JP2013245187A - Biofilm inhibitor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a biofilm inhibitor which can suppress a biofilm to which conventional antimicrobial agents are poorly effective.SOLUTION: A biofilm inhibitor includes a monoglyceride of a 6-12C medium chain fatty acid. More preferably, the biofilm inhibitor contains the monoglyceride of the 6-12C medium chain fatty acid and an antimicrobial agent selected from phenol antimicrobial agents, terpenoid essential oils, phenylpropanoid essential oils and a mixture thereof.

Description

  [Technical Field] The present invention relates to a biofilm inhibitor and a composition for oral cavity for suppressing a biofilm, including a biofilm inhibitor and a biofilm inhibitor, comprising monoglycerides of medium chain fatty acids having 6 to 12 carbon atoms.

A biofilm (also called a biofilm) is a structure formed by microorganisms such as bacteria. In general, a biofilm is a material in which bacterial aggregates covered with glycocalyx consisting of exopolysaccharides adhere to the surface of a substance (Japanese Society of Periodontology (2007) Glossary of Medical and Dental Medicine Publishing Co., Ltd.). Kitchen slime and dental plaque are typical biofilms. Bacteria in the biofilm coexist and coexist with glycocalyx and have a barrier function on the surface. Therefore, the bacteria in the biofilm can protect themselves from phagocytosis by neutrophils and the like. Furthermore, since it is difficult for the antibacterial agent to penetrate deep into the biofilm, it is difficult to destroy, kill and suppress the biofilm and the bacteria in the biofilm only with the conventional antibacterial agent. As described above, since biofilms are resistant to immunity and antibacterial agents and cause various diseases, many studies have been conducted to effectively act bactericides on biofilms.
Conventionally, examples of using polyglycerin fatty acid esters and monoglycerin fatty acid esters in denture cleaning compositions and oral compositions are known (Patent Documents 1 to 4), but specific monoglycerin fatty acid esters and monoglycerin are known. There is no disclosure that a mixture of fatty acid ester and antimicrobial component can be used as a biofilm inhibitor. Patent Document 5 discloses an antibacterial composition containing a specific monoglycerin fatty acid ester, but that a specific monoglycerin fatty acid ester or a mixture of a monoglycerin fatty acid ester and an antibacterial component can be used as a biofilm inhibitor. It is not disclosed.

JP 2010-6720 A JP 2011-241167 A JP 2011-195498 A International Publication WO2011 / 0777847 Pamphlet JP 2010-163397 A JP 2008-303188 A

The first object of the present invention is to provide a biofilm inhibitor capable of suppressing biofilms that are difficult to be effective with conventional antibacterial agents.
The second object of the present invention is to provide an oral composition, a cleaning composition or a cosmetic for suppressing a biofilm containing the biofilm inhibitor.
A third object of the present invention is to provide a method for inhibiting a biofilm, characterized in that the biofilm inhibitor is applied to the surface on which the biofilm is formed.

As a result of intensive studies, the present inventors have found that biofilms can be significantly suppressed by using monoglycerides of medium chain fatty acids having 6 to 12 carbon atoms alone or in combination with monoglycerides of medium chain fatty acids and antibacterial components. The headline and the present invention were completed. Specifically, examples of aspects that the present invention can take include the following.
[1]
A biofilm inhibitor comprising monoglycerides of medium chain fatty acids having 6 to 12 carbon atoms.
[2]
The biofilm inhibitor according to [1], further comprising an antibacterial component selected from phenolic antibacterial agents, terpenoid essential oils, phenylpropanoid essential oils, and mixtures thereof.
[3]
The biofilm inhibitor according to [1] or [2], wherein the content of monoglyceride of the medium chain fatty acid is 0.01 to 10% by mass with respect to the mass of the biofilm inhibitor.
[4]
The biofilm inhibitor according to [2] or [3], wherein the content of the antibacterial component is 0.005 to 5% by mass with respect to the mass of the biofilm inhibitor.
[5]
The monoglyceride of the medium chain fatty acid is selected from the group consisting of glyceryl monocaproate, glyceryl monocaprylate, glyceryl monocaprate, glyceryl monolaurate, and mixtures thereof, according to any one of [1] to [4]. Biofilm inhibitor.
[6]
The biofilm inhibitor according to any one of [1] to [4], wherein the monoglyceride of the medium chain fatty acid is glyceryl monocaprylate.
[7]
The biofilm inhibitor according to any one of [2] to [6], wherein the antibacterial component is selected from the group consisting of isopropylmethylphenol, triclosan, and hinokitiol.
[8]
In any one of [2] to [6], the antibacterial component is a terpenoid or phenylpropanoid essential oil selected from the group consisting of eucalyptus oil, mint oil, clove oil, cinnamon oil and mixtures thereof. The biofilm inhibitor as described.
[9]
The composition for oral cavity for suppressing a biofilm containing the biofilm inhibitor of any one of [1]-[8].
[10]
A cleaning composition for suppressing a biofilm, comprising the biofilm inhibitor according to any one of [1] to [8].
[11]
Cosmetics for suppressing a biofilm, including the biofilm inhibitor according to any one of [1] to [8].
[12]
A method for inhibiting a biofilm, comprising applying the biofilm inhibitor according to any one of [1] to [8] to a surface on which a biofilm is formed.

The biofilm inhibitor of the present invention exhibits a high bactericidal effect against plaque, denture plaque, and skin diseases derived from biofilm, which are in the form of biofilm that is difficult to be effective with conventional antibacterial agents. It is effective as a film inhibitor.
The biofilm inhibitor of the present invention suitably suppresses (reduces) bacteria in a biofilm by using monoglyceride of a medium chain fatty acid having 6 to 12 carbon atoms alone or in combination with the monoglyceride of the medium chain fatty acid and an antibacterial component. Kill, remove, prevent).
By adding the biofilm inhibitor of the present invention to oral compositions such as toothpastes, oral moisturizers, mouthwashes, etc., it is possible to suitably remove plaque and the like related to oral biofilms. .
In addition, the present invention uses a medium chain fatty acid monoglyceride having 6 to 12 carbon atoms and a specific antibacterial component in combination with a biofilm as compared with the case of the medium chain fatty acid monoglyceride or the antibacterial component alone. This produces a synergistic effect that can be significantly suppressed.
The biofilm inhibitor of the invention can suitably remove a biofilm that causes skin diseases when used in cosmetics.
By adding the biofilm inhibitor of the invention to the cleaning agent, slime and stickiness derived from the biofilm can be suitably removed.
The biofilm inhibitor of the invention can suitably remove Candida-derived denture plaques and the like by adding it to a denture cleaning agent or the like.

[Biofilm inhibitor]
The biofilm inhibitor of the present invention can contain a monoglyceride of a medium chain fatty acid having 6 to 12 carbon atoms and an antibacterial component.
Here, as described above, the biofilm is also called a fungal membrane and is a structure formed by microorganisms such as bacteria. Examples of microorganisms include facultative anaerobic gram-positive cocci such as Streptococcus mutans and Streptococcus aureus, obligate anaerobic gram-negative bacteria such as periodontitis bacteria (Porphyromonas gingivalis), and Candida And fungi such as (Candida albicans). In particular, Streptococcus mutans, the causative agent of caries, decomposes various sugars to produce a large number of organic acids such as lactic acid.For example, in the teeth, cells are separated from teeth by insoluble glucan produced from sucrose. Adhere and form a biofilm.
In addition, the biofilm inhibitor referred to here restricts the growth of the biofilm, as well as prevention of biofilm adhesion, prevention of deposition, decomposition / removal of the attached biofilm, suppression of bacteria in the biofilm, death, removal, etc. In addition, it means to include an agent that suppresses and removes biofilm. In particular, plaque is a typical biofilm in which anaerobic bacteria are gathered. Plaque is produced by first adsorbing the pellicle, which is an organic substance mainly composed of salivary glycoprotein, on the surface of the enamel of the tooth to coat the tooth, and bacteria adhere to the pellicle, causing a metabolic reaction. Insoluble glucan adhered firmly to the tooth surface.

[Medium chain fatty acid monoglyceride]
The monoglycerides of medium chain fatty acids that can be used in the present invention are monoglycerides of medium chain fatty acids having 6 to 12 carbon atoms, preferably 6 to 10 carbon atoms, more preferably 7 to 9 carbon atoms. Examples of the monoglyceride of a medium chain fatty acid that can be preferably used in the present invention include glyceryl monocaproate, glyceryl monocaprylate, glyceryl monocaprate and glyceryl monolaurate, and more preferably glyceryl monocaprylate.
The medium-chain fatty acid monoglyceride is preferably used together with the antibacterial component described later. However, the biofilm inhibitor containing the medium-chain fatty acid monoglyceride and not including the antibacterial component is sufficient for the desired effect of the present invention. It can be demonstrated.
The content of the monoglyceride of the medium chain fatty acid is, for example, 0.01 to 10% by mass, preferably 0.05 to 5% by mass, more preferably 0.1 to 1% with respect to the total mass of the biofilm inhibitor. It is suitable that it is mass%.
In addition, when the biofilm inhibitor containing the medium-chain fatty acid monoglyceride is used in a composition such as an oral composition, the content of the medium-chain fatty acid monoglyceride in the composition is based on the total mass of the composition. For example, 0.01 to 25% by mass, preferably 0.05 to 20% by mass, more preferably 0.1 to 10% by mass is appropriate.

[Antimicrobial component]
The present invention uses a medium chain fatty acid monoglyceride having 6 to 12 carbon atoms in combination with a specific antibacterial component, thereby making the biofilm significant compared to the case of the medium chain fatty acid monoglyceride or the antibacterial component alone. It has been found that there is a synergistic effect that can be suppressed. The antimicrobial component that can be used in the present invention is selected from, for example, phenolic antimicrobial agents, terpenoid essential oils, phenylpropanoid essential oils, analogs thereof, and mixtures thereof.
Examples of the phenolic antibacterial agent include isopropylmethylphenol, triclosan, hinokitiol, thymol and the like.
Examples of the phenylpropanoid essential oil include clove oil, fennel oil, cinnamon oil, eugenol, anethole, cinnamaldehyde, and cinnamaldehyde.
Examples of the terpenoid essential oil include mint oil, eucalyptus oil, orange oil, turpentine oil, peppermint oil, spearmint oil, camphor oil, saim oil, perilla oil, tea tree oil, lemon oil, sage oil, rosemary oil, l- Limonene, l-menthol, menthone, α-pinene, citral, cineole, camphor and the like can be mentioned.
The mixture of the phenolic antibacterial agent, terpenoid essential oil, and phenylpropanoid essential oil may be any combination of two or more antibacterial components. For example, the phenolic antibacterial agent and phenylpropanoid essential oil or terpenoid A combination of one type of antibacterial component from a combination with an essential oil, a phenolic antibacterial agent, a phenylpropanoid essential oil and a terpenoid essential oil is preferred. More specifically, the antibacterial component that can be used in the present invention is preferably a combination of isopropylmethylphenol and eucalyptus oil and / or mint oil, a combination of hinokitiol and clove oil and / or mint oil, and the like.

The content of the antibacterial component is, for example, 0.005 to 5% by mass, preferably 0.008 to 2% by mass, and more preferably 0.01 to 1% by mass with respect to the total mass of the biofilm inhibitor. It is appropriate to be.
Moreover, the mass ratio of monoglyceride having 6 to 12 carbon atoms contained in the biofilm inhibitor and the antibacterial component is, for example, 100: 1 to 1: 100, preferably 50: 1 to 1:50, More preferably, the ratio is 10: 1 to 1:20.
Furthermore, when using the biofilm inhibitor containing the said antibacterial component for compositions, such as a composition for oral cavity, content of the antibacterial component in a composition is 0.001 with respect to the whole mass of a composition, for example. It is suitable that it is 10-10 mass%, Preferably it is 0.005-5 mass%, More preferably, it is 0.01-2 mass%.

[Other ingredients]
In addition to the above active ingredients, the biofilm inhibitor of the present invention includes abrasives, wetting agents, solvents, binders, fragrances, excipients, sweeteners, pH adjusters, preservatives, emulsifiers, solubilizers, Foaming agents, lubricants, surfactants, oils, pigments, antioxidants, other agents, and the like can be appropriately blended. These additives are usually used in pharmaceutical compositions, oral compositions or food formulation designs, and can be appropriately selected within a range not impairing the effects of the present invention, and can be blended in an appropriate blending amount. it can. The following are mentioned as an example of such an additive.

Examples of the abrasive include calcium carbonate, calcium phosphate, dicalcium phosphate, calcium pyrophosphate, insoluble calcium metaphosphate, hydrous silicic acid, anhydrous silicic acid, titanium dioxide, amorphous silica, crystalline silica, aluminosilicate, and aluminum oxide. Aluminum hydroxide, resin, hydroxyapatite and the like can be blended alone or in combination of two or more. The blending amount is generally 3 to 60% by mass with respect to the total amount of the biofilm inhibitor.
As the wetting agent, for example, polyhydric alcohols such as glycerin, sorbitol, polyethylene glycol, propylene glycol, ethylene glycol, 1,3-butylene glycol, polypropylene glycol, xylitol, maltitol, lactitol, alone or in combination of two or more. Can be blended. The blending amount is generally 0.1 to 50% by mass with respect to the total amount of the biofilm inhibitor.

As a solvent, organic solvents, such as alcohol, and water are preferable, for example, ethanol, propyl alcohol, isopropyl alcohol, etc. are mentioned, and especially ethanol is preferable. These alcohols can be blended alone or in combination of two or more. The blending amount is generally 99.9% by mass or less, preferably 0.1 to 30% by mass with respect to the total amount of the biofilm inhibitor.
Examples of the binder include cellulose derivatives such as carrageenan, carboxymethylcellulose and sodium carboxymethylcellulose, alkali metal alginates such as sodium alginate, gums such as xanthan gum, tragacanth gum and gum arabic, and synthetic viscosities such as polyvinyl alcohol and sodium polyacrylate. Examples of the binder include inorganic binders such as silica gel, aluminum silica gel, and bee gum. The blending amount is generally 0.5 to 10% by mass with respect to the total amount of the biofilm inhibitor.

As fragrances, known fragrance ingredients such as strawberry flavor, apple flavor, banana flavor, pineapple flavor, grape flavor, mango flavor, butter flavor, milk flavor, fruit mix flavor, tropical fruit flavor, etc. are used in combination. be able to. The amount is generally 0.0001 to 1.0 mass% with respect to the total amount of the biofilm inhibitor.
Examples of excipients include sucrose, lactose, starch, glucose, crystalline cellulose, mannitol, sorbit, xylitol, erythritol, palatinit, palatinose, maltitol, trehalose, lactitol, lactulose, reduced starch sugar, reduced isomaltoligosaccharide. , Coupling sugar, gum base, gum arabic, gelatin, cetylmethylcellulose, light anhydrous silicic acid, magnesium aluminate, calcium aluminate metasilicate, sodium bicarbonate, calcium phosphate and the like. The blending amount is generally 0.01 to 30% by mass with respect to the total amount of the biofilm inhibitor.

Examples of the sweetener include palatinit, aspartame, saccharin sodium, acesulfame potassium, stevioside, neohesperidyl dihydrochalcone, glycyrrhizin, perillalmine, thaumatin, asparatylphenylalanyl methyl ester, ρ-methoxycinnamic aldehyde and the like. These can be blended singly or in combination of two or more. The compounding quantity is 0.01-1 mass% normally with respect to the whole biofilm inhibitor, Preferably it is 0.05-0.5 mass%.
As a pH adjuster, for example, citric acid, phosphoric acid, pantothenic acid, malic acid, pyrophosphoric acid, lactic acid, tartaric acid, glycerophosphoric acid, acetic acid, nitric acid, or these chemically possible such as disodium hydrogen phosphate A salt, sodium hydroxide, etc. are mentioned, These can be mix | blended individually or in combination of 2 or more types so that pH of a composition may become an appropriate range. The compounding quantity is 0.01-2 mass% normally with respect to a biofilm inhibitor.

Examples of the preservative include p-hydroxybenzoates, benzoic acid and salts thereof, salicylic acid and salts thereof, sorbic acid and salts thereof, phenoxyethanol, and alkyldiaminoethylglycine hydrochloride. The blending amount is generally 0.005 to 5% by mass with respect to the total amount of the biofilm inhibitor.
Examples of the emulsifier include polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, polyoxyethylene hydrogenated castor oil, sodium stearoyl lactate, soybean Examples thereof include phospholipids and alkyltrimethylammonium chloride. The blending amount is generally 0.05 to 30% by mass with respect to the total amount of the biofilm inhibitor.
Examples of the solubilizer include esters, polyethylene glycol derivatives, polyoxyethylene hydrogenated castor oil, sorbitan fatty acid esters, sulfated fatty alcohols, and the like. The blending amount is generally 0.05 to 30% by mass with respect to the total amount of the biofilm inhibitor.
Examples of the foaming agent include sodium lauryl sulfate, sodium lauroyl sarcosine, sodium alkylsulfosuccinate, sodium coconut oil fatty acid sodium monoglycerol sulfonate, sodium α-olefin sulfonate, N-acyl glutamate and the like, 2- Alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, maltitol fatty acid ester, sucrose fatty acid ester, polyglycerin fatty acid ester, fatty acid diethanolamide, polyoxyethylene sorbitan monostearate, polyoxyethylene hydrogenated castor oil, Examples thereof include polyoxyethylene fatty acid esters, and one or more of these can be used in combination.

Examples of the lubricant include magnesium stearate, sucrose fatty acid ester, talc, and hardened oil.
Examples of the oil include oils other than the essential oil used as an antibacterial component and the oil used as the perfume, such as coconut oil, olive oil, sesame oil, peanut oil, parsley oil, parsley seed oil, safflower oil, and the like.
Examples of the surfactant include sodium lauryl sulfate, sodium α-olefin sulfonate, sodium dodecylbenzene sulfonate, sodium lauryl sulfoacetate, sodium N-lauroyl sarcosinate, N-acyl glutamate, sucrose fatty acid ester, polyoxy Ethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene block copolymer, alkyl glycosides, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, alkyl dimethylamine oxide, lauryl ethanol amide, sodium cocoyl sarcosine, N-lauroylmethyl taurine A sodium solution etc. are mentioned. The blending amount is generally 0 to 30% by mass with respect to the total amount of the biofilm inhibitor.
In addition to the above-mentioned components, for example, pigments such as Blue No. 1, pigments such as titanium dioxide, antioxidants such as dibutylhydroxytoluene, chelating agents such as edetate, cha extract, tea dry distillation liquid, sodium glutamate And so on.

The oral composition of the present invention can also contain medicinal ingredients such as a moisturizer, antibacterial agent, anti-inflammatory agent, fluoride, vitamin agent, herbal extract and the like. These medicinal ingredients can be appropriately selected from those that can be used for pharmaceuticals, foods, and cosmetics.
Examples of humectants include amino acids or salts thereof, pyrrolidone carboxylic acid, mucin, hyaluronic acid or salts thereof, mucopolysaccharides such as chondroitin sulfate, sodium lactate, urea, panthenol, aloe extract, rosemary extract, thyme extract, tea extract Examples include natural extract components such as (cha dry distillation extract), so-called extracellular matrices such as collagen and elastin. What is necessary is just to select these 1 type, or 2 or more types of combinations suitably.
Examples of antibacterial agents include cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride, decalinium chloride, chlorhexidine hydrochloride, chlorhexidine sodium gluconate, bisabolol chlorhexidine, lactoferrin, paraben, butylparaben and the like. These 1 type (s) or 2 or more types can be used in combination.
Examples of the anti-inflammatory agent include lysozyme chloride, ε-aminocaproic acid, aluminum hydroxyl allantoin, glycyrrhetinic acid, glycyrrhizinate, guaiazulene sulfonic acid, dl-α-tocopherol acetate and the like.
Examples of the fluoride include sodium fluoride, potassium fluoride, sodium monofluorophosphate, stannous fluoride, and the like.
Examples of vitamins include vitamins A such as retinoic acid and β-carotene, pantothenic acid or salts thereof, vitamins B such as niacin and biotin, vitamins C such as ascorbic acid or salts thereof, α-tocopherol and the like Vitamin E, folic acid and the like.
Examples of herbal extracts include chamomile extract, valerian extract, jujube extract, hop extract, ramender extract, linden extract, quince extract, goldfish extract, kumazasa extract, gummy extract, clove extract, dentistine carrot extract, salvia extract, mukuroji extract, etc. Can be mentioned.
In general, the concentration of the moisturizer, antibacterial agent, anti-inflammatory agent, fluoride, vitamin agent, herbal extract and other medicinal ingredients is suitably in the range of 0.001 to 5.0 mass%, more preferably. Is in the range of 0.01 to 1.0 mass%.

  The biofilm inhibitor of the present invention can have various shapes, for example, liquid (emulsified form, solubilized form), liquid form, gel form, paste form, tablet, effervescent tablet, powder form, granule Or the like.

[Composition Containing Biofilm Inhibitor]
The present invention may be a composition comprising the biofilm inhibitor. Examples of the composition include an oral composition, a cosmetic composition, a detergent composition, and a skin composition.
The composition for oral cavity is a composition for the purpose of suppressing the biofilm in the oral cavity. Examples of oral compositions include toothpastes, liquid dentifrices, oral moisturizers, mouthwashes, and the like. Examples of the cosmetic composition include lotion, facial cleansing foam, makeup remover, milky lotion, cream, eyeliner, cosmetic liquid, ointment, oil, pack and the like. Examples of detergent compositions include tooth-related cleaning agents such as denture cleaning agents (liquids, powders, tablets, etc.), shampoos, rinses, body shampoos, conditioners and other hair-related cleaning agents, soaps and hand soaps. And general household cleaners such as liquid detergents, kitchen detergents, dishwashing detergents, bathroom detergents, toilet detergents and pipe detergents.
Hereinafter, specific examples of the biofilm inhibitor of the present invention and the composition containing the biofilm inhibitor will be described, but it is clearly specified that the examples are not intended to limit the scope of the present invention. Keep it. In addition, in the following examples, unless otherwise specified, the unit of the blending amount is mass%.

[Biofilm suppression method]
The present invention also relates to a method for suppressing a biofilm by applying the biofilm inhibitor to a predetermined place. Specifically, by applying the biofilm inhibitor to the surface on which the biofilm has already been formed by coating or the like, the biofilm formed on the surface can be suppressed, reduced, or removed. Examples of such surfaces include the human body surface such as the oral cavity, teeth, hair, and skin, and other than the human body such as dentures, tableware, kitchens, kitchen utensils, toilets, toilet articles, bathrooms, bathroom utensils, pipes, furniture, and walls. Surface. The amount of the biofilm inhibitor applied to the surface is, for example, 0.01 to ² g, preferably 0.05 to 1.5 g, more preferably 0.1 to 1 g per 1 cm ^{2 of the} surface. Is appropriate.

[Production of biofilm]
Streptococcus mutans JCM5705 was precultured in SCD medium (Wako Pure Chemical Industries, Ltd.) for 24 hours at 32.5 ° C. to obtain a precultured bacterial solution. The obtained precultured bacterial solution was added to 1% sucrose-containing SCD medium so that the cell concentration was 10 ⁷ CFU / mL to obtain a cultured bacterial solution, and 2 mL of the cultured bacterial solution was seeded on a 24-well plate. . The seeded culture solution was anaerobically cultured at 37 ° C. for 48 hours to obtain a biofilm.

[Manufacture of biofilm inhibitors]
The components of Examples and Comparative Examples shown in Tables 1A and B and Tables 2A and B below were dissolved in 12.5% by mass ethanol (EtOH) to obtain test solutions.
[Biofilm suppression test]
The produced Streptococcus mutans biofilm was washed twice with 0.01 ml / l phosphate buffered saline (PBS) (Wako Pure Chemical Industries, Ltd.) to remove floating bacteria. After adding 2 ml of the above test solution to the biofilm in the 24-well plate, leave it for 30 minutes (Tables 1A and B) or 10 minutes (Tables 2A and B), suck out and remove all the supernatant, and then add LP to the residue. Diluted liquid (diluted liquid of lectin and polysorbate 80 containing 1 g of casein peptone, 0.7 g of lecithin, 20 g of polysorbate 80 and 8.3 g of purified water per liter of purified water) (Digo, Wako Pure Chemical Industries, Ltd.) 2 mL was added, and the biofilm was peeled from the well plate using an ultrasonic homogenizer (BRANSON SONIFIER). 1 mL of the bacterial solution containing the peeled biofilm is serially diluted with 9 ml of LP diluent (same as above), and 1 ml of the diluted solution of the obtained bacterial solution is smeared on the SCDLP agar medium (Wako Pure Chemical Industries, Ltd.) The viable cell count was determined by the pour culture method. Here, the pour culture method involves mixing and solidifying a sample solution and an agar medium in a petri dish, culturing under aerobic conditions at 32.5 ° C., and visually measuring the number of colonies generated after the culture. To determine the number of viable bacteria.

Table 1A

Table 1B

Table 2A

Table 2B

  As can be understood from the comparison between the above-mentioned Example 1 and Comparative Example 1, and Examples 6 and 11 and Comparative Example 6, the biofilm inhibitor containing a monoglyceride of a medium chain fatty acid having 6 to 12 carbon atoms of the present invention is In addition, bacteria (Streptococcus mutans) in biofilms are significantly suppressed. Moreover, in the biofilm inhibitor containing the monoglyceride of the C6-C12 medium chain fatty acid of this invention, and a phenol type fungicide, a terpenoid type, or a phenylpropanoid type essential oil (Examples 2-5 and Examples 7- 10 and Examples 12 to 15), compared with the case of monoglycerides having 6 to 12 carbon atoms monoglyceride alone (Examples 1 and 6 and 11) and antibacterial components alone (Comparative Examples 2 to 5 and 7 to 10). Thus, it was possible to dramatically suppress bacteria.

[Prescription example]
The following shows a formulation example of the composition of the present invention prepared by using glyceryl caprylate as a monoglyceride of the medium chain fatty acid of the present invention, further using an antibacterial component that can be used in the present invention, and mixing with other components. . The unit of the amount is mass%.
<Example 16>
<Toothpaste>
Glyceryl caprylate 0.5
Isopropylmethylphenol 0.1
Calcium hydrogen phosphate 40.0
Silicic anhydride 5.0
Glycerin 15.0
Sodium carboxymethylcellulose 2.0
Sorbit solution 10.0
Fragrance 1.0
Sodium lauryl sulfate 0.1
P-Hydroxybenzoate ester 0.2
Sodium fluoride 0.2
Cetylpyridinium chloride 0.05
Purified water remaining
Total 100%

<Example 17>
<Toothpaste>
Glyceryl caprylate 0.5
Triclosan 0.02
Aluminum hydroxide 35.0
Glycerin 15.0
Crystalline cellulose 10.0
Polyethylene glycol 10.0
Hydroxypropyl cellulose 2.0
Fragrance 1.0
Sodium lauryl sulfate 0.1
Butylparaben 0.2
Saccharin sodium 0.1
Dl-α-tocopherol acetate 0.1
Cetylpyridinium chloride 0.05
Purified water remaining
Total 100%

<Example 18>
<Toothpaste>
Glyceryl caprylate 0.5
Hinokitiol 0.02
Calcium carbonate 25.0
Sorbit liquid 15.0
Glycerin 10.0
Silicic anhydride 5.0
Sodium carboxymethylcellulose 2.0
Fragrance 1.0
Sodium lauryl sulfate 0.5
Saccharin sodium 0.05
Cetylpyridinium chloride 0.05
Purified water remaining
Total 100%

<Example 19>
<Toothpaste>
Glyceryl caprylate 0.2
Clove oil 0.2
Glycerin 25.0
Calcium pyrophosphate 25.0
Silicic anhydride 5.0
Sodium carboxymethylcellulose 1.0
Fragrance 1.0
Sodium lauryl sulfate 0.5
Saccharin sodium 0.05
Cetylpyridinium chloride 0.05
Purified water remaining
Total 100%

<Example 20>
<Toothpaste>
Glyceryl caprylate 0.2
Isopropylmethylphenol 0.1
Eucalyptus oil 0.2
Silicic anhydride 20.0
70% sorbite solution 20.0
Glycerin 20.0
Propylene glycol 3.0
Sodium lauryl sulfate 1.7
Polyethylene glycol 1.0
Carrageenan 1.0
Fragrance 1.0
Titanium dioxide 0.5
Methyl paraoxybenzoate 0.2
Cetylpyridinium chloride 0.05
Purified water remaining
Total 100%

<Example 21>
<Toothpaste>
Glyceryl caprylate 0.2
Hinokitiol 0.02
Peppermint oil 0.5
Aluminum hydroxide 30.0
Glycerin 20.0
Sodium chloride 10.0
Silicic anhydride 5.0
Polyoxyethylene hydrogenated castor oil 3.0
Sodium lauryl sulfate 1.8
Sodium carboxymethylcellulose 1.0
Polyethylene glycol 1.0
Fragrance 1.0
P-Hydroxybenzoate ester 0.2
Dl-α-tocopherol acetate 0.1
Purified water remaining
Total 100%

<Example 22>
<Toothpaste>
Glyceryl caprylate 0.2
Isopropylmethylphenol 0.1
Eucalyptus oil 0.2
Peppermint oil 0.5
Calcium pyrophosphate 32.0
Glycerin 20.0
Silica anhydride 6.0
Sodium carboxymethylcellulose 1.0
Glycyrrhetinic acid 1.0
Polyethylene glycol 1.0
Fragrance 0.1
ε-aminocaproic acid 0.1
Dl-α-tocopherol acetate 0.1
Purified water remaining
Total 100%

<Example 23>
<Toothpaste>
Glyceryl caprylate 0.5
Hinokitiol 0.02
Clove oil 0.2
Peppermint oil 0.5
Glycerin 20.0
Calcium pyrophosphate 16.0
Silicic acid 7.0
Fragrance 1.0
Sodium carboxymethylcellulose 0.8
Sodium lauryl sulfate 0.6
Carrageenan 0.6
Lysozyme chloride 0.4
Stevia extract 0.1
Chlorhexidine gluconate 0.05
Purified water remaining
Total 100%

<Example 24>
<Oral moisturizer (gel type)>
Glyceryl caprylate 0.2
Eucalyptus oil 0.2
Sodium carboxymethylcellulose 3.5
Glycerin 15.0
Propylene glycol 5.0
Sodium benzoate 0.3
Cetylpyridinium chloride 0.01
Citric acid 0.23
Sodium citrate 1.1
Purified water remaining
Total 100%

<Example 25>
<Oral moisturizer (gel type)>
Glyceryl caprylate 0.5
Isopropylmethylphenol 0.1
Peppermint oil 0.5
Glycerin 25.0
Carrageenan 0.6
Sodium carboxymethylcellulose 1.4
Sodium benzoate 0.3
Citric acid 0.2
Sodium citrate 0.3
Trimethylglycine 0.5
Polyoxyethylene hydrogenated castor oil 0.5
Lactoferrin 0.01
Mucin 0.01
Hyaluronic acid 0.005
Purified water remaining
Total 100%

<Example 26>
<Oral moisturizer (gel type)>
Glyceryl caprylate 0.2
Hinokitiol 0.02
Clove oil 0.2
Glycerin 15.0
Carrageenan 0.8
Sodium alginate 1.8
Propylene glycol 10.0
Polyoxyethylene hydrogenated castor oil 3.0
Sodium benzoate 0.5
Citric acid 0.04
Disodium hydrogen phosphate 0.1
Edetate disodium 0.2
Ethanol 2.0
Xylitol 5.0
Menthol 0.01
Fragrance 0.1
Hyaluronic acid 0.005
Dipotassium glycyrrhizinate 0.015
Purified water remaining
Total 100%

The liquid dentifrices and mouthwashes of Examples 27 to 38 can be used by being stored in a spray container and sprayed into the oral cavity.
<Example 27>
<Liquid dentifrice>
Glyceryl caprylate 0.5
Isopropylmethylphenol 0.1
Ethanol 2.0
Agar 1.5
Polyoxyethylene hydrogenated castor oil 1.5
Fragrance 0.4
Paraoxybenzoic acid ester 0.1
Saccharin sodium 0.05
Purified water remaining
Total 100%

<Example 28>
<Liquid dentifrice>
Glyceryl caprylate 0.5
Triclosan 0.02
Aluminum hydroxide 10.0
Glycerin 10.0
Polyoxyethylene hydrogenated castor oil 0.5
Carrageenan 0.5
Ethanol 0.5
Fragrance 0.4
Paraoxybenzoic acid ester 0.1
Saccharin sodium 0.05
Purified water remaining
Total 100%

<Example 29>
<Liquid dentifrice>
Glyceryl caprylate 0.5
Hinokitiol 0.02
Glycerin 15.0
Polyethylene glycol 10.0
Silicic anhydride 3.0
Calcium hydrogen phosphate 2.0
Sodium carboxymethylcellulose 2.0
Polyoxyethylene hydrogenated castor oil 1.0
Aluminosilicate 0.5
Fragrance 0.5
Paraben 0.1
Purified water remaining
Total 100%

<Example 30>
<Liquid dentifrice>
Glyceryl caprylate 0.2
Isopropylmethylphenol 0.1
Triclosan 0.02
Glycerin 10.0
Aluminum hydroxide 10.0
Agar 1.0
Ethanol 0.5
Polyoxyethylene hydrogenated castor oil 0.5
Carrageenan 0.5
Fragrance 0.4
Paraoxybenzoic acid ester 0.1
Cetylpyridinium chloride 0.05
Purified water remaining
Total 100%

<Example 31>
<Liquid dentifrice>
Glyceryl caprylate 0.2
Eucalyptus oil 0.2
Glycerin 20.0
Sorbit liquid 25.0
Xanthan gum 1.0
Sodium carboxymethylcellulose 0.5
Fragrance 0.5
Polyoxyethylene hydrogenated castor oil 0.5
Sodium lauryl sulfate 0.5
Paraoxybenzoic acid ester 0.1
Purified water remaining
Total 100%

<Example 32>
<Liquid dentifrice>
Glyceryl caprylate 0.5
Isopropylmethylphenol 0.1
Eucalyptus oil 0.2
70% sorbite solution 25.0
Silica anhydride 10.0
Glycerin 10.0
Xanthan gum 1.0
Xylitol 1.0
Fragrance 0.5
Ethyl paraoxybenzoate 0.1
Butyl paraoxybenzoate 0.05
Purified water remaining
Total 100%

<Example 33>
<Liquid dentifrice>
Glyceryl caprylate 0.5
Isopropylmethylphenol 0.1
Peppermint oil 0.1
Polyoxyethylene hydrogenated castor oil 5.0
Ethanol 5.0
Xylitol 5.0
Sodium citrate 0.15
Citric acid 0.1
Saccharin sodium 0.1
Edetate disodium 0.1
Paraoxybenzoic acid ester 0.1
Fragrance 0.1
Aluminum chlorohydroxyl allantoin 0.01
Purified water remaining
Total 100%

<Example 34>
<Liquid dentifrice>
Glyceryl caprylate 0.5
Isopropylmethylphenol 0.1
Hinokitiol 0.02
Clove oil 0.2
Ethanol 10.0
Polyethylene glycol 2.0
Polyoxyethylene hydrogenated castor oil 2.0
Sodium benzoate 1.0
Fragrance 0.4
Aluminum chlorohydroxyl allantoin 0.2
Edetate disodium 0.2
Cha dry distillation solution 0.1
Stevia extract 0.05
Aluminum lactate 0.01
Cetylpyridinium chloride 0.05
Purified water remaining
Total 100%

<Example 35>
<Liquid dentifrice>
Glyceryl caprylate 0.2
Eucalyptus oil 0.2
Peppermint oil 0.5
Hydrous silicate 1.0
Silica anhydride 10.0
Glycerin 25.0
Fragrance 1.0
Carboxymethyl cellulose 1.0
Sorbitol 50.0
Polyoxyethylene hydrogenated castor oil 0.5
Paraoxybenzoic acid ester 0.1
Sodium lauryl sulfate 1.0
Purified water remaining
Total 100%

<Example 36>
<Mouthwash>
Glyceryl caprylate 0.5
Eucalyptus oil 0.2
Peppermint oil 0.2
Ethanol 20.0
Fragrance 1.0
Saccharin sodium 0.05
Chlorhexidine hydrochloride 0.01
Laurylethanolamide 0.3
Purified water remaining
Total 100%

<Example 37>
<Mouthwash>
Glyceryl caprylate 0.5
Peppermint oil 0.2
Xylitol 2.5
Denatured alcohol No.56 5.0
Glycerin 5.0
Polyoxyethylene hydrogenated castor oil 0.5
Dipotassium glycyrrhizinate 0.1
Sodium citrate 0.12
Citric acid 0.03
Ethyl paraoxybenzoate 0.05
Propyl paraoxybenzoate 0.05
Fragrance 0.1
Purified water remaining
Total 100%

<Example 38>
<Denture cleaner (liquid)>
Glyceryl caprylate 5
Hinokitiol 0.02
Clove oil 0.5
Ethanol 60.0
Sodium lauroyl sarcosinate 20.0
EDTA sodium 6.0
Chlorhexidine sodium gluconate 2.0
Fragrance 1.0
Purified water remaining
Total 100%
The above ingredients were mixed well to form a liquid. The 0.5-1.5 g was dissolved in 100-150 mL of water and used.

<Example 39>
<Denture cleaner (powder)>
Glyceryl caprylate 5
Eucalyptus oil 0.5
Peppermint oil 0.5
Sodium bicarbonate 31.0
Citric acid 25.0
Sodium lauryl sulfate 6.0
Polyethylene glycol 2.0
Fragrance 1.0
Purified water remaining
Total 100%
The above ingredients were mixed well to obtain a powder. The 1.0-2.5 g was dissolved in 100-150 mL of water and used.

<Example 40>
<Denture cleaner (tablets)>
Glyceryl caprylate 0.5
Isopropylmethylphenol 0.1
Sodium bicarbonate 30.0
Tartaric acid 27.0
Sodium cocoyl sarcosinate 5.0
Sodium lauryl sulfate 5.0
Benzalkonium chloride 2.0
EDTA sodium 5.0
Polyethylene glycol 2.0
Fragrance 1.0
Purified water remaining
Total 100%
The above ingredients were mixed well, and 2-3 g thereof was tableted with a tableting machine. One tablet was dissolved in 100 to 150 mL of water and used.

<Example 41>
<Face-wash form>
Glyceryl caprylate 1
Isopropylmethylphenol 0.1
Peppermint oil 0.1
Myristic acid 20.0
Palmitic acid 5.0
Lauric acid diethanolamide 3.5
Polyethylene glycol distearate (140) 1.0
Polyethylene glycol 400 5.0
N-lauroylmethyl taurine sodium solution 8.0
Glycerin 20.0
Sorbit liquid 3.0
Edetate disodium 0.05
Dibutylhydroxytoluene 0.05
Potassium hydroxide 5.3
Fragrance 0.1
Purified water remaining
100%

<Example 42>
<Liquid detergent>
Glyceryl caprylate 5
Isopropylmethylphenol 0.1
Eucalyptus oil 0.5
Lauryl glucoside 15.0
Sodium lauryl sulfate 10.0
Ethanol 5.0
Polypropylene glycol 2.0
Fragrance 0.1
Purified water remaining
100%

The biofilm was successfully suppressed (removed) by applying the compositions of Examples 16 to 40 described above to the denture surface on which plaques and biofilms were formed. In addition, the number of viable biofilms was <10 to 1.0 × 10 ⁷ CFU / ml. Furthermore, the compositions of Examples 41 and 42 were also able to suppress (remove) the biofilm satisfactorily when applied to the surface on which the biofilm was formed. In addition, the number of viable biofilms was <10 to 1.0 × 10 ⁷ CFU / ml. It was found that all the compositions of the present invention in Examples 16 to 40 suppressed the number of viable biofilms by 50% or more.

Claims (12)

  A biofilm inhibitor comprising monoglycerides of medium chain fatty acids having 6 to 12 carbon atoms.   The biofilm inhibitor according to claim 1, further comprising an antibacterial component selected from a phenolic antibacterial agent, a terpenoid essential oil, a phenylpropanoid essential oil, and a mixture thereof.   The biofilm inhibitor of Claim 1 or 2 whose content of the monoglyceride of the said medium chain fatty acid is 0.01-10 mass% with respect to the mass of the said biofilm inhibitor.   The biofilm inhibitor of Claim 2 or 3 whose content of the said antibacterial component is 0.005-5 mass% with respect to the mass of the said biofilm inhibitor.   The bio according to any one of claims 1 to 4, wherein the monoglyceride of the medium chain fatty acid is selected from the group consisting of glyceryl monocaproate, glyceryl monocaprylate, glyceryl monocaprate, glyceryl monolaurate, and mixtures thereof. Film inhibitor.   The biofilm inhibitor according to any one of claims 1 to 4, wherein the monoglyceride of the medium chain fatty acid is glyceryl monocaprylate.   The biofilm inhibitor according to any one of claims 2 to 6, wherein the antibacterial component is selected from the group consisting of isopropylmethylphenol, triclosan, and hinokitiol.   7. The antibacterial component according to claim 2, wherein the antibacterial component is a terpenoid or phenylpropanoid essential oil selected from the group consisting of eucalyptus oil, mint oil, clove oil, cinnamon oil and mixtures thereof. Biofilm inhibitor.   The composition for oral cavity for suppressing a biofilm containing the biofilm inhibitor of any one of Claims 1-8.   The cleaning composition for suppressing a biofilm containing the biofilm inhibitor of any one of Claims 1-8.   Cosmetics for suppressing a biofilm comprising the biofilm inhibitor according to any one of claims 1 to 8.   A method for inhibiting a biofilm, comprising applying the biofilm inhibitor according to any one of claims 1 to 8 to a surface on which the biofilm is formed.