Night spray type anti-caries spray as well as preparation method and application thereof

Abstract

The invention relates to the technical field of oral care, in particular to a night spray type anti-caries spray as well as a preparation method and application of the night spray type anti-caries spray. 0.1%-0.3% of a grapefruit seed extract; 0.1 to 0.5 percent of sodium hyaluronate; 2-5% of xylitol; 0.02 to 0.05 percent of menthol; 0.05 to 0.12 percent of dipotassium glycyrrhizinate; 0.05 to 0.10 percent of potassium sorbate; through the synergistic effect of the sodium fluoride, the grapefruit seed extract and the xylitol, a three-dimensional protection system capable of promoting remineralization, resisting bacteria in a broad spectrum and specifically inhibiting deformation hammer balls is formed, and the anti-caries effect at night is remarkably improved.

Description

Technical Field

[0001] This invention relates to the field of oral care technology, specifically to a nighttime spray-type anti-caries spray, its preparation method, and its application, particularly suitable for nighttime oral care for wearers of invisible aligners and retainers. Background Technology

[0002] With the increasing popularity of invisible orthodontic technology, the number of people using invisible aligners and retainers is growing. However, during the wearing of invisible aligners and retainers, especially during sleep at night, the reduction in saliva secretion and the decrease in oral self-cleaning function, coupled with the microenvironment formed between the invisible aligners and teeth, makes it very easy for bacteria in the mouth to multiply rapidly, accelerate acid production, and cause problems such as tooth decay and tooth sensitivity.

[0003] Currently, oral care products on the market mainly include regular toothpaste and mouthwash, but these products are insufficient to meet the specific needs of wearers of invisible aligners. In the prior art, US Patent US20040136930A1 discloses an oral care composition containing grapefruit seed extract and fluoride, but this composition lacks a specific design for long-lasting nighttime protection; Chinese Patent CN112618413A discloses an oral care product containing hyaluronic acid, mainly for moisturizing the oral mucosa, without addressing its synergistic effect with fluoride or its nighttime anti-caries function; Chinese Patent CN101416926B discloses a grapefruit extract mouth spray and its preparation method, but only focuses on breath freshening function, without addressing anti-caries and special application scenarios for aligners.

[0004] Studies published by Pan PC et al. in Caries Res 2013 showed that grapefruit seed extract has significant anti-caries activity; studies published by Li X et al. in Oral Dis 2014 confirmed the synergistic remineralization effect of fluoride and calcium phosphate. However, no studies have yet integrated these ingredients into a spray formulation and systematically designed specifically for the nighttime protection needs of wearers of invisible aligners and retainers.

[0005] Therefore, there is an urgent need to develop an anti-caries spray specifically designed for wearers of nighttime invisible aligners and retainers, achieving multiple functions such as long-lasting caries prevention, antibacterial properties, and a comfortable experience. Summary of the Invention

[0006] The purpose of this invention is to overcome the shortcomings of the prior art and provide a nighttime spray-type anti-caries spray, its preparation method and application, which solves the special needs of nighttime oral care for wearers of invisible aligners and retainers through the synergistic effect of multiple active ingredients.

[0007] To achieve the above objectives, the present invention provides the following technical solution:

[0008] This nighttime spray-type anti-caries spray contains the following components by weight percentage: sodium fluoride 0.02-0.05%; grapefruit seed extract 0.1-0.3%; sodium hyaluronate 0.1-0.5%; xylitol 2-5%; menthol 0.02-0.05%; dipotassium glycyrrhizate 0.05-0.12%; potassium sorbate 0.05-0.10%; deionized water to bring the total to 100%.

[0009] Preferably, the sodium fluoride content is 0.024%, which is equivalent to 900-1000 ppm fluorine.

[0010] Preferably, the sodium hyaluronate has a molecular weight of 1.0-2.0 × 10⁻⁶. 6 Da is used to form a sustained-release framework, prolonging the release time of fluoride ions.

[0011] Preferably, the pH value of the spray is 6.8-7.2, and the spray has stable physical properties, without precipitation or stratification, when stored at 4°C for 12 months.

[0012] This invention also provides a method for preparing the above-mentioned night-use spray-type anti-caries spray, comprising the following steps:

[0013] (1) Add deionized water to the reaction vessel and heat to 40±2℃;

[0014] (2) Add sodium fluoride, dipotassium glycyrrhizate and potassium sorbate in sequence under stirring, and stir until completely dissolved;

[0015] (3) Dissolve sodium hyaluronate in a small amount of deionized water to make a sodium hyaluronate solution, and then slowly add it to the solution in step (2) and stir for 30-60 minutes;

[0016] (4) Add xylitol to the solution from step (3) and stir until completely dissolved;

[0017] (5) Dissolve grapefruit seed extract in food-grade ethanol to prepare a solution with a concentration of 5-10%, and then add it to the solution in step (4) and stir for 15-30 minutes.

[0018] (6) Dissolve menthol in a small amount of food-grade ethanol, add it to the solution in step (5), and stir well;

[0019] (7) Adjust the pH value to 6.8-7.2;

[0020] (8) Add deionized water to 100% of the total weight and stir well;

[0021] (9) Sterilization through 0.22μm microporous membrane filtration;

[0022] (10) Fill into sterile spray bottles to obtain the finished product.

[0023] Preferably, the concentration of the food-grade ethanol in step (5) is 75-95%, and the amount used is 5-10 times the weight of the grapefruit seed extract.

[0024] Preferably, in step (7), the pH value is adjusted using citric acid solution or sodium bicarbonate solution.

[0025] The present invention also provides a method for applying the above-mentioned night-use spray-type anti-caries spray, comprising the following steps:

[0026] (1) After brushing your teeth before bed, spray the night spray type anti-caries spray evenly 2-4 times on the inner surface of the invisible aligner or retainer in your mouth;

[0027] (2) Immediately after spraying, wear the invisible aligner or retainer in your mouth;

[0028] (3) Wear it all night and remove it to wash it the next morning.

[0029] Preferably, the invisible aligner or retainer is made of TPU or PU material.

[0030] Preferably, the night-use spray-type anti-caries spray is used to prevent tooth decay, promote enamel remineralization, inhibit the growth of oral flora at night, and extend the cleaning time of invisible aligners or retainers.

[0031] The beneficial effects of this invention include:

[0032] 1. Multiple Synergistic Protection: This invention utilizes the synergistic effect of sodium fluoride, grapefruit seed extract, and xylitol to form a three-dimensional protection system that "promotes remineralization + broad-spectrum antibacterial + specific inhibition of Streptococcus mutans", significantly improving the nighttime caries prevention effect.

[0033] 2. Long-lasting sustained-release design: Sodium hyaluronate and sodium fluoride form a unique sustained-release system. Through hydrogen bonding at the molecular level, a network sustained-release framework is constructed, extending the effective duration from the traditional 2-3 hours to the entire nighttime sleep cycle (6-8 hours).

[0034] 3. Excellent material compatibility: After rigorous testing and verification, the product is fully compatible with TPU / PU braces. After 7 days of testing, there was no color change, no softening, and the surface remained intact, ensuring long-term safe and reliable use.

[0035] 4. Innovative application scenarios: Designed specifically for nighttime braces wear, it adopts a unique usage method of "spraying into the inside of the braces before wearing" to form a closed, long-lasting sustained-release system to meet the needs of specific groups.

[0036] 5. Enhanced comfort: The addition of dipotassium glycyrrhizate as an anti-inflammatory ingredient, along with an appropriate amount of menthol, provides a cooling sensation without causing irritation, significantly improving the user experience. Detailed Implementation

[0037] The present invention will be further described in detail below with reference to specific embodiments, but the scope of protection of the present invention is not limited thereto. Unless otherwise stated, all percentages used herein are weight percentages.

[0038] Description of raw materials used in this invention:

[0039] Sodium fluoride, purity ≥99.0%;

[0040] Grapefruit seed extract, standard, containing ≥95.0% total flavonoids, Extrasynthese GmbH, Germany;

[0041] Sodium hyaluronate, molecular weight 1.5 × 10⁻⁶ 6 Da, purity ≥ 98.0%;

[0042] Xylitol, food grade, purity ≥99.0%;

[0043] Menthol, a natural extract, with a purity of ≥98.0%;

[0044] Dipotassium glycyrrhizate, standard, purity ≥98.0%;

[0045] Potassium sorbate, food grade, purity ≥99.0%;

[0046] Food-grade ethanol, 95%, analytical grade;

[0047] Deionized water, resistivity ≥18.2 MΩ·cm.

[0048] Example 1

[0049] This nighttime spray-type anti-caries spray contains the following components by weight percentage: sodium fluoride 0.02%; grapefruit seed extract 0.1%; sodium hyaluronate 0.1%; xylitol 2%; menthol 0.02%; dipotassium glycyrrhizate 0.05%; potassium sorbate 0.05%; deionized water to bring the total to 100%.

[0050] The preparation method includes the following steps:

[0051] (1) Add 450ml of deionized water to a 1L reactor and heat to 40℃;

[0052] (2) Add 0.2g sodium fluoride, 0.5g dipotassium glycyrrhizate and 0.5g potassium sorbate in sequence under stirring at 300rpm, and stir for 20 minutes until completely dissolved;

[0053] (3) Dissolve 1g of sodium hyaluronate in 50ml of deionized water to make a sodium hyaluronate solution, and then slowly add it to the solution in step (2) at a rate of 5ml / min and stir for 30 minutes.

[0054] (4) Add 20g xylitol to the solution in step (3) and stir for 15 minutes until completely dissolved;

[0055] (5) Dissolve 1g of grapefruit seed extract in 10ml of 75% food-grade ethanol to make a 10% solution, and then add it to the solution in step (4) and stir for 15 minutes.

[0056] (6) Dissolve 0.2g of menthol in 2ml of food-grade ethanol, add it to the solution in step (5), and stir for 10 minutes until homogeneous;

[0057] (7) Adjust the pH to 6.8 using 0.1 mol / L citric acid solution;

[0058] (8) Add deionized water to 1000g of total weight and stir for 5 minutes until homogeneous;

[0059] (9) Use a 0.22μm microporous membrane for filtration and sterilization;

[0060] (10) Fill into sterile spray bottles to obtain the finished product.

[0061] Example 2

[0062] This nighttime spray-type anti-caries spray contains the following components by weight percentage: sodium fluoride 0.05%; grapefruit seed extract 0.3%; sodium hyaluronate 0.5%; xylitol 5%; menthol 0.05%; dipotassium glycyrrhizate 0.12%; potassium sorbate 0.10%; deionized water to bring the total to 100%.

[0063] The preparation method includes the following steps:

[0064] (1) Add 400ml of deionized water to a 1L reactor and heat to 42℃;

[0065] (2) Add 0.5g sodium fluoride, 1.2g dipotassium glycyrrhizate and 1.0g potassium sorbate in sequence under stirring at 350rpm, and stir for 25 minutes until completely dissolved;

[0066] (3) Dissolve 5g of sodium hyaluronate in 100ml of deionized water to make a sodium hyaluronate solution, and then slowly add it to the solution in step (2) at a rate of 3ml / min and stir for 60 minutes.

[0067] (4) Add 50g xylitol to the solution in step (3) and stir for 20 minutes until completely dissolved;

[0068] (5) Dissolve 3g of grapefruit seed extract in 15ml of 95% food-grade ethanol to make a 20% solution, then add it to the solution in step (4) and stir for 30 minutes.

[0069] (6) Dissolve 0.5g of menthol in 5ml of food-grade ethanol, add it to the solution in step (5), and stir for 15 minutes until homogeneous;

[0070] (7) Adjust the pH to 7.2 using a 0.5 mol / L sodium bicarbonate solution;

[0071] (8) Add deionized water to 1000g of total weight and stir for 10 minutes until homogeneous;

[0072] (9) Use a 0.22μm microporous membrane for filtration and sterilization;

[0073] (10) Fill into sterile spray bottles to obtain the finished product.

[0074] Example 3

[0075] This nighttime spray-type anti-caries spray contains the following components by weight percentage: 0.024% sodium fluoride (approximately 900 ppm fluoride); 0.2% grapefruit seed extract; 0.3% sodium hyaluronate; 3.5% xylitol; 0.035% menthol; 0.08% dipotassium glycyrrhizate; 0.07% potassium sorbate; and deionized water to bring the total to 100%.

[0076] The preparation method includes the following steps:

[0077] (1) Add 430ml of deionized water to a 1L reactor and heat to 40±1℃;

[0078] (2) Add 0.24g sodium fluoride, 0.8g dipotassium glycyrrhizate and 0.7g potassium sorbate in sequence under stirring at 320rpm, and stir for 22 minutes until completely dissolved;

[0079] (3) Dissolve 3g of sodium hyaluronate in 70ml of deionized water to make a sodium hyaluronate solution, and then slowly add it to the solution in step (2) at a rate of 4ml / min and stir for 45 minutes.

[0080] (4) Add 35g xylitol to the solution in step (3) and stir for 18 minutes until completely dissolved;

[0081] (5) Dissolve 2g of grapefruit seed extract in 12ml of 85% food-grade ethanol to make a 16.7% solution, then add it to the solution in step (4) and stir for 20 minutes.

[0082] (6) Dissolve 0.35g of menthol in 3.5ml of food-grade ethanol, add it to the solution in step (5), and stir for 12 minutes until homogeneous;

[0083] (7) Adjust the pH to 7.0 using a 0.2 mol / L citric acid solution;

[0084] (8) Add deionized water to 1000g of total weight and stir for 8 minutes until homogeneous;

[0085] (9) Use a 0.22μm microporous membrane for filtration and sterilization;

[0086] (10) Fill into sterile spray bottles to obtain the finished product.

[0087] Example 4

[0088] This nighttime spray-type anti-caries spray contains the following components by weight percentage: sodium fluoride 0.035%; grapefruit seed extract 0.15%; sodium hyaluronate 0.2%; xylitol 4%; menthol 0.03%; dipotassium glycyrrhizate 0.1%; potassium sorbate 0.08%; deionized water to bring the total to 100%.

[0089] The preparation method includes the following steps:

[0090] (1) Add 420ml of deionized water to a 1L reactor and heat to 41℃;

[0091] (2) Add 0.35g sodium fluoride, 1.0g dipotassium glycyrrhizate and 0.8g potassium sorbate in sequence under stirring at 330rpm, and stir for 23 minutes until completely dissolved;

[0092] (3) Dissolve 2g of sodium hyaluronate in 60ml of deionized water to make a sodium hyaluronate solution, and then slowly add it to the solution in step (2) at a rate of 4.5ml / min and stir for 40 minutes.

[0093] (4) Add 40g xylitol to the solution in step (3) and stir for 16 minutes until completely dissolved;

[0094] (5) Dissolve 1.5g of grapefruit seed extract in 10ml of 80% food-grade ethanol to make a 15% solution, then add it to the solution in step (4) and stir for 25 minutes.

[0095] (6) Dissolve 0.3g of menthol in 3ml of food-grade ethanol, add it to the solution in step (5), and stir for 10 minutes until homogeneous;

[0096] (7) Adjust the pH to 7.1 using a 0.3 mol / L sodium bicarbonate solution;

[0097] (8) Add deionized water to 1000g of total weight and stir for 7 minutes until homogeneous;

[0098] (9) Use a 0.22μm microporous membrane for filtration and sterilization;

[0099] (10) Fill into sterile spray bottles to obtain the finished product.

[0100] Example 5

[0101] This nighttime spray-type anti-caries spray contains the following components by weight percentage: sodium fluoride 0.04%; grapefruit seed extract 0.25%; sodium hyaluronate 0.4%; xylitol 4.5%; menthol 0.04%; dipotassium glycyrrhizate 0.11%; potassium sorbate 0.09%; deionized water to bring the total to 100%.

[0102] The preparation method includes the following steps:

[0103] (1) Add 410ml of deionized water to a 1L reactor and heat to 40±2℃;

[0104] (2) Add 0.4g sodium fluoride, 1.1g dipotassium glycyrrhizate and 0.9g potassium sorbate in sequence under stirring at 340rpm, and stir for 24 minutes until completely dissolved;

[0105] (3) Dissolve 4g of sodium hyaluronate in 80ml of deionized water to make a sodium hyaluronate solution, and then slowly add it to the solution in step (2) at a rate of 4ml / min and stir for 55 minutes.

[0106] (4) Add 45g xylitol to the solution in step (3) and stir for 17 minutes until completely dissolved;

[0107] (5) Dissolve 2.5g of grapefruit seed extract in 15ml of 90% food-grade ethanol to make a 16.7% solution, then add it to the solution in step (4) and stir for 28 minutes.

[0108] (6) Dissolve 0.4g of menthol in 4ml of food-grade ethanol, add it to the solution in step (5), and stir for 13 minutes until homogeneous;

[0109] (7) Adjust the pH to 6.9 using 0.25 mol / L citric acid solution;

[0110] (8) Add deionized water to 1000g of total weight and stir for 9 minutes until homogeneous;

[0111] (9) Use a 0.22μm microporous membrane for filtration and sterilization;

[0112] (10) Fill into sterile spray bottles to obtain the finished product.

[0113] Comparative Example 1

[0114] The nighttime spray-type anti-caries spray comprises the following components by weight percentage: sodium fluoride 0.024%; grapefruit seed extract 0.2%; xylitol 3.5%; menthol 0.035%; dipotassium glycyrrhizate 0.08%; potassium sorbate 0.07%; and deionized water to 100%. Compared to Example 3, it does not contain sodium hyaluronate.

[0115] The preparation method is basically the same as in Example 3, but the step of adding sodium hyaluronate is omitted. Specifically, it includes the following steps:

[0116] (1) Add 500ml of deionized water to a 1L reactor and heat to 40±1℃;

[0117] (2) Add 0.24g sodium fluoride, 0.8g dipotassium glycyrrhizate and 0.7g potassium sorbate in sequence under stirring at 320rpm, and stir for 22 minutes until completely dissolved;

[0118] (3) Add 35g xylitol to the solution in step (2) and stir for 18 minutes until completely dissolved;

[0119] (4) Dissolve 2g of grapefruit seed extract in 12ml of 85% food-grade ethanol to make a 16.7% solution, then add it to the solution in step (3) and stir for 20 minutes.

[0120] (5) Dissolve 0.35g of menthol in 3.5ml of food-grade ethanol, add it to the solution in step (4), and stir for 12 minutes until homogeneous;

[0121] (6) Adjust the pH to 7.0 using a 0.2 mol / L citric acid solution;

[0122] (7) Add deionized water to 1000g of total weight and stir for 8 minutes until homogeneous;

[0123] (8) Use a 0.22μm microporous membrane for filtration and sterilization;

[0124] (9) Fill into sterile spray bottles to obtain the finished product.

[0125] Comparative Example 2

[0126] This nighttime spray-type anti-caries spray comprises the following components by weight percentage: sodium fluoride 0.024%; sodium hyaluronate 0.3%; xylitol 3.5%; menthol 0.035%; dipotassium glycyrrhizate 0.08%; sodium sorbate 0.07%; and deionized water to 100%. Compared to Example 3, it does not contain grapefruit seed extract.

[0127] The preparation method is basically the same as in Example 3, but the step of adding grapefruit seed extract is omitted. Specifically, it includes the following steps:

[0128] (1) Add 430ml of deionized water to a 1L reactor and heat to 40±1℃;

[0129] (2) Add 0.24g sodium fluoride, 0.8g dipotassium glycyrrhizate and 0.7g potassium sorbate in sequence under stirring at 320rpm, and stir for 22 minutes until completely dissolved;

[0130] (3) Dissolve 3g of sodium hyaluronate in 70ml of deionized water to make a sodium hyaluronate solution, and then slowly add it to the solution in step (2) at a rate of 4ml / min and stir for 45 minutes.

[0131] (4) Add 35g xylitol to the solution in step (3) and stir for 18 minutes until completely dissolved;

[0132] (5) Dissolve 0.35g of menthol in 3.5ml of food-grade ethanol, add it to the solution in step (4), and stir for 12 minutes until homogeneous;

[0133] (6) Adjust the pH to 7.0 using a 0.2 mol / L citric acid solution;

[0134] (7) Add deionized water to 1000g of total weight and stir for 8 minutes until homogeneous;

[0135] (8) Use a 0.22μm microporous membrane for filtration and sterilization;

[0136] (9) Fill into sterile spray bottles to obtain the finished product.

[0137] Comparative Example 3

[0138] The nighttime spray-type anti-caries spray comprises the following components by weight percentage: sodium fluoride 0.024%; grapefruit seed extract 0.2%; sodium hyaluronate 0.3%; xylitol 3.5%; menthol 0.035%; potassium sorbate 0.07%; and deionized water to 100%. Compared to Example 3, it does not contain dipotassium glycyrrhizate.

[0139] The preparation method is basically the same as in Example 3, but the addition step of dipotassium glycyrrhizate is omitted. Specifically, it includes the following steps:

[0140] (1) Add 430ml of deionized water to a 1L reactor and heat to 40±1℃;

[0141] (2) Add 0.24g sodium fluoride and 0.7g potassium sorbate sequentially under stirring at 320rpm, and stir for 22 minutes until completely dissolved;

[0142] (3) Dissolve 3g of sodium hyaluronate in 70ml of deionized water to make a sodium hyaluronate solution, and then slowly add it to the solution in step (2) at a rate of 4ml / min and stir for 45 minutes.

[0143] (4) Add 35g xylitol to the solution in step (3) and stir for 18 minutes until completely dissolved;

[0144] (5) Dissolve 2g of grapefruit seed extract in 12ml of 85% food-grade ethanol to make a 16.7% solution, then add it to the solution in step (4) and stir for 20 minutes.

[0145] (6) Dissolve 0.35g of menthol in 3.5ml of food-grade ethanol, add it to the solution in step (5), and stir for 12 minutes until homogeneous;

[0146] (7) Adjust the pH to 7.0 using a 0.2 mol / L citric acid solution;

[0147] (8) Add deionized water to 1000g of total weight and stir for 8 minutes until homogeneous;

[0148] (9) Use a 0.22μm microporous membrane for filtration and sterilization;

[0149] (10) Fill into sterile spray bottles to obtain the finished product.

[0150] Comparative Example 4

[0151] This nighttime spray-type anti-caries spray comprises the following components by weight percentage: 0.11% sodium fluoride (approximately 5000 ppm fluoride, equivalent to a conventional fluoride concentration); 3.5% xylitol; 0.035% menthol; 0.07% potassium sorbate; and deionized water to bring the total to 100%. Compared to Example 3, it is free of sodium hyaluronate, grapefruit seed extract, and dipotassium glycyrrhizate, and the sodium fluoride concentration is increased to a conventional level.

[0152] The preparation method includes the following steps:

[0153] (1) Add 500ml of deionized water to a 1L reactor and heat to 40±1℃;

[0154] (2) Add 1.1g sodium fluoride and 0.7g potassium sorbate sequentially under stirring at 320rpm, and stir for 25 minutes until completely dissolved;

[0155] (3) Add 35g xylitol to the solution in step (2) and stir for 18 minutes until completely dissolved;

[0156] (4) Dissolve 0.35g of menthol in 3.5ml of food-grade ethanol, add it to the solution in step (3), and stir for 12 minutes until homogeneous;

[0157] (5) Adjust the pH to 7.0 using a 0.2 mol / L citric acid solution;

[0158] (6) Add deionized water to 1000g of total weight and stir for 8 minutes until homogeneous;

[0159] (7) Use a 0.22μm microporous membrane for filtration and sterilization;

[0160] (8) Fill into sterile spray bottles to obtain the finished product.

[0161] Comparative Example 5

[0162] Commercially available fluoride mouthwash contains 0.05% sodium fluoride (approximately 1000 ppm fluoride), has no special sustained-release system, and is not a spray formulation.

[0163] To verify the technical effects of the present invention, the following tests were conducted on the above embodiments and comparative examples:

[0164] Test 1: Antibacterial and bacteriostatic experiment

[0165] Test method: The standard plate count method was used, with Streptococcus mutans as the indicator bacterium, to determine the antibacterial effect of each preparation. The specific steps were as follows: the activated bacterial solution was inoculated onto a solid culture medium to achieve a colony density of approximately 102. 6 CFU / ml bacterial suspension. Spread 0.1 ml of the bacterial suspension evenly in a petri dish, add 20 μl of the test sample, and incubate at 37℃ for 24 hours. Count the colonies and calculate the inhibition rate. Inhibition rate (%) = (number of colonies in the control group - number of colonies in the test group) / number of colonies in the control group × 100%. Repeat the test three times for each sample and take the average value.

[0166] The test results are shown in Table 1:

[0167] Table 1. Inhibition rate (%) of each sample against Streptococcus mutans

[0168] sample Antibacterial rate (%) Example 1 98.5 Example 2 99.7 Example 3 99.3 Example 4 99.1 Example 5 99.5 Comparative Example 1 97.2 Comparative Example 2 65.4 Comparative Example 3 98.8 Comparative Example 4 75.3 Comparative Example 5 68.9

[0169] Results Analysis: As shown in Table 1, Examples 1-5 all exhibited excellent antibacterial effects, with inhibition rates all above 98%. Comparative Example 1 (without sodium hyaluronate) showed a slightly lower antibacterial effect, but still maintained a high level. Comparative Example 2 (without grapefruit seed extract) showed a significantly lower inhibition rate, only 65.4%, indicating that grapefruit seed extract is the key component in the formulation that exerts a broad-spectrum antibacterial effect. Comparative Example 3 (without dipotassium glycyrrhizate) still showed a relatively high inhibition rate, indicating that dipotassium glycyrrhizate's main function is not antibacterial. Comparative Example 4 (high concentration of fluoride but lacking synergistic components) and Comparative Example 5 (commercially available product) both showed poor antibacterial effects, confirming the superiority of the multi-component synergistic antibacterial properties of this invention.

[0170] Test 2: Remineralization Experiment

[0171] Test Method: An in vitro artificial demineralization-remineralization model was used to evaluate the remineralization effect of each preparation. The specific steps were as follows: Fresh, healthy human third molars were selected and cut into enamel blocks of 6mm × 4mm × 2mm. After polishing with sandpaper, the blocks were treated with an acid etchant (pH 4.5 lactate buffer) for 24 hours to prepare initial demineralized samples. The samples were randomly divided into 12 groups and immersed in different test solutions at 37℃ for 14 days, with the solution changed daily. Subsequently, the microhardness value (VHN) of the enamel surface was measured using a microhardness tester. The hardness recovery rate (%) was calculated as: (hardness value after remineralization - hardness value after demineralization) / (hardness value of healthy enamel - hardness value after demineralization) × 100%. Each group of samples was tested 5 times, and the average value was taken.

[0172] The test results are shown in Table 2:

[0173] Table 2. Enamel remineralization effect of each sample

[0174] sample Hardness recovery rate (%) Duration of action (h) Example 1 19.5 5.2 Example 2 25.8 7.6 Example 3 23.7 6.8 Example 4 24.2 6.5 Example 5 25.1 7.2 Comparative Example 1 18.3 2.8 Comparative Example 2 17.9 6.4 Comparative Example 3 22.8 6.7 Comparative Example 4 21.5 2.5 Comparative Example 5 18.7 2.3

[0175] Results Analysis: As shown in Table 2, Examples 1-5 all exhibited good remineralization effects, with hardness recovery rates of 19.5%-25.8% and durations of action ranging from 5.2 to 7.6 hours, covering the entire nighttime sleep cycle. Comparative Example 1 (without sodium hyaluronate) showed some remineralization effect, but its duration of action was significantly shortened to 2.8 hours, confirming the key role of sodium hyaluronate in prolonging the sustained-release time of fluoride. Comparative Example 2 (without grapefruit seed extract) showed a slightly weaker remineralization effect; Comparative Example 4 (high concentration of fluoride but lacking synergistic components) showed a slightly better remineralization effect, but its duration of action was short; Comparative Example 5 (commercially available product) showed poor remineralization effect and duration of action. These results fully demonstrate the innovative design of the unique sustained-release system formed by sodium hyaluronate and sodium fluoride in this invention, which can significantly prolong the remineralization time.

[0176] Test 3: Material Compatibility Test

[0177] Test Method: Samples from Examples 1-5 and Comparative Examples 1-5 were uniformly sprayed onto standard TPU and PU clear aligner test pieces, respectively, and immersed in a simulated oral environment at 37°C for 7 days, with fresh samples replaced daily. Subsequently, surface changes were observed using an optical microscope, color difference ΔE was measured using a colorimeter, and the surface hardness change rate (%) was determined using a hardness tester: (hardness value after treatment - hardness value before treatment) / hardness value before treatment × 100%. Each group of samples was tested three times, and the average value was taken.

[0178] The test results are shown in Table 3:

[0179] Table 3. Compatibility of each sample with TPU / PU material

[0180] sample Color difference value ΔE Hardness change rate (%) Surface integrity score (1-5 points) Example 1 0.6 -1.2 5 Example 2 0.9 -1.8 4 Example 3 0.5 -1.5 5 Example 4 0.7 -1.4 5 Example 5 0.8 -1.6 4 Comparative Example 1 0.8 -1.7 4 Comparative Example 2 1.2 -2.3 4 Comparative Example 3 2.5 -3.8 3 Comparative Example 4 3.2 -5.6 2 Comparative Example 5 2.8 -4.2 3

[0181] Note: Surface integrity rating criteria: 5 points = no change at all; 4 points = slight change but does not affect use; 3 points = significant change but normal function; 2 points = significant change that may affect use; 1 point = severe change and unsuitable for use.

[0182] Results Analysis: Table 3 shows that Examples 1-5 exhibited excellent compatibility with TPU / PU materials, with color difference values ​​ΔE all less than 1.0, hardness change rates within -1.8%, and surface integrity scores of 4-5 points, indicating that long-term use of the products will not significantly affect the orthodontic appliance material. Comparative Examples 1-2 showed good compatibility; Comparative Example 3 (without dipotassium glycyrrhizate) showed slightly poorer compatibility, indicating that dipotassium glycyrrhizate plays an important role in reducing material irritation; Comparative Examples 4-5 showed poor compatibility, especially with large color difference values ​​and hardness change rates, which may lead to discoloration and softening of the orthodontic appliance with long-term use, affecting its service life and effectiveness.

[0183] Test 4: User Experience Evaluation

[0184] Testing Method: Thirty volunteers currently wearing invisible aligners or retainers were recruited and randomly divided into 10 groups of 3. Each group used samples from Examples 1-5 and Comparative Examples 1-5 for a 14-day practical use test. The method of use was as follows: after brushing teeth before bed, the test sample was evenly sprayed three times onto the inside of the aligner, which was then worn overnight. It was removed and cleaned the next morning. After the test, volunteers rated the product's convenience, smell, taste, comfort, and cleaning effect on a 10-point scale (1 point = very poor, 10 points = excellent).

[0185] The test results are shown in Table 4:

[0186] Table 4 User experience scores for each sample (out of 10)

[0187] sample convenience odor taste Comfort Cleaning effect Overall score Example 1 8.7 8.5 8.3 8.6 8.4 8.5 Example 2 8.8 9.1 8.7 8.2 9.2 8.8 Example 3 9.2 9 9.1 9.3 9 9.1 Example 4 8.9 8.8 8.6 9 8.8 8.8 Example 5 9 9.2 8.9 8.7 9.1 9 Comparative Example 1 8.8 8.7 8.4 8.5 8.2 8.5 Comparative Example 2 8.7 8.6 8.3 6.2 6.5 7.7 Comparative Example 3 8.6 8.5 7.2 5.4 8.3 7.6 Comparative Example 4 8.5 6.3 5.8 4.7 7.8 6.6 Comparative Example 5 7.2 7.5 7 6.8 7.3 7.2

[0188] Results Analysis: As shown in Table 4, Examples 1-5 all received high user experience scores, with overall scores ranging from 8.5 to 9.1. Example 3 performed best, achieving an overall score of 9.1. Comparative Example 1 (without sodium hyaluronate) showed slightly lower cleaning effectiveness; Comparative Example 2 (without grapefruit seed extract) scored lower in both comfort and cleaning effectiveness; Comparative Example 3 (without dipotassium glycyrrhizate) showed significantly lower scores in both taste and comfort, confirming the important role of dipotassium glycyrrhizate in improving oral comfort; Comparative Example 4 (high concentration of fluoride but lacking synergistic components) scored lower in odor, taste, and comfort; Comparative Example 5 (commercially available product) scored lower in all aspects, especially in convenience. These results indicate that the product formulation and usage of this invention have gained high user approval, particularly demonstrating significant advantages in comfort and cleaning effectiveness.

[0189] Based on the above test results, combined with molecular mechanisms and interaction principles, the core innovations and synergistic effects of this invention can be analyzed as follows:

[0190] 1. Synergistic sustained-release mechanism of sodium fluoride and sodium hyaluronate:

[0191] Sodium hyaluronate, as a high-molecular-weight polysaccharide, typically has a molecular weight of 1.0-2.0 × 10⁻⁶. 6 Between the Da and D molecules, the molecular chain contains a large number of carboxyl and hydroxyl groups, which can form hydrogen bonds with fluoride ions. At the molecular level, the linear molecular chain of sodium hyaluronate exhibits a meandering, random coil structure in aqueous solution. When it comes into contact with fluoride ions, it forms a loose complex through electrostatic interactions and hydrogen bonding. This complex forms a network-like slow-release framework on the tooth surface, allowing for the continuous and stable release of fluoride ions as the hyaluronic acid molecules slowly hydrolyze.

[0192] This synergistic effect of sodium hyaluronate and sodium fluoride explains the significantly shortened remineralization duration in Comparative Example 1 (without sodium hyaluronate). As shown in Test 2, the duration of action in Examples 1-5 reached 5.2-7.6 hours, while that in Comparative Example 1 was only 2.8 hours, fully demonstrating the key role of sodium hyaluronate in constructing the sustained-release system.

[0193] 2. The complementary protective mechanism of grapefruit seed extract and fluoride:

[0194] Grapefruit seed extract is rich in flavonoids (such as naringin and naringenin) and polyphenols, which possess broad-spectrum antibacterial activity. Its antibacterial mechanism primarily involves disrupting bacterial cell membrane structure, inhibiting the activity of key bacterial enzymes, and interfering with bacterial biofilm formation. Fluoride, on the other hand, exerts its anti-caries effect mainly through mechanisms such as promoting calcium phosphate deposition, inhibiting bacterial glycolysis, and reducing bacterial acid production.

[0195] The synergistic effect of the two forms a dual protective barrier of "reducing acid formation and enhancing acid resistance". The results of Test 1 show that the antibacterial rate of Comparative Example 2 (without grapefruit seed extract) is only 65.4%, which is far lower than the 98.5%-99.7% of Examples 1-5, confirming the key antibacterial role of grapefruit seed extract in the formulation.

[0196] 3. The anti-inflammatory and soothing effects of dipotassium glycyrrhizate:

[0197] Dipotassium glycyrrhizate is a natural sweetener that also possesses significant anti-inflammatory and mucosal protective effects. Its molecular structure contains a steroid nucleus and a glycoside moiety, enabling it to bind to specific receptors on cell membranes, inhibiting the synthesis and release of inflammatory mediators (such as prostaglandins and leukotrienes), and alleviating local inflammatory responses and irritation symptoms.

[0198] The results of Tests 3 and 4 showed that Comparative Example 3 (without dipotassium glycyrrhizate) performed significantly worse in terms of material compatibility and user comfort, particularly in terms of taste score (7.2 points) and comfort score (5.4 points), which were significantly lower than Example 3 (9.1 points and 9.3 points, respectively). This confirms the important role of dipotassium glycyrrhizate in improving product comfort, especially for patients with sensitive teeth or those experiencing tooth sensitivity in the early stages of orthodontic treatment.

[0199] 4. Synergistic effect mechanism of multiple components:

[0200] This invention, through the precise formulation and synergistic effect of multiple components, forms a unique three-dimensional protective system of "broad-spectrum antibacterial + sustained-release remineralization + soothing protection". This system exerts maximum effectiveness in the special oral environment during nighttime sleep: First, grapefruit seed extract and xylitol synergistically inhibit the growth of oral pathogens; second, sodium hyaluronate and sodium fluoride form a sustained-release system to continuously promote enamel remineralization; finally, dipotassium glycyrrhizate provides soothing protection, reducing discomfort during use.

[0201] Comparative Example 4 (high concentration of fluoride but lacking synergistic components) and Comparative Example 5 (commercially available product) performed poorly in all tests, especially in terms of duration of action and user experience. This fully demonstrates that simply increasing the concentration of fluoride cannot achieve the comprehensive protective effect of this invention. The synergistic effect of multiple components is the core innovation of this invention.

[0202] In summary, this invention, through the synergistic effect of precisely proportioned multi-component formulation, forms a highly effective anti-caries spray specifically designed for wearers of nighttime invisible aligners and retainers. It achieves multiple functions including long-lasting caries prevention, antibacterial properties, and a comfortable experience, filling a market gap and possessing significant innovative value and application prospects.

Claims

1. A nighttime spray-type anti-caries spray, characterized in that, The spray comprises the following components by weight percentage: Sodium fluoride 0.02-0.05%; Grapefruit seed extract 0.1-0.3%; Sodium hyaluronate 0.1-0.5%; Xylitol 2-5%; Menthol 0.02-0.05%; Dipotassium glycyrrhizate 0.05-0.12%; Potassium sorbate 0.05-0.10%; Add deionized water to bring the total to 100%.

2. The night-use spray-type anti-caries spray according to claim 1, characterized in that, The sodium fluoride content is 0.024%, which is equivalent to 900-1000 ppm fluorine.

3. The night-use spray-type anti-caries spray according to claim 1, characterized in that, The molecular weight of the sodium hyaluronate is 1.0-2.0 × 10⁻⁶. 6 Da is used to form a sustained-release framework, prolonging the release time of fluoride ions.

4. The night-use spray-type anti-caries spray according to claim 1, characterized in that, The spray has a pH value of 6.8-7.2, and its physical properties remain stable for 12 months when stored at 4°C, without precipitation or stratification.

5. The method for preparing a nighttime spray-type anti-caries spray as described in any one of claims 1-4, characterized in that, Includes the following steps: (1) Add deionized water to the reaction vessel and heat to 40±2℃; (2) Add sodium fluoride, dipotassium glycyrrhizate and potassium sorbate in sequence under stirring, and stir until completely dissolved; (3) Dissolve sodium hyaluronate in a small amount of deionized water to make a sodium hyaluronate solution, and then slowly add it to the solution in step (2) and stir for 30-60 minutes; (4) Add xylitol to the solution from step (3) and stir until completely dissolved; (5) Dissolve grapefruit seed extract in food-grade ethanol to prepare a solution with a concentration of 5-10%, and then add it to the solution in step (4) and stir for 15-30 minutes. (6) Dissolve menthol in a small amount of food-grade ethanol, add it to the solution in step (5), and stir well; (7) Adjust the pH value to 6.8-7.2; (8) Add deionized water to 100% of the total weight and stir well; (9) Sterilization through 0.22μm microporous membrane filtration; (10) Fill into sterile spray bottles to obtain the finished product.

6. The preparation method according to claim 5, characterized in that, The concentration of food-grade ethanol in step (5) is 75-95%, and the amount used is 5-10 times the weight of grapefruit seed extract.

7. The preparation method according to claim 5, characterized in that, In step (7), the pH value is adjusted using citric acid solution or sodium bicarbonate solution.

8. The method of applying the night-use spray-type anti-caries spray as described in any one of claims 1-4, characterized in that, Includes the following steps: (1) After brushing your teeth before bed, spray the night spray type anti-caries spray evenly 2-4 times on the inner surface of the invisible aligner or retainer in your mouth; (2) Immediately after spraying, wear the invisible aligner or retainer in your mouth; (3) Wear it all night and remove it to wash it the next morning.

9. The application method according to claim 8, characterized in that, The invisible orthodontic appliance or retainer is made of TPU or PU material.

10. The application method according to claim 8, characterized in that, The nighttime spray-type anti-caries spray is used to prevent tooth decay, promote enamel remineralization, inhibit the growth of oral flora at night, and extend the cleaning time of invisible aligners or retainers.