Bacteriostatic and anti-inflammatory gargle and preparation method thereof

Abstract

The invention provides an antibacterial and anti-inflammatory gargle and a preparation method thereof, and belongs to the technical field of oral care, the antibacterial and anti-inflammatory gargle comprises the following components by weight: 1-20% of an antibacterial repairing agent, 1-3% of a synergist, 1-8% of a nano composite active agent, 1-3% of a surfactant, 0.1-0.5% of a stabilizer, 0.1-0.5% of a preservative, and the balance of water; the antibacterial repairing agent comprises a honeysuckle flower extract, a wrinkled gianthyssop herb extract, a liquorice root extract, a salvia officinalis extract, a centella asiatica extract and a myrrh extract; the synergist is a tea polyphenol-lactoferrin compound. The traditional Chinese medicine compound regulates the whole oral cavity micro-ecology, the modern compound components and the nanotechnology strengthen the local curative effect, the cooperation of macroscopic regulation and microcosmic precision is achieved, and the traditional Chinese medicine compound is free of chemical preservatives, mild, free of stimulation and suitable for special people who use the traditional Chinese medicine compound for a long time and suffer from dental ulcer and the like.

Description

Technical Field

[0001] The present invention relates to the technical field of oral care, and in particular to an antibacterial and anti-inflammatory mouthwash and a preparation method thereof. Background Art

[0002] In modern life, people are increasingly prioritizing oral health. With the diversification of diets and the accelerated pace of life, the incidence of various oral diseases is on the rise, and oral health issues are becoming increasingly prominent. Common oral diseases such as oral ulcers, pharyngitis, laryngitis, tonsillitis, gingivitis, and bad breath seriously impact people's daily lives and work. This is particularly true for patients with recurrent oral ulcers, whose recurring symptoms significantly reduce their quality of life. While toothbrushing, as a primary method of daily oral hygiene, can remove plaque to a certain extent, it has limitations. Studies have shown that conventional toothbrushing only removes 40%-50% of plaque from tooth surfaces, making it difficult to thoroughly clean hidden areas within the mouth, such as deep in the gingival sulcus, adjacent tooth surfaces, between teeth, and the tongue coating. These areas are prone to residual plaque and soft deposits, providing a breeding ground for bacteria and potentially causing oral diseases.

[0003] As an important oral care product, mouthwash can penetrate deep into various parts of the oral cavity through the flow of liquid, assisting in cleaning areas that are difficult to reach with brushing, and plays an indispensable role in oral care. However, there are many problems with the mouthwashes currently on the market. In order to achieve a bactericidal effect, many mouthwashes add a large amount of chemical bactericides, such as cetylpyridinium chloride and triclosan. Although long-term use of such mouthwashes can inhibit the growth of oral bacteria to a certain extent, it will disrupt the original balance of oral flora. Imbalance of flora may lead to problems such as bad breath and tooth decay. At the same time, some chemical bactericides may also irritate the oral mucosa and cause allergic reactions. For example, some mouthwashes use ingredients such as eugenol and limonene, which can easily cause allergies in users.

[0004] Furthermore, some existing mouthwashes are limited in their functionality and offer less than satisfactory results. They fail to effectively relieve oral and gingival inflammation and may even cause significant irritation to oral wounds. Furthermore, mouthwashes often have poor long-term effects and are unable to moisturize the mouth and freshen breath for extended periods. Summary of the Invention

[0005] The object of the present invention is to provide an antibacterial and anti-inflammatory mouthwash and a preparation method thereof, so as to solve the problems raised in the above background technology.

[0006] To achieve the above object, the present invention provides the following technical solutions:

[0007] An antibacterial and anti-inflammatory mouthwash comprises the following components, measured in percentage by weight: 1-20% of an antibacterial restorative agent, 1-3% of a synergist, 1-8% of a nanocomposite active agent, 1-3% of a surfactant, 0.1-0.5% of a stabilizer, and 0.1-0.5% of a preservative, with the balance being water; the antibacterial restorative agent comprises honeysuckle flower extract, patchouli extract, liquorice extract, sage extract, Centella asiatica extract, and myrrh extract; and the synergist is a tea polyphenol-lactoferrin complex.

[0008] Preferably, the raw materials used in the antibacterial repair agent include, by weight, 5-10 parts of honeysuckle, 3-6 parts of patchouli, 2-5 parts of licorice, 2-5 parts of sage, 1-3 parts of Centella asiatica and 0.1-0.5 parts of myrrh.

[0009] Specifically, the honeysuckle flower extract extraction method includes: crushing the honeysuckle flower, adding it to deionized water, ultrasonically extracting it three times at 50-60°C, centrifuging it after the extraction is completed, collecting the supernatant, concentrating it under reduced pressure, and then drying it;

[0010] The Patchouli extract method includes crushing Patchouli, adding deionized water, heating to 70-80°C, and performing reflux extraction three times while collecting the volatile oil. After extraction, the extract is centrifuged to remove the supernatant, which is then combined with the supernatant after inclusion complexation with β-cyclodextrin (inclusion ratio 1:8, stirring at 60°C for 2 hours), concentrated under reduced pressure, and dried.

[0011] The licorice extract extraction method includes: crushing the licorice, then adding 0.5-1% sodium hydroxide at a material-liquid ratio of 1:8, heating to 60-80°C and stirring for extraction three times, then adjusting the pH to 2-3 with 2M hydrochloric acid, standing for 2 hours, centrifuging at 3000 rpm to collect the precipitate, then dissolving the precipitate with 70% ethanol, heating and refluxing for 1 hour, filtering, and concentrating under reduced pressure to recover ethanol, diluting with water and adjusting the pH to 7-8 with 2M ammonia water or sodium hydroxide, and finally concentrating under reduced pressure and drying;

[0012] The sage extract extraction method includes: crushing the sage, then adding 50% ethanol solution, ultrasonically extracting at 40-50°C for 3 times, centrifuging to obtain the supernatant, concentrating under reduced pressure and then drying;

[0013] The extraction method of Centella asiatica extract is the same as that of honeysuckle flower extract;

[0014] The myrrh extract extraction method includes: crushing the myrrh, adding 50-70% ethanol solution, ultrasonic extraction at 40-50°C for 3 times, centrifuging to obtain the supernatant, recovering the ethanol by vacuum distillation, adding β-cyclodextrin at an inclusion ratio of 1:1, stirring at 50°C to form a water-soluble inclusion complex, and then concentrating under reduced pressure and drying.

[0015] Preferably, the tea polyphenols-lactoferrin complex is prepared according to the following steps:

[0016] S1, dissolving lactoferrin in phosphate buffer to prepare LF solution; dissolving tea polyphenols in ethanol solution to prepare TP solution;

[0017] S2, slowly drop the TP solution into the LF solution, stir and mix to form a homogeneous system;

[0018] S3, slowly adding anhydrous ethanol or acetone dropwise to the homogeneous system under stirring, continuously stirring, and then standing at low temperature for aging;

[0019] S4, centrifuge at low temperature, collect the precipitate, wash, and freeze-dry.

[0020] Preferably, the mass ratio of tea polyphenols to lactoferrin is (1-3):1; in step S2, the concentration of ethanol is 1-50%; in step S4, the dripping rate of anhydrous ethanol or acetone is 1 mL / min, and the dripping amount is 1-3 times the volume of the aqueous phase.

[0021] Preferably, the preparation method of the nanocomposite active agent comprises the following steps:

[0022] A1, dissolving PFC in deionized water to prepare a PFC solution; dissolving vitamin E in anhydrous ethanol to prepare a vitamin E solution; dissolving xylitol in deionized water and adding a small amount of sodium alginate to prepare a xylitol solution;

[0023] A2, drop the vitamin E solution into the PFC solution, homogenize with ultrasound, then add the xylitol solution and stir evenly to obtain a mixed solution;

[0024] A3, evaporating the mixed solution under reduced pressure to remove ethanol, dialysis purification, and freeze-drying to obtain a nanocomposite active agent.

[0025] Preferably, the mass ratio of vitamin E to PFC is (8-16):1, the mass ratio of xylitol to PFC is (1-3):1, and the added amount of sodium alginate is 0.1% of the mass of xylitol.

[0026] Preferably, the preparation method of PFC comprises the following steps:

[0027] B1, low molecular weight chitosan (deacetylation degree ≥90%, molecular weight 5-10 kDa) was selected and its C-6 hydroxyl group was modified with succinic anhydride under weak acidic conditions to form a zwitterionic structure;

[0028] B2, using the block copolymer Pluronic F127, with acrylate groups introduced into its PEG segment;

[0029] B3, through Michael addition reaction, the modified Pluronic F127 reacts with the modified chitosan under alkaline conditions to form PFC.

[0030] Preferably, in step B1, the weakly acidic condition is pH=5.0-6.5, the degree of substitution of succinic anhydride is 5-10%, and in step B3, the alkaline condition is pH=7-8, and the grafting ratio of chitosan and Pluronic F127 is 10-20%.

[0031] Preferably, the surfactant comprises one or a combination of yucca extract and quince bark extract; the stabilizer comprises fenugreek gum; and the preservative comprises one or a combination of oregano oil and grapefruit seed extract.

[0032] Specifically, the yucca extract extraction method includes drying and crushing the yucca rhizomes, adding deionized water, ultrasonically extracting at 60-80° C. for three times, filtering and combining the filtrate, concentrating under reduced pressure to a thick paste, centrifuging at 5000 rpm, and taking the supernatant.

[0033] The extraction method of the soap bark extract is the same as that of the yucca extract, and the raw material used is the soap bark.

[0034] The method for extracting grapefruit seed extract includes crushing grapefruit seeds, adding 50-70% ethanol, ultrasonic extraction at 40-60°C for 3 times, reflux extraction at 60-70°C for 2 hours, filtering and combining the filtrate, removing ethanol by vacuum distillation to obtain a thick paste extract, and freeze-drying.

[0035] The present invention also discloses a method for preparing an antibacterial and anti-inflammatory mouthwash, comprising the following steps:

[0036] C1, dissolve the stabilizer in deionized water, add surfactant, and stir until uniformly dispersed to obtain solution ①;

[0037] C2, add the pre-dissolved antibacterial repair agent to solution ①, stir evenly, adjust the pH to 6.5-7.5, add the synergist, stir evenly at low speed, and obtain solution ②;

[0038] C3, disperse the nanocomposite active agent in deionized water, then add it to solution ②, then add the preservative, and homogenize to obtain.

[0039] The beneficial effects of the above technical solution of the present invention are as follows:

[0040] The whole prescription of the present invention is based on the principle of "clearing away heat without damaging yin, and removing dampness without being too dry", with antibacterial and repairing agents as the core. It contains extracts of honeysuckle, patchouli, licorice, sage, Centella asiatica and myrrh, etc., with a combination of warm and cold properties, which can not only clear away excess heat and dampness, but also avoid damage to the stomach due to excessive cold. It has synchronous antibacterial, anti-inflammatory and repairing effects on multiple targets. Surfactants, stabilizers and preservatives are all added natural components to avoid irritation and damage from chemical reagents, making it suitable for long-term gargling conditioning.

[0041] The synergist of this invention uses molecular composite technology to create a synergistic "natural antibacterial-immunomodulatory" system. Tea polyphenols and lactoferrin form a complex through hydrogen bonding and hydrophobic interactions. The phenolic hydroxyl groups of tea polyphenols bind to the amino groups of lactoferrin, enhancing lactoferrin's affinity for pathogen cell membranes while protecting the tea polyphenols from rapid degradation by oral enzymes, thereby prolonging their duration of action. The complex is naturally derived and non-cytotoxic.

[0042] The present invention prepares nanoactive agents through polymer carrier design and functional component loading. Chitosan modification enhances water solubility and mucosal adhesion time. Acrylate groups are introduced into the PEG end hydroxyl group of Pluronic F127 to improve the vitamin E encapsulation capacity. The two are added to form a stable copolymer. Salivary amylase can slowly degrade the chitosan glycosidic bonds, triggering the sustained release of xylitol. Lipase on the mucosal surface can decompose the PPO segment of Pluronic F127, gradually releasing vitamin E, achieving a time-series synergy of rapid antibacterial and long-lasting repair. At the same time, the nanoparticle size is smaller than the gaps in the mucus layer and can penetrate deep into the mucosal surface to exert its effect. At the same time, the positive charge of PFC interacts with the negative charge of the mucosa, further improving the adsorption efficiency.

[0043] This Traditional Chinese Medicine formula regulates the overall oral microecology. Modern composite ingredients and nanotechnology enhance local therapeutic effects, achieving a synergistic effect of "macro-regulation + micro-precision." It is chemical-preservative-free, mild, and non-irritating, making it suitable for long-term use and for those with oral ulcers. Through molecular compounding and nanocarrier preparation technology, this formula addresses the poor water solubility and susceptibility of natural ingredients to inactivation, improving product stability and bioavailability. DETAILED DESCRIPTION

[0044] The following examples are provided for a better understanding of the present invention and are not intended to limit the best mode of implementation. They do not limit the content and scope of protection of the present invention. Any product identical or similar to the present invention obtained by anyone under the guidance of the present invention or by combining the features of the present invention with other prior arts shall fall within the scope of protection of the present invention.

[0045] If no specific experimental steps or conditions are specified in the examples, the conventional experimental steps or conditions described in the literature in this field can be used. If the manufacturer of the reagents or instruments is not specified, they are all commercially available conventional reagents.

[0046] Example

[0047] An antibacterial and anti-inflammatory mouthwash comprises the following components, measured in weight percentage: 1-20% antibacterial repair agent, 1-3% synergist, 1-8% nanocomposite active agent, 1-3% surfactant, 0.1-0.5% stabilizer and 0.1-0.5% preservative, with the balance being water;

[0048] Among them, the antibacterial repair agent includes honeysuckle extract, patchouli extract, licorice extract, sage extract, Centella asiatica extract and myrrh extract; the raw materials used in the antibacterial repair agent include 5-10 parts of honeysuckle, 3-6 parts of patchouli, 2-5 parts of licorice, 2-5 parts of sage, 1-3 parts of Centella asiatica and 0.1-0.5 parts of myrrh in parts by weight.

[0049] Specifically, the nanocomposite active agent is prepared from Pluronic F127-chitosan graft copolymer (PFC), xylitol and vitamin E; the enhancer is a tea polyphenol-lactoferrin complex; the stabilizer includes fenugreek gum; the surfactant includes one or a combination of two of yucca extract and soap bark extract; and the preservative includes one or a combination of two of oregano oil and grapefruit seed extract.

[0050] The tea polyphenols-lactoferrin complex is prepared according to the following steps:

[0051] S1, dissolving lactoferrin (purity ≥90%) in phosphate buffer (0.01 M) with a pH of 6.0-7.0 to prepare a 0.5-1 mg / mL LF solution; dissolving tea polyphenols (purity ≥95%) in 1-50% ethanol solution to prepare a 1-2 mg / mL TP solution;

[0052] S2, slowly drop the TP solution into the LF solution, stir and mix at 200-300 rpm for 10 min to form a uniform aqueous phase;

[0053] S3, under stirring, slowly add anhydrous ethanol or acetone to the mixture at a rate of 1 mL / min, with the volume ratio of the added amount to the aqueous phase in S3 being (1-3):1. After the addition is complete, continue stirring for 30 minutes, then let it stand at 4°C for 2 hours;

[0054] S4, after aging, centrifuge at 8000g for 15min at 4°C, collect the precipitate, wash three times with 70% ethanol, and freeze-dry to obtain a powdered complex.

[0055] The mass ratio of tea polyphenols to lactoferrin is (1-3):1; in step S4, the dripping rate of anhydrous ethanol or acetone (preferably anhydrous ethanol) is 1 mL / min, and the dripping amount is 1-3 times the volume of the aqueous phase.

[0056] Tea polyphenols contain polyphenols such as catechins, which have broad-spectrum antimicrobial properties. However, they are susceptible to oxidation and discoloration. In acidic environments, they may electrostatically bind to lactoferrin, leading to protein precipitation. Lactoferrin chelates iron ions or disrupts bacterial structure, stagnating or killing bacterial growth. It also modulates the host immune response, promoting inflammation and tissue repair, but its stability is poor. By preparing a tea polyphenol-lactoferrin complex, the antimicrobial activity can be synergistically enhanced, while simultaneously improving the antioxidant and degradation resistance of both, avoiding system compatibility issues associated with direct addition.

[0057] The preparation method of the nanocomposite active agent comprises the following steps:

[0058] 1. PFC preparation

[0059] a) Chitosan modification:

[0060] 1 g of low molecular weight chitosan (degree of deacetylation ≥90%, molecular weight 5-10 kDa) was dissolved in 10 mL of 1% 1-ethyl-3-methylimidazolium acetate solution (w / v) and stirred in a 60°C water bath until transparent. Succinic anhydride, calculated based on a 20% excess molar number of chitosan C-6 hydroxyl groups, was weighed and dissolved in 5 mL of anhydrous DMF and ultrasonically mixed. The succinic anhydride-DMF solution was slowly dripped into the chitosan ion solution while maintaining the pH of the system at 5.0-6.5. The reaction was carried out in a 50°C water bath for 4 h, and then the solution was transferred to a dialysis bag with a molecular weight cutoff of 4.0 kDa and dialyzed with distilled water for 48 h to remove impurities such as unreacted succinic anhydride, small molecular byproducts, and solvent. After dialysis, the solution was freeze-dried to obtain white flocculent modified chitosan.

[0061] b) Pluronic F127 modification: 1 g of Pluronic F127 (polyethylene glycol-polypropylene glycol-polyethylene glycol, PEG-PPO-PEG, molecular weight 12.6 kDa) was weighed and dissolved in 10 mL of anhydrous DMSO and stirred until completely dissolved. One equivalent of acrylic acid, 1.2 equivalents of EDC, and 1.2 equivalents of NHS were then added, mixed by sonication, and the pH was adjusted to 7-8 by the addition of TEA. The reaction mixture was stirred at room temperature for 24 h. The reaction solution was centrifuged at 10,000 rpm for 10 min. Ten volumes of cold ether were slowly added dropwise to the supernatant, and stirred until a white precipitate formed. The precipitate was collected by centrifugation, washed, and dried to obtain a white powder.

[0062] c) Copolymerization Synthesis: Dissolve 0.5 g of the modified chitosan prepared in step a) in 10 mL of phosphate buffer to obtain Solution A. Weigh the white powder prepared in step b) (calculated to a grafting efficiency of 10-20%) and dissolve it in 5 mL of phosphate buffer. Ultrasonic dispersion is performed to obtain Solution B. Slowly add Solution B to Solution A and stir at room temperature, maintaining the pH between 8.0 and 9.0 to prevent amino group protonation. The reaction is continued for 6 hours, and the grafting efficiency is monitored regularly. After the reaction is completed, add an equal volume of anhydrous ethanol, transfer the mixture to a dialysis bag with a cutoff of 10 kDa, and dialyze against phosphate buffer for 24 hours. The dialyzate is then freeze-dried to obtain PFC.

[0063] Through the molecular structure design of "core-shell" graft copolymer (PFC), the hydrophilic segment uses chitosan. In a weakly acidic environment, the amino groups on the chitosan molecular chain will be protonated to form positively charged -NH3 + , and specifically adheres to the negatively charged surface of the oral mucosa (salivary mucin) through classical action, thereby prolonging the retention time of the nanocomposite active agent in the oral mucosa; the hydrophobic segment adopts the block copolymer Pluronic F127 (polyethylene glycol-polypropylene glycol-polyethylene glycol, PEG-PPO-PEG), in which the PPO segment is the hydrophobic core, which can dissolve fat-soluble vitamin E; the PEG segments at both ends are hydrophilic chains, and acrylate groups are introduced to synthesize Pluronic F127-chitosan graft copolymer (PFC) through Michael addition reaction. By controlling the grafting rate at 10~20%, it can ensure that the hydrophobic region forms a stable drug core, and the hydrophilic region retains sufficient adhesion groups to maintain its adhesion performance to the mucosa.

[0064] In addition, by modifying chitosan, a carboxyl group was introduced into the C-6 hydroxyl group to form a zwitterionic structure (-NH3 + / -COO - ), which not only has electrostatic adsorption but also hydrogen bonding, enhancing its interaction with the mucosa. On the other hand, it also improves the water solubility of chitosan in a neutral environment, allowing it to maintain good performance in a wider pH environment. By introducing acrylate groups into the PEG segment of Pluronic F127, the encapsulation capacity of vitamin E is enhanced through hydrophobic interactions, thereby improving its stability and delivery efficiency.

[0065] Specifically, the molecular formula of DMF is C3H7NO, the molecular formula of DMSO is C2H6OS, and the molecular formula of EDC is C8H 17 The molecular formula of N3 and NHS is C4H5NO3, and the molecular formula of TEA is C6H 15 NO3.

[0066] 2. Preparation of Nanomicelles

[0067] d) dissolving PFC in deionized water to prepare a 20 mg / mL PFC solution; dissolving vitamin E in anhydrous ethanol to prepare a 10 mg / mL vitamin E solution; dissolving xylitol in deionized water and adding sodium alginate at a concentration of 0.1% by weight of xylitol to prepare a 50 mg / mL xylitol solution;

[0068] e) Add the vitamin E solution dropwise to the PFC solution, maintaining the system temperature ≤15°C and pH 6.0-7.0, and homogenize at 300W ultrasonic for 5-8 minutes. Immediately add the xylitol solution (pre-cooled to 4°C, pH matching that of the PFC-vitamin E mixed solution) and stir at 200-500 rpm to obtain a mixed solution.

[0069] f) The mixed solution is evaporated under reduced pressure to remove ethanol, and then dialyzed for purification and freeze-dried to obtain a nanocomposite active agent.

[0070] Wherein, in step d), the volume ratio of vitamin E solution to PFC solution is (4-8):1, and the mass ratio of xylitol to PFC is (1-3):1.

[0071] The hydrophobic segment (PPO chain) of PFC spontaneously aggregates in aqueous solution due to hydrophobic interactions to form a core; the hydrophilic segment (PEG chain + chitosan amino group) extends outward to form a hydration layer, which encapsulates vitamin E (dissolved in the PPO core) and xylitol (adsorbed on the chitosan shell) to form core-shell nanomicelles.

[0072] The preparation method of the above-mentioned antibacterial and anti-inflammatory mouthwash comprises the following steps:

[0073] C1, slowly add stabilizer to deionized water at 30-40℃, stir at 200rpm for 10min, then add surfactant, stir and disperse for 5min to obtain solution ①;

[0074] C2, slowly add the antibacterial repair agent (pre-dissolved in deionized water) to solution ①, adjust and maintain the pH to 6.5-7.5, then add the synergist, stir at 150 rpm for 15 minutes, and obtain solution ②;

[0075] C3, add the nanocomposite active agent (pre-dispersed in deionized water) to solution ②, then add the preservative, and homogenize to obtain.

[0076] Example 1

[0077] The preparation method of the antibacterial and anti-inflammatory mouthwash in the above embodiment is adopted, wherein the following components are included in weight percentage: 10% antibacterial repair agent, 2% synergist, 3% nanocomposite active agent, 2% yucca extract, 0.3% fenugreek gum and 0.2% grapefruit seed extract, and the balance is water;

[0078] The antibacterial repair agent includes honeysuckle flower extract, patchouli extract, liquorice extract, sage extract, Centella asiatica extract and myrrh extract. The raw materials used include 7 parts of honeysuckle flower, 4 parts of patchouli, 4 parts of liquorice, 3 parts of sage, 2 parts of Centella asiatica and 0.2 parts of myrrh in parts by weight.

[0079] Example 2

[0080] The method for preparing the antibacterial and anti-inflammatory mouthwash of the above embodiment is adopted, wherein the mouthwash comprises the following components, calculated by weight percentage: 3% antibacterial repair agent, 3% synergist, 8% nanocomposite active agent, 1% Quillaja bark extract, 0.1% fenugreek gum and 0.1% oregano oil, and the balance is water;

[0081] The antibacterial repair agent includes honeysuckle flower extract, patchouli extract, liquorice extract, sage extract, Centella asiatica extract and myrrh extract. The raw materials used include 8 parts of honeysuckle flower, 5 parts of patchouli, 3 parts of liquorice, 2 parts of sage, 2 parts of Centella asiatica and 0.3 parts of myrrh in parts by weight.

[0082] Example 3

[0083] The preparation method of the antibacterial and anti-inflammatory mouthwash in the above embodiment is adopted, wherein the following components are included in weight percentage: 5% antibacterial repair agent, 3% synergist, 6% nanocomposite active agent, 0.5% yucca extract, 0.5% quince bark extract, 0.2% fenugreek gum, 0.1% oregano oil and 0.1% grapefruit seed extract, and the balance is water;

[0084] The antibacterial repair agent includes honeysuckle flower extract, patchouli extract, liquorice extract, sage extract, Centella asiatica extract and myrrh extract. The raw materials used include 10 parts of honeysuckle flower, 6 parts of patchouli, 2 parts of liquorice, 4 parts of sage, 3 parts of Centella asiatica and 0.5 parts of myrrh in parts by weight.

[0085] Example 4

[0086] The preparation method of the antibacterial and anti-inflammatory mouthwash in the above embodiment is adopted, wherein the following components are included in weight percentage: 8% antibacterial repair agent, 1% synergist, 5% nanocomposite active agent, 3% yucca extract, 0.4% fenugreek gum, 0.1% oregano oil and 0.3% grapefruit seed extract, and the balance is water;

[0087] The antibacterial repair agent includes honeysuckle flower extract, patchouli extract, liquorice extract, sage extract, Centella asiatica extract and myrrh extract. The raw materials used include 5 parts of honeysuckle flower, 3 parts of patchouli, 2 parts of liquorice, 2 parts of sage, 1 part of Centella asiatica and 0.1 part of myrrh in parts by weight.

[0088] Example 5

[0089] The preparation method of the antibacterial and anti-inflammatory mouthwash in the above embodiment is adopted, wherein the following components are included in weight percentage: 12% antibacterial repair agent, 1% synergist, 1% nanocomposite active agent, 2% yucca extract, 0.5% fenugreek gum and 0.5% grapefruit seed extract, and the balance is water;

[0090] The antibacterial repair agent includes honeysuckle flower extract, patchouli extract, liquorice extract, sage extract, Centella asiatica extract and myrrh extract. The raw materials used include 9 parts of honeysuckle flower, 5 parts of patchouli, 4 parts of liquorice, 3 parts of sage, 2 parts of Centella asiatica and 0.4 parts of myrrh in parts by weight.

[0091] Comparative Example 1

[0092] The difference between the remaining Example 1 is that the honeysuckle extract is not added to the antibacterial repair agent.

[0093] Comparative Example 2

[0094] The difference between the remaining examples 1 is that no sage extract is added to the antibacterial repair agent.

[0095] Comparative Example 3

[0096] The remaining Example 1 differs in that no synergist is added.

[0097] Comparative Example 4

[0098] The difference between the remaining examples 1 is that the synergists include tea polyphenols and lactoferrin, which are added independently without being compounded.

[0099] Comparative Example 5

[0100] The difference between the remaining examples 1 is that no nano-active composite agent is added.

[0101] Comparative Example 6

[0102] The difference between the remaining examples 1 is that no nanocomposite active agent is prepared, but xylitol and vitamin E are directly added, and the two are added independently.

[0103] Comparative Example 7

[0104] The difference between the remaining examples 1 is that chitosan is not modified during the preparation of the nanocomposite active agent.

[0105] Examples 1 to 5 and Comparative Examples 1 to 7 were tested according to the following method:

[0106] According to 5.1.1 Quantitative antibacterial test of suspension in WS / T 605-2019 "Evaluation Methods for Antibacterial and Antibacterial Effects", the mouthwash stock solution was used with an action time of 2 minutes to determine the antibacterial rate. The results are shown in Table 1.

[0107] Table 1 Results of in vitro antibacterial test of mouthwash

[0108] Staphylococcus aureus inhibition rate Escherichia coli inhibition rate Helicobacter pylori inhibition rate Example 1 98.7% 96.1% 95.7% Example 2 99.3% 94.5% 94.8% Example 3 98.1% 95.8% 95.0% Example 4 97.5% 95.6% 94.3% Example 5 98.8% 96.7% 96.2% Comparative Example 1 85.4% 78.0% 75.9% Comparative Example 2 88.2% 82.9% 80.5% Comparative Example 3 92.6% 88.5% 85.1% Comparative Example 4 93.0% 89.2% 87.4% Comparative Example 5 88.9% 83.3% 80.6% Comparative Example 6 90.3% 85.6% 82.8% Comparative Example 7 93.4% 89.1% 86.7%

[0109] KB cells were cultured adherently in a culture incubator at 37°C and 5% CO2 using DMEM medium. The medium was changed every 2 days. When the cell confluence reached 70-80%, the cells were passaged at a ratio of 1:4. After passage 4, the old medium was discarded, the cells were gently washed twice with PBS, and then serum-free medium containing 1 μg / mL lipopolysaccharide was added. The cell suspension was taken and plated at 5×10 4 Cells were seeded at a concentration of 100 cells / mL in several 24-well plates (1 mL / well). The KB cell inflammation model was induced in an incubator for 10 h. The mouthwashes of Examples 1 to 5 and Comparative Examples 1 to 8 were then added to a final volume of 1 mL, and cultured to the endpoint (12 h). The concentration of the diluted mouthwash was 5%.

[0110] The supernatants of the above treatments were collected and the cytokine levels of IL-6, IL-8 and TNF-α in the supernatants were detected by enzyme-linked immunosorbent assay. The results are shown in Table 2 below.

[0111] Table 2 Cytokine level detection results

[0112] IL-6 (%) IL-8 (%) TNF-α (%) Example 1 28.3% 32.7% 25.0% Example 2 35.5% 38.2% 32.8% Example 3 35.1% 38.4% 30.9% Example 4 32.6% 35.0% 28.3% Example 5 30.7% 33.2% 27.5% Comparative Example 1 55.1% 58.8% 52.4% Comparative Example 2 58.9% 61.0% 55.6% Comparative Example 3 65.3% 68.1% 60.7% Comparative Example 4 52.5% 55.2% 48.0% Comparative Example 5 70.8% 73.4% 65.9% Comparative Example 6 50.3% 53.6% 47.1% Comparative Example 7 40.5% 43.7% 36.2%

[0113] Note: The cytokine level of the normal inflammation model group was taken as 100% as the control. The lower the value, the stronger the anti-inflammatory effect.

[0114] By comparing the test data of Examples 1 to 5 and Comparative Examples 1 to 7 in Tables 1 and 2, it can be seen that the antibacterial repair agent provides natural antibacterial ingredients, the synergist enhances the interaction between the ingredients, and the nanocomposite active agent improves the delivery efficiency through the carrier effect. The three work together to make the antibacterial rate greater than 94%, which is significantly higher than the antibacterial rate of the control group in which a single ingredient is missing (≤88.9%). In addition, the relative levels of key inflammatory factors such as IL-6, IL-8 and TNF-α in the examples (maximum 35.5%, 38.4%, 32.8%) are significantly lower than those in the control group (minimum 40.5%, 43.7%, 36.2%).

[0115] Another 50 volunteers aged between 15 and 55 were randomly divided into 5 groups and used the mouthwash prepared in Examples 1 to 5 for 7 days, once in the morning, noon, and evening, 20 mL each time, gargling for 2 minutes and then spitting out. After the use, all volunteers reported no oral irritation. Among them, those suffering from oral ulcers, periodontal disease, and bad breath had their oral conditions significantly improved after use.

[0116] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention and are not limiting. Other modifications or equivalent substitutions made to the technical solution of the present invention by ordinary technicians in this field should be included in the scope of the claims of the present invention as long as they do not depart from the spirit and scope of the technical solution of the present invention.

Claims

1. An antibacterial and anti-inflammatory mouthwash, characterized in that: The invention comprises the following components in weight percentage: 1-20% antibacterial repair agent, 1-3% synergist, 1-8% nanocomposite active agent, 1-3% surfactant, 0.1-0.5% stabilizer and 0.1-0.5% preservative, with the balance being water; the antibacterial repair agent comprises honeysuckle extract, patchouli extract, liquorice extract, sage extract, Centella asiatica extract and myrrh extract; the synergist is a tea polyphenol-lactoferrin complex.

2. The antibacterial and anti-inflammatory mouthwash according to claim 1, characterized in that: Calculated by weight, the raw materials used in the antibacterial repair agent include 5-10 parts of honeysuckle flowers, 3-6 parts of patchouli, 2-5 parts of licorice, 2-5 parts of sage, 1-3 parts of centella asiatica and 0.1-0.5 parts of myrrh.

3. The antibacterial and anti-inflammatory mouthwash according to claim 1, characterized in that: The surfactant comprises one or a combination of yucca extract and soap bark extract; the stabilizer comprises fenugreek gum; and the preservative comprises one or a combination of oregano oil and grapefruit (Opilia Roxb) seed extract.

4. The antibacterial and anti-inflammatory mouthwash according to claim 1, characterized in that The tea polyphenols-lactoferrin complex was prepared according to the following steps: S1, dissolving lactoferrin in phosphate buffer to prepare LF solution; dissolving tea polyphenols in ethanol solution to prepare TP solution; S2, slowly drop the TP solution into the LF solution, stir and mix to form a homogeneous system; S3, slowly adding anhydrous ethanol or acetone dropwise to the homogeneous system under stirring, continuously stirring, and then standing at low temperature for aging; S4, centrifuge at low temperature, collect the precipitate, wash, and freeze-dry.

5. The antibacterial and anti-inflammatory mouthwash according to claim 4, characterized in that The mass ratio of tea polyphenols to lactoferrin is (1-3):1; in step S1, the concentration of ethanol is 1-50%; in step S3, the drop rate of anhydrous ethanol or acetone is 1 mL / min, and the drop amount is 1-3 times the volume of the aqueous phase.

6. The antibacterial and anti-inflammatory mouthwash according to claim 1, characterized in that The preparation method of the nanocomposite active agent comprises the following steps: A1, dissolving PFC in deionized water to prepare a PFC solution; dissolving vitamin E in anhydrous ethanol to prepare a vitamin E solution; dissolving xylitol in deionized water and adding a small amount of sodium alginate to prepare a xylitol solution; A2, dropwise add the vitamin E solution into the PFC solution, homogenize with ultrasonication, then add the xylitol solution and stir evenly to obtain a mixed solution; A3, evaporating the mixed solution under reduced pressure to remove ethanol, dialysis purification, and freeze-drying to obtain a nanocomposite active agent.

7. The antibacterial and anti-inflammatory mouthwash according to claim 6, characterized in that The mass ratio of vitamin E to PFC is (8-16):1, the mass ratio of xylitol to PFC is (1-3):1, and the added amount of sodium alginate is 0.1% of the mass of xylitol.

8. The antibacterial and anti-inflammatory mouthwash according to claim 6, characterized in that The preparation method of PFC comprises the following steps: B1, chitosan with a molecular weight of 5-10 kDa was selected and its C-6 hydroxyl group was modified with succinic anhydride under weak acidic conditions to form a zwitterionic structure; B2, using the block copolymer Pluronic F127, with acrylate groups introduced into its PEG segment; B3, the modified Pluronic F127 is reacted with the modified chitosan under alkaline conditions through Michael addition reaction to form PFC.

9. The antibacterial and anti-inflammatory mouthwash according to claim 7, characterized in that: In step B1, the weakly acidic condition is pH=5.0~6.5, the substitution degree of succinic anhydride is 5~10%, and in step B3, the alkaline condition is pH=7~8, and the grafting rate of chitosan and PluronicF127 is 10~20%.

10. A method for preparing a mouthwash, using the antibacterial and anti-inflammatory mouthwash according to any one of claims 1 to 9, characterized in that: The following steps are involved: C1, dissolve the stabilizer in deionized water, add surfactant, and stir until uniformly dispersed to obtain solution ①; C2, add the pre-dissolved antibacterial repair agent to solution ①, stir evenly, adjust the pH to 6.5-7.5, add the synergist, stir evenly at low speed, and obtain solution ②; C3, disperse the nanocomposite active agent in deionized water, then add it to solution ②, then add the preservative, and homogenize to obtain.