Anti-caries mouthwash composition as well as preparation method and application thereof

Abstract

According to the anti-caries mouthwash composition provided by the invention, the effective components of mouthwash comprise fluoride, casein phosphopeptides-amorphous calcium phosphate (CPP-ACP) and bioactive glass (BAG) in a specific ratio, and the chemical composition, surface modification and particle size distribution of the bioactive glass are limited, so that the anti-caries mouthwash composition can be used for preventing caries on the premise of reducing the concentration of the fluoride. The anti-caries effect is not obviously worsened, and meanwhile, a better remineralization effect is achieved.

Description

Technical Field

[0001] The invention relates to the field of oral care, and in particular to an anti-caries mouthwash composition and a preparation method and application thereof. Background Art

[0002] Fluoride is a widely used ingredient in oral care products and is valued for its effectiveness in preventing tooth decay. In mouthwash, fluoride mainly exists in the form of sodium fluoride, which can enhance the acid resistance of teeth and improve the acid resistance of teeth by forming fluoroapatite, thereby reducing the occurrence of tooth decay. Fluoride can also promote the deposition of minerals on the surface of teeth, enhance the remineralization process of teeth, and help repair early caries.

[0003] Although fluoride is beneficial for oral health, excessive use may pose health risks. Especially for teenagers, because their teeth and bones are still developing, they are more sensitive to fluoride. Excessive intake of fluoride can cause dental fluorosis, a condition in which white spots or brown spots appear on the surface of teeth, affecting the appearance. More seriously, long-term excessive intake of fluoride may affect bone health and cause skeletal fluorosis. In addition, due to their young age, teenagers are more likely to accidentally ingest fluoride mouthwash, which can easily lead to acute fluoride poisoning and pose a threat to their health.

[0004] Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) is a natural ingredient extracted from milk that stabilizes calcium and phosphate ions and promotes tooth remineralization. Fluoride improves the acid resistance of teeth by forming fluorapatite, while CPP-ACP provides calcium and phosphate ions to promote mineral deposition on the tooth surface.

[0005] Due to the risk of excessive fluoride intake, the concentration of fluoride in mouthwash needs to be adjusted. However, reducing the fluoride concentration will affect its caries-preventive effect, especially in high-risk populations. In addition, the reduction of fluoride concentration may lead to a decrease in the remineralization effect of CPP-ACP, because the effect of CPP-ACP depends on the presence of fluoride. Therefore, it is necessary to find a way to compensate for the lack of caries-preventive effect and remineralization effect caused by the reduction of fluoride concentration, while maintaining the safety and efficacy of the product. Summary of the invention

[0006] The present invention aims to provide an anti-caries mouthwash composition, which has no significant deterioration in anti-caries effect under the premise of reducing the fluoride concentration, and has a good remineralization effect. The present invention achieves the above-mentioned goal by including a specific ratio of fluoride, casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and bioactive glass (BAG) in the mouthwash active ingredients, and limiting the chemical composition, surface modification and particle size distribution of the bioactive glass. In addition, the present invention also provides a method for preparing the anti-caries mouthwash composition and its application in oral care. The details are as follows:

[0007] In one aspect of the present invention, there is provided an anti-caries mouthwash composition, comprising an active ingredient and deionized water, based on 100% by total weight of the anti-caries mouthwash composition, the active ingredient comprises:

[0008] Fluoride, 100-900 ppm;

[0009] Casein phosphopeptide-amorphous calcium phosphate, 2.0-8.0wt%;

[0010] Bioactive glass, 2.0-5.0wt%;

[0011] The chemical composition of the bioactive glass includes, by weight percentage:

[0012] 45-55% SiO 2 ;

[0013] 20-30% CaO;

[0014] 5-15% P 2 O 5 ;

[0015] 5-15% Na 2 O;

[0016] The bioactive glass is in the form of spherical particles, at least 50% of which have a particle size between 0.1 and 10 μm, and an average particle size between 3 and 20 μm.

[0017] In one embodiment, the bioactive glass is surface treated with aminosilane to make the surface of the bioactive glass aminated, and the relative content of the surface aminated is 30%-80%.

[0018] In one embodiment, the content of fluoride is 200 ppm-500 ppm based on 100% of the total weight of the anticaries mouthwash composition.

[0019] In one embodiment, the pH value of the anti-caries mouthwash composition is 7-7.5, and a pH stabilizer is used to maintain the pH value within the above range. The pH stabilizer is selected from one or more of sodium dihydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, citric acid, sodium citrate, sodium bicarbonate and sodium carbonate, among which disodium hydrogen phosphate is preferred.

[0020] In one embodiment, the fluoride is selected from one or more of sodium fluoride, ammonium fluoride, strontium fluoride, barium fluoride and stannous fluoride, among which sodium fluoride is preferred.

[0021] In one embodiment, the molar ratio of calcium to phosphate in the casein phosphopeptide-amorphous calcium phosphate is 1.1-1.45, preferably 1.2-1.4.

[0022] In one embodiment, the anti-caries mouthwash composition may further include one or more of a stabilizer, a sweetener, a flavor, and an antibacterial agent.

[0023] In one embodiment, the stabilizer is selected from one or more of hydroxypropyl methylcellulose (HPMC), hydroxyethyl cellulose (HEC), carbomer resin or sodium alginate.

[0024] In one embodiment, the sweetener is selected from one or more of xylitol, sorbitol, sucralose, aspartame or stevia extract.

[0025] In one embodiment, the fragrance is selected from one or more of peppermint oil, tea tree oil, lemon oil or wintergreen oil.

[0026] In one embodiment, the antibacterial agent is selected from one or more of chlorhexidine, sodium benzoate, parabens or tea tree oil.

[0027] In another aspect of the present invention, a method for preparing an anti-caries mouthwash composition is provided, the method comprising the following steps:

[0028] Weigh sodium fluoride and dissolve it in deionized water to form a 100-900 ppm fluoride solution;

[0029] Weigh casein phosphopeptide-amorphous calcium phosphate, the weight of which is 2.0-8.0% of the total weight of the mouthwash;

[0030] Weigh the bioactive glass, the weight of which is 2.0-5.0% of the total weight of the mouthwash, and the chemical composition of the bioactive glass, by weight percentage, includes 45-55% SiO 2 , 20-30% CaO, 5-15% P 2 O 5 and 5-15% Na2 O, and the bioactive glass is in the form of spherical particles, at least 50% of which have a particle size between 0.1 and 10 μm, and an average particle size between 3 and 20 μm;

[0031] The fluoride solution, casein phosphopeptide-amorphous calcium phosphate and bioactive glass are mixed, and a pH stabilizer and the remaining deionized water are added to adjust the total content to 100 wt % and the pH value to 7-7.5 to form an anti-caries mouthwash composition.

[0032] Optionally, in one of the solutions, before adding the pH stabilizer and the remaining deionized water, one or more of a stabilizer, a sweetener, a flavor, and an antibacterial agent are added in a weight ratio.

[0033] In one embodiment, the bioactive glass is ball milled and screened to obtain the particle size and average particle diameter.

[0034] Optionally, in one of the solutions, the bioactive glass is surface treated, specifically comprising:

[0035] The bioactive glass is contacted with a 2-5 wt % aminosilane aqueous solution for 20-60 min at a contact temperature of 25-40° C.;

[0036] The contacted bioactive glass particles are then heated to 60-100° C. for a heat treatment of 30-120 minutes, and then washed with deionized water to remove unreacted aminosilane and by-products; and then dried to remove residual moisture to obtain surface-treated bioactive glass.

[0037] The present invention also provides an application of the anti-caries mouthwash composition in oral care, wherein the mouth is rinsed with 20-40 ml of the anti-caries mouthwash twice a day for 20-40 seconds before spitting out.

[0038] Compared with the prior art, the present invention has the following beneficial effects:

[0039] (1) By reducing the fluoride concentration to no more than 1000 ppm, the risk of dental fluorosis and skeletal fluorosis is reduced. At the same time, by adding two active ingredients, CPP-ACP and bioactive glass (BAG), the caries prevention effect that may be reduced due to the reduction of fluoride concentration is compensated. CPP-ACP and BAG can provide the necessary calcium and phosphate ions, which work together with fluoride to promote the remineralization of the tooth surface and enhance the acid resistance of teeth, thereby effectively preventing caries in a low-fluoride environment.

[0040] (2) The particle size of bioactive glass is strictly controlled between 0.1-10 μm, with at least 50% of the particle size within this range and an average particle size of 3-20 μm. This control helps to improve the dispersibility of BAG in mouthwash and ensure its uniform distribution in the oral cavity, thereby more effectively contacting the tooth surface and promoting remineralization. At the same time, BAG particles of appropriate size can dissolve faster and provide continuous ion release, which helps the remineralization effect of CPP-ACP. It is speculated that CPP-ACP needs to work synergistically with soluble calcium and phosphate ions to form stable mineral deposits. BAG particles are biocompatible, so there will be no adverse reactions after accidental ingestion.

[0041] (3) Furthermore, the present invention performs aminosilane surface treatment on BAG to aminate its surface, which enhances the compatibility and biological activity of BAG with oral tissues. The aminated surface can improve the adsorption capacity of BAG, allowing it to more effectively capture and retain calcium and phosphate ions in the oral cavity, thereby enhancing the remineralization effect. In addition, this surface treatment also enhances the interaction between BAG and CPP-ACP, because the amino group can form a stable complex with the phosphate group in CPP-ACP, further enhancing the synergistic effect of the two. DETAILED DESCRIPTION

[0042] Although the present invention has been described to a certain extent, it is obvious that appropriate changes in various conditions can be made without departing from the spirit and scope of the present invention. It is understood that the present invention is not limited to the embodiments described, but belongs to the scope of the claims, which includes equivalent replacements of each factor described.

[0043] In the anti-caries mouthwash composition provided by the present invention, the effective ingredients include at least fluoride, casein phosphopeptide-amorphous calcium phosphate and bioactive glass, wherein compared with the tooth remineralization composition (such as CN103764102A) in the prior art in which the fluoride is usually preferably above 0.1wt%, the fluoride content in the present invention is 100-900ppm, preferably 200ppm-500ppm. By reducing the amount of fluoride used, the risk of dental fluorosis caused by excessive intake of fluoride can be reduced, especially in children and adolescents, whose teeth and bones are still developing and more sensitive to fluoride. At the same time, for children at risk of accidental ingestion, the risk of acute fluoride poisoning caused by accidental ingestion is reduced. Although the content of fluoride is reduced, the synergistic effect with CPP-ACP and bioactive glass can enhance the effect of low-concentration fluoride, and can also achieve its ability to enhance the acid resistance of teeth, form fluorapatite to improve the acid resistance of teeth, and reduce the occurrence of dental caries. The fluoride is selected from one or more of sodium fluoride, ammonium fluoride, strontium fluoride, barium fluoride and stannous fluoride. Sodium fluoride is preferred in view of solubility in water, easy control of dosage, safety and cost.

[0044] The term remineralization in the present invention refers to the crystallization of inorganic salts in the tooth structure.

[0045] Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) is a natural bioactive material extracted and processed from casein in milk through a special process. It consists of two parts: casein phosphopeptide (CPP) and amorphous calcium phosphate (ACP). CPP is a phosphorylated peptide segment of casein with excellent mineral binding ability, while ACP is an amorphous calcium phosphate with high solubility and ion release ability. CPP-ACP has a significant remineralization effect. It can stably provide calcium and phosphate ions, which are essential for the remineralization of teeth and help repair early caries and self-repair of teeth. When CPP-ACP works together with fluoride, it can improve the bioavailability of fluoride and enhance its anti-caries effect. At the same time, it promotes the formation of more acid-resistant fluoroapatite on the tooth surface, thereby improving the acid resistance of teeth. Because it is derived from milk, CPP-ACP has good biocompatibility, is safe and harmless to the human body, and is relatively stable in the oral environment. It can slowly release mineral ions in saliva and maintain the dynamic balance of mineral ions in the mouth.

[0046] In the anti-caries mouthwash composition, based on the total weight of the anti-caries mouthwash composition as 100wt%, the content of CPP-ACP is 2.0-8.0wt%, preferably 3.0-6.0wt%, and more preferably 3.5-5.0wt%. If the content of CPP-ACP is lower than 2.0wt%, it is not possible to provide sufficient calcium and phosphate ions to achieve effective tooth remineralization and anti-caries effects; if the content of CPP-ACP is higher than 8.0wt%, the viscosity of the mouthwash increases significantly, resulting in reduced stability of the mouthwash, affecting the taste of the mouthwash and user acceptance, and the tooth remineralization effect is not obvious.

[0047] The molar ratio of calcium and phosphate in the casein phosphopeptide-amorphous calcium phosphate is 1.1-1.45, preferably 1.2-1.4, and the casein phosphopeptide part can stabilize amorphous calcium phosphate, thereby slowly releasing calcium and phosphorus ions in the oral cavity, promoting the concentration of calcium and phosphorus ions in saliva, promoting remineralization, and improving the conversion rate of fluoroapatite without excessive use of fluoride, so that the acid resistance is not affected. Experiments have found that if the molar ratio is too low, the calcium-phosphorus ratio is too different from the calcium-phosphorus ratio of natural teeth, and the hardness and acid resistance of remineralization are insufficient. If the molar ratio is close to 1.5, that is, when casein phosphopeptide is not present, the release of amorphous calcium phosphate is too fast, which is not conducive to the conversion of fluoroapatite in a low-concentration fluoride environment, and the ability to prevent caries and acid resistance will also be reduced.

[0048] In the anti-caries mouthwash composition of the present invention, the selection and property optimization of bioactive glass (BAG) are the key to achieving its excellent anti-caries and remineralization performance. The chemical composition, particle morphology and surface treatment of BAG are carefully designed to ensure its maximum bioactivity and remineralization potential in oral care products. The weight of BAG is 2.0-5.0wt% of the total weight of the mouthwash, preferably 3.0-4.0wt%. When the content of BAG is too low, it cannot react chemically quickly when in contact with body fluids, and cannot provide a platform for rapid response and ion release; when the content of BAG is too high, it will change the taste of the mouthwash, making it too viscous or granular, thereby reducing the experience of the mouthwash.

[0049] The chemical composition of BAG is precisely formulated to simulate the natural mineral composition of teeth. The main components of BAG and their weight percentage ranges are as follows: Silicate (SiO2): 45-55% of the total weight, preferably 48-52%, as the structural framework of BAG, providing the material with the necessary mechanical strength and chemical stability. Calcium (CaO): 20-30% of the total weight, preferably 22-28%, is one of the main components of tooth hydroxyapatite, and works together with phosphate to help form mineral deposits on the tooth surface. Phosphate (P 2 O 5): 5-15% of the total weight, preferably 7-13%, participates in the tooth remineralization process together with calcium and promotes the repair of tooth hard tissue. 2 O): 5-15% of the total weight, preferably 7-13%, helps regulate the dissolution rate of BAG in the oral environment, ensures the continuous release of ions, and improves the biocompatibility of the material. This specific chemical composition enables BAG to respond quickly in the oral environment and effectively release ions that are beneficial to teeth.

[0050] BAG is a spherical particle, wherein at least 50% of the particle size is between 0.1-10 μm, more preferably between 2-8 μm, and the average particle size is 3-20 μm; preferably 5-15 μm, more preferably 6-12 μm. Spherical particles can provide a larger contact area on the tooth surface due to their uniform geometric shape, which helps to increase the contact points between BAG and the tooth surface, thereby improving the transfer efficiency of remineralization ions. When the particle size and particle distribution are within the above range, it helps to evenly distribute BAG in the oral fluid environment and enhance its physical adsorption capacity on the tooth surface, making the attachment of BAG to the tooth surface more stable, prolonging its residence time in the oral cavity, and helping to control the release rate of ions. Its dispersion uniformity and particle size ensure that the bioactive glass will not cause adverse effects on the oral environment due to excessive local ion concentration when releasing beneficial ions.

[0051] Furthermore, by using aminosilane for surface amination treatment, the surface activity of BAG is enhanced through surface amination, and its compatibility with oral tissue is improved. This treatment gives the BAG surface a positive charge, which helps to adsorb bacteria and food residues in the mouth and enhance the cleaning effect of mouthwash. And the experiment unexpectedly showed that BAG with an amination surface can better promote the redeposition of CPP-ACP on the tooth surface. It is speculated that the possible reason is that the amination surface of BAG provides more adsorption sites, and the surface of BAG after aminosilane treatment has a positive charge, while the phosphate group in CPP-ACP has a negative charge. This mutual attraction between positive and negative charges can enhance the binding force between the two, thereby promoting their co-deposition on the tooth surface to form a more stable complex, which helps to form a uniform remineralization layer on the tooth surface. The relative content of surface amination can be measured by X-ray photoelectron spectroscopy (XPS) or Fourier transform infrared spectroscopy (FTIR). The degree of surface amination is determined by the relative ratio to the maximum surface amination. The relative content of surface amination is 30%-80%, preferably 40%-60%. When the surface amination is within this range, the cleaning effect and the binding with CPP-ACP can be balanced. If the degree of amination is too high, the BAG surface will be too active, the dissolution rate of BAG will be accelerated, which is not conducive to its binding with CPP-ACP and leads to reduced stability in the oral environment. If the degree of amination is too low, the significance of surface treatment cannot be reflected.

[0052] In order to ensure that the BAG particles are uniform in size and morphology, a ball milling process is used for preparation. For example, ball milling can be performed according to the following steps: first, the BAG raw material and the ball milling medium (such as ceramic balls, zirconia balls or stainless steel balls) are placed in a ball mill, and the ball-to-material ratio is controlled to be 10:1 to 30:1, and then the ball milling is performed at a speed of 60-100rpm for 1-8 hours to ensure that the raw materials are fully ground and mixed; during the ball milling process, the raw material particles are impacted and rubbed by the ball milling medium, and gradually reduced to the required size; after the ball milling is completed, the ball milling medium is separated from the BAG particles by screening or filtration, and the BAG particles are cleaned and dried to remove any residual impurities and fine powder; finally, the size distribution of the BAG particles is tested by laser particle size analysis and other technologies to ensure that it meets the specific particle size requirements and uniformity standards. This process ensures that the BAG particles meet the product requirements for particle size and distribution, and improves the stability and biological activity of BAG in mouthwash.

[0053] In the anti-caries mouthwash composition of the present invention, the surface treatment process of bioactive glass (BAG) is to enhance its compatibility with oral tissues and improve its remineralization efficiency. Specifically, BAG is first contacted with a 2-5wt% aqueous solution of aminosilane. This process is carried out at a temperature of 25-40°C and lasts for 20-60 minutes to ensure that the aminosilane can effectively adhere to the surface of BAG. Subsequently, the BAG particles treated with aminosilane are heat treated at a temperature of 60-100°C for 30-120 minutes. This step helps to cure the aminosilane layer and enhance its chemical bonding with the BAG surface. After heat treatment, the BAG particles are thoroughly washed with deionized water to remove all unreacted aminosilanes and possible by-products. Finally, the residual moisture on the surface of the particles is removed by drying to obtain BAG with an amino group-treated surface. This treatment not only enhances the surface activity of BAG, but also helps its stability and biological activity in mouthwash.

[0054] It should be noted that although both BAG and CPP-ACP have the function of providing phosphate and calcium ions, the role of BAG is mainly reflected in its ability to undergo rapid chemical reactions when in contact with body fluids, thus providing a platform for rapid response and ion release, while CPP-ACP provides a continuous ion supply and a stable remineralization environment, and can provide a long-lasting and stable release of calcium and phosphate ions. In addition, the presence of casein phosphopeptides is beneficial for transporting fluoride ions, calcium ions and phosphate ions to deep lesions, thereby promoting remineralization.

[0055] Since a slightly alkaline environment (pH value close to 7 or slightly higher than 7) can increase the concentration of calcium and phosphate ions in saliva, it is conducive to mineral deposition and thus promotes tooth remineralization, while an acidic environment (pH value lower than 5.5) will dissolve hydroxyapatite on the surface of teeth, resulting in mineral loss, thereby increasing the risk of tooth demineralization. Therefore, the pH value of the anti-caries mouthwash composition of the present invention is 7-7.5, and a pH stabilizer is used to maintain the pH value within the above range. The pH stabilizer is selected from one or more of sodium dihydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, citric acid, sodium citrate, sodium bicarbonate and sodium carbonate, among which disodium hydrogen phosphate is preferred.

[0056] The anti-caries mouthwash composition of the present invention may also include one or more of a stabilizer, a sweetener, a flavor, and an antibacterial agent. These additives may be common additives in the art, for example, the stabilizer is selected from one or more of hydroxypropyl methylcellulose (HPMC), hydroxyethyl cellulose (HEC), carbomer resin or sodium alginate; the sweetener is selected from one or more of xylitol, sorbitol, sucralose, aspartame or stevia extract; the flavor is selected from one or more of peppermint oil, tea tree oil, lemon oil or wintergreen oil; the antibacterial agent is selected from one or more of chlorhexidine, sodium benzoate, parabens or tea tree oil. The corresponding content is also the conventional content in the art. Based on actual needs, those skilled in the art can think of configuring the corresponding content when there is no obvious mutual interference between the formulas.

[0057] In another aspect of the present invention, a method for preparing an anti-caries mouthwash composition is provided. The method is not particularly special and mainly comprises mixing the respectively prepared active ingredients in sequence, and making up the balance with deionized water and a pH stabilizer and adjusting the pH to be within the range of 7-7.5. The preparation method specifically comprises the following steps:

[0058] Weigh sodium fluoride and dissolve it in deionized water to form a 100-900 ppm fluoride solution;

[0059] Weigh casein phosphopeptide-amorphous calcium phosphate, the weight of which is 2.0-8.0wt% of the total weight of the mouthwash;

[0060] Weigh the bioactive glass, the weight of which is 2.0-5.0 wt% of the total weight of the mouthwash. The chemical composition of the bioactive glass, by weight percentage, includes 45-55% SiO 2 , 20-30% CaO, 5-15% P 2 O 5 and 5-15% Na 2 O, and the bioactive glass is in the form of spherical particles, at least 50% of which have a particle size between 0.1 and 10 μm, and an average particle size between 3 and 20 μm;

[0061] The fluoride solution, casein phosphopeptide-amorphous calcium phosphate and bioactive glass are mixed, and a pH stabilizer and the remaining deionized water are added to adjust the total content to 100 wt % and the pH value to 7-7.5 to form an anti-caries mouthwash composition.

[0062] Optionally, in one of the solutions, before adding the pH stabilizer and the remaining deionized water, one or more of a stabilizer, a sweetener, a flavor, and an antibacterial agent are added in a weight ratio.

[0063] The invention also provides an application of the anti-caries mouthwash composition in oral care, wherein the composition is used twice a day, and 20-40 ml of the mouthwash is used for gargling each time for 20-40 seconds before spitting out.

[0064] 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.

[0065] 1. Preparation of Anti-caries Mouthwash Compositions in Examples and Comparative Examples

[0066] Example 1

[0067] Table 1 is the ingredient list of Example 1:

[0068]

[0069] The bioactive glass will first be produced according to the conventional melt quenching route according to the raw material ratio. It is melted in a platinum crucible at a temperature between 1400 and 1550°C. The resulting glass melt is quenched to room temperature by pouring directly into water to produce granular glass material, which is dried and then placed in a ball mill together with zirconium oxide balls. The ball-to-material ratio is controlled to 20:1, and the glass is ball-milled at a speed of 100 rpm for 2 hours and sieved.

[0070] Example 2

[0071] Table 2 is the ingredient list of Example 2:

[0072]

[0073] The bioactive glass will first be produced according to the conventional melt quenching route according to the raw material ratio. It is melted in a platinum crucible at a temperature between 1400 and 1550°C. The resulting glass melt is quenched to room temperature by pouring directly into water to produce granular glass material, which is dried and then placed in a ball mill together with zirconium oxide balls. The ball-to-material ratio is controlled at 20:1, and the ball milling is carried out at a speed of 100 rpm for 2 hours and sieved.

[0074] The screened bioactive glass was contacted with a 3 wt % aminosilane aqueous solution for 30 min at a temperature of 30° C. The temperature was then raised to 80° C. for 40 min of heat treatment and the glass was washed with deionized water to obtain a bioactive glass with a relative surface aminated content of 52.6%.

[0075] Example 3

[0076] Table 3 is the ingredient list of Example 3:

[0077]

[0078] The preparation of the bioactive glass was similar to that of Example 2. By adjusting the raw material ratio, ball-to-material ratio, rotation speed, and ball milling time, 52.2% of the particles were between 0.1 and 10 μm, and the average particle size was 14.3 μm. By controlling the concentration of the aminosilane aqueous solution, the contact time and temperature, and the heat treatment conditions, the relative content of surface amination of the bioactive glass was 31.1%.

[0079] Example 4

[0080] Table 4 is the ingredient list of Example 4:

[0081]

[0082]

[0083] The preparation of the bioactive glass is similar to that of Example 2. By adjusting the raw material ratio, ball-to-material ratio, rotation speed, and ball milling time, 96.5% of the particles are between 0.1 and 10 μm, and the average particle size is 7.4 μm. By controlling the concentration of the aminosilane aqueous solution, the contact time and temperature, and the heat treatment conditions, the relative content of surface amination of the bioactive glass is 78.6%.

[0084] Comparative Example 1

[0085] Compared with Example 2, sodium fluoride was not added, and the content of deionized water was adaptively adjusted to a total of 100 g of the anticaries mouthwash composition, and other conditions remained unchanged.

[0086] Comparative Example 2

[0087] Compared with Example 2, 0.15 g of sodium fluoride was added, and the content of deionized water was adaptively adjusted to a total of 100 g of the anti-caries mouthwash composition, and other conditions remained unchanged.

[0088] Comparative Example 3

[0089] Compared with Example 2, no CPP-ACP was added, and the content of deionized water was adaptively adjusted to a total amount of 100 g of the anticaries mouthwash composition, while other conditions remained unchanged.

[0090] Comparative Example 4

[0091] Compared with Example 2, no bioactive glass was added, and the content of deionized water was adaptively adjusted to a total of 100 g of the anticaries mouthwash composition, while other conditions remained unchanged.

[0092] Comparative Example 5

[0093] Compared with Example 2, the added bioactive glass components are: 60% SiO 2 、20%CaO、10%P 2 O 5 、10%Na 2 O, other conditions remain unchanged.

[0094] Comparative Example 6

[0095] Compared with Example 2, the calcium-phosphorus molar ratio of CPP-ACP is 1:1, and other conditions remain unchanged.

[0096] Comparative Example 7

[0097] Compared with Example 2, the calcium-phosphorus molar ratio of CPP-ACP is 1.5, and other conditions remain unchanged.

[0098] Comparative Example 8

[0099] Compared with Example 2, 23% of the particles of the bioactive glass are between 0.1 and 10 μm, with an average particle size of 21.5 μm, and other conditions remain unchanged.

[0100] Comparative Example 9

[0101] Compared with Example 2, 98% of the particles of the bioactive glass are between 0.1 and 10 μm, with an average particle size of 2.1 μm, and other conditions remain unchanged.

[0102] Comparative Example 10

[0103] Compared with Example 2, the pH stabilizer introduced was 0.5 g of sodium dihydrogen phosphate, the pH value was adjusted to 6.7, and other conditions remained unchanged.

[0104] 2. Tooth enamel caries prevention test

[0105] One hundred third molars freshly extracted (within 1 month) due to impaction or orthodontics in the oral and maxillofacial surgery clinic were collected (with ethical approval and patient consent). The inclusion criteria for the ex vivo teeth were: no caries, no cracks, no abnormal morphology and color, and no pigmentation on the tooth surface. The ex vivo teeth were placed in 75% alcohol by volume and stored at 4°C for later use.

[0106] Establishment of enamel demineralization model: a small enamel block (enamel thickness of about 1 mm, length and width of about 3-4 mm) was prepared by a low-speed cutter under running water cooling, and a large enamel block was prepared and embedded in resin. The enamel was polished to a mirror surface, ultrasonically rinsed, and rinsed with deionized water and stored in a refrigerator at 4°C for use. The enamel block was immersed in demineralization solution (acetic acid solution pH = 4.0) for 24 hours to obtain a demineralized in vitro tooth model.

[0107] The demineralized in vitro tooth model was immersed in 100 ml of the mouthwash composition samples of Examples 1-4 and Comparative Examples 1-10 for 1 minute and placed in air at room temperature for 5 hours. 4 Each enamel sample was immersed in water for 15 seconds to erode. The samples were then rinsed thoroughly with distilled water and stored in a humid environment for 24 hours to observe the development of caries. The results were quantitatively visualized through image display using the tooth autofluorescence effect through quantitative light-guided fluorescence technology (QLF), and the caries area of ​​each enamel sample was quantitatively calculated.

[0108] 3. In vitro simulated remineralization test

[0109] Experimental methods:

[0110] One hundred third molars freshly extracted (within 1 month) due to impaction or orthodontics in the oral and maxillofacial surgery clinic were collected (with ethical approval and patient consent). The inclusion criteria for the ex vivo teeth were: no caries, no cracks, no abnormal morphology and color, and no pigmentation on the tooth surface. The ex vivo teeth were placed in 75% alcohol by volume and stored at 4°C for later use.

[0111] Establishment of enamel demineralization model: a small enamel block (enamel thickness of about 1 mm, length and width of about 3-4 mm) was prepared by a low-speed cutter under running water cooling, and a large enamel block was prepared and embedded in resin. The enamel was polished to a mirror surface, ultrasonically rinsed, and rinsed with deionized water and stored in a refrigerator at 4°C for use. The enamel block was immersed in demineralization solution (acetic acid solution pH = 4.0) for 24 hours to obtain a demineralized in vitro tooth model.

[0112] The demineralized in vitro tooth models were immersed in 100 ml of mouthwash composition samples of Examples 1-4 and Comparative Examples 1-10, and taken out after 5 minutes, 10 minutes, 20 minutes, 30 minutes and 60 minutes, respectively, and the growth rate of remineralization in the thickness direction of the cross section was observed by SEM.

[0113] Table 5 shows the caries area and remineralization thickness at different times in the enamel anti-caries test and in vitro simulated remineralization test for Examples 1-4 and Comparative Examples 1-10.

[0114]

[0115]

[0116] It can be seen that Examples 1-4 satisfy the synergy of sodium fluoride, CPP-ACP and bioactive glass within a reasonable range, and it can be seen that the ideal degree can be achieved in inhibiting the occurrence of caries and forming the speed and thickness of the remineralization of the enamel surface. However, when no sodium fluoride is added to Comparative Example 1, caries are easily generated; if fluoride is excessive in Comparative Example 2, fluoride brings brown spots; Comparative Example 3 does not contain CPP-ACP in the components, not only caries are generated, but also stable remineralization cannot be achieved, and no remineralization occurs around the caries; and Comparative Example 4 does not contain bioactive glass and When the components of the bioactive glass in Comparative Example 5 are different from those in the present invention, the remineralization speed and thickness are insufficient; when the calcium-phosphorus molar ratio of CPP-ACP in Comparative Examples 6 and 7 is not within the range, the particle size of the bioactive glass in Comparative Examples 8 and 9 is not within the range, and when the pH of the composition in Comparative Example 10 is acidic, the caries prevention ability is reduced, and the remineralization speed and thickness are not good. This proves that only when the specific combination of sodium fluoride, CPP-ACP and bioactive glass in the present invention is met, can both caries prevention effect and remineralization effect be achieved under low fluoride concentration conditions.

[0117] 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 anti-caries mouthwash composition, characterized in that: The composition comprises active ingredients and deionized water, based on the total weight of the anti-caries mouthwash composition being 100%, the active ingredients include: Fluoride, 100-900 ppm; Casein phosphopeptide-amorphous calcium phosphate, 2.0-8.0wt%; Bioactive glass, 2.0-5.0wt%; The chemical composition of the bioactive glass includes, by weight percentage: 45-55% SiO2; 20-30% CaO; 5-15% P2O5; 5-15% Na2O; The bioactive glass is in the form of spherical particles, at least 50% of which have a particle size between 0.1 and 10 μm, and an average particle size between 3 and 20 μm.

2. The anti-caries mouthwash composition according to claim 1, characterized in that The bioactive glass is surface treated with aminosilane to make the surface of the bioactive glass aminated, and the relative content of the surface aminated is 30%-80%.

3. The anti-caries mouthwash composition according to claim 1, characterized in that The content of the fluoride is 200 ppm-500 ppm based on 100% of the total weight of the anti-caries mouthwash composition.

4. The anti-caries mouthwash composition according to claim 1, characterized in that The pH value of the anti-caries mouthwash composition is 7-7.5, and a pH stabilizer is used to maintain the pH value within the above range. The pH stabilizer is selected from one or more of sodium dihydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, citric acid, sodium citrate, sodium bicarbonate and sodium carbonate.

5. The anti-caries mouthwash composition according to claim 1, characterized in that The fluoride is selected from one or more of sodium fluoride, ammonium fluoride, strontium fluoride, barium fluoride and stannous fluoride.

6. The anti-caries mouthwash composition according to claim 1, characterized in that: The molar ratio of calcium to phosphate in the casein phosphopeptide-amorphous calcium phosphate is 1.1-1.

45.

7. The anti-caries mouthwash composition according to claim 1, characterized in that The anti-caries mouthwash composition may further include one or more of a stabilizer, a sweetener, a flavor, and an antibacterial agent; wherein the stabilizer is selected from one or more of hydroxypropyl methylcellulose (HPMC), hydroxyethyl cellulose (HEC), carbomer resin or sodium alginate; and / or The sweetener is selected from one or more of xylitol, sorbitol, sucralose, aspartame or stevia extract; and / or The fragrance is selected from one or more of peppermint oil, tea tree oil, lemon oil or wintergreen oil; and / or The antibacterial agent is selected from one or more of chlorhexidine, sodium benzoate, parabens or tea tree oil.

8. A method for preparing the anti-caries mouthwash composition according to claim 1, characterized in that: The following steps are involved: Weigh sodium fluoride and dissolve it in deionized water to form a 100-900 ppm fluoride solution; Weigh casein phosphopeptide-amorphous calcium phosphate, the weight of which is 2.0-8.0% of the total weight of the mouthwash; Weighing bioactive glass, the weight of which is 2.0-5.0% of the total weight of the mouthwash, the chemical composition of the bioactive glass, by weight percentage, includes 45-55% SiO2, 20-30% CaO, 5-15% P2O5 and 5-15% Na2O, and the bioactive glass is spherical particles, at least 50% of the particles have a size between 0.1-10 μm, and the average particle size is 3-20 μm; The fluoride solution, casein phosphopeptide-amorphous calcium phosphate and bioactive glass are mixed, and a pH stabilizer and the remaining deionized water are added to adjust the total content to 100 wt % and the pH value to 7-7.5 to form an anti-caries mouthwash composition.

9. The method for preparing the anti-caries mouthwash composition according to claim 8, characterized in that: The bioactive glass is subjected to a ball milling process and screening to obtain the particle size and average particle size, and the bioactive glass is subjected to a surface treatment, specifically comprising: The bioactive glass is contacted with a 2-5 wt % aminosilane aqueous solution for 20-60 min at a contact temperature of 25-40° C.; The contacted bioactive glass particles are then heated to 60-100° C. for a heat treatment of 30-120 minutes, and then washed with deionized water to remove unreacted aminosilane and by-products; and then dried to remove residual moisture to obtain surface-treated bioactive glass.

10. Use of the anti-caries mouthwash composition according to claim 1 in oral care, characterized in that Rinse your mouth with 20-40 ml of the anti-caries mouthwash twice a day for 20-40 seconds and then spit it out.

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