Oral care solution composition containing glucanase as well as preparation method and application of oral care solution composition

Abstract

According to the oral care solution composition disclosed by the invention, glucanase is encapsulated by using a pH sensitive microcapsule, so that the stability and activity of enzyme in a complex oral environment are maintained. The pH-sensitive microcapsule is prepared from boric acid modified poly (2-hydroxyethyl methacrylate) (PHEMA), a boric acid group serves as a lactic acid specific ligand and is covalently bound and polymerized with a monomer of HEMA to form a pH-sensitive polymer, and in an oral acidic environment, disintegration of the polymer promotes release of glucanase, it is ensured that enzyme is released at a needed place and time, and the pH-sensitive microcapsule has the advantages that the pH-sensitive microcapsule can be used for preparing the oral cavity. Therefore, glucan in the oral cavity is accurately decomposed, bacterial adhesion and biofilm formation are reduced, and improvement of oral cavity microorganism balance and improvement of user experience are facilitated.

Description

Technical Field

[0001] The invention relates to the field of oral care, and in particular to an oral care liquid containing glucanase, and a preparation method and application thereof. Background Art

[0002] Oral care solution, as a common oral care product, is mainly used to assist in cleaning the oral cavity, removing food debris, preventing tooth decay, reducing gingivitis and eliminating bad breath. It plays an important role in maintaining oral hygiene and promoting oral health.

[0003] Adding dextranase to oral care solution can effectively decompose dextran in the mouth due to its unique biocatalytic function. These polysaccharides are one of the main factors leading to the formation of dental plaque. Dental plaque not only affects oral hygiene, but is also closely related to a variety of oral diseases, such as caries and periodontal disease. Through its enzymatic activity, dextranase can decompose dextran into smaller sugar molecules, thereby reducing bacterial attachment and biofilm formation, helping to maintain oral health.

[0004] CN104188860B discloses a mouthwash containing enzymes and tangerine peel extract and a preparation method thereof. A combination of three enzymes, α-glucanase, β-glucanase and α-amylase, is disclosed, which act together on the polysaccharide components in dental plaque. α-glucanase and β-glucanase catalyze hydrolysis of specific glycosidic bonds of α-glucan and β-glucan, respectively, while α-amylase randomly cuts off α-1,4-glucan chains. This synergistic effect can effectively degrade dental plaque and destroy the basis for bacterial growth. In addition, tangerine peel extract and mint extract are added to the mouthwash to enhance the oral antibacterial effect and freshen breath.

[0005] CN108186384A provides a mouthwash and a preparation method thereof, which contains a variety of enzyme preparations including glucanase. These enzyme preparations include glucanase, glucose oxidase, polyphenol oxidase, lysozyme, etc., which act together in the oral environment to exert their respective biocatalytic effects. The role of glucanase in this formula is to decompose glucan in the oral cavity, help remove tooth stains and inhibit the growth of dental plaque. At the same time, the mouthwash formula is weakly acidic, does not contain irritating ingredients such as alcohol, and is mild and non-irritating to the oral cavity.

[0006] Patents CN104188860B and CN108186384A respectively disclose a mouthwash containing enzymes and tangerine peel extracts and a preparation method thereof, as well as a mouthwash and a preparation method thereof. These products are intended to improve oral health, reduce the formation of dental plaque, inhibit the growth of oral bacteria, and have a fresh breath effect through specific enzyme preparations.

[0007] Although the prior art has provided oral care products containing glucanase, these products still face some key problems in practical application. The main problems include the stability and activity of the enzyme in the complex environment of the oral cavity, the efficiency of enzyme release, and the impact on the balance of oral microorganisms. In addition, existing products may lack responsiveness to specific oral conditions, resulting in inaccurate enzyme release, thus affecting the care effect and user experience. Summary of the invention

[0008] The present invention aims to provide an oral care solution containing glucanase, which can more efficiently identify and respond to oral bacterial metabolites, and can maintain the stability and activity of glucan in the complex environment of the oral cavity. The present invention promotes the release of glucanase from the polymer encapsulation material in the acidic environment of the oral cavity by selecting a specific polymer encapsulation material and a lactic acid-specific ligand to act together in the oral environment, thereby achieving the above-mentioned goal. The specific technical scheme is as follows:

[0009] The present invention provides an oral care liquid composition, comprising the following components:

[0010] Dextranase as an active ingredient, and pH-sensitive polymer microcapsules, wherein the dextranase is encapsulated in the pH-sensitive polymer microcapsules to constitute pH-sensitive microcapsules encapsulating dextranase;

[0011] The pH-sensitive polymer microcapsules account for 0.5 wt% to 2 wt% of the total weight of the oral care solution composition; comprising boric acid-modified poly 2-hydroxyethyl methacrylate;

[0012] The activity units of the glucanase encapsulated by the polymer microcapsules are 50 to 100 units per milliliter in the oral care liquid composition;

[0013] The boric acid modification refers to using a compound containing a boric acid group as a lactic acid-specific ligand to covalently bind to a 2-hydroxyethyl methacrylate monomer, wherein the molar ratio of the boric acid group to the 2-hydroxyethyl methacrylate is 1:0.95 to 1:1.05;

[0014] The average particle size of the pH-sensitive polymer microcapsules is 3-50 μm. In one embodiment, the compound containing a boronic acid group is one or more of boric acid, sodium borate, potassium borate, and vinyl borate; preferably boric acid;

[0015] In one embodiment, the oral care liquid composition further comprises the following components based on the total weight of the composition:

[0016] Fluoride: 0.01wt%-0.05wt%, preferably 0.02wt%-0.04wt%;

[0017] Antibacterial agent: 0.02wt% to 0.5wt%, preferably 0.05wt% to 0.3wt%;

[0018] Moisturizer: 0.2wt%-1.0wt%, preferably 0.4wt% to 0.6wt%;

[0019] Flavor: 0.01wt%-0.2wt%, preferably 0.02wt%-0.1wt%;

[0020] Preservative: 0.05wt%-0.3wt%, preferably 0.1wt%-0.2wt%;

[0021] The balance was deionized water.

[0022] In one embodiment, the fluoride is selected from sodium fluoride or ammonium fluoride; preferably sodium fluoride;

[0023] In one embodiment, the antibacterial agent is selected from one or more of triclosan, chlorhexidine, benzalkonium chloride or tea tree oil; preferably triclosan;

[0024] In one embodiment, the moisturizing agent is selected from one or more of glycerin, propylene glycol, sorbitol, polyethylene glycol or sodium hyaluronate; preferably glycerin;

[0025] In one embodiment, the flavor is selected from peppermint oil, spearmint oil, wintergreen oil or vanilla extract.

[0026] In one embodiment, the preservative is selected from one or more of phenoxyethanol, parabens, santolin or sodium dehydroacetate.

[0027] The present invention also provides a method for preparing an oral care liquid composition, comprising the following steps:

[0028] (1) Preparation of pH-sensitive microcapsule dispersion system for encapsulating glucanase:

[0029] a. dissolving 2-hydroxyethyl methacrylate monomer in deionized water to form a prepolymer solution;

[0030] b. Weigh a compound containing a boronic acid group according to a molar ratio of 1:0.95 to 1:1.05 and dissolve it in the prepolymer solution in step a to form a uniform solution;

[0031] c. mixing the glucanase and the emulsifier in deionized water to form an aqueous emulsion;

[0032] d. The HEMA solution of the compound containing the boronic acid group formed in step b is mixed with the aqueous emulsion containing the glucanase in step c, a crosslinking agent and an initiator are added, and an emulsion polymerization reaction is carried out at a temperature of 40-70° C. for 2-5 hours to form cured microcapsules;

[0033] e. After the reaction is completed, unreacted raw materials and by-products are removed by centrifugation and filtration, and the pH-sensitive microcapsules encapsulating glucanase are collected. The average particle size of the pH-sensitive microcapsules is 3-50 μm.

[0034] (2) Preparation of oral care solution:

[0035] g. The microcapsules prepared in step e are dispersed in deionized water according to the desired ratio;

[0036] h. Weigh fluoride, antibacterial agent, moisturizer, fragrance and preservative respectively and dissolve them in the microcapsule solution in the desired proportion;

[0037] i. Stir the mixed solution until all ingredients are evenly dispersed.

[0038] In one embodiment, the emulsifier in step c is selected from one or more of Tween 80, Span 80, alkyl acrylate copolymer and lecithin, preferably Tween 80.

[0039] In one of the schemes, the cross-linking agent in step d is selected from one or more of N,N'-methylenebisacrylamide, melamine formaldehyde resin, ethylene glycol dimethacrylate, and hydroxyethyl acrylate, preferably N,N'-methylenebisacrylamide, and the initiator is selected from one or more of ammonium persulfate, potassium persulfate, bis(persulfate) dicarbonate, and 2,2'-azobisisobutyronitrile, preferably 2,2'-azobisisobutyronitrile.

[0040] The invention also provides an application of the oral care liquid composition in oral care.

[0041] Compared with the prior art, the present invention has the following beneficial effects:

[0042] The oral care solution of the present invention encapsulates dextranase using pH-sensitive microcapsules, achieving the maintenance of the stability and activity of the enzyme in the complex oral environment. These microcapsules are made of poly(2-hydroxyethyl methacrylate) (PHEMA) modified with boric acid. The boric acid group, as a specific ligand for lactic acid, covalently binds to and polymerizes with the monomers of HEMA to form a pH-sensitive polymer. In the acidic oral environment, the disintegration of this polymer promotes the release of dextranase, ensuring that the enzyme is released where and when it is needed, thereby precisely decomposing dextran in the oral cavity, reducing bacterial adhesion and biofilm formation, and contributing to improving the oral microbial balance and enhancing the user experience. Poly(2-hydroxyethyl methacrylate) has excellent biocompatibility and does not cause additional impacts on the oral environment. After cross-linking, it can absorb water in the oral care solution to form a hydrogel, which can control the release rate of dextranase. The softness and smoothness of the PHEMA hydrogel give it a good taste in the oral care solution, and users will feel comfortable when using it. Detailed Embodiments

[0043] Although the present invention has been described to a certain extent, it is obvious that appropriate changes can be made to various conditions without departing from the spirit and scope of the present invention. It is understood that the present invention is not limited to the described embodiments, but falls within the scope of the claims, which include equivalent replacements for each factor described.

[0044] <Dextranase>

[0045] The dextranase described in the present invention is an enzyme capable of decomposing dextran, usually derived from microorganisms such as bacteria and fungi. In the present invention, dextranase is used as an active ingredient to recognize and respond to oral bacterial metabolites, improving the effect of oral care. Specifically, dextranase catalyzes enzymatic reactions in the oral cavity, specifically hydrolyzing the β-1,3 and / or β-1,4 glycosidic bonds of β-dextran to produce oligosaccharides or monosaccharides. This hydrolysis helps reduce the level of dextran in the oral cavity, decreasing bacterial adhesion and biofilm formation. The active content of dextranase in the oral care solution composition is 50 - 100 units per milliliter, preferably 60 - 80 units per milliliter. If the active content is too high, it will cause dextranase to decompose dextran too quickly in the oral cavity, not only affecting the balance of normal oral flora but also causing discomfort or irritation to the oral mucosa due to the excessive activity of the enzyme. In addition, too high an activity may shorten the service life of the product because the stability of the enzyme will decrease due to excessive reactions. If the active content is too low, it may result in dextranase being unable to effectively decompose dextran in the oral cavity, thereby weakening the benefits of the product for oral health. Low-activity enzymes may not be sufficient to combat bacterial accumulation and biofilm formation in the oral cavity, which may reduce the overall effect of the care solution.

[0046] <pH-Sensitive Microcapsules>

[0047] In the present invention, the pH sensitive microcapsules are specifically boric acid modified poly(2-hydroxyethyl methacrylate) polymer microcapsules, which can be used to achieve sensitive response to pH changes in the oral environment, thereby controlling the release of glucanase. The acidification of the oral environment is mainly due to the metabolic activity of bacteria in the oral cavity. These bacteria produce acidic substances, such as lactic acid, by decomposing food residues and intracellular organic matter. In particular, in dental plaque formed on the surface of teeth, bacteria actively metabolize sugars to generate a large amount of acidic byproducts, resulting in a decrease in the local pH value, making the oral environment acidic. This acidic environment not only promotes the growth of more bacteria, but also may cause tooth minerals to dissolve, thereby increasing the risk of caries. In an acidic environment, the boric acid group can react with the surrounding hydroxyl or carboxyl groups to form a borate ester bond. This bond has different stabilities at different pH values, so that the polymer microcapsules can respond and release encapsulated substances at specific pH values. It can be seen that boric acid-modified poly(2-hydroxyethyl methacrylate) can adjust the solubility and porosity of microcapsules to achieve controlled release of glucanase in the acidic environment of the oral cavity by forming dynamic borate bonds, which helps to provide higher concentrations of enzymes in areas where bacteria are active and glucan accumulates more, thereby more effectively decomposing glucan and reducing the formation of dental plaque. At the same time, this pH sensitivity also helps to protect glucanase from being prematurely degraded by other enzymes or chemicals in the oral cavity, prolonging its active time in the oral cavity.

[0048] As a biocompatible material, PHEMA has been widely studied and used in the biomedical field, including drug delivery systems. Its chemical stability and biocompatibility ensure the safety and effectiveness of microcapsules in oral care solutions. Through boric acid modification, PHEMA has gained sensitivity to changes in the pH of the oral environment, making this microcapsule an ideal choice for achieving precise release of active ingredients in oral care solutions.

[0049] Boric acid modification is achieved by covalently binding a compound containing a boronic acid group as a lactic acid-specific ligand to HEMA, and the molar ratio of the boronic acid group to HEMA is precisely controlled in the range of 1:0.95 to 1:1.05. This ratio is chosen to ensure the stability of the microcapsules in the oral environment and the effective response at an appropriate pH value. The average particle size of the polymer microcapsules is 3-50μm, which is conducive to the uniform dispersion of the microcapsules in the oral care solution, and also facilitates the contact of the microcapsules with the teeth and gums in the oral cavity, thereby effectively releasing the glucanase when needed. The particle size is regulated by the amount of emulsifier added, the stirring conditions, and the temperature, time and concentration of the initiator of the reaction.

[0050] <Preparation of pH-sensitive microcapsule dispersion system for encapsulating glucanase>

[0051] In the oral care solution, the glucanase is encapsulated in pH-sensitive microcapsules and dispersed in the oral care solution. Therefore, the present invention also discloses a method for preparing a pH-sensitive microcapsule dispersion system encapsulating the glucanase:

[0052] a. dissolving 2-hydroxyethyl methacrylate in deionized water to form a prepolymer solution;

[0053] b. Weigh a compound containing a boronic acid group in a molar ratio of 1:0.95 to 1:1.05 and dissolve it in the prepolymer solution in step a to form a uniform solution;

[0054] c. mixing the glucanase and the emulsifier in deionized water to form an aqueous emulsion;

[0055] d. The prepolymer homogeneous solution of the boronic acid group-containing compound formed in step b is mixed with the aqueous emulsion containing glucanase in step c, a crosslinking agent and an initiator are added, and an emulsion polymerization reaction is carried out at a temperature of 40-70° C. for 2-5 hours to form cured microcapsules;

[0056] Wherein, taking the total solid content of the pH sensitive microcapsules encapsulating glucanase as 100wt%, the content of HEMA before the reaction is about 66wt%-72wt%, the content of the compound containing boronic acid groups is about 22wt%-24wt%, and the molar ratio of boronic acid groups to HEMA is 1:0.95-1:1.05. The content of emulsifier is 0.5wt%-3wt%, the content of cross-linking agent is 1wt%-5wt%, the content of initiator is 0.1wt%-0.5wt%, and the content of glucanase with a specific activity of 1000 units / mg is about 0.5wt%-1.5wt%.

[0057] The compound containing a boric acid group is one or more of boric acid, sodium borate, potassium borate, and vinyl borate; preferably boric acid;

[0058] The emulsifier is selected from one or more of Tween 80, Span 80, alkyl acrylate copolymer and lecithin, preferably Tween 80.

[0059] The crosslinking agent is selected from one or more of N,N'-methylenebisacrylamide, melamine formaldehyde resin, ethylene glycol dimethacrylate, and hydroxyethyl acrylate, preferably N,N'-methylenebisacrylamide; the initiator is selected from one or more of ammonium persulfate, potassium persulfate, bis(persulfate) dicarbonate, and 2,2'-azobisisobutyronitrile, preferably 2,2'-azobisisobutyronitrile.

[0060] e. After the reaction is completed, the unreacted raw materials and by-products are removed by centrifugation and filtration, and the pH-sensitive microcapsules encapsulating glucanase are collected, and the average particle size is 3-50 μm. In order to ensure the stability of the pH-sensitive microcapsules encapsulating glucanase, the pH-sensitive microcapsules encapsulating glucanase are dried at low temperature under reduced pressure, and the low-temperature drying temperature is controlled in the range of 35-55°C.

[0061] <Preparation of oral care solution>

[0062] The preparation of the oral care solution of the present invention is not particularly limited. The prepared pH-sensitive microcapsules encapsulating glucanase are mixed with other effective components in the oral care solution in proportion and uniformly dispersed in deionized water.

[0063] Other effective components of the oral care solution include, but are not limited to, fluoride, antibacterial agent, moisturizer, flavor and preservative. Fluoride can enhance the acid resistance of tooth enamel, reduce the dissolution of tooth minerals, thereby reducing the risk of caries, and can also promote the redeposition of minerals on the tooth surface and help repair early caries. It is selected from sodium fluoride or ammonium fluoride; preferably sodium fluoride. The content is 0.01wt%-0.05wt%, preferably 0.02wt%-0.04wt%.

[0064] The antibacterial agent can inhibit the growth and reproduction of bacteria, reduce bad breath, and prevent the formation of dental plaque. It is selected from one or more of triclosan, chlorhexidine, benzalkonium chloride or tea tree oil; preferably triclosan; the content is 0.02wt% to 0.5wt%, preferably 0.05wt% to 0.3wt%.

[0065] The humectant helps to keep the mouth moist and avoid oral dryness, and is selected from one or more of glycerol, propylene glycol, sorbitol, polyethylene glycol or sodium hyaluronate; preferably glycerol; the content is 0.2wt%-1.0wt%, preferably 0.4wt% to 0.6wt%.

[0066] The flavor helps to improve the taste and smell of the oral care solution and provide fresh breath, and is selected from peppermint oil, spearmint oil, wintergreen oil or vanilla extract, with a content of 0.01wt%-0.2wt%, preferably 0.02wt%-0.1wt%.

[0067] The preservative is used to extend the shelf life of the product and prevent the growth and reproduction of microorganisms in the product during storage, and is selected from one or more of phenoxyethanol, parabens, santolin or sodium dehydroacetate, 0.05wt%-0.3wt%, preferably 0.1wt%-0.2wt%.

[0068] The oral care solution of the present invention may contain any effective ingredient, as long as the component has no effect on the stability of the pH-sensitive microcapsules encapsulating glucanase, does not reduce the activity of glucanase, and has a positive effect on the oral care solution within a reasonable content range.

[0069] The oral care liquid composition and the preparation method thereof provided by the present invention are described in detail below in conjunction with the examples, but they should not be construed as limiting the scope of protection of the present invention. In addition, if no specific conditions are specified in the examples of the present invention, the conventional conditions or the conditions recommended by the manufacturer are used; if the manufacturer of the reagents or instruments is not specified, they are all conventional products that can be purchased commercially.

[0070] 1. Preparation of oral care liquid composition in Examples and Comparative Examples

[0071] Example 1

[0072] The materials are prepared according to the content ratio in the following table:

[0073]

[0074] Preparation steps:

[0075] HEMA was dissolved in deionized water to form a prepolymer solution, and boric acid was dissolved in the prepolymer solution to form a uniform solution; β-1,3 glucanase (provided by Shanghai Yuanye Biotechnology Co., Ltd., with a specific activity of 1000 units / mg) was mixed with Tween 80 in deionized water to form an aqueous phase emulsion; the HEMA solution of boric acid was mixed with the aqueous phase emulsion containing glucanase, N,N'-methylenebisacrylamide and 2,2'-azobisisobutyronitrile were added, and an emulsion polymerization reaction was carried out at 60°C for 4 hours to form solidified microcapsules. After the reaction was completed, the unreacted raw materials and by-products were removed by centrifugation and filtration, and the pH-sensitive microcapsules were collected and dried for use, with an average particle size of 27.5μm.

[0076] The dried pH sensitive microcapsules were dispersed in deionized water, sodium fluoride, triclosan, glycerin, peppermint oil and phenoxyethanol were weighed respectively, dissolved in the microcapsule solution, and the mixed solution was stirred until all the ingredients were evenly dispersed to obtain the oral care solution of Example 1.

[0077] Example 2

[0078] The materials are prepared according to the content ratio in the following table:

[0079]

[0080]

[0081] Preparation steps:

[0082] HEMA was dissolved in deionized water to form a prepolymer solution, sodium borate (anhydrous Na3BO3) was dissolved in the prepolymer solution to form a uniform solution; β-1,3 glucanase (provided by Shanghai Yuanye Biotechnology Co., Ltd., with a specific activity of 1000 units / mg) was mixed with Tween 80 in deionized water to form an aqueous phase emulsion; the HEMA solution of sodium borate was mixed with the aqueous phase emulsion containing glucanase, N,N'-methylenebisacrylamide and 2,2'-azobisisobutyronitrile were added, and an emulsion polymerization reaction was carried out at 70°C for 5 hours to form cured microcapsules. After the reaction was completed, the unreacted raw materials and by-products were removed by centrifugation and filtration, and the pH-sensitive microcapsules were collected and dried for use, with an average particle size of 12.1 μm.

[0083] The dried pH sensitive microcapsules were dispersed in deionized water, sodium fluoride, triclosan, glycerin, peppermint oil and phenoxyethanol were weighed respectively, dissolved in the microcapsule solution, and the mixed solution was stirred until all the ingredients were evenly dispersed to obtain the oral care solution of Example 2.

[0084] Example 3

[0085] Compared with Example 1, the contents of the emulsifier and the cross-linking agent are 0.005 g and 0.01 g respectively. When other conditions remain unchanged, the average particle size is 48.9 μm.

[0086] Example 4

[0087] Compared with Example 1, fluoride among other effective components is not added, and other conditions remain unchanged.

[0088] Comparative Example 1

[0089] The materials are prepared according to the content ratio in the following table:

[0090]

[0091] Preparation steps:

[0092] Glucanase (specific activity of 1000 units / mg) was directly dispersed in deionized water, sodium fluoride, triclosan, glycerol, peppermint oil and phenoxyethanol were weighed respectively, dissolved in the microcapsule solution, and the mixed solution was stirred until all the ingredients were evenly dispersed to obtain the oral care solution of Comparative Example 1.

[0093] Comparative Example 2

[0094] The materials are prepared according to the content ratio in the following table:

[0095]

[0096]

[0097] Preparation steps:

[0098] HEMA was dissolved in deionized water to form a prepolymer solution, and β-1,3 glucanase (provided by Shanghai Yuanye Biotechnology Co., Ltd., with a specific activity of 1000 units / mg) and Tween 80 were mixed in deionized water to form an aqueous phase emulsion; the HEMA prepolymer solution was mixed with the aqueous phase emulsion containing glucanase, and N,N'-methylenebisacrylamide and 2,2'-azobisisobutyronitrile were added to carry out an emulsion polymerization reaction at 60°C for 4 hours to form cured microcapsules. After the reaction was completed, the unreacted raw materials and by-products were removed by centrifugation and filtration, and the pH-sensitive microcapsules were collected and dried for use, with an average particle size of 26.8μm.

[0099] The dried pH sensitive microcapsules were dispersed in deionized water, sodium fluoride, triclosan, glycerin, peppermint oil and phenoxyethanol were weighed respectively, dissolved in the microcapsule solution, and the mixed solution was stirred until all the ingredients were evenly dispersed to obtain the oral care solution of Comparative Example 2.

[0100] Comparative Example 3

[0101] The materials are prepared according to the content ratio in the following table:

[0102]

[0103]

[0104] Preparation steps:

[0105] Lactic acid and glycolic acid were dissolved in deionized water at a molar ratio of 3:1, and the total weight of the monomers was 1 g to form a prepolymer solution. Boric acid was dissolved in the prepolymer solution to form a uniform solution. β-1,3 glucanase (provided by Shanghai Yuanye Biotechnology Co., Ltd., with a specific activity of 1000 units / mg) was mixed with Tween 80 in deionized water to form an aqueous emulsion. The PLGA precursor solution of boric acid was mixed with the aqueous emulsion containing glucanase, and N,N"-methylenebisacrylamide and 2,2'-azobisisobutyronitrile were added to carry out an emulsion polymerization reaction at 60°C for 4 hours to form cured microcapsules. After the reaction was completed, the unreacted raw materials and by-products were removed by centrifugation and filtration, and the pH-sensitive microcapsules were collected and dried for use. The average particle size was 17.4 μm.

[0106] The dried pH sensitive microcapsules were dispersed in deionized water, sodium fluoride, triclosan, glycerin, peppermint oil and phenoxyethanol were weighed respectively, dissolved in the microcapsule solution, and the mixed solution was stirred until all the ingredients were evenly dispersed to obtain the oral care solution of Comparative Example 3.

[0107] 2. Dextran Decomposition Test

[0108] Experimental methods:

[0109] 1.0 g of dextran was weighed and dissolved in 99 ml of deionized water to prepare a 1% w / v dextran solution. The solution was adjusted to different pH values ​​(within the range of 5-8) by adding hydrochloric acid, sodium hydroxide and phosphate (PBS) buffer. 1 ml of the dextran solution was added to a test tube, and then 4 ml of the samples of Examples 1-4 and Comparative Examples 1-3 were added and mixed. The mixture was added to a 37°C water bath and allowed to stand for 30 minutes.

[0110] Take out the test tube from the water bath, add 0.5 ml of solution A (0.1 g / ml NaOH) and 0.5 ml of solution B (0.05 g / ml CuSO4), mix well, put the test tube back into the water bath, heat to 50°C for 5 minutes, and observe the color change and precipitation effect of the solution in the test tube.

[0111] The color changes and precipitation effects of Examples 1-4 and Comparative Examples 1-3 are shown in the following table:

[0112]

[0113] The principle used in this experiment is that glucanase decomposes glucan to produce reducing sugars, which reduce the water-soluble blue divalent copper ions in Fehling's test solution to water-insoluble reddish brown monovalent copper ions (cuprous oxide), resulting in a reddish brown precipitate. It can be seen that in Example 1-4, pH-sensitive microcapsules are used to encapsulate glucanase, and pH-sensitive microcapsules release glucanase in glucan solutions in a slant acidic or neutral environment, and then decompose glucan. In a weakly alkaline environment, glucanase is not released, which means that in the oral environment, only in places where bacterial metabolism is active and acidic byproducts appear, the glucanase encapsulated by the pH-sensitive microcapsules will be released in large quantities, thereby completing the decomposition of the glucan at the place, which is conducive to the glucanase not being prematurely degraded by other enzymes or chemicals in the oral cavity, and prolonging its activity time in the oral cavity. Comparative Example 1 is a case without encapsulation, and it will degrade the glucan in any scenario. If it is not modified with boric acid or other encapsulating polymers are used, it does not have the pH response ability, and thus will not release the glucanase in time.

[0114] 3. Glucanase release rate test experiment

[0115] Experimental methods:

[0116] Using soybean agar plates as culture medium, culture mutans Streptococcus in an anaerobic environment at 37°C for 3 days. After the culture is completed, carefully pick the colonies using an inoculation loop and transfer them to the pre-prepared Todd Hewitt broth medium, and culture them under anaerobic conditions at 37°C for 18 hours. Thereafter, take out 10mL of the culture solution and add it to a culture dish containing 2mL Todd Hewitt broth medium (to which 1wt% glucan has been added). Culture in an anaerobic environment at 37°C for 6 hours. Take 10ml of the oral care solution of Examples 1-4 and Comparative Examples 1-3 and 10ml of deionized water as a blank control group and add them to a culture dish with 10ml of glucan (1wt%) solution, and continue to culture in a 37°C water bath for 24h.

[0117] During this process, 2 ml of culture medium was collected at 0, 4, 8, 12 and 24 h respectively, 3 mL of PBS buffer was added to rinse the test tube containing the culture medium twice, the liquid was poured out, 3 mL of sodium hydroxide (0.5 M) solution was added, and a vortex oscillator was used to shake and disperse the residual dental plaque, and then the absorbance (550 nm) of the liquid in the test tube was detected.

[0118] Plaque removal rate = (absorbance of PBS buffer - absorbance of blank control) / absorbance of blank control

[0119] The dental plaque removal rates (%) of Examples 1-4 and Comparative Examples 1-3 at different time periods are shown in the following table:

[0120]

[0121]

[0122] This table reflects the continuous inhibition and removal of dental plaque after using oral care solutions of different samples. It can be seen that the oral care solution compositions of Examples 1-4 can provide 24 hours of dental plaque inhibition on the basis of the encapsulation of dextranase by pH-responsive microcapsules, indicating that dextranase can be continuously released from pH-responsive microcapsules, thereby maintaining a relatively long period of inhibition of bacteria. On the other hand, it also shows that pH-responsive microcapsules can be well retained in the oral environment, and after the oral care solution is spit out, most of them can interact deeply with the oral mucosa in the form of gel. The dextranase in Comparative Example 1, which is not microencapsulated, can only decompose dextran in a short time, thereby playing an antibacterial role, and cannot permanently control the environment for bacterial growth. Comparative Examples 2 and 3 are microcapsules that do not have the degradation that is regulated under pH-responsive conditions, and therefore are not suitable for continuous antibacterial in the oral environment.

[0123] The above is only a preferred embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art can easily think of changes or substitutions within the technical scope disclosed by the present invention, which should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention should be based on the protection scope of the claims.

Claims

1. An oral care liquid composition, characterized in that: Based on the total weight of the composition, the following components are included: Glucanase as an active ingredient, and pH-sensitive polymer microcapsules, wherein the glucanase is encapsulated in the pH-sensitive polymer microcapsules to form pH-sensitive microcapsules encapsulating glucanase; the pH-sensitive polymer microcapsules account for 0.5wt% to 2wt% of the total weight of the oral care liquid composition; poly(2-hydroxyethyl methacrylate) modified with boric acid; Fluoride: 0.01wt%-0.05wt%; Antimicrobial agent: 0.02wt% to 0.5wt%; Moisturizer: 0.2wt%-1.0wt%; Flavor: 0.01wt%-0.2wt%; Preservative: 0.05wt%-0.3wt%; The balance is deionized water; Furthermore, the activity unit of the glucanase encapsulated by the polymer microcapsules is 50 to 100 units per milliliter in the oral care liquid composition; The boric acid modification refers to using a compound containing a boric acid group as a lactic acid-specific ligand to covalently bind to a 2-hydroxyethyl methacrylate monomer, wherein the molar ratio of the boric acid group to the 2-hydroxyethyl methacrylate is 1:0.95 to 1:1.05; The average particle size of the pH-sensitive polymer microcapsules is 3-50 μm.

2. The oral care liquid composition according to claim 1, characterized in that The compound containing a boric acid group is one or more of boric acid, sodium borate, potassium borate and vinyl borate.

3. The oral care liquid composition according to claim 1, characterized in that The fluoride is selected from sodium fluoride or ammonium fluoride.

4. The oral care liquid composition according to claim 1, characterized in that The antibacterial agent is selected from one or more of triclosan, chlorhexidine, benzalkonium chloride or tea tree oil.

5. The oral care liquid composition according to claim 1, characterized in that: The moisturizing agent is selected from one or more of glycerin, propylene glycol, sorbitol, polyethylene glycol or sodium hyaluronate.

6. The oral care liquid composition according to claim 1, characterized in that: The flavor is selected from peppermint oil, spearmint oil, wintergreen oil or vanilla extract; and The preservative is selected from one or more of phenoxyethanol, parabens, santolin or sodium dehydroacetate.

7. The method for preparing the oral care liquid composition according to claim 1, characterized in that: The steps include: (1) Preparation of pH-sensitive microcapsule dispersion system for encapsulating glucanase: a. dissolving 2-hydroxyethyl methacrylate monomer in deionized water to form a prepolymer solution; b. Weigh a compound containing a boronic acid group according to a molar ratio of 1:0.95 to 1:1.05 and dissolve it in the prepolymer solution in step a to form a uniform solution; c. mixing the glucanase and the emulsifier in deionized water to form an aqueous emulsion; d. The HEMA solution of the compound containing the boronic acid group formed in step b is mixed with the aqueous emulsion containing the glucanase in step c, a crosslinking agent and an initiator are added, and an emulsion polymerization reaction is carried out at a temperature of 40-70° C. for 2-5 hours to form cured microcapsules; e. After the reaction is completed, unreacted raw materials and by-products are removed by centrifugation and filtration, and the pH-sensitive microcapsules encapsulating glucanase are collected. The average particle size of the pH-sensitive microcapsules is 3-50 μm. (2) Preparation of oral care solution: g. The microcapsules prepared in step e are dispersed in deionized water according to the desired ratio; h. Weigh fluoride, antibacterial agent, moisturizer, fragrance and preservative respectively and dissolve them in the microcapsule solution in the desired proportion; i. Stir the mixed solution until all ingredients are evenly dispersed.

8. The method for preparing the oral care liquid composition according to claim 7, characterized in that: The emulsifier in step c is selected from one or more of Tween 80, Span 80, alkyl acrylate copolymer and lecithin.

9. The method for preparing the oral care liquid composition according to claim 7, characterized in that: The crosslinking agent in step d is selected from one or more of N,N'-methylenebisacrylamide, melamine formaldehyde resin, ethylene glycol dimethacrylate, and hydroxyethyl acrylate; The initiator is selected from one or more of ammonium persulfate, potassium persulfate, bis(persulfate) dicarbonate, and 2,2'-azobisisobutyronitrile.

10. Use of the oral care liquid composition according to claim 1 in oral care.

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