereof is preferably 30 to 95% by mass, more preferably 35 to 90% by mass. %. By setting this range, it is possible to further improve the fluorine content in the polymer compound having a monofluorophosphoric acid structure by increasing the difluorophosphoric acid concentration in the reaction solution. The molar ratio between the hydroxyl group in the polymer compound and difluorophosphoric acid or a salt thereof can be appropriately changed according to the ratio of the monofluorophosphate structure in the target polymer compound, but the hydroxyl group: difluorophosphoric acid or its Salt (molar ratio) = 1: 1 to 10 is preferable, and 1: 1 to 3 is more preferable.

  In addition, (A) (co) polymer or (B) polysaccharide is one or two kinds selected from dimethyl sulfoxide, trimethyl phosphate, triethyl phosphate, tripropyl phosphate, tributyl phosphate and triphenyl phosphate. When making it react in the aprotic solvent which consists of the above solvent, it is preferable that the difluoro phosphoric acid with respect to a hydroxyl group or its salt (molar ratio) shall be 5 or more, More preferably, it is 7-100, More preferably, it is 11-11. 60. The reaction temperature between the hydroxyl group and difluorophosphoric acid is preferably a reaction temperature equal to or higher than the melting point, particularly in the case of a solvent having a melting point of 0 ° C. or higher, such as dimethyl sulfoxide. -50 ° C, preferably 25-40 ° C. The reaction time is preferably 1 to 72 hours.

  Since unreacted difluorophosphoric acid remains in the reaction product, it should be removed by drying under reduced pressure, or reacted with a basic aqueous solution such as sodium hydroxide or potassium hydroxide to give a monofluorophosphate. Is preferred. The reaction solution may or may not be filtered, but it is preferable to filter in order to remove a trace amount of insoluble matter. In the procedure for filtration, the monofluorophosphorylated polymer compound may be neutralized after filtration after dialysis, or may be filtered after dialysis and neutralization.

  In the monofluorophosphorylated polymer compound of the present invention, a part or all of the hydrogen atoms of the hydroxyl group in (A) (co) polymer or (B) polysaccharide is substituted with the monofluorophosphate group, A) a (co) polymer or (B) a polysaccharide having a monofluorophosphate group introduced therein and monofluorophosphorylated. For example, in the case of (A) (co) polymer, when a part or all of the hydrogen atoms of the hydroxyl group of the acrylamide derivative having a hydroxyl group is substituted with the monofluorophosphate group, and the structural unit (2) is present And substituted with a monofluorophosphate group as shown in the following formula (3).

（式中、Ｒ¹、Ｒ²及びＭは上記と同じ。）

(Wherein R ¹ , R ² and M are the same as above)

  In the case of a monofluorophosphorylated polymer compound in which some or all of the hydrogen atoms of the hydroxyl group in the (A) (co) polymer or (B) polysaccharide are substituted with the monofluorophosphate group, all structural units The proportion of the structural unit having a monofluorophosphate group (structure) is preferably 5% by mass or more, more preferably 5 to 50% by mass, and still more preferably 10 to 30% by mass. The upper limit may be 100% by mass, and is appropriately selected according to the proportion of structural units other than this monomer. For example, the upper limit is appropriately selected as 95% by mass, 80% by mass, and the like.

  In the case of (A) (co) polymer, the proportion of each structural unit in the resulting monofluorophosphorylated polymer compound is the proportion of each structural unit in (A) (co) polymer used for monofluorophosphorylation. Can be adjusted. For example, the (A) (co) polymer is an acrylamide derivative having a hydroxyl group of 5 to 100% by mass, preferably 30 to 95% by mass, a cationic monomer of 0 to 95% by mass, preferably 0 to 65% by mass, In addition, a (co) polymer containing 0 to 95% by mass, preferably 0 to 40% by mass of a hydrophobic nonionic monomer as a structural unit can be used. In addition, the said range includes the range containing the polymer (homopolymer) of an acrylamide derivative, The ratio of the structural unit is suitably selected from the said and following range. The monofluorophosphorylated polymer compound in the present invention includes, for example, a monomer having a monofluorophosphate group of 5 to 100% by mass, an acrylamide derivative having a hydroxyl group of 0 to 95% by mass, a cationic monomer of 0 to 65% by mass, and a hydrophobic group. It can be expressed as a (co) polymer containing 0 to 40% by mass of a nonionic monomer as a constituent unit.

  Among these, from the viewpoint of further improving the fluorine retention in the oral cavity, the (A) (co) polymer includes an acrylamide derivative having a hydroxyl group and a cationic monomer and / or a hydrophobic nonionic monomer as constituent units. A copolymer may be used as a monofluorophosphorylated polymer compound that is a copolymer containing a monomer having a monofluorophosphate group and a cationic monomer and / or a hydrophobic nonionic monomer as constituent units. In addition, in order to further improve the retention, a cationic monomer and a hydrophobic nonionic monomer are used in combination, and as the (A) (co) polymer, an acrylamide derivative having a hydroxyl group, a cationic monomer, and a hydrophobic nonionic monomer are used. Monofluorophosphorylation, which is a copolymer containing a monomer having a monofluorophosphate group, a cationic monomer, and a hydrophobic nonionic monomer as a constituent unit, using a copolymer containing an ionic monomer as a constituent unit A high molecular compound is preferable.

  The monofluorophosphorylated polymer compound may be a copolymer containing, as necessary, an acrylamide derivative having a hydroxyl group as a constituent unit. In addition, "as needed" includes the case where all of the acrylamide derivatives having a hydroxyl group are substituted with a hydrogen atom of the hydroxyl group with a monofluorophosphate group and the case where a part thereof is substituted. Monomers having a monofluorophosphate group include acrylamide derivatives in which a hydrogen atom of a hydroxyl group is substituted with a monofluorophosphate group, and monomers having other monofluorophosphate groups.

  (A) The ratio of the cationic monomer in the copolymer and the monofluorophosphorylated polymer compound is preferably 65% by mass or less from the viewpoint of preventing a decrease in the fluorine introduction rate, and 10 to 65 from the viewpoint of further improving the retention. % By mass is more preferable, 20 to 40% by mass is further preferable, and 25 to 35% by mass is particularly preferable. In addition, the proportion of the hydrophobic nonionic monomer in the (A) (co) polymer and the monofluorophosphorylated polymer compound is 40% by mass or less from the viewpoint of preventing the solubility of the monofluorophosphorylated polymer compound from decreasing. From the point which improves a retention property, 5-40 mass% is more preferable, 10-35 mass% is further more preferable, 15-30 mass% is especially preferable. When the proportion of the hydrophobic nonionic monomer exceeds 40% by mass, the solubility may be lowered. However, when the copolymer (A) and the monofluorophosphorylated polymer compound are a copolymer containing a cationic monomer and / or a hydrophobic nonionic monomer as a structural unit, the cationic monomer and the hydrophobic nonionic monomer The ratios of N are not 0 at the same time.

  (A) When the copolymer is a copolymer containing an acrylamide derivative having a hydroxyl group and a cationic monomer and / or a hydrophobic nonionic monomer as constituent units, (A) an acrylamide having a hydroxyl group in the copolymer The ratio of the derivative is preferably 30 to 95% by mass from the comprehensive viewpoints such as improvement of fluorine retention in the oral cavity, prevention of reduction in fluorine introduction rate, and prevention of reduction in solubility of monofluorophosphorylated polymer compound, and the like. -60 mass% is more preferable, and 35-50 mass% is further more preferable.

In addition, from a comprehensive viewpoint such as improvement of fluorine retention in the oral cavity, prevention of decrease in fluorine introduction rate, and prevention of decrease in solubility of monofluorophosphorylated polymer compound, monofluorophosphorylated polymer compound is monofluorophosphorus. A copolymer containing an acid group-containing monomer, a hydroxyl group-containing acrylamide derivative, a cationic monomer, and a hydrophobic nonionic monomer in the following proportions is preferable.
5 to 50% by weight of a monomer having a monofluorophosphate group, preferably 10 to 30% by weight, more preferably 12 to 29% by weight,
The acrylamide derivative having a hydroxyl group is 0 to 77% by mass, more preferably 10 to 70% by mass, further preferably 0 to 60% by mass, particularly preferably 15 to 45% by mass, and most preferably 19 to 35% by mass. .
10 to 65% by weight of the cationic monomer, preferably 20 to 40% by weight, more preferably 25 to 35% by weight
5-40% by weight of hydrophobic nonionic monomer, preferably 10-35% by weight, more preferably 15-30% by weight
The case of 0% by mass of the acrylamide derivative having a hydroxyl group refers to the case where all of the acrylamide derivatives having a hydroxyl group are substituted with a hydrogen atom of the hydroxyl group by a monofluorophosphate group.

  The fluorine introduction rate (mass%) of the monofluorophosphorylated polymer compound is preferably from 0.1 to 15 mass%, more preferably from 0.5 to 5 mass%. When the amount is less than 0.1% by mass, a sufficient fluorine release amount may not be obtained. The introduction rate of the monofluorophosphorylated polymer compound can be appropriately adjusted by selecting the type of reaction solvent, the amount of difluorophosphoric acid, the reaction time, and the reaction temperature. In addition, the fluorine introduction rate (mass%) in this invention is based on the following measuring method.

<Fluorine introduction rate>
2.4 g of a 1 mol / L perchloric acid aqueous solution is added to 1.6 g of the 0.1% by mass aqueous solution of the polymer compound, placed in a sealed tube with a lid made of PE, and heated at 105 ° C. for 10 minutes. Thereafter, 0.4 g of the liquid is collected and mixed with 1.6 g of 1 mol / L potassium citrate buffer (pH 5.5), and then the fluorine amount: X _p (ppm) is quantified with a fluorine electrode meter. The mass concentration of fluorine with respect to the total mass of the polymer compound (fluorine introduction rate: F (mass%)) is calculated by the following formula.
F = [Xp (ppm) × (0.4 + 1.6) /0.4× (1.6 + 2.4) /1.6/10000] (mass% of F) /0.1 (high monofluorophosphorylation level) (% By mass of molecular compound) × 100
= Xp × 1.25
More specifically, it depends on the “fluorine introduction rate” measurement method of the example.

  The weight average molecular weight (Mw) of the monofluorophosphorylated polymer compound in the present invention is preferably 1,000 to 1,000,000 from the viewpoint of release / sustained release of fluorine by the oral enzyme of the monofluorophosphate group, 000 to 500,000 are more preferable, and 10,000 to 300,000 are more preferable. When the molecular weight is less than 1,000, there is a possibility that the retention in the oral cavity is insufficient. The weight average molecular weight was measured by gel permeation chromatography using a water-soluble polymer compound after monofluorophosphorylation as a sample, water containing 10 mM sodium nitrate and 20 vol% acetonitrile as an eluent, and pullulan standard. The molecular weight is calculated in terms of Specifically, it is based on description of the Example mentioned later. The molecular weight of the monofluorophosphorylated polymer compound of the present invention can be controlled by adjusting the polymerization conditions such as the amount of initiator used, the type of polymerization solvent, and the monomer concentration during polymerization.

The monofluorophosphorylated polymer compound of the present invention is preferably water-soluble because it can be easily treated. In the present invention, the term “water-soluble” means a value that shows a value of 80% or more in the following water-solubility evaluation method. The filtration is used as a suitable means for obtaining a water-soluble polymer compound.
<Water-soluble>
A mixed solution (a) of 0.5 g of the polymer compound and 10 g of water was prepared, put into a glass container and shaken at 25 ° C. for 24 hours, and then subjected to a centrifugal separation operation (3000 G (29419.95 m / s ² ), 15 minutes) and divided into a polymer compound solution part (b) and an insoluble part (c). The mass M [g] of the polymer compound solution part (b) is measured. The appropriate amount (about 2 g) of the polymer compound solution part (b) was transferred to an infrared moisture meter, and when the fluctuation range of moisture (mass%) for 2 minutes at 110 ° C. became 0.1 mass% or less, the end point (polymer compound) The mass of the polymer compound in the polymer compound solution part (b) is measured under the condition that the moisture in the solution part (b) is lost and becomes only the polymer compound) and used for the infrared moisture meter. From the mass of the polymer compound solution part (b), the polymer compound concentration D [%] in the polymer compound solution part (b) is calculated. In the measurement using this infrared moisture meter, the mass of the polymer compound solution part (b) at the start of measurement is taken as 100, the water in the polymer compound solution part (b) after the measurement is lost, and the polymer The mass of only the compound is displayed as a relative value. Therefore, for example, if the value represented by this relative value is “1”, the polymer compound concentration D [%] in the polymer compound solution part (b) is 1% by mass.
By multiplying the polymer compound concentration D [%] in the polymer compound solution part (b) thus obtained by the mass M [g] of the polymer compound solution part (b), a polymer compound is obtained. The mass W _d [g] of the dissolved polymer compound in the solution part (b) is determined.
W _d [g] = M [g] × D [%]
From the obtained value of W _d [g], the dissolution rate R of 0.5 g of the polymer compound in 10 g of water is calculated by the following formula.
R = W _d /0.5×100

  The monofluorophosphorylated polymer compound of the present invention has a large amount of fluorine, and when applied to the oral cavity, fluorine is released and sustainedly released by an enzymatic reaction and is stable against hydrolysis. It is preferable to mix in the composition for use. In addition, fluorine can be retained by adhesion of the monofluorophosphorylated polymer compound to the oral cavity.

  The content of the monofluorophosphorylated polymer compound in the oral composition is preferably 0.01 to 20% by mass, more preferably 0.1 to 10% by mass. When the content of the monofluorophosphorylated polymer compound is less than 0.01% by mass, a satisfactory blending effect may not be obtained, and when it exceeds 20% by mass, the usability of the composition may be deteriorated.

  Examples of the oral composition of the present invention include dentifrices, mouth washes, tooth surface coating agents, patches, denture cleaning agents, chewing gums, troches and the like. Depending on the dosage form, other additives can be blended as optional components.

  Examples of optional components include surfactants, detergents, wetting agents, thickeners, abrasives, binders, thickeners, oils, polymer compounds other than the water-soluble polymer compound of the present invention, antiseptics, and the like. Agents, clathrate compounds, antioxidants / antioxidants, chelating agents, inorganic powders, gum bases, acidulants, softeners, colorants, brighteners, emulsifiers, sweeteners, pH adjusters, fragrances, pigments, crude drugs, Examples include sugars, salts, amino acids, medicinal components other than those described above, antibacterial agents, and solvents such as water, ethanol, isopropyl alcohol, ethylene glycol, and glycerin.

  EXAMPLES Hereinafter, although a preparation example, an Example, and a comparative example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example.

[Preparation Example 1] Preparation of N- (2-hydroxyethyl) acrylamide (HEAA) polymer 85 g of ethanol was placed in a 300 mL four-necked separable flask equipped with a stirrer, a reflux condenser and a nitrogen inlet tube, and stirred. Then, nitrogen gas was introduced from the nitrogen introduction tube. Next, while heating in an oil bath at 90 ° C., a monomer solution prepared by mixing 30 g of N- (2-hydroxyethyl) acrylamide (manufactured by Kojin) with 50 g of ethanol and 2,2′-azobis (2-methyl) A polymerization initiator solution in which 0.50 g of butyronitrile (trade name V-59: manufactured by Wako Pure Chemical Industries, Ltd.) was dissolved in 35 g of ethanol was continuously added dropwise over 1 hour to conduct a polymerization reaction.
After completion of the dropwise addition, heating was continued for 5 hours while introducing nitrogen, and the reaction solution was dialyzed in running water for 3 days (fraction molecular weight of dialysis membrane 14,000, manufactured by Sanko Junyaku Co., Ltd.). By removing water with an evaporator and freeze-drying (NEOCOOL, manufactured by Yamato Scientific Co., Ltd.), 25 g of N- (2-hydroxyethyl) acrylamide (HEAA) polymer was obtained.

[Preparation Example 2] Preparation of N- (2-hydroxyethyl) methacrylamide (HEMAA) polymer In Preparation Example 1, N- (2-hydroxyethyl) acrylamide (manufactured by Kojin) was changed to N- (2-hydroxyethyl). N, except that the amount of 2,2′-azobis (2-methylbutyronitrile) (trade name V-59: manufactured by Wako Pure Chemical Industries, Ltd.) was 0.45 g as methacrylamide (manufactured by ABCR) 26 g of-(2-hydroxyethyl) methacrylamide (HEMAA) polymer was obtained.

[Preparation Example 3] Preparation of N- (hydroxymethyl) acrylamide (HMAA) polymer In Preparation Example 1, N- (2-hydroxyethyl) acrylamide (manufactured by Kojin) was changed to N- (hydroxymethyl) acrylamide (manufactured by Tokyo Chemical Industry). N- (hydroxymethyl) acrylamide in the same manner except that the amount of 2,2′-azobis (2-methylbutyronitrile) (trade name V-59: manufactured by Wako Pure Chemical Industries) was 0.57 g. 25 g of (HMAA) polymer was obtained.

[Preparation Example 4] Preparation of N- (hydroxymethyl) methacrylamide (HMMAA) polymer In Preparation Example 1, N- (2-hydroxyethyl) acrylamide (manufactured by Kojin) was changed to N- (hydroxymethyl) methacrylamide (ABCR). 24 g of N- (hydroxymethyl) methacrylamide (HMMAA) polymer was obtained in the same manner except that it was made.

[Preparation Example 5] Preparation of N- (diethylene glycol) acrylamide (DEGAA) polymer In Preparation Example 1, N- (2-hydroxyethyl) acrylamide (manufactured by Kojin) was changed to N- (diethylene glycol) acrylamide (manufactured by Tokyo Chemical Industry). , 2,2′-azobis (2-methylbutyronitrile) (trade name V-59: manufactured by Wako Pure Chemical Industries, Ltd.) except that the amount was 0.36 g, N- (diethylene glycol) acrylamide (DEGAA) 25 g of polymer was obtained.

[Preparation Example 6] Preparation of N- (diethylene glycol) methacrylamide (DEGMAA) polymer In Preparation Example 1, N- (2-hydroxyethyl) acrylamide (manufactured by Kojin) was changed to N- (diethylene glycol) methacrylamide (manufactured by Tokyo Chemical Industry). N- (diethylene glycol) methacrylamide in the same manner except that the amount of 2,2′-azobis (2-methylbutyronitrile) (trade name V-59: manufactured by Wako Pure Chemical Industries) was 0.33 g. 24 g of (DEGMAA) polymer was obtained.

[Preparation Example 7] Preparation of N- [tris (hydroxymethyl) methyl] acrylamide (THMMAA) polymer In Preparation Example 1, N- (2-hydroxyethyl) acrylamide (manufactured by Kojin) was changed to N- [Tris (hydroxymethyl). ) Methyl] acrylamide (manufactured by Kanto Chemical Co., Inc.), except that the amount of 2,2′-azobis (2-methylbutyronitrile) (trade name V-59: manufactured by Wako Pure Chemical Industries) was 0.33 g. Thus, 22 g of N- [tris (hydroxymethyl) methyl] acrylamide (THMMAA) polymer was obtained.

[Comparative Preparation Example 8] Preparation of hydroxyethyl acrylate (HEA) polymer In Preparation Example 1, except that N- (2-hydroxyethyl) acrylamide (manufactured by Kojin) was changed to hydroxyethyl acrylate (manufactured by Kojin), In the same manner, 26 g of a hydroxyethyl acrylate polymer (HEA) was obtained.

[Preparation Example 9] Preparation of N- (2-hydroxyethyl) acrylamide (HEAA) / N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) = 90/10 copolymer Stirrer, reflux condenser and nitrogen 85 g of ethanol was put into a 300 mL four-necked separable flask equipped with an introduction tube, and nitrogen gas was introduced from the nitrogen introduction tube while stirring. Next, while heating in a 90 ° C. oil bath, 27 g of N- (2-hydroxyethyl) acrylamide (manufactured by Kojin), N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) (manufactured by Kojin) ) A polymerization initiator prepared by dissolving 3 g of 50 g of ethanol in a monomer solution and 0.42 g of 2,2′-azobis (2-methylbutyronitrile) (trade name V-59: manufactured by Wako Pure Chemical Industries, Ltd.) in 35 g of ethanol. The solution was continuously added dropwise over 1 hour to carry out the polymerization reaction.
After completion of the dropwise addition, heating was continued for 5 hours while introducing nitrogen, and the reaction solution was dialyzed in running water for 3 days (fraction molecular weight of dialysis membrane 14,000, manufactured by Sanko Junyaku Co., Ltd.). By removing water with an evaporator and freeze-drying (NEOCOOL, manufactured by Yamato Scientific Co., Ltd.), N- (2-hydroxyethyl) acrylamide (HEAA) / N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) = 25 g of 90/10 copolymer was obtained.

[Preparation Example 10] Preparation of N- (2-hydroxyethyl) acrylamide (HEAA) / N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) = 60/40 copolymer In Preparation Example 9, N- ( The amount of 2-hydroxyethyl) acrylamide (manufactured by Kojin) was 18 g, the amount of N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) (manufactured by Kojin) was 12 g, and 2,2′-azobis (2 N- (2-hydroxyethyl) acrylamide (HEAA) / N, N-, except that the amount of -methylbutyronitrile) (trade name V-59: manufactured by Wako Pure Chemical Industries, Ltd.) was 0.48 g. 24 g of dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) = 60/40 copolymer was obtained.

[Preparation Example 11] Preparation of N- (2-hydroxyethyl) acrylamide (HEAA) / N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) = 35/65 copolymer In Preparation Example 9, N- ( The amount of 2-hydroxyethyl) acrylamide (manufactured by Kojin) is 10.5 g, the amount of N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) (manufactured by Kojin) is 19.5 g, and 2,2 ′ -N- (2-hydroxyethyl) acrylamide (HEAA) / except that the amount of azobis (2-methylbutyronitrile) (trade name V-59: manufactured by Wako Pure Chemical Industries) was 0.36 g. 23 g of N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) = 35/65 copolymer was obtained.

[Preparation Example 12] Preparation of N- (2-hydroxyethyl) acrylamide (HEAA) / N, N-dimethylaminopropylacrylamide (DMAPAA) = 60/40 copolymer In Preparation Example 9, N- (2-hydroxyethyl) ) 18g of acrylamide (manufactured by Kojin), N, N-dimethylaminopropyl acrylamide methyl chloride (DMAPAA-Q) (manufactured by Kojin) 12g of N, N-dimethylaminopropyl acrylamide (DMAPAA) (manufactured by Kojin) N- (2-hydroxyethyl), except that the amount of 2,2′-azobis (2-methylbutyronitrile) (trade name V-59: manufactured by Wako Pure Chemical Industries) was 0.45 g. ) Acrylamide (HEAA) / N, N-dimethylaminopropylacrylamide (DMAPAA) = 60/40 copolymer 26g was obtained.

[Preparation Example 13] Preparation of N- (2-hydroxyethyl) acrylamide (HEAA) / N, N-dimethylaminoethylmethyl chloride methacrylate (DMC) = 60/40 copolymer N- (2 -Hydroxyethyl) acrylamide (manufactured by Kojin) in an amount of 18 g, N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) (manufactured by Kojin) in N, N-dimethylaminoethyl methyl chloride methacrylate (DMC) (Mitsubishi Gas Chemical Co., Ltd.) 12 g, except that the amount of 2,2′-azobis (2-methylbutyronitrile) (trade name V-59: manufactured by Wako Pure Chemical Industries) was 0.46 g, N- (2-hydroxyethyl) acrylamide (HEAA) / N, N-dimethylaminoethyl methacrylate (DMC) = 60 / 25 g of 40 copolymer was obtained.

[Preparation Example 14] Preparation of N- (2-hydroxyethyl) acrylamide (HEAA) / N, N-dimethylaminoethyl methacrylate (DM) = 60/40 copolymer In Preparation Example 9, N- (2-hydroxy 18 g of ethyl) acrylamide (manufactured by Kojin), N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) (manufactured by Kojin) with N, N-dimethylaminoethyl methacrylate (DM) (manufactured by Tokyo Chemical Industry) N- (2-), except that the amount of 2,2′-azobis (2-methylbutyronitrile) (trade name V-59: manufactured by Wako Pure Chemical Industries) was 0.49 g. 27 g of hydroxyethyl) acrylamide (HEAA) / N, N-dimethylaminoethyl methacrylate (DM) = 60/40 copolymer was obtained.

[Preparation Example 15] Preparation of N- (2-hydroxyethyl) acrylamide (HEAA) / lauryl methacrylate (LMA) = 95/5 copolymer In Preparation Example 9, N- (2-hydroxyethyl) acrylamide (Kojin) 28.5 g, N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) (manufactured by Kojin) to 1.5 g of lauryl acrylate (LMA) (manufactured by Tokyo Chemical Industry), and 2,2 ′ -N- (2-hydroxyethyl) acrylamide (HEAA) / except that the amount of azobis (2-methylbutyronitrile) (trade name V-59: manufactured by Wako Pure Chemical Industries) was 0.47 g. 25 g of lauryl methacrylate (LMA) = 95/5 copolymer was obtained.

[Preparation Example 16] Preparation of N- (2-hydroxyethyl) acrylamide (HEAA) / lauryl methacrylate (LMA) = 90/10 copolymer In Preparation Example 9, N- (2-hydroxyethyl) acrylamide (Kojin) 27 g, N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) (manufactured by Kojin) is 3 g of lauryl acrylate (LMA) (manufactured by Tokyo Chemical Industry), and 2,2′-azobis (2 N- (2-hydroxyethyl) acrylamide (HEAA) / lauryl methacrylate (trade name V-59: manufactured by Wako Pure Chemical Industries, Ltd.) except that the amount was 0.44 g. LMA) = 90/10 copolymer 23g was obtained.

[Preparation Example 17] Preparation of N- (2-hydroxyethyl) acrylamide (HEAA) / lauryl methacrylate (LMA) = 80/20 copolymer In Preparation Example 9, N- (2-hydroxyethyl) acrylamide (Kojin) 24 g, N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) (manufactured by Kojin) is 6 g of lauryl acrylate (LMA) (manufactured by Tokyo Chemical Industry), and 2,2′-azobis (2 N- (2-hydroxyethyl) acrylamide (HEAA) / lauryl methacrylate (trade name V-59: manufactured by Wako Pure Chemical Industries, Ltd.) except that the amount was 0.44 g. LMA) = 80/20 copolymer 25g was obtained.

[Preparation Example 18] Preparation of N- (2-hydroxyethyl) acrylamide (HEAA) / stearyl methacrylate (StMA) = 90/10 copolymer In Preparation Example 9, N- (2-hydroxyethyl) acrylamide (Kojin) 27 g, N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) (manufactured by Kojin) is 3 g of stearyl methacrylate (StMA) (manufactured by Tokyo Chemical Industry), and 2,2′-azobis (2 N- (2-hydroxyethyl) acrylamide (HEAA) / stearyl methacrylate (trade name V-59: manufactured by Wako Pure Chemical Industries, Ltd.) except that the amount was 0.43 g. StMA)) = 90/10 copolymer 25 g was obtained.

[Preparation Example 19] Preparation of N- (2-hydroxyethyl) acrylamide (HEAA) / hexyl methacrylate (HMA) = 90/10 copolymer In Preparation Example 9, N- (2-hydroxyethyl) acrylamide (Kojin) 27 g, N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) (manufactured by Kojin) is 3 g of hexyl methacrylate (HMA) (manufactured by Tokyo Chemical Industry), and 2,2′-azobis (2 N- (2-hydroxyethyl) acrylamide (HEAA) / hexyl methacrylate (trade name V-59: manufactured by Wako Pure Chemical Industries, Ltd.) except that the amount was 0.47 g. HMA) = 90/10 copolymer 23g was obtained.

[Preparation Example 20] Preparation of N- (2-hydroxyethyl) acrylamide (HEAA) / butyl methacrylate (BMA) = 90/10 copolymer In Preparation Example 9, N- (2-hydroxyethyl) acrylamide (Kojin) 27 g, N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) (manufactured by Kojin) is 3 g of butyl methacrylate (BMA) (manufactured by Tokyo Chemical Industry), and 2,2′-azobis (2 N- (2-hydroxyethyl) acrylamide (HEAA) / butyl methacrylate (-methylbutyronitrile) (trade name V-59: manufactured by Wako Pure Chemical Industries, Ltd.) except that the amount was 0.48 g. BMA) = 90/10 copolymer 23g was obtained.

[Preparation Example 21] N- (2-hydroxyethyl) acrylamide (HEAA) / N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) / lauryl methacrylate (LMA) = 35/35/30 Preparation 85 g of ethanol was put into a 300 mL four-necked separable flask equipped with a stirrer, a reflux condenser and a nitrogen introduction tube, and nitrogen gas was introduced from the nitrogen introduction tube while stirring. Next, while heating in an oil bath at 90 ° C., 10.5 g of N- (2-hydroxyethyl) acrylamide (manufactured by Kojin), N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) (Manufactured) 10.5 g, lauryl methacrylate (LMA) (manufactured by Tokyo Chemical Industry Co., Ltd.) 9 g of a monomer solution mixed with ethanol 50 g, 2,2′-azobis (2-methylbutyronitrile) (trade name V-59: A polymerization initiator solution prepared by dissolving 0.45 g (manufactured by Wako Pure Chemical Industries, Ltd.) in 35 g of ethanol was continuously added dropwise over 1 hour to conduct a polymerization reaction.
After completion of the dropwise addition, heating was continued for 5 hours while introducing nitrogen, and the reaction solution was dialyzed in running water for 3 days (fraction molecular weight of dialysis membrane 14,000, manufactured by Sanko Junyaku Co., Ltd.). , N- (2-hydroxyethyl) acrylamide (HEAA) / N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) / by removing water by evaporator and freeze-drying (NEOCOOL, manufactured by Yamato Scientific Co., Ltd.) 26 g of lauryl methacrylate (LMA) = 35/35/30 copolymer was obtained.

[Preparation Example 22] N- (2-hydroxyethyl) acrylamide (HEAA) / N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) / lauryl methacrylate (LMA) = 50/25/25 copolymer Preparation In Preparation Example 20, N- (2-hydroxyethyl) acrylamide (manufactured by Kojin), N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) (manufactured by Kojin), lauryl methacrylate (LMA) (Tokyo) The amount of 2,2′-azobis (2-methylbutyronitrile) (trade name V-59: manufactured by Wako Pure Chemical Industries, Ltd.) is 0.38 g. N- (2-hydroxyethyl) acrylamide (HEAA) / N, N-dimethylaminopropylacrylic except that Bromide methyl chloride was obtained (DMAPAA-Q) / lauryl methacrylate (LMA) = 50/25/25 copolymer 22 g.

[Preparation Example 23] Preparation of N- (2-hydroxyethyl) acrylamide (HEAA) / N, N-dimethylaminoethyl methacrylate methyl chloride (DMC) / stearyl acrylate (StA) = 50/35/15 copolymer In Preparation Example 20, the amount of N- (2-hydroxyethyl) acrylamide (manufactured by Kojin) was 15 g, and N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) (manufactured by Kojin) was added to methacrylic acid N, N -Dimethylaminoethyl methyl chloride (DMC) (manufactured by Mitsubishi Gas Chemical) 10.5 g, lauryl methacrylate (LMA) (manufactured by Tokyo Chemical Industry) is stearyl acrylate (StA) (manufactured by Tokyo Chemical Industry) 4.5 g, Except that the amount of '-azobis (2-methylbutyronitrile) (trade name V-59: manufactured by Wako Pure Chemical Industries, Ltd.) was 0.39 g In the same manner, N- (2-hydroxyethyl) acrylamide (HEAA) / N, N-dimethylaminoethyl methacrylate methyl chloride (DMC) / stearyl acrylate (StA) = 50/35/15 copolymer 23 g Got.

[Preparation Example 24] Preparation of N- (2-hydroxyethyl) acrylamide (HEAA) / N, N-dimethylaminopropylacrylamide (DMAPAA) / hexyl methacrylate (HMA) = 45/35/20 copolymer Preparation Example 20 In this case, the amount of N- (2-hydroxyethyl) acrylamide (manufactured by Kojin) was 13.5 g, and N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) (manufactured by Kojin) was N, N-dimethylamino. 10.5 g of propylacrylamide (DMAPAA) (manufactured by Kojin), lauryl methacrylate (LMA) (manufactured by Tokyo Chemical Industry) is 6 g of hexyl methacrylate (HMA) (manufactured by Tokyo Chemical Industry), and 2,2′-azobis (2-methyl) Butylonitrile) (trade name V-59: manufactured by Wako Pure Chemical Industries, Ltd.) 26 g of (2-hydroxyethyl) acrylamide (HEAA) / N, N-dimethylaminopropylacrylamide (DMAPAA) / hexyl methacrylate (HMA) = 45/35/20 copolymer was obtained.

[Preparation Example 25] N- (2-hydroxyethyl) acrylamide (HEAA) / N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) / butyl methacrylate (BMA) = 35/35/30 Preparation In Preparation Example 20, the amount of N- (2-hydroxyethyl) acrylamide (manufactured by Kojin) was 10.5 g, and N, N-dimethylaminopropylacrylamide methyl chloride (DMAPAA-Q) (manufactured by Kojin) was 10. 5 g, lauryl methacrylate (LMA) (manufactured by Tokyo Chemical Industry) is changed to 9 g of butyl methacrylate (BMA) (manufactured by Tokyo Chemical Industry), and 2,2′-azobis (2-methylbutyronitrile) (trade name V-59: Japanese N- (2-Hydroxyethyl) acrylamide (HEAA) / N in the same manner except that the amount of the product was 0.41 g. It was obtained N- dimethylaminopropyl acrylamide methyl chloride (DMAPAA-Q) / butyl methacrylate (BMA) = 35/35/30 copolymer 26 g.

[Example 1]
1 g of N- (2-hydroxyethyl) acrylamide (HEAA) polymer prepared according to the above preparation example was dissolved in 9 g of dimethyl sulfoxide (dry: manufactured by MERCK), then placed in a 50 mL two-necked eggplant flask, and nitrogen gas was added. Introduced. While immersing the flask in a water bath at 25 ° C., 8 mL of difluorophosphoric acid (0.5 hydrate, manufactured by Shinquest, specific gravity 1.58) was gradually added dropwise (the HEAA polymer hydroxyl group and difluorophosphoric acid The molar ratio is hydroxyl group: difluorophosphoric acid = 1: 14.3). After stirring for 5 hours, a 25% by mass aqueous sodium hydroxide solution was added dropwise to neutralize to pH 7. The reaction solution was dialyzed in running water for 72 hours (dialysis membrane molecular weight cut off 14,000, manufactured by Sanko Junyaku Co., Ltd.) and filtered using filter paper (101, manufactured by Advantech Toyo Co., Ltd.), and then aqueous sodium hydroxide solution To pH 7. Finally, water was removed by an evaporator and freeze-drying (NEOCOOL, manufactured by Yamato Scientific Co., Ltd.) to obtain 0.8 g of sodium monofluorophosphate N- (2-hydroxyethyl) acrylamide polymer.

The sodium monofluorophosphate HEAA polymer of Example 1 has structural units of the following formulas (4) and (5). In the formula, M represents a hydrogen atom or a sodium atom. The ratio of the structural unit (4) to the total structural unit was 27% by mass, and the ratio of (5) was 73% by mass.

[Examples 2 to 7]
The N- (2-hydroxyethyl) acrylamide polymer was prepared in the same manner as in Example 1 except that the pre-reaction polymer compound described in Table 1 was changed. From the polymer compound obtained in the above preparation example, Sodium monofluorophosphate N- (2-hydroxyethyl) methacrylamide copolymer (hydroxyl group of polymer compound before reaction: difluorophosphoric acid = 1: 16.0), sodium monofluorophosphate N- (hydroxymethyl) ) Acrylamide copolymer (hydroxyl group of polymer compound before reaction: difluorophosphoric acid = 1: 12.5), sodium monofluorophosphate N- (hydroxymethyl) methacrylamide copolymer (hydroxyl group of polymer compound before reaction) : Difluorophosphoric acid = 1: 14.3), sodium monofluorophosphate N- (diethylene glycol) acrylamide copolymer (Hydroxyl group of polymer compound before reaction: difluorophosphoric acid = 1: 19.8), sodium monofluorophosphate N- (diethylene glycol) methacrylamide copolymer (hydroxyl group of polymer compound before reaction: difluorophosphoric acid = 1: 21.5), sodium monofluorophosphate N- [tris (hydroxymethyl) methyl] acrylamide copolymer (hydroxyl group of polymer compound before reaction: difluorophosphoric acid = 1: 21.7) .8 g was obtained.

  In Examples 2-6, the ratio (mass%) of the structural unit (monomer) having a monofluorophosphate group (structure) with respect to the total structural units: the structural unit (mass%) of the acrylamide derivative having a hydroxyl group is the example. 2 23% by mass: 77% by mass, Example 3 25% by mass: 75% by mass, Example 4 23% by mass: 77% by mass, Example 5 29% by mass: 71% by mass, Example 6 26% by mass: 74 It was mass%. In addition, based on the said result, the ratio of each structural unit in a monofluoro phosphorylated polymer compound is shown in a table | surface. "F-" indicates that the hydrogen atom of the hydroxyl group is substituted with a monofluorophosphate group, and F-HEAA indicates N- (wherein the hydrogen atom of the hydroxyl group is substituted with a monofluorophosphate group. 2-hydroxyethyl) acrylamide.

[Examples 8 to 13]
A N- (2-hydroxyethyl) acrylamide polymer was prepared in the same manner as in Example 1 except that the pre-reaction polymer compound described in Tables 2 and 3 was changed to N- (2-hydroxyethyl) acrylamide / N, N-dimethylaminopropylacrylamide methyl chloride copolymer (hydroxyl group of pre-reaction polymer: difluorophosphoric acid = 1: 14.8), sodium monofluorophosphate N- (2-hydroxyethyl) acrylamide / N , N-dimethylaminopropylacrylamide methyl chloride copolymer (hydroxyl group of the pre-reaction polymer compound: difluorophosphoric acid = 1: 17.7), sodium monofluorophosphate N- (2-hydroxyethyl) acrylamide / N, N-dimethylaminopropylacrylamide methyl chloride copolymer Hydroxyl group of compound: difluorophosphoric acid = 1: 19.9), sodium monofluorophosphate N- (2-hydroxyethyl) acrylamide / N, N-dimethylaminopropylacrylamide copolymer (hydroxyl group of polymer compound before reaction) : Difluorophosphoric acid = 1: 15.8), sodium monofluorophosphate N- (2-hydroxyethyl) acrylamide / methacrylic acid N, N-dimethylaminoethylmethyl chloride copolymer (hydroxyl group of polymer compound before reaction) : Difluorophosphoric acid = 1: 17.3), sodium monofluorophosphate N- (2-hydroxyethyl) acrylamide / N, N-dimethylaminoethyl methacrylate copolymer (hydroxyl group of polymer compound before reaction: difluoro 0.8 g of phosphoric acid = 1: 15.5) was obtained.

[Examples 14 to 19]
Prepared in the same manner as in Example 1 except that the N- (2-hydroxyethyl) acrylamide polymer was changed to the pre-reaction polymer described in Table 4, and sodium monofluorophosphate N- (2-hydroxy) Ethyl) acrylamide / lauryl methacrylate copolymer (hydroxyl group of polymer compound before reaction: difluorophosphoric acid = 1: 14.7), sodium monofluorophosphate N- (2-hydroxyethyl) acrylamide / lauryl methacrylate copolymer Polymer (hydroxyl group of polymer compound before reaction: difluorophosphoric acid = 1: 15.5), sodium monofluorophosphate N- (2-hydroxyethyl) acrylamide / lauryl methacrylate copolymer (polymer compound before reaction Hydroxyl group: difluorophosphoric acid = 1: 16.5), sodium monofluorophosphate N- (2-hydride) Xylethyl) acrylamide / stearyl methacrylate copolymer (hydroxyl group of pre-reaction polymer: difluorophosphoric acid = 1: 16.6), sodium monofluorophosphate N- (2-hydroxyethyl) acrylamide / hexyl methacrylate Polymer (hydroxyl group of polymer compound before reaction: difluorophosphoric acid = 1: 14.7), sodium monofluorophosphate N- (2-hydroxyethyl) acrylamide / butyl methacrylate copolymer (polymer compound before reaction Each of 0.8 g of hydroxyl group: difluorophosphoric acid = 1: 14.5) was obtained.

[Examples 20 to 24]
Prepared in the same manner as in Example 1 except that the N- (2-hydroxyethyl) acrylamide polymer was changed to the pre-reaction polymer compounds described in Tables 5 and 6, and sodium monofluorophosphate N- (2 -Hydroxyethyl) acrylamide / N, N-dimethylaminopropylacrylamide methyl chloride / lauryl methacrylate copolymer (hydroxyl group of the pre-reaction polymer compound: difluorophosphoric acid = 1: 21.1), sodium monofluorophosphate N -(2-hydroxyethyl) acrylamide / N, N-dimethylaminopropylacrylamide methyl chloride / lauryl methacrylate copolymer (hydroxyl group of polymer compound before reaction: difluorophosphoric acid = 1: 19.1), monofluorophosphoric acid Sodiumated N- (2-hydroxyethyl) acrylamide / methac N, N-dimethylaminoethylmethyl chloride / stearyl methacrylate copolymer (hydroxyl group of polymer compound before reaction: difluorophosphoric acid = 1: 18.8), sodium monofluorophosphate N- (2-hydroxy) Ethyl) acrylamide / N, N-dimethylaminopropylacrylamide / hexyl methacrylate copolymer (hydroxyl group of polymer compound before reaction: difluorophosphoric acid = 1: 17.9), sodium monofluorophosphate N- (2- 0.8 g each of hydroxyethyl) acrylamide / N, N-dimethylaminopropylacrylamide methyl chloride / butyl methacrylate copolymer (hydroxyl group of polymer compound before reaction: difluorophosphoric acid = 1: 18.9) was obtained.

  The ratio of each structural unit in the monofluoro phosphorylated polymer compound in Examples 8 to 24 is shown in Tables 2 to 6.

[Example 25]
1 g of hydroxypropylcellulose (HPC-L, manufactured by Nippon Soda Co., Ltd.) was dissolved in 9 g of tetrahydrofuran (dehydrated: manufactured by Kanto Chemical Co., Inc.), and then placed in a 50 mL two-necked eggplant flask, and nitrogen gas was introduced. While immersing the flask in a water bath at 25 ° C., 4 mL of difluorophosphoric acid (0.5 hydrate, manufactured by Synquest, specific gravity 1.58) was gradually added dropwise (with hydroxyl group of hydroxypropylcellulose and difluorophosphoric acid). The molar ratio is hydroxyl group: difluorophosphoric acid = 1: 27.2). After stirring for 5 hours, a 25% by mass aqueous sodium hydroxide solution was added dropwise to neutralize to pH 7. The reaction solution was dialyzed in running water for 72 hours (dialysis membrane molecular weight cut off 14,000, manufactured by Sanko Junyaku Co., Ltd.) and filtered using filter paper (101, manufactured by Advantech Toyo Co., Ltd.), and then aqueous sodium hydroxide solution To pH 7. Finally, water was removed by an evaporator and freeze-drying (NEOCOOL, manufactured by Yamato Scientific Co., Ltd.) to obtain 0.8 g of sodium fluoropropylcellulose monofluorophosphate.

Sodium monofluorophosphate hydroxypropylcellulose of Example 25 has the following structure.

[Example 26]
The hydroxypropyl cellulose was prepared in the same manner as in Example 1 except that hydroxypropyl cellulose (HPC-SSL, manufactured by Nippon Soda Co., Ltd.) was used, to obtain 0.8 g of monofluorophosphoric acid sodium hydroxypropyl cellulose.

[Example 27]
1 g of hydroxypropylmethylcellulose (HPMC, 2208, manufactured by Shin-Etsu Chemical Co., Ltd.) was placed in a 50 mL two-necked eggplant flask as it was, and nitrogen gas was introduced. While immersing the flask in a room temperature water bath, 4 mL of difluorophosphoric acid was gradually added dropwise. After stirring for 4 hours, a 25% by mass aqueous sodium hydroxide solution was added dropwise to neutralize to pH 7. The reaction solution was dialyzed in running water for 72 hours, filtered using filter paper (101, manufactured by ADVANTEC), and then adjusted to pH 7 with an aqueous sodium hydroxide solution. Finally, water was removed by an evaporator and lyophilization to obtain monofluorophosphoric acid sodium hydroxypropylmethylcellulose.

[Examples 28 to 33]
Hydroxypropylmethylcellulose, hydroxyethylcellulose (CF-G, manufactured by Sumitomo Seika), ethylcellulose (N-10, manufactured by HERCULES), methylcellulose (MC, METOLOSE-SM, manufactured by Shin-Etsu Chemical), cellulose (Selfia, manufactured by Asahi Kasei Kogyo) , Hydroxypropyl starch (HPS-101 (W), manufactured by Freund Corporation), and cationized cellulose (manufactured by Lion Corporation), except that it was prepared in the same manner as in Example 27. Sodium fluoroethyl phosphate, Sodium cellulose monofluorophosphate, Sodium cellulose monofluorophosphate, Sodium monofluorophosphate hydroxypropyl starch, Monofluorophosphate To obtain a thorium cationic cellulose.

The N- (2-hydroxyethyl) acrylamide polymer obtained in Preparation Example 1 and the sodium monofluorophosphate N- (2-hydroxyethyl) acrylamide polymer obtained in Example 1 were added in 0.1 wt. The solution was dissolved in mass% and measured by proton nuclear magnetic resonance spectroscopy ( ¹ H-NMR; 270 MHz). The results are shown in FIGS. When a monofluorophosphate ester is formed by reaction with difluorophosphoric acid, a polymer compound having a hydroxyl group in the molecule shifts the proton peak of the methylene adjacent to the hydroxyl group, so that a covalent bond is formed by ¹ H-NMR measurement. It is possible to determine.

In the case of “N- (2-hydroxyethyl) acrylamide polymer”, the proton peak of methylene adjacent to the hydroxyl group appeared at 3.5 to 3.7 ppm (peak area relative value: 2.00), but difluorophosphoric acid and In the “monofluorophosphate sodium-substituted N- (2-hydroxyethyl) acrylamide polymer”, which is a reaction product of the above, the peak of 3.5 to 3.7 ppm decreases (peak area relative value: 1.23), Instead, a peak appeared at 3.7 to 4.1 ppm (peak area relative value: 0.57). And other peaks did not shift.
From this result, the monofluorophosphoric acid sodium-ized N- (2-hydroxyethyl) acrylamide polymer obtained in Example 1 shows that the hydroxyl group of the N- (2-hydroxyethyl) acrylamide polymer is different from that of monofluorophosphoric acid. It was confirmed that a covalent bond was formed.

[Comparative Example 1]
Prepared in the same manner as in Example 1 except that the N- (2-hydroxyethyl) acrylamide polymer was changed to 2-hydroxyethyl acrylate (HEA) polymer (hydroxyl group: difluorophosphoric acid = 1: 14.4). 0.8 g of 2-hydroxyethyl acrylate monosodium monofluorophosphate was obtained.

[Comparative Example 2] Mixture of N- (2-hydroxyethyl) acrylamide polymer and monofluorophosphoric acid 8.26 g of N- (2-hydroxyethyl) acrylamide polymer obtained in Preparation Example 1 above and monofluorophosphoric acid Comparative Example 2 was obtained by uniformly mixing 1.74 g of disodium (SMFP, manufactured by Rhodia Nikka). (Fluorine concentration of Comparative Example 2: 2.3 mass%)

The following measurement and evaluation (1-4) were performed about the monofluoro phosphorylated polymer compound obtained in the Example.
1. Weight average molecular weight (Mw)
Water containing 10 mM sodium nitrate and 20 vol% acetonitrile as an eluent, measured by gel permeation chromatography, converted to a pullulan standard (P-82, Showa Denko) with a molecular weight of 5,800 to 853,000, weight average Molecular weight was calculated. Specifically, the dried product was dissolved in water containing 10 mM sodium nitrate and 20 vol% acetonitrile to prepare a 0.5 mass% solution. Tosoh Co., Ltd. TSK-GelG2500PWXL and TSK-GelGMPWXL were connected and installed in the column, the column oven set temperature was 40 ° C., the eluent was water containing 10 mM sodium nitrate and 20 vol% acetonitrile, and the flow rate was 0.5 mL / min, detection was performed by RI.

2. Fluorine introduction rate 2.4 g of a 1 mol / L perchloric acid aqueous solution was added to 1.6 g of a 0.1% by mass polymer compound aqueous solution, placed in a sealed tube with a lid made of PE, and heated at 105 ° C. for 10 minutes. . Thereafter, 0.4 g of the liquid was collected and mixed with 1.6 g of 1 mol / L potassium citrate buffer (pH 5.5), and then the fluorine amount was measured with a fluorine electrode meter (Expandable Ion Analyzer EA920, manufactured by Orion): X _p (ppm) was quantified. The mass concentration of fluorine (fluorine introduction rate: F (mass%)) relative to the total mass of the polymer compound was calculated by the following formula.
F = X _p × 1.25

3. A mixed solution (a) of 0.5 g of a water-soluble polymer compound and 10 g of water was prepared, placed in a glass container and shaken at 25 ° C. for 24 hours, and then subjected to a centrifugal separation operation (3000 G (29419.95 m / s ² ), 15 minutes), and was divided into a polymer compound solution part (b) and an insoluble part (c). The mass M [g] of the polymer compound solution part (b) was measured. Polymer compound solution part (b) About 2 g of an appropriate amount is transferred to an infrared moisture meter (FD-620, manufactured by Kett Electric Laboratory Co., Ltd.), and the fluctuation range of moisture (mass%) at a temperature of 110 ° C. for 2 minutes is 0.1. In the polymer compound solution part (b) under the condition that the end point (the water content in the polymer compound solution part (b) is lost and only the polymer compound is present) when the amount becomes less than mass%. The polymer compound mass was measured, and the polymer compound concentration D [%] in the polymer compound solution part (b) was calculated from the mass of the polymer compound solution part (b) used in the infrared moisture meter. In the measurement using this infrared moisture meter, the mass of the polymer compound solution part (b) at the start of measurement is taken as 100, the water in the polymer compound solution part (b) after the measurement is lost, and the polymer The mass of only the compound is displayed as a relative value. Therefore, for example, if the value represented by this relative value is “1”, the polymer compound concentration D [%] in the polymer compound solution part (b) is 1% by mass.
By multiplying the polymer compound concentration D [%] in the polymer compound solution part (b) thus obtained by the mass M [g] of the polymer compound solution part (b), a polymer compound is obtained. The mass W _d [g] of the dissolved polymer compound in the solution part (b) was determined.
W _d [g] = M [g] × D [%]
From the value of W _d [g] obtained, the dissolution rate R of 0.5 g of the polymer compound in 10 g of water was calculated by the following formula. R = 80% or more is defined as “◯”.
R = W _d /0.5×100

4). Hydrolysis stability (i) The polymer compound was dissolved in 0.1% by mass in the following pH 1.2 hydrochloric acid buffer solution. The hydrochloric acid buffer solution was prepared by diluting 322.5 mL of 0.2 mol / L hydrochloric acid and 250 mL of 0.2 mol / L potassium chloride aqueous solution to 1 L with pure water. After storing this at 40 ° C. for 24 hours, 4 g of the sample solution was placed in an ultrafiltration membrane (Amicon Ultra-4, manufactured by MILLIPORE) having a molecular weight cut off of 10,000, which was rinsed 5 times with nanopure water, and 3000G (29419). (.95 m / s ² ) for 15 minutes. 1 g of the filtrate was collected, diluted to 20 g with nanopure water, and the amount of decomposed organic matter after storage treatment: C ₁ was measured with a total organic carbon meter.
(Ii) Next, separately from this, immediately after the polymer compound is sufficiently dissolved in nanopure water at 0.1% by mass, 4 g of the sample solution is rinsed with nanopure water five times in the same manner as described above. The resultant was put in an ultrafiltration membrane having a molecular weight cut-off of 10,000, and subjected to centrifugal filtration at 3000 G (29419.95 m / s ² ) for 15 minutes. 1 g of the filtrate was collected, diluted to 20 g with nanopure water, and the decomposition organic content: C ₀ in the case of no storage treatment (blank) was measured with a total organic carbon meter.
(Iii) Finally, 0.2 g of 0.1 mass% polymer compound aqueous solution prepared with nanopure water was further diluted to 20 g with nanopure water, and the total organic content of the polymer compound aqueous solution was measured with a total organic carbon meter: C _t was measured.
From (i) to (iii), the carbon decomposition rate by storage treatment: T was calculated by the following equation.
T (%) = [(C ₁ −C ₀ ) × 20 (20 times dilution) / (C _t × 100 (100 times dilution))] × 100
Evaluation criteria ○: T is 0.5% or less Δ: T is larger than 0.5%, 1% or less ×: T is larger than 1%

5. Fluorine retention -1
The polymer compound was dissolved in pure water so that the fluorine concentration was 950 ppm, and the pH was adjusted to 7 to 8 with a 1N sodium hydroxide aqueous solution (Kanto Chemical). This polymer compound solution (fluorine concentration: 950 ppm, pH = 7-8) was added to a primary coat 6-well petri dish (MULTIWELL ^™ PRIMARIA ^™ 6 well (well surface area 9.2 cm ² , manufactured by Nippon Becton Dickinson; 1g was added to the surface treated with a positive surface) and allowed to stand at room temperature for 3 minutes.After that, the treatment solution was sucked and removed as much as possible, and then 1g of pure water was added to spread the pure water on the bottom of the petri dish. After confirmation, suction was removed as much as possible, and 1 g of pure water was added once again, and the same operation was performed.
Thereafter, 1 g of a 1 mol / L perchloric acid aqueous solution was added to the petri dish, an evaporation prevention seal was attached, and the mixture was heated at 105 ° C. for 10 minutes. Thereafter, the fluorine amount F (ppm) was measured with a fluorine electrode meter (Expandable Ion Analyzer EA920, manufactured by Orion). The resulting fluorine content F (ppm), based on the following equation to determine the dish fluorine amount staying in the (surface area ^{9.2cm 2) F'(μg / 9.2cm} 2).
F ′ (μg / 9.2 cm ² ) = 1 × 10 ⁶ (μg) × F (ppm) / 10 ⁶

以下、表中において、ＤＭＳＯ：ジメチルスルホキシド，ＴＨＦ：テトラヒドロフランを示す。

Hereinafter, DMSO: dimethyl sulfoxide, THF: tetrahydrofuran are shown in the table.

  Regarding Examples 1, 9, 15, 20, 25 and 33, the following 5. Fluorine release properties were evaluated. The results are also shown in Table 8.

5. Fluorine-releasing property 0.1 g of 70 units / g acid phosphatase (potato-derived) phosphate buffer (pH 7) was added to 4.9 g of an aqueous solution of 0.1% by mass polymer compound and shaken at 37 ° C. for 24 hours. Saved while. Thereafter, 0.4 g of the liquid was collected and mixed with 1.6 g of 1 mol / L potassium citrate buffer (pH 5.5), and then the fluorine in the liquid was measured with a fluorine electrode meter (Expandable Ion Analyzer EA920, manufactured by Orion). Amount: _Xe (ppm) was measured. Separately from this, 0.4 g of 0.1% by mass polymer compound aqueous solution was collected and mixed with 1.6 g of 1 mol / L potassium citrate buffer (pH 5.5), and then the solution was measured with a fluorine electrode meter. Fluorine content in the solution: X ₀ (ppm) was measured. The fluorine release property was evaluated according to the following evaluation criteria.
Evaluation criteria ◎: X _e -X ₀ is more than 0.3ppm ○: X _e -X ₀ is 0.3ppm or less beyond the 0.1ppm △: X _e -X ₀ is 0.1ppm in excess of 0.05ppm X: X _e -X ₀ is 0.05 ppm or less

  Regarding Examples 1, 9, 15, 20, 25 and 33 and Comparative Examples 1 and 2, the following 6. Fluorine sustained release was evaluated. The results are shown in Table 9.

6). Evaluation of Fluoride Slow Release Property 0.1 g of 70 units / g acid phosphatase (potato-derived) phosphate buffer (pH 7) was added to 4.9 g of an aqueous solution of 0.1% by mass polymer compound (preparation of two), 1 One was stored for 12 hours and the other for 24 hours with shaking at 37 ° C. Thereafter, 0.4 g of each solution was collected, mixed with 1.6 g of 1 mol / L potassium citrate buffer (pH 5.5), and then mixed with a fluorine electrode meter (Expandable Ion Analyzer EA920, manufactured by Orion). Fluorine content (12 hours later: X ₁₂ , 24 hours later X ₂₄ (ppm)) was measured. Separately from this, 0.4 g of 0.1% by mass polymer compound aqueous solution was collected and mixed with 1.6 g of 1 mol / L potassium citrate buffer (pH 5.5), and then the solution was measured with a fluorine electrode meter. Fluorine content in the solution: X ₀ (ppm) was measured. Fluorine slow release: S was evaluated according to the following evaluation criteria.
S (%) = (X ₁₂ −X ₀ ) / (X ₂₄ −X ₀ ) × 100
Evaluation criteria ○: S is 50% or more and less than 90%, and fluorine release occurs relatively uniformly over 24 hours (high sustained release property).
Δ: S is 90% or more and less than 95%, and fluorine release occurs relatively unevenly over 24 hours (low release property is low).
X: S is 95% or more and 100% or less, and fluorine release occurs relatively non-uniformly over 24 hours (slow release properties are hardly seen).

[Example 34]
<Mouthwash>
A mouthwash having the following composition was prepared by the following method.
A specified amount of purified water was put into a stainless steel vessel equipped with a three-one motor and a stirrer having rotating blades, and the sodium monofluorophosphate N- (2-hydroxyethyl) acrylamide polymer obtained in Example 1 was used. A phase A was obtained by adding and dissolving water-soluble components such as a surfactant and a pH adjuster with stirring. On the other hand, in a separate stainless steel container equipped with a three-one motor and a stirrer having rotating blades, a prescribed amount of an organic solvent such as propylene glycol and glycerin is added, and oil-soluble components such as fragrances are stirred among the blended components. Charged and dissolved to obtain phase B. Furthermore, B phase was added to A phase, and it stirred for 30 minutes, and it was set as the uniform solution, and 100 g of mouthwashes were obtained.

実施例３４，３５で得られた口腔用組成物について、下記評価７を行った。結果を表１２に示す。[Example 35]
<Dentifrice>
A dentifrice having the following composition was prepared by the following method.
A phase A was prepared by mixing and dissolving water-soluble components (monofluorophosphorylated hydroxypropyl cellulose prepared in Example 25, nonionic surfactant, sodium saccharin, 70% sorbite solution, etc.) in purified water at room temperature. On the other hand, B phase was prepared by dissolving and dispersing sodium carboxymethyl cellulose and sodium polyacrylate at room temperature in propylene glycol. Next, B phase was added and mixed in A phase under stirring, and C phase was prepared.
Furthermore, C phase and sodium lauryl sulfate, fragrance, anhydrous silicic acid, etc. are mixed at room temperature using a small vacuum crusher (manufactured by Ishiyama Works), defoamed by depressurization to 4 kPa, and 100 g of dentifrice is obtained. It was.

The following evaluation 7 was performed on the oral compositions obtained in Examples 34 and 35. The results are shown in Table 12.

7). Fluorine retention -2
In the case of dentifrice (Example 35) after preparing the preparations described in Examples 34 and 35 by a conventional method, 10 g of artificial saliva (CaCl ₂ = 1.5 mmol / L, KH ₂ PO ₄ = 5. 0 mmol / L, acetic acid = 100 mmol / L, NaCl = 100 mmol / L, balance = water; pH 7.0) were mixed and stirred (assuming a dentifrice diluted 3-fold in the oral cavity). After stirring, the mixture was centrifuged (3000 rpm, 10 minutes) with a centrifuge (Centifige 5804R, Hamburg, Germany), and the resulting supernatant was used as a treatment solution. In the case of a mouthwash (Example 16), 0.5 g of artificial saliva was mixed with 5 g of the agent and stirred (assuming a mouthwash that is slightly diluted in the oral cavity) as a treatment liquid. Each treatment solution (5 g) was injected into a primary-coated 100 mm standard dish (Nippon Becton Dickinson). In the case of a dentifrice, the treatment solution was discarded after being held for 5 minutes and washed with 2 g of ultrapure water. . In the case of a mouthwash, the treatment liquid was discarded after being held for 30 seconds, and washing was not performed. After each treatment, 1 mL of phosphate buffer (pH 5) containing 5 units / mL of acid phosphatase (from potato; Sigma) was injected into the dish and allowed to stand for 24 hours. Fluoride ions were released from the fluorophosphorylated polymer. The fluoride ion concentration in the phosphate buffer was measured with an ion chromatograph (ICS-2000; Dionex). The measurement was performed at N = 2, and the average value was used for the determination.
<Ion chromatograph measurement conditions>
Separation column: IonPac AS20,
Guard column: NG-1, column temperature: 30 ° C, detector temperature: 35 ° C,
Eluent: 55 mM potassium hydroxide, flow rate: 1.2 mL / min, introduction amount: 20 μL
<Criteria>
A: Fluoride ion concentration is 0.5 ppm or more and less than 1.0 ppm B: Fluoride ion concentration is 0.1 ppm or more and less than 0.5 ppm X: Fluoride ion concentration is less than 0.1 ppm

Claims (7)

A polymer having a weight average molecular weight of 1,000 to 1,000,000, wherein part or all of the hydrogen atoms of the hydroxyl group in the polymer compound selected from the group consisting of the following (A) and (B) is substituted with a monofluorophosphate group Monofluorophosphorylated polymer compound.
(A) (Co) polymer (B) polysaccharide containing an acrylamide derivative having a hydroxyl group as a constituent unit   The acrylamide derivatives having a hydroxyl group of (A) are N- (2-hydroxyethyl) (meth) acrylamide, N- (hydroxymethyl) (meth) acrylamide, N- (polyethylene glycol) (meth) acrylamide and N- [ The monofluorophosphorylated polymer compound according to claim 1, which is an acrylamide derivative selected from tris (hydroxymethyl) methyl] acrylamide.   The monofluorophosphorylated polymer compound according to claim 1 or 2, wherein (A) is a copolymer containing an acrylamide derivative having a hydroxyl group and a cationic monomer and / or a hydrophobic nonionic monomer as constituent units.   The monofluorophosphorylated polymer according to claim 3, wherein the monofluorophosphorylated polymer compound is a copolymer containing a monomer having a monofluorophosphate group and a cationic monomer and / or a hydrophobic nonionic monomer as constituent units. High molecular compound. Cationic monomers are selected N, N-dimethyl (meth) acrylamide, N, N-dimethylaminopropyl (meth) acrylamide), a (meth) acrylic acid N, N-dimethylamino ethyl Le及 beauty these ammonium quaternary compound claim 3 or 4 Symbol mounting monofluorophosphate oxide polymer compound is a monomer. Hydrophobic nonionic monomers include methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, butyl (meth) acrylate, pentyl (meth) acrylate, hexyl (meth) acrylate, ( meth) acrylate, 2-ethylhexyl (meth) acrylate, octyl (meth) acrylate, stearyl (meth) acrylate, cyclohexyl any of claims 3-5 which is a monomer selected from (meth) acrylic acid benzyl, and styrene The monofluorophosphorylated polymer compound according to claim 1. Said (B) is hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, methyl cellulose, ethyl cellulose, cellulose scan or monofluorophosphate oxide polymer compound according to claim 1 wherein the hydroxypropyl starch.

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