Oral care compositions and uses

Abstract

The present invention discloses an oral care composition and use thereof, the oral care composition comprises a compound represented by formula (I) and oral excipients, by controlling the concentration or dosage of a component (a) in the oral care composition, the oral care composition can generate a drug effective concentration in the range of 1.35-13mM in the oral cavity after being applied to the oral cavity, 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

Technical Field

[0001] The present invention relates to the field of oral care, and in particular to an oral care composition and use thereof which can improve the microenvironment of oral flora and thus improve periodontal-related diseases or conditions. Background Art

[0002] Different bacteria in the mouth work together to maintain and build a healthy oral environment. When bad eating habits, excessive use of drugs, and other reasons cause the oral flora to be dysregulated or unbalanced, problems such as bad breath and oral ulcers are likely to occur, and may even further lead to gum or periodontal diseases. Therefore, a balanced oral flora is essential for a good oral condition.

[0003] An important feature of oral flora imbalance is the rapid proliferation of harmful bacteria such as Porphyromonas gingivalis. Currently, inhibitory drugs have no biased inhibition of oral flora. Some drugs can control the number of bacteria in the mouth to a certain extent, but the effect is general. At the same time, beneficial bacteria are inhibited or killed, which is not conducive to the control of oral flora. Summary of the invention

[0004] In order to solve at least part of the technical problems in the prior art, the present invention provides an oral care composition and use thereof. Specifically, the present invention includes the following contents.

[0005] The first aspect of the present invention provides an oral care composition comprising:

[0006] (a) a compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof:

[0007]

[0008] in:

[0009] R1 is H or CH3;

[0010] R2 is H, CH3 or OCH3;

[0011] R3 is OH or OCH3,

[0012] and (b) oral excipients.

[0013] In the present invention, preferably, the compound represented by (I) is:

[0014]

[0015] In the present invention, preferably, the concentration or amount of component (a) in the oral care composition is controlled so that the oral care composition can produce a drug effective concentration in the range of 1.35-13 mM in the oral cavity after being applied to the oral cavity.

[0016] In a preferred embodiment of the present invention, component (b) comprises at least one of abrasives, thickeners, surfactants, preservatives, wetting agents, sweeteners and flavoring agents.

[0017] In a preferred embodiment of the present invention, the oral care composition comprises at least one of toothpaste, tooth gel, subgingival gel, mouthwash, mouth spray, lozenge, chewable tablet, chewing gum, tooth whitening strips, dental floss and dental floss coating.

[0018] In a preferred embodiment of the present invention, the oral care composition can effectively inhibit Porphyromonas gingivalis, but has no obvious killing effect on Lactobacillus reuteri.

[0019] Another aspect of the present invention provides a compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof, or use of any one of the oral care compositions in oral care:

[0020]

[0021] in:

[0022] R1 is H or CH3;

[0023] R2 is H, CH3 or OCH3;

[0024] R3 is OH or OCH3.

[0025] In a preferred embodiment of the present invention, for the use, the compound shown in (I) or a pharmaceutically acceptable salt thereof can effectively inhibit Porphyromonas gingivalis, but does not show obvious killing effect on Lactobacillus reuteri.

[0026] In a preferred embodiment of the present invention, according to the use of the present invention, 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 so that after the oral care composition is applied to the oral cavity, it can produce a drug effective concentration in the range of 1.35-13 mM in the oral cavity.

[0027] In a preferred embodiment of the present invention, according to the use of the present invention, wherein the oral care includes regulating the oral flora microenvironment, thereby improving oral diseases or conditions.

[0028] In a preferred embodiment of the present invention, according to the use of 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.

[0029] In a preferred embodiment of the present invention, according to the use of the present invention, wherein the oral flora microenvironment includes increasing the proportion of beneficial bacteria in the oral cavity, and / or reducing the proportion of harmful bacteria.

[0030] In a preferred embodiment of the present invention, according to the use of the present invention, the care further includes substantially maintaining the total amount of oral flora.

[0031] In a preferred embodiment of the present invention, according to the use of 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.

[0032] The oral care composition of the present invention contains a specific compound represented by 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 flora microenvironment and flora imbalance, thereby avoiding oral diseases such as gum or periodontal diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 Live / Dead staining of the killing of Porphyromonas gingivalis by Compound 1 of Formula I.

[0034] Figure 2 A toothpaste containing compound 1 of formula I.

[0035] Figure 3 The preventive and therapeutic effect of compound 1 toothpaste of formula I on alveolar bone destruction caused by periodontitis in mice in vivo (left figure) and micro-CT bone absorption height quantitative analysis (right figure). DETAILED DESCRIPTION

[0036] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0037] It should be understood that the terms described in the present invention are only for describing special embodiments and are not intended to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that the upper and lower limits of the scope and each intermediate value therebetween are specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the described range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0038] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as commonly understood by those skilled in the art to which the invention belongs. Although the present invention describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials related to the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0039] Herein, the term "oral care composition" refers to a product that is applied to the oral cavity and retained in the oral cavity for a sufficient period of time to contact the tooth surface or oral tissue, particularly a product that has a beneficial effect on the oral cavity. The product form of the oral care composition is not specific, including but not limited to toothpaste, tooth gel, subgingival gel, mouthwash, mouth spray, lozenge, chewable tablet, chewing gum, tooth whitening strips, dental floss and dental floss coating. The form of the oral care composition is not limited, including but not limited to solid, liquid, powder, paste or a combination thereof.

[0040] In a preferred embodiment of the present invention, the term "compound represented by formula (I)" herein has antibacterial activity, in particular, a compound having specific killing activity against harmful oral bacteria, and its structure is shown below:

[0041]

[0042] in:

[0043] R1 is H or CH3;

[0044] R2 is H, CH3 or OCH3;

[0045] R3 is OH or OCH3.

[0046] In a preferred embodiment of the present invention, the compound represented by formula (I) of the present invention may be, for example, one of the following compounds:

[0047]

[0048]

[0049]

[0050] The compound represented by formula (I) of the present invention can be a natural compound or an artificially synthesized compound. The natural compound can be obtained by, for example, extracting from plants such as Litsea cubeba. Specifically, it can be obtained by alcohol extraction, water extraction or a combination of the two.

[0051] The crystallinity of the compound represented by formula (I) of the present invention is not limited and may be amorphous and / or any crystalline form.

[0052] In a preferred embodiment of the present invention, herein, the concentration or amount of the compound represented by formula (I) in the oral care composition is controlled so that after the oral care composition is applied to the oral cavity, it can produce an effective antibacterial concentration in the oral cavity. The specific concentration or amount is not particularly limited. The effective antibacterial concentration is generally in the range of 1.35-13mM, preferably in the range of 1.5-12mM, such as 1.4mM, 1.5mM, 1.6mM, 1.7mM, 1.8mM, 1.9mM, 2mM, 2.2mM, 2.5mM, 3mM, 3.5mM, 4mM, Effective drug concentrations such as 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 range, but have no substantial effect on beneficial bacteria such as Lactobacillus reuteri and the total amount of oral flora, thereby achieving selective antibacterial effect and further achieving the purpose of regulating the oral flora.

[0053] 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 the beneficial bacteria and / or the oral flora as a whole, and even affects 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 unable to effectively inhibit or reduce harmful bacteria due to the small amount, and the purpose of regulating the oral flora of the present application cannot be achieved.

[0054] Herein, the term "oral adjuvant" includes any material that can be used in the field of oral care. Illustrative examples include, but are not limited to, abrasives, thickeners, surfactants, preservatives, wetting agents, sweeteners, aromatics, etc. The oral adjuvant of the present invention can be a combination of one or more of the above.

[0055] Herein, the term "abrasive" refers to fine particles with polishing and cleaning effects, examples of which include, but are not limited to, calcium 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, aluminum oxide, aluminum oxide hydrate, calcined aluminum oxide, aluminum silicate, insoluble sodium metaphosphate, insoluble potassium metaphosphate, insoluble magnesium carbonate, zirconium silicate, particulate thermosetting resins and other suitable abrasive materials. Based on the total weight of the oral care composition, the amount of abrasive is 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%.

[0056] As used herein, the term "thickener" refers to a substance used to provide a gel-like structure to a composition to stabilize the composition, such as toothpaste, from phase separation. Examples of thickeners include, but are not limited to, polysaccharides, polymers and / or inorganic thickeners.

[0057] Herein, "polysaccharide" suitable for use as thickener of the present invention is not particularly limited, and its non-limiting examples include but are not limited to starch, starch glycerol, gum, carrageenan, sodium alginate, agar, pectin, gelatin, cellulose compounds. Examples of gums include but are not limited to, for example, karaya gum (gum karaya), tragacanth gum, gum arabic, gum ghatti, gum arabic, 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. The present invention can use one or a combination of the above-mentioned polysaccharides.

[0058] Herein, examples of "polymers" suitable for use as the thickening agent of the present invention include polyethylene glycol (PEG), polyvinyl pyrrolidone (PVP), polyacrylic acid, copolymers of maleic anhydride and methyl vinyl ether, and cross-linked polyacrylic acid polymers.

[0059] Herein, examples of "inorganic thickeners" suitable for use as thickeners in the present invention include, but are not limited to, silicon dioxide, magnesium aluminum silicate (colloidal magnesium aluminum silicate), natural and synthetic clays such as hectorite clay, and the like.

[0060] Herein, based on the weight of the oral care composition, the thickener is generally used in an amount of 0.01% to about 15%, 0.1% to about 10%, about 0.2% to about 5% or about 0.5% to about 2%, and the thickener can be one or more of the above-mentioned thickeners.

[0061] As used herein, the term "surfactant" refers to a detersive material used to impart detergency and foaming properties to an oral care composition. Suitable surfactants include anionic, cationic, nonionic, zwitterionic surfactants, and the like.

[0062] Herein, 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 sarcosinates such as sodium lauroyl sarcosinate, taurates, sodium lauryl sulfoacetate, sodium lauroyl isethionate, sodium lauryl polyoxyethylene ether carboxylate, and sodium dodecylbenzene sulfonate. The present invention can use one of the above-mentioned surfactants, or can use two or more anionic surfactants in combination.

[0063] In certain embodiments, the anionic surfactants of the present invention utilize alkyl phosphates, thereby having a strong affinity for the enamel surface and sufficient surface binding propensity to desorb surface membrane proteins and remain attached to the enamel surface.

[0064] In certain embodiments, the anionic surfactants of the present invention are sarcosinates, isethionates and taurates, such as alkali metal salts or ammonium salts. Examples of such surfactants include lauroyl sarcosinates, myristoyl sarcosinates, palmitoyl sarcosinates, stearoyl sarcosinates, oleoyl sarcosinates, or combinations thereof.

[0065] Herein, suitable cationic surfactants for use as the present invention include, for example, quaternary ammonium compound derivatives containing long alkyl chains of 8 to 18 carbon atoms, such as lauryltrimethylammonium chloride; cetylpyridinium chloride; hexadecyltrimethylammonium bromide; hexadecylpyridinium fluoride, or combinations thereof.

[0066] Herein, suitable nonionic surfactants for use as the present invention include, for example, compounds generated by the condensation of an alkylene oxide group with an organic hydrophobic compound which itself may be aliphatic or alkyl aromatic. Examples of suitable nonionic surfactants may include poloxamers, polyethylene oxide condensates of alkylphenols, products derived from the condensation of ethylene oxide with the reaction product of propylene oxide and ethylenediamine, ethylene oxide condensates of fatty alcohols, long chain tertiary amine oxides, long chain tertiary phosphine oxides, long chain dialkyl sulfoxides, and combinations of these substances. Other suitable nonionic surfactants include alkyl glucamides, alkyl glucosides, and / or combinations thereof.

[0067] Herein, suitable for use as amphoteric surfactants of the present 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, for example, carboxyl, sulfonate, sulfate, phosphate or phosphonate. 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. Amido betaine can be exemplified by cocoamidoethyl betaine, cocoamidopropyl betaine (CADB) and lauroamidopropyl betaine. Other suitable amphoteric surfactants include betaines, sultaines, sodium lauryl amphoacetate, alkyl amphodiacetates and / or combinations thereof.

[0068] In certain embodiments, the surfactant of the present invention may also 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, vegetable oils, passionflower oil, candelilla wax, coconut oil base caprylate, caprate, dioctyl ether, lauryl alcohol, myristate tetradecyl ester, dioctyl ether, caprylic acid, caprylate, caprylate, caprylate, undecane, tridecane, decyl oleate, decyl oleate, palmitic acid hexadecyl ester, stearic acid, palmitic acid, stearyl glyceride, hydrogenated, non-hydrogenated or partially hydrogenated vegetable glycerides, polyglyceryl-2 dipolyhydroxystearate, sixteen / octadecanol, sucrose polystearate, glycerol, stearyl alcohol, hydrolyzed, partially water Hydrolyzed or unhydrolyzed vegetable protein, hydrolyzed, partially hydrolyzed or unhydrolyzed wheat protein hydrolysate, polyglyceryl-3 diisostearate, glyceryl oleate, myristyl alcohol, cetyl alcohol, sodium cetearyl sulfate, cetearyl alcohol, glyceryl laurate, capric triglyceride, cocoyl glycerides, lecithin, dicaprylyl ether, xanthan gum, sodium coco sulfate, ammonium lauryl sulfate, sodium cocoyl sulfate, sodium cocoyl glutamate, polyalkyl glucosides such as decyl glucoside, cetearyl glucoside, cetearyl polyglucoside, cocoyl glucoside and lauryl glucoside and / or combinations thereof.

[0069] Herein, the surfactant is generally used in an amount of about 0.01% to about 15%, about 0.3% to about 10%, or about 0.3% to about 2.5%, based on the total weight of the oral care composition.

[0070] As used herein, the term "preservative" refers to a substance added to an oral care composition to prevent mold or bacterial growth, examples of which include, but are not limited to, methylparaben, propylparaben, benzoic acid, and sodium benzoate.

[0071] As used herein, 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, glycerol, erythritol, xylitol, sorbitol, mannitol, butylene glycol, lactitol, hydrogenated starch hydrolysate, and / or mixtures thereof. Based on the gross weight of the oral care composition, the humectant is generally used in an amount of 0% to about 70%, about 5% to about 50%, about 10% to about 60%, or about 20% to about 50%.

[0072] Herein, the term "sweetener" refers to a substance added to an oral care composition to impart a pleasant taste thereto. Suitable sweeteners include saccharin (e.g., sodium saccharin, potassium saccharin, or calcium saccharin), cyclamate (e.g., sodium, potassium, or calcium salts), acesulfame-K, afritoin, neohesperidin dihydrochalcone, aminated glycyrrhizin, dextrose, levulose, sucrose, mannose, sucralose, stevioside, and glucose.

[0073] Herein, the term "aromatic agent" is a substance added to an oral care composition to improve or change its taste or produce a pleasant feeling, examples of which include peppermint, spearmint, and wintergreen. Exemplarily, the oral care composition includes peppermint oil, which is mainly composed of menthol, menthone, and menthyl acetate. Herein, based on the total weight of the oral composition, the amount of the aromatic agent is generally about 0.001% to about 2%, alternatively 0.01% to about 1.75%, alternatively 0.1% to about 1.5%, and alternatively 0.5% to about 1.25%.

[0074] In a preferred embodiment, the oral care composition of the present invention does not include any antibacterial or inhibitory ingredients other than the compound represented by formula (I) or its pharmaceutically acceptable salt, crystalline form, prodrug, derivative.

[0075] Herein, the oral care composition optionally comprises a buffer. The buffer can be a weak acid or a weak base, and it can maintain a specific pH at a selected position in the oral cavity. For example, the buffer can maintain the pH of the tooth surface to alleviate the influence of plaque acid produced by bacteria. Suitable buffer systems can include phosphates, citrates, carbonates / bicarbonates, tris buffer, imidazoles, urea, borates and / or combinations thereof. Suitable buffers include bicarbonates, such as sodium bicarbonate, glycine, orthophosphate, arginine, urea and / or combinations thereof. Based on the gross weight of the oral care composition, the amount of the buffer is generally from about 1% to about 30%, from about 5% to about 25% or from about 10% to about 20%.

[0076] Herein, the oral care composition optionally further comprises beneficial ions, examples of which include fluoride ions and calcium ions. Such beneficial ions can be provided by compounds containing corresponding ions. Exemplary soluble compounds containing fluoride ions 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 50ppm to about 5000ppm, preferably from about 500ppm to about 3000ppm. For this reason, the amount of the compound containing fluoride ions in the oral care composition is from about 0.0025% to about 5%, from about 0.01% to about 10%, from about 0.2% to about 1%, from about 0.5% to about 1.5%, or from about 0.3% to about 0.6% based on the total weight of the oral care composition.

[0077] In certain embodiments, oral care compositions of the present invention optionally include calcium ions. Required calcium ions can be provided by compounds containing calcium ions. Examples of compounds containing calcium ions 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 compound containing calcium ions in the oral care compositions is 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% based on the oral care compositions gross weight.

[0078] Herein, the term "care" refers to taking certain measures to improve the oral microenvironment of the oral flora, so as to be more conducive to human health. Care herein refers in particular to improving the oral microenvironment of the oral flora by means of an oral composition. The improvement includes increasing the proportion of beneficial bacteria in the oral cavity, and / or reducing the proportion of harmful bacteria. Preferably, the total amount of oral flora is substantially maintained at the same time. The term "substantially" means that there is no substantial adverse effect on the total amount of oral flora or beneficial bacteria. For example, there is no adverse effect such as inhibition or killing on the total amount of oral flora or beneficial bacteria, or the inhibition and killing thereof are 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%. The care of the present invention also includes improving diseases or conditions caused by an imbalance of flora, including periodontal-related diseases or conditions, such as atrophy and / or loss of periodontal soft tissue, alveolar bone resorption and / or decreased bone density.

[0079] Herein, the term "microflora microenvironment" is also referred to as "microecological flora", which refers to the microorganisms in the oral cavity, especially the bacterial colony ecology, which is the ecosystem required for a normal oral cavity. These bacteria and the oral environment of the human body form a unity of mutual dependence, mutual restriction and influence. The microflora microenvironment usually includes harmful bacteria, beneficial bacteria or probiotics, and neutral bacteria.

[0080] In this article, the term "harmful bacteria" refers to a type of bacteria that are harmful to oral health or can produce substances that are harmful to the oral cavity. Once the number of such bacteria grows out of control, it will cause a variety of diseases in the oral cavity, including bad breath, oral ulcers, gum or periodontal diseases, etc.

[0081] Herein, the term "probiotics" also referred to as "beneficial bacteria" refers to a class of bacteria that are essential for oral health and can synthesize various vitamins and other beneficial ingredients. Examples of beneficial bacteria include, but are not limited to, bifidobacteria, lactobacilli such as Lactobacillus reuteri, lactic acid bacteria, and the like.

[0082] In this article, the term "neutral bacteria" refers to a type of bacteria in the mouth that has a dual role. Under normal circumstances, it is beneficial to health, but once it proliferates out of control or moves from the intestine to other parts of the body, it may cause many diseases.

[0083] Example

[0084] Example 1: In vitro antibacterial experiment of compound 1 of formula I.

[0085] Compound 1 of formula I was co-cultured with Porphyromonas gingivalis, a harmful bacterium that can cause periodontitis, Lactobacillus reuteri, a probiotic for the oral cavity, and the oral flora of clinically healthy subjects for 24 hours, and the inhibitory effect of the compound of formula II on Porphyromonas gingivalis, a harmful bacterium that can cause periodontitis, was investigated as a comparison. The inhibitory effect of the compound on various bacteria was evaluated by ELISA reading quantification and plaque biofilm crystal violet staining.

[0086]

[0087] 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 the compound of formula II for inhibiting the growth of Porphyromonas gingivalis was 6.75 mM.

[0088] In addition, compound 1 of formula I had no significant killing effect on Lactobacillus reuteri and oral bacterial populations of clinically healthy subjects, and did not show significant killing effect even when the concentration of compound 1 of formula I reached 10 mM. The minimum inhibitory concentration of compound 1 of formula I on Lactobacillus reuteri was 13.5 mM.

[0089] The ratio of live bacteria (green fluorescence) to dead bacteria (red fluorescence) of Porphyromonas gingivalis after the intervention of compound 1 of formula I was marked by Live / Dead staining, as shown in FIG. Figure 1 As shown, compound 1 of formula I exhibits a good killing effect on Porphyromonas gingivalis in vitro.

[0090] Example 2: Toothpaste containing compound 1 of formula I and in vivo test in mice.

[0091] A toothpaste composition containing compound 1 of formula I is prepared, which contains 0.2% by mass of compound 1 of formula I. After the toothpaste composition is applied to the oral cavity, compound 1 of formula I can produce an effective concentration of about 10mM in the oral cavity. The other components of the toothpaste composition are: 25% glycerol; 24% silicon dioxide; 5% sodium N-lauroyl sarcosinate; 2% carboxymethyl cellulose; 2% xanthan gum, and the remaining components are ultrapure water. Various raw materials are mixed according to the formula ratio, and a homogenizer is used to mix to ensure uniform distribution of the ingredients and fine texture. The mixed toothpaste composition is as follows Figure 2 shown.

[0092] The maxillary second molars of 6-week-old C57BL / 6J male mice were ligated with 5-0 nylon thread, and then the mice were inoculated with Porphyromonas gingivalis every other day for 4 weeks. Micro-CT detection showed obvious alveolar bone resorption and root bifurcation exposure in the maxillary second molars of mice, confirming that the mouse periodontal disease model was successfully established.

[0093] Four mice were selected from the healthy control group (Control), four mice from the periodontitis group (Periodontitis) with successful periodontal disease model, and four mice from the periodontitis + compound 1 toothpaste treatment group (LA) with successful periodontal disease model. Figure 2 The mice were subjected to a daily toothbrush intervention using the indicated brushes and the prepared toothpaste. Micro-CT examinations were performed on these mice 4 weeks later, and the results were shown in Figure 3 The results showed that the alveolar bone absorption height of the healthy mice group was 84.26±10.91mm, and the alveolar bone absorption height of the periodontitis mice group was 609.83±110.46mm. The alveolar bone absorption height of the mice group treated with periodontitis + compound 1 toothpaste was 214.26±61.00mm, which shows that the toothpaste containing compound 1 of formula I can significantly inhibit the alveolar bone destruction and absorption caused by periodontal disease.

[0094] Although the present invention has been described with reference to exemplary embodiments, it should be understood that the present invention is not limited to the disclosed exemplary embodiments. Various adjustments or changes may be made to the exemplary embodiments of the present specification without departing from the scope or spirit of the present invention. The scope of the claims should be based on the broadest interpretation to cover all modifications and equivalent structures and functions.

Claims

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

2. The oral care composition according to claim 1, characterized in that The compound shown in (I) is:

3. The oral care composition according to claim 1, characterized in that The concentration or amount of component (a) in the oral care composition is controlled so that the oral care composition can produce a drug effective concentration in the range of 1.35-13 mM in the oral cavity after being applied to the oral cavity.

4. The oral care composition according to claim 1, characterized in that Component (b) includes at least one of an abrasive, a thickener, a surfactant, a preservative, a humectant, a sweetener, and a flavoring agent.

5. The oral care composition according to claim 1, characterized in that The oral care composition includes 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 teeth whitening strip, a dental floss, and a dental floss coating.

6. The oral care composition according to claim 1, characterized in that It effectively inhibits Porphyromonas gingivalis, but does not show a significant killing effect on Lactobacillus reuteri.

7. Use of a compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof, or an oral care composition according to any one of claims 1 to 5 in the preparation of an oral care product, characterized in that: The compound has the following structure: in: R1 is H or CH3; R2 is H, CH3 or OCH3; R3 is OH or OCH3.

8. The use according to claim 7, characterized in that The compound shown in (I) or a pharmaceutically acceptable salt thereof effectively inhibits Porphyromonas gingivalis, but does not show a significant killing effect on Lactobacillus reuteri.

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

10. The use according to claim 7, characterized in that The oral care product is used in at least one of the following situations: regulating the oral flora microenvironment, thereby improving oral diseases or conditions. Preferably, the oral diseases or conditions include oral ulcers, periodontal soft tissue atrophy and / or loss, alveolar bone resorption and / or decreased bone density.

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