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 that is effective against bacteria that cause bad breath and periodontal disease, and that can prevent or improve bad breath and / or periodontal disease. [Background technology]

[0002] Unpleasant odors emanating from the mouth can be a nuisance to those around you and can hinder social communication. Therefore, reducing bad breath is linked to maintaining good social communication as well as overall health, and research and development into substances that can reduce bad breath has been conducted from various perspectives.

[0003] Periodontal disease is an inflammatory disease caused by bacterial infection. It not only leads to tooth loss, but also has been shown to have a toxic effect on the digestive tract when periodontal disease bacteria are swallowed, alter the intestinal flora, and even invade the blood circulation directly from periodontal tissues, causing damage to blood vessels and various organs.

[0004] It is well known that oral halitosis is most commonly caused by volatile sulfur compounds (VSCs), such as methyl mercaptan, hydrogen sulfide, and dimethyl sulfide. These VSCs are produced by the metabolism of anaerobic bacteria present in the oral cavity. Bacteria such as Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythensis, Campylobacter rectus, Treponema denticola, and Fusobacterium nucleatum, which are also pathogens of periodontal disease, are known to produce particularly strong VSCs. 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 components such as cysteine ​​and methionine present in proteins in saliva, sloughed epithelial cells, and food residues. To fundamentally suppress bad breath, it is essential to kill or inhibit the growth 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 toothpaste that contains copper gluconate and zinc chloride, as well as xanthan gum or hydroxyethyl cellulose, and has improved astringent properties 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 until now that the combined use of a copper compound, a zinc compound, and L-menthol can dramatically kill or inhibit the growth of bacteria that cause bad breath and periodontal disease. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] Japanese Patent Application Laid-Open No. 2013-001701 [Patent Document 2] Japanese Patent Application Laid-Open No. 2011-105682 [Patent Document 3] Japanese Patent Application Laid-Open No. 2004-018470 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 improve 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] The present inventors have conducted extensive research to solve these problems and have found that a combination of a copper compound, a zinc compound, and L-menthol exhibits excellent antibacterial and salivary secretion effects, leading to the completion of the present invention. That is, the present invention is a composition for preventing or ameliorating 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 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, copper chlorophyllin sodium, 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) The composition according to any one of (1) to (4), which is used for preventing or improving bad breath and / or periodontal disease. [Effects of the Invention]

[0012] According to the present invention, it is possible to provide a composition having excellent antibacterial activity for preventing or ameliorating bad breath and / or periodontal disease. The composition of the present invention kills or inhibits the growth of bacteria that cause bad breath and periodontal disease in the oral cavity, and the saliva produced by the saliva secretion-promoting effect of the composition of the present invention kills or inhibits the growth of the causative bacteria. [Brief explanation of the drawings]

[0013] [Figure 1]The bacterial concentration is shown when the culture medium contains only bacterial solution (control), the culture medium contains 0.001% copper gluconate, 0.01% zinc chloride, or 0.001% L-menthol, the culture medium contains 0.001% copper gluconate and 0.01% zinc chloride, and the culture medium contains 0.001% copper gluconate, 0.01% zinc chloride, and the culture medium contains the test substance to make 0.001% L-menthol. [Figure 2] The graph shows 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. DETAILED DESCRIPTION OF THE INVENTION

[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 growth 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 is an inorganic or organic salt of copper, and may be any salt that is used as a raw material for pharmaceuticals, foods, and cosmetics, and examples thereof 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 lauroylsarcosine, copper fluorosilicate, copper fluoroborate, zinc undecylenate, copper chlorophyllin sodium, and copper chlorophyll, and preferably copper sulfate, copper gluconate, copper chlorophyllin sodium, or copper chlorophyll, and more preferably copper gluconate.

[0017] The "zinc compound" used in the present invention is an inorganic or organic salt of zinc, and may be any salt that is used as a raw material for pharmaceuticals, foods, and cosmetics, and examples thereof include 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, zinc glutamate, zinc phosphate, zinc phosphate, zinc phosphate, zinc phosphate, zinc glutamate ... Examples include zinc lyserophosphate, zinc glycolate, zinc picolinate, zinc ascorbate, zinc bisglycinate, zinc lysinate, zinc methioninate, zinc pyroate, zinc oleate, zinc stearate, zinc lauroylsarcosinate, zinc fluorosilicate, zinc fluoroborate, and zinc undecylenate, and preferred examples include zinc oxide, zinc carbonate, zinc chloride, zinc sulfate, zinc gluconate, zinc undecylenate, low-temperature-baked zinc oxide, zinc paraphenolsulfonate, zinc palmitate, zinc pyrithione, zinc myristate, and zinc laurate, and more preferred examples include zinc chloride.

[0018] The "L-menthol" used in the present invention may be used as a single L-menthol preparation, 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 are easily available. They can also be produced by known methods.

[0019] The present invention is used as a medicine, a quasi-drug, a cosmetic, etc.

[0020] The form of the present invention and the method of application to the oral cavity are not particularly limited. Examples include mouthwash (mouth rinse), toothpaste, liquid toothpaste, tooth powder, gum, lozenges, buccal tablets, gingival adhesive tape preparations, oral gel preparations, oral ointments, oral sprays, oral pastes, oral pastes, oral pills, oral tablets, oral powders, oral powders, oral liquids, oral suspensions, oral emulsions, oral granules, and oral capsules. Preferred are mouthwash (mouth rinse), toothpaste, liquid toothpaste, and 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, 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 commercially available ingredient used in pharmaceuticals, foods, and cosmetics, such as 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 needed.

[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 needed.

[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 a combination of two or more of these can 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, sorbic acid, benzoic acid, dehydroacetic acid, propionic acid, and salts thereof, etc. 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 a combination of two or more of these can be appropriately selected and blended.

[0031] A 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 ointment, abrasives, foaming agents, and thickening agents are used as appropriate.

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

[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 examples.

[0035] (Example 1) Growth inhibition test of bacteria causing bad breath (1) Test substance Copper gluconate (hereinafter, GCu) and zinc chloride (hereinafter, ZnCl2) were manufactured by Wako Pure Chemical Industries, Ltd., and L-menthol (hereinafter, Men) was manufactured by Suzuki Menthol. (2) Test strain In this test, Prevotella intermedia ATCC 25611, which is well known as a bacterium that causes bad breath and periodontal disease, was used. (3) Test method: Preparation of bacterial solution Prevotella intermedia was cultured anaerobically on an anerobic Columbia rabbit blood agar medium (Becton Dickinson Japan) at 35°C for 48 to 72 hours, and then suspended in sterile saline to obtain approximately 3.0 × 10 8 A bacterial solution of approximately 10 CFU / mL was prepared. 7 The bacterial solution was prepared so that the concentration was CFU / mL. (4) Test method: Preparation of test solution The test substances copper gluconate, zinc chloride, and L-menthol were prepared in the medium to their respective final concentrations, and 0.1 volume of Prevotella intermedia bacterial solution was added to 9.9 volumes of this to prepare the test solution. After culturing this at 35°C under anaerobic conditions for 24 hours, the number of viable bacteria per mL (CFU / mL) was measured. (5) Test results The results of measuring the viable bacterial count for each test substance and the control (bacterial solution only) are shown in Table 1 and Figure 1. 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 exhibits excellent antibacterial activity against the bacteria that cause bad breath and periodontal disease.

[0036] [Table 1]

[0037] (Example 2) Salivary secretion promotion test (1) Test substance Copper gluconate and zinc chloride were manufactured by Wako Pure Chemical Industries, Ltd., 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 acclimatization. (3) Test method After the quarantine and acclimation period (7 days), 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 sutures to prevent the administered solution from entering the stomach. Next, 100 μL of 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 sodium solution: referred to as CMC aqueous solution) was administered into the oral cavity using a micropipette. Similarly, a test substance administration solution prepared using a mixture of 4 mg / mL copper gluconate, 10 mg / mL zinc chloride, and 10 mg / mL L-menthol in a vehicle (4% aqueous carboxymethylcellulose sodium solution: referred to as CMC aqueous solution) was administered in an amount of 100 μL into the oral cavity using a micropipette. As a control, a vehicle (4% CMC aqueous solution) was administered into the oral cavity in the same amount (100 μL) as the test substance. Ten minutes after administration of the vehicle or test substance, the vehicle or test solution was wiped from the oral cavity using a tared cotton ball. The weight of the wiped cotton ball plus the weight of the vehicle or test substance was subtracted from the weight of the wiped cotton ball to estimate the amount of saliva secreted during administration. Immediately after wiping the vehicle or administration solution from the oral cavity, a weighed cotton ball 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 one. 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 the control (vehicle) (n=6 for each) are shown in Table 2 and Figure 2, respectively. As can be seen from Table 2 and Figure 2, the unexpected result was that the combined use of copper gluconate, zinc chloride, and L-menthol exhibited an excellent 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 Using the ingredients and amounts shown in Table 3, a paste-type toothpaste 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 Using the ingredients and amounts shown in Table 5, prepare an oral ointment according to the usual method.

[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 tablets Take the ingredients and amounts in Table 7 and prepare oral tablets in accordance with the "Oral Tablets" section of the Japanese Pharmacopoeia General Provisions for Preparations. Manufacture.

[0048] [Table 7]

Claims

[Claim 1] A saliva secretion stimulant containing copper gluconate, zinc chloride, and L-menthol as active ingredients.

Images