Nano-particle self-assembly method in mouth wash preparation process and application of nano-particle self-assembly method

Abstract

The invention relates to the technical field of mouth wash preparation, and discloses a nano-particle self-assembly method in the mouth wash preparation process and application of the nano-particle self-assembly method in the mouth wash preparation process, and the nano-particle self-assembly method comprises the following steps: step 1, preparation of a matrix solution: accurately weighing 1-10g / L of sugar such as glucose, fructose and lactose, using vacuum drying to remove possible moisture when necessary, and preparing the matrix solution; the preparation method comprises the following steps: selecting a weakly acidic buffer solution, such as an acetic acid-sodium acetate buffer solution, adjusting the pH value of the solution to 6.5-7.2, accurately monitoring and adjusting by using a pH meter to ensure that the solution is close to neutral, reduce the irritation to the oral environment and improve the compatibility of active ingredients, slowly adding sugar into the weakly acidic buffer solution prepared in advance, and stirring at normal temperature. According to the nano-particle self-assembly method in the mouth wash preparation process and the application of the nano-particle self-assembly method, functional active components are stably dispersed in the solution in a nano-particle form with uniform particle size through a nano-particle self-assembly technology, and component precipitation or non-uniform distribution caused by difference of physicochemical properties is avoided.

Description

Technical Field

[0001] The invention relates to the technical field of mouthwash preparation, in particular to a nanoparticle self-assembly method in a mouthwash preparation process and application thereof. Background Art

[0002] Mouthwash is a common oral care product widely used for daily oral cleaning and disease prevention. In the prior art, mouthwash is usually prepared through the following processes: preparation of base liquid, dissolution and uniform dispersion of active ingredients, antiseptic and stabilization treatment of preparations, etc. The main components of mouthwash include antibacterial agents, preservatives, lubricants and flavor regulators. These ingredients work synergistically to give mouthwash the functions of freshening breath, inhibiting bacterial growth and relieving gingival inflammation.

[0003] Traditional mouthwash formulations usually contain a variety of functional ingredients, such as antibacterial agents, fresheners, and anti-inflammatory ingredients. Due to the different physical and chemical properties of these ingredients, they are prone to uneven effects when mixed. For example, some ingredients may be water-soluble, while others are oil-soluble. Different affinities between different types of molecules may lead to mutual repulsion or undesirable interactions, making it impossible to form a stable and uniform solution. This mismatched affinity will cause precipitates or precipitation in the solution, ultimately affecting the stability of the mouthwash. Many active ingredients, especially large molecules or low-polarity ingredients, have low solubility in water and are prone to precipitation or agglomeration in such water-based solutions. In addition, the direct mixing preparation method also brings about functional heterogeneity. Due to the interaction between active ingredients or due to uneven dispersion of raw materials, the functional ingredients are often not evenly distributed in the mixed solution. This will lead to "functional deviation" in the efficacy of the mouthwash. For example, some ingredients with strong antibacterial effects may be concentrated on the surface or bottom of the mouthwash, resulting in unstable effects when rinsing. At the same time, if the concentration of a certain ingredient is too high, it will aggravate the irritation to the oral mucosa and cause discomfort; while the concentration of other ingredients may be too low and fail to exert their expected effects. These problems lead to defects such as poor stability, uneven effects and high irritation in the traditional mouthwash formula during use, which cannot meet the ideal requirements of oral care. Summary of the invention

[0004] 1. Technical issues to be solved

[0005] In view of the deficiencies in the prior art, the present invention provides a nanoparticle self-assembly method for a mouthwash preparation process and its application, which solves the problems of uneven formulation, poor stability, unstable effect and high irritation to the oral mucosa caused by differences in the physicochemical properties of the ingredients of traditional mouthwash.

[0006] (II) Technical solution

[0007] To achieve the above object, the present invention provides the following technical solution: a method for self-assembly of nanoparticles in a mouthwash preparation process, comprising the following steps:

[0008] Step 1: Preparation of the matrix solution: Select a weakly acidic buffer solution and adjust the pH of the solution to between 6.5 and 7.2 to reduce irritation to the oral environment and improve the compatibility of the active ingredients; slowly add sugar to the pre-prepared weakly acidic buffer solution and stir at 25°C-30°C until a uniform and transparent matrix solution is formed;

[0009] Step 2, ingredient selection and weighing: weighing functional active ingredients, including: protease, concentration range: 0.02% to 0.12%, natural antimicrobial peptide, concentration range: 0.01% to 0.1%, menthol, concentration range: 0.01% to 0.08%; adding them to the previously prepared matrix solution to form a mixed solution, maintaining the pH in the range of 6.5-7.2, using the positive charge of sugar and the negative charge / polar molecules of the active ingredients, with the help of electrostatic interaction, inducing the functional active ingredients to gradually adsorb on the sugar molecular chain to form nanoparticles; filtering to obtain a primary nanoparticle suspension;

[0010] Step 3, particle self-assembly induction and particle size control: weigh 0.1% to 0.3% concentration of protease and dissolve it in deionized water, and stir until it is completely dissolved to prepare a uniform complexing agent solution; stir and mix the complexing agent solution with the primary nanoparticle suspension to obtain a suspension mixture; heat the suspension mixture, homogenize it, let it stand, and then cool it; after cooling, use a buffer solution to adjust the solution pH to 6.5-7.2 to balance the particle surface charge and enhance the biocompatibility of the suspension; filter to obtain a nanoparticle suspension;

[0011] Step 4: Stir and mix the nanoparticle suspension and the mouthwash base liquid; slowly add the dispersant polysorbate 80 into the mixed liquid, stir and disperse it, and then cool it; filter it to obtain the mouthwash.

[0012] Furthermore, the step 1 is specifically as follows: accurately weighing sugar, the sugar is 1-10g / L; selecting a weak acidic buffer solution, acetic acid-sodium acetate buffer, using a pH meter for accurate monitoring and adjustment, and adjusting the solution pH to between 6.5 and 7.2; slowly adding sugar to the pre-prepared weak acidic buffer solution, stirring at 25°C-30°C until a uniform and transparent matrix solution is formed; placing the obtained matrix solution in an ultrasonic processor or a vacuum degassing device for 5 minutes to 15 minutes to remove microbubbles generated during the mixing process; using a 0.22μm microporous filter to filter the matrix solution to remove incompletely dissolved solid impurities or bacteria, improve the purity of the solution, and lay a foundation for the subsequent stable formation of nanoparticles.

[0013] Further, the step 2 is specifically as follows: dissolving the oil-soluble component, menthol, in a trace amount of ethanol; dissolving the water-soluble components, protease and natural antimicrobial peptide, in an appropriate amount of deionized water, respectively, to ensure that the solution is uniform and transparent; under stirring conditions, slowly adding the functional active ingredient solution dropwise to the previously prepared matrix solution, and performing real-time pH monitoring at the same time to ensure that the solution pH is maintained in the range of 6.5-7.2; placing the mixed solution in an ultrasonic processor, the frequency range: 40kHz-60kHz, controlling the processing time to be 5 minutes to 15 minutes, setting a circulation mode to avoid local overheating of the solution, and regulating the temperature not to exceed 30°C; allowing the mixed solution to stand for 30 minutes, during which the nanoparticle formation process is monitored by a dynamic light scattering instrument to ensure that the nanoparticle size distribution is uniform, and the nanoparticle size is 50nm-200nm; after standing, stirring again at a low speed for 15 minutes, the rotation speed is 100-200rpm, and the mixed solution is finely filtered using a 0.45μm filter membrane;

[0014] The step three is as follows: weighing 0.1% to 0.3% protease and dissolving it in deionized water at 55-60° C., stirring it at 300 rpm with a magnetic stirrer until it is completely dissolved to prepare a uniform complexing agent solution; then slowly adding the complexing agent solution to the primary nanoparticle suspension in a titration manner, the entire dropping process lasts for 15 minutes to 20 minutes, the stirring speed is maintained at 300 rpm, and after the addition is completed, stirring is continued for 15 minutes to obtain a suspension mixture; heating the suspension mixture to 55° C.-65° C., maintaining this temperature range for 10 minutes to 15 minutes, and setting the medium speed stirring speed to 200 rpm. During the process, samples need to be taken regularly to check the transparency and dispersibility of the solution to ensure that the suspension The suspension mixture is kept stable and no particle flocculation occurs; the heated suspension mixture is transferred to a high-pressure homogenizer, the equipment pressure is set in the range of 50MPa-100MPa, and 2-3 cycles are performed. The high-pressure homogenization effectively disperses the nanoparticles and controls their particle size distribution within 50nm-100nm. The temperature is maintained at 25℃-30℃ during the homogenization; after the homogenization treatment is completed, the suspension mixture is immediately placed at 4℃ for 30 minutes to allow the particles to slowly cool to below room temperature; after cooling, the pH value of the solution is adjusted to 6.5-7.2 with a buffer solution; the suspension mixture is filtered through a 0.22μm microporous filter membrane to remove large-sized particles and trace impurities to obtain a nanoparticle suspension.

[0015] Further, the step 4 is specifically as follows: the mouthwash base liquid includes deionized water, a moisturizing agent glycerin and a surfactant; wherein the surfactant is poloxamer, hydrogenated castor oil, and betaine, which are premixed in a mass ratio of 1:1:0.05, and the temperature of the mouthwash base liquid is maintained at 25°C-30°C to ensure that the viscosity is moderate and is conducive to the uniform dispersion of the nanoparticles; the nanoparticle suspension is slowly added to the mouthwash base liquid, and a magnetic stirrer is used to stir for 15 minutes during the addition process, and the stirring speed is 200rpm to ensure that the nanoparticles are fully fused with the base liquid and formed. The invention discloses a homogeneous system; slowly adding the dispersant polysorbate 80 into the mixed solution in an amount of 0.02% to 0.05%, stirring for 30 minutes, and increasing the stirring speed to 400 rpm; then performing 20 kHz ultrasonic treatment through an ultrasonic dispersion device, controlling the ultrasonic power at 150 W, setting the total time to 10 minutes, and stopping the ultrasonic treatment for 5 seconds every 2 minutes; after the ultrasonic dispersion is completed, transferring the mixed solution to a cooling water bath for rapid cooling, cooling to 4° C. and maintaining for 10 minutes; after the cooling is completed, filtering the mixed solution through a 0.45 μm membrane to obtain a mouthwash.

[0016] Preferably, in step 1, a small amount of pH stabilizer: sodium dihydrogen phosphate, disodium hydrogen phosphate, citric acid, sodium citrate is added to the matrix solution.

[0017] Preferably, in the step 2, during the dissolution and addition of the active ingredient, the solution temperature is strictly controlled to 25°C ± 2°C, and a temperature-controlled agitator or cooling device is provided to ensure temperature stability during the entire stirring process; in the step 3, during the process of slowly adding the complexing agent solution to the primary nanoparticle suspension in a titration manner, the drop rate of the complexing agent is controlled to be no more than 2 mL per minute, and the stirring speed is ensured to be uniform and stable during the entire dropwise addition process; in the step 4, after adding the mouthwash base solution, the size and surface charge of the nanoparticles are monitored in real time by a particle size analyzer; the cooled suspension is placed in a 4°C environment for 30 minutes, and the particle size is continuously detected by dynamic light scattering during this process.

[0018] Preferably, the mouthwash samples are subjected to multiple cycle tests under different storage conditions (such as room temperature, 4°C, room temperature, etc.) to observe the stability changes of the particles under different environmental conditions.

[0019] Preferably, in the subsequent surface modification step, natural plant extracts such as green tea and chamomile are used in combination with antimicrobial peptides.

[0020] An application of a nanoparticle mouthwash also includes the following applications:

[0021] The nanoparticles have a particle size range of 50nm-100nm, and the nanoparticles are surface-modified composite materials, the modified layer is composed of natural plant extracts or antibacterial components, and the mass ratio of the base liquid to the particles is 90:10 to 75:25, preferably 90:10.

[0022] Preferably, the nanoparticles are used for daily oral care, and are particularly suitable for alleviating gum problems, alleviating symptoms of oral ulcers, and effectively preventing the occurrence of periodontal disease.

[0023] (III) Beneficial effects

[0024] Compared with the prior art, the present invention provides a nanoparticle self-assembly method and application in the preparation process of mouthwash, which has the following beneficial effects:

[0025] 1. The nanoparticle self-assembly method and application of the mouthwash preparation process, through the nanoparticle self-assembly technology, the functional active ingredients (such as protease, natural antimicrobial peptide, menthol) are stably dispersed in the solution in the form of nanoparticles with uniform particle size, avoiding precipitation or uneven distribution of ingredients due to differences in physical and chemical properties.

[0026] 2. The nanoparticle self-assembly method and application in the preparation process of the mouthwash enhance the structural stability and suspension stability of the particles through the design of double-layer nanoparticles and the electrostatic adsorption mechanism; at the same time, through strict pH and temperature control, as well as pH stabilizers, the stability of the solution and its ability to resist environmental disturbances are improved.

[0027] 3. The nanoparticle self-assembly method and application in the mouthwash preparation process use natural plant extracts or antibacterial ingredients to modify the surface of nanoparticles, reduce the irritation that may be caused by traditional chemical ingredients, and provide a milder basic environment through sugar molecular chains and buffer systems.

[0028] 4. The nanoparticle self-assembly method and application in the preparation process of the mouthwash. The composite modification of the nanoparticle surface enhances the antibacterial properties and local therapeutic effects of the particles; the particles have stronger adhesion, which prolongs their residence time in the oral cavity, thereby ensuring the long-lasting effect of the functional ingredients.

[0029] 5. The nanoparticle self-assembly method and application in the preparation process of the mouthwash utilizes a process combining ultrasonic treatment, high-pressure homogenization and low-speed stirring to ensure uniform particle formation and stable particle size distribution; impurities and unreacted products are eliminated through dynamic light scattering detection and multi-step filtration.

[0030] 6. The nanoparticle self-assembly method and application in the preparation process of the mouthwash. The nanoparticles can effectively inhibit the proliferation of harmful bacteria and maintain the health of gums and oral mucosa, while promoting inflammation healing and preventing the occurrence of periodontal disease. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 A schematic diagram of a nanoparticle self-assembly method and its application process in a mouthwash preparation process proposed by the present invention;

[0032] Figure 2 A table for collecting information after the test of the experimental subjects of the product of the present invention;

[0033] Figure 3 This is a comparison chart of the antibacterial effects of the self-assembled nanoparticle mouthwash of the present invention and traditional mouthwash. DETAILED DESCRIPTION

[0034] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0035] See also Figure 1-Figure 3 , a nanoparticle self-assembly method for preparing a mouthwash, comprising the following steps:

[0036] Step 1. Preparation of matrix solution: Accurately weigh sugars, such as glucose, fructose and lactose, with a sugar content of 1-10 g / L. If necessary, use vacuum drying to remove possible moisture. Select a weakly acidic buffer solution, such as acetic acid-sodium acetate buffer. Use a pH meter for precise monitoring and adjustment. Adjust the solution pH to between 6.5 and 7.2 to ensure that it is close to neutral, reduce irritation to the oral environment, and improve the compatibility of active ingredients. Slowly add sugar to the pre-prepared weakly acidic buffer solution and stir at room temperature until a uniform and transparent matrix solution is formed. The entire stirring process The temperature must be strictly controlled at 25°C-30°C to avoid molecular chain degradation or performance loss, maintain the molecular integrity of sugars and provide a stable solution matrix. The resulting matrix solution is placed in an ultrasonic processor or vacuum degasser for 5 to 15 minutes to remove microbubbles generated during the mixing process to avoid uneven polymerization or unstable finished products during the subsequent self-assembly process. The matrix solution is filtered using a 0.22 μm microporous filter to remove incompletely dissolved solid impurities or possible bacterial contamination, improve the purity of the solution, and lay the foundation for the subsequent stable formation of nanoparticles.

[0037] Step 2: Ingredient selection and weighing: Weigh the functional active ingredients, including: protease, concentration range: 0.02% to 0.12%, natural antimicrobial peptide, concentration range: 0.01% to 0.1%, menthol, concentration range: 0.01% to 0.08%, dissolve the oil-soluble ingredient, menthol, in a trace amount of ethanol to improve its solubility; dissolve the water-soluble ingredients, protease and natural antimicrobial peptide, in an appropriate amount of deionized water to ensure that the solution is uniform and transparent, which helps to enhance the dispersibility and compatibility of different active ingredients. Slowly mix the functional ingredients under stirring. The active ingredient solution was added dropwise to the previously prepared matrix solution, and real-time pH monitoring was performed to ensure that the solution pH was maintained in the range of 6.5-7.2. Stable pH could inhibit sugar degradation and promote electrostatic adsorption self-assembly of primary nanoparticles. The mixed solution was placed in an ultrasonic processor with a frequency range of 40kHz-60kHz. The processing time was controlled to be 5 minutes to 15 minutes. The circulation mode was set to avoid local overheating of the solution. Ultrasonic treatment can effectively break up the agglomeration of the active ingredient and improve the dispersion effect. At the same time, the temperature was controlled not to exceed 30°C to avoid heat sensitivity. Active ingredients, such as antimicrobial peptides, have decreased activity. To protect the biological efficacy of active ingredients and ensure the uniformity of the solution, the mixed solution was allowed to stand for 30 minutes. The positive charge of sugar and the negative charge / polarity of active ingredients were used to induce the functional active ingredients to gradually adsorb on the sugar molecular chain with the help of electrostatic interaction. This step achieved the fixation of active ingredients and significantly increased the loading rate. The nanoparticle formation process was monitored by a dynamic light scattering instrument to ensure that the nanoparticle size distribution was uniform. The nanoparticle size was 50nm-200nm, which met the microscopic stability requirements of mouthwash. After standing, it was again Stir at a low speed of 100-200 rpm for 15 minutes to enhance the uniformity of the solution and avoid the deposition or aggregation of nanoparticles. This process provides guarantee for the uniformity of the subsequent finished product. Finely filter the mixed solution with a 0.45 μm filter membrane to remove a small amount of unreacted impurities or macromolecular aggregates, improve the stability and purity of the nanoparticle solution, ensure the stable dispersion of the active ingredients in the matrix solution, and use the electrostatic adsorption mechanism to achieve efficient self-assembly of primary nanoparticles. At the same time, enhance the fixation and efficacy of functional ingredients and optimize the actual application effect of mouthwash.

[0038] Step 3, particle self-assembly induction and particle size control: weigh 0.1% to 0.3% concentration of protease and dissolve it in deionized water at 55-60°C, stir it at 300 rpm with a magnetic stirrer until it is completely dissolved, prepare a uniform complexing agent solution, and then slowly add the complexing agent solution to the primary nanoparticle suspension by titration. The entire dropping process lasts for 15 minutes to 20 minutes, and the stirring speed is maintained at 300 rpm to ensure that the complexing agent is evenly dispersed to avoid local aggregation that causes instability or uneven size of nanoparticles. After the addition is completed, continue stirring Stir for 15 minutes to allow the sugar and protease to fully cross-link and form a stable double-layer nanoparticle structure. After the addition is completed, heat the suspension mixture to 55°C-65°C and maintain this temperature range for 10 minutes to 15 minutes. Set the medium stirring speed to 200rpm. The heat energy accelerates the cross-linking reaction between the sugar chain and the complexing agent, stabilizes the framework of the double-layer structure and enhances the particle strength. During the process, samples should be taken regularly to check the transparency and dispersibility of the solution to ensure that the suspension remains stable and there is no particle flocculation. Transfer the heated suspension mixture to a high-pressure homogenizer. In the machine, the equipment pressure is set in the range of 50MPa-100MPa, and 2-3 cycles are performed as needed. High-pressure homogenization effectively disperses the nanoparticles and controls their particle size distribution within 50nm-100nm, thereby improving the consistency and functionality of the product. The temperature is maintained at 25℃-30℃ during homogenization to avoid damage to the particle structure caused by equipment heating and ensure the stability of the active ingredients. After homogenization, dynamic light scattering (DLS) is used to detect the particle size distribution of the particles in real time to confirm that the target standard is met. After the homogenization treatment is completed, the suspension mixture is immediately placed at 4℃ for 30 minutes to allow the particles to slowly cool to below room temperature to avoid thermal stress affecting the morphology and stability of the nanoparticles, and further optimize the long-term storage performance of the suspension. After cooling, the pH value of the solution is adjusted to 6.5-7.2 with a buffer solution to balance the surface charge of the particles and enhance the biocompatibility of the suspension. Finally, the suspension mixture is filtered through a 0.22μm microporous filter membrane to remove large-sized particles and trace impurities that may be generated during the production process, significantly improving the purity of the solution and the uniformity of the nanoparticles.

[0039] Step 4: slowly add the prepared nanoparticle suspension to the mouthwash base liquid, the mouthwash base liquid includes deionized water, humectant glycerin and surfactant, the surfactant such as poloxamer, hydrogenated castor oil, betaine, premixed at a mass ratio of 1:1:0.05, the mouthwash base liquid temperature is maintained at 25°C-30°C, ensuring that the viscosity is moderate and conducive to the uniform dispersion of the nanoparticles, the stirring speed is maintained at 200rpm during the addition of the nanoparticle suspension, and the magnetic stirrer is used for stirring for 15 minutes to ensure that the nanoparticles are fully fused with the base liquid and form a uniform system, the dispersant polysorbate 80 is slowly added to the mixed solution at an addition amount of 0.02% to 0.05%, and the mixture is stirred again for 30 minutes, and the stirring speed is increased to 400rpm to further improve the viscosity. The dispersion of nanoparticles in the base liquid is improved, and the suspension stability of the particles is enhanced. Subsequently, 20kHz ultrasonic treatment is performed through an ultrasonic dispersion device, and the ultrasonic power is controlled at 150W. The total time is set to 10 minutes. The ultrasound is stopped for 5 seconds every 2 minutes to prevent the solution from overheating and causing the nanoparticle structure to be destroyed. At the same time, the particles are evenly dispersed to the nanoscale. After the ultrasonic dispersion is completed, the mixed solution is transferred to a cooling water bath for rapid cooling. The mixture is cooled to 4°C and maintained for 10 minutes to slow down the aggregation tendency of the particles during the dispersion process and enhance the long-term stability of the finished mouthwash. After cooling, the mixed solution is filtered through a 0.45μm membrane to remove any residual particle agglomerates or impurities, which significantly improves the purity of the mouthwash and the consistency of the particle function. The final mixed solution is the finished functional mouthwash.

[0040] In step 4, the cooled suspension is placed in a 4°C environment for 30 minutes, and the particle size is continuously detected by dynamic light scattering during this process. This operation helps to slowly cool the suspension and avoid particle aggregation due to rapid cooling. At the same time, by real-time monitoring of the dispersion of the particles, the uniformity and functionality of the final mouthwash are ensured.

[0041] In step 3, during the process of slowly adding the complexing agent solution into the primary nanoparticle suspension by titration, the dropping rate of the complexing agent is controlled to be no more than 2 mL per minute, and the stirring speed is ensured to be uniform and stable during the entire dropping process.

[0042] In order to ensure the stability of the molecules and optimize the self-assembly effect of the nanoparticles, in step one, a small amount of pH stabilizer, such as sodium dihydrogen phosphate, disodium hydrogen phosphate, citric acid, sodium citrate, is added to the matrix solution to enhance the buffering capacity of the pH value and avoid the pH deviating from the target range due to changes in the external environment or temperature, thereby affecting the formation process of the nanoparticles. This measure can further ensure the stability of the solution and the self-assembly effect.

[0043] In step 2, during the dissolution and addition of the active ingredient, the solution temperature is strictly controlled to 25°C ± 2°C, and a temperature-controlled agitator or cooling device is used to ensure temperature stability during the entire stirring process to avoid degradation or incomplete dissolution of the active ingredient due to temperature changes. In addition, before the subsequent mixing and self-assembly process, a short preheating is performed to make the solution temperature uniform, further improving the self-assembly efficiency.

[0044] In step 4, after adding the mouthwash base liquid, the size and surface charge of the nanoparticles are monitored in real time by a particle size analyzer to ensure the stable dispersion and appropriate surface charge of the particles in the finished mouthwash product, and to ensure the effective adhesion and stability of the particles in the oral cavity. This monitoring helps to adjust the stirring and ultrasonic treatment parameters and further optimize the performance of the final product.

[0045] By subjecting mouthwash samples to multiple cycle tests under different storage conditions (such as normal temperature, 4°C, room temperature, etc.), the stability changes of particles under different environmental conditions are observed to ensure that the finished product does not precipitate, aggregate or lose active ingredients over a long period of time. This test helps to verify the storage performance and long-term stability of mouthwash.

[0046] In the subsequent surface modification step, a composite modification of natural plant extracts (such as green tea, chamomile, etc.) and antimicrobial peptides is used instead of a single component. By using a composite modification layer, not only the antibacterial and anti-inflammatory effects of the particles can be enhanced, but also the biocompatibility and adhesion of the particles in the oral cavity can be improved. This composite modification method can provide a stronger local therapeutic effect and is particularly suitable for relieving oral ulcers and gingivitis.

[0047] An application of a nanoparticle mouthwash also includes the following applications:

[0048] The particle size of the nanoparticles ranges from 50nm to 100nm, and the nanoparticles are surface-modified composite materials. The modified layer is composed of natural plant extracts or antibacterial ingredients. The mass ratio of the base liquid to the particles is 90:10 to 75:25, preferably 90:10. The mouthwash not only enhances the dispersibility, stability and durability of the particles by surface-modifying the nanoparticles, but also increases its antibacterial and anti-inflammatory effects by implanting natural antibacterial ingredients such as plant extracts. The modified nanoparticles can accurately target harmful bacteria in the oral cavity, further enhancing the cleaning and protection effects. At the same time, this innovative modification method can also reduce the problem of excessive oral irritation that users may encounter in long-term use, effectively protect gum health, and provide a mild and Efficient oral care experience. Nanoparticles are used for daily oral care, especially for alleviating gum problems, reducing oral ulcer symptoms, and effectively preventing the occurrence of periodontal disease. Since the nanoparticles used have a particle size range of 50nm-100nm, nanoparticles in this range have significant surface effects and size effects, which enable them to penetrate deeper into the gums and oral ulcers. Smaller particles can effectively break through the barrier of the oral mucosa, improve the adhesion and residence time of the particles in the oral cavity, thereby enhancing the sustained effect of active ingredients (such as antibacterial ingredients). In addition, the surface modification layer of the nanoparticles contains natural plant extracts or antibacterial ingredients (such as silver, zinc or polyphenols). This modification gives the particles anti-inflammatory and antibacterial properties, which can Effective against common pathogens in the oral cavity. Nanoparticles have a large specific surface area, which enables them to effectively adsorb and carry a variety of drug molecules or active ingredients, enhancing the bioavailability of the ingredients. In terms of alleviating gum problems, modified nanoparticles can promote blood circulation, improve local microcirculation, relieve oral ulcer symptoms, and stimulate the regeneration of gum cells. After adhering to the gums and oral ulcer sites, nanoparticles can not only provide long-term antibacterial protection, but also enhance the healing ability of inflamed areas, which provides support for the natural repair process in the mouth. By modifying the surface of nanoparticles, they can be selectively adsorbed on areas with gingivitis or oral ulcers, providing stronger local therapeutic effects in these areas. The precise transmission of nanoparticles The delivery effect effectively promotes local blood circulation, relieves inflammation, reduces bleeding, and increases the healing speed of oral ulcers. By reducing the proliferation of harmful bacteria in the mouth and their invasion of the gums, nanoparticles create a more stable and healthy microecological environment inside the mouth, which is important for effectively preventing the occurrence of periodontitis. Because one of the key causes of periodontal disease is the continuous accumulation and reproduction of bacteria in the gums, the use of nanoparticles for control can effectively curb this problem. The modified nanoparticles use natural plant extracts or antibacterial ingredients as modifiers. Compared with the common chemical drugs in traditional mouthwashes, this can reduce the side effects and irritation risks caused by long-term use. For people with sensitive oral cavity (such as patients with gum problems or ulcers),This gentle and highly effective protection provides better user experience and safety.

[0049] Typical cases:

[0050] A 25-year-old female had long-term problems such as bad breath, bleeding gums, and plaque accumulation. She had tried a variety of conventional mouthwashes, but the effects were not significant. She also felt that traditional mouthwashes were very irritating and caused oral discomfort after use.

[0051] Experimental process:

[0052] In the first week of using the self-assembled nanoparticle mouthwash, users felt that the freshness and comfort of the mouth were greatly improved, and the irritation after rinsing was significantly reduced. In the second week of continuous use, gum bleeding and bad breath were significantly reduced, and oral hygiene was significantly improved. After one month, the user's oral health condition improved greatly, the gums no longer bleed, there is no obvious plaque on the surface of the teeth, bad breath completely disappeared, and the user feels a lasting freshness in the mouth without any discomfort.

[0053] The experiment shows that self-assembled nanoparticle mouthwash can significantly improve oral health, especially in the prevention and improvement of common problems such as bad breath, bleeding gums, and dental plaque, and is superior to traditional mouthwash.

[0054] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device. In the absence of further restrictions, the elements defined by the sentence "comprise a ..." do not exclude the existence of other identical elements in the process, method, article or device including the elements.

Claims

1. A method for self-assembly of nanoparticles in a mouthwash preparation process, characterized in that: The following steps are involved: Step 1: Preparation of the matrix solution: Select a weakly acidic buffer solution and adjust the pH of the solution to between 6.5 and 7.2 to reduce irritation to the oral environment and improve the compatibility of the active ingredients; slowly add sugar to the pre-prepared weakly acidic buffer solution and stir at 25°C-30°C until a uniform and transparent matrix solution is formed; Step 2, ingredient selection and weighing: weighing functional active ingredients, including: protease, concentration range: 0.02% to 0.12%, natural antimicrobial peptide, concentration range: 0.01% to 0.1%, menthol, concentration range: 0.01% to 0.08%; adding them to the previously prepared matrix solution to form a mixed solution, maintaining the pH in the range of 6.5-7.2, using the positive charge of sugar and the negative charge / polar molecules of the active ingredients, with the help of electrostatic interaction, inducing the functional active ingredients to gradually adsorb on the sugar molecular chain to form nanoparticles; filtering to obtain a primary nanoparticle suspension; Step 3, particle self-assembly induction and particle size control: weigh 0.1% to 0.3% concentration of protease and dissolve it in deionized water, and stir until it is completely dissolved to prepare a uniform complexing agent solution; stir and mix the complexing agent solution with the primary nanoparticle suspension to obtain a suspension mixture; heat the suspension mixture, homogenize it, let it stand, and then cool it; after cooling, use a buffer solution to adjust the solution pH to 6.5-7.2 to balance the particle surface charge and enhance the biocompatibility of the suspension; filter to obtain a nanoparticle suspension; Step 4: Stir and mix the nanoparticle suspension and the mouthwash base liquid; slowly add the dispersant polysorbate 80 into the mixed liquid, stir and disperse it, and then cool it; filter it to obtain the mouthwash.

2. The method for self-assembly of nanoparticles in a mouthwash preparation process according to claim 1, characterized in that: The step 1 is specifically as follows: accurately weighing sugar, the sugar is 1-10g / L; selecting a weak acidic buffer solution, acetic acid-sodium acetate buffer, using a pH meter to accurately monitor and adjust, and adjusting the solution pH to between 6.5 and 7.2; slowly adding sugar to the pre-prepared weak acidic buffer solution, stirring at 25°C-30°C until a uniform and transparent matrix solution is formed; placing the obtained matrix solution in an ultrasonic processor or a vacuum degassing device for 5 minutes to 15 minutes to remove microbubbles generated during the mixing process; using a 0.22μm microporous filter to filter the matrix solution to remove incompletely dissolved solid impurities or bacteria, thereby improving the purity of the solution and laying a foundation for the subsequent stable formation of nanoparticles.

3. The method for self-assembly of nanoparticles in a mouthwash preparation process according to claim 2, characterized in that: The step 2 is specifically as follows: dissolving the oil-soluble component, menthol, in a trace amount of ethanol; dissolving the water-soluble components, protease and natural antimicrobial peptide, in an appropriate amount of deionized water, respectively, to ensure that the solution is uniform and transparent; Under stirring conditions, slowly add the functional active ingredient solution dropwise to the previously prepared matrix solution, and perform real-time pH monitoring at the same time to ensure that the pH of the solution is maintained in the range of 6.5-7.2; place the mixed solution in an ultrasonic processor with a frequency range of 40kHz-60kHz, control the processing time to be 5 minutes to 15 minutes, set the circulation mode to avoid local overheating of the solution, and adjust the temperature not to exceed 30°C; let the mixed solution stand for 30 minutes, during which the nanoparticle formation process is monitored by a dynamic light scattering instrument to ensure that the nanoparticle size distribution is uniform and the nanoparticle size is 50nm-200nm; after standing, stir again at a low speed for 15 minutes at a rotation speed of 100-200rpm, and finely filter the mixed solution using a 0.45μm filter membrane; The step three is as follows: weighing 0.1% to 0.3% protease and dissolving it in deionized water at 55-60° C., stirring it at 300 rpm with a magnetic stirrer until it is completely dissolved to prepare a uniform complexing agent solution; then slowly adding the complexing agent solution to the primary nanoparticle suspension in a titration manner, the entire dropping process lasts for 15 minutes to 20 minutes, the stirring speed is maintained at 300 rpm, and after the addition is completed, stirring is continued for 15 minutes to obtain a suspension mixture; heating the suspension mixture to 55° C.-65° C., maintaining this temperature range for 10 minutes to 15 minutes, and setting the medium speed stirring speed to 200 rpm. During the process, samples need to be taken regularly to check the transparency and dispersibility of the solution to ensure that the suspension The suspension mixture is kept stable and no particle flocculation occurs; the heated suspension mixture is transferred to a high-pressure homogenizer, the equipment pressure is set in the range of 50MPa-100MPa, and 2-3 cycles are performed. The high-pressure homogenization effectively disperses the nanoparticles and controls their particle size distribution within 50nm-100nm. The temperature is maintained at 25℃-30℃ during the homogenization; after the homogenization treatment is completed, the suspension mixture is immediately placed at 4℃ for 30 minutes to allow the particles to slowly cool to below room temperature; after cooling, the pH value of the solution is adjusted to 6.5-7.2 with a buffer solution; the suspension mixture is filtered through a 0.22μm microporous filter membrane to remove large-sized particles and trace impurities to obtain a nanoparticle suspension.

4. The method for self-assembly of nanoparticles in a mouthwash preparation process according to claim 3, characterized in that: The specific steps of step 4 are as follows: the mouthwash base liquid includes deionized water, humectant glycerin and a surfactant; wherein the surfactant is poloxamer, hydrogenated castor oil and betaine, which are premixed at a mass ratio of 1:1:0.05, and the temperature of the mouthwash base liquid is maintained at 25°C-30°C to ensure that the viscosity is moderate and conducive to the uniform dispersion of the nanoparticles; the nanoparticle suspension is slowly added to the mouthwash base liquid, and a magnetic stirrer is used to stir for 15 minutes during the addition process, and the stirring speed is 200rpm to ensure that the nanoparticles are fully fused with the base liquid and form a uniform system; slowly adding the dispersant polysorbate 80 in an amount of 0.02% to 0.05% to the mixed solution, stirring again for 30 minutes, and increasing the stirring speed to 400rpm; then performing 20kHz ultrasonic treatment through an ultrasonic dispersion device, controlling the ultrasonic power at 150W, setting the total time to 10 minutes, and stopping the ultrasound for 5 seconds every 2 minutes; after the ultrasonic dispersion is completed, transferring the mixed solution to a cooling water bath for rapid cooling, cooling to 4°C and maintaining for 10 minutes; after the cooling is completed, filtering the mixed solution through a 0.45μm membrane to obtain a mouthwash.

5. The method for self-assembly of nanoparticles in a mouthwash preparation process according to claim 2, characterized in that: In the step 1, a small amount of pH stabilizer: sodium dihydrogen phosphate, disodium hydrogen phosphate, citric acid, sodium citrate is added to the base solution.

6. The method for self-assembly of nanoparticles in a mouthwash preparation process according to claim 4, characterized in that: In the step 2, during the dissolution and addition of the active ingredient, the solution temperature is strictly controlled to 25°C±2°C, and a temperature-controlled stirrer or cooling device is provided to ensure temperature stability during the entire stirring process; in the step 3, during the process of slowly adding the complexing agent solution to the primary nanoparticle suspension in a titration manner, the drop rate of the complexing agent is controlled to be no more than 2 mL per minute, and the stirring speed is ensured to be uniform and stable during the entire dropwise addition process; in the step 4, after adding the mouthwash base solution, the size and surface charge of the nanoparticles are monitored in real time by a particle size analyzer; the cooled suspension is placed in a 4°C environment for 30 minutes, and the particle size is continuously tested by dynamic light scattering during this process.

7. The method for self-assembly of nanoparticles in a mouthwash preparation process according to claim 1, characterized in that: The mouthwash samples were subjected to multiple cycle tests under different storage conditions to observe the changes in the stability of the particles under different environmental conditions.

8. The method for self-assembly of nanoparticles in a mouthwash preparation process according to claim 1, characterized in that: In the subsequent surface modification step, natural plant extracts such as green tea and chamomile are used in combination with antimicrobial peptides.

9. An application of a nanoparticle mouthwash, characterized in that: The nanoparticle self-assembly method used in the preparation process of a mouthwash according to any one of claims 1 to 8 above also includes the following applications: The nanoparticles have a particle size range of 50nm-100nm, and the nanoparticles are surface-modified composite materials, the modified layer is composed of natural plant extracts or antibacterial components, and the mass ratio of the base liquid to the particles is 90:10 to 75:25, preferably 90:

10.

10. The use of a nanoparticle mouthwash according to claim 9, characterized in that: Nanoparticles are used for daily oral care and are particularly suitable for alleviating gum problems, reducing oral ulcer symptoms, and effectively preventing the occurrence of periodontal disease.

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