WO2001051530A1

WO2001051530A1 - Lowly irritant high-molecular antimicrobial agent

Info

Publication number: WO2001051530A1
Application number: PCT/JP2001/000167
Authority: WO
Inventors: Isei Hisamitsu; Hodaka Ito; Masanori Uda; Tatsu Miyamoto; Takao Ishida; Masaharu Ikemori
Original assignee: Fancl Corporation
Priority date: 2000-01-14
Filing date: 2001-01-12
Publication date: 2001-07-19
Also published as: JP3786874B2; JPWO2001051530A1

Abstract

A lowly irritant and lowly skin-penetrant antimicrobial polymer to be added to antimcirobial preparations, external preparations for the skin, detergent compositions, and so on, which polymer comprises an antimicrobial monomer and is substantially free from monomers or oligomers; a process for producing the polymer by anionic polymerization; and antimicrobial preparations, external preparations for the skin, and detergent compositions, containing the polymer.

Description

Specification

Hypoallergenic polymer antibacterial agent

[Technical field]

The present invention relates to an antibacterial polymer, a method for producing the same, and an antibacterial agent, a skin external preparation or a detergent composition containing the antibacterial polymer.

[Background technology]

In recent years, consumers have been interested in skin irritation of external preparations such as pharmaceuticals and cosmetics, and there has been a demand for the development of less irritating raw materials. Most skin irritation is caused by the penetration of the raw material through the stratum corneum and into the skin. Antimicrobial agents are necessary for preserving external preparations and cleaning compositions, but it is not necessary that the antimicrobial agents penetrate into the skin, and it is desirable that they do not penetrate into the skin from the viewpoint of irritation. One of the solutions is to increase the molecular size of antibacterial agents and reduce skin permeability.

For example, as an ultraviolet absorber, a polymer obtained by polymerizing a monomer having an ultraviolet absorbing group into a polymer has been proposed (JP-A-3-22013, JP-A-6-73336). No. 9, Japanese Patent Application Laid-Open No. H10-231341, Japanese Patent Application Laid-Open No. H10-231468).

Antibacterial agents include those called antibacterial active polymers or polymer antibacterial agents that aim at low toxicity and low irritation, and polythion-type antibacterial agents have been studied in the past. No. 2, p87, 1995). However, the use of cationic antibacterial agents has been limited because the effects of the salts are lost due to the presence of salts.

Poly-P-vinylphenol has been reported as a nonionic antibacterial polymer (antibacterial and antifungal vol.8, No.9, pi, 1980). In thermal polymerization and radical polymerization), a large amount of monomer remains and skin irritation cannot be reduced. [Disclosure of the Invention]

An object of the present invention is to provide an antibacterial polymer having low skin permeability and low irritation, which is suitably blended in an antibacterial agent, an external preparation for skin, or a cleaning composition, and a method for producing the same. .

The present inventors have conducted intensive studies to solve the above problems, and as a result, synthesized a polymer having an antibacterial monomer as a polymerization component by controlling the molecular weight distribution, and obtained a residual monomer, and a dimer, The inventors have clarified that a material having low skin permeability and low irritation can be obtained by eliminating oligomers such as trimers to such an extent that they are not substantially contained, thereby completing the present invention.

That is, the present invention is a polymer containing an antimicrobial monomer as a polymerization component and containing substantially no monomer or oligomer.

In the present invention, the antibacterial monomer has the general formula (I)

Hydro represented by

Or the general formula (II) CH ₂ two C- R

I

c = o

I

N H

I

Y (I D

(Meth) acryloylamines represented by the formula: In the present invention, the term “(meth) atalyloylamines” refers to acryloylamines and / or metaatalyloylamines.

Further, the polymer of the present invention may be a polymer containing a copolymer component other than the antibacterial monomer, and a vinyl monomer is preferable as the copolymer component.

The polymer of the present invention is preferably produced by an anion polymerization method. Furthermore, the present invention also relates to an antibacterial agent, an external preparation for skin and a detergent composition containing the polymer.

In the present invention, since the antibacterial polymer contains substantially no monomer or oligomer, skin irritation caused by permeation of the low-molecular antibacterial agent through the skin can be reduced. The substantially free of monomer or oligomer one present invention, the analysis results by the gel permeation click port Matogurafi one (GPC), although containing organic amount of monomer and oligomer refers to a 5 weight ^_0/0 or less, It is more desirable that monomers and oligomers are not detected by GPC.

The monomer constituting the polymer of the present invention is a compound having both a molecular structure having antibacterial activity and a polymerizable molecular structure. Molecular structures having antibacterial activity include, for example, quaternary ammonium salts, biguanides, phosphonium salts, pyridinium salts, phenol, benzoic acid, 2-hydroxy-2,4,6-cycloheptatrienone, stipitatic acid, polyvalent Functional groups composed of alcohols and the like are included. Examples of the polymerizable molecular structure include functional groups consisting of ethylene, propene, amino group, and carboxyl group. Can be.

As a typical example of the monomer, for example, the general formula (I)

ol

H

(I)

(Where n is an integer of 0 to 2 and X represents a hydrogen atom or a halogen atom). In this case, the bonding position of the hydroxyalkyl group to the ethylene group is not limited, but it is preferable that the hydroxyl group is bonded to the para position. Among the monomers represented by the general formula (I), a particularly preferred monomer is P-hydroxystyrene.

Further, examples of the monomer include, for example, a compound represented by the general formula (II)

CHU two C—R

I

C20

I

NH

I

Y (I I)

(Where Y is a polyhydric alcohol structure composed of an alkyl chain and a hydroxyl group, and R represents a hydrogen atom or a methyl group). (Meth) acryloylamines can also be mentioned. . Monomers represented by the general formula (II) include N- (l, 3-dihydroxyl-oxybutyl) acrylamide (Y = -CH ₂ -CHOH-CH ₂ -CH ₂ OH), N- (l , 2-dihydroxypentyl) acrylamide (Y =-(CH ₂ ) ₃ CHOH-CH ₂ OH). N-acrylonitrile (hydroxymethyl) aminomethane (Y = C (CH ₂ OH) ₃ ) is preferred.

A polymer substantially free of monomers and oligomers can be produced, for example, by the following method. Anion polymerization method

Anion polymerization initiators include, for example, alkyllithium, metal naphthalene, Grignard reagents, dialkylmagnesium, metal alkoxides, pyridine, etc.Select an appropriate initiator in relation to physical properties such as the resonance stabilization energy of the monomer be able to.

The initiator is added to the reaction system in the entire amount at once. The reaction temperature is desirably in the range of 150 to 0 ° C, particularly -100 ^^-40 ° C. The anion polymerization is generally performed under a high vacuum called a break seal method, but can also be performed under an argon atmosphere or a nitrogen atmosphere.

The average molecular weight of the obtained polymer can be controlled by the amount of the initiator used and the reaction time.

The reaction is stopped by adding a compound having active hydrogen, for example, water or methanol.

After completion of the reaction, impurities, by-products, a solvent, and the like are separated from the reaction mixture by a solvent precipitation method, a solvent extraction method, or the like, so that a desired polymer can be obtained. Production method 2: Fractionation method

From a polymer synthesized by any polymerization method such as thermal polymerization or radical polymerization, only a polymer with a specific molecular weight is separated using a device that can be separated according to molecular weight, for example, GPC (gel permeation chromatography). Production method 3: Method using peptide synthesizer

When the target polymer material is a peptide, it can be produced, for example, as follows using a peptide synthesizing apparatus which has been remarkably developed in recent years.

A resin to which the carboxyl group end of 9-fluorenylmethyloxycarbonyl (Fmoc) amino acid is bonded is packed into a column, the Fmoc protecting group is removed, and the amino group is released. Let it form (force ring).

By repeating the above deprotection and coupling, a peptide having the target amino acid sequence is synthesized from the carboxyl terminal to the amino terminal. After the elongation of the peptide chain is completed, the target peptide is obtained by cleaving from the resin and then removing the protecting groups of the Fmoc and amino acid side chains.

Although the step of forming peptide bonds proceeds with a reaction yield of 99% or more, the final product is a mixture of impurities, and is purified by high-performance liquid chromatography (HPLC). Although the molecular weight of the polymer of the present invention is not particularly limited, the number average molecular weight is preferably 1,000 or more, and particularly preferably 2,500 or more, in order to exhibit the effect of reducing skin irritation. From the viewpoint of reducing skin irritation, the higher the molecular weight, the better. However, since the antibacterial activity decreases as the molecular weight increases, the molecular weight is preferably 100,000 or less, particularly 50,000 or less. For example, the molecular weight of the polymer of the present invention can be selected preferably from 1,000 to: L00,000, particularly preferably from 2,500 to 50,000.

Further, the molecular weight distribution of the polymer of the present invention is preferably narrow. When the molecular weight distribution is represented by the ratio Mw / Mn between the weight average molecular weight (Mw) and the number average molecular weight (Mn), Mw / Mn is preferably 1.4 or less, particularly 1.2 or less, and particularly preferably 1.15 or less. Further, the polymer of the present invention can contain one or more kinds of monomers, if necessary, as a copolymer component in the antibacterial monomer as long as the effects of the present invention are not impaired. Copolymerizable monomers include, for example, hydroxyshethyl methacrylate, hydroxyshethyl acrylate, N, N-dimethylaminopropylacrylamide, N-bulpyrrolidone, N-isopropylamide, 2-meta Atariloyloxyethyl phosphorylcholine and the like. The amount of the copolymer component other than the antibacterial monomer is 90% by weight or less, preferably 70% by weight or less. The polymer of the present invention can be widely applied as a component with low skin irritation to cosmetics, detergents, pharmaceuticals, quasi-drugs, etc. applied to the outer skin, and its dosage form is also aqueous, solubilizing It can take a wide range of dosage forms such as system, emulsification system, powder system, oil system, gel system, ointment system, aerosol system, water-oil 2-layer system, water-oil-powder 3-layer system. In other words, if it is a basic cosmetic, it can be widely applied in the form of facial cleanser, lotion, milky lotion, cream, gel, essence (cosmetic), pack mask, shaving cosmetic, etc. It is. Further, if it is a drug or a quasi-drug, it can be widely applied to various ointments and the like. And the dosage form and form which the polymer of the present invention can take are not limited to these dosage forms and forms. According to the present invention, known base components are widely used and blended according to the desired dosage form and form as long as the desired effects of the present invention are not impaired by their blending. be able to.

That is, natural animal and vegetable oils such as olive oil, avocado oil, rice oil, grape seed oil, macadamia nut oil, corn oil, rapeseed oil, castor oil, castor oil, coconut oil, sucrose, beef tallow, horse oil, egg yolk oil, etc. Waxes such as jojoba oil, beeswax, candelilla wax, carnauba wax and lanolin; polybutene, squalane, Hydrocarbons such as liquid paraffin, paraffin, petrolatum; lauric acid, myristic acid, noremitic acid, stearic acid, behenic acid, oleic acid, isostearic acid, linoleic acid, linolenic acid, hydroxyxtearic acid, etc. Fatty acids such as cetanol, stearyl alcohol, behenyl alcohol, octynoledodecanol, cholesterol and phytosterol; and higher alcohols; isonoel isononanoate, isosecetyl octanoate, octyldodecyl myristate, and no. Esters such as isopropyl luminate, isocetyl stearate, and glyceryl tri-2-ethylhexanoate; silicone oils such as methylpolysiloxane, methylhydrogenpolysiloxane, pentasiloxane with decamethinole resin, and methylphenyl / repolysiloxane; Polyhydric alcohols such as ethylene glycol, glycerin, diglycerin, 1,3-butylene glycol, 1,2-pentanediol; saccharides such as sorbitanore, mannitol, glucose, maltitol; gum arabic, carrageenan, xanthan gum, guar gum, Water-soluble polymers such as carboxyvinyl polymer and alkyl-modified carboxyvinyl polymer; organic solvents such as ethanol; powders such as titanium dioxide, myric, talc, kaolin, and titanium dioxide-coated mica; Nonionic surfactants such as tyleneoctyldodecyl ether, polyoxyethylene polyoxypropylene lauryl ether, ethylene glycol monostearate, polyoxyethylene sorbitan tristearate, and polyoxyethylene hydrogenated castor oil; stearyltrimethylammonium Cationic surfactants such as dimethyl chloride, benzalkonium chloride, laurylamine oxide; anionic surfactants such as sodium panolemitate, sodium laurate, potassium lauricular sulfate, alkyl sulfate triethanolamine ether, and acylmethyltitanate Antioxidants or antioxidants such as tocopherol, propyl gallate, ascorbic acid, and quinic acid; fresheners such as menthol, potato oil, methyl salicylate; pigments; ; Or according to the formulation in accordance with the desired dosage form of purified water and the like, it may be used in combination. Specific of the present invention Examples of prescribing examples will be described in Examples described later. [Brief description of drawings]

FIG. 1 shows an NMR spectrum of the poly (P-hydroxystyrene) obtained in Synthesis Example 1.

FIG. 2 shows a gel-permeation chromatograph of the poly (P-hydroxystyrene) obtained in Synthesis Example 1.

FIG. 3 shows a comparison of the molecular weight and molecular weight distribution of the poly (P-hydroxystyrene) obtained in Synthesis Example 1 and a commercially available poly (P-hydroxystyrene).

[Best Mode for Carrying Out the Invention]

Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto. Synthesis example

Synthesis of P-hydroxystyrene

200 ml of a 1.5 mol / l potassium hydroxide aqueous solution was added to 0.1 mol of P-acetoxystyrene, and the mixture was hydrolyzed for 3 hours. Carbon dioxide was bubbled into the solution after the reaction to obtain a white precipitate. The white precipitate was purified by a recrystallization method using n-hexane to obtain 0.067 mol of P-hydroxystyrene (yield 67%). 0.037 mol of the P-hydroxystyrene obtained above was dissolved in 0.08 mol of triethylamine, and a solution of 0.04 mol of tert-butyldimethylchlorosilane in tetrahydrofuran was added at 145 ° C., and the mixture was reacted for 24 hours. After the reaction, add distilled water and vigorously After shaking, the mixture was allowed to stand, the aqueous phase was discarded, and then tert-butyl dimethyl / resilyloxystyrene was obtained by distillation under reduced pressure.

Synthesis of poly (tert-butyldimethylsilyloxystyrene)

5 nmol of tert-butyldimethylsilyloxystyrene obtained above was dissolved in 10 ml of tetrahydrofuran under an atmosphere of argon, 20 mmol of triethylamine was added, and n-butyllithium lOmmol of a polymerization initiator was added. The reaction was carried out for 15 minutes, and the reaction was stopped by adding methanol. Poly (tert-butyldimethylsilyloxystyrene) was recovered from the reaction mixture.

Synthesis of poly (P-hydroxystyrene)

0.5 g of the poly (tert-butyldimethylsilyloxystyrene) obtained above was dissolved in 10 ml of acetone, and 1 ml of hydrogen bromide was added. The mixture was refluxed at 50 ° C for 3 hours, and the obtained reaction mixture was distilled water. Was added dropwise to obtain poly (P-hydroxystyrene) as a precipitate. Synthesis example 2

Synthesis of poly (tert-butyldimethylsilyloxystyrene-trimethylsilyloxhexyl methacrylate) block polymer

5 mmol of tert-butyldimethylsilyloxystyrene obtained in Synthesis Example 1 was dissolved in 10 ml of tetrahydrofuran under an argon atmosphere, 20 mmol of triethylamine was added, and 13 mmol of a polymerization initiator n-butyllithium was added. The reaction was carried out at 15 ° C for 15 minutes. Next, 13 mmol of diphenylethylene was added by a syringe and the mixture was further reacted for 10 minutes. Then, 5 mmol of trimethylsilyloxhexyl methacrylate was added by a syringe and reacted for 10 minutes, and methanol was added to stop the reaction.

Synthesis of poly (P-hydroxystyrene-hydroxyxenotin methacrylate) block polymer

Poly (tert-butyldimethylsilyloxystyrene-trimethylsilinole obtained above) Dissolve 0.5 g of block polymer in 10 ml of acetone, add 1 ml of hydrogen bromide, reflux at 50 ° C for 3 hours, and drop the resulting reaction mixture into distilled water. Poly (P-hydroxystyrene-hydroxyshethyl methacrylate) block polymer was obtained as a precipitate. Synthesis example 3

Synthesis of N-acryloyl tris (trimethylsilyloxymethyl) amino methane

0.05 mol of N-atalylitol tris (hydroxymethyl) aminomethane was dissolved in O.lmol of triethylamine, and a solution of 0.055 mol of trimethylchlorosilane in tetrahydrofuran was added at _45 ° C and reacted for 12 hours. After completion of the reaction, distilled water was added, and the mixture was vigorously shaken. After standing still, the aqueous phase was discarded. Thereafter, N-acrylonitrile (trimethylsilyloxymethyl) aminoaminomethane was obtained by distillation under reduced pressure.

Poly (N-acryloyltris (trimethylsilyloxymethyl) amino methane)

5mniol of N-acryloynoretris (trimethylsilyloxymethyl) aminomethan obtained above was dissolved in 10ml of tetrahydrofuran under an argon atmosphere, 20mmol of triethylamine was added, and the polymerization initiator n-butyllithium lOmmol was added. The reaction was carried out at 74 ° C for 20 minutes, and the reaction was stopped by adding methanol. Poly (N-acrylonitrile (trimethylsilyloxymethyl) aminomethane) was recovered from the reaction mixture.

Synthesis of poly (N-acryloyltris (hydroxymethyl) aminomethane)

0.4 g of the poly (N-acrylonitrile (trimethylsilyloxymethyl) aminomethane) obtained above was dissolved in 10 ml of acetone, 2 ml of hydrochloric acid was added, and the mixture was refluxed at 50 ° C. for 3 hours. The mixture was dropped into getyl ether to obtain poly (N-acryloyl tris (hydroxymethyl) amino methane) as a precipitate. Physical property measurement

The poly (P-hydroxystyrene) obtained in Synthesis Example 1 above was a pale yellow powder, and its structure was confirmed by 400 MHz Ή-NMR (JXM-EX400 manufactured by JEOL Ltd.) (FIG. 1.0 ppm = Standard, 0.8-2.4 ppm = CH ₂ —CH, 3.3 and 4.9 ppm = solvent, 6.3-6.8 ppm = aromatic ring). The molecular weight and molecular weight distribution were measured by GPC (columns GPC806, 804,802 in series, manufactured by Shimadzu Corporation) (Fig. 2). As a result of the measurement, it was confirmed that a polymer having a number average molecular weight of 2945, a weight average molecular weight of 3377, a molecular weight distribution of 1.15, a narrow molecular weight distribution, and no residual monomers, dimers, trimers, etc. was synthesized. . The molecular weight distribution is shown in Fig. 3 in comparison with commercially available poly (P-hydroxystyrene). C in Fig. 3 is the poly (P-hydroxystyrene) from this synthesis example, A is a commercial product A (Marcarinka I MS-1 manufactured by Maruzen Petrochemical Co., Ltd.), and B is a commercial product B (Maruzen Petrochemical) Marcalinka MS S-2). In the product of the present invention, a peak identified as a monomer, dimer, or trimer is not detected, whereas in a commercial product, a peak identified as a monomer, dimer, or trimer appears. When the monomer and oligomer contents were calculated from the area ratio, it was found that A was 23.4% and B was 6.0%.

The poly (P-hydroxystyrene-hydroxyxethyl methacrylate) block polymer obtained in Synthesis Example 2 and the poly (N-acryloyl tris (hydroxymethyl) aminomethane) obtained in Synthesis Example 3 were also As in Synthesis Example 1, the structure was confirmed by 400 MHz Ή-NMR, the molecular weight and the molecular weight distribution were measured by GPC, and the polymer having a narrow molecular weight distribution and no residual monomer, dimer, trimer, etc. It was confirmed that was synthesized. Antibacterial measurement

The poly (P-hydroxystyrene) obtained in Synthesis Example 1 and the poly (P-hydroxystyrene) obtained in Synthesis Example 2 Roxystyrene-hydroxyxethyl methacrylate) block polymer (hereinafter sometimes referred to as poly (P-hydroxystyrene-block-hydroxyxethyl methacrylate)) and the poly ( The antibacterial activity of N-acryloyl tris (hydroxymethyl) aminomethane against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida and mold was evaluated by a challenge test method based on USP XXII. As comparative examples, a solution containing no antibacterial agent, methylparaben known as an antibacterial agent, P-hydroxystyrene as a monomer, N-acryloyl tris (hydroxymethyl) amino methane and poly (P-vinyl) were used. The antimicrobial activity of commercial products A and B of phenol was also measured (Table 1). Based on USP XXII, bacteria decreased to less than 0.1% of inoculated bacteria within 14 days, and then 0.1% or less to 28 ° C, and fungi within 14 days equal to or less than inoculated bacteria, and thereafter A pass (〇) was made if the same was held until the 28th. Antibacterial activity evaluation results

〇: Bacterial survival rate is below standard value

X: Bacterial viability is above the reference value From the results, it was found that the compound of the present invention showed sufficient antibacterial activity against a wide variety of bacteria such as bacteria, Candida, and rot, similarly to conventional antibacterial agents. Measurement of skin permeability

Three-dimensional cultured skin model sandwiched between (LSE-Hi _g h, Toyobo Co., Ltd.) a lateral second chamber one diffusion cell, phosphate buffered saline antimicrobial agent to the donor side, placed in phosphate buffered salt solution receiver side Was. The system was maintained at 37 ° C, and after a predetermined time, the donor side and the receiver side were sampled, the drug amount ratio between the donor side and the receiver side was measured by HPLC, and the transmittance was calculated (Table 2).

Table 2 Three-dimensional cultured skin model transmittance

From the results, it was confirmed that the skin permeability of the compound of the present invention was significantly reduced by the polymerization. Stimulus measurement

Using a three-dimensional cultured skin model (LSE-high, manufactured by Toyobo Co., Ltd.), a toxicity test on human fibroblasts was performed. In the test, the test substance dissolved in an appropriate solvent for which no irritation was confirmed was applied to LSE-high for a predetermined time. After that, the living cells absorb MTT (3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium bromide). It was when using the MTT Atsusi method for determining the cell viability from the intensity of blue-violet product is emitted, the concentration was calculated (EC ₅₀ value) showing 50% cell viability (Table 3).

Table 3

Toxicity test for human fibroblasts via artificial skin

From the results, it was found that the compound of the present invention was found to penetrate into the skin as compared to the commercially available products in which methylparaben and monomers such as P-hydroxystyrene, N-acryloyl tris (hydroxymethyl) aminomethane, and monomer, dimer or trimer remain. It was confirmed that the irritation was significantly reduced. Next, a formulation example of a skin external preparation and a cleaning composition containing the hypoallergenic polymer antibacterial agent of the present invention will be described. No skin irritation or antimicrobial agent precipitation was observed in any of the skin external preparations and cleaning compositions after standing at room temperature for 3 months, and stable skin external preparations and cleaning compositions could be produced. Formulation Example 1 "O / W emulsion"

(Ingredients) (% by weight)

Microcrystalline wax 1.0 Beeswax 2.0

Adsorbed and purified lanolin 2.0

Liquid isoparaffin 30.0

Sosolebitan sesquioleate estenole 4.0

Polyoxyethylene sorbitan monooleate (20E.O.) 1.0

Aluminum stearate 0.2

Hypoallergenic antibacterial agent obtained in Synthesis Example 1 0.4

Glycerin 8.0

Purified water balance

(Production method) Add glycerin to purified water, mix and heat to 70 ° C. Heat and dissolve the other ingredients to 70 ^DC . The above-mentioned aqueous phase component is gradually added to the oil phase component while stirring, and then uniformly emulsified by a homogenizer. After emulsification, cool to 30 ° C with a heat exchanger. Formulation 2 "Facial cleansing cream"

(Ingredients) (Weight / ₀ )

N-acyl-sodium L-glutamate 25.0

Palmitic acid3.0

Polyoxyethylene polyoxypropylene dalycol 5.0

Glycerin 20.0

Maltitol 15.0

Hypoallergenic antibacterial agent obtained in Synthesis Example 1 0.4

Purified water balance

(Production method) Add glycerin and maltitol to purified water and heat to 70 ° C. Add sodium N-acyl-L-glutamate to this and dissolve (aqueous phase). On the other hand, Heating dissolved palmitic acid, polyoxyethylene polyoxypropylene da a recall were mixed by stirring added to the water phase of the above, _c Patchitesu you want to stir cooled by up to 30 ° C heat exchanger after degassing

A 24-hour human patch test was conducted on the compositions of Formulation Example 1 and Formulation Example 2 for 50 subjects, and the safety assessment to judge a positive or more reaction as positive by the primary stimulus according to Japanese standards was conducted. (Table 4).

Table 4 Patch test results

No response, ±: mild erythema, +: erythema, + erythema and edema

: Erythema and edema and papules or vesicles, + — + +: Great vesicles From the results, it was confirmed that the compound of the present invention, the external preparation for skin and the cleaning composition had no skin irritation.

[Possibility of industrial use]

Since the polymer of the present invention contains substantially no monomer or oligomer, the antibacterial activity against various bacterial species is maintained in the same manner as the antibacterial low molecular weight compound or the antimicrobial monomer, and the antibacterial low molecular weight compound is obtained. Alternatively, it has a remarkable effect that skin penetration is significantly lower than that of antibacterial monomers, and the skin is excellent in safety. Therefore, the polymer of the present invention is extremely useful as an antibacterial agent, especially as an antibacterial agent and antiseptic for skin external preparations and cleaning compositions.

Claims

The scope of the claims

1. A polymer that contains an antimicrobial monomer as a polymerization component and contains substantially no monomer or oligomer.

2. The antibacterial monomer has the following general formula (I)

(Wherein n is an integer of 0 to 2, and X represents a hydrogen atom or a halogen atom).

3. The antibacterial monomer has the following general formula (II)

CH ₂ two CR

I

C = 〇

I

NH

I

Y (I I)

(Where Y is a polyhydric alcohol structure composed of an alkyl chain and a hydroxyl group, and R is a hydrogen atom or a methyl group). Polymer.

4. The polymer according to any one of claims 1 to 3, wherein a copolymer component other than the antibacterial monomer is contained as a polymer component.

5. The polymer according to claim 4, comprising a vinyl monomer as a copolymer component.

6. The method for producing a polymer according to any one of claims 1 to 5, which is produced by an anion polymerization method.

7. An antibacterial agent containing the polymer according to any one of claims 1 to 5.

8. An external preparation for skin containing the polymer according to any one of claims 1 to 5.

9. A cleaning composition comprising the polymer according to any one of claims 1 to 5.