Oral care composition for preventing and treating periodontitis

Abstract

The invention discloses an oral care composition for preventing and treating periodontitis, the oral care composition comprises a compound shown in a formula (I) and oral auxiliary materials, by controlling the concentration or dosage of a component (a) in the oral care composition, the oral care composition can generate the effective drug concentration in the range of 1.35-13mM in the oral cavity after being applied to the oral cavity, and the oral care composition can be used for preventing and treating periodontitis. According to the invention, porphyromonas gingivalis can be more effectively inhibited, and meanwhile, a beneficial bacterium lactobacillus reuteri and the total amount of flora in oral cavities of healthy people are not substantially influenced, so that the oral flora microenvironment and flora imbalance can be effectively improved, and oral related diseases can be further avoided or prevented.

Description

[0001] This application is a divisional application of CN202411309479.7, filed on September 19, 2024, entitled "Oral care composition and uses", which is incorporated herein by reference in its entirety. TECHNICAL FIELD

[0002] The present application relates to the field of oral care, in particular to an oral care composition and uses capable of improving the microenvironment of oral flora, and further improving periodontal related diseases or conditions. BACKGROUND

[0003] Different bacteria in the oral cavity work together to maintain and build a healthy oral environment. When poor eating habits, overuse of drugs, and other reasons cause oral flora imbalance or imbalance, problems such as halitosis, oral ulcers, and even gum or periodontal related diseases may occur. Therefore, oral flora balance is crucial for good oral health.

[0004] An important feature of oral flora imbalance is the rapid proliferation of harmful bacteria such as Porphyromonas gingivalis. Current inhibitory drugs have no bias in inhibiting oral flora. Some drugs can control the number of bacteria in the oral cavity to some extent, but the effect is generally poor, and the beneficial bacteria are inhibited or killed, which is not conducive to the control of oral flora. SUMMARY

[0005] To solve at least some of the technical problems in the prior art, the present application provides an oral care composition for preventing and treating periodontitis. Specifically, the present application includes the following content.

[0006] In a first aspect of the present application, an oral care composition is provided, comprising:

[0007] (a) a compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof:

[0008]

[0009] wherein:

[0010] R1 is H or CH3;

[0011] R2 is H, CH3, or OCH3;

[0012] R1 is OH or OCH3,

[0013] and (b) an oral adjuvant.

[0014] In the present application, preferably, the compound represented by (I) is:

[0015]

[0016] In this invention, preferably, the concentration or amount of component (a) in the oral care composition is controlled so that the oral care composition can produce an effective drug concentration in the oral cavity in the range of 1.35-13 mM after being applied to the oral cavity.

[0017] In a preferred embodiment of the present invention, component (b) includes at least one of abrasive, thickener, surfactant, preservative, humectant, sweetener and flavoring agent.

[0018] In a preferred embodiment of the present invention, the oral care composition includes at least one of toothpaste, teeth whitening gel, subgingival gel, mouthwash, mouth spray, lozenges, chewing tablets, chewing gum, teeth whitening strips, dental floss, and dental floss coating.

[0019] In a preferred embodiment of the present invention, the oral care composition can effectively inhibit Porphyromonas gingivalis without producing a significant killing effect on Lactobacillus reuteri.

[0020] Another aspect of the present invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof, or any of the oral care compositions, in oral care:

[0021]

[0022] in:

[0023] R1 is H or CH3;

[0024] R2 is H, CH3, or OCH3;

[0025] R1 is OH or OCH3.

[0026] In a preferred embodiment of the invention, for the stated use, the compound shown in (I) or a pharmaceutically acceptable salt thereof is effective in inhibiting Porphyromonas gingivalis without showing a significant killing effect on Lactobacillus reuteri.

[0027] In a preferred embodiment of the invention, according to the intended use, the concentration or amount of component (a), i.e., the compound represented by formula (I) or a pharmaceutically acceptable salt thereof, in the oral care composition is controlled such that the oral care composition, after being applied to the oral cavity, can produce an effective drug concentration in the oral cavity in the range of 1.35-13 mM.

[0028] In a preferred embodiment of the present invention, according to the intended use described herein, the oral care includes regulating the oral microenvironment to improve oral diseases or conditions.

[0029] In a preferred embodiment of the present invention, according to the use described in the present invention, the oral disease or condition includes oral ulcers, periodontal soft tissue atrophy and / or loss, alveolar bone resorption and / or decreased bone density.

[0030] In a preferred embodiment of the present invention, according to the intended use described herein, the oral microenvironment includes increasing the proportion of beneficial bacteria in the oral cavity and / or decreasing the proportion of harmful bacteria.

[0031] In a preferred embodiment of the invention, according to the intended use, the care further includes substantially maintaining the total oral flora.

[0032] In a preferred embodiment of the present invention, according to the use described in the present invention, the oral disease or condition includes oral ulcers, periodontal soft tissue atrophy and / or loss, alveolar bone resorption and / or decreased bone density.

[0033] The oral care composition of the present invention contains a specific compound of formula (I) or a pharmaceutically acceptable salt thereof, which can more effectively control harmful bacteria in the oral cavity, while having no substantial effect on beneficial bacteria and the total amount of oral flora, thereby effectively improving the oral microenvironment and flora imbalance, and thus avoiding oral diseases such as gingival or periodontal diseases. Attached Figure Description

[0034] Figure 1 Live / Dead staining of compound 1 of Formula I against Porphyromonas gingivalis.

[0035] Figure 2 Toothpaste containing compound I.

[0036] Figure 3 The in vivo preventive and therapeutic effects of compound 1 toothpaste of Formula I on alveolar bone destruction caused by periodontitis in mice (left figure) and quantitative analysis of bone resorption height by micro-CT (right figure). Detailed Implementation

[0037] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0038] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that the upper and lower limits of the range and each intermediate value between them are specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, are also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0039] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0040] In this document, the term "oral care composition" refers to a product applied to the oral cavity and retained in the oral cavity for a sufficient duration to contact the tooth surface or oral tissues, particularly a product that has beneficial effects on the oral cavity. The product form of oral care compositions is not specific and includes, but is not limited to, toothpaste, teething gel, subgingival gel, mouthwash, mouth spray, lozenges, chewing tablets, chewing gum, teeth whitening strips, dental floss, and dental floss coatings. The physical form of oral care compositions is not limited and includes, but is not limited to, solid, liquid, powder, paste, or combinations thereof.

[0041] In a preferred embodiment of the present invention, the term "compound represented by formula (I)" is used herein to refer to compounds with antibacterial activity, particularly compounds with specific killing activity against oral harmful bacteria, the structure of which is shown below:

[0042]

[0043] in:

[0044] R1 is H or CH3;

[0045] R2 is H, CH3, or OCH3;

[0046] R1 is OH or OCH3.

[0047] In a preferred embodiment of the present invention, the compound represented by formula (I) may be, for example, one of the following compounds:

[0048]

[0049]

[0050]

[0051] The compound represented by formula (I) of this invention can be a natural compound or a synthetic compound. Natural compounds can be obtained, for example, from plants such as *Litsea cubeba*. Specifically, they can be obtained by alcohol extraction, water extraction, or a combination of both.

[0052] The crystallinity of the compound represented by formula (I) of this invention is not limited, and it can be amorphous and / or any crystal form.

[0053] In a preferred embodiment of the present invention, the concentration or amount of the compound represented by formula (I) in the oral care composition is controlled such that the oral care composition produces an effective antibacterial concentration in the oral cavity after application. The specific concentration or amount is not particularly limited, but the effective antibacterial concentration is generally in the range of 1.35-13 mM, preferably in the range of 1.5-12 mM, such as 1.4 mM, 1.5 mM, 1.6 mM, 1.7 mM, 1.8 mM, 1.9 mM, 2 mM, 2.2 mM, 2.5 mM, 3 mM, 3.5 mM, 4 mM, etc. Effective drug concentrations of 4.5mM, 5mM, 5.5mM, 6mM, 6.5mM, 7mM, 7.5mM, 8mM, 8.5mM, 9mM, 9.5mM, 10mM, 10.5mM, 11mM, 11.5mM, 12mM, and 12.5mM can effectively control, inhibit, or reduce the concentration of harmful bacteria, especially Porphyromonas gingivalis, within the above ranges, without substantially affecting beneficial bacteria such as Lactobacillus reuteri or the total amount of oral flora. This achieves selective antibacterial activity and thus regulates the oral flora.

[0054] In a preferred embodiment of the present invention, if the concentration of the compound represented by formula (I) in the oral cavity is too high, it tends to have an adverse effect on beneficial bacteria and / or the overall oral flora, and may even affect health. On the other hand, if the concentration of the compound represented by formula (I) in the oral cavity is too low, it tends to be insufficient to effectively inhibit or reduce harmful bacteria, and thus fails to achieve the purpose of regulating the oral flora as described in this application.

[0055] In this document, the term "oral excipients" includes any material that can be used in the field of oral care. Exemplary examples include, but are not limited to, abrasives, thickeners, surfactants, preservatives, humectants, sweeteners, and flavorings. The oral excipients of the present invention may be one or more combinations of the above.

[0056] In this document, the term "abrasive" refers to fine particles that have polishing and cleaning properties, examples of which include, but are not limited to, calcium-based abrasives and / or non-calcium abrasives. Examples of non-calcium abrasives include bentonite, silica gel, precipitated silica, amorphous precipitated silica, silica hydrate, perlite, titanium dioxide, calcium pyrophosphate, calcium hydrogen phosphate dihydrate, alumina, alumina hydrate, calcined alumina, aluminum silicate, insoluble sodium metaphosphate, insoluble potassium metaphosphate, insoluble magnesium carbonate, zirconium silicate, particulate thermosetting resins, and other suitable abrasive materials. The abrasive is used in amounts of approximately 5% to approximately 70%, approximately 10% to approximately 50%, approximately 10% to approximately 60%, approximately 20% to approximately 50%, approximately 25% to approximately 40%, or approximately 1% to approximately 50% by weight of the oral care composition.

[0057] In this document, the term "thickener" refers to a substance used to provide a gel-like structure to a composition, thereby stabilizing the composition, such as toothpaste, and preventing phase separation. Examples of thickeners include, but are not limited to, polysaccharides, polymers, and / or inorganic thickeners.

[0058] In this document, the term "polysaccharide" suitable for use as a thickener in this invention is not particularly limited, and non-limiting examples include, but are not limited to, starch, starch glycerol, gums, carrageenan, sodium alginate, agar, pectin, gelatin, and cellulose compounds. Examples of gums include, but are not limited to, gum carrageenan (guiding gum), tragacanth gum, gum arabic, solanum, xanthan gum, guar gum, and cellulose gum. Examples of cellulose compounds include, for example, cellulose, microcrystalline cellulose, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxymethyl cellulose, hydroxymethyl carboxypropyl cellulose, methyl cellulose, ethyl cellulose, and sulfated cellulose. This invention may use one or more of the above-mentioned polysaccharides in combination.

[0059] Examples of “polymers” suitable for use as thickeners in this invention include polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), polyacrylic acid, copolymers of maleic anhydride and methyl vinyl ether, and crosslinked polyacrylic acid polymers.

[0060] In this document, "inorganic thickeners" suitable for use as thickeners in this invention include, but are not limited to, silica, magnesium aluminum silicate (colloidal magnesium aluminum silicate), natural and synthetic clays, such as lithium montmorillonite clay, etc.

[0061] In this document, based on the weight of the oral care composition, the amount of thickener is generally from 0.01% to about 15%, from 0.1% to about 10%, from about 0.2% to about 5%, or from about 0.5% to about 2%, and the thickener may be one or more of the above-mentioned thickeners.

[0062] In this article, the term "surfactant" refers to a cleaning material used to impart detergency and foaming properties to oral care compositions. Suitable surfactants include anionic, cationic, nonionic, and amphoteric surfactants.

[0063] In this document, examples suitable for use as anionic surfactants include, for example, water-soluble salts of alkyl sulfates having 8 to 20 carbon atoms in the alkyl group and water-soluble salts of sulfonated monoglycerides of fatty acids having 8 to 20 carbon atoms. Examples of such anionic surfactants include, but are not limited to, sodium lauryl sulfate (SLS) and sodium coconut monoglyceride sulfonate. Other suitable anionic surfactants include sarcosine salts such as sodium lauroyl sarcosinate, taurine, sodium lauryl sulfoacetate, sodium lauroyl hydroxyethyl sulfonate, sodium lauryl polyoxyethylene ether carboxylate, and sodium dodecylbenzene sulfonate. The present invention may use one of the above-described surfactants, or a combination of two or more anionic surfactants.

[0064] In some embodiments, the anionic surfactant of the present invention uses an alkyl phosphate, thereby having a strong affinity for the enamel surface and a sufficient tendency to bind to the surface to desorb the membrane proteins and retain them attached to the enamel surface.

[0065] In some embodiments, the anionic surfactant of the present invention is a sarcosine salt, hydroxyethyl sulfonate, or taurine salt, such as an alkali metal salt or an ammonium salt. Examples of such surfactants include lauroyl sarcosine, myristoyl sarcosine, palmitoyl sarcosine, stearoyl sarcosine, oleoyl sarcosine, or combinations thereof.

[0066] In this document, suitable cationic surfactants for use in the present invention include, for example, quaternary ammonium compound derivatives comprising long alkyl chains containing 8 to 18 carbon atoms, such as lauryltrimethylammonium chloride; cetylpyridinium chloride; hexadecyltrimethylammonium bromide; hexadecylpyridinium fluoride, or combinations thereof.

[0067] In this document, suitable nonionic surfactants for use in this invention include, for example, compounds formed by the condensation of an epoxy alkyl group with an organic hydrophobic compound that may itself be aliphatic or alkyl aromatic. Examples of suitable nonionic surfactants may include poloxamer, polyethylene oxide condensates of alkylphenols, products derived from the condensation of ethylene oxide with the reaction products of propylene oxide and ethylenediamine, polyethylene oxide condensates of fatty alcohols, long-chain tertiary amine oxides, long-chain tertiary phosphine oxides, long-chain dialkyl sulfoxides, and combinations thereof. Other suitable nonionic surfactants include alkyl glucosamides, alkyl glucosides, and / or combinations thereof.

[0068] In this document, suitable amphoteric surfactants for use in this invention include derivatives of aliphatic quaternary ammonium, phosphonium, and sulfonium compounds, wherein the aliphatic group may be linear or branched, and one of the aliphatic substituents contains 8 to 18 carbon atoms, and one of the aliphatic substituents contains an anionic water-solubilizing group, such as a carboxyl, sulfonate, sulfate, phosphate, or phosphonate group. Typical alkyl dimethyl betaines include decyl betaine or 2-(N-decyl-N,N-dimethylamine) acetate, cocoyl betaine or 2-(N-cocoyl-N,N-dimethylamine) acetate, tetradecyl betaine, palmityl betaine, lauryl betaine, hexadecyl betaine, hexadecyl betaine, stearyl betaine, etc. Amide betaines can be exemplified by cocamidoethyl betaine, cocamidopropyl betaine (CADB), and lauramide propyl betaine. Other suitable amphoteric surfactants include betaine, sulfobetaine, sodium lauryl amphoteric acetate, alkyl amphoteric diacetate and / or combinations thereof.

[0069] In some embodiments, the surfactants of the present invention may further include one or more natural and / or naturally derived surfactants. Natural surfactants may include surfactants derived from natural products and / or minimally processed or unprocessed surfactants. Natural surfactants may include: hydrogenated, non-hydrogenated, or partially hydrogenated vegetable oils, plant oils, passion fruit oil, candelilla wax, cocoyl caprylate, caprylate, dioctyl ether, lauryl alcohol, tetradecyl myristate, dioctyl ether, caprylic acid, octyl ester, octyl caprylate, octyl caprylate, undecane, tridecane, decyl oleate, decyl oleate, hexadecyl palmitate, stearic acid, palmitic acid, glyceryl stearate, hydrogenated, non-hydrogenated, or partially hydrogenated vegetable glycerides, polyglycerol-2-dipolyhydroxystearate, hexadecyl / octadecanol, sucrose polystearate, glycerol, octadecyl alcohol, hydrolyzed, partially water-soluble... Hydrolyzed or unhydrolyzed plant proteins, hydrolyzed, partially hydrolyzed or unhydrolyzed wheat protein hydrolysates, polyglycerol-3 diisostearate, glyceryl oleate, myristol, hexadecyl alcohol, sodium hexadecylstearyl sulfate, hexadecylstearyl alcohol, glyceryl laurate, triglyceride caprylate, cocoglycerol, lecithin, dioctyl ether, xanthan gum, sodium cocosulfate, ammonium dodecyl sulfate, sodium cocosulfate, sodium cocoglutamate, polyalkyl glucosides such as decyl glucoside, hexadecylstearyl glucoside, hexadecylstearyl polyglucoside, cocoglycoside and lauryl glucoside and / or combinations thereof.

[0070] In this article, the amount of surfactant used is generally from about 0.01% to about 15%, from about 0.3% to about 10%, or from about 0.3% to about 2.5% based on the total weight of the oral care composition.

[0071] In this article, the term "preservative" refers to a substance added to an oral care composition to prevent it from becoming moldy or bacterially grown, examples of which include, but are not limited to, methylparaben, propylparaben, benzoic acid, and sodium benzoate.

[0072] In this document, the term "humectant" refers to a substance used to increase the consistency or mouthfeel of an oral care composition and to prevent it from drying out. Suitable examples of humectants include, but are not limited to, polyethylene glycol, propylene glycol, glycerin, erythritol, xylitol, sorbitol, mannitol, butylene glycol, lactitol, hydrogenated starch hydrolysate, and / or mixtures thereof. Based on the total weight of the oral care composition, the amount of humectant used is generally from 0% to about 70%, from about 5% to about 50%, from about 10% to about 60%, or from about 20% to about 50%.

[0073] In this article, the term "sweetener" refers to a substance added to an oral care composition to impart a pleasant taste. Suitable sweeteners include saccharin (such as sodium saccharin, potassium saccharin, or calcium saccharin), cyclosulfonates (such as sodium, potassium, or calcium salts), acesulfame K, arbutin, neohesperidin dihydrochalcone, aminoglycoside, dextrose, levulose, sucrose, mannose, sucralose, stevia, and glucose.

[0074] In this document, the term "fragrant agent" is a substance added to an oral care composition to improve or alter its taste or produce a pleasant sensation, examples of which include peppermint, spearmint, and wintergreen. Exemplarily, an oral care composition includes peppermint oil, which is primarily composed of menthol, menthone, and menthyl acetate. In this document, the amount of fragrant agent used is generally from about 0.001% to about 2% based on the total weight of the oral composition, alternatively from 0.01% to about 1.75%, alternatively from 0.1% to about 1.5%, and alternatively from 0.5% to about 1.25%.

[0075] In a preferred embodiment, the oral care composition of the present invention does not contain any antibacterial or inhibitory components other than the compound of formula (I) or its pharmaceutically acceptable salts, crystalline forms, prodrugs, or derivatives thereof.

[0076] In this document, the oral care composition optionally includes a buffer. The buffer may be a weak acid or a weak base that can maintain a specific pH at selected sites in the oral cavity. For example, a buffer can maintain the pH of the tooth surface to mitigate the effects of plaque acid produced by bacteria. Suitable buffering systems may include phosphates, citrates, carbonates / bicarbonates, tris(hydroxymethyl)aminomethane buffers, imidazoles, ureas, borates, and / or combinations thereof. Suitable buffers include bicarbonates, such as sodium bicarbonate, glycine, orthophosphates, arginine, urea, and / or combinations thereof. Based on the total weight of the oral care composition, the amount of buffer is generally from about 1% to about 30%, from about 5% to about 25%, or from about 10% to about 20%.

[0077] In this document, the oral care composition may optionally further comprise beneficial ions, examples of which include fluoride ions and calcium ions. Such beneficial ions can be provided by compounds containing the corresponding ions. Exemplary fluoride-containing soluble compounds include, but are not limited to, stannous fluoride, sodium fluoride, titanium fluoride, calcium fluoride, calcium phosphate silicate fluoride, potassium fluoride, amine fluoride, sodium monofluorophosphate, zinc fluoride, and / or mixtures thereof. In the oral care composition, the concentration of fluoride ions is generally from about 50 ppm to about 5000 ppm, preferably from about 500 ppm to about 3000 ppm. Therefore, the amount of the fluoride-containing compound in the oral care composition is based on the total weight of the oral care composition as about 0.0025% to about 5%, about 0.01% to about 10%, about 0.2% to about 1%, about 0.5% to about 1.5%, or about 0.3% to about 0.6%.

[0078] In some embodiments, the oral care composition of the present invention optionally comprises Ca ions. The desired Ca ions can be provided by a Ca-containing compound. Examples of Ca-containing compounds include, but are not limited to, calcium chloride, calcium nitrate, calcium phosphate, calcium lactate, calcium oxalate, calcium oxide, calcium gluconate, calcium citrate, calcium bromide, calcium iodate, calcium iodide, hydroxyapatite, fluorapatite, calcium sulfate, calcium glycerophosphate, and / or combinations thereof. The amount of the calcium-containing compound in the oral care composition is based on the total weight of the oral care composition as about 5% to about 70%, about 10% to about 50%, about 10% to about 60%, about 20% to about 50%, about 25% to about 40%, or about 1% to about 50%.

[0079] In this document, the term "care" refers to taking certain measures to improve the oral microenvironment, thereby making it more beneficial to human health. Care in this document specifically refers to improving the oral microenvironment through oral compositions. This improvement includes increasing the proportion of beneficial bacteria in the oral cavity and / or decreasing the proportion of harmful bacteria. Preferably, it also substantially maintains the total oral microbiota. The term "substantially" means that there is no substantial adverse effect on the total oral microbiota or beneficial bacteria. For example, there is no adverse effect on the total oral microbiota or beneficial bacteria, or the inhibition or killing is less than 20%, preferably less than 15%, more preferably less than 10%, such as less than 9%, less than 8%, less than 7%, less than 6%, less than 5%, less than 4%, less than 3%, less than 2%, less than 1%, or less than 1%. The care of this invention also includes improving diseases or conditions caused by microbiota imbalance, including periodontal-related diseases or conditions, such as periodontal soft tissue atrophy and / or loss, alveolar bone resorption and / or decreased bone density.

[0080] In this article, the term "microbial microenvironment," also known as "microecological microbiota," refers to the community ecology of microorganisms, especially bacteria, in the oral cavity. It is an ecosystem necessary for a normal oral cavity, and these bacteria form a unified entity with the human oral environment, mutually dependent, mutually restrictive, and mutually influential. The microbial microenvironment typically includes harmful bacteria, beneficial bacteria or probiotics, and neutral bacteria.

[0081] In this article, the term "harmful bacteria" refers to a class of bacteria that are harmful to oral health or can produce substances harmful to the oral cavity. Once the number of such bacteria grows out of control, it can cause a variety of oral diseases, including bad breath, oral ulcers, and gingival or periodontal diseases.

[0082] In this article, the term "probiotics," also known as "beneficial bacteria," refers to a class of bacteria essential for oral health, which can synthesize various vitamins and other beneficial components. Examples of beneficial bacteria include, but are not limited to, Bifidobacteria, lactobacilli such as Lactobacillus reuteri, and other lactic acid bacteria.

[0083] In this article, the term "neutral bacteria" refers to a type of bacteria in the oral cavity that has a dual function: they are beneficial to health under normal circumstances, but can cause many diseases if they proliferate uncontrollably or migrate from the intestines to other parts of the body.

[0084] Example

[0085] Example 1: In vitro antibacterial experiment of compound 1 of formula I.

[0086] Compound 1 of Formula I was co-cultured for 24 hours with *Porphyromonas gingivalis*, a harmful bacterium that causes periodontitis, *Lactobacillus reuteri*, a probiotic in the oral cavity, and the oral flora of healthy clinical subjects. As a comparison, the inhibitory effect of compound II on *Porphyromonas gingivalis* was investigated. The inhibitory effects of the compounds on various bacteria were assessed by quantifying the results using an ELISA reader and by crystal violet staining of plaque biofilms.

[0087]

[0088] The results showed that compound 1 of formula I significantly inhibited the growth of Porphyromonas gingivalis, with a minimum inhibitory concentration of 1.35 mM. In contrast, the minimum inhibitory concentration of compound II of formula II inhibited the growth of Porphyromonas gingivalis by 6.75 mM.

[0089] Furthermore, compound 1 of Formula I showed no significant bactericidal effect against either *Lactobacillus reuteri* or the oral bacterial population of healthy clinical subjects, even at a concentration of 10 mM. The minimum inhibitory concentration (MIC) of compound 1 of Formula I against *Lactobacillus reuteri* is 13.5 mM.

[0090] The ratio of live (green fluorescence) to dead (red fluorescence) Porphyromonas gingivalis after intervention with compound 1 of formula I was marked by Live / Dead staining. Figure 1 As shown, compound 1 of formula I exhibits excellent in vitro killing effect against Porphyromonas gingivalis.

[0091] Example 2: Toothpaste containing compound 1 of formula I and in vivo mouse test.

[0092] A toothpaste composition containing compound 1 of formula I was prepared, comprising 0.2% by weight of compound 1 of formula I. When applied to the oral cavity, the toothpaste composition produces an effective concentration of approximately 10 mM of compound 1 of formula I. Other components of the toothpaste composition are: 25% glycerin; 24% silica; 5% sodium N-lauroyl sarcosinate; 2% carboxymethyl cellulose; 2% xanthan gum; and the remainder is ultrapure water. The various raw materials were mixed according to the formulation proportions, and a homogenizer was used to ensure uniform distribution of the components and a fine texture. The mixed toothpaste composition is as follows: Figure 2 As shown.

[0093] The maxillary second molars of 6-week-old male C57BL / 6J mice were ligated with 5-0 nylon sutures. Following this, *Porphyromonas gingivalis* smears were applied to the oral cavity of the mice every other day for 4 weeks. Micro-CT scans revealed significant alveolar bone resorption and root bifurcation exposure in the maxillary second molars, confirming the successful establishment of the mouse periodontal disease model.

[0094] Four healthy control mice (Control), four mice with successfully modeled periodontitis, and four mice with successfully modeled periodontitis treated with compound 1 toothpaste (LA) were selected. The periodontitis treated with compound 1 toothpaste was then administered to the mice. Figure 2 The mice were treated with the brushes and the prepared toothpaste once daily. After 4 weeks, these mice underwent micro-CT scans, and the results were as follows... Figure 3 The results showed that the alveolar bone resorption height in the healthy mouse group was 84.26±10.91 mm, while that in the periodontitis-affected mouse group was 609.83±110.46 mm. The alveolar bone resorption height in the periodontitis mouse group treated with compound 1 toothpaste was 214.26±61.00 mm. This indicates that toothpaste containing compound 1 can significantly inhibit alveolar bone resorption caused by periodontal disease.

[0095] Although the invention has been described with reference to exemplary embodiments, it should be understood that the invention is not limited to the disclosed exemplary embodiments. Various adjustments or changes may be made to the exemplary embodiments described in this specification without departing from the scope or spirit of the invention. The scope of the claims should be interpreted in the broadest possible sense to cover all modifications and equivalent structures and functions.

Claims

1. An oral care composition characterized in that, Compositions comprising: (a) a compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof: wherein: R1 is H or CH3; R2 is H, CH3 or OCH3; R3 is OH or OCH3, and (b) an oral vehicle.

2. The oral care composition of claim 1, wherein, The compound represented by the formula (I) is:

3. The oral care composition of claim 1, wherein, The concentration or amount of the component (a) in the oral care composition is controlled so that the oral care composition is capable of producing a pharmaceutically effective concentration in the range of 1.35-13 mM in the oral cavity after the oral care composition is applied to the oral cavity.

4. The oral care composition of claim 1, wherein, The component (b) comprises at least one of an abrasive, a thickening agent, a surfactant, a preservative, a humectant, a sweetener and a flavoring agent.

5. The oral care composition of claim 1, wherein, The oral care composition comprises at least one of a toothpaste, a tooth gel, a subgingival gel, a mouthwash, a mouth spray, a lozenge, a chewable tablet, a chewing gum, a tooth whitening strip, a dental floss and a dental floss coating.

6. The oral care composition of claim 1, wherein, It is effective in inhibiting P. gingivalis without showing significant killing effect on Lactobacillus reuteri.

7. Use of a compound of formula (I) or a pharmaceutically acceptable salt thereof, or an oral care composition according to any one of claims 1 to 5, in the manufacture of an oral care product, characterised in that, The compound has the following structure: wherein: R1 is H or CH3; R2 is H, CH3 or OCH3; R1 is OH or OCH3.

8. Use according to claim 7, characterized in that, The compound represented by the formula (I) or a pharmaceutically acceptable salt thereof is effective in inhibiting P. gingivalis without showing significant killing effect on Lactobacillus reuteri.

9. Use according to claim 7, characterized in that, The concentration or amount of the compound represented by the formula (I) or a pharmaceutically acceptable salt thereof in the oral care composition is controlled so that the oral care composition is capable of producing a pharmaceutically effective concentration in the range of 1.35-13 mM in the oral cavity after the oral care composition is applied to the oral cavity.

10. Use according to claim 7, characterized in that, The oral care product is used in at least one of the following situations: modulating the microenvironment of the oral flora, thereby improving an oral disease or condition, preferably, the oral disease or condition comprises oral ulcer, periodontal soft tissue atrophy and / or loss, alveolar bone resorption and / or bone density reduction.

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