JP2000143440A - Bactericidal agent comprising string-shaped giant micelle - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a bactericidal agent comprising a string-shaped giant micelle, capable of effectively residing in tissue of oral cavity and skin, and capable of effectively exhibiting a strong bactericidal action for a long period. SOLUTION: This bactericidal agent comprises a string-shaped giant micelle comprising a cationic bactericidal agent and an anionic additive and having viscoelasticity, wherein an alkylpyridinium compound is preferably used as the cationic bactericidal agent, and a salicylic acid salt, etc., is preferably used as the anionic additive.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a bactericidal agent consisting of giant string-like micelles which stay on the mucous membrane or skin surface of a living body for a long time and have excellent bactericidal effect and have viscoelasticity.

[0002]

2. Description of the Related Art
Various bactericides are blended as active ingredients in cosmetics and the like, and the bactericidal action has been effective in inhibiting plaque formation and preventing gingivitis in the oral cavity, and washing, disinfecting, and disinfecting the skin and mucous membranes. .

However, according to the study of the present inventors,
The germicidal properties and duration of the bactericidal power of these bactericides are very short, and it is difficult to say that cosmetics or the like containing the above-mentioned bactericides show sufficient bactericidal and cleaning effects. It is desired to improve.

The present invention has been made to meet the above-mentioned demands, and has as its object to provide a bactericidal agent which stays on the surface of a living body including an oral cavity for a long time and has an excellent bactericidal effect.

[0005]

Means for Solving the Problems and Embodiments of the Invention The inventors of the present invention have made intensive studies on retaining a bactericide on the surface of a living body for a long time and exerting its bactericidal effect sufficiently. As is evident, when a large string-like micelle having viscoelasticity is formed by using a cationic fungicide in combination with an anionic additive, unexpectedly, the retention of the huge string-like micelle fungicide on the biological surface is surprising. It has been found that the bactericidal effect is effectively exhibited over a long period of time, the bactericidal effect is improved, and the above object can be achieved.

That is, a surfactant in an aqueous medium forms a molecular aggregate at a critical micelle concentration or higher. In this case, the most common form of micelles is spherical micelles, but depending on the concentration of the surfactant and the polarity of the dispersion medium, other molecular aggregates, for example, disk-shaped or rod-shaped, also appear. It is known. The concentration at which micelles other than spheres appear largely depends on the chemical structure of the surfactant, the presence or absence of added salts, and the concentration. Giant string-like micelles are micellar systems in which string-like micelles are formed from fairly low concentrations and have a pronounced viscoelasticity due to their entanglement. Such a giant micelle system is also formed by a system of sodium lauryl sulfate or a nonionic surfactant, but giant string-like micelles having viscoelasticity include, in particular, cetyltrimethylammonium bromide, cetylpyridinium bromide, etc. It is known to form in systems with added salts ("Surface" 1991, 399, 29; "Surface" 1997, 10, 35).

The present inventor has proposed an anionic additive capable of forming a giant string micelle with such a cationic surfactant (cationic bactericide) and the cationic surfactant such as salicylic acid or a salt thereof. The present inventors have found that giant string-like micelles having viscoelasticity and staying on a living mucous membrane or skin surface for a long time to give an excellent bactericidal effect, and have accomplished the present invention.

Hereinafter, the present invention will be described in more detail.
The fungicide of the present invention is a viscoelastic giant string micelle fungicide comprising a cationic fungicide and an anionic additive.

As the cationic bactericide used in the present invention, alkylpyridinium, which is also a cationic surfactant, and other cationic surfactants are suitably used.

[0010] Examples of the alkylpyridinium salt include cetylpyridinium chloride and cetylpyridinium bromide. Other cationic germicides include, in particular, mono-long-chain alkyltri-short-chain alkylammonium salts such as cetyltrimethylammonium chloride and cetyltrimethylammonium bromide. Among them, those having 14 to 16 carbon atoms of a hydrophobic group such as cetylpyridinium chloride, cetylpyridinium bromide, cetyltrimethylammonium chloride and cetyltrimethylammonium bromide are preferred. Other cationic germicides include benzethonium chloride and benzalkonium chloride. In addition, these cationic fungicides can be used individually by 1 type or in combination of 2 or more types.

On the other hand, examples of the anionic additive include salicylic acid and salicylates such as sodium salicylate and potassium salicylate. One of these can be used alone, or two or more can be used in combination.

The bactericide of the present invention is formed by forming the viscoelastic giant string micelle with the cationic bactericide and the anionic additive. In this case, the cationic bactericide and the anionic additive are used. Is a weight ratio of 1:
0.05 to 1:20 is desirable, and 1 is more desirable.
0.1 to 1:10. When the amount of the anionic additive is too small, giant string-like micelles are not formed, and sufficient bactericidal properties and retention properties at the application site are not exhibited. On the other hand, when the amount of the anionic additive is too large, the formation of the giant micelles does not proceed any more, and the formation of the giant string-like micelles once formed may be suppressed by the excess additive.

The bactericide of the present invention can be used for cosmetics for oral cavity, hair, skin, etc., for example, toothpaste, liquid toothpaste,
Oral cosmetics applied to oral tissues such as dentifrices such as Jinsei toothpaste, mouthwashes, tablets, chewing gum, mouth fresheners, hair cosmetics applied to hair such as shampoos, rinses, hair tonics, hair creams, hair treatments, Basic cosmetics and packs that are suitable for skin, such as body cosmetics such as body shampoo, body cream and body lotion, burnishing cream, nourishing cream, emollient cream, cold cream, hand cream, lotion and cleansing cream , Suntan cream, suntan oil, depilatory,
Special cosmetics such as antiperspirants, hair tonics, hair liquids,
It is preferably blended in male cosmetics such as hair cream, pomade, shaving cream, shaving lotion and the like.

In this case, it is preferable that the above-mentioned cationic bactericide is added to these compositions so as to be 0.005 to 4% (% by weight, hereinafter the same), particularly 0.01 to 2%. If the amount is too small, giant string-like micelles may not be formed, and sufficient sterilization may not be exhibited.
If the amount is too large, an unpleasant taste and astringency may occur when applied to the oral cavity, and a pruritus may rarely occur when applied to the skin. On the other hand, the anionic additive is contained in the composition in an amount of 0.01%.
It is preferable to mix so as to be 5 to 5%, particularly 0.05 to 1%. If the amount is too small, giant string-like micelles with the cationic germicide cannot be formed, and a sufficient bactericidal effect cannot be exhibited, and the retention duration at the application site becomes insufficient. On the other hand, if the amount is too large, a peculiar off-taste may be felt when applied to the oral cavity, and in rare cases when applied to the skin, redness and itching may appear.

As the components of the composition such as the above-mentioned cosmetics and the like, known appropriate components can be used in a usual amount according to the kind and purpose, and can be prepared according to a conventional method.

[0016]

Industrial Applicability The giant string micellar fungicide of the present invention effectively stays in oral tissues and skin, and exhibits a high sterilizing power over a long period of time.

[0017]

EXAMPLES The present invention will be specifically described below with reference to examples and formulation examples, but the present invention is not limited to the following examples.

Example 1 The following experiment was carried out for the purpose of examining the adsorption and retention of giant string-like micelles on teeth. After adsorbing 20 mg of hydroxyapatite (BIO-GEL HTP; manufactured by Bio-Rad; hereinafter abbreviated as HA) in 20 mg of physiological saline, saliva from which bacterial cells, food residues and the like were removed was added to saliva.
It was coated with a saliva component (pellicle) by immersion for an hour. After washing the saliva-coated HA with physiological saline,
2 mL of the test solution shown in Table 1 was added, followed by gentle stirring at 37 ° C. for 20 minutes. After the treatment, the HA was washed with physiological saline, and the adsorbed and retained giant string micelles were separated from acetonitrile:
HA was extracted from the HA by adding 2 mL of a 0.1% phosphoric acid = 1: 3 solution and stirring for 30 seconds, and quantified using a high performance liquid chromatograph (HPLC) under the following conditions. (1) HPLC quantitative condition (salicylate) Column: Inertsil C8, 250 × 4.6 mm I.C. D Mobile phase: acetonitrile: 0.1% phosphoric acid = 1: 3 Elution rate: 1.0 mL / min. Detector: UV 254 nm Column temperature: 40 ° C. (2) HPLC quantification conditions (cationic activator) Column: Inertsil C8, 150 × 4.6 mmI. D Mobile phase: acetonitrile: 0.1 M Na perchlorate = 3: 2 Elution rate: 1.0 mL / min. Detector: RI Column temperature: 40 ° C. Retain antimicrobial activity HA 10 mg, add 200 μL of sterile physiological saline, and repeat washing twice. 200 μL of the test solution of Table 1 was added,
Let stand for 3 minutes at room temperature. Then, sterile physiological saline 200
Wash twice with μL to remove excess sample solution. TH
It was added B medium (DIFCO Inc.) 200 [mu] L, repeating the two-step dilutions each HA beads to 8 times (dilution 2 ¹ -
²⁸ ). 100 μL of THB medium was added, and the final volume was 200 μL.
μL. S. mutans 10449 bacterial solution 20μ
L was ingested and anaerobically cultured at 37 ° C. for 18 hours, and the degree of development was visually observed. Macroscopic criteria ×: 2 ¹ ~2 ³ dilution (high concentration) in stunted antibacterial activity △: 2 ⁴ ~2 ⁶ dilution (medium density) in stunted antibacterial activity ○: 2 ⁷ ~2 ⁹ Growth inhibition and antibacterial activity at low dilutions

[0019]

[Table 1]

Example 2 The following experiment was conducted for the purpose of examining the adsorption and retention of giant string micelles on mucous membranes and skin. Adsorption amount Collagen membrane (Nippi, hereinafter abbreviated as CM) 40mg
Was washed with physiological saline, and then immersed in saliva from which cells, food residues and the like had been removed for 1 hour, thereby coating with saliva components (pellicle). After washing the saliva-coated HA with physiological saline, 2 mL of a test solution shown in Table 2 was added thereto.
Gently stirred for 20 minutes. After the treatment, the CM was washed with physiological saline, and the adsorbed and retained giant string micelles were extracted from the CM by adding 2 mL of acetonitrile: 0.1% phosphoric acid = 1: 3 solution and stirring for 30 seconds. Then, quantification was performed using a high performance liquid chromatograph (HPLC) under the following conditions. (1) HPLC quantitative condition (salicylate) Column: Inertsil C8, 250 × 4.6 mm I.C. D Mobile phase: acetonitrile: 0.1% phosphoric acid = 1: 3 Elution rate: 1.0 mL / min. Detector: UV 254 nm Column temperature: 40 ° C. (2) HPLC quantification conditions (cationic activator) Column: Inertsil C8, 150 × 4.6 mmI. D Mobile phase: acetonitrile: 0.1 M Na perchlorate = 3: 2 Elution rate: 1.0 mL / min. Detector: RI Column temperature: 40 ° C. Antibacterial activity 200 μL of sterile physiological saline is added to CM having a diameter of 10 mm, and washing is repeated twice. Add 200 μL of the test solution in Table 2 and allow to stand at room temperature for 3 minutes. Thereafter, the sample is washed twice with 200 μL of sterile physiological saline to remove excess sample solution. The treated CM was placed at the center of a blood agar medium uniformly coated with Staphylococcus aureus and anaerobically cultured at 37 ° C. for 48 hours.
The degree of growth of bacteria around the CM when the CM was removed was visually observed. Visual judgment criteria ×: Bacterial growth inhibition circle with a diameter of 0 to 10 mm Δ: Bacterial growth inhibition circle with a diameter of 10 to 20 mm ○: Bacterial growth inhibition circle with a diameter of 20 mm or more

[0021]

[Table 2]

Hereinafter, examples of the composition of the fungicide of the present invention are shown. [Formulation Example 1] Toothpaste Silicic anhydride 20% Xylitol 5 Sorbitol 10 Xanthan gum 1 Carboxymethylcellulose 1.5 Sodium lauryl sulfate 1.5 Saccharin sodium 0.5 Sodium salicylate 0.2 Cetylpyridinium chloride 0.02 Perfume 1.0 Water Appropriate amount 100% in total

[Formulation Example 2] Liquid dentifrice Silicic anhydride 30% Sorbit 20 Glycerin 40 Propylene glycol 4 Carrageenan 1 Saccharin sodium 0.1 Sodium lauryl sulfate 2 Salicylic acid 0.15 Cetyltrimethylammonium chloride 0.03 Fragrance 1.2 Water 100%

[Formulation Example 3] Liquid dentifrice xylitol 6% ethanol 8 polyoxyethylene hydrogenated castor oil 0.7 citric acid 0.02 sodium citrate 0.2 glycerin 2 saccharin sodium 0.1 sodium salicylate 0.2 cetylpyridinium chloride 0 .02 Perfume 0.4 Water Dosage meter 100%

[Formulation Example 4] Liquid dentifrice Sorbitol 5% Tranexamic acid 0.05 Citric acid 0.01 Sodium citrate 0.2 Ethanol 5 Saccharin sodium 0.1 Sodium salicylate 0.2 Cetylpyridinium chloride 0.01 Water-soluble fragrance 0 .5 water dosage meter 100%

[Formulation Example 5] Shampoo triethanolamine alkyl sulfate 15% lauric acid diethanolamide 4 ethanolamine qs paraoxybenzoate 0.5 sodium salicylate 0.2 cetyltrimethylammonium chloride 0.03 fragrance 0.3 legal dye trace Water dosage meter 100%

[Formulation Example 6] Lotion Locus of magnesium ascorbate phosphate 4% Propylene glycol 2 Oxybenzone 5 Citric acid Appropriate amount Paraoxybenzoate 0.4 Salicylic acid 0.1 Cetyltrimethylammonium bromide 0.01 Perfume 0.2 Legal dye Trace water appropriate meter 100%

[Formulation Example 7] Pack Sorbit 5% titanium oxide 10 kaolin 5 polyvinyl alcohol 10 paraoxybenzoate 0.5 dimethylsiloxane / methyl (polyoxy10 ethylene) siloxane copolymer sodium salicylate 0.1 cetylpyridinium chloride 0. 01 Fragrance 0.5 Legal dye Trace water qs 100%

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI theme coat ゛ (reference) // A61K 7/075 A61K 7/075 7/16 7/16 F term (reference) 4C076 AA09 AA12 BB22 BB31 CC41 DD02 DD37 DD38 DD43 DD58 EE06 EE27 EE33 FF17 FF31 FF63 GG45 4C083 AB172 AB242 AB442 AC102 AC122 AC132 AC302 AC432 AC472 AC482 AC542 AC622 AC692 AC782 AC852 AC862 AD112 AD152 AD272 AD352 BB48 CC04 CC07 CC38 CC41 4C083 AA30 MA57B

Claims (1)

[Claims] A viscoelastic giant string micelle fungicide comprising a cationic fungicide and an anionic additive.