WO2009081611A1 - Antibacterial agent and composition for the oral cavity, food and drink containing the same - Google Patents

Antibacterial agent and composition for the oral cavity, food and drink containing the same Download PDF

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Publication number
WO2009081611A1
WO2009081611A1 PCT/JP2008/063643 JP2008063643W WO2009081611A1 WO 2009081611 A1 WO2009081611 A1 WO 2009081611A1 JP 2008063643 W JP2008063643 W JP 2008063643W WO 2009081611 A1 WO2009081611 A1 WO 2009081611A1
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Prior art keywords
acid
antibacterial agent
fatty acid
acid monoglyceride
glycerin
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PCT/JP2008/063643
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French (fr)
Japanese (ja)
Inventor
Yasuo Tanaka
Shuji Kanatani
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Taiyo Corporation
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Publication of WO2009081611A1 publication Critical patent/WO2009081611A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/37—Esters of carboxylic acids
    • A61K8/375—Esters of carboxylic acids the alcohol moiety containing more than one hydroxy group
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A23L33/12—Fatty acids or derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • A61K31/231—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having one or two double bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • A61K31/232—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having three or more double bonds, e.g. etretinate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to an antibacterial agent for oral use containing ⁇ -linolenic acid monoglyceride or linoleic acid monoglyceride as an active ingredient, and further relates to an oral composition and food and drink containing the antibacterial agent.
  • Fatty acid monoglyceride (also referred to as monoacylglycerol or glycerin fatty acid ester) is a kind of oil and fat, and is a substance in which glycerin and fatty acid are combined one by one.
  • Fatty acid monoglycerides are emulsifiers widely used in processed foods (margarine, chocolate, ice cream, bread, cakes, etc.) as food additives.
  • glycerin organic acid fatty acid esters for example, glycerin acetic acid fatty acid ester, glycerin lactic acid fatty acid ester, glycerin citric acid fatty acid ester, glycerin succinic acid fatty acid ester
  • polyglycerin fatty acid esters for example, polyglycerin fatty acid ester, polyglycerin condensation
  • Ricinoleic acid esters and the like are also used as emulsifiers in processed foods (hereinafter, glycerin organic acid fatty acid esters and polyglycerin fatty acid esters are collectively referred to as “glycerin fatty acid derivatives”).
  • medium chain fatty acid monoglycerides are known to have antibacterial activity and are used for antibacterial purposes against heat-resistant spores and yeasts.
  • perfume such as organic acid, hinokitiol, benzoic acid, salicylic acid, thymol, eugenol, bisabolol, etc., monoglyceride of long chain fatty acid, siglycerin fatty acid ester, polyglycerin fatty acid ester, amino acid quaternary ammonium salt, polylysine, ethanol, Attempts have been made to enhance the antibacterial effect by using glycine, lysozyme and the like together (see Patent Documents 1 to 6).
  • Periodontal disease is thought to be a mixed infection caused by anaerobic bacteria present in the plaque in the periodontal pocket.
  • knitted anaerobic bacteria such as Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum (F. nucleatum) are known.
  • Streptococcus mutans S. mutans is known as a causative bacterium of dental caries.
  • polyglycerin fatty acid esters and fatty acid glycerin esters other than the above diglycerin fatty acid ester, sucrose fatty acid ester, polyoxyethylene sorbitan fatty acid ester
  • polyglycerin fatty acid esters and fatty acid glycerin esters other than the above diglycerin fatty acid ester, sucrose fatty acid ester, polyoxyethylene sorbitan fatty acid ester
  • antibacterial activity is relatively low Decline.
  • antibacterial agents for example, phenolic, benzoic acid, sorbic acid, organic halogen, pyridinium salts, and thiazole antibacterial agents are known, but many of these are in terms of safety. There is a problem.
  • examples of natural antibacterial agents include ethanol, polylysine, lysozyme, protamine, lactoferrin, glycine, chitosan, thymol, eugenol, oily licorice extract, ashitaba extract, bamboo extract, and spice extract. Since these natural antibacterial agents are natural materials, they are highly safe, but none of them is satisfactory in terms of antibacterial activity.
  • the present invention has been made in view of the above circumstances, and its purpose is a novel that has high safety, excellent blending characteristics, and strong antibacterial activity against periodontal disease causative bacteria and caries causative bacteria. It is to provide an antibacterial agent for oral cavity.
  • the gist of the present invention is as follows. [1] An oral antibacterial agent comprising ⁇ -linolenic acid monoglyceride or linoleic acid monoglyceride as an active ingredient, [2] A composition for oral cavity containing the antibacterial agent according to [1], [3] A food or drink containing the antibacterial agent according to [1].
  • a novel antibacterial agent for oral cavity having high safety, excellent blending characteristics, and strong antibacterial activity against periodontal disease causative bacteria and caries causative bacteria.
  • Porphyromonas gingivalis Porphyromonas gingivalis (P. gingivalis), Fusobacterium nucleatum (F. atumnucleatum) (both causing periodontal disease) and Streptococcus mutans (causative fungus for caries)
  • High antibacterial activity for this reason, prevention of a periodontal disease, a decayed tooth, etc. can be easily performed by mix
  • the antibacterial agent of the present invention is characterized in that ⁇ -linolenic acid monoglyceride or linoleic acid monoglyceride is an active ingredient.
  • the ⁇ -linolenic acid monoglyceride is a compound in which one molecule of ⁇ -linolenic acid and one molecule of glycerin are ester-bonded
  • the linoleic acid monoglyceride is a compound in which one molecule of linoleic acid and one molecule of glycerin are ester-bonded.
  • ⁇ -linolenic acid monoglyceride or linoleic acid monoglyceride is used as an active ingredient, in addition to the active ingredient, at least one fatty acid molecule having 8 to 24 carbon atoms and glycerin, diglycerin, triglycerin, etc.
  • Other fatty acid glycerin ester in which one molecule of glycerin component is ester-bonded may be contained.
  • fatty acids constituting other fatty acid glycerin esters include octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, dodecanoic acid, tridecanoic acid, tetradecanoic acid, pentadecanoic acid, hexadecanoic acid, heptadecanoic acid, octadecanoic acid, myristoleic acid , Palmitooleic acid, oleic acid, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid and the like.
  • the content of ⁇ -linolenic acid monoglyceride or linoleic acid monoglyceride in the antibacterial agent is preferably 5% by weight or more in the total fatty acid glycerin ester, 20% by weight % Or more is more preferable.
  • ⁇ -Linolenic acid monoglyceride can be produced by a known method, for example, a method of esterifying ⁇ -linolenic acid and glycerin using a chemical catalyst or an enzyme (lipase).
  • linoleic acid monoglyceride can be produced in the same manner as ⁇ -linolenic acid monoglyceride by using linoleic acid instead of ⁇ -linolenic acid.
  • a method using lipase is preferable because it can be produced under mild conditions.
  • ⁇ -Linolenic acid monoglyceride or linoleic acid monoglyceride as a reaction raw material is usually pure ⁇ -linolenic acid or linoleic acid, but hydrolyzes fats and oils containing ⁇ -linolenic acid triglyceride and linoleic acid triglyceride.
  • a mixture of ⁇ -linolenic acid and linoleic acid obtained in this manner can also be used.
  • fats and oils include higher vegetable oils such as linseed oil, sesame oil, rosehip oil, evening primrose oil, borage oil, and the like, which can be used as they are or after being purified.
  • the fatty acid as the reaction raw material can also be obtained by producing microorganisms such as mold and lactic acid bacteria.
  • the lipase used as a catalyst is not particularly limited as long as it recognizes glycerides as a substrate.
  • examples include monoglyceride lipase, mono and diglyceride lipase, triglyceride lipase, cutinase, esterase and the like.
  • a lipase is preferable, and a lipase that recognizes fatty acid monoglyceride and / or fatty acid diglyceride as a substrate and recognizes fatty acid triglyceride as a substrate is particularly preferable.
  • Such lipases include monoglyceride lipase, mono and diglyceride lipase and the like.
  • lipases examples include Penicillium genus, Pseudomonas genus, Burkholderia genus, Alcaligenes genus, Staphylococcus genus, Bacillus genus, candy genus Lipases derived from microorganisms such as Candida, Geotrichum, Rhizopus, Rhizomucor, Mucor, Aspergillus, Pseudozyme are used. . More preferred are lipases derived from the genus Penicillium and Bacillus. These lipases are generally commercially available and are readily available.
  • the lipase may be purified (including crude and partial purification). Furthermore, it may be used in a free form or may be used by being immobilized on a carrier such as an ion exchange resin, a porous resin, ceramics or calcium carbonate.
  • a carrier such as an ion exchange resin, a porous resin, ceramics or calcium carbonate.
  • the amount of the lipase used in the esterification reaction may be appropriately determined depending on the reaction temperature, reaction time, pressure (degree of decompression) and the like, and is not particularly limited, but is preferably 1 unit per gram of reaction mixture ( U) to 10,000 U.
  • 1 U of enzyme activity refers to the amount of enzyme that liberates 1 ⁇ mol of fatty acid per minute in the hydrolysis of olive oil.
  • the amount of enzyme that liberates 1 ⁇ mol of oleic acid per minute in hydrolysis of oleic acid monoglyceride In the case of monoglyceride lipase or mono- and diglyceride lipase, the amount of enzyme that liberates 1 ⁇ mol of oleic acid per minute in hydrolysis of oleic acid monoglyceride.
  • the ⁇ -linolenic acid and linoleic acid used in the esterification reaction may be in any form of free type, metal salt type, and ester type.
  • the free form is preferred in that the esterification reaction easily proceeds.
  • the amount of glycerin used for the esterification reaction is not particularly limited. Usually, the molar amount is preferably 1 to 10 times, more preferably 1 to 5 times the amount of 1 mol of free ⁇ -linolenic acid (or linoleic acid).
  • ⁇ -linolenic acid monoglyceride is produced with high purity when ⁇ -linolenic acid and glycerin are used as reaction raw materials by appropriately adjusting the reaction temperature, reaction time, pressure (decompression degree), etc. in the esterification reaction.
  • linoleic acid monoglyceride can be produced with high purity.
  • the reaction temperature is preferably 30 to 60 ° C.
  • the reaction time is preferably 30 to 60 hours
  • the pressure is preferably 0.1 to 30 mmHg.
  • the esterification reaction may be a stationary reaction, various stirring methods, shaking methods, ultrasonic methods, nitrogen blowing methods, circulating mixing methods using pumps, mixing methods using valves or pistons, or combinations thereof May be carried out while mixing the reaction solution.
  • any isolation / purification method can be adopted.
  • the isolation / purification method include deoxidation, washing with water, distillation, solvent extraction, ion exchange chromatography, silica gel column chromatography, membrane separation, and combinations of these methods. Note that the reaction mixture may be used as it is.
  • the antibacterial agent of the present invention includes Porphyromonas gingivalis (P. gingivalis), Fusobacterium nucleatum (F. nucleatum) (cause of periodontal disease), and Streptococcus mutans (causative agent of caries) High antibacterial activity.
  • the antibacterial agent of the present invention exhibits high antibacterial activity against the above bacteria. For this reason, prevention of a periodontal disease, a decayed tooth, etc. can be easily performed by mix
  • the content of the antibacterial agent in the oral composition (or in the food or drink) is usually 0.0001 to 50% by weight, preferably 0.001 to 5% by weight.
  • the form of the antibacterial agent of the present invention can be appropriately changed according to the type of oral composition and food and drink, and for example, granular, pasty, solid, liquid and the like can be adopted.
  • oral compositions include toothpaste, mouthwash, mouth freshener, and mouth spray.
  • examples of the food and drink include chewing gum, candy, tablet confectionery, film food, beverage, and confectionery.
  • antibacterial agent of the present invention When the antibacterial agent of the present invention is blended with the above oral composition or food and drink, one or more other antibacterial agents may be used in combination.
  • Other antibacterial agents that can be used in combination include, for example, cetylpyridinium chloride, decalinium chloride, benzalkonium chloride, chlorohexidine, triclosan, isopropylmethylphenol, ofloxacin, iodine, sodium fluoride, benzoic acid series, sorbic acid series, and organic halogen series.
  • Benzimidazole fungicides metal ions such as silver and copper, lecithin, sucrose fatty acid ester, medium chain fatty acid monoglyceride, polyoxyethylene sorbitan fatty acid ester, ethanol, propylene glycol, polylysine, lysozyme, protamine, propolis, lactoferrin,
  • metal ions such as silver and copper, lecithin, sucrose fatty acid ester, medium chain fatty acid monoglyceride, polyoxyethylene sorbitan fatty acid ester, ethanol, propylene glycol, polylysine, lysozyme, protamine, propolis, lactoferrin
  • Examples include glycine, chitosan, thymol, eugenol, oily licorice extract, mulberry white skin extract, ashitaba extract, spice extract, and plant extract extracts such as polyphenols.
  • the oral composition or the food or drink can be blended with commonly used components depending on the type of oral composition or food or drink.
  • ingredients include sugars, artificial sweeteners, fruit juices, chewing gum bases, acidulants, purified water, alcohols, oily ingredients, surfactants, thickeners, preservatives, moisturizers, powders, fragrances, pigments, emulsifiers.
  • PH adjuster deodorant, calcium stearate, sodium pyrophosphate, calcium phosphate, silicon dioxide, caffeine, vitamins, enzymes, ceramides, sterols, antioxidants, singlet oxygen scavenger, UV absorber, whitening Agents, anti-inflammatory agents, and other antibacterial agents.
  • examples of the saccharide include fructose, glucose, maltose, starch, dextrin, starch syrup, reduced malt starch syrup, maltose, palatinose, reduced palatinose, sorbitol, xylitol, trehalose, erythritol, sucralose, and the like.
  • artificial sweeteners include aspartame and saccharin.
  • examples of the oil component include liquid paraffin, petrolatum, solid paraffin, lanolin, lanolin fatty acid derivatives, dimethylpolysiloxane, higher alcohol higher fatty acid esters, fatty acids, long-chain amidoamines, animal and vegetable oils and the like.
  • Surfactants include polyoxyethylene hydrogenated castor oil, isostearyl glycerin ether, polyoxyethylene alkyl ether, glycerin fatty acid ester, polyethylene glycol, sorbitan monostearate, polyoxyethylene monostearate sorbitan, polyoxyethylene lauryl ether phosphorus Acid salt, N-stearoyl-N-methyl taurate, lauryl phosphate, monomyristyl phosphate, monocetyl phosphate, polyoxyethylene lauryl ether sulfate, lauryl sulfate triethanolamine, polyoxyethylene lauryl ether sulfate triethanolamine, etc. Is mentioned.
  • Examples of the thickener include water-soluble polymer compounds such as carboxyvinyl polymer, carboxymethylcellulose, polyvinyl alcohol, carrageenan, and gelatin.
  • Examples of the humectant include propylene glycol, glycerin, sorbitol, xylitol, and maltitol.
  • Examples of the powder include talc, sericite, mica, kaolin, silica, bentonite, zinc white, and mica.
  • a known device capable of producing the above-described form can be suitably used. Since the antibacterial agent of the present invention is excellent in blending characteristics, the antibacterial agent does not precipitate as crystals from the produced oral composition or food and drink.
  • a composition having an ⁇ -linolenic acid monoglyceride content of 85% by weight in the oil layer was obtained.
  • the obtained reaction product was repeatedly extracted by silica gel column chromatography to obtain a purified product having an ⁇ -linolenic acid monoglyceride content of 97% by weight.
  • linseed oil-derived fatty acid monoglyceride product of the present invention
  • linseed oil is hydrolyzed to produce a linseed oil-derived fatty acid, which is esterified in the presence of lipase using glycerin as a reaction raw material
  • Derived fatty acid monoglycerides were produced.
  • Manufacture of fatty acid derived from linseed oil In a 1 L circular reaction kettle, 80 ml of 12 mol / l sodium hydroxide aqueous solution and 250 ml of ethanol were mixed. Under a nitrogen stream, 100 g of linseed oil was added to the above mixture and gently mixed.
  • the mixture was saponified and decomposed by standing at 60 ° C. for 30 minutes. After the reaction, 200 ml of cold water was added, and the cooled reaction product was neutralized by adding concentrated hydrochloric acid. After neutralization, 300 ml of n-hexane was added, and a hexane layer containing linseed oil-derived free fatty acid was extracted. After extraction, the resulting hexane layer was desolvated to obtain 90 g of linseed oil-derived free fatty acid.
  • the obtained reaction product was repeatedly extracted with silica gel column chromatography to obtain a purified product having a linseed oil-derived fatty acid monoglyceride content of 98% by weight.
  • the fatty acid composition in the fatty acid monoglyceride derived from linseed oil is as follows: palmitic acid 4.9%, stearic acid 3.3%, oleic acid 16.9%, linoleic acid 16.7%, ⁇ -linolenic acid 57.4% The other was 0.8%.
  • the product of the present invention was prepared stepwise so that the final concentration in the medium was 1.5 ppm, 3 ppm, 6 ppm, 12 ppm, 25 ppm, 50 ppm, 100 ppm, 200 ppm, 400 ppm.
  • About 1 ⁇ 10 8 CFU / ml of Porphyromonas gingivalis (JCM5175), Fusobacterium nucleatum (ATCC25586) or Streptococcus mutans (S. mutans) was used for these sample solutions.
  • 0.1 ml of each culture solution of (JCM2151)) was added, and the mixture was stirred and cultured at 37 ° C. for 24 hours under aerobic conditions.
  • the antibacterial effect is judged visually, and compared to the above-mentioned microorganism-free test group, the minimum concentration required to prevent the growth of the test group in which turbidity due to microbial growth is not observed as having antibacterial effect (hereinafter referred to as “minimum”).
  • the growth inhibitory concentration was measured.
  • using cetylpyridinium chloride and oleic acid monoglyceride known as oral antibacterial agents produced in “1. Production Examples of Monoglycerides of Various Fatty Acids”
  • Inhibitory concentrations were measured. Table 1 shows the results.
  • the product of the present invention is an excellent antibacterial against any strain of P. gingivalis, Fusobacterium nucleatum, or Streptococcus mutans. It turns out that an effect is shown.
  • Chewing gum base 35.0 parts by weight Calcium carbonate 2.0 Maltitol 50.0 Erythritol 5.0 Reduced palatinose 5.0 Fragrance 1.0 ⁇ -Linolenic acid monoglyceride 0.5 Purified water 1.5 100.0 (Manufacturing method) After the chewing gum base was warmed and softened to 70 ° C., calcium carbonate, maltitol, erythritol, reduced palatinose and purified water were mixed little by little while keeping the mixture warm. Next, a mixture of a fragrance and ⁇ -linolenic acid monoglyceride was added to the sugar-mixed gum base obtained by the above mixing, and further mixed.
  • the chewing gum containing ⁇ -linolenic acid monoglyceride had a good taste without impairing the physical properties of the gum base.
  • ⁇ Toothpaste> Dicalcium phosphate 50.0 parts by weight Glycerin 20.0 Sorbitol 10.0 Sodium lauryl sulfate 1.0 Carrageenan 1.0 Fragrance 0.5 ⁇ -Linolenic acid monoglyceride 0.2 Purified water 18.0 100.7 (Manufacturing method) After mixing glycerin, sorbitol, sodium lauryl sulfate, carrageenan and purified water, dicalcium phosphate was mixed. Next, the resulting mixture was mixed with a fragrance and ⁇ -linolenic acid monoglyceride to obtain a toothpaste. (Composition characteristics) The toothpaste containing ⁇ -linolenic acid monoglyceride was stable without impairing the physical properties and had a good flavor.
  • ⁇ Mouthwash> Ethanol 15.0 parts by weight Polyoxyethylene hydrogenated castor oil 2.5 Glycerin 8.0 Saccharin sodium 0.5 Sodium benzoate 0.1 Fragrance 0.1 Linoleic acid monoglyceride 0.1 Dye 0.001 Purified water 75.0 101.3 (Manufacturing method) Polyoxyethylene hydrogenated castor oil was dissolved by heating in an ethanol / glycerin mixed solution, and then purified water was added to dissolve. Subsequently, saccharin sodium, sodium benzoate, a fragrance, linoleic acid monoglyceride and a dye were added to the obtained lysate and dissolved and mixed to obtain a mouthwash. (Composition characteristics) The linoleic acid monoglyceride-added mouthwash had good solubility during processing, no precipitate was formed, and the flavor was also good.
  • the antibacterial agent of the present invention is excellent in antibacterial effect against periodontal disease causative bacteria and caries causative bacteria, and therefore, for example, oral compositions such as toothpaste, mouthwash, mouth freshener, mouth spray, and chewing gum It is suitable as a compounding ingredient of foods and drinks such as candy, tablet confectionery, film-like food, beverage, and confectionery.

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Abstract

It is intended to provide a novel antibacterial agent for the oral cavity which has a high safety, excellent blending properties and a potent antibacterial activity against bacteria causative of periodontal diseases and bacteria causative of dental caries. An antibacterial agent characterized by comprising α-linolenic acid monoglyceride or linoleic acid monoglyceride as the active ingredient. This antibacterial agent is appropriately usable as a component of a composition for the oral cavity, a food and a drink.

Description

抗菌剤及びそれを含有する口腔用組成物並びに飲食品Antibacterial agent, oral composition containing it, and food and drink
　本発明はα－リノレン酸モノグリセリドまたはリノール酸モノグリセリドを有効成分とする口腔用抗菌剤に関し、さらには、前記抗菌剤を含有する口腔用組成物および飲食品に関する。 The present invention relates to an antibacterial agent for oral use containing α-linolenic acid monoglyceride or linoleic acid monoglyceride as an active ingredient, and further relates to an oral composition and food and drink containing the antibacterial agent.
　脂肪酸のモノグリセリド（モノアシルグリセロールまたはグリセリン脂肪酸エステルともいう）は油脂の一種で、グリセリンと脂肪酸が１個ずつ結合した物質である。脂肪酸のモノグリセリドは食品添加物として加工食品（マーガリン、チョコレート、アイスクリーム、パン、ケーキなど）に幅広く使用されている乳化剤である。 Fatty acid monoglyceride (also referred to as monoacylglycerol or glycerin fatty acid ester) is a kind of oil and fat, and is a substance in which glycerin and fatty acid are combined one by one. Fatty acid monoglycerides are emulsifiers widely used in processed foods (margarine, chocolate, ice cream, bread, cakes, etc.) as food additives.
　また、グリセリン有機酸脂肪酸エステル（例えば、グリセリン酢酸脂肪酸エステル、グリセリン乳酸脂肪酸エステル、グリセリンクエン酸脂肪酸エステル、グリセリンコハク酸脂肪酸エステルなど）やポリグリセリン脂肪酸エステル類（例えば、ポリグリセリン脂肪酸エステル、ポリグリセリン縮合リシノール酸エステルなど）も加工食品の乳化剤として使用されている（以下、グリセリン有機酸脂肪酸エステルとポリグリセリン脂肪酸エステル類をあわせて「グリセリン脂肪酸誘導体」という）。 Also, glycerin organic acid fatty acid esters (for example, glycerin acetic acid fatty acid ester, glycerin lactic acid fatty acid ester, glycerin citric acid fatty acid ester, glycerin succinic acid fatty acid ester) and polyglycerin fatty acid esters (for example, polyglycerin fatty acid ester, polyglycerin condensation) Ricinoleic acid esters and the like are also used as emulsifiers in processed foods (hereinafter, glycerin organic acid fatty acid esters and polyglycerin fatty acid esters are collectively referred to as “glycerin fatty acid derivatives”).
　上述した脂肪酸のモノグリセリドおよびグリセリン脂肪酸誘導体のうち、中鎖脂肪酸のモノグリセリドには抗菌活性を有するものが知られており、耐熱性芽胞菌や酵母に対する抗菌目的で使用されている。また、長鎖脂肪酸のモノグリセリドに対して有機酸、ヒノキチオール、安息香酸、サリチル酸、チモール、オイゲノール、ビサボロール等の香料、シグリセリン脂肪酸エステル、ポリグリセリン脂肪酸エステル、アミノ酸第４級アンモニウム塩、ポリリジン、エタノール、グリシン、リゾチーム等を併用し、抗菌効果を増強させることが試みられている（特許文献１～６参照）。 Among the above-mentioned fatty acid monoglycerides and glycerin fatty acid derivatives, medium chain fatty acid monoglycerides are known to have antibacterial activity and are used for antibacterial purposes against heat-resistant spores and yeasts. Also, perfume such as organic acid, hinokitiol, benzoic acid, salicylic acid, thymol, eugenol, bisabolol, etc., monoglyceride of long chain fatty acid, siglycerin fatty acid ester, polyglycerin fatty acid ester, amino acid quaternary ammonium salt, polylysine, ethanol, Attempts have been made to enhance the antibacterial effect by using glycine, lysozyme and the like together (see Patent Documents 1 to 6).
特開２００５－１７９２１１号公報Japanese Patent Laid-Open No. 2005-179211 特開２００３－１８３１０５号公報JP 2003-183105 A 特開２００３－１２４１１号公報JP 2003-12411 A 特開２００２－２１２０２１号公報Japanese Patent Laid-Open No. 2002-212021 特開２００１－１７１３７号公報JP 2001-17137 A 特開２０００－２７０８２１号公報JP 2000-270821 A
　歯肉炎や歯周炎などの歯周病の罹患率は厚生労働省の統計によると４０才以上の国民の８０％以上であり、口腔内の国民病として大変重要な問題である。また、今後高齢化がさらに進む中で、歯周病の予防対策は急務である。歯周病は歯周ポケットの歯垢中に存在する嫌気性細菌による混合感染症と考えられている。歯周病と最も関連が深い細菌として、ポルフィロモナス・ジンジバリス（P. gingivalis）やフソバクテリウム・ヌクレアタム（F. nucleatum）などの編性嫌気性細菌が知られている。また、虫歯（う蝕）の原因菌としてはストレプトコッカス・ミュータンス（S. mutans）が知られている。 The prevalence of periodontal diseases such as gingivitis and periodontitis is more than 80% of the population over 40 years old according to statistics from the Ministry of Health, Labor and Welfare, which is a very important issue as a national disease in the oral cavity. In addition, as the population ages further, preventive measures for periodontal disease are urgently needed. Periodontal disease is thought to be a mixed infection caused by anaerobic bacteria present in the plaque in the periodontal pocket. As bacteria most closely related to periodontal disease, knitted anaerobic bacteria such as Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum (F. nucleatum) are known. Further, Streptococcus mutans (S. mutans) is known as a causative bacterium of dental caries.
　そこで、従来から、歯周病の原因菌や虫歯の原因菌に対し、抗菌剤として上述した中鎖脂肪酸のモノグリセリドが使用されてきた。 Therefore, conventionally, monoglycerides of the above-mentioned medium chain fatty acids have been used as antibacterial agents against periodontal disease causative bacteria and caries causative bacteria.
　しかしながら、中鎖脂肪酸のモノグリセリドはある程度の抗菌活性を有しているが、脂溶性のため水やアルコールに対する溶解度が低く、物性的に結晶が析出しやすいため実用的でない。このため、好適な添加量で口腔用組成物や飲食品に配合するには不適当である。 However, although monoglycerides of medium chain fatty acids have some antibacterial activity, they are impractical because they are fat-soluble and have low solubility in water and alcohol, and crystals tend to precipitate out physically. For this reason, it is unsuitable to mix | blend with the composition for oral cavity and food-drinks with a suitable addition amount.
　また、上記のポリグリセリン脂肪酸エステル類や上記以外の脂肪酸グリセリンエステル（ジグリセリン脂肪酸エステル、ショ糖脂肪酸エステル、ポリオキシエチレンソルビタン脂肪酸エステル）は、比較的水に対する溶解度が向上するが、抗菌活性は相対的に低下する。 Moreover, although the above-mentioned polyglycerin fatty acid esters and fatty acid glycerin esters other than the above (diglycerin fatty acid ester, sucrose fatty acid ester, polyoxyethylene sorbitan fatty acid ester) have relatively improved solubility in water, antibacterial activity is relatively low Decline.
　さらに、上記以外の抗菌剤としては、例えば、フェノール系、安息香酸系、ソルビン酸系、有機ハロゲン系、ピリジニウム塩、チアゾール系の抗菌剤が知られているが、これらの多くは安全性の面で問題がある。 Furthermore, as antibacterial agents other than the above, for example, phenolic, benzoic acid, sorbic acid, organic halogen, pyridinium salts, and thiazole antibacterial agents are known, but many of these are in terms of safety. There is a problem.
　一方、天然系抗菌剤としては、例えば、エタノール、ポリリジン、リゾチーム、プロタミン、ラクトフェリン、グリシン、キトサン、チモール、オイゲノール、油性甘草エキス、アシタバ抽出エキス、竹抽出エキス、香辛料抽出物が挙げられる。これらの天然系抗菌剤は天然系素材であるため安全性は高いが、いずれも抗菌活性の点で満足いくものではない。 On the other hand, examples of natural antibacterial agents include ethanol, polylysine, lysozyme, protamine, lactoferrin, glycine, chitosan, thymol, eugenol, oily licorice extract, ashitaba extract, bamboo extract, and spice extract. Since these natural antibacterial agents are natural materials, they are highly safe, but none of them is satisfactory in terms of antibacterial activity.
　本発明は、上記事情に鑑みてなされたものであり、その目的は、安全性が高く、配合特性に優れ、かつ歯周病の原因菌や虫歯の原因菌に対して強い抗菌活性を有する新規の口腔用抗菌剤を提供することにある。 The present invention has been made in view of the above circumstances, and its purpose is a novel that has high safety, excellent blending characteristics, and strong antibacterial activity against periodontal disease causative bacteria and caries causative bacteria. It is to provide an antibacterial agent for oral cavity.
　本発明者らは、上記課題を解決するため鋭意検討した結果、α－リノレン酸モノグリセリドとリノール酸モノグリセリドが歯周病の原因菌や虫歯の原因菌に対して強力な抗菌活性を示し、かつ配合特性にも優れることを見出し、本発明を完成した。 As a result of intensive studies to solve the above-mentioned problems, the present inventors have shown that α-linolenic acid monoglyceride and linoleic acid monoglyceride have strong antibacterial activity against periodontal disease causative bacteria and caries causative bacteria, and are formulated. The inventors have found that the properties are excellent and completed the present invention.
　すなわち、本発明の要旨は以下のとおりである。
〔１〕　α－リノレン酸モノグリセリドまたはリノール酸モノグリセリドを有効成分とする口腔用抗菌剤、
〔２〕　前記〔１〕記載の抗菌剤を含有する口腔用組成物、
〔３〕　前記〔１〕記載の抗菌剤を含有する飲食品。 That is, the gist of the present invention is as follows.
[1] An oral antibacterial agent comprising α-linolenic acid monoglyceride or linoleic acid monoglyceride as an active ingredient,
[2] A composition for oral cavity containing the antibacterial agent according to [1],
[3] A food or drink containing the antibacterial agent according to [1].
　本発明によれば、安全性が高く、配合特性に優れ、かつ歯周病の原因菌や虫歯の原因菌に対して強い抗菌活性を有する新規の口腔用抗菌剤が提供される。特に、抗菌活性については、ポルフィロモナス・ジンジバリス（P. gingivalis）やフソバクテリウム・ヌクレアタム（F. nucleatum）（ともに歯周病の原因菌）およびストレプトコッカス・ミュータンス（S. mutans）（虫歯の原因菌）に対して高い抗菌活性を示す。このため、本発明に係る抗菌剤を口腔用組成物や飲食品に配合することで、歯周病、虫歯などの予防が容易に実行可能となる。 According to the present invention, a novel antibacterial agent for oral cavity having high safety, excellent blending characteristics, and strong antibacterial activity against periodontal disease causative bacteria and caries causative bacteria is provided. In particular, for antibacterial activity, Porphyromonas gingivalis (P. gingivalis), Fusobacterium nucleatum (F. atumnucleatum) (both causing periodontal disease) and Streptococcus mutans (causative fungus for caries) ) High antibacterial activity. For this reason, prevention of a periodontal disease, a decayed tooth, etc. can be easily performed by mix | blending the antibacterial agent which concerns on this invention with a composition for oral cavity, or food-drinks.
　本発明の抗菌剤は、α－リノレン酸モノグリセリドまたはリノール酸モノグリセリドを有効成分とする点に特徴がある。α－リノレン酸モノグリセリドとは、α－リノレン酸１分子とグリセリン１分子とがエステル結合した化合物であり、リノール酸モノグリセリドとは、リノール酸１分子とグリセリン１分子とがエステル結合した化合物である。 The antibacterial agent of the present invention is characterized in that α-linolenic acid monoglyceride or linoleic acid monoglyceride is an active ingredient. The α-linolenic acid monoglyceride is a compound in which one molecule of α-linolenic acid and one molecule of glycerin are ester-bonded, and the linoleic acid monoglyceride is a compound in which one molecule of linoleic acid and one molecule of glycerin are ester-bonded.
　α－リノレン酸モノグリセリドまたはリノール酸モノグリセリドを有効成分とする場合、抗菌活性を損なわない範囲で、該有効成分以外に炭素数が８～２４の脂肪酸１分子以上とグリセリン、ジグリセリンまたはトリグリセリンなどのグリセリン成分１分子とがエステル結合した他の脂肪酸グリセリンエステルが含有されていてもよい。 When α-linolenic acid monoglyceride or linoleic acid monoglyceride is used as an active ingredient, in addition to the active ingredient, at least one fatty acid molecule having 8 to 24 carbon atoms and glycerin, diglycerin, triglycerin, etc. Other fatty acid glycerin ester in which one molecule of glycerin component is ester-bonded may be contained.
　他の脂肪酸グリセリンエステルを構成する脂肪酸としては、例えば、オクタン酸、ノナン酸、デカン酸、ウンデカン酸、ドデカン酸、トリデカン酸、テトラデカン酸、ペンタデカン酸、ヘキサデカン酸、ヘプタデカン酸、オクタデカン酸、ミリストレイン酸、パルミトオレイン酸、オレイン酸、エイコサペンタエン酸、ドコサペンタエン酸、ドコサヘキサエン酸などが挙げられる。上記の脂肪酸グリセリンエステルが抗菌剤の構成成分として含まれる場合、抗菌剤中のα－リノレン酸モノグリセリドまたはリノール酸モノグリセリドの含量は、全脂肪酸グリセリンエステル中５重量％以上とすることが好ましく、２０重量％以上とすることがより好ましい。 Examples of fatty acids constituting other fatty acid glycerin esters include octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, dodecanoic acid, tridecanoic acid, tetradecanoic acid, pentadecanoic acid, hexadecanoic acid, heptadecanoic acid, octadecanoic acid, myristoleic acid , Palmitooleic acid, oleic acid, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid and the like. When the fatty acid glycerin ester is included as a constituent of the antibacterial agent, the content of α-linolenic acid monoglyceride or linoleic acid monoglyceride in the antibacterial agent is preferably 5% by weight or more in the total fatty acid glycerin ester, 20% by weight % Or more is more preferable.
　α－リノレン酸モノグリセリドは公知の方法で製造することができ、例えば、化学触媒または酵素（リパーゼ）を用いてα－リノレン酸とグリセリンとをエステル化する方法を挙げることができる。また、リノール酸モノグリセリドは、α－リノレン酸に代えてリノール酸を用いることにより、α－リノレン酸モノグリセリドと同様の方法で製造することができる。本発明では、上記の方法のうち、温和な条件で製造できる点で、リパーゼを用いる方法が好適である。 Α-Linolenic acid monoglyceride can be produced by a known method, for example, a method of esterifying α-linolenic acid and glycerin using a chemical catalyst or an enzyme (lipase). In addition, linoleic acid monoglyceride can be produced in the same manner as α-linolenic acid monoglyceride by using linoleic acid instead of α-linolenic acid. In the present invention, among the above methods, a method using lipase is preferable because it can be produced under mild conditions.
　α－リノレン酸モノグリセリドまたはリノール酸モノグリセリドの反応原料としての脂肪酸は、通常α－リノレン酸またはリノール酸の純品が用いられるが、α－リノレン酸のトリグリセリド及びリノール酸のトリグリセリドを含む油脂を加水分解して得られるα－リノレン酸とリノール酸の混合物を用いることもできる。かかる油脂としては、例えば、亜麻仁油、エゴマ油、ローズヒップ油、月見草油、ボラージ油などの高等植物油などが挙げられ、これらは、そのままで、または精製して用いることができる。また、上記反応原料としての脂肪酸はカビや乳酸菌などの微生物生産により得ることもできる。 α-Linolenic acid monoglyceride or linoleic acid monoglyceride as a reaction raw material is usually pure α-linolenic acid or linoleic acid, but hydrolyzes fats and oils containing α-linolenic acid triglyceride and linoleic acid triglyceride. A mixture of α-linolenic acid and linoleic acid obtained in this manner can also be used. Examples of such fats and oils include higher vegetable oils such as linseed oil, sesame oil, rosehip oil, evening primrose oil, borage oil, and the like, which can be used as they are or after being purified. Moreover, the fatty acid as the reaction raw material can also be obtained by producing microorganisms such as mold and lactic acid bacteria.
　触媒として使用されるリパーゼは、グリセリド類を基質として認識するものであれば特に限定されない。例えば、モノグリセリドリパーゼ、モノおよびジグリセリドリパーゼ、トリグリセリドリパーゼ、クチナーゼ、エステラーゼなどが挙げられる。これらの中でもリパーゼが好ましく、特に脂肪酸トリグリセリドを基質としてほとんど認識せず、脂肪酸モノグリセリドおよび／または脂肪酸ジグリセリドを基質として認識するリパーゼが好ましい。このようなリパーゼとして、モノグリセリドリパーゼ、モノおよびジグリセリドリパーゼなどが挙げられる。 The lipase used as a catalyst is not particularly limited as long as it recognizes glycerides as a substrate. Examples include monoglyceride lipase, mono and diglyceride lipase, triglyceride lipase, cutinase, esterase and the like. Among these, a lipase is preferable, and a lipase that recognizes fatty acid monoglyceride and / or fatty acid diglyceride as a substrate and recognizes fatty acid triglyceride as a substrate is particularly preferable. Such lipases include monoglyceride lipase, mono and diglyceride lipase and the like.
　このようなリパーゼとしては、例えば、ペニシリウム（Penicillium）属、シュードモナス（Pseudomonas）属、バークホルデリア（Burkholderia）属、アルカリゲネス（Alcaligenes）属、スタフィロコッカス（Staphylococcus）属、バシラス（Bacillus）属、キャンディダ（Candida）属、ゲオトリカム（Geotrichum）属、リゾプス（Rhizopus）属、リゾムコール（Rhizomucor）属、ムコール（Mucor）属、アスペルギルス（Aspergillus）属、シュードチマ（Pseudozyme）属などの微生物由来のリパーゼが用いられる。より好ましくはペニシリウム（Penicillium）属、バシラス（Bacillus）属由来のリパーゼである。これらのリパーゼは一般に市販されており、容易に入手可能である。 Examples of such lipases include Penicillium genus, Pseudomonas genus, Burkholderia genus, Alcaligenes genus, Staphylococcus genus, Bacillus genus, candy genus Lipases derived from microorganisms such as Candida, Geotrichum, Rhizopus, Rhizomucor, Mucor, Aspergillus, Pseudozyme are used. . More preferred are lipases derived from the genus Penicillium and Bacillus. These lipases are generally commercially available and are readily available.
　リパーゼは精製（粗精製および部分精製を含む）されたものを用いてもよい。さらに、遊離型のまま使用してもよく、あるいはイオン交換樹脂、多孔性樹脂、セラミックス、炭酸カルシウムなどの担体に固定化して使用してもよい。 The lipase may be purified (including crude and partial purification). Furthermore, it may be used in a free form or may be used by being immobilized on a carrier such as an ion exchange resin, a porous resin, ceramics or calcium carbonate.
　エステル化反応に使用されるリパーゼの量は、反応温度、反応時間、圧力（減圧度）などにより適宜決定すればよく、特に限定されるものではないが、好ましくは反応混合液１ｇ当たり１単位（Ｕ）～１００００Ｕである。酵素活性の１Ｕとは、リパーゼの場合、オリーブ油の加水分解において１分間に１μモルの脂肪酸を遊離する酵素量をいう。モノグリセリドリパーゼ、あるいはモノおよびジグリセリドリパーゼの場合は、オレイン酸モノグリセリドの加水分解において、１分間に１μモルのオレイン酸を遊離する酵素量である。 The amount of the lipase used in the esterification reaction may be appropriately determined depending on the reaction temperature, reaction time, pressure (degree of decompression) and the like, and is not particularly limited, but is preferably 1 unit per gram of reaction mixture ( U) to 10,000 U. In the case of lipase, 1 U of enzyme activity refers to the amount of enzyme that liberates 1 μmol of fatty acid per minute in the hydrolysis of olive oil. In the case of monoglyceride lipase or mono- and diglyceride lipase, the amount of enzyme that liberates 1 μmol of oleic acid per minute in hydrolysis of oleic acid monoglyceride.
　エステル化反応に使用されるα－リノレン酸およびリノール酸は、遊離型、金属塩型、およびエステル型のいずれの形態でもよい。本発明においては、エステル化反応が進行しやすい点で、遊離型が好ましい。 The α-linolenic acid and linoleic acid used in the esterification reaction may be in any form of free type, metal salt type, and ester type. In the present invention, the free form is preferred in that the esterification reaction easily proceeds.
　エステル化反応に使用されるグリセリンの量は特に限定されない。通常、遊離型のα－リノレン酸（またはリノール酸）１モル量に対して、好ましくは１～１０倍モル量、より好ましくは１～５倍モル量である。 The amount of glycerin used for the esterification reaction is not particularly limited. Usually, the molar amount is preferably 1 to 10 times, more preferably 1 to 5 times the amount of 1 mol of free α-linolenic acid (or linoleic acid).
　本発明では、エステル化反応において反応温度、反応時間、圧力（減圧度）などを適宜調整することにより、α－リノレン酸とグリセリンを反応原料とする場合は、α－リノレン酸モノグリセリドを純度よく製造することができ、リノール酸とグリセリンを反応原料とする場合は、リノール酸モノグリセリドを純度よく製造することができる。反応温度は好ましくは３０～６０℃であり、反応時間は好ましくは３０～６０時間であり、圧力は好ましくは０．１～３０ｍｍＨｇである。また、リパーゼの活性を維持するため、α－リノレン酸（またはリノール酸）とグリセリンの合計量に対して０．３～３重量％の水を添加することが好ましい。 In the present invention, α-linolenic acid monoglyceride is produced with high purity when α-linolenic acid and glycerin are used as reaction raw materials by appropriately adjusting the reaction temperature, reaction time, pressure (decompression degree), etc. in the esterification reaction. In the case where linoleic acid and glycerin are used as reaction raw materials, linoleic acid monoglyceride can be produced with high purity. The reaction temperature is preferably 30 to 60 ° C., the reaction time is preferably 30 to 60 hours, and the pressure is preferably 0.1 to 30 mmHg. In order to maintain the activity of lipase, it is preferable to add 0.3 to 3% by weight of water with respect to the total amount of α-linolenic acid (or linoleic acid) and glycerin.
　エステル化反応は静置反応でもよいし、各種の撹拌法、振盪法、超音波法、窒素などの吹き込み法、ポンプなどによる循環混合法、弁またはピストンを用いる混合法などにより、あるいはこれらの組み合わせにより、反応液を混合しながら行ってもよい。 The esterification reaction may be a stationary reaction, various stirring methods, shaking methods, ultrasonic methods, nitrogen blowing methods, circulating mixing methods using pumps, mixing methods using valves or pistons, or combinations thereof May be carried out while mixing the reaction solution.
　反応混合液から、α－リノレン酸モノグリセリド（またはリノール酸モノグリセリド）を単離・精製する方法としては、任意の単離・精製法を採用し得る。単離・精製方法としては、例えば、脱酸、水洗、蒸留、溶媒抽出、イオン交換クロマトグラフィー、シリカゲルカラムクロマトグラフィー、膜分離など、およびこれらの方法の組み合わせが挙げられる。なお、反応混合液をそのまま使用してもよい。 As the method for isolating and purifying α-linolenic acid monoglyceride (or linoleic acid monoglyceride) from the reaction mixture, any isolation / purification method can be adopted. Examples of the isolation / purification method include deoxidation, washing with water, distillation, solvent extraction, ion exchange chromatography, silica gel column chromatography, membrane separation, and combinations of these methods. Note that the reaction mixture may be used as it is.
　本発明の抗菌剤は、ポルフィロモナス・ジンジバリス（P. gingivalis）やフソバクテリウム・ヌクレアタム（F. nucleatum）（歯周病の原因菌）およびストレプトコッカス・ミュータンス（S. mutans）（虫歯の原因菌）に対して高い抗菌活性を示す。 The antibacterial agent of the present invention includes Porphyromonas gingivalis (P. gingivalis), Fusobacterium nucleatum (F. nucleatum) (cause of periodontal disease), and Streptococcus mutans (causative agent of caries) High antibacterial activity.
　本発明の抗菌剤は、上記の細菌類に対して高い抗菌活性を示す。このため、本発明に係る抗菌剤を口腔用組成物や飲食品に配合することで、歯周病、虫歯などの予防が容易に実行可能となる。口腔用組成物中（または飲食品中）の抗菌剤の含量は、通常０．０００１～５０重量％であり、好ましくは０．００１～５重量％である。 The antibacterial agent of the present invention exhibits high antibacterial activity against the above bacteria. For this reason, prevention of a periodontal disease, a decayed tooth, etc. can be easily performed by mix | blending the antibacterial agent which concerns on this invention with a composition for oral cavity, or food-drinks. The content of the antibacterial agent in the oral composition (or in the food or drink) is usually 0.0001 to 50% by weight, preferably 0.001 to 5% by weight.
　本発明の抗菌剤の形態は、口腔用組成物および飲食品の種類に応じて適宜変更可能であり、例えば、粒状、ペースト状、固形状、液体状などが採用できる。 The form of the antibacterial agent of the present invention can be appropriately changed according to the type of oral composition and food and drink, and for example, granular, pasty, solid, liquid and the like can be adopted.
　口腔用組成物としては、例えば、練り歯磨き、マウスウォッシュ、口中清涼剤、口中スプレーなど挙げられる。飲食品としては、例えば、チューインガム、キャンディー、錠菓、フィルム状食品、飲料、菓子などが挙げられる。 Examples of oral compositions include toothpaste, mouthwash, mouth freshener, and mouth spray. Examples of the food and drink include chewing gum, candy, tablet confectionery, film food, beverage, and confectionery.
　上記の口腔用組成物または飲食品に本発明の抗菌剤を配合する場合、他の抗菌剤の１種または２種以上を併用してもよい。併用できる他の抗菌剤としては、例えば、塩化セチルピリジニウム、塩化デカリニウム、塩化ベンザルコニウム、クロロヘキシジン、トリクロサン、イソプロピルメチルフェノール、オフロキサシン、ヨウ素、フッ化ナトリウム、安息香酸系、ソルビン酸系、有機ハロゲン系、ベンズイミダゾール系の殺菌剤、銀、銅などの金属イオン、レシチン、ショ糖脂肪酸エステル、中鎖脂肪酸モノグリセリド、ポリオキシエチレンソルビタン脂肪酸エステル、エタノール、プロピレングリコール、ポリリジン、リゾチーム、プロタミン、プロポリス、ラクトフェリン、グリシン、キトサン、チモール、オイゲノール、油性甘草エキス、桑白皮エキス、アシタバ抽出エキス、香辛料抽出物、ポリフェノールなどの植物抽出物エキスなどが挙げられる。 When the antibacterial agent of the present invention is blended with the above oral composition or food and drink, one or more other antibacterial agents may be used in combination. Other antibacterial agents that can be used in combination include, for example, cetylpyridinium chloride, decalinium chloride, benzalkonium chloride, chlorohexidine, triclosan, isopropylmethylphenol, ofloxacin, iodine, sodium fluoride, benzoic acid series, sorbic acid series, and organic halogen series. , Benzimidazole fungicides, metal ions such as silver and copper, lecithin, sucrose fatty acid ester, medium chain fatty acid monoglyceride, polyoxyethylene sorbitan fatty acid ester, ethanol, propylene glycol, polylysine, lysozyme, protamine, propolis, lactoferrin, Examples include glycine, chitosan, thymol, eugenol, oily licorice extract, mulberry white skin extract, ashitaba extract, spice extract, and plant extract extracts such as polyphenols.
　上記の口腔用組成物または飲食品には、本発明に係る抗菌剤の抗菌作用を阻害しない限り、口腔用組成物または飲食品の種類に応じて常用される成分を配合することができる。
かかる成分としては、糖類、人工甘味料、果汁、チューインガムベース、酸味料、精製水、アルコール類、油性成分、界面活性剤、増粘剤、防腐剤、保湿剤、粉体、香料、色素、乳化剤、ｐＨ調整剤、消臭剤、ステアリン酸カルシウム、ピロリン酸ナトリウム、リン酸カルシウム、二酸化ケイ素、カフェイン、ビタミン類、酵素、セラミド類、ステロール類、抗酸化剤、一重項酸素消去剤、紫外線吸収剤、美白剤、抗炎症剤、他の抗菌剤などが挙げられる。 As long as the antibacterial action of the antibacterial agent according to the present invention is not inhibited, the oral composition or the food or drink can be blended with commonly used components depending on the type of oral composition or food or drink.
Such ingredients include sugars, artificial sweeteners, fruit juices, chewing gum bases, acidulants, purified water, alcohols, oily ingredients, surfactants, thickeners, preservatives, moisturizers, powders, fragrances, pigments, emulsifiers. , PH adjuster, deodorant, calcium stearate, sodium pyrophosphate, calcium phosphate, silicon dioxide, caffeine, vitamins, enzymes, ceramides, sterols, antioxidants, singlet oxygen scavenger, UV absorber, whitening Agents, anti-inflammatory agents, and other antibacterial agents.
　具体的には、糖類としては、果糖、グルコース、マルトース、デンプン、デキストリン、水飴、還元麦芽水飴、マルチトース、パラチノース、還元パラチノース、ソルビトール、キシリトール、トレハロース、エリスリトール、スクラロースなどが挙げられる。人工甘味料としては、アスパルテーム、サッカリンなどが挙げられる。油性成分としては、流動パラフィン、ワセリン、固形パラフィン、ラノリン、ラノリン脂肪酸誘導体、ジメチルポリシロキサン、高級アルコール高級脂肪酸エステル類、脂肪酸、長鎖アミドアミン類、動植物油脂などが挙げられる。界面活性剤としては、ポリオキシエチレン硬化ヒマシ油、イソステアリルグリセリンエーテル、ポリオキシエチレンアルキルエーテル、グリセリン脂肪酸エステル、ポリエチレングリコール、モノステアリン酸ソルビタン、ポリオキシエチレンモノステアリン酸ソルビタン、ポリオキシエチレンラウリルエーテルリン酸塩、Ｎ－ステアロイル－Ｎ－メチルタウリン塩、ラウリルリン酸、リン酸モノミリスチル、リン酸モノセチル、ポリオキシエチレンラウリルエーテル硫酸塩、ラウリル硫酸トリエタノールアミン、ポリオキシエチレンラウリルエーテル硫酸トリエタノールアミンなどが挙げられる。増粘剤としては、カルボキシビニルポリマー、カルボキシメチルセルロース、ポリビニルアルコール、カラギーナン、ゼラチンなどの水溶性高分子化合物が挙げられる。保湿剤としては、プロピレングリコール、グリセリン、ソルビトール、キシリトール、マルチトールなどが挙げられる。粉体としては、タルク、セリサイト、マイカ、カオリン、シリカ、ベントナイト、亜鉛華、雲母などが挙げられる。 Specifically, examples of the saccharide include fructose, glucose, maltose, starch, dextrin, starch syrup, reduced malt starch syrup, maltose, palatinose, reduced palatinose, sorbitol, xylitol, trehalose, erythritol, sucralose, and the like. Examples of artificial sweeteners include aspartame and saccharin. Examples of the oil component include liquid paraffin, petrolatum, solid paraffin, lanolin, lanolin fatty acid derivatives, dimethylpolysiloxane, higher alcohol higher fatty acid esters, fatty acids, long-chain amidoamines, animal and vegetable oils and the like. Surfactants include polyoxyethylene hydrogenated castor oil, isostearyl glycerin ether, polyoxyethylene alkyl ether, glycerin fatty acid ester, polyethylene glycol, sorbitan monostearate, polyoxyethylene monostearate sorbitan, polyoxyethylene lauryl ether phosphorus Acid salt, N-stearoyl-N-methyl taurate, lauryl phosphate, monomyristyl phosphate, monocetyl phosphate, polyoxyethylene lauryl ether sulfate, lauryl sulfate triethanolamine, polyoxyethylene lauryl ether sulfate triethanolamine, etc. Is mentioned. Examples of the thickener include water-soluble polymer compounds such as carboxyvinyl polymer, carboxymethylcellulose, polyvinyl alcohol, carrageenan, and gelatin. Examples of the humectant include propylene glycol, glycerin, sorbitol, xylitol, and maltitol. Examples of the powder include talc, sericite, mica, kaolin, silica, bentonite, zinc white, and mica.
　上記の口腔用組成物または飲食品に本発明の抗菌剤を配合する際は、上述した形態を製造し得る公知の装置（パドルミキサー、ホモミキサー、ホモジナイザーなど）が好適に使用できる。本発明の抗菌剤は配合特性に優れるので、製造された口腔用組成物または飲食品から該抗菌剤が結晶として析出することはない。 When blending the antibacterial agent of the present invention into the oral composition or food / beverage product, a known device (paddle mixer, homomixer, homogenizer, etc.) capable of producing the above-described form can be suitably used. Since the antibacterial agent of the present invention is excellent in blending characteristics, the antibacterial agent does not precipitate as crystals from the produced oral composition or food and drink.
　以下、試験例などにより本発明をさらに詳しく説明するが、本発明はこれらによりなんら限定されるものではない。 Hereinafter, the present invention will be described in more detail with reference to test examples, but the present invention is not limited thereto.
１．　各種脂肪酸のモノグリセリドの製造例
1-1.　α―リノレン酸モノグリセリド（本発明品）の製造例
　約３０ｍｌのバイアル瓶中に、１０ｇのα―リノレン酸／グリセリン（１／２（モル比））の混液、０．１ｇの水、および２００Ｕのモノおよびジグリセリドリパーゼ（天野エンザイム社製、ペニシリウム・カマンベルティ（P. camembertii）由来、商品名「リパーゼＧ」）を添加し、マグネチックスターラーで撹拌しながら、３５℃、２ｍｍＨｇで４８時間反応させた。反応終了後、油層のα－リノレン酸モノグリセリドの含量が８５重量％の組成物を得た。得られた反応品をシリカゲルカラムクロマトグラフィーにて繰り返し抽出し、α―リノレン酸モノグリセリドの含量が９７重量％の精製物を得た。 1. Production examples of monoglycerides of various fatty acids
1-1. Production example of α-linolenic acid monoglyceride (product of the present invention) In a 30 ml vial, 10 g of α-linolenic acid / glycerin (1/2 (molar ratio)) mixed solution, 0.1 g of water , And 200 U mono- and diglyceride lipase (Amano Enzyme, P. camembertii, trade name “Lipase G”) was added and stirred at 35 ° C. and 2 mmHg for 48 hours while stirring with a magnetic stirrer. Reacted for hours. After completion of the reaction, a composition having an α-linolenic acid monoglyceride content of 85% by weight in the oil layer was obtained. The obtained reaction product was repeatedly extracted by silica gel column chromatography to obtain a purified product having an α-linolenic acid monoglyceride content of 97% by weight.
1-2.　　亜麻仁油由来脂肪酸モノグリセリド（本発明品）の製造例
　まず、亜麻仁油を加水分解して亜麻仁油由来脂肪酸を製造し、これとグリセリンを反応原料としてリパーゼの存在下エステル化して亜麻仁油由来脂肪酸モノグリセリドを製造した。
（亜麻仁油由来脂肪酸の製造）
　１Ｌの円形反応釜中に１２mol／ｌの水酸化ナトリウム水溶液８０ｍｌとエタノール２５０ｍｌを混合した。窒素気流下、亜麻仁油１００ｇを上記混合物に添加し静かに混合した。混合物を６０℃で３０分間静置することによりケン化分解した。反応後冷水２００ｍｌを加え、次いで冷却した反応物に濃塩酸を添加し中和した。中和後、ｎ－ヘキサン３００ｍｌを加え、亜麻仁油由来遊離脂肪酸を含むヘキサン層を抽出した。抽出後、得られたヘキサン層を脱溶媒し、亜麻仁油由来遊離脂肪酸を９０ｇ得た。
（エステル化）
　約３０ｍｌのバイアル瓶中に、１０ｇの亜麻仁油由来脂肪酸／グリセリン（１／２（モル比））の混液、０．１ｇの水、および２００Ｕのモノおよびジグリセリドリパーゼ（天野エンザイム社製、ペニシリウム・カマンベルティ（P. camembertii）由来、商品名「リパーゼＧ」）を添加し、マグネチックスターラーで撹拌しながら、３５℃、２ｍｍＨｇで４８時間反応させた。反応終了後、油層の亜麻仁油由来脂肪酸モノグリセリドの含量が８０重量％の組成物を得た。得られた反応品をシリカゲルカラムクロマトグラフィーにて繰り返し抽出し、亜麻仁油由来脂肪酸モノグリセリドの含量が９８重量％の精製物を得た。
（脂肪酸組成）
　得られた亜麻仁油由来脂肪酸モノグリセリド中の脂肪酸組成は、パルミチン酸４．９％、ステアリン酸３．３％、オレイン酸１６．９％、リノール酸１６．７％、α－リノレン酸５７．４％、その他０．８％であった。 1-2. Production example of linseed oil-derived fatty acid monoglyceride (product of the present invention) First, linseed oil is hydrolyzed to produce a linseed oil-derived fatty acid, which is esterified in the presence of lipase using glycerin as a reaction raw material, Derived fatty acid monoglycerides were produced.
(Manufacture of fatty acid derived from linseed oil)
In a 1 L circular reaction kettle, 80 ml of 12 mol / l sodium hydroxide aqueous solution and 250 ml of ethanol were mixed. Under a nitrogen stream, 100 g of linseed oil was added to the above mixture and gently mixed. The mixture was saponified and decomposed by standing at 60 ° C. for 30 minutes. After the reaction, 200 ml of cold water was added, and the cooled reaction product was neutralized by adding concentrated hydrochloric acid. After neutralization, 300 ml of n-hexane was added, and a hexane layer containing linseed oil-derived free fatty acid was extracted. After extraction, the resulting hexane layer was desolvated to obtain 90 g of linseed oil-derived free fatty acid.
(Esterification)
In an approximately 30 ml vial, 10 g of linseed oil-derived fatty acid / glycerin (1/2 (molar ratio)), 0.1 g of water, and 200 U of mono- and diglyceride lipase (Amano Enzyme, Penicillium Kaman) Berty (P. camembertii origin, trade name “Lipase G”) was added and reacted at 35 ° C. and 2 mmHg for 48 hours while stirring with a magnetic stirrer. After completion of the reaction, a composition having a content of 80% by weight of linseed oil-derived fatty acid monoglyceride in the oil layer was obtained. The obtained reaction product was repeatedly extracted with silica gel column chromatography to obtain a purified product having a linseed oil-derived fatty acid monoglyceride content of 98% by weight.
(Fatty acid composition)
The fatty acid composition in the fatty acid monoglyceride derived from linseed oil is as follows: palmitic acid 4.9%, stearic acid 3.3%, oleic acid 16.9%, linoleic acid 16.7%, α-linolenic acid 57.4% The other was 0.8%.
1-3.　リノール酸モノグリセリド（本発明品）の製造例
　約３０ｍｌのバイアル瓶中に、１００ｇのリノール酸／グリセリン（１／２（モル比））の混液、０．１ｇの水、および２００Ｕのモノおよびジグリセリドリパーゼ（天野エンザイム社製、ペニシリウム・カマンベルティ（P. camembertii）由来、商品名「リパーゼＧ」）を添加し、マグネチックスターラーで撹拌しながら、３５℃、２ｍｍＨｇで４８時間反応させた。反応終了後、油層のリノール酸モノグリセリドの含量が８３重量％の組成物を得た。得られた反応品をシリカゲルカラムクロマトグラフィーにて繰り返し抽出し、リノール酸モノグリセリドの含量が９７重量％の精製物を得た。 1-3. Production Example of Linoleic Acid Monoglyceride (Product of the Present Invention) In an approximately 30 ml vial, 100 g of linoleic acid / glycerin (1/2 (molar ratio)) mixture, 0.1 g of water, and 200 U of Mono and diglyceride lipase (manufactured by Amano Enzyme, derived from P. camembertii, trade name “Lipase G”) was added and reacted at 35 ° C. and 2 mmHg for 48 hours while stirring with a magnetic stirrer. . After completion of the reaction, a composition having a content of linoleic acid monoglyceride in the oil layer of 83% by weight was obtained. The obtained reaction product was repeatedly extracted with silica gel column chromatography to obtain a purified product having a linoleic acid monoglyceride content of 97% by weight.
1-4.　オレイン酸モノグリセリド（比較品）の製造例
　約３０ｍｌのバイアル瓶中に、１０ｇのオレイン酸／グリセリン（１／２（モル比））の混液、０．１ｇの水、および２００Ｕのリパーゼ（天野エンザイム社製、ペニシリウム・カマンベルティ（P. camembertii）由来、商品名「リパーゼＧ」）を添加し、マグネチックスターラーで撹拌しながら、３５℃、２ｍｍＨｇで４８時間反応させた。反応終了後、油層のオレイン酸モノグリセリドの含量が８５重量％の組成物を得た。得られた反応品をシリカゲルカラムクロマトグラフィーにて繰り返し抽出し、オレイン酸モノグリセリドの含量が９７重量％の精製物を得た。 1-4. Production Example of Oleic Acid Monoglyceride (Comparative Product) In a 30-ml vial, 10 g of oleic acid / glycerin (1/2 (molar ratio)) mixture, 0.1 g of water, and 200 U of lipase (Amano Enzyme, P. camembertii, trade name “Lipase G”) was added, and the mixture was stirred at 35 ° C. and 2 mmHg for 48 hours while stirring with a magnetic stirrer. After completion of the reaction, a composition having an oleic acid monoglyceride content of 85% by weight in the oil layer was obtained. The obtained reaction product was repeatedly extracted with silica gel column chromatography to obtain a purified product having an oleic acid monoglyceride content of 97% by weight.
２．　ポルフィロモナス・ジンジバリス（P. gingivalis）、フソバクテリウム・ヌクレアタム（F. nucleatum）及びストレプトコッカス・ミュータンス（S. mutans）に対する抗菌効果
　９６穴深型マイクロプレートにあらかじめ滅菌処理済の培地（日本製薬社製、商品名「ＧＡＭブイヨン液体培地」）０．５ｍｌを添加し、本発明品（α―リノレン酸モノグリセリド、亜麻仁油由来脂肪酸モノグリセリド、リノール酸モノグリセリド（それぞれ、「１．各種脂肪酸のモノグリセリドの製造例」で製造したもの））を０．５ｍｌ添加し、本発明品を培地中最終濃度で1.5ppm、３ppm、６ppm、１２ppm、２５ppm、５０ppm、１００ppm、２００ppm、４００ppmになるよう段階的に調製した。これらの試料溶液に対し、約１×１０８ＣＦＵ／ｍｌのポルフィロモナス・ジンジバリス（P. gingivalis（JCM5175））、フソバクテリウム・ヌクレアタム（F. nucleatum（ATCC25586））またはストレプトコッカス・ミュータンス（S. mutans（JCM2151)）の各培養菌液を０．１ｍｌ添加し、撹拌後好気条件下で３７℃、２４時間培養を行った。抗菌効果の判定は目視で行い、上記微生物の無添加試験区と比較し、微生物増殖による濁りの見られない試験区を抗菌効果有りとして発育を阻止するために必要な最低濃度（以下、「最小発育阻止濃度」という）を測定した。また、比較例として、口腔用抗菌剤として知られている塩化セチルピリジニウムおよびオレイン酸モノグリセリド（「１．各種脂肪酸のモノグリセリドの製造例」で製造したもの）を用いて、上記と同様の方法により最小発育阻止濃度を測定した。表１に結果を示す。 2. Antibacterial effect against P. gingivalis, F. nucleatum, and S. mutans 96-well deep microplate pre-sterilized medium (manufactured by Nippon Pharmaceutical Co., Ltd.) , 0.5 ml of a trade name “GAM bouillon liquid medium”), the product of the present invention (α-linolenic acid monoglyceride, linseed oil-derived fatty acid monoglyceride, linoleic acid monoglyceride (respectively, “1. Examples of production of monoglycerides of various fatty acids”) The product of the present invention was prepared stepwise so that the final concentration in the medium was 1.5 ppm, 3 ppm, 6 ppm, 12 ppm, 25 ppm, 50 ppm, 100 ppm, 200 ppm, 400 ppm. About 1 × 10 8 CFU / ml of Porphyromonas gingivalis (JCM5175), Fusobacterium nucleatum (ATCC25586) or Streptococcus mutans (S. mutans) was used for these sample solutions. 0.1 ml of each culture solution of (JCM2151)) was added, and the mixture was stirred and cultured at 37 ° C. for 24 hours under aerobic conditions. The antibacterial effect is judged visually, and compared to the above-mentioned microorganism-free test group, the minimum concentration required to prevent the growth of the test group in which turbidity due to microbial growth is not observed as having antibacterial effect (hereinafter referred to as “minimum”). The growth inhibitory concentration ”was measured. In addition, as a comparative example, using cetylpyridinium chloride and oleic acid monoglyceride known as oral antibacterial agents (produced in “1. Production Examples of Monoglycerides of Various Fatty Acids”) Inhibitory concentrations were measured. Table 1 shows the results.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
　表１より、ポルフィロモナス・ジンジバリス（P. gingivalis）、フソバクテリウム・ヌクレアタム（F. nucleatum）またはストレプトコッカス・ミュータンス（S. mutans）のいずれの菌種に対しても、本発明品は優れた抗菌効果を示すことが分かった。 From Table 1, the product of the present invention is an excellent antibacterial against any strain of P. gingivalis, Fusobacterium nucleatum, or Streptococcus mutans. It turns out that an effect is shown.
５．配合特性
＜チューインガム＞
チューインガムベース　　　　　　　　３５．０重量部
炭酸カルシウム　　　　　　　　　　　　２．０
マルチトール　　　　　　　　　　　　５０．０
エリスリトール　　　　　　　　　　　　５．０
還元パラチノース　　　　　　　　　　　５．０
香料　　　　　　　　　　　　　　　　　１．０
α－リノレン酸モノグリセリド　　　　　０．５
精製水　　　　　　　　　　　　　　　　１．５　
　　　　　　　　　　　　　　　　　１００．０
（製法）
　チューインガムベースを７０℃に加温軟化させた後、保温撹拌しながら炭酸カルシウム、マルチトール、エリスリトール、還元パラチノースおよび精製水を少量ずつ混和した。次いで、上記混和により得られた糖類混和ガムベース中に香料とα－リノレン酸モノグリセリドの混合物を添加し、さらに混和した。最後に、得られた混和物を薄い板状に整形してチューインガムを得た。
（配合特性）
　α－リノレン酸モノグリセリド配合チューインガムはガムベースの物性を損なうことなく、風味良好であった。 5). Formulation characteristics <chewing gum>
Chewing gum base 35.0 parts by weight Calcium carbonate 2.0
Maltitol 50.0
Erythritol 5.0
Reduced palatinose 5.0
Fragrance 1.0
α-Linolenic acid monoglyceride 0.5
Purified water 1.5
100.0
(Manufacturing method)
After the chewing gum base was warmed and softened to 70 ° C., calcium carbonate, maltitol, erythritol, reduced palatinose and purified water were mixed little by little while keeping the mixture warm. Next, a mixture of a fragrance and α-linolenic acid monoglyceride was added to the sugar-mixed gum base obtained by the above mixing, and further mixed. Finally, the resulting blend was shaped into a thin plate to obtain a chewing gum.
(Composition characteristics)
The chewing gum containing α-linolenic acid monoglyceride had a good taste without impairing the physical properties of the gum base.
＜キャンディー＞
グラニュー糖　　　　　　　　　　　　６０．０重量部
水飴　　　　　　　　　　　　　　　　５５．０
クエン酸　　　　　　　　　　　　　　　１．０
香料　　　　　　　　　　　　　　　　　０．２
α－リノレン酸モノグリセリド　　　　　０．１　
　　　　　　　　　　　　　　　　　１１６．３
（製法）
　グラニュー糖と水飴を１５０℃に加温軟化後、１２０℃まで放置冷却し、次いでクエン酸、香料とα－リノレン酸モノグリセリドを添加し混合した。次いで、得られた混合物を容器に充填しキャンディーにした。
（配合特性）
　α－リノレン酸モノグリセリドを添加したキャンディーは褐変化を伴うことなく、風味良好であった。 <Candy>
Granulated sugar 60.0 parts by weight Minamata 55.0
Citric acid 1.0
Fragrance 0.2
α-Linolenic acid monoglyceride 0.1
116.3
(Manufacturing method)
Granulated sugar and starch syrup were warmed and softened to 150 ° C. and allowed to cool to 120 ° C., and then citric acid, flavor and α-linolenic acid monoglyceride were added and mixed. The resulting mixture was then filled into a container to make a candy.
(Composition characteristics)
The candy to which α-linolenic acid monoglyceride was added had a good taste without browning.
＜錠菓＞
マルチトール　　　　　　　　　　　　８０．０重量部
還元パラチノース　　　　　　　　　　１９．７
香料　　　　　　　　　　　　　　　　　０．２
リノール酸モノグリセリド　　　　　　　０．１　
　　　　　　　　　　　　　　　　　１００．０
（製法）
　マルチトールと還元パラチノースを粉体混合後、香料とリノール酸モノグリセリドを添加した。得られた混合物は打錠し、錠菓とした。
（配合特性）
　混合物は容易に打錠時に固形化し、形状の部分崩壊も見られなかった。且つ風味も良好であった。 <Tablets>
Maltitol 80.0 parts by weight Reduced palatinose 19.7
Fragrance 0.2
Linoleic acid monoglyceride 0.1
100.0
(Manufacturing method)
After powder mixing of maltitol and reduced palatinose, a fragrance and linoleic acid monoglyceride were added. The obtained mixture was tableted into a tablet confection.
(Composition characteristics)
The mixture easily solidified upon tableting, and no partial collapse of the shape was observed. And the flavor was also good.
＜練り歯磨き＞
第２リン酸カルシウム　　　　　　　　　５０．０重量部
グリセリン　　　　　　　　　　　　　　２０．０
ソルビトール　　　　　　　　　　　　　１０．０
ラウリル硫酸ナトリウム　　　　　　　　　１．０
カラギーナン　　　　　　　　　　　　　　１．０
香料　　　　　　　　　　　　　　　　　　０．５
α－リノレン酸モノグリセリド　　　　　　０．２
精製水　　　　　　　　　　　　　　　　１８．０　
　　　　　　　　　　　　　　　　　　１００．７
（製法）
　グリセリン、ソルビトール、ラウリル硫酸ナトリウム、カラギーナンおよび精製水を混合後、第２リン酸カルシウムを混和した。次いで、得られた混和物に香料とα－リノレン酸モノグリセリドを混合して練り歯磨きとした。
（配合特性）
　α－リノレン酸モノグリセリド配合練り歯磨きは物性を損なうことなく安定であり、風味も良好であった。 <Toothpaste>
Dicalcium phosphate 50.0 parts by weight Glycerin 20.0
Sorbitol 10.0
Sodium lauryl sulfate 1.0
Carrageenan 1.0
Fragrance 0.5
α-Linolenic acid monoglyceride 0.2
Purified water 18.0
100.7
(Manufacturing method)
After mixing glycerin, sorbitol, sodium lauryl sulfate, carrageenan and purified water, dicalcium phosphate was mixed. Next, the resulting mixture was mixed with a fragrance and α-linolenic acid monoglyceride to obtain a toothpaste.
(Composition characteristics)
The toothpaste containing α-linolenic acid monoglyceride was stable without impairing the physical properties and had a good flavor.
＜マウスウォッシュ＞
エタノール　　　　　　　　　　　　　　１５．０重量部
ポリオキシエチレン硬化ヒマシ油　　　　　２．５
グリセリン　　　　　　　　　　　　　　　８．０
サッカリンナトリウム　　　　　　　　　　０．５
安息香酸ナトリウム　　　　　　　　　　　０．１
香料　　　　　　　　　　　　　　　　　　０．１
リノール酸モノグリセリド　　　　　　　　０．１
色素　　　　　　　　　　　　　　　　　　０．００１
精製水　　　　　　　　　　　　　　　　７５．０　　　
　　　　　　　　　　　　　　　　　　１０１．３
（製法）
ポリオキシエチレン硬化ヒマシ油をエタノール／グリセリン混合液で加温溶解後、精製水を加え溶解させた。次いで、得られた溶解物にサッカリンナトリウム、安息香酸ナトリウム、香料、リノール酸モノグリセリドおよび色素を添加し溶解混和してマウスウォッシュを得た。
（配合特性）
　リノール酸モノグリセリド添加マウスウォッシュは加工時の溶解性は良好であり、沈殿形成は見られず、風味も良好であった。 <Mouthwash>
Ethanol 15.0 parts by weight Polyoxyethylene hydrogenated castor oil 2.5
Glycerin 8.0
Saccharin sodium 0.5
Sodium benzoate 0.1
Fragrance 0.1
Linoleic acid monoglyceride 0.1
Dye 0.001
Purified water 75.0
101.3
(Manufacturing method)
Polyoxyethylene hydrogenated castor oil was dissolved by heating in an ethanol / glycerin mixed solution, and then purified water was added to dissolve. Subsequently, saccharin sodium, sodium benzoate, a fragrance, linoleic acid monoglyceride and a dye were added to the obtained lysate and dissolved and mixed to obtain a mouthwash.
(Composition characteristics)
The linoleic acid monoglyceride-added mouthwash had good solubility during processing, no precipitate was formed, and the flavor was also good.
　本発明の抗菌剤は、歯周病の原因菌や虫歯の原因菌に対する抗菌効果に優れるので、例えば、練り歯磨き、マウスウォッシュ、口中清涼剤、口中スプレーなどの口腔用組成物や、例えば、チューインガム、キャンディー、錠菓、フィルム状食品、飲料、菓子などの飲食品の配合成分として好適である。 The antibacterial agent of the present invention is excellent in antibacterial effect against periodontal disease causative bacteria and caries causative bacteria, and therefore, for example, oral compositions such as toothpaste, mouthwash, mouth freshener, mouth spray, and chewing gum It is suitable as a compounding ingredient of foods and drinks such as candy, tablet confectionery, film-like food, beverage, and confectionery.

Claims (3)

  1. 　α－リノレン酸モノグリセリドまたはリノール酸モノグリセリドを有効成分とする口腔用抗菌剤。 An oral antibacterial agent containing α-linolenic acid monoglyceride or linoleic acid monoglyceride as an active ingredient.
  2. 　請求項１記載の抗菌剤を含有する口腔用組成物。 An oral composition containing the antibacterial agent according to claim 1.
  3. 　請求項１記載の抗菌剤を含有する飲食品。 A food or drink containing the antibacterial agent according to claim 1.
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JP2014091682A (en) * 2012-11-01 2014-05-19 Riken Vitamin Co Ltd Bacteriostatic agent for intraoral anaerobic bacteria
JP2014091683A (en) * 2012-11-01 2014-05-19 Riken Vitamin Co Ltd Bacteriostatic agent for intraoral aerobic bacteria
WO2016072435A1 (en) * 2014-11-06 2016-05-12 日本メナード化粧品株式会社 Agent for maintaining stem cells in undifferentiated state and agent for promoting growth thereof

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