JP2023080246A - Composition containing copper compound, zinc compound, and L-menthol - Google Patents

Abstract

The present invention provides a composition that is effective against causative bacteria of halitosis and periodontal disease and that can prevent or improve halitosis and/or periodontal disease. Kind Code: A1 An oral composition containing a copper compound, a zinc compound, and L-menthol. [Selection figure] None

Description

TECHNICAL FIELD The present invention relates to a composition that is effective against causative bacteria of halitosis and periodontal disease, and that can prevent or improve halitosis and/or periodontal disease.

An unpleasant odor emanating from the oral cavity is an obstacle to social communication because it makes people around people feel uncomfortable. Therefore, since reducing halitosis leads to the maintenance of good social communication as well as the health of the whole body, research and development have been conducted from various viewpoints on substances that reduce halitosis.

Periodontal disease is an inflammatory disease caused by bacterial infection. Periodontal disease not only leads to tooth loss, but also affects the gastrointestinal tract with toxins and changes in the intestinal flora due to the swallowing of periodontal disease bacteria. and has been shown to be detrimental to various organs.

It is well known that volatile sulfur compounds (VSCs) such as methyl mercaptan, hydrogen sulfide, and dimethyl sulfide are the most common causes of halitosis in the oral cavity. Such volatile sulfur compounds are produced by metabolism of anaerobic bacteria living in the oral cavity. In particular, Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythensis, Campylobacter rectus, Treponema denticola, which are also pathogenic bacteria of periodontal disease Bacteria such as Treponema denticola and Fusobacterium nucleatum are said to have a high VSC-producing ability, which is why the oral cavity of periodontal disease patients has a particularly strong foul odor.
VSC, the causative agent of bad breath, is produced when oral bacteria metabolize proteins in saliva, components such as cysteine and methionine present in deciduous epithelial cells, and food residues as substrates. In order to fundamentally suppress it, it is essential to suppress the sterilization or proliferation of intraoral bacteria as in periodontal disease.

It is known that copper compounds and zinc compounds have a bactericidal action (Patent Document 1), and there is a dentifrice with an astringent feeling and improved stringiness, containing xanthan gum or hydroxyethyl cellulose in copper gluconate and zinc chloride. It is known (patent document 2).

As for menthol, a technique has been disclosed in which menthol-based peppermint oil and the like are used as antibacterial agents for food fragrances. (Patent Document 3).

However, it has not been known so far that the combined use of a copper compound, a zinc compound and L-menthol can dramatically suppress the sterilization or growth of causative bacteria of halitosis and periodontal disease.

Japanese Unexamined Patent Application Publication No. 2013-001701 JP 2011-105682 A Japanese Patent Application Laid-Open No. 2004-018470

An object of the present invention is to provide a composition that can prevent or improve halitosis and/or periodontal disease by sterilizing or inhibiting the growth of bacteria that cause halitosis and periodontal disease. It is to be.

The inventors of the present invention have conducted intensive research to solve such problems, and found that a combination of a copper compound, a zinc compound, and L-menthol exhibits excellent antibacterial and salivary effects, and developed the present invention. completed. That is, the present invention is a composition for preventing or improving halitosis and/or periodontal disease, containing a copper compound, a zinc compound, and L-menthol.

That is, the present invention relates to the following (1) to (5).
(1) An oral composition containing a copper compound, a zinc compound, and L-menthol.
(2) The composition according to (1), wherein the copper compound is one or more selected from the group consisting of copper sulfate, copper gluconate, sodium copper chlorophyllin, and copper chlorophyll.
(3) Zinc compounds include zinc oxide, zinc carbonate, zinc chloride, zinc sulfate, zinc gluconate, zinc undecylenate, low temperature calcined zinc oxide, zinc paraphenolsulfonate, zinc palmitate, zinc pyrithione, zinc myristate, and The composition according to (1) or (2), which is one or more selected from the group consisting of zinc laurate.
(4) The composition according to (1), wherein the copper compound is copper gluconate and the zinc compound is zinc chloride.
(5) The composition according to any one of (1) to (4), which is used for prevention or improvement of halitosis and/or periodontal disease.

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a composition for preventing or improving halitosis and/or periodontal disease, which has an excellent antibacterial action. The composition of the present invention sterilizes or inhibits the growth of causative bacteria of bad breath and periodontal disease in the oral cavity, and the saliva produced by the saliva secretion-promoting action of the composition of the present invention kills the causative bacteria. Or suppress its proliferation.

A culture solution containing only bacterial solution (control), a solution containing 0.001% copper gluconate, 0.01% zinc chloride, or 0.001% L-menthol, and 0.001% copper gluconate and 0.01% zinc chloride. 0.001% copper gluconate, 0.01% zinc chloride, and 0.001% L-menthol. 3 shows the results of total salivary secretion for 30 minutes after administration of vehicle only (control), administration solution containing copper gluconate and zinc chloride, and administration solution containing copper gluconate and zinc chloride plus L-menthol, respectively. .

In the present invention, "prevention" means preventing the onset of halitosis and/or periodontal disease by sterilizing causative bacteria of halitosis and periodontal disease or suppressing growth of the bacteria.

In the present invention, "improvement" means alleviating the symptoms of halitosis and/or periodontal disease by reducing causative bacteria of halitosis and periodontal disease.

The "copper compound" used in the present invention is an inorganic salt or an organic salt of copper, and may be used as a raw material for pharmaceuticals, foods, and cosmetics. Copper chloride, copper iodate, copper chloride, copper sulfate, copper nitrate, copper acetate, copper lactate, copper butyrate, copper formate, copper citrate, copper phosphate, copper gluconate, copper aspartate, copper glutamate, copper propionate , copper oxalate, copper phytate, copper tartrate, copper malate, copper succinate, copper malonate, copper maleate, copper benzoate, copper salicylate, copper fumarate, copper glycerate, copper glycerophosphate, copper glycolate , copper picolinate, copper ascorbate, copper bisglycinate, copper lysinate, copper methionate, copper pidolate, copper oleate, copper stearate, copper lauroyl sarcosine, copper fluorosilicate, copper fluoroborate, zinc undecylenate , sodium copper chlorophyllin, or copper chlorophyll, preferably copper sulfate, copper gluconate, sodium copper chlorophyllin, or copper chlorophyll, more preferably copper gluconate.

The "zinc compound" used in the present invention is an inorganic salt or an organic salt of zinc, and may be used as a raw material for pharmaceuticals, foods and cosmetics. Zinc chloride, zinc iodate, zinc chloride, zinc sulfate, zinc nitrate, zinc acetate, zinc lactate, zinc butyrate, zinc formate, zinc citrate, zinc phosphate, zinc gluconate, zinc aspartate, zinc glutamate, zinc propionate , zinc oxalate, zinc phytate, zinc tartrate, zinc malate, zinc succinate, zinc malonate, zinc maleate, zinc benzoate, zinc salicylate, zinc fumarate, zinc glycerate, zinc glycerophosphate, zinc glycolate , zinc picolinate, zinc ascorbate, zinc bisglycinate, zinc lysinate, zinc methionate, zinc pidolate, zinc oleate, zinc stearate, zinc lauroylsarcosine, zinc fluorosilicate, zinc fluoroborate, or undecylenic acid Zinc and the like, preferably zinc oxide, zinc carbonate, zinc chloride, zinc sulfate, zinc gluconate, zinc undecylenate, low temperature calcined zinc oxide, zinc paraphenolsulfonate, zinc palmitate, zinc pyrithione, myristic acid Zinc or zinc laurate, more preferably zinc chloride.

The “L-menthol” used in the present invention may be used as a single agent of L-menthol, or may be used as a cooling agent or fragrance containing L-menthol.
The above-mentioned "copper compound", "zinc compound" and "L-menthol" used in the present invention are commercially available as raw materials for quasi-drugs, foods or cosmetics, are easily available, and can be obtained by a known method. can also be manufactured.

INDUSTRIAL APPLICABILITY The present invention is used as pharmaceuticals, quasi-drugs, cosmetics and the like.

The form of the present invention and the method of application to the oral cavity are not particularly limited. For example, mouthwash (mouthwash), toothpaste, liquid toothpaste, toothpaste, gum, lozenge, buccal tablet, gingival tape preparation, oral gel preparation, oral ointment, oral spray , oral paste, oral paste, oral pill, oral tablet, oral powder, oral powder, oral liquid, oral suspension, oral emulsion, oral cavity Examples include granules for internal use and capsules for intraoral use. Mouthwashes, toothpastes, liquid toothpastes or toothpastes are preferred.

In the present invention, the content of the copper compound in the composition is preferably 0.001 to 10% by weight, more preferably 0.01 to 1% by weight.

In the present invention, the concentration of the zinc compound in the composition is preferably 0.001-1% by weight, more preferably 0.01-0.1% by weight.

In the present invention, the amount of L-menthol blended in the composition is preferably 0.001 to 5% by weight, more preferably 0.01 to 1% by weight.

In the present invention, the copper compound, zinc compound, and L-menthol can be mixed at any ratio and used.

In the present invention, wetting agents, pH adjusters, corrigents, preservatives, fragrances, solubilizers and the like can be added as appropriate.

As the humectant, any one commercially available as a raw material for pharmaceuticals, foods, and cosmetics may be used. Examples include polyhydric alcohols, more specifically sorbitol, glycerin, concentrated glycerin, ethylene glycol, propylene glycol, and 1,3-butylene. Glycol, propanediol (1,3-propanediol), polyethylene glycol, polypropylene glycol, xylit, maltit, lactit, trehalose, sodium hyaluronate, hydrolyzed collagen, etc., and a combination of one or more of these It can be appropriately selected and blended as needed.

The pH of the composition for periodontal disease or halitosis of the present invention is preferably in the range of 4.5 to 8.0. Examples of pH adjusters that can be used in the present invention include phosphoric acid, sodium monohydrogen phosphate, sodium dihydrogen phosphate, potassium monohydrogen phosphate, potassium dihydrogen phosphate, citric acid, malic acid, pyrophosphoric acid, and tartaric acid. , acetic acid or salts thereof, sodium hydroxide and the like. One or a combination of two or more of these can be appropriately selected and blended as necessary.

Examples of flavoring agents include saccharin, sodium saccharin, disodium glycyrrhizinate, trisodium glycyrrhizinate, sucrose, glucose, fructose, lactose, honey, aspartame, stevia, sucralose, xylitol, inositol, D-sorbitol, D-mannitol, raffinose, lactulose, lactitol, erythritol, reduced palatinose, palatinose, palatinit, acesulfame K, maltose, maltosyltrehalose or maltitol. One or a combination of two or more of these can be appropriately selected and blended.

Examples of antiseptics include parabens (paraoxybenzoic acid esters) such as methylparaben, ethylparaben, isopropylparaben, propylparaben, butylparaben, isobutylparaben, and benzylparaben, alcohols such as phenoxyethanol and ethanol, or sorbic acid and benzoin. acid, dehydroacetic acid, propionic acid, salts thereof, and the like. One or a combination of two or more of these can be appropriately selected and blended.

Flavors include, for example, L-menthol, peppermint, spearmint or fruit flavors, peppermint oil and the like. Perfumes also have the advantage of stimulating salivation. One or a combination of two or more of these can be appropriately selected and blended.

A solubilizer may be added to promote the dissolution of the above-mentioned additives and medicinal ingredients in water, which is the main base of the present invention. Examples of such solubilizers include polyhydric alcohols such as propylene glycol, dipropylene glycol, butylene glycol and polyethylene glycol. One or a combination of two or more of these can be appropriately selected and blended.

In addition, in the case of toothpaste and ointment, abrasives, foaming agents and thickeners are used as appropriate.

The present invention can further contain medicinal ingredients such as antibacterial agents, anti-inflammatory agents, fluorides, vitamins, crude drug extracts and plaque-degrading enzymes. These medicinal ingredients are not particularly limited as long as they can be used for pharmaceuticals and the like.

The present invention will be described in more detail below with reference to Examples and Formulation Examples, but the scope of the present invention is not limited to these.

(Example 1) Growth inhibition test of halitosis-causing bacteria (1) Test substances Copper gluconate (hereinafter referred to as GCu) and zinc chloride (hereinafter referred to as ZnCl ₂ ) are manufactured by Wako Pure Chemical Industries, Ltd. L-menthol (hereinafter referred to as Men) is I used one made by Suzuki Hakka.
(2) Test bacterial strain In this test, Prevotella intermedia ATCC 25611, which is well known as a causative bacterium of halitosis and periodontal disease, was used.
(3) Test method: Bacterial solution preparation
Prevotella intermedia is anaerobically cultured on Anero-Colombian rabbit blood agar medium (Nippon Becton Dickinson) at 35°C for 48-72 hours, then suspended in sterilized physiological saline to prepare a bacterial solution of approximately 3.0×10 ⁸ CFU/mL. bottom. Furthermore, a bacterial solution was prepared using GAM broth so as to have a concentration of about 10 ⁷ CFU/mL.
(4) Test method: Preparation of test solution Copper gluconate, zinc chloride, and L-menthol test substances were prepared in the medium so that each final concentration was obtained. was added to prepare a test solution. After culturing this at 35° C. under anaerobic conditions for 24 hours, the number of viable bacteria per 1 mL (CFU/mL) was measured.
(5) Test results Table 1 and Fig. 1 show the results of measuring the viable count of each test substance and control (bacterial solution only), respectively. From Table 1 and Figure 1, the combined use of copper gluconate (GCu), zinc chloride (ZnCl ₂ ) and L-menthol (Men) has a dramatic effect on the bacteria causing bad breath and periodontal disease. An unexpected result was obtained that it was expressed in

(Example 2) Saliva Secretion Stimulating Action Test (1) Test Substances Copper gluconate and zinc chloride were manufactured by Wako Pure Chemical Industries, and L-menthol was manufactured by Suzuki Minka.
(2) Animals used Slc: Wistar male rats [Japan SLC Co., Ltd.] 6-week-old male rats were purchased, quarantined and acclimatized.
(3) Test method After completing the quarantine and acclimation period (7 days), rats were anesthetized by intraperitoneal administration of urethane (1 g/kg) and α-chloralose (25 mg/kg), and a tracheal cannula was placed to secure the airway. The esophagus was ligated with a suture to prevent the administration solution from flowing into the stomach.
Next, a mixture of copper gluconate 4 mg/mL and zinc chloride 10 mg/mL was prepared using a medium (4% carboxymethylcellulose sodium aqueous solution: CMC aqueous solution), and 100 µL of the test substance administration solution was administered intraorally with a micropipette. bottom.
Similarly, a mixture of copper gluconate 4 mg/mL, zinc chloride 10 mg/mL, and L-menthol 10 mg/mL was prepared using a medium (4% sodium carboxymethylcellulose aqueous solution: CMC aqueous solution). 100 μL of was administered into the oral cavity with a micropipette.
As a control, a medium (4% CMC aqueous solution) was administered intraorally in the same amount (100 μL) as the test substance.
Ten minutes after vehicle or test substance administration, the oral cavity was wiped with a tared cotton ball. The amount of saliva produced during dosing was estimated by subtracting the tare and the weight of the vehicle or test article dosing solution from the weight after wiping.
A tared cotton ball was placed in the oral cavity immediately after wiping the oral cavity of the vehicle or dosing solution. For any group, the cotton ball was replaced every 10 minutes, and the amount of saliva secreted was measured by subtracting the weight after replacement. Measurements were carried out up to 30 minutes later.
(4) Test results Table 2 and Figure 2 show the measurement results of total salivary secretion for 30 minutes after administration of each test substance and control (vehicle) (both n = 6).
From Table 2 and FIG. 2, an unexpected result was obtained that the combined use of copper gluconate, zinc chloride and L-menthol exhibited an approximately 400-fold superior saliva secretion-promoting effect compared to the control.

(Formulation Examples 1, 2, 3, 4, 5) Dentifrice Using the components and amounts shown in Table 3, a paste dentifrice is produced according to a conventional method.

(Formulation Examples 6, 7, 8, 9, 10) Mouthwash Using the components and amounts shown in Table 4, prepare a mouthwash according to a conventional method.

(Formulation Example 11) Oral Ointment The ingredients and amounts shown in Table 5 are used to produce an oral ointment according to a conventional method.

(Formulation Example 12) Lozenge A lozenge is produced by taking the ingredients and amounts shown in Table 6 and following the section "Lozenge" in the General Rules for Pharmaceutical Preparations of the Japanese Pharmacopoeia.

(Formulation Example 13) Tablets for oral use Taking the ingredients and amounts shown in Table 7, tablets for oral use are produced in accordance with the section "Tablets for oral use" in the General Rules for Pharmaceutical Preparations of the Japanese Pharmacopoeia.

Claims (2)

An antibacterial agent for killing or inhibiting growth of Prevotella intermedia, comprising a copper compound, a zinc compound, and L-menthol. 2. The antibacterial agent according to claim 1, which is a saliva secretion stimulant.

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