JP6471407B2 - Oral or throat composition - Google Patents

Description

  The present invention relates to an oral or throat composition having a bactericidal effect on a biofilm.

  Conventionally, compositions aimed at preventing the occurrence of caries, periodontal disease, bad breath, cold, etc., so-called dental rinses, mouthwashes and the like have been provided.

  As such a composition, it is considered effective to use a component having an excellent sterilizing effect and cleaning effect, and many components having such an action have been proposed. However, although a certain effect can be obtained, there are many cases where a sufficient effect cannot be exhibited.

  As a result of recent research, it has been clarified that it is very important to remove biofilms in order to prevent caries, periodontal disease, bad breath, colds, etc. A biofilm is a group of microorganisms that exist widely in nature, and is a slimy mucoid bacterial mass, with each bacterium wearing a polysaccharide garment. Specifically, this includes slime of sewer pipes and plaque (plaque), but such biofilms have extremely strong resistance to existing antibacterial agents and cleaning agents. The biofilm is formed in the oral cavity such as teeth or in the throat, which causes caries, periodontal disease, bad breath, cold, pneumonia, and the like.

  For biofilms formed on teeth, removal by brushing is most effective. However, even if a toothbrush or an interdental brush is used, there are sites where these are difficult to reach. Use of a composition containing a bactericide such as dental rinse is considered effective for sterilization of a biofilm formed in such a site. In the throat, brushing is impossible, so use of a mouthwash or a spray is useful.

  However, biofilms have a large number of bacteria that gather together and have poor permeability and are sticky and difficult to peel off. Therefore, it is not easy to sterilize the biofilm, and as described above, it has extremely strong resistance to existing sterilizing agents and cleaning agents. So far, proposals have been made regarding a bactericidal component (see Patent Document 1) and a cleaning component (see Patent Document 2) for removing a biofilm, but it is difficult to say that a sufficient effect has been obtained. .

JP 2013-151474 A JP2013-1810111A

  In view of the circumstances as described above, an object of the present invention is to provide an oral or throat composition having an excellent bactericidal action on a biofilm.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have encapsulated a phenolic fungicide in a liposome containing a hydrogenated phospholipid, so that the oral cavity or throat has a biofilm bactericidal effect. The present inventors have found that a composition for use can be provided, and have completed the present invention.

That is, the present invention
[1] A composition for oral cavity or throat containing a liposome containing a bactericidal agent, wherein the bactericidal agent is a phenolic bactericidal agent, and the liposome comprises a hydrogenated phospholipid. , Oral or throat compositions,
[2] The composition for oral cavity or throat according to [1], wherein the phenolic fungicide is isopropylmethylphenol,
[3] The composition for oral cavity or throat according to [1] or [2], wherein the phenolic fungicide encapsulated in the liposome is contained in an amount of 125 μg / mL or more with respect to the composition for oral cavity or throat,
[4] The composition for oral cavity or throat according to any one of [1] to [3], wherein the phospholipid constituting the liposome contains 60% by weight or more of hydrogenated phospholipid.
About.

  The composition for oral cavity or throat according to the present invention as described above has an excellent bactericidal action on biofilms.

Results of bactericidal evaluation test. Results of bactericidal evaluation test. Results of bactericidal evaluation test.

  The composition for oral cavity or throat according to the present invention includes a liposome containing a bactericidal agent, the bactericidal agent is a phenolic bactericidal agent, and the liposome further includes a hydrogenated phospholipid. . And by taking such a structure, the high bactericidal effect with respect to a biofilm is acquired.

  A phenolic fungicide is used as the fungicide. As the phenolic fungicide, known phenolic fungicides can be widely used. Specific examples include, but are not limited to, isopropylmethylphenol (4-Isopropyl-3-methylphenol, hereinafter referred to as IMP), cresol (methylphenol), triclosan, and the like. However, among these phenolic fungicides, IMP is preferable and has a particularly effective bactericidal action.

  Liposomes are monolayers formed by self-assembly of phospholipids, or lipid complexes composed of a plurality of layers. Based on the number of lipid bilayers, two liposomes, multilamellar liposomes (MLV) and single membrane liposomes are used. are categorized. The unilamellar liposomes are further classified into SUV (small unilamella vesicle), LUV (large unilamella vesicle), GUV (giant unilamella vesicle), etc., and any of these may be used.

  The liposome encapsulating the bactericide is not particularly limited as long as it contains at least a hydrogenated phospholipid. Examples of phospholipids that form liposomes include hydrogenated phospholipids, hydrogenated glycerophospholipids, hydrogenated sphingophospholipids, hydrogenated lecithin (hydrogenated phosphatidylcholine: eg, hydrogenated soybean lecithin, hydrogenated egg yolk lecithin, hydrogenated corn Lecithin, hydrogenated cottonseed oil lecithin, etc.), as well as non-hydrogenated compounds, lecithin (soy lecithin, corn lecithin, cottonseed oil lecithin, egg yolk lecithin, egg white lecithin), phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, Glycerophospholipids such as phosphatidylic acid, sphingophospholipids such as sphingomyelin, phospholipid derivatives obtained by introducing polyethyleneglycol or aminoglycans into the phospholipids, hydroxylated lecithin, lysoleci It may be mixed down. Preferred is a phospholipid containing hydrogenated glycerophospholipid, and more preferred is a phospholipid containing hydrogenated lecithin. Usually, hydrogenated phospholipids with a phosphatidylcholine content of 50% by mass or more (eg hydrogenated soybean lecithin, hydrogenated soybean phospholipid, hydrogenated egg yolk oil, hydrogenated egg yolk phospholipid, hydrogenated egg yolk lecithin, etc.) Among them, hydrogenated soybean phospholipid can be more preferably used, and those having a phosphatidylcholine content of 60% by mass or more can be more preferably used.

  The hydrogenated phospholipid is, for example, as “hydrogenated egg yolk lecithin” “egg yolk lecithin PL-100P (phosphatidylcholine (hereinafter abbreviated as PC)” content 80%; manufactured by Kewpie Co., Ltd.) Resinol Y-10M (PC60%), Resinol Y-10E (PC85%; manufactured by Nikko Chemical Co., Ltd.), and as hydrogenated soybean phospholipid, SLP-PC70HS (PC70%; Sakai Oil Co., Ltd.) Manufactured), LIPOID P75-3 (PC70%), LIPOID P100-3 (PC90%; manufactured by LIPID), PHOSPHOLIPON 80H (PC70%), PHOSPHOLIPON 90H (PC90%; manufactured by LIPOID), Resinol S-10M (PC60%) ), Resinol S-10E (PC 80%; day Chemical Co., Ltd.), COATSOME NC-21 (PC90%), COATSOME NC-61 (PC60%; manufactured by NOF Corporation), etc., but are of course limited to these. It is not a thing.

  Such hydrogenated phospholipids preferably account for 60% by weight or more of the phospholipids constituting the liposome, and thereby can effectively exert the bactericidal power of the bactericide contained therein.

  The size of the liposome used is preferably 10 to 1000 nm, more preferably 10 to 600 nm, and still more preferably 20 to 300 nm, with an average particle diameter or an average outer diameter (hereinafter referred to as an average particle diameter). Further, from the viewpoint of stability, it is preferable that there is less variation in the average particle diameter of the liposome. For this reason, the number of liposomes in which the difference between the upper and lower limit values such as the average particle diameter is within 1000 nm, more preferably within 300 nm, is preferably 60% or more, more preferably 80% or more in all liposomes.

  As a method for producing liposomes, a known method can be widely adopted. The production method of the liposome suspension is not particularly limited. (1) An aqueous solution containing a pH adjuster, a polyhydric alcohol, a saccharide, etc. after homogeneously mixing phospholipids, components encapsulated in liposomes, and other antioxidants (2) Phospholipids, components encapsulated in liposomes, other antioxidants, etc. are dissolved in alcohol, polyhydric alcohol, etc., pH adjuster, polyhydric alcohol, saccharide, etc. A method of preparing liposomes by hydration with an aqueous solution containing them, (3) using ultrasound, a French press or a homogenizer, complexing phospholipids, components encapsulated in liposomes, and other antioxidants in water, Method of preparation, (4) Phospholipids, components encapsulated in liposomes, other antioxidants, etc. are mixed and dissolved in ethanol, and this ethanol solution A method of preparing liposomes to remove ethanol was added to the aqueous potassium chloride solution can be used. For example, a phospholipid containing a predetermined amount of hydrogenated phospholipid is solubilized with an appropriate organic solvent such as ethanol, and the solvent is removed under reduced pressure to create a membrane lipid, which is water, buffer solution, saccharide After adding the aqueous solution, etc., it can be obtained by, for example, stirring at about 1000 to 3000 rpm for about 2 to 5 minutes to prepare a liposome suspension. It can also be prepared by adding a predetermined amount of the phospholipid dissolved in, for example, ethanol to water, a buffer solution, or a saccharide-containing aqueous solution and stirring with a high-pressure homogenizer or the like.

  Liposomes include not only phenolic fungicides such as IMP, but also oily ingredients, lipids, water-soluble substances, physiologically active substances and the like, for example, antioxidants such as tocopherol and ascorbic acid, lactic acid, citric acid and the like. Organic acids such as acids, lipids such as phosphatidylglycerol and phosphatidylethanolamine, natural polymers such as chitosan, fucoidan and hyaluronic acid, synthetic polymers such as polyethylene glycol and carboxyvinyl polymer, carbohydrates such as trehalose, lactulose and maltitol Furthermore, a polyol such as glycerin may be formulated by encapsulating it within a range not impairing the effects of the present invention. The term “encapsulation” as used herein refers to various forms such as when encapsulated inside the liposome, when included in the liposome membrane, or when attached to the outer surface of the liposome membrane.

  Liposomes are produced as liposome suspensions having a continuous layer of a solvent such as water. The obtained liposome suspension may be used as it is, or may be used after being dried by freeze drying or spray drying. Development into various dosage forms is possible by drying in particular.

  Liposomes may be coated on the outer surface for purposes such as improving stability. Known coating agents can be widely used as the coating agent, and examples thereof include coating with a polysaccharide containing a sulfate group. The sulfate group-containing polysaccharide preferably has a molecular weight of about 5,000 to 300,000. More specifically, in addition to polysaccharides that originally contain sulfate groups, such as fucoidan, carrageenan, agar, heparin, etc., such as chondroitin sulfate and dermatan sulfate, originally have no sulfate groups. It may be a sulfated polysaccharide, and is not limited to these. Of these, fucoidan and carrageenan are preferable, and fucoidan is particularly preferable.

  When the sulfate group-containing polysaccharide is used as the coating agent, the amount used is preferably 10 to 500 parts by weight, more preferably 20 to 200 parts by weight, with respect to 100 parts by weight of phosphatidylcholine contained in the liposome.

  As a method of coating the liposome with the coating agent, a known method can be widely adopted. Specifically, it can be carried out by adding a coating agent to a liposome suspension encapsulating a phenolic fungicide and the like and stirring at about 1000 to 3000 rpm for 2 to 5 minutes, but is not limited thereto. is not. Moreover, the aspect in which a some liposome is contained in one coating film | membrane may be sufficient.

  Regarding the potential of the liposome surface, the Zeta potential is preferably -100 to 100 meV.

  As content contained with respect to the whole composition for oral cavity or pharynx which concerns on this invention of the phenol-type disinfectant included in a liposome, 100-3000 microgram / mL is preferable and 125-1000 microgram / mL is more preferable. In a solution in which a phenolic disinfectant is simply dissolved, a phenolic disinfectant is prepared in a low concentration range such as 100 to 1000 μg / mL, that is, a low concentration range such as 100 to 400 μg / mL. A sufficient bactericidal effect by the bactericide cannot be obtained. However, by adopting the configuration of the present invention, a sufficient sterilizing effect can be obtained even in such a low concentration range.

  The composition for oral cavity or throat of the present invention is used for disinfection or cleaning in the oral cavity or throat, and is appropriately prepared in the form of liquid, liquid, paste, or the like. Specifically, toothpastes such as toothpaste, liquid dentifrice, liquid dentifrice, moisturized dentifrice, mouthwash, mouth spray, oral application agent, oral gel, oral ointment, throat spray, mouthwash, pasta, soft In addition to general pastes, throat coating agents, chewable tablets, lozenges, drop agents and the like, they can also be prepared as tablets, candy, chewing gum, etc., and these can be prepared by conventional methods.

  In order to prepare these various dosage forms, in addition to the composition essential to the present invention, a base component according to the dosage form can be blended as necessary within the range that does not impair the effects of the present invention. Specifically, for example, wetting agents, flavoring agents, surfactants, sweeteners, abrasives, binders, sugar alcohols, preservatives, coloring agents, pH adjusters, solvents such as water, various active ingredients, etc. Can be blended.

  For example, when used as a liquid dentifrice, in addition to the liposome encapsulating the phenolic fungicide as described above, the wetting agent is 0.1 to 20% by weight and the flavoring agent is 0 to 0% with respect to the entire liquid dentifrice. 3 wt% and surfactant may be added in an amount of 0.5 to 5 wt%, but are not particularly limited thereto.

  For example, when used as a mouthwash, similarly, 1 to 30% by weight of a wetting agent, 0 to 1% by weight of a flavoring agent, and 0.001 to 5% by weight of a surfactant with respect to the whole mouthwash. However, the present invention is not limited to this.

  A well-known thing can be widely used as a wetting agent. Specifically, polyhydric alcohols such as sorbit, glycerin, ethylene glycol, propylene glycol, 1,3-butylene glycol, polyethylene glycol, polypropylene glycol, xylit, maltite, and lactit are used alone or in combination of two or more. However, the present invention is not limited to these.

  A well-known thing can be widely used also as a flavoring agent. Specifically, menthol, anethole, carvone, eugenol, limonene, peppermint oil, spearmint oil, winter green, methyl salicylate, cionel, thymol, clove oil, eucalyptus oil, rosemary oil, sage oil, lemon oil, orange oil, Osimene oil, citronellol, methyl eugenol and the like can be mentioned. These flavoring agents can be blended alone or in combination of two or more.

  As the surfactant, known ones can be widely used. Specifically, sodium alkyl sulfate such as sodium lauryl sulfate and sodium myristyl sulfate, N-acyl glutamate such as sodium N-palmitoyl glutamate, sugar fatty acid ester such as sucrose fatty acid ester, maltose fatty acid ester and lactose fatty acid ester, poly Oxyethylene alkyl ethers, alkyl glucosides, fatty acid alkanolamides, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monostearate, polyoxyethylene hydrogenated castor oil, sorbitan fatty acid esters, N-alkyldiaminoethylglycine such as fatty acid monoglyceride, N-lauryldiaminoethylglycine, N-myristyldiethylglycine, N- Alkyl -N- carboxymethyl ammonium betaine, although surfactants such as lauryl dimethylamino acetic acid betaine without limitation. These surfactants can be blended alone or in combination of two or more.

  Known sweeteners can be widely used as sweeteners. Specifically, sodium saccharin, acesulfame potassium, stevioside, neohesperidyl dihydrochalcone, glycyrrhizin, perilartine, thaumatin, asparatylphenylalanyl methyl ester, α-methoxycinnamic aldehyde, xylit, sucrose, sucralose, palatinose, palatinit Erythritol, maltitol and the like can be blended. These sweeteners can be blended alone or in combination of two or more, but are not limited thereto.

  A well-known thing can be widely used also as an abrasive | polishing agent. For example, silica-based abrasives such as crystalline silica, amorphous silica, silica gel, aluminosilicate, zeolite, calcium hydrogen phosphate anhydrate, calcium hydrogen phosphate dihydrate, calcium pyrophosphate, calcium carbonate, aluminum hydroxide , Alumina, magnesium carbonate, tribasic magnesium phosphate, zirconium silicate, tribasic calcium phosphate, hydroxyapatite, quaternary calcium phosphate, synthetic resin-based abrasive, etc. can be used alone or in combination of two or more thereof. It is not limited to.

  A well-known thing can be widely used also as a binder. Specifically, pullulan, gelatin, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, carrageenan, sodium alginate, xanthan gum, sodium polyacrylate, gum arabic, guar gum, locust bean gum, polyvinyl alcohol, polyvinylpyrrolidone, etc. Although it can use individually or in combination of 2 or more types, it is not limited to these.

  Known sugar alcohols can be widely used. For example, erythritol, xylitol, sorbitol, mannitol and the like can be used alone or in combination of two or more, but are not limited thereto.

  A well-known thing can be widely used also as a preservative. Specific examples include parabens such as methyl paraben, ethyl paraben, propyl paraben, and butyl paraben, sodium benzoate, phenoxyethanol, and alkyldiaminoethyl glycine hydrochloride, but are not limited thereto.

  A well-known thing can be widely used also as a coloring agent. Specific examples include legal dyes such as Blue No. 1, Yellow No. 4, Red No. 202, and Green No. 3, mineral dyes such as ultramarine blue, enhanced ultramarine blue, and bitumen, and titanium oxide, but are not limited thereto.

  Moreover, a well-known thing can be widely used also as a pH adjuster. Specific examples include citric acid, phosphoric acid, malic acid, pyrophosphoric acid, lactic acid, tartaric acid, glycerophosphoric acid, acetic acid, nitric acid, or a chemically possible salt thereof, sodium hydroxide, and the like. It can mix | blend individually or in combination of 2 or more types so that pH of a thing may be the range of 5-8.

  As the solvent, besides the water described above, known solvents can be widely used, and there is no particular limitation.

  Also as a chemical | medical agent component, a well-known thing can be widely used as needed. Specifically, as other medicinal agents, fluorine compounds such as sodium fluoride, sodium monofluorophosphate, stannous fluoride; dextranase, mutanase, amylase, protease, lytic enzyme (Litec Enzyme), etc. Enzymes: tranexamic acid, ε-aminocaproic acid, aluminum chlorohydroxy allantoin, allantoin, dihydrocholesterol, glycyrrhizic acid, glycyrrhetinic acid, bisabolol, isopropylmethylphenol, glycerophosphoric acid, chlorophyll, copper gluconate, sodium chloride, water-soluble inorganic phosphate compound , Chlorhexidine salts, triclosan, cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride; acetic acid-dl-α-tocopherol, pyridoxine acetate, ascorbic acid or a salt thereof Vitamins such as thyme, plant extracts such as argon, etc. are mentioned, and there is no particular limitation. These may be used alone or in combination of two or more.

  As other base components, alcohols, silicon, apatite, white petrolatum, paraffin, liquid paraffin, microcrystalline wax, squalane and the like can be added as necessary.

  The embodiments of the present invention have been described above, but the present invention is not limited to these examples, and can of course be implemented in various forms without departing from the gist of the present invention.

  Hereinafter, based on an Example, Embodiment of this invention is described more concretely, This invention is not limited to these.

Example 1
After adding IMP and hydrogenated phospholipid (trade name: Coatsome NC-61, manufactured by NOF Corporation) as a bactericidal agent to a mixed solvent in which 16.7% by weight of butanol and 8.3% by weight of sucrose are dissolved in water The liposome was encapsulated in a liposome using a high-pressure atomizer, and the liposome encapsulating the bactericide was extracted by ultrafiltration to obtain a preparation solution. The IMP and hydrogenated phospholipid in the obtained preparation liquid were 0.105 and 1.02% by weight, respectively. The prepared solution is diluted twice with water, and then the concentration is adjusted with a solution obtained by diluting the mixed solvent with water (hereinafter referred to as a two-fold diluted mixed solvent). The total amount was 525 μg / mL. Thereafter, serial dilution was further performed twice with a 2-fold diluted mixed solvent, and IMP was 525, 262.5, 131.3, 65.6, 32.8, 16.4, 8 with respect to the entire liposome suspension. A liposome suspension encapsulating IMP was obtained at a concentration of 2 μg / mL.

(Comparative Example 1)
IMP was serially diluted with a 2-fold diluted mixed solvent to obtain solutions having respective IMP concentrations of 500, 250, 125, 62.5, 31.3, 15.6, and 7.8 μg / mL.

(Comparative Example 2)
Only phospholipids without hydrogen addition (product name: PIPS Nagase, manufactured by Nagase Sangyo) are used as the phospholipids constituting the liposome, and the concentrations of IMP and hydrogen-free phospholipids in the prepared solution obtained by ultrafiltration are respectively 0.95 and 0.67% by weight, and the concentration of IMP in the whole liposome suspension was 475, 237.5, 118.8, 59.4, 29.7, 14.8, 7.4 μg / mL. Except for the above, the same operation as in Example 1 was carried out to obtain a liposome suspension encapsulating each concentration of IMP.

(Comparative Example 3)
Using hinokitiol instead of IMP, the concentration of hinokitiol and hydrogenated phospholipid in the preparation obtained by ultrafiltration is 0.071 and 0.28% by weight, respectively, and the liposome suspension of hinokitiol The same procedure as in Example 1 was performed except that the total concentration was 355, 177.5, 88.8, 44.4, 22.2, 11.1, 5.5 μg / mL, and the hinokitiol at each concentration was An encapsulated liposome suspension was obtained.

(Comparative Example 4)
Hinokitiol was serially diluted with a 2-fold diluted mixed solvent to obtain solutions having respective concentrations of 350, 175, 87.5, 43.8, 21.9, 10.9, and 5.5 μg / mL.

(Comparative Example 5)
Using cetylpyridinium chloride (hereinafter referred to as CPC) instead of IMP, the concentrations of CPC and hydrogenated phospholipid in the preparation obtained by ultrafiltration were 0.116 and 0.88% by weight, respectively. The same operation as in Example 1 was carried out except that the concentration of CPC with respect to the whole liposome suspension was 580, 290, 145, 73, 36.3, 18.1, 9.1 μg / mL. A liposome suspension encapsulating CPC was obtained.

(Comparative Example 6)
CPC was serially diluted with a 2-fold diluted mixed solvent to obtain solutions having respective concentrations of 600, 300, 150, 75, 37.5, 18.8, and 9.4 μg / mL.

(Comparative Example 7)
IMP and hydrogenated phospholipid were added at 0.105% and 1.02% by weight, respectively, to a mixed solvent in which 16.7% by weight of butanol and 8.3% by weight of sucrose were dissolved in water, and dissolved. The obtained solution was serially diluted with a 2-fold diluted mixed solvent obtained by diluting the mixed solvent with water twice, and IMP was 525, 262.5, 131.3, 65.6, 32 with respect to the entire solution. The solution which becomes 0.8, 16.4, 8.2 μg / mL was obtained.

(Comparative Example 8)
The same operation as in Comparative Example 7 was performed except that no IMP was added to obtain a solution.

(Bactericidal evaluation method)
Streptococcus mutans ATCC25715 was cultured in a BHI liquid medium at 37 ° C. for 18 hours. Then, using a liquid medium in which 5% sucrose was dissolved in BHI, the bacterial solution was treated with O.D. D ₆₆₀ was adjusted to 1.0. The obtained bacterial solution was applied to a 96-well plate at 100 μL / well and cultured at 37 ° C. under anaerobic conditions for 24 hours to form a biofilm on the bottom of each well. As the number of wells for forming a biofilm, 3 wells were prepared for each of the Examples and Comparative Examples, and 6 wells were prepared for a 2-fold diluted mixed solvent as a control group.
Thereafter, the medium was removed from each well, washed with PBS, 100 μL each of the two-fold diluted mixed solvents as Examples, Comparative Examples, and Control Groups were applied and allowed to stand at 37 ° C. for 15 minutes. Washed 3 times. After removing the washed PBS, 100 μL of AlamarBlue (registered trademark) solution diluted 10-fold with PBS was added to each well and allowed to stand at 37 ° C. for 120 minutes in the dark. Thereafter, the fluorescence intensity was measured with a fluorescence plate reader under the conditions of an excitation wavelength of 560 nm and a fluorescence wavelength of 590 nm, and the viable cell ratios of Examples and Comparative Examples were calculated. The viable cell rate was calculated as a percentage of the fluorescence intensity of each well of the example and the comparative example with respect to the average value of the fluorescence intensity of 6 wells prepared as a control group. The data was tabulated using the average value ± standard deviation of each of the three wells of the examples and comparative examples.

(Study on encapsulation in liposomes and phospholipids constituting liposomes)
Each concentration solution of Example 1, Comparative Example 1 and Comparative Example 2 was used, and each bactericidal evaluation was performed. For Comparative Example 1, two groups were prepared for comparison with both Example 1 and Comparative Example 2. In addition, a significant difference test was performed by the Student t test between Example 1 and Comparative Example 1 and Comparative Example 1 and Comparative Example 2 at the corresponding corresponding concentrations, and there was a significant difference when p value <0.05. It was. Here, in the comparison of Example 1 and Comparative Examples 1 and 2, the IMP concentrations subjected to the evaluation test are different accurately. However, since all three cases were evaluated in a concentration range close to 500, 250, 125, 62.5, 31.3, 15.6, 7.8 μg / mL, 500, 250, 125 from the high concentration side, respectively. , 62.5, 31.3, 15.6, 7.8 μg / mL, assuming that the evaluation test was performed, a significant difference test was performed, and the results were displayed in the graph of FIG. As a result, in the comparison between Example 1 and Comparative Example 1, a significant difference was confirmed in the viable cell rate in the concentration range of 125 μg / mL. As a result, it was confirmed that by incorporating IMP in liposomes formed with hydrogenated phospholipid, an effective bactericidal action was exhibited in a concentration range of 125 μg / mL or more. On the other hand, in Comparative Example 2 in which IMP was encapsulated in liposomes formed with non-hydrogen-added phospholipid, a significant difference in bactericidal effect could not be confirmed as compared with the case where IMP was not encapsulated in liposomes.

(Disinfectant study)
Using the solutions of each concentration of Comparative Examples 3 to 6, each bactericidal evaluation was performed and compared with the results of Example 1 and Comparative Example 1. Here, in the comparison between Comparative Examples 3 and 4 and Comparative Examples 5 and 6, the concentrations of hinokitiol and CPC subjected to the evaluation test are slightly different. However, since Comparative Example 3 is the concentration subjected to the evaluation test in Comparative Example 4, and Comparative Example 5 is performing the evaluation test in a concentration range close to the concentration subjected to the evaluation test in Comparative Example 6, Comparative Example 3 is a comparative example. 4 and Comparative Example 5 were regarded as having been subjected to an evaluation test at the same concentration as Comparative Example 6, and were compared and displayed in the graph of FIG. As a result, as shown in FIG. 2, a significant improvement in the bactericidal effect due to the inclusion of hinokitiol and CPC in liposomes containing hydrogenated phospholipids could not be confirmed.

(Examination of the relationship between hydrogenated phospholipids and IMP)
Enhancement of the sterilizing effect of IMP by encapsulating in hydrogenated phospholipid occurs not only by encapsulating IMP in liposomes containing hydrogenated phospholipid, but simply by coexisting with hydrogenated phospholipid. Therefore, bactericidal evaluation was performed using each concentration solution of Example 1, Comparative Example 1, Comparative Example 7, and Comparative Example 8. In Example 1, Comparative Example 7 and Comparative Example 8, the evaluation test was performed in the concentration range of 525, 262.5, 131.3, 65.6, 32.8, 16.4, 8.2 μg / mL. However, these concentrations are close to the concentration ranges of 500, 250, 125, 62.5, 31.3, 15.6, and 7.8 μg / mL set in Comparative Example 1. Therefore, in all examples and comparative examples in this evaluation test, evaluation tests were performed at concentrations of 500, 250, 125, 62.5, 31.3, 15.6, and 7.8 μg / mL from the high concentration side. The data was aggregated. As a result, as shown in FIG. 3, only Example 1 has a significant bactericidal effect, and Comparative Example 7 in which hydrogenated phospholipid and IMP are mixed is more sterilized than Comparative Example 1 as well as Example 1. It was confirmed that the effect was weak. From the above, it was confirmed that IMP exhibits an excellent bactericidal effect when encapsulated in liposomes containing hydrogenated phospholipids.

  Hereinafter, production examples will be given. Each production example is produced by a conventional method. Unless otherwise specified, the numerical values in each production example indicate “% by weight”. The present invention is not limited to these production examples.

(Production Example 1) Mouthwashing agent Component Compounding amount Liposome suspension A 12.5
Glycerin 10
Propylene glycol 5
Citric acid 0.01
Trisodium citrate 0.1
Methyl paraoxybenzoate 0.1
Fragrance 0.05
Saccharin sodium 0.02
Purified water balance Total 100

Liposome suspension A
IMP 0.1
Hydrogenated soybean phospholipid (LIPOID P-75-3 (manufactured by LIPOID)) 0.5
Ethyl alcohol 5
Purified water 94.4

(Production Example 2) Mouthwashing agent Component Compounding amount Liposome suspension B 5
Glycerin 10
Propylene glycol 5
Xylitol 2
Sodium hydroxide 0.2
Fragrance 0.1
Methyl paraoxybenzoate 0.1
White shellac 0.1
Edetate disodium 0.05
Dipotassium glycyrrhizinate 0.05
Sodium bicarbonate 0.03
Saccharin sodium 0.01
Blue No. 1 0.0002
Purified water balance Total 100

Liposome suspension B
IMP 2
Hydrogenated soybean phospholipid (Resinol S-10E (Nikko Chemical Co., Ltd.)) 5
Xanthan gum 0.1
Chondroitin sulfate 0.05
Water-soluble collagen 0.05
Purified water 92.8

(Manufacture example 3) Gel agent for oral cavity Ingredient Compounding quantity Liposome suspension C2
Sodium alginate 3
Sodium hyaluronate 2
Glycerin 10
Propylene glycol 5
Citric acid 0.01
Trisodium citrate 0.1
Methyl paraoxybenzoate 0.1
Fragrance 0.05
Saccharin sodium 0.02
Purified water balance Total 100

Liposome suspension C
IMP 2.5
Hydrogenated soybean phospholipid (Coatsome NC-61 (manufactured by NOF Corporation)) 15
Water-soluble collagen peptide 0.5
Chondroitin sulfate 0.1
1,3-butylene glycol 10
Purified water 71.9

(Production Example 4) Oral gel agent Component Compounding amount Liposome suspension D 2
Glycerin 25
Hydrogenated starch degradation product 10
Propylene glycol 2
Sodium polyacrylate 1.5
Methyl benzoate 0.1
Purified water balance Total 100

Liposome suspension D
IMP 1
Hydrogenated egg yolk phospholipid (Resinol Y-10E (Nikko Chemical Co., Ltd.)) 7
Ethanol 7
Purified water 85

(Production Example 5) Ingredients in Chewable Tablets, 1 Tablet (500 mg) Ingredients Compounding amount Powdered liposome (* 1) 5 mg
Xylitol 150mg
Hydroxypropylcellulose 20mg
Magnesium stearate 2mg
The remaining mannitol (* 1) powdered liposome has a composition of 5% IMP, 50% hydrogenated soybean phospholipid, and 45% crystalline cellulose.

(Production Example 6) Throat spray (component in 50 mL)
Ingredients Blending amount Liposome suspension E 5mg
Fructose glucose liquid sugar 1000mg
Sucralose 10mg
Citric acid 400mg
Sodium citrate 200mg
Fragrance Trace amount Sodium benzoate 50mg
Purified water balance

Liposome suspension E
Hydrogenated soybean phospholipid (PHOSPHOLIPON 90H (manufactured by LIPOID)) 3
IMP 0.5
Water-soluble collagen peptide 5
Vegetable ceramide 1
1,3-butylene glycol 5
Glycerin 10
Purified water balance

(Production Example 7) Film preparation Ingredient Compounding amount Powdered liposome (* 2) 5
Hydroxypropyl methylcellulose 16
Starch 25
Crystalline cellulose 1.5
Pullulan 1.5
Sucrose fatty acid ester 1.5
Aspartame 1
Fragrance 1
Glycerin 2
Maltitol 14
Lactose balance Total 100
(* 2) The powdered liposome has a composition of 5% IMP, 50% hydrogenated soybean phospholipid, and 45% crystalline cellulose.

Claims (1)

A composition for the oral cavity or throat containing liposomes containing a bactericidal agent,
The sterilizing agent is isopropyl methyl phenol,
The liposome comprises a hydrogenated phospholipid, and the phospholipid constituting the liposome contains 60% by weight or more of a hydrogenated phospholipid,
A bactericidal agent is contained in the oral cavity or throat composition in an amount of 262.5 μg / mL or more,
Oral or throat composition.

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