Buccal element as well as preparation method and application thereof

Abstract

The invention discloses a buccal element as well as a preparation method and application thereof, and belongs to the technical field of oral cleaning supplies. The method comprises the following steps: firstly, adding 2.8 to 3.5 parts of glacial acetic acid, 0.005 to 0.015 part of sodium benzoate, 0.005 to 0.015 part of sodium cyclamate, 0.08 to 0.12 part of lactic acid and 0.04 to 0.06 part of citric acid into 100 parts of water, and mixing to form acetic acid mother liquor; then, putting 3.7-4.6 parts of sodium bicarbonate and 0.08-0.12 part of calcium carbonate into a container, adding the acetic acid mother solution into the container, and stirring to form a mixed solution; adjusting the pH value of the mixed solution to 6.8-7.2, then sequentially adding 0.08-0.12 part by weight of lovastatin, 0.02-0.04 part by weight of peppermint water and 0.08-0.12 part by weight of a clove extracting solution, and uniformly stirring, so as to obtain the traditional Chinese medicine composition. The method disclosed by the invention is simple, and the prepared buccal essence is non-toxic and non-irritant, is high in decayed tooth inhibition rate and can quickly relieve decayed tooth pain and dentin hypersensitivity.

Description

Technical Field

[0001] This invention relates to a lozenge, its preparation method, and its application, belonging to the technical field of oral hygiene products. Background Technology

[0002] Dental diseases, especially dental caries, are a major health problem affecting populations worldwide. The World Health Organization lists dental caries as one of the three most important diseases to prevent and control after cardiovascular disease and cancer. Its high incidence and wide distribution pose a serious threat to people's oral health and quality of life. Therefore, choosing suitable oral hygiene products is crucial for preventing and repairing dental caries.

[0003] Traditional lozenge products are mostly designed based on the "anti-acid theory." Their core mechanism is to neutralize oral acidic substances by adding weak alkaline ingredients (such as sodium bicarbonate) to inhibit the metabolic activity of acid-producing bacteria, or to add fluorides (such as sodium fluoride) to form fluorapatite to enhance the acid resistance of enamel.

[0004] However, these products have significant limitations in practical use. They have limited effectiveness in preventing and treating dental caries, and they usually contain alcohol and other irritating ingredients that can irritate the oral mucosa. Summary of the Invention

[0005] To address the problems in the prior art, this invention provides a mouth lozenge, its preparation method, and its application. This invention prepares the mouth lozenge by first preparing an acetic acid mother liquor, then mixing the acetic acid mother liquor with sodium bicarbonate and calcium carbonate to form a mixed solution, adjusting the pH, and then adding the remaining components. This invention has a simple preparation method, and the prepared mouth lozenge is non-toxic and non-irritating, has a high caries inhibition rate, and can quickly relieve caries pain and dentin hypersensitivity.

[0006] To achieve the above technical objectives, the technical solution of the present invention is as follows: A method for preparing a lozenge includes the following steps: (1) Add 2.8-3.5 parts of glacial acetic acid, 0.005-0.015 parts of sodium benzoate, 0.005-0.015 parts of cyclamate, 0.08-0.12 parts of lactic acid and 0.04-0.06 parts of citric acid to 100 parts of water and mix to form acetic acid mother liquor; (2) Place 3.7-4.6 parts of sodium bicarbonate and 0.08-0.12 parts of calcium carbonate in a container, add the acetic acid mother liquor described in step (1) to the container, stir, and form a mixture; (3) Adjust the pH of the mixture in step (2) to 6.8-7.2, and then add 0.08-0.12 parts of Lobenqing, 0.02-0.04 parts of peppermint water and 0.08-0.12 parts of clove extract in sequence, and stir evenly; All the above quantities are by weight.

[0007] This application uses water, glacial acetic acid, sodium benzoate, cyclamate, lactic acid, citric acid, sodium bicarbonate, calcium carbonate, sorbitol, peppermint water, and clove extract in appropriate proportions as raw materials for the lozenge. The preparation method involves first pre-dissolving glacial acetic acid, sodium benzoate, cyclamate, lactic acid, and citric acid in water to prepare an acetic acid stock solution. Then, the acetic acid stock solution is mixed with sodium bicarbonate and calcium carbonate to form a mixed solution. After adjusting the pH, sorbitol, peppermint water, and clove extract are added. This preparation method is simple, and the prepared lozenge is non-toxic and non-irritating, containing a large amount of sodium acetate and an effective calcium source. This enhances the stability, antibacterial properties, and antistatic remineralization effect of the lozenge, thereby improving its effectiveness in preventing and treating dental caries.

[0008] Sodium benzoate, cyclamate, and citric acid in the raw materials of this application are prone to forming agglomerated particles in the solid state. The active ingredients in benzoate, peppermint water, and clove extract are unstable in excessively acidic or alkaline environments. If the raw materials are directly mixed to form a mixed liquid during the preparation of the lozenge, it is easy to cause uneven dispersion and local violent reactions. This will not only affect the batch-to-batch effect and taste of the lozenge, but also the localized heat concentration may destroy the stability of eugenol in sodium benzoate and clove extract and cause menthol in peppermint water to volatilize. Citric acid may also react locally with calcium carbonate to form calcium citrate precipitate, resulting in waste of calcium source. At the same time, local excessive acidity or alkalinity is likely to occur, thereby destroying the stability of the active ingredients in benzoate, peppermint water, and clove extract. This application first pre-dissolves glacial acetic acid, sodium benzoate, cyclamate, lactic acid, and citric acid in water to prepare an acetic acid stock solution. This not only transforms the solid components into a molecularly uniformly dispersed solution but also reduces the concentration gradient between the acid and alkali and dilutes the strength of the acid solution. When it is subsequently mixed with sodium bicarbonate and calcium carbonate to form a mixed solution, the regional component concentration is more uniform, and the reaction between components is milder, avoiding side reactions and ensuring the efficiency of effective calcium source generation. Secondly, adjusting the pH before adding sorbitol, peppermint water, and clove extract provides a stable environment for the effective components in sorbitol, peppermint water, and clove extract, preventing the decomposition of the effective components in sorbitol, peppermint water, and clove extract and the volatilization of menthol. This helps to ensure the content of other effective components in the oral lozenge and allows it to be directly adapted to the oral physiological environment without the need for secondary pH adjustment.

[0009] Preferably, the weight ratio of glacial acetic acid, lactic acid, citric acid, sodium bicarbonate, and calcium carbonate is 3:0.1:0.05:(4.0-4.15):0.1.

[0010] This application designs the ratio of organic acids (glacial acetic acid, citric acid, lactic acid) to sodium bicarbonate and calcium carbonate to prepare a mouthwash with better stability, antistatic remineralization effect and antibacterial properties. Moreover, this design ratio can make the mixture in step (2) naturally present a weak acidity (pH≤7), which fundamentally avoids the risks of calcium carbonate residue and pH change that may occur in the "alkali first and acid later" adjustment. It is beneficial to increase the effective calcium source content in the mouthwash and maintain the stability of the system and more accurately control the pH of the mixture. In addition, it can reduce the amount of sodium bicarbonate used for subsequent pH adjustment, which is beneficial to reduce the difficulty of pH adjustment of the mixture and avoid large pH fluctuations. It is also beneficial to prevent calcium ion precipitation caused by local over-alkali.

[0011] More preferably, the weight ratio of glacial acetic acid, lactic acid, citric acid, sodium bicarbonate, and calcium carbonate is 3:0.1:0.05:4.0:0.1.

[0012] More preferably, the weight ratio of water, glacial acetic acid, sodium benzoate, cyclamate, sorbitol, peppermint water, and clove extract is 100:3:0.01:0.01:0.1:0.03:0.1. The inventors also discovered in their research that when 3 parts by weight of glacial acetic acid, 0.01 parts by weight of sodium benzoate, 0.01 parts by weight of cyclamate, 0.1 parts by weight of lactic acid, and 0.05 parts by weight of citric acid are pre-dissolved in 100 parts by weight of water to prepare an acetic acid stock solution, and then the acetic acid stock solution is mixed with 4 parts by weight of sodium bicarbonate and 0.1 parts by weight of calcium carbonate to form a mixed solution, and the pH is adjusted to 7, and then 0.1 parts by weight of lopinaquinone, 0.03 parts by weight of peppermint water, and 0.1 parts by weight of clove extract are added to prepare a lozenge, the raw material calcium carbonate is almost completely converted into an effective calcium source in the lozenge. The calcium source utilization rate is high, and the effective calcium source in the lozenge mainly exists in the form of calcium acetate and citric acid chelated calcium. The synergistic effect of calcium acetate and citric acid chelated calcium can achieve rapid replenishment and continuous release of calcium ions, which is beneficial to optimizing the stability, antibacterial properties, antistatic remineralization effect, and clinical anti-caries effect of the lozenge.

[0013] Preferably, the effective concentration of benzalkonium chloride in the lobenqing is 1.7 g / L-2.1 g / L, the mass percentage of menthol in the peppermint water is 0.05%-0.2%, and the mass percentage of eugenol in the clove extract is 1%-5%.

[0014] Preferably, in step (3), the pH of the mixture is adjusted to 7. Adjusting the pH of the mixture to 7 can provide a more stable environment for the excipients Lobenzin, peppermint water and clove extract, and is more compatible with the oral physiological environment, which is beneficial to reducing discomfort in sensitive people.

[0015] Preferably, before adjusting the pH of the mixture, it should be allowed to stand until no more bubbles are produced. Sodium bicarbonate, calcium carbonate, and acetic acid mother liquor undergo a chemical reaction. During the reaction, the pH of the mixture changes dynamically. If intervention occurs midway, such as adding alkali to adjust the pH, the premature introduction of alkali will neutralize unreacted acetic acid, reducing the concentration of acetic acid in the reaction solution. This affects the reaction between acetic acid and calcium carbonate, thus reducing the amount of calcium acetate produced. Simultaneously, it may cause the pH at the point of addition to be too high, causing the already formed calcium acetate to reprecipitate, reducing the effective calcium source content, and ultimately affecting the oral cavity's effectiveness in preventing and treating dental caries. This application, by allowing the mixture to stand until no more bubbles are produced before adjusting the pH, ensures that sodium bicarbonate, calcium carbonate, and acetic acid mother liquor react completely and fully, which helps to increase the effective calcium source content and avoids waste of calcium source materials.

[0016] Preferably, adjusting the pH of the mixture specifically includes the following steps: testing the pH value of the mixture; if the pH is less than the target range, an appropriate amount of alkaline pH adjuster needs to be added until the pH of the mixture reaches the target range; if the pH is within the target range, no further action is required.

[0017] More preferably, the alkaline pH adjuster is sodium bicarbonate. Compared to other alkaline pH adjusters such as sodium carbonate, sodium bicarbonate is mild and non-irritating, and it can slowly release OH- in solution. - It can accurately and stably control the pH of the mixture within the target range, and can also avoid side reactions caused by local over-alkalinity. In addition, sodium bicarbonate is compatible with Lobenzin and peppermint water.

[0018] A mouthwash prepared using the above-described method.

[0019] An application of a mouth lozenge prepared using the above method in the prevention and treatment of dental caries.

[0020] Preferably, the steps for using the oral lozenge include: 2-3 times daily, holding 5ml in the mouth for 30 seconds to 2 minutes each time and then spitting it out. Detailed Implementation

[0021] Traditional oral lozenges are mostly designed based on the "acid-resistant theory." Their core mechanism involves adding weakly alkaline ingredients (such as sodium bicarbonate) to neutralize acidic substances in the mouth and inhibit the metabolic activity of acid-producing bacteria, or adding fluorides (such as sodium fluoride) to form fluorapatite to enhance the acid resistance of enamel. However, these products have significant limitations in practical use. Their effectiveness in preventing and treating dental caries is limited, and they usually contain alcohol and other irritating ingredients that can irritate the oral mucosa.

[0022] In the bioelectrochemical theory of dental caries, superoxide anion free radicals (O2) produced by cariogenic bacteria in dental plaque in the carious lesion area... - This will trigger a redox reaction, leading to a local electron imbalance, O2- Carrying a negative charge, it creates a negative potential region on the enamel surface, attracting positively charged cariogenic bacteria and acidic substances (such as H+). + These molecules aggregate to form a "bioelectric circuit." This current accelerates the dissolution of hydroxyapatite (the main component of tooth enamel).

[0023] Based on this, this application aims to design a novel anti-caries oral lozenge to improve the early caries inhibition rate and alleviate caries pain and dentin hypersensitivity symptoms caused by caries progression. The inventors discovered in their research that when water, glacial acetic acid, sodium benzoate, cyclamate, lactic acid, citric acid, sodium bicarbonate, calcium carbonate, sorbitol, peppermint water, and clove extract are selected as raw materials to prepare the oral lozenge, different preparation processes and raw material ratios, especially the ratio of organic acids (glacial acetic acid, citric acid, lactic acid) to sodium bicarbonate and calcium carbonate, result in significant differences in the form and content of the effective components, particularly the effective calcium source, in the oral lozenge. This will have different effects on the stability, charge neutralization efficiency, remineralization performance, and antibacterial properties of the oral lozenge, thereby affecting its clinical anti-caries effect.

[0024] Through extensive research, the inventors discovered that when appropriate proportions of water, glacial acetic acid, sodium benzoate, cyclamate, lactic acid, citric acid, sodium bicarbonate, calcium carbonate, sorbitol, peppermint water, and clove extract are used as raw materials for the lozenge and a suitable preparation process is employed, the resulting lozenge is non-toxic and non-irritating, and contains a large amount of sodium acetate and an effective calcium source. The sodium acetate and effective calcium source release acetate ions and a large number of cations (Na+). + / Ca 2+ Acetate ions can penetrate dental plaque biofilm, interfere with bacterial metabolism, and reduce oxygen anion free radicals (O2). - The generation of ) and the release of cations (Na) + / Ca 2+ It can react with O2 on the surface of tooth enamel. - It combines with and neutralizes negative charges, blocking the free electron oxidation and corrosion reaction that leads to tooth decay, and effectively dissociates the calcium source into Ca. 2+ It can remineralize in the demineralized areas of tooth enamel to form a dense mineralized protective film, which is beneficial to improve the stability, antibacterial properties, and antistatic remineralization effect of oral saliva, thereby improving the early caries inhibition rate and alleviating caries pain and dentin hypersensitivity symptoms caused by caries progression.

[0025] The inventors also discovered in their research that when 3 parts by weight of glacial acetic acid, 0.01 parts by weight of sodium benzoate, 0.01 parts by weight of cyclamate, 0.1 parts by weight of lactic acid, and 0.05 parts by weight of citric acid are pre-dissolved in 100 parts by weight of water to prepare an acetic acid mother liquor, and then this mother liquor is mixed with 4 parts by weight of sodium bicarbonate and 0.1 parts by weight of calcium carbonate to form a mixed solution, and the pH is adjusted to 7, 0.1 parts by weight of sorbitol, 0.03 parts by weight of peppermint water, and 0.1 parts by weight of clove extract are added to prepare the lozenge, the original... Almost all of the calcium carbonate in the oral lozenge is converted into an effective calcium source, resulting in high calcium utilization. The effective calcium source in the oral lozenge mainly exists in the form of calcium acetate and citrate chelated calcium. The synergistic effect of calcium acetate and citrate chelated calcium can achieve rapid replenishment and continuous release of calcium ions, which is beneficial to optimizing the stability, antibacterial properties, antistatic remineralization effect, and clinical caries prevention effect of the oral lozenge. The early caries inhibition rate of this oral lozenge reaches 90%, and it can quickly relieve caries pain and dentin hypersensitivity symptoms caused by caries progression, with effects seen on the same day.

[0026] The features of the present invention will be further illustrated below with reference to specific embodiments, but this does not limit the scope of the claims of the present invention in any way.

[0027] All raw materials involved in the embodiments of this application are commercially available. Among them, Luobenqing is from Lost Pharmaceutical Co., Ltd. in Shantou Free Trade Zone. The measured concentration of benzalkonium chloride, the active ingredient in Luobenqing, is 2g / L. The peppermint water is from Zhongxiang Natural Plants. The measured content (mass percentage) of menthol in the peppermint water is 0.1%. The clove extract is from Meiyi Biotechnology. The measured content (mass percentage) of eugenol in the clove extract is 1%.

[0028] Example 1 This embodiment provides a lozenge, which is prepared according to the following steps: Add 3 kg of glacial acetic acid, 10 g of sodium benzoate, 10 g of cyclamate, 100 g of lactic acid, and 50 g of citric acid to 100 kg of water to form an acetic acid mother liquor. Place 4.0 kg of sodium bicarbonate and 100 g of calcium carbonate in a container, and slowly add the above acetic acid mother liquor to the container, stirring until well mixed to form a mixture. Let the mixture stand until no more bubbles are produced, and test the pH value of the mixture. If the pH is less than 7, add sodium bicarbonate until the pH of the mixture is 7. Then, add 100 g of sorbitol, 30 g of peppermint water, and 100 g of clove extract in sequence, stir well, let stand, and filter.

[0029] In this embodiment, the oral occlusive solution becomes clear and transparent after standing.

[0030] Example 2 This embodiment provides a lozenge, which is prepared according to the following steps: Add 3 kg of glacial acetic acid, 10 g of sodium benzoate, 10 g of cyclamate, 100 g of lactic acid, and 50 g of citric acid to 100 kg of water to form an acetic acid mother liquor. Place 4.1 kg of sodium bicarbonate and 100 g of calcium carbonate in a container, and slowly add the above acetic acid mother liquor to the container, stirring until well mixed to form a mixture. Let the mixture stand until no more bubbles are produced, and test the pH value of the mixture. If the pH is less than 7, add sodium bicarbonate until the pH of the mixture is 7. Then, add 100 g of sorbitol, 30 g of peppermint water, and 100 g of clove extract in sequence, stir well, let stand, and filter.

[0031] In this embodiment, the oral antagonist solution became slightly turbid after standing.

[0032] Example 3 This embodiment provides a lozenge, which is prepared according to the following steps: Add 3 kg of glacial acetic acid, 10 g of sodium benzoate, 10 g of cyclamate, 100 g of lactic acid, and 50 g of citric acid to 100 kg of water to form an acetic acid mother liquor. Place 4.15 kg of sodium bicarbonate and 100 g of calcium carbonate in a container, and slowly add the above acetic acid mother liquor to the container, stirring until well mixed to form a mixture. Let the mixture stand until no more bubbles are produced, and test the pH value of the mixture. If the pH is less than 7, add sodium bicarbonate until the pH of the mixture is 7. Then, add 100 g of sorbitol, 30 g of peppermint water, and 100 g of clove extract in sequence, stir well, let stand, and filter.

[0033] In this embodiment, the oral antagonist solution became turbid after standing.

[0034] Example 4 This embodiment provides a lozenge, which is prepared according to the following steps: Add 2.8 kg of glacial acetic acid, 5 g of sodium benzoate, 5 g of cyclamate, 90 g of lactic acid, and 45 g of citric acid to 100 kg of water to form an acetic acid mother liquor. Place 3.7 kg of sodium bicarbonate and 90 g of calcium carbonate in a container, and slowly add the above acetic acid mother liquor to the container, stirring until well mixed to form a mixture. Let the mixture stand until no more bubbles are produced, adjust the pH of the mixture to 7, and then add 80 g of sorbitol, 20 g of peppermint water, and 80 g of clove extract, stirring until well mixed, letting stand, and filtering.

[0035] Example 5 This embodiment provides a lozenge, which is prepared according to the following steps: Add 3.2 kg of glacial acetic acid, 15 g of sodium benzoate, 10 g of cyclamate, 110 g of lactic acid, and 55 g of citric acid to 100 kg of water to form an acetic acid mother liquor. Place 4.6 kg of sodium bicarbonate and 90 g of calcium carbonate in a container, and slowly add the above acetic acid mother liquor to the container, stirring until well mixed to form a mixture. Let the mixture stand until no more bubbles are produced, adjust the pH of the mixture to 7, and then add 120 g of sorbitol, 40 g of peppermint water, and 120 g of clove extract, stirring until well mixed, letting stand, and filtering.

[0036] Comparative Example 1 This comparative example provides a lozenge prepared according to the following steps: Add 3 kg of glacial acetic acid, 10 g of sodium benzoate, 10 g of cyclamate, 100 g of lactic acid, and 50 g of citric acid to 100 kg of water to form an acetic acid mother liquor. Place 4.2 kg of sodium bicarbonate and 100 g of calcium carbonate in a container, and slowly add the above acetic acid mother liquor to the container, stirring until well mixed to form a mixture. Let the mixture stand until no more bubbles are produced, adjust the pH of the mixture to 7, and then add 100 g of sorbitol, 30 g of peppermint water, and 100 g of clove extract in sequence, stirring until well mixed, letting stand, and filtering.

[0037] In this comparative example, the oral content of the oral content showed a precipitate at the bottom of the solution after standing.

[0038] Comparative Example 2 This comparative example provides a lozenge prepared according to the following steps: Add 3 kg of alginic acid, 10 g of sodium benzoate, 10 g of cyclamate, 100 g of lactic acid, and 50 g of citric acid to 100 kg of water to form an acetic acid mother liquor. Place 4.0 kg of sodium bicarbonate and 100 g of calcium carbonate in a container, and slowly add the above acetic acid mother liquor to the container, stirring until well mixed to form a mixture. Let the mixture stand until no more bubbles are produced, adjust the pH of the mixture to 7, and then add 100 g of sorbitol, 30 g of peppermint water, and 100 g of clove extract in sequence, stirring until well mixed, letting stand, and filtering.

[0039] In this comparative example, the oral content of the oral content showed a precipitate at the bottom of the solution after standing.

[0040] Comparative Example 3 This comparative example provides a mouthwash, which is Colgate Fluoride Mouthwash (Icy Mint Flavor).

[0041] Test case 1. Stability test Take 100ml of the oral lozenges prepared in Examples 1-3 and Comparative Examples 1-2, bottle them, seal them, and use them as samples for the cold and hot cycle stability test. Place each sample in a -5℃ environment for 24 hours and then transfer it to a 40℃ environment for 24 hours (one cycle). Perform 5 cycles. After the cycle, observe the stratification and precipitation of the samples, detect the pH value, calcium ion concentration, and benzalkonium chloride content of the samples, and calculate the pH value change (△pH = detected value - initial value, the same below), calcium ion retention rate (= calcium ion concentration at detection / initial calcium ion concentration × 100%, the same below), and benzalkonium chloride retention rate (= benzalkonium chloride concentration at detection / initial benzalkonium chloride concentration × 100%, the same below). The results are shown in Table 1 below.

[0042] 100 ml of the oral lozenges prepared in Examples 1-3 and Comparative Examples 1-2 were bottled and sealed as samples for long-term storage stability test. Each sample was stored in an environment of 25℃±2℃ and relative humidity of 60%±5% for 12 months. The pH value, calcium ion concentration and benzalkonium chloride content of the samples were measured at 0 days, 6 months and 12 months, and the sample ΔpH, calcium ion retention rate and benzalkonium chloride retention rate were calculated. The results are shown in Table 2 below.

[0043] In the tests conducted in this application, the pH value of the samples was determined according to standard QB / T 2945-2012 (measurement temperature was 25℃±2℃, stirring speed was 100-200r / min), the calcium ion concentration was determined according to GB 5009.92-2016, and 10g / L lanthanum nitrate solution was used as the release agent for detection. The benzalkonium chloride content was determined according to QB / T 5452-2019, and the chromatographic column was C18 (250mm×4.6mm, 5μm) for detection.

[0044] Table 1 Results of thermal cycling stability test

[0045] Table 2 Long-term storage stability test results

[0046] As shown in the table above, the stability of the oral lozenge prepared in Example 1 is higher than that in Comparative Example 1. The reason for this difference may be that the effective calcium source in oral lozenge 1 is different from that in Comparative Example 1. The effective calcium source in oral lozenge 1 is mainly in the form of calcium acetate and citrate chelated calcium, which has a significant advantage in low-temperature solubility. Moreover, the cyclic structure of citrate chelated calcium can also hinder calcium-acid complexation, thus facilitating long-term storage. In addition, the oral lozenge contains a high-concentration sodium acetate-calcium acetate buffer system, which has a strong temperature buffering capacity, which helps to minimize pH fluctuations and protect the effective components in Lobenqing. In contrast, the effective calcium source in oral lozenge prepared in Comparative Example 1 is mainly in the form of calcium lactate. Calcium lactate is easily precipitated at low temperatures, resulting in a significant decrease in calcium ion retention. Furthermore, the single sodium acetate buffer in this oral lozenge is prone to alkalinity shift due to acetic acid volatilization during temperature cycling and long-term storage. This alkalinity shift will accelerate the deactivation of the effective components in Lobenqing. Comparative Example 2 showed the worst stability of the oral content, possibly because the sodium alginate in it undergoes conformational changes during thermal cycling and long-term storage, forming a cross-linked network. This causes calcium ions to be encapsulated in the gel network and difficult to release. Furthermore, the oral content lacks an effective buffer system. Sodium alginate produces free acid at high temperatures and generates additional organic acids as a carbon source during long-term storage under microbial metabolism. All of these factors contribute to a significant decrease in pH, thereby promoting the hydrolysis of the active ingredients in Lobenqing.

[0047] 2. Charge neutralization efficiency test: The oral fillers provided in Examples 1-3 and Comparative Examples 1-2 were used as test samples, and physiological saline was used as a blank sample to conduct charge neutralization efficiency performance tests. All samples were tested under the same conditions. Fresh bovine tooth enamel from the same batch was ground into powder with an average particle size of 10-50 μm. The enamel powder was dispersed in 10 mL of artificial saliva (pH=7, formulation according to ISO / TR 10271, with 20 mM HEPES buffer added), and ultrasonically dispersed for 15 minutes to prepare a stable suspension. 1 mL of the oral filler sample to be tested was added to 10 mL of the above suspension and ultrasonically mixed for 2 minutes. Using a Malvern Zetasizer Nano ZS nanometer, electrophoretic light scattering (ELS) was employed, following ISO 26824:2013 standard, to measure the change in Zeta potential over 0-30 minutes at 37°C. The potential was measured again after 24 hours. The charge neutralization rate k and the 24-hour stability Δζ were calculated. The charge neutralization rate k was calculated using the formula: k = ( g 15 - g 0 ) / 15min, ζ0: initial Zeta potential (0min), ζ 15The Zeta potential at the 15th minute is calculated as follows: Δζ = (24-hour potential - initial potential) / initial potential. The results are shown in the table below.

[0048]

[0049] As shown in the table above, the charge neutralization efficiency of the oral lozenges prepared in Examples 1-3 is good. Among them, Example 1 has the highest charge neutralization efficiency. This may be because the sodium acetate, effective calcium source calcium acetate, and citrate chelated calcium in the oral lozenge of Example 1 can work synergistically. Sodium acetate and calcium acetate dominate the initial neutralization, and a large number of cations (Na+, Na+, and calcium acetate) are released in a short time. + / Ca 2 + The rapid reduction of the zeta potential, followed by the continuous dissociation of calcium citrate chelate to replenish calcium ions, effectively inhibits the decline of the zeta potential. Therefore, its charge neutralization rate and 24-hour stability are the best. The table above also shows that the charge neutralization efficiency of Comparative Example 1 and Comparative Example 2 oral contents is much lower than that of Example 1. This may be because, although Comparative Example 1 oral contents contain sodium acetate, the actual concentration of calcium ions dissociated from its effective calcium source is low, and there is no chelated calcium to provide additional calcium ion replenishment. Therefore, its charge neutralization efficiency is significantly lower than that of Example 1. Comparative Example 2 oral contents mainly rely on sodium alginate in artificial saliva... + -Ca 2+ It exchanges and releases calcium ions, but the concentration of calcium ions is extremely low, so its charge neutralization efficiency is the worst.

[0050] 3. Remineralization performance test: The oral nasal extracts provided in Examples 1-3 and Comparative Examples 1-2 were used as test samples, and physiological saline was used as blank samples. The remineralization performance test was carried out in accordance with ISO 28399:2021 and ISO 14577:2015. All samples were tested under the same test conditions.

[0051] Fresh bovine tooth enamel from the same batch was polished into a 1×1×0.1cm thin slice, ultrasonically cleaned, and dried. The non-test surface was sealed with nail polish, exposing only 1cm. 2 The test area was selected. Thin slices of enamel were placed in artificial caries solution (0.1 mol / L lactate buffer, pH=4.5, the same below), shaken at 37°C for 24 hours to demineralize, rinsed with deionized water, dried, and weighed. The demineralized enamel was then immersed in the test sample (pH=7), shaken at 37°C for 7 days, with the mouthwash changed daily. After remineralization, it was rinsed with deionized water, dried, and weighed.

[0052] Acid etching treatment: The remineralized enamel was placed in artificial caries solution with the same solid-liquid ratio and shaken at 37°C for 24 hours. After acid etching, it was rinsed with deionized water, dried, and weighed (recorded as m3). The acid loss rate and remineralization rate were calculated. The results are shown in the table below.

[0053] Nanoindentation test: Remineralized enamel was taken, cut along its cross-section, and polished to expose the interface between the mineralized and demineralized layers. Using a nanoindenter (Bruker Hysitron TI 980), five repeated indentations were made on the surface of the mineralized layer (50 μm from the interface) using a Berkovich indenter. A load of 100 μN was applied for 10 seconds, followed by a 5-second hold time and a 10-second unload time. The spacing between adjacent indentations was no less than 50 μm. The nanohardness (H) was calculated and averaged. The results are shown in the table below.

[0054]

[0055] As can be seen, the oral occlusive agent of Example 1 exhibits the best acid etching stability, with its mineralized layer hardness approaching that of healthy bovine tooth enamel. This may be because the sodium acetate-acetic acid buffer system in the oral occlusive agent of Example 1 helps to reduce the pH drop under acid etching conditions, providing a stable microenvironment for calcium and phosphorus deposition, and chelating calcium to continuously release Ca. 2+ Can fill the gap in early Ca 2+ PO4 in artificial saliva 3- Micropores in the mineralized layer formed by remineralization. Comparative Example 1, due to the difference in its effective calcium source form compared to Example 1, was unable to continuously release Ca. 2+ To optimize the mineralized layer structure, its acid etching stability and mineralized layer hardness are significantly lower than those of Example 1. Comparative Example 1, due to the lack of an effective calcium source, has the worst acid etching stability and the lowest mineralized layer hardness.

[0056] 4. In vitro antibacterial test The oral lozenges provided in Examples 1-3 and Comparative Examples 1-2 were used for antibacterial tests according to the suspension quantitative test method in WS / T 650-2019. All samples were tested under the same conditions. The test targets were Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 25922), Candida albicans (ATCC 10231), and Streptococcus, a common oral pathogen. The action times were 30 seconds and 2 minutes, respectively. The results are shown in the table below:

[0057] As shown in the table above, the oral antibacterial agent in Example 1 exhibits the best antibacterial effect, with an inhibition rate of 99.9% against Escherichia coli, Staphylococcus aureus, Candida albicans, and Streptococcus after 2 minutes of action and over 98% after 30 seconds of action. In contrast, the oral antibacterial agent in Comparative Example 1 shows an inhibition rate of less than 90% against Escherichia coli, Staphylococcus aureus, Candida albicans, and Streptococcus after 30 seconds of action, while the oral antibacterial agent in Comparative Example 2 shows an inhibition rate of less than 80% against Escherichia coli, Staphylococcus aureus, Candida albicans, and Streptococcus after 30 seconds of action.

[0058] 5. Toxicological tests The oral lozenges provided in Examples 1-3 and Comparative Examples 1-2 were used as test samples. Following GB / T 21603-2008, 20 SPF-grade mice (half male and half female, weighing 18-22g) were selected for oral gavage tests using the maximum limit method (5000mg / kg). The symptoms of poisoning and mortality were observed within 14 days. The results showed that the LD50 of each oral lozenge... 50 All are >5000mg / kg, which, according to the classification standard of GB / T21603-2008, belongs to the practically non-toxic category.

[0059] Referring to Appendix D of QB / T 2945-2012 "Oral Cleaning and Care Solution", six New Zealand rabbits (weighing 2.0-2.5 kg) were selected. 0.5 mL of oral lozenges was applied to the buccal mucosa of the rabbits for 7 consecutive days. The lozenges were scored on a three-tiered scale: redness and swelling (0-3 points), ulceration (0-3 points), and discharge (0-3 points), with a total score of 0-9. The daily irritation index (ISI) was calculated. The results showed that the daily irritation index of each oral lozenge was less than 0.5, indicating that they were all non-irritating products.

[0060] Application examples To verify the clinical efficacy of the oral lozenges of this application in preventing early caries, relieving caries-related toothache, and improving dentin hypersensitivity, this application selected the oral lozenges provided in Example 1, the oral lozenges provided in Comparative Example 3, and a placebo for clinical case trials. The clinical trials of this application have been approved through ethical review. The placebo used in the clinical trials was prepared by pre-dissolving 3 kg of glacial acetic acid, 10 g of sodium benzoate, 10 g of cyclamate, 100 g of lactic acid, and 50 g of citric acid in 100 kg of water to prepare an acetic acid stock solution. This stock solution was then mixed with 4 kg of sodium chloride and 100 g of 0.2 wt.% xylitol to form a mixture. After standing, sodium chloride was added until the pH of the mixture was 7. Then, 100 g of polysorbate 80, 30 g of peppermint water, and 100 g of 1 wt.% clove flavoring solution were added. Its appearance, pH value (7.0±0.2), odor, and sensory characteristics were not statistically different from those of the oral lozenges of Example 1.

[0061] Experimental institution: Former Yunnan University of Traditional Chinese Medicine Integrated Traditional and Western Medicine Outpatient Department, No. 86, Baita Road, Kunming; 1. Caries prevention test Subjects: 177 subjects in the experimental group, 177 subjects in the blank group, and 177 subjects in the control group. The subjects in the experimental group were healthy children aged 3-4 years with intact teeth and no caries. Among them, there were 87 males and 90 females. There were 44 males aged 3 years, 43 males aged 4 years, 46 females aged 3 years, and 44 females aged 4 years. The subjects in the blank group and the control group had the same age, gender, and number as the experimental group. Reagents: The experimental group used the oral lozenge provided in Example 1, the blank group used a placebo, and the control group used the oral lozenge provided in Comparative Example 3; Experimental method: Subjects in the experimental group, blank group, and control group used the corresponding reagents twice a day, holding 5 ml for 30 seconds each time and spitting it out. They were followed up for 3 years, and the results are shown in the table below.

[0062]

[0063] As shown in the table above, in the experimental group, children aged 3-4 years without caries who used the oral remedy of this application to prevent caries until the age of 6-7 had a caries rate that did not exceed 3%, and the average inhibition rate of caries over three years reached 90.0%. In contrast, in the control group, children aged 3-4 years without caries who used traditional oral remedies had a caries rate of 14.1% until the age of 6-7, and the average inhibition rate of caries over three years was only 31.1%. This indicates that the oral remedy of this application has a very good preventive effect on caries.

[0064] 2. Treatment trial for toothache caused by caries Subjects: The experimental group consisted of 107 children aged 7-8 with dental caries, including 50 males and 57 females. Among them, 28 were 7-year-old males with 29 caries, 22 were 8-year-old males with 24 caries, 30 were 7-year-old females with 32 caries, and 27 were 8-year-old females with 30 caries. The control group and blank group had the same age, gender, and number of subjects as the experimental group, but the total number of caries in the control group was 118 and the total number of caries in the blank group was 112. Reagents: The experimental group used the oral lozenge provided in Example 1, the blank group used a placebo, and the control group used the oral lozenge provided in Comparative Example 3; Experimental method: Subjects in the experimental group, blank group, and control group used the corresponding reagents twice a day, holding 5 ml for 30 seconds each time and then spitting it out. They were followed up for 2 years, and the results are shown in the table below.

[0065]

[0066] As shown in the table above, in the experimental group, children with caries treated with the oral lozenges of this application achieved an average pain relief rate of 96.3% within three days. The number of caries teeth increased by only 2.6% after one year and by only 3.3% in the second year. In contrast, in the control group, children with caries treated with traditional oral lozenges achieved an average pain relief rate of only 65.3% within three days. The number of caries teeth increased by 8.5% after one year and by 12.5% ​​in the second year. This demonstrates that the oral lozenges of this application have a therapeutic effect on toothache caused by caries and a good effect on preventing the recurrence of caries.

[0067] 3. Dentin hypersensitivity test Subjects: The experimental group consisted of 57 subjects aged 30-60 years with dentin hypersensitivity (sensitive to acid and unable to bite hard objects) but without obvious caries. There were 30 males and 27 females. The subjects in the control group and blank group had the same age, gender, and number as the experimental group. Reagents: The experimental group used the oral lozenge provided in Example 1, the blank group used a placebo, and the control group used the oral lozenge provided in Comparative Example 3; Experimental method: Subjects in the experimental group, blank group, and control group used the corresponding reagents twice a day, holding 5 ml for 30 seconds each time and spitting it out. They were followed up for 5 days, and the results are shown in the table below.

[0068]

[0069] As shown in the table above, in the experimental group of dentin hypersensitivity subjects treated with the oral lozenge of this application, the on-day effectiveness (ability to eat acidic and hard foods) rate was 82.40%, and the five-day effectiveness rate reached 94.70%. In contrast, in the control group of dentin hypersensitivity subjects treated with traditional oral lozenges, the on-day effectiveness rate was only 36.8%, and the five-day effectiveness rate was only 49.1%. This indicates that the oral lozenge of this application can relieve dentin hypersensitivity symptoms more quickly and has a more significant and lasting effect.

[0070] It is understood that the above detailed description of the present invention is for illustrative purposes only and is not intended to limit the technical solutions described in the embodiments of the present invention. Those skilled in the art should understand that modifications or equivalent substitutions can still be made to the present invention to achieve the same technical effects; as long as the usage requirements are met, they are all within the protection scope of the present invention.

Claims

1. A method for preparing a lozenge, characterized in that, Includes the following steps: (1) Add 2.8-3.5 parts of glacial acetic acid, 0.005-0.015 parts of sodium benzoate, 0.005-0.015 parts of cyclamate, 0.08-0.12 parts of lactic acid and 0.04-0.06 parts of citric acid to 100 parts of water and mix to form acetic acid mother liquor; (2) Place 3.7-4.6 parts of sodium bicarbonate and 0.08-0.12 parts of calcium carbonate in a container, add the acetic acid mother liquor described in step (1) to the container, stir, and form a mixture; (3) Adjust the pH of the mixture in step (2) to 6.8-7.2, and then add 0.08-0.12 parts of Lobenqing, 0.02-0.04 parts of peppermint water and 0.08-0.12 parts of clove extract in sequence, and stir evenly; All the above quantities are by weight.

2. The method for preparing lozenges as described in claim 1, characterized in that, The weight ratio of glacial acetic acid, lactic acid, citric acid, sodium bicarbonate, and calcium carbonate is 3:0.1:0.05:(4.0-4.15):0.

1.

3. The method for preparing lozenges as described in claim 2, characterized in that, The weight ratio of glacial acetic acid, lactic acid, citric acid, sodium bicarbonate, and calcium carbonate is 3:0.1:0.05:4.0:0.

1.

4. The method for preparing lozenges as described in claim 2, characterized in that, The weight ratio of water, glacial acetic acid, sodium benzoate, cyclamate, sorbitol, peppermint water, and clove extract is 100:3:0.01:0.01:0.1:0.03:0.

1.

5. The method for preparing lozenges as described in claim 1, characterized in that, In step (3), adjust the pH of the mixture to 7.

6. The method for preparing lozenges according to any one of claims 1-5, characterized in that, Before adjusting the pH of the mixture, it must be allowed to stand until no more bubbles are produced.

7. The method for preparing lozenges according to any one of claims 1-5, characterized in that, Adjusting the pH of the mixture involves the following steps: testing the pH value of the mixture; if the pH is lower than the target range, an appropriate amount of alkaline pH adjuster needs to be added until the pH of the mixture reaches the target range; if the pH is within the target range, no further action is required.

8. The method for preparing lozenges as described in claim 7, characterized in that, The alkaline pH adjuster is sodium bicarbonate.

9. A lozenge prepared by any one of the preparation methods described in claims 1-8.

10. The use of the oral lozenge as described in claim 8 in the prevention and treatment of dental caries.

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