Composition containing a copper compound, a zinc compound, and L-menthol

Abstract

To provide a composition that is effective against bacteria causing an oral malodor and / or periodontitis, and can prevent or improve an oral malodor and / or periodontitis.SOLUTION: An oral composition contains a copper compound, a zinc compound, and L-menthol.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a composition which is effective against bacteria causing bad breath and periodontal disease and is capable of preventing or ameliorating bad breath and / or periodontal disease. [Background technology]

[0002] Unpleasant odors emanating from the mouth make people around you feel uncomfortable and are an obstacle to social communication. Therefore, since reducing bad breath leads to maintaining good social communication as well as overall health, research and development has been carried out from various perspectives on substances that reduce bad breath.

[0003] Periodontal disease is an inflammatory disease caused by bacterial infection. Periodontal disease not only leads to tooth loss, but also has the potential to cause toxic effects on the digestive tract when periodontal disease bacteria are swallowed, to change the intestinal flora, and to directly invade the blood circulation from periodontal tissues, causing damage to blood vessels and various organs.

[0004] It is well known that in most cases, bad breath is caused by volatile sulfur compounds (VSCs) such as methyl mercaptan, hydrogen sulfide, and dimethyl sulfide. These volatile sulfur compounds are produced by the metabolism of anaerobic bacteria living in the oral cavity. In particular, bacteria such as Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythensis, Campylobacter rectus, Treponema denticola, and Fusobacterium nucleatum, which are also pathogenic bacteria of periodontal disease, are said to have a high VSC production ability, and therefore the oral cavity of patients with periodontal disease produces a particularly strong foul odor. VSCs, the substances that cause bad breath, are produced when oral bacteria metabolize substrates such as cysteine ​​and methionine present in salivary proteins, sloughed epithelial cells, and food residues. To fundamentally prevent bad breath, it is essential to kill or inhibit the proliferation of oral bacteria, just as with periodontal disease.

[0005] Copper compounds and zinc compounds are known to have bactericidal effects (Patent Document 1), and a dentifrice that contains copper gluconate and zinc chloride, as well as xanthan gum or hydroxyethyl cellulose, and has improved astringent sensation and spinnability is known (Patent Document 2).

[0006] Regarding menthol, a technology has been disclosed in which food flavoring ingredients, such as peppermint oil containing menthol as a main component, are used as antibacterial agents (Patent Document 3).

[0007] However, it has not been known that the combined use of a copper compound, a zinc compound, and L-menthol can dramatically kill or inhibit the proliferation of bacteria that cause bad breath and periodontal disease. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] JP 2013-001701 A [Patent Document 2] JP 2011-105682 A [Patent Document 3] JP 2004-018470 A Summary of the Invention [Problem to be solved by the invention]

[0009] An object of the present invention is to provide a composition that can prevent or ameliorate bad breath and / or periodontal disease by killing or inhibiting the growth of bacteria that cause bad breath and periodontal disease. [Means for solving the problem]

[0010] In the course of intensive research to solve the above problems, the present inventors have found that a combination of a copper compound, a zinc compound, and L-menthol exhibits excellent antibacterial and saliva secretion effects, and have completed the present invention. That is, the present invention is a composition for preventing or improving bad breath and / or periodontal disease, which contains a copper compound, a zinc compound, and L-menthol.

[0011] That is, the present invention relates to the following (1) to (5). (1) An oral composition comprising 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) The composition according to (1) or (2), wherein the zinc compound is one or more selected from the group consisting of 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 zinc laurate. (4) The composition according to (1), wherein the copper compound is copper gluconate and the zinc compound is zinc chloride. (5) A composition according to any one of (1) to (4) for use in the prevention or amelioration of bad breath and / or periodontal disease. Effect of the Invention

[0012] According to the present invention, a composition for preventing or improving bad breath and / or periodontal disease having an excellent antibacterial effect can be provided. The composition of the present invention kills or inhibits the proliferation of bacteria causing bad breath and periodontal disease in the oral cavity, and saliva produced by the saliva secretion promoting effect of the composition of the present invention kills or inhibits the proliferation of the causative bacteria. [Brief description of the drawings]

[0013] [Figure 1]The concentrations of bacteria when cultured for 24 hours are shown in the table below: culture medium containing only bacteria (control); culture medium to which 0.001% copper gluconate, 0.01% zinc chloride, or 0.001% L-menthol has been added; culture medium to which 0.001% copper gluconate and 0.01% zinc chloride have been added; and culture medium to which the test substance has been added so that the copper gluconate, zinc chloride, and L-menthol are each 0.001%. [Diagram 2] The results of the total saliva secretion volume for 30 minutes after administration of the vehicle alone (control), a solution containing copper gluconate and zinc chloride, and a solution containing copper gluconate, zinc chloride, and L-menthol are shown. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] In the present invention, "prevention" means preventing the onset of bad breath and / or periodontal disease by killing the bacteria that cause bad breath and periodontal disease or inhibiting the proliferation of the bacteria.

[0015] In the present invention, "improvement" means alleviating the symptoms of bad breath and / or periodontal disease by reducing the bacteria that cause bad breath and periodontal disease.

[0016] The "copper compound" used in the present invention refers to an inorganic or organic salt of copper, and may be any salt that is used as a raw material for pharmaceuticals, foods, and cosmetics. Examples of the copper compound include copper oxide, copper borate, copper carbonate, copper fluoride, 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, and the like. Examples of the copper chlorophyll include copper, copper glycerate, copper glycerophosphate, copper glycolate, copper picolinate, copper ascorbate, copper bisglycinate, copper lysinate, copper methionine, copper pyrophosphate, copper oleate, copper stearate, copper lauroyl sarcosine, copper fluorosilicate, copper fluoroborate, zinc undecylenate, copper chlorophyllin sodium, and copper chlorophyll. Preferred examples include copper sulfate, copper gluconate, copper chlorophyllin sodium, and copper chlorophyll. More preferred examples include copper gluconate.

[0017] The "zinc compound" used in the present invention refers to an inorganic or organic salt of zinc, and may be any salt that is used as a raw material for pharmaceuticals, foods, and cosmetics. For example, zinc oxide, zinc borate, zinc carbonate, zinc fluoride, 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 ... Examples of the zinc glycerophosphate include zinc glycolate, zinc picolinate, zinc ascorbate, zinc bisglycinate, zinc lysinate, zinc methionine, zinc pyroate, zinc oleate, zinc stearate, zinc lauroyl sarcosine, zinc fluorosilicate, zinc fluoroborate, and zinc undecylenate. Preferred examples 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 zinc laurate. More preferred examples include zinc chloride.

[0018] The "L-menthol" used in the present invention may be L-menthol alone, or a cooling agent or fragrance containing L-menthol may be used. The above-mentioned "copper compound", "zinc compound" and "L-menthol" used in the present invention are commercially available as quasi-drugs, food products or cosmetic ingredients and can be easily obtained, or can be produced by known methods.

[0019] The present invention is used as medicines, quasi-drugs, cosmetics, etc.

[0020] 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, tooth powder, gum, lozenge, buccal tablet, gum-adhesive 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 granule, or oral capsule may be mentioned. Preferably, mouthwash (mouthwash), toothpaste, liquid toothpaste, or tooth powder.

[0021] In the present invention, the amount of the copper compound in the composition is preferably 0.001 to 10% by weight, and more preferably 0.01 to 1% by weight.

[0022] In the present invention, the concentration of the zinc compound in the composition is preferably 0.001 to 1% by weight, and more preferably 0.01 to 0.1% by weight.

[0023] In the present invention, the amount of L-menthol blended in the composition is preferably 0.001 to 5% by weight, and more preferably 0.01 to 1% by weight.

[0024] In the present invention, the copper compound, zinc compound, and L-menthol can be mixed in any ratio.

[0025] In the present invention, wetting agents, pH adjusting agents, flavoring agents, preservatives, fragrances, solubilizing agents, etc. may be added as appropriate.

[0026] The humectant may be any one that is commercially available as a pharmaceutical, food, or cosmetic ingredient, and examples thereof include polyhydric alcohols, and more specifically, sorbitol, glycerin, concentrated glycerin, ethylene glycol, propylene glycol, 1,3-butylene glycol, propanediol (1,3-propanediol), polyethylene glycol, polypropylene glycol, xylitol, maltitol, lactite, trehalose, sodium hyaluronate, hydrolyzed collagen, and the like. One or a combination of two or more of these may be appropriately selected and blended as necessary.

[0027] The pH of the composition for periodontal disease or bad breath 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, tartaric acid, acetic acid or salts thereof, sodium hydroxide, etc. One or a combination of two or more of these can be appropriately selected and blended as necessary.

[0028] Examples of flavoring agents include saccharin, saccharin sodium, 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, and maltitol. One or more of these may be appropriately selected and blended.

[0029] Examples of preservatives include parabens (paraoxybenzoic acid esters) such as methylparaben, ethylparaben, isopropylparaben, propylparaben, butylparaben, isobutylparaben, and benzylparaben, alcohols such as phenoxyethanol and ethanol, and sorbic acid, benzoic acid, dehydroacetic acid, propionic acid, and salts thereof. One or a combination of two or more of these can be appropriately selected and blended.

[0030] Examples of flavorings include L-menthol, peppermint, spearmint, or fruit flavorings, peppermint oil, etc. Flavorings also have the advantage of stimulating saliva secretion. One or more of these can be appropriately selected and blended.

[0031] The solubilizer may be added to promote dissolution of the 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 may be appropriately selected and blended.

[0032] In addition, in the case of toothpaste and ointments, abrasives, foaming agents, and thickening agents are appropriately used.

[0033] The present invention can further contain medicinal ingredients such as antibacterial agents, anti-inflammatory agents, fluorides, vitamins, herbal extracts, plaque decomposing enzymes, etc. These medicinal ingredients are not particularly limited as long as they can be used in medicines, etc. EXAMPLES

[0034] 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.

[0035] (Example 1) Growth inhibition test of bacteria causing bad breath (1) Test substance Copper gluconate (GCu) and zinc chloride (ZnCl2) were manufactured by Wako Pure Chemical Industries, and L-menthol (Men) was manufactured by Suzuki Mint. (2) Test strains In this study, Prevotella intermedia ATCC 25611, a bacterium well known to cause halitosis and periodontal disease, was used. (3) Test method: Preparation of bacterial solution Prevotella intermedia was cultured anaerobically on an anerobic culture medium (Becton Dickinson Japan) at 35°C for 48–72 hours, and then suspended in sterile saline to obtain a cell count of approximately 3.0 × 10 8 A bacterial solution with a CFU / mL concentration was prepared. 7 A bacterial solution was prepared so as to obtain a CFU / mL concentration. (4) Test method: Preparation of test solution The test substances copper gluconate, zinc chloride, and L-menthol were prepared in the medium to the respective final concentrations, and 0.1 volume of Prevotella intermedia bacteria solution was added to 9.9 volumes of the medium to prepare the test solution. After culturing this at 35°C under anaerobic conditions for 24 hours, the viable cell count per mL (CFU / mL) was measured. (5) Test results The results of the viable cell counts for each test substance and the control (bacterial solution only) are shown in Table 1 and Figure 1, respectively. Table 1 and Figure 1 show the unexpected result that the combined use of copper gluconate (GCu), zinc chloride (ZnCl2) and L-menthol (Men) dramatically demonstrated excellent antibacterial effects against the bacteria that cause bad breath and periodontal disease.

[0036] [Table 1]

[0037] (Example 2) Saliva secretion promotion test (1) Test substance Copper gluconate and zinc chloride were manufactured by Wako Pure Chemical Industries, and L-menthol was manufactured by Suzuki Mint. (2) Animals used Slc: Wistar male rats (Japan SLC Co., Ltd.), 6 weeks old, were purchased and subjected to quarantine and acclimation. (3) Test method After completing the quarantine and acclimation period (7 days), the rats were anesthetized by intraperitoneal administration of urethane (1 g / kg) and α-chloralose (25 mg / kg), a tracheal cannula was inserted to secure the airway, and the esophagus was ligated with suture to prevent the administered solution from entering the stomach. Next, a test substance administration solution prepared using a mixture of 4 mg / mL copper gluconate and 10 mg / mL zinc chloride in a vehicle (4% aqueous carboxymethylcellulose solution: referred to as CMC aqueous solution) was administered in an amount of 100 μL into the oral cavity using a micropipette. Similarly, a mixture of 4 mg / mL copper gluconate, 10 mg / mL zinc chloride, and 10 mg / mL L-menthol was prepared using a vehicle (4% aqueous carboxymethylcellulose solution: referred to as CMC aqueous solution) and 100 μL of the test substance administration solution was administered into the oral cavity using a micropipette. As a control, a vehicle (aqueous solution of 4% CMC) was administered into the oral cavity in the same amount (100 μL) as that of the test substance. Ten minutes after administration of the vehicle or test substance, the vehicle or test solution in the oral cavity was wiped off with a cotton ball whose tare weight had been measured. The amount of saliva secreted during administration was estimated by subtracting the weight of the cotton ball and the vehicle or test solution from the weight of the wiped off tissue. Immediately after wiping the vehicle or administration solution from the oral cavity, a cotton ball with a measured tare weight was placed in the oral cavity. For both groups, the cotton ball was replaced every 10 minutes, and the amount of saliva secreted was measured by subtracting the weight of the replaced cotton ball from the weight of the new cotton ball. Measurements were continued for up to 30 minutes. (4) Test results The results of measuring the total saliva secretion volume for 30 minutes after administration of each test substance and control (vehicle) (n=6 for each) are shown in Table 2 and FIG. 2, respectively. As shown in Table 2 and FIG. 2, the unexpected result was that the combined use of copper gluconate, zinc chloride and L-menthol exhibited a saliva secretion promoting effect that was approximately 400 times greater than that of the control.

[0038] [Table 2]

[0039] (Formulation Examples 1, 2, 3, 4, 5) Dentifrice The ingredients and amounts shown in Table 3 are taken and a paste-type dentifrice is prepared according to a conventional method.

[0040] [Table 3]

[0041] (Formulation Examples 6, 7, 8, 9, 10) Mouthwash Take the ingredients and amounts shown in Table 4 and prepare mouthwash according to conventional methods.

[0042] [Table 4]

[0043] (Formulation Example 11) Oral ointment Take the ingredients and amounts in Table 5 and prepare an oral ointment in the usual manner.

[0044] [Table 5]

[0045] (Formulation Example 12) Lozenges Using the ingredients and amounts in Table 6, prepare lozenges in accordance with the "Troches" section of the Japanese Pharmacopoeia General Provisions for Preparations.

[0046] [Table 6]

[0047] (Formulation Example 13) Oral Tablet Take the ingredients and amounts in Table 7 and prepare oral tablets in accordance with the General Provisions for Preparations of the Japanese Pharmacopoeia, section "Oral Tablets." Manufacture.

[0048] [Table 7]

Claims

[Claim 1] An oral composition containing copper gluconate, zinc chloride, and L-menthol, which is used on a subject carrying Prevotella intermedia, a bacterium that causes bad breath and / or periodontal disease, the oral composition being for killing or inhibiting the growth of Prevotella intermedia, preventing or ameliorating bad breath and / or periodontal disease, and promoting saliva secretion.

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