JP6848021B2 - Oral composition for suppressing the generation of methyl mercaptan - Google Patents

Description

The present invention relates to an oral composition for suppressing the generation of methyl mercaptan. More specifically, an oral composition containing a plant extract having an effect of suppressing the production of methyl mercaptan, and more particularly, an oral cavity selected from chewing gum agents, candy agents, troches, tablets, chewable tablets, and beverages. Regarding the composition for use.

Methyl mercaptan is known as a so-called malodorous substance having a low odor threshold that causes an offensive odor even at a low concentration, but it is also a substance that has various adverse effects on the living body.
In the human body, methyl mercaptan is known to be produced as a metabolite by bacteria assimilating sulfur-containing foods such as onions and cabbage, and proteins and peptides containing sulfur-containing amino acids. Especially in the oral cavity and pharynx, since various tissues form a complicated morphology, food residues that can be a source of methyl mercaptan are likely to remain, and bacteria such as plaque that are difficult to physically and chemically remove. Since it is a site where the breeding environment is easily adjusted, it is considered that methyl mercaptan is likely to occur. The generation of methyl mercaptan in these oral cavity and pharynx causes the development of halitosis.

Therefore, conventionally, attempts have been made to prevent the above-mentioned events derived from methyl mercaptan by removing / deodorizing methyl mercaptan and suppressing its production. For example, from the viewpoint of removing and deodorizing methyl mercaptan, a method using a cyclodextrin derivative (Patent Document 1), animal and plant extracts (Patent Documents 2 and 3) and molybdenum (Patent Document 4), and suppression of methyl mercaptan production. From this point of view, a long-chain alkyroyl zarcosine salt based on a specific metal (Patent Document 5).
A method of allowing a combination of a legume extract and a specific compound (Patent Document 6) to act on the genus Fuzobacterium, which is one of the bacteria producing methyl mercaptan, and a plant extract (Patent Documents 7 and 8).
), 3-Chloro-DL-alanine (Non-Patent Document 1), zinc chloride (Non-Patent Document 2), epigallocatechin gallate (Non-Patent Document 3), and other compounds are involved in the production of methyl mercaptan. There are methods such as inhibiting the activity of methioninase. However, none of these methods have been sufficiently effective, and the use of sufficient amounts may cause difficulty in palatability and safety concerns, so the problem has not yet been sufficiently solved. However, it is desired to provide a safer and more effective method.

JP-A-2007-169228 Japanese Unexamined Patent Publication No. 64-26512 Japanese Unexamined Patent Publication No. 2010-280591 Japanese Unexamined Patent Publication No. 2010-111591 Japanese Unexamined Patent Publication No. 61-37720 Japanese Unexamined Patent Publication No. 2002-114658 Japanese Unexamined Patent Publication No. 2008-31062 Japanese Unexamined Patent Publication No. 2010-265215

Yoshimura M, FEBS Letter 523, 119-122, 2002 Yamashita Y, J Dent Hlth 56, 335, 2006 Sakurai K, Y, J Dent Hlth 59, 391, 2009

An object of the present invention is to provide an oral composition for suppressing the generation of methyl mercaptan, which is a main cause of halitosis.

As a result of diligent studies in view of such circumstances, the present inventors have surprisingly found that the olive leaf extract has an excellent effect of suppressing the generation of methyl mercaptan, and have completed the present invention.

That is, the present invention particularly provides an oral composition for suppressing the generation of methyl mercaptan according to the following items 1 to 4.
Item 1. An oral composition for suppressing the generation of methyl mercaptan containing an olive leaf extract as an active ingredient.
Item 2. Item 2. The oral cavity for suppressing the generation of methyl mercaptan according to Item 1, wherein the oral composition is any one selected from the group consisting of chewing gum agents, candy agents, troche agents, tablets, chewable tablets, and beverages. Composition for.
Item 3. Item 2. Oral mouth for suppressing the generation of methyl mercaptan according to any one of Item 1 or 2, wherein the olive leaf extract is 0.001 to 10% by mass in terms of solid matter with respect to the total amount of the composition. Composition.
Item 4. The oral composition for suppressing the generation of methyl mercaptan according to any one of Items 2 or 3, further comprising one or more selected from the group consisting of xylitol, maltitol, erythritol, and palatinit.

The oral composition for suppressing the production of methyl mercaptan of the present invention can prevent bad breath by suppressing the production of methyl mercaptan in the oral cavity. Also, because it is a material that has eating experience,
Since there is no concern about safety even when ingested for a long period of time, it can be applied prophylactically to oral compositions for daily use.

The methyl mercaptan generation inhibitory component of the present invention is a plant extract obtained by extracting olive leaves with a solvent. In the specification of the present application, the compounding ratio represents the compounding mass ratio unless otherwise specified.

The olive leaf extract used in the present invention is an extract of leaves of a plant belonging to the genus Olive of the Oleaceae family. Specific examples of the olive genus of the Oleaceae family include olive (Olea europaea Linne) and its cognate species (eg, Olea welwitschii, Olea panicu).
There are more than 500 varieties, such as lata), but typical examples of varieties are Nevadi Bronco, Manzanillo, Picual, Hoji Blanco, Albekina, Catamara, Koroneiki, Pitchorine, Paragon, Wagaberdal, Mission. , Washington, Western Australia Mission, South Australia Bendal, Azapa, Barnea, Koroneiki Bra, Goldal, Frantio, Leccino, Cipressino, Lucca,
Ascolana Terena, Collegilla, Moroiolo, Black Italian, Collatina, Helena, Rossiora, One Seven Seven, El Greco, Hardy's Mammoth, etc. The olive leaf extract is obtained by extracting the leaves of these plants of the genus Olive of the Oleaceae family using an organic solvent, water or a mixture of an organic solvent and water. Among them, a mixed solution of water and ethanol is particularly preferable, and the mixing ratio of the mixed solution is, for example, about 10 in the volume ratio of water: ethanol.
0: 1 to about 1: 200 is preferable, about 20: 1 to 1:20 is more preferable, and about 1: 9 to 1
1 is the most preferable. The temperature of the solvent at the time of extraction may be in the range of about -4 ° C to about 200 ° C, but is preferably about 30 ° C to about 150 ° C, more preferably about 40 ° C to about 80 ° C. These olive leaf extracts are olive leaf extract BG (50% 1,3-butylene glycol aqueous solution: manufactured by Maruzen Pharmaceutical Co., Ltd.), olive leaf dried extract (powder: manufactured by Ask Pharmaceutical Co., Ltd.), olive leaf extract (Tama Biochemical). (Manufactured by Eisai Food Chemical Co., Ltd.), Opiece (powder: manufactured by Eisai Food Chemical Co., Ltd.)
Powder: Eisai Food Chemical Co., Ltd.), Olive leaf extract (30% ethanol aqueous solution: Nippon Powder Chemical Co., Ltd.), Olive leaf extract powder (Powder: Nippon Powder Chemical Co., Ltd.), Olive leaf extract (Bioactives Japan Co., Ltd.) It can be obtained as such.

The methyl mercaptan generation inhibitory component of the present invention is usually applied to the oral cavity by blending it in an oral composition. The oral composition that can be blended is not particularly limited, but can be used in the form (dosage form) of a chewing gum agent, a candy agent, a troche agent, a tablet agent, a chewable tablet agent, a granule capsule, a beverage, or the like. .. Among these, the forms such as tablets and candy are preferable, and the forms such as tablets and candy are most preferable.

The methyl mercaptan generation inhibitory component is usually blended in an amount of 0.001 to 10% by mass with respect to these oral compositions in terms of solid matter. If it is less than 0.001% by mass, the desired effect cannot be expected, and if it is more than 10% by mass, the flavor (astringency, etc.) derived from the extract is strongly felt, and the palatability is deteriorated, which is not preferable.

The more optimal blending amount differs depending on the dosage form of the oral composition, and the specifics are as follows. The blending amount is the mass% in terms of solid content with respect to the total amount of the oral composition. In the case of olive leaf extract, the tablet preparation and the candy preparation are preferably blended in an amount of 0.1 to 10% by mass.

In the oral composition containing the methyl mercaptan generation inhibitory component of the present invention, a component that can be usually blended in the oral composition may be further blended as long as the effect of the present invention is not impaired.

As the surfactant, a nonionic surfactant, an anionic surfactant or an amphoteric surfactant can be blended. Specifically, the nonionic surfactant includes sugar fatty acid esters such as sucrose fatty acid ester, maltose fatty acid ester, and lactose fatty acid ester, fatty acid alkanolamides, sorbitan fatty acid ester, fatty acid monoglyceride, and polyoxyethylene addition coefficient of 4 to 15. , Polyoxyethylene alkyl ether system with an alkyl group having 10 to 18 carbon atoms or polyoxyethylene alkylphenyl ether having a polyoxyethylene addition coefficient of 10 to 18 and an alkyl group having 9 carbon atoms, diethyl sebacate, poly Oxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene sorbit fatty acid ester, polyethylene glycol fatty acid ester, polyethylene lanolin, polyethylene sterol, polyethylene lanolin alcohol, alkyl glucoside, polyoxyethylene polyoxy Examples include propylene block copolymers. Examples of the anionic surfactant include sulfate ester salts such as sodium lauryl sulfate and sodium polyoxyethylene lauryl ether sulfate, sulfosuccinates such as sodium lauryl sulfosuccinate and sodium polyoxyethylene lauryl ether sulfosuccinate, cocoyl sarcosine sodium, and lauroyl methyl alanine. Examples thereof include acyl amino acid salts such as sodium and sodium cocoyl methyl taurine. Examples of the amphoteric ion surfactant include betaine acetate-type surfactants such as lauryldimethylaminoacetate betaine and betaine coconut oil fatty acid amide propyldimethylaminoacetate, and imidazoline-type activators such as N-cocoyl-N-carboxymethyl-N-hydroxyethylethylenediamine sodium. Examples thereof include activators and amino acid-type activators such as N-lauryldiaminoethylglycine. These surfactants can be used alone or in combination of two or more.

Flavoring agents include, for example, menthol, carboxylic, methyl salicylate, vanillin, benzyl succinate, methyl eugenol, anetol, limonene, osimene, n-decyl alcohol, methyl acetate, citronenyl acetate, cineol, ethyllinalol, crocodile, thyme. , Natsumeg, Sparemint oil, Peppermint oil, Lemon oil, Orange oil, Sage oil, Rosemary oil, Silica skin oil, Perilla oil, Winter green oil, Chome oil, Eucalyptus oil, Pimento oil, Tea tree oil, Tabana oil, Star Examples include anis oil, fennel oil, mint oil, basil oil and the like. These fragrances can be used alone or in combination of two or more.

Examples of the polishing agent include abrasive silica such as abrasive precipitated silica and abrasive gel silica, calcium hydrogen phosphate / dihydrate and anhydride, calcium phosphate, calcium tertiary phosphate, magnesium tertiary phosphate, calcium pyrophosphate, hydroxyapatite. , Insoluble sodium metaphosphate, aluminum silicate, zirconium silicate, calcium silicate, calcium carbonate, magnesium carbonate, alumina, aluminum hydroxide, calcium sulfate, polymethylmethacrylate, pamisu (pallet stone), bentonite, synthetic resin, etc. Be done. These abrasives can be used alone or in combination of two or more.

Examples of the binder include cellulose derivatives such as sodium carboxymethyl cellulose, carboxymethyl ethyl cellulose salt, hydroxyethyl cellulose, hydroxypropyl cellulose and hydroxypropyl methyl cellulose, microbially produced polymers such as xanthan gum and gellan gum, tragant gum, karaya gum, arabia gum, carrageenan and dextrin. Natural polymers such as natural polymers or rubbers, synthetic polymers such as polyvinyl alcohol and polyvinylpyrrolidone, inorganic binders such as thickening silica and bee gum, O- [2 chloride
-Hydroxy-3- (trimethylammonio) propyl] Cationic binders such as hydroxyethyl cellulose can be mentioned. These binders can be used alone or in combination of two or more.

Examples of sweeteners include saccharin, sodium saccharin, acesulfarm potassium, stevia extract, stebioside, neoheseridyldihydrocalcone, glycyrrhizin, perillartine, soumatin, aspartylphenylalanine methyl ester, methoxycinnamic aldehyde, sucralose, palatinose, palatinit, and erythritol. , Maltitol, xylitol, lactitol and the like. These sweeteners
It can be used alone or in combination of two or more.

Examples of the wetting agent include glycerin, ethylene glycol, propylene glycol, 1
, 3-Propanediol, 1,3-butylene glycol, sorbitol, polyethylene glycol, polypropylene glycol and the like can be used alone or in combination of two or more.

Examples of the preservative include parabens such as methylparaben and propylparaben, and benzoates such as sodium benzoate. These preservatives alone or 2
More than seeds can be used in combination.

The pH adjuster includes citric acid, phosphoric acid, malic acid, gluconic acid, maleic acid, aspartic acid, succinic acid, glucuronic acid, fumaric acid, glutamic acid, adipic acid, salts thereof, hydrochloric acid, and sodium hydroxide. , Potassium hydroxide, sodium silicate and the like. These components can be contained in the oral composition of the present invention alone or in combination of two or more. The pH of the oral composition of the present invention is not particularly limited as long as it can be used in the oral cavity, but is usually pH 3.0 to 10.5, preferably pH 5.5 to 8.
It is 0.

As medicinal ingredients, in addition to cetylpyridinium chloride as a disinfectant, cationic disinfectants such as chlorhexidine hydrochloride, chlorhexidine gluconate, benzethonium chloride, and benzalkonium chloride; amphoteric disinfectants such as dodecyldiaminoethylglycine; isopropylmethylphenol, Non-ionic bactericides such as triclosan; enzymes such as dextranase, amylase, protease, mutanase, lysozyme, lytic enzyme (lytecenzyme); glycyrrhizinates such as glycyrrhetinic acid and dipotassium glycyrrhizinate as anti-inflammatory agents; as blood circulation promoters Nicotinic acid or tocopherol acetate, etc .; tranexamic acid, epsilon aminocaproic acid, etc. as antiplasmin agents; ascorbic acid, etc. as bleeding improvers; allantin, etc. as tissue repair agents; fluorine compounds such as sodium fluoride as remineralizing agents; other water-soluble Examples thereof include plant extracts extracted with a sex solvent, chlorophyridinium, sodium chloride, caropeptide, zinc chloride, hinokithiol and the like, and these can be blended alone or in combination of two or more.

Among the above components, the oral composition containing xylitol, maltitol, erythritol, and palatinit suppresses the astringency and bitterness of the methyl mercaptan generation inhibitory component contained in the oral composition, and the preference of the oral composition. It is preferable because it enhances the sex. For the total amount of composition
It is preferably blended in an amount of 1 to 10% by mass, and more preferably blended in an amount of 5 to 10% by mass.
If it is blended in an amount of more than 10% by mass, it is not preferable because the possibility that crystals such as xylitol are precipitated from the composition adhering to the discharge port of the container or the inside of the cap when the oral composition is used.

Hereinafter, the present invention will be specifically described, but the present invention is not limited to the following examples. Unless otherwise specified, "%" indicates "mass%".

Evaluation of the effect of suppressing the generation of methyl mercaptan The effect of suppressing the generation of methyl mercaptan was measured according to the following method.
770 μL of salt buffer, 100 μL of test solution, bacterial suspension 10 in a 15 mL glass bottle
After adding 0 μL and shaking lightly by hand, 30 μL of 33 mM L-methionine buffer solution was added, and the cells were cultured at 37 ° C. for 90 minutes. Immediately after culturing, 500 μL of a 3M aqueous phosphoric acid solution was added, the mixture was stirred, and the mixture was allowed to stand for 10 minutes. Then, 1 mL of gas was collected from the head space of a glass bottle and injected into a gas chromatograph to quantify methyl mercaptan. The analytical conditions are the same as those described in the above-mentioned evaluation of the removal effect of methyl mercaptan. For the methyl mercaptan generation suppression rate (%), the amount of methyl mercaptan when the test solution is added is Ki, and the amount of methyl mercaptan when a salt buffer is added instead of the test solution is K0. Calculated using. As a blank, a 40 mM potassium phosphate buffer solution (pH 7.7) containing 50 mM sodium chloride was used. The results obtained are shown in Table 2.

Occurrence suppression rate (%) = [(K0-Ki) / K0] × 100

The bacteria, reagents, test solution, medium, and bacterial suspension used in the test were as follows.
Bacteria used: Porphyromonas gingivalis W83 strain (hereinafter, may be abbreviated as Pg)
Salt buffer: A 40 mM potassium dihydrogen phosphate aqueous solution was added to a 40 mM dipotassium hydrogen phosphate aqueous solution to adjust the pH to 7.7. 1 L of the solution was taken, 2.92 g of sodium chloride was added, and the solution was sterilized by heating.
Test solution: Each subject was prepared using a salt buffer solution so as to have a specified concentration in terms of solid matter.
Medium: First, 0.25 g of hemin was dissolved in 5 mL of 1N sodium hydroxide, and 20 mL of distilled water was further added to prepare a solution A. A solution prepared by dissolving 0.025 g of menadione in 25 mL of 99% ethyl alcohol was used as solution B. The solution A and solution B are mixed and hemin, menadione
A solution was prepared. The medium was TSB 40 g, hemin, menadione solution 1 mL, Yeast product.
1 g was dissolved in 0.9 L of distilled water and autoclaved. This medium is hereinafter referred to as "TSB + h, m, y".
Bacterial suspension: Pg is inoculated into TSB + h, m, y 10 ml, anaerobically cultured at 37 ° C. for 24-48 hr, and then this culture solution is added to 100 ml of new TSB + h, m, y and 24 at 37 ° C.
The cells were anaerobically cultured for ~ 48 hr. This bacterium culture solution was centrifuged at 8000 × g for 10 minutes, washed with salt buffer, suspended in salt buffer, and adjusted to about 0.3 at OD550 nm. 33 mM L-methionine salt buffer solution: L- Methionin was prepared using the above-mentioned salt buffer solution so as to have a final concentration of 33 mM, and was sterilized by filtration.
3M aqueous solution of phosphoric acid: Phosphoric acid and distilled water were used to prepare a final concentration of 3M.

The following subjects were used.
Olive leaf extract: Opiece (powder: manufactured by Eisai Food & Chemical Co., Ltd.)
Novara fruit extract: Falcolex Novara B (manufactured by Ichimaru Falcos)
Hawthorn extract: Falcolex hawthorn B (manufactured by Ichimaru Falcos)

As shown in Table 1, it was found that the olive leaf extract has an excellent effect of suppressing the generation of methyl mercaptan. In particular, it was found that when 0.001% by mass or more was blended, a suppressing effect of 50% or more was obtained, and when 0.01% by mass or more was blended, a suppressing effect of 75% or more was obtained.
On the other hand, it was found that the Novara fruit extract and the hawthorn extract did not have any inhibitory effect even though they were blended in an amount of 0.01% by mass or more.

Evaluation of Bitterness / Astringency Suppressing Effect The bitterness / astringency suppressing effect of an oral composition containing a methyl mercaptan generation inhibitor was evaluated according to the following method.
Examples 1 to 6 and Comparative Example 1 manufactured by a conventional method were subjected to an absolute evaluation based on a five-level score based on the following criteria using five specialized panels. For evaluation, take 10 ml of each subject and put about 2 in the mouth.
After containing for 0 seconds, it was exhaled and evaluated by the sensation immediately after that. The obtained evaluation points were totaled, the average value of the evaluation points was calculated for each evaluation item, and the results are shown in Table 3.
Evaluation score 5: Feel weak
4: Feel a little weak
3: I can't say either
2: Feel a little strong
1: Feel strong

As shown in Table 2, when xylitol, maltitol, and erythritol are added in an amount of 1 to 10% by mass based on the total amount of the oral composition, the bitterness and astringency of the oral composition containing the olive leaf extract are significantly suppressed. I understood it.

Hereinafter, the formulations of examples of oral compositions containing the methyl mercaptan generation inhibitor according to the present invention will be given, but the present invention is not limited to the following formulations.

Prescription example 1
Granule capsules were prepared according to a conventional method.
Granule capsules were prepared by encapsulating 60 parts by weight of the in-capsule solution with 40 parts by weight of the inner capsule film made of gelatin and sorbitol, and further sugar-coating with 110 parts by weight of the outer capsule film made of sugar.

In-capsule solution
Proportion proportion
Olive leaf extract 10.0
Vitamin C 7.2
Vitamin E 2.4
Glycerin fatty acid ester 1.0
Safflower oil residue
Total 60

Inner capsule film
Proportion proportion
Gelatin 36.0
Sorbitol remnants
Total 40

Outer capsule film
Proportion proportion
Eggshell calcium 1.0
Gum arabic 0.6
Shellac 0.3
Gelatin 0.2
Carbana wax 0.1
Aspartame 0.1
Fragrance 0.4
Palatinit remnants
110 in total

Claims (2)

For humans (excluding those who develop methyl mercaptan in the oral cavity and pharynx) containing olive leaf extract as an active ingredient, for suppressing the generation of methyl mercaptan by oral porphyromonas gingivalis, Oral composition. The oral composition according to claim 1, which satisfies 1, 2, or 3 requirements selected from the group consisting of the following requirements (i), (ii), and (iii).
(I) The olive leaf extract is contained in an amount of 0.001 to 10% by mass in terms of solid matter with respect to the total amount of the composition.
(Ii) Further, it contains one or more selected from the group consisting of xylitol, maltitol, erythritol, and palatinit.
(Iii) A chewing gum agent, a candy agent, a troche agent, a tablet agent, a chewable tablet agent, a granule capsule agent or a beverage.