JP2019043848A - Oral candida bactericide and denture detergent composition - Google Patents

Abstract

The present invention provides an oral Candida bactericidal agent and a denture detergent composition which is an oral probiotic and which exerts a high bactericidal effect against Candida which is a denture-adhering microbe.
SOLUTION: An oral Candida antifungal agent comprising (A) an alkylamine oxide, (A) a denture detergent composition comprising an alkylamine oxide, and (B) (B-1) an anionic interface. The above denture cleaner composition containing an active agent and / or (B-2) a betaine amphoteric surfactant.
【Selection chart】 None

Description

  TECHNICAL FIELD The present invention relates to an oral candida fungicide having high bactericidal activity against candida bacteria, which are indigenous bacteria in the oral cavity, and a denture cleaner composition containing the same.

  Hygiene management of dentures is important for denture wearers in maintaining oral health. However, the oral care of elderly people wearing dentures is not sufficient even for healthy people, and often requires poor care for the care recipient.

Denture plaques, which are stains attached to dentures, are similar to the structure and structure of microorganisms found in normal dental plaques, but in denture plaques, the composition ratio of Candida albicans is slightly higher than dental plaques. It has been reported. Candida is known to cause oral diseases such as denture stomatitis and canker sores, among which oral candidiasis is a disease strongly associated with the elderly, and is an abnormality of Candida which is an oral habit bacteria. It is thought to develop as an opportunistic infection due to proliferation.
Therefore, denture cleansers are required to have high detergency against Candida, which adheres to dentures, as well as detergency against dirt.

  In dentures, the bad breath causing bacteria Fusobacterium nucleatum (F. nucleatum), periodontitis porphyromonas gingivalis and baionella parvula (P. gingivalis, V. parvula), the caries causing Streptococcus mutans (S) A variety of bacteria have been established such as C. albicans, which is a fungus, but the fungi such as Candida are more difficult to be killed than other bacteria, and they are used to kill fungi. It is generally considered necessary to use cationic germicides such as quaternary ammonium salts.

  However, when a cationic bactericidal agent is blended in a denture cleaner, a substance that affects the bactericidal activity can not be blended, and an anionic surfactant having a high cleansing effect on protein stains can not be blended, so There have been problems in the development of denture cleaners having high bactericidal effects and cleaning effects against protein stains.

  Patent Document 1 (Japanese Patent No. 3362403) proposes that a combination of sorbic acid or a salt thereof and benzoic acid or a salt thereof be used in combination with a mouthwash for denture users for preventing the growth of Candida bacteria in the oral cavity. Patent Document 2 (Japanese Patent Application Laid-Open No. 63-14714) proposes a denture detergent composition containing a water-soluble chitin and chitosans and having high ability to desorb Candida from the denture.

Patent No. 3362403 Japanese Patent Application Laid-Open No. 63-14714 Japanese Patent Application Publication No. 2001-510076 Patent No. 5346455 gazette Japanese Patent Application Publication No. 11-510550 Japanese Patent Application Publication No. 2014-520137

  Therefore, development of a bactericidal agent for oral cavity applicable to denture cleansers, which has high bactericidal activity against Candida which is a denture-adhering bacteria present in the oral cavity, has been desired.

  The present invention has been made in view of the above circumstances, and an object of the present invention is to provide an oral Candida bactericidal agent and a denture cleaner composition which exerts a high bactericidal effect on Candida bacteria which are indigenous bacteria in the oral cavity. .

  As a result of intensive investigations to achieve the above object, the present inventors found that alkylamine oxide is higher than Candida albicans which is an oral cavity resident and is a denture-adhering fungus that constitutes denture plaques. It was found that it exerts a bactericidal effect and is effective as a Candida bactericidal agent for oral cavity, particularly for dentures. In addition, it has been found that, by blending this alkylamine oxide as a Candida bactericidal agent into a denture detergent composition, it is possible to impart an excellent bactericidal effect to kill Candida bacteria effectively in a relatively short period of time. I came to make an invention.

More specifically, although the surfactant exhibits some degree of antibacterial and bactericidal activity, it is generally not thought or recognized that the surfactant alone can satisfactorily sterilize and clean the denture. . On the other hand, the effectiveness of the bactericidal agent differs depending on the bacterial species, and even if a certain bacterium can be killed, it is not always possible to kill even different bacteria having different bacterial species. On the other hand, in the present invention, the surfactant (A) alkylamine oxide exerts a remarkable bactericidal effect against Candida bacteria, and in particular, in denture cleaning, it can not be achieved by other surfactants. And give exceptional effects.
Furthermore, in the present invention, when the component (A) is combined with the (B) (B-1) anionic surfactant and / or (B-2) betaine amphoteric surfactant, the combination of such surfactants is excellent. It provides a bactericidal effect and a sufficient and appropriate cleansing effect, which also makes it possible to effectively sterilize and wash the denture with a relatively gentle action.

  Detergent compositions disclosed in Patent Documents 3 to 6 (Japanese Patent Publication Nos. 2001-510076, 5346455, 11-510550, and 2014-520137), and antibacterial cleaning The agent composition may be formulated with an amine oxide surfactant, and Patent Literatures 3 and 4 are the antibacterial agents of E. coli, Staphylococci and Pseudomonas aeruginosa, and Patent Literature 5 is a detergent having detergency and gloss of the surfactant. Patent document 6 is the improvement of the antibacterial and bactericidal properties of a cationic surfactant having antibacterial and bactericidal properties in a topical antibacterial detergent composition such as hand wash and body wash. From Patent Documents 3 to 6, the specific Candida bactericidal action of alkylamine oxide and its application to denture cleansers can not be recalled.

Accordingly, the present invention provides the following oral Candida albicans bactericide and a denture cleaner composition.
[1]
(A) An oral candida fungicide comprising an alkylamine oxide.
[2]
The oral-use Candida bactericidal agent as described in [1] whose (A) component is the alkyl dimethyl amine oxide whose carbon number of the alkyl group is 12-18.
[3]
(A) A denture cleaner composition comprising an alkylamine oxide.
[4]
The denture detergent composition as described in [3] whose (A) component is the alkyl dimethyl amine oxide whose carbon number of an alkyl group is 12-18.
[5]
The denture detergent composition as described in [3] or [4] which contains 0.05-20 mass% of (A) component.
[6]
Furthermore, the denture detergent composition as described in [3], [4] or [5] which contains (B) (B-1) anionic surfactant and / or (B-2) betaine amphoteric surfactant. .
[7]
The denture detergent composition as described in [6] whose (A) / (B) which shows the compounding ratio of (A) component and (B) component is 1-10 as mass ratio.
[8]
The denture detergent composition as described in [6] or [7] which contains 0.01-10 mass% of (B) components.
[9]
The denture detergent composition in any one of [3]-[8] whose content of a cationic surfactant is 0-0.03 mass%.
[10]
The denture detergent composition in any one of [3]-[9] whose content of peroxide is 0-0.03 mass%.
[11]
The denture detergent composition in any one of [3]-[10] whose pH in 25 degreeC of a composition is 5-9.
[12]
The denture detergent composition in any one of [3]-[11] prepared to the liquid formulation.

  According to the present invention, it is possible to provide an oral Candida bactericidal agent and a denture detergent composition which is an oral probiotic and which exerts a high bactericidal effect against Candida which is a denture-adhering microbe. Furthermore, according to the present invention, it is possible to provide a sufficient and appropriate cleaning effect together with the above-mentioned bactericidal effect.

Hereinafter, the present invention will be described in more detail.
In the present invention, the alkylamine oxide of the component (A) is an active ingredient of Candida microbicide, and an alkyldimethylamine oxide having 12 to 18 carbon atoms in the alkyl group can be used. Specifically, lauryl dimethylamine oxide and the like can be mentioned.
As the alkylamine oxide, trade name "Cadenax DM12D-W" (lauryl dimethyl amine oxide) manufactured by Lion Specialty Chemicals Ltd. may be used.

  The alkylamine oxide of component (A) is preferably used at a concentration of 0.05 to 20% (% by mass, hereinafter the same), and more preferably 0.05 to 10%. In order to sufficiently exert the bactericidal effect on Candida, the use concentration is preferably 0.05% or more, and it is preferably 20% or less, when it is added to the denture cleanser, the denture may be nullified. It is suitable for preventing bitterness from remaining.

In the present invention, the alkylamine oxide of the component (A) is suitably blended in a denture cleaner composition as a Candida microbicide.
The compounding amount of the alkylamine oxide of the component (A) in the denture cleaner composition is preferably such that the use concentration of the alkylamine oxide is within the above range, and preferably 0.05 to 20% with respect to the entire composition. And more preferably 0.05 to 10%.

  In addition to the alkylamine oxide of the component (A), the denture detergent composition further contains (B) (B-1) an anionic surfactant and / or (B-2) a betaine amphoteric surfactant. It is preferable to mix | blend. When the component (B) is blended, the cleaning effect on denture stains is improved. The component (B) may be either the (B-1) anionic surfactant or the (B-2) betaine amphoteric surfactant alone, but the (B-1) anionic surfactant (B-2) A betaine amphoteric surfactant may be used in combination.

Examples of the (B-1) anionic surfactant include alkyl sulfates, α-olefin sulfonates, acyl amino acid salts, acyl methyl taurine, alkyl phosphates and the like. Among them, alkyl sulfates and α-olefin sulfonates are particularly preferable from the viewpoint of detergency for denture stains.
Examples of the alkyl sulfate include sodium lauryl sulfate and the like, and commercially available products such as manufactured by Toho Chemical Industry Co., Ltd. can be used.
As the α-olefin sulfonate, an alkali metal salt such as sodium or potassium of an α-olefin sulfonic acid having 14 to 16 carbon atoms can be used, preferably an α-olefin sulfonate having 14 carbon atoms, in particular It is a sodium salt (common name; sodium tetradecene sulfonate). These are commercially available products that can be used for oral preparations, for example, trade name “K Lipolan PJ-400CJ (powder)” and “Lipolan LB-440 (liquid) manufactured by Lion Specialty Chemicals Co., Ltd. ) Can be used.

(B-2) Betaine As the amphoteric surfactant, alkyl acetate betaine, fatty acid amidopropyl betaine, alkyl-N-carboxymethyl-N-hydroxyethyl imidazolinium betaine and the like can be mentioned.
The alkyl acetate betaine is preferably an alkyl group having 12 to 16 carbon atoms, and examples thereof include lauryl dimethylamino acetate betaine. Specifically, commercially available products such as Dai-ichi Kogyo Seiyaku Co., Ltd. can be used.
As fatty acid amidopropyl betaine, what has carbon number 12-16 of a fatty acid is preferable, for example, coconut oil fatty acid amido propyl betaine etc. are mentioned. Specifically, commercially available products such as Sanyo Chemical Industries, Ltd. can be used.
As the alkyl-N-carboxymethyl-N-hydroxyethyl imidazolinium betaine, specifically, commercially available products such as Lion Specialty Chemicals Ltd. can be used.

  As for the compounding quantity, when mix | blending (B) component, 0.01 to 10% of the whole composition is preferable, More preferably, it is 0.01 to 5%.

Furthermore, when the component (B) is compounded, it is possible that the compounding ratio of the component (A) to the component (B) (the components (B-1) and / or (B-2)) is within the specific range. The bactericidal effect against bacteria and the cleaning effect against denture stain are further improved.
The mass ratio of (A) / (B) indicating the mixing ratio of the component (A) to the component (B) is preferably 1 to 10, more preferably 2 to 10.
Further, within the range of the mass ratio of (A) / (B), (A) / (B-1) is preferably 5 to 10, more preferably 6 to 10, and (A) / (B −) 2) is preferably 2-5, more preferably 2-4. Within this range, the bactericidal effect and the cleaning effect are more excellent.

  The denture cleaner composition of the present invention can be prepared in various dosage forms in the form of solids such as tablets and granules, liquids such as aqueous solutions and emulsions, and gels such as pastes and creams. preferable. In addition to the above components, other known components can be blended as needed depending on the form and dosage form. For example, in liquid preparations, perfumes, solvents, coloring agents and the like can be mentioned.

  As a flavoring agent, spearmint oil, peppermint oil, anise oil, eucalyptus oil, winter green oil, cassia oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, mint oil, cardamom oil, coriander oil, mandarin oil, Natural flavors such as lime oil, lavender oil, rosemary oil, laurel oil, camomile oil, caraway oil, marjoram oil, bay oil, lemongrass oil, origanum oil, pine needle oil, shinnamonburk oil, and menthol, Menthon, carboxylic, ethyl butyrate, vanillin, ethyl maltol, anethole, methyl salicylate, cinnamic aldehyde, cineole, eugenol, ethyl vanillin, maltol, limonene, citronellol, linalool, linalyl acetate, menthyl acetate, pine , Single-component perfumes such as octylaldehyde, citral, pregone, carbyl acetate, anisaldehyde, ginger oleoresin, creosol, dl-camphor, etc., and ethyl acetate, allylcyclohexane propionate, methyl anthranilate, ethyl methyl phenyl glyci Use conventional amounts of known perfumes used in oral preparations such as various compound perfumes including single-piece perfumes such as date, undecalactone, hexanal, ethyl alcohol, propyl alcohol, butanol, isoamyl alcohol and / or natural perfumes Can.

  Water (ion-exchanged water) is usually used as the solvent, but polyhydric alcohols and the like can also be added at about 5 to 20%.

  As a coloring agent, Red No. 2, Red No. 3, Red No. 225, Red No. 226, Yellow No. 4, Yellow No. 5, Yellow No. 205, Blue No. 1, Blue No. 2, Blue No. 201, Blue No. 201, Blue No. 204, Green No. 3, etc., and legal dyes, caramel dyes, safflower dyes, gardenia dyes, cochineal dyes, annatto dyes, mica titanium, titanium oxide and the like.

In the present invention, since the alkylamine oxide is blended as a Candida germicidal agent, particularly a quaternary ammonium salt having a bactericidal action effective for Candida germicidal action, for example, a cationic surfactant such as cetyl pyridinium chloride, or dentures As components for detergents, peroxides such as sodium percarbonate and sodium perborate, hypochlorous acid or salts thereof which are generally used may not be required to be blended, but may be 0%, but if blended, the respective blending The amount is preferably 0.03% or less, particularly 0.01% or less.
In addition, a bactericidal agent such as isopropylmethylphenol which is a non-ionic bactericidal agent effective for oral bacteria other than Candida can be added in an effective amount as long as the effects of the present invention are not impaired.

  The pH at 25 ° C of the composition is preferably 5 to 9, more preferably 5 to 7. A pH adjuster may be added to adjust the pH. Examples of pH adjusters include sodium hydroxide, hydrochloric acid, phosphoric acid or salts thereof, citric acid or salts thereof, sodium carbonate, sodium hydrogencarbonate, boric acid or salts thereof and the like.

The denture cleaner composition of the present invention can be used in a conventional manner, and the denture cleaner composition may be used as it is or in an aqueous solution obtained by dispersing or dissolving the denture cleaner composition in water as necessary. The denture can be dipped and then used with water if necessary. In this case, when the denture is immersed, it is desirable that the use concentration of the component (A) be in the above range.
In the case of a liquid preparation, it may be a type used as it is without dilution, or a concentration type which is diluted with water at the time of use and applied to a denture. When the concentration type is used, the concentration of the component (A) when the composition is diluted 5- to 500-fold, particularly 10- to 200-fold, from the viewpoint of usability and solubility is the above-mentioned concentration It is preferable to design the formulation concentration to be within the range.
In the case of a solid preparation, the denture is immersed after being dispersed and dissolved in water, but it may be designed so that the concentration of the component (A) at the time of immersion falls within the above-mentioned use concentration range.
The immersion time of the denture is preferably 1 minute or more, and more preferably 5 minutes or more.

  EXAMPLES The present invention will be specifically described below by showing experimental examples, examples and comparative examples, and formulation examples, but the present invention is not limited to the following examples. In the following examples,% indicates% by mass unless otherwise specified.

[Experimental Example 1]
The denture detergent composition (test sample) of the composition shown in Table 1 was prepared by the following method, and the bactericidal activity against Candida was evaluated by the following method. The results are shown in Table 1.

<1. Evaluation method of bactericidal effect against Candida bacteria>
1-1. Preparation of test bacterial solution Candida albicans ATCC 10231 was inoculated in Difco's Potato Dextrose Agar medium (PDA medium) with a platinum loop and precultured at 25 ° C. The grown colonies were collected using a platinum loop and suspended in saline, and the turbidity at 660 nm was adjusted to 2.0.
1-2. Preparation of test sample The surfactant shown in Table 1 was blended so as to have an AI (pure content) concentration in the table, and the pH was adjusted to become the value in the table as a sample.
1-3. Evaluation method of bactericidal activity 0.1 mL of the test solution prepared in 1-1 above is added to 4 mL of the test sample prepared in 1-2 above, and after mixing by a vortex mixer, 5 at room temperature I left for a minute. Thereafter, 0.444 mL of the above mixed solution was mixed with 4 mL of SCDLP (Soybean-Casein Digest Agar with Lecithin & Polysorbate 80) liquid medium manufactured by Daigo Co., Ltd. to inactivate the reaction (in this step, 10 ¹ dilution). Subsequently, a 10-fold dilution series was prepared in inactivated medium, 50 μL each of 10 ¹ , 10 ³ and 10 ⁵ dilutions were smeared on PDA medium, cultured at 25 ° C., and the number of grown colonies was counted.
From the number of colonies counted, the log reduction value was determined, and the bactericidal effect against Candida was evaluated according to the following criteria.
Evaluation criteria of bactericidal effect against Candida bacteria ○: Log reduction value is 3 Log ₁₀ or more in action for 5 minutes ×: Log reduction value is less than 3 Log _{10 in} action for 5 minutes

[Experimental Example 2]
A denture detergent composition (test sample) having the composition shown in Table 2 was prepared by the following method, and the bactericidal effect against Candida bacteria was evaluated by the above method. Moreover, the cleaning power to denture stain was evaluated by the following method. The results are shown in Table 2. In addition, component amounts (%) in the table are all use concentrations (concentrations at the time of immersion) (hereinafter, the same).
Further, the pH (25 ° C.) of the denture cleaner composition was in the range of 5 to 9 in all cases.

<2. Evaluation method of detergency for denture stains>
2-1. Preparation method of tannin iron stain adhesion acrylic board After treating an acrylic board surface (made by Kuraray Co., Ltd., 10 mm long × 10 mm wide × 5 mm thick) by sandblasting, an ultrasonic cleaner containing a neutral detergent (trade name: Ultrasonic cleaner AU-80C (manufactured by Aiwa Medical Industry Co., Ltd.) was applied for 5 minutes and rinsed with water. After the ultrasonic cleaning was repeated three times, the coating was naturally dried, and the Lab value (L0) of the acrylic plate before tannin iron stain was measured. Repeat the operation of repeatedly immersing the above acrylic plate in 0.5% albumin aqueous solution → tannin extract solution → 0.6% iron (III) ammonium citrate aqueous solution for 30 minutes each time 10 times, and after air-drying at room temperature for 1 day It was washed with running water and again air-dried to prepare a colored acrylic plate.
For tannin extract, put 50g of Japanese tea (Ito En), 5 bags of black tea (Lipton brisket tea bag), 12g of instant coffee (Nezcafe) in 1,200 ml of boiled ion-exchanged water, and leave it overnight. The black tea was removed by filtration and prepared.
The color of the surface of the produced colored acrylic plate was measured, and the value was defined as the Lab value (L1).
2-2. Preparation of test sample The cleaning agent composition shown in Table 2 was formulated to be the AI concentration shown in the table.

2-3. Evaluation method of tannin iron stain removal effect The tannin iron stain attached acrylic plate prepared in the above 2-1 is immersed in the denture detergent composition of each example shown in Table 2 for 5 minutes, washed, and one day at room temperature. After air-drying, the plate was washed with running water, air-dried again, and after drying, the Lab value (L2) of the acrylic plate was measured.
The tannin iron stain removal rate was determined by the following formula.
Tannin iron stain removal rate (%) = [(L1-L2) / (L1-L0)] × 100
From the obtained tannin iron stain removal rate, the detergency against denture stain was evaluated according to the following criteria.
Evaluation criteria of detergency against denture stains :: tannin iron stain removal rate of 30% or more ○: tannin iron stain removal rate of 20% to less than 30% Δ: tannin iron stain removal rate of 10% to less than 20% ×: tannin iron stain removal Less than 10%

Details of the main raw materials used are shown below.
(A) lauryldimethylamine oxide:
Made by Lion Specialty Chemicals Co., Ltd. (trade name: Cadenax DM12
D-W)
(B)
(B-1) α-olefin sulfonate sodium:
Lion Specialty Chemicals Co., Ltd. (trade name: Liporan LB-
440)
(B-1) Sodium lauryl sulfate: Toho Chemical Industry Co., Ltd. product (B-2) lauryl dimethylamino acetic acid betaine:
Daiichi Kogyo Seiyaku Co., Ltd. (trade name: Amogen S-H)
(B-2) Alkyl-N-carboxymethyl-N-hydroxyethyl imidazolinium salt
Tyne (30% aqueous solution):
Made by Lion Specialty Chemicals Co., Ltd. (trade name: Enazicor C-
40H)
(B-2) Coconut oil fatty acid amidopropyl betaine (30% aqueous solution):
Sanyo Chemical Industries, Ltd. made (brand name: Rebon 2000)

  Next, an example of prescription is shown. The denture cleanser composition of the formulation example was excellent in the bactericidal effect on Candida bacteria, and the cleaning power on denture stain was also good.

Formulation Example 1 Liquid denture cleanser (diluted with water 1 to 200 times, soaking denture)
Lauryl dimethylamine oxide 10%
Hydroxyethanediphosphonic acid 5
Sodium hydroxide 2.5
Ion exchange water
100.0% in total

Claims (12)

  (A) An oral candida fungicide comprising an alkylamine oxide.   The oral cavity Candida bactericidal agent according to claim 1, wherein the component (A) is an alkyldimethylamine oxide having 12 to 18 carbon atoms in the alkyl group.   (A) A denture cleaner composition comprising an alkylamine oxide.   The denture cleaner composition according to claim 3, wherein the component (A) is an alkyldimethylamine oxide in which the carbon number of the alkyl group is 12-18.   The denture detergent composition according to claim 3 or 4, which contains 0.05 to 20% by mass of the component (A).   The denture detergent composition according to claim 3, 4 or 5, further comprising (B) (B-1) anionic surfactant and / or (B-2) betaine amphoteric surfactant.   The denture detergent composition according to claim 6, wherein (A) / (B), which indicates the blending ratio of the component (A) to the component (B), is a mass ratio of 1 to 10.   The denture detergent composition according to claim 6 or 7, which contains 0.01 to 10% by mass of the component (B).   The denture detergent composition according to any one of claims 3 to 8, wherein the content of the cationic surfactant is 0 to 0.03 mass%.   The denture cleaner composition according to any one of claims 3 to 9, wherein the content of the peroxide is 0 to 0.03 mass%.   The denture detergent composition according to any one of claims 3 to 10, wherein the pH of the composition at 25 ° C is 5 to 9.   The denture detergent composition according to any one of claims 3 to 11, which is prepared in a liquid formulation.