A highly effective antibacterial oral care fluid and a method of making the same

Abstract

The application belongs to the technical field of oral care, and particularly relates to a high-efficiency antibacterial oral care solution and a preparation method thereof. The high-efficiency antibacterial oral care solution comprises the following components in parts by weight: 0.01-0.5 parts of zinc lactate, 0.1-2 parts of plant polyphenol extract, 0.05-0.3 parts of N-trimethyl chitosan, 0.5-2 parts of a buffer, 5-15 parts of a humectant, 0.05-0.2 parts of a membrane permeation enhancer, 0.01-0.1 parts of a peppermint essence, and 80-94 parts of deionized water. The preparation method is to first form a zinc-polyphenol complex by mixing zinc lactate and plant polyphenol extract, and then form a stable ternary complex system by electrostatic interaction between the zinc-polyphenol complex and N-trimethyl chitosan. The application solves the technical problems of poor compatibility and short action time of traditional oral care solutions, and has excellent effects of synergistic antibacterial enhancement and long-lasting action.

Description

Technical Field

[0001] This invention belongs to the field of oral care technology, specifically relating to a highly effective antibacterial oral care solution and its preparation method. Background Technology

[0002] Oral diseases such as tooth decay, gingivitis, and halitosis are mostly caused by oral pathogens, such as Streptococcus mutans and Porphyromonas gingivalis, and the biofilms they form. Existing oral care solutions mainly include chemical antibacterial agents (such as chlorhexidine and triclosan), natural extracts (such as tea tree oil and propolis), and alcohol-based preparations. However, these solutions have significant drawbacks: long-term use of chemical antibacterial agents easily leads to bacterial resistance, oral microecological imbalance, and tooth discoloration; natural extracts have weak antibacterial effects and short duration of action; alcohol-based preparations cause oral dryness, mucosal irritation, and low patient compliance. Furthermore, existing technologies often employ simple physical mixing of multiple active ingredients, lacking synergistic chemical reactions between components, resulting in poor physical compatibility. During storage, phase separation or precipitation of active ingredients easily occurs, affecting product uniformity and stability. Moreover, the active ingredients fail to form a stable complex structure, making them easily and quickly cleared by saliva in the oral cavity, resulting in a short duration of action.

[0003] Therefore, there is an urgent need to develop a highly effective antibacterial oral care solution that has stronger antibacterial efficacy, longer-lasting effect, can effectively inhibit biofilm formation, and is safe to use. Summary of the Invention

[0004] To address the shortcomings of existing technologies, this invention provides a highly efficient antibacterial oral care solution and its preparation method. The core innovation of this invention lies in the following: by designing a specific ratio of plant polyphenols and metal ions, an in-situ complexation reaction is carried out under mild pH conditions to generate a stable nanoscale metal-polyphenol complex. At the same time, this invention introduces N-trimethyl chitosan with a strong positive charge, which interacts with the metal-polyphenol complex through electrostatic interaction to form a stable ternary complex system. This ternary complex system not only prolongs the action time and enhances the permeability of biofilms, but also achieves a highly efficient and stable antibacterial effect.

[0005] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0006] This invention provides a highly effective antibacterial oral care solution, comprising the following components by weight: 0.01-0.5 parts zinc lactate, 0.1-2 parts plant polyphenol extract, 0.05-0.3 parts N-trimethyl chitosan, 0.5-2 parts buffer, 5-15 parts humectant, 0.05-0.2 parts membrane permeability enhancer, 0.01-0.1 parts peppermint flavor, and 80-94 parts deionized water.

[0007] Further, the preparation method of the N-trimethyl chitosan is as follows: (1) weigh chitosan, disperse it in isopropanol, add sodium hydroxide solution with a concentration of 40-50wt% under stirring, and alkalize and activate it at 60-70℃ for 2-3 hours; (2) cool the reaction system to 40-50℃, slowly add iodomethane under nitrogen protection, and after the addition is complete, raise the temperature to 60-70℃ and continue the reaction for 12-24 hours; (3) after the reaction is completed, cool to room temperature, filter and collect the solid, wash it with 80-95% ethanol solution until neutral, and vacuum dry it at 50-60℃ to constant weight. After pulverizing and sieving, the N-trimethyl chitosan is obtained.

[0008] Furthermore, the plant polyphenol extract is any one of green tea polyphenols, grape seed polyphenols, or olive leaf polyphenols, with a polyphenol content of 78%-90%; the buffer is a citric acid-sodium citrate buffer system used to maintain a suitable pH range of 5.8-6.2; the humectant is glycerin or sorbitol; and the membrane permeation enhancer is azone.

[0009] This invention also provides a method for preparing a highly effective antibacterial oral care solution, comprising the following steps:

[0010] S1: Preparation of N-trimethyl chitosan solution: First, divide the deionized water into four parts. Then, weigh N-trimethyl chitosan and slowly add it to the first part of the deionized water, which is preheated to 40-50℃. Stir and dissolve the solution at 400-600 rpm for 1-2 hours to prepare an N-trimethyl chitosan solution with a mass concentration of 0.5%-1% for later use.

[0011] S2: Preparation of plant polyphenol extract: Mix the plant polyphenol extract with the second part of deionized water at a material-liquid ratio of 1:10-1:20, add cellulase at a weight of 0.5%-1% of the plant polyphenol extract, and enzymatically hydrolyze for 30-60 minutes at 40-50℃ and pH 5.0-6.0. After filtration, a clear plant polyphenol extract is obtained.

[0012] S3: Complexation and compounding reaction: Zinc lactate was dissolved in the deionized water in the third part, and the pH was adjusted to 5.8-6.2 with the addition of buffer. The plant polyphenol extract obtained in S2 was slowly added to it. The reaction was carried out at 35℃±2℃ and 300-500rpm for 1 hour, so that the zinc ions in zinc lactate and the ortho-phenolic hydroxyl groups in the plant polyphenol extract molecules could undergo a complexation reaction to form a zinc-polyphenol complex dispersion. Then, the N-trimethyl chitosan solution prepared in S1 was slowly added dropwise under continuous stirring. After the addition was completed, the reaction was continued at a constant temperature for 0.5-1 hour, so that the strongly positively charged N-trimethyl chitosan and the negatively charged zinc-polyphenol complex could form a stable ternary complex system through electrostatic interaction, and a complex dispersion was obtained.

[0013] S4: Mixing and preparation: Add humectant, membrane permeability enhancer, peppermint flavor and the remaining deionized water in sequence to the complex dispersion obtained in S3. After stirring evenly, filter through a 0.22μm microporous membrane for sterilization and fill into a container to obtain the highly effective antibacterial oral care solution.

[0014] Compared with the prior art, the beneficial effects of the present invention are:

[0015] (1) This invention uses zinc lactate, plant polyphenol extract and N-trimethyl chitosan as core active components. First, the zinc ions in zinc lactate undergo a complexation reaction with the ortho-phenolic hydroxyl groups in the plant polyphenol extract molecules. Then, it interacts electrostatically with the strongly positively charged N-trimethyl chitosan to form a stable ternary complex. This solves the technical problem of poor compatibility and easy phase separation or inactivation when multiple active ingredients in traditional oral care solutions are simply physically mixed. Moreover, this ternary complex organically combines the antibacterial effect of zinc lactate with the membrane-destructive effect of plant polyphenols with the cationic antibacterial effect and membrane adsorption effect of N-trimethyl chitosan, resulting in a significant synergistic antibacterial effect and helping to delay the development of drug resistance.

[0016] (2) In the preparation process, the stability of the ternary complex is ensured by controlling the reaction conditions. It can be firmly adsorbed onto the oral mucosa and tooth surface by means of its electrostatic binding structure and the bioadhesiveness of N-trimethyl chitosan, which can prolong the action time of the active ingredients and achieve long-lasting antibacterial effect. At the same time, the strong positive charge of N-trimethyl chitosan and the membrane permeability enhancer azone added to the formula have a synergistic permeation-promoting effect, which can penetrate the negatively charged dental plaque biofilm matrix, solve the technical bottleneck that conventional antibacterial ingredients are difficult to reach the deep infection area due to the biofilm barrier, and thus achieve effective removal of deep colonies.

[0017] (3) The present invention uses a citric acid-sodium citrate buffer system to precisely maintain the pH of the product in a weakly acidic range of 5.8-6.2, which is close to the pH of a healthy oral environment, thus minimizing potential irritation to tooth enamel and oral mucosa; the selected glycerin or sorbitol as a moisturizer, together with peppermint flavoring, provide a good oral moist feeling and fresh taste, suitable for long-term daily use. Attached Figure Description

[0018] Figure 1 This is a structural diagram of the N-trimethylchitosan prepared in this invention;

[0019] Figure 2 This is a diagram illustrating the chemical synthesis process of the N-trimethylchitosan prepared in this invention. Detailed Implementation

[0020] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0021] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those familiar to those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to this invention. The preferred embodiments and materials described herein are for illustrative purposes only and do not limit the scope of this application.

[0022] The N-trimethylchitosan in the following examples was prepared according to the method described in the invention, and its synthesis process is as follows: Figure 1 Unless otherwise specified, all other materials used are new materials purchased from the market.

[0023] Example 1: This example provides a highly effective antibacterial oral care solution, the raw materials of which include the following parts by weight: 0.01 parts zinc lactate, 0.1 parts green tea polyphenol extract (polyphenol content is 85%), 0.05 parts N-trimethyl chitosan, 0.5 parts citric acid-sodium citrate buffer, 5 parts glycerin, 0.05 parts azone, 0.01 parts peppermint flavor, and 80 parts deionized water.

[0024] The preparation method of the N-trimethyl chitosan is as follows: (1) Weigh 10g of chitosan, disperse it in 100mL of isopropanol, add 20mL of sodium hydroxide solution with a concentration of 40wt% under stirring, and alkalize and activate it at 60℃ for 2 hours; (2) Cool the reaction system to 40℃, slowly add 15mL of iodomethane under nitrogen protection, and after the addition is complete, raise the temperature to 60℃ and continue the reaction for 12 hours; (3) After the reaction is completed, cool to room temperature, filter and collect the solid, wash it with 80% ethanol solution until neutral, and vacuum dry it at 50℃ to constant weight. After pulverizing and passing it through a 100-mesh sieve, the N-trimethyl chitosan is obtained.

[0025] This embodiment also provides a method for preparing a highly effective antibacterial oral care solution, including the following steps:

[0026] S1: Preparation of N-trimethyl chitosan solution: Weigh 0.5g of N-trimethyl chitosan and slowly add it to 40 parts of deionized water preheated to 40℃. Stir at 400rpm for 1 hour to dissolve and prepare an N-trimethyl chitosan solution with a mass concentration of 0.5%.

[0027] S2: Preparation of plant polyphenol extract: Mix green tea polyphenol extract with 2 parts deionized water at a material-to-liquid ratio of 1:20, add cellulase at a weight of 0.5% of the green tea polyphenol extract, and enzymatically hydrolyze for 60 minutes at 40℃ and pH 5.0. After filtration, a clear plant polyphenol extract is obtained.

[0028] S3: Complexation and compounding reaction: Zinc lactate was dissolved in 10 parts of deionized water, and the pH was adjusted to 5.8 with the addition of citrate-sodium citrate buffer. The plant polyphenol extract obtained in S2 was slowly added to it, and the reaction was carried out at 33°C and 300 rpm for 1 hour to form a zinc-polyphenol complex dispersion. Then, the N-trimethyl chitosan solution prepared in S1 was slowly added dropwise under continuous stirring. After the addition was completed, the reaction was continued at a constant temperature for 1 hour, so that the strongly positively charged N-trimethyl chitosan and the negatively charged zinc-polyphenol complex formed a stable ternary complex system through electrostatic interaction, and the complex dispersion was obtained.

[0029] S4: Mixing and preparation: Add glycerin, azone, peppermint flavoring and the remaining 28 parts of deionized water to the complex dispersion obtained in S3 in sequence. After stirring evenly, filter through a 0.22μm microporous membrane for sterilization and fill into the container to obtain the highly effective antibacterial oral care solution.

[0030] Example 2: This example provides a highly effective antibacterial oral care solution, the raw materials of which include the following parts by weight: 0.25 parts zinc lactate, 1.0 part grape seed polyphenol extract (polyphenol content is 78%), 0.15 parts N-trimethyl chitosan, 1.0 part citric acid-sodium citrate buffer, 10 parts sorbitol, 0.1 part azone, 0.05 parts peppermint flavor, and 87.45 parts deionized water.

[0031] The preparation method of the N-trimethyl chitosan is as follows: (1) Weigh 10g of chitosan, disperse it in 100mL of isopropanol, add 25mL of sodium hydroxide solution with a concentration of 45wt% under stirring, and alkalize and activate it at 65℃ for 2.5 hours; (2) Cool the reaction system to 45℃, slowly add 20mL of iodomethane under nitrogen protection, and after the addition is complete, raise the temperature to 65℃ and continue the reaction for 18 hours; (3) After the reaction is completed, cool to room temperature, filter and collect the solid, wash it with 90% ethanol solution until neutral, and vacuum dry it at 55℃ to constant weight. After pulverizing and passing it through a 100-mesh sieve, the N-trimethyl chitosan is obtained.

[0032] This embodiment also provides a method for preparing a highly effective antibacterial oral care solution, including the following steps:

[0033] S1: Preparation of N-trimethyl chitosan solution: Weigh 1.0g of N-trimethyl chitosan and slowly add it to 50 parts of deionized water preheated to 45℃. Stir at 500rpm for 1.5 hours to dissolve and prepare an N-trimethyl chitosan solution with a mass concentration of 0.8% for later use.

[0034] S2: Preparation of plant polyphenol extract: Grape seed polyphenol extract is mixed with 15 parts of deionized water at a material-liquid ratio of 1:15. Cellulase is added at a weight of 0.8% of the grape seed polyphenol extract. The mixture is enzymatically hydrolyzed at 45℃ and pH 5.5 for 45 minutes. After filtration, a clear plant polyphenol extract is obtained.

[0035] S3: Complexation and compounding reaction: Zinc lactate was dissolved in 12 parts of deionized water, and the pH was adjusted to 6.0 with citrate-sodium citrate buffer. The plant polyphenol extract obtained in S2 was slowly added to it, and the reaction was carried out at 35°C and 400 rpm for 1 hour to form a zinc-polyphenol complex dispersion. Then, the N-trimethyl chitosan solution prepared in S1 was slowly added dropwise under continuous stirring. After the addition was completed, the reaction was continued at a constant temperature for 0.75 hours, so that the strongly positively charged N-trimethyl chitosan and the negatively charged zinc-polyphenol complex formed a stable ternary complex system through electrostatic interaction, and the complex dispersion was obtained.

[0036] S4: Mixing and preparation: Sorbitol, azone, peppermint flavoring and the remaining 10.45 parts of deionized water are added sequentially to the complex dispersion obtained in S3. After stirring evenly, the mixture is filtered through a 0.22μm microporous membrane for sterilization and then filled to obtain the highly effective antibacterial oral care solution.

[0037] Example 3: This example provides a highly effective antibacterial oral care solution, the raw materials of which include the following parts by weight: 0.5 parts zinc lactate, 2.0 parts olive leaf polyphenol extract (polyphenol content is 90%), 0.3 parts N-trimethyl chitosan, 2.0 parts citrate-sodium citrate buffer, 15 parts glycerin, 0.2 parts azone, 0.1 parts peppermint flavor, and 94 parts deionized water.

[0038] The preparation method of the N-trimethyl chitosan is as follows: (1) Weigh 10g of chitosan, disperse it in 100mL of isopropanol, add 30mL of 50wt% sodium hydroxide solution under stirring, and alkalize and activate it at 70℃ for 3 hours; (2) Cool the reaction system to 50℃, slowly add 25mL of iodomethane under nitrogen protection, and after the addition is complete, raise the temperature to 70℃ and continue the reaction for 24 hours; (3) After the reaction is completed, cool to room temperature, filter and collect the solid, wash it with 95% ethanol solution until neutral, and vacuum dry it at 60℃ to constant weight. After pulverizing and passing it through a 100-mesh sieve, the N-trimethyl chitosan is obtained.

[0039] This embodiment also provides a method for preparing a highly effective antibacterial oral care solution, including the following steps:

[0040] S1: Preparation of N-trimethyl chitosan solution: Weigh 1.5g of N-trimethyl chitosan and slowly add it to 60 parts of deionized water preheated to 50℃. Stir at 600rpm for 2 hours to dissolve and prepare an N-trimethyl chitosan solution with a mass concentration of 1%.

[0041] S2: Preparation of plant polyphenol extract: Mix olive leaf polyphenol extract with 20 parts of deionized water at a material-to-liquid ratio of 1:10, add cellulase at a weight of 1% of olive leaf polyphenol extract, and enzymatically hydrolyze for 30 minutes at 50℃ and pH 6.0. After filtration, a clear plant polyphenol extract is obtained.

[0042] S3: Complexation and compounding reaction: Zinc lactate was dissolved in 10 parts of deionized water, and the pH was adjusted to 6.2 with the addition of citrate-sodium citrate buffer. The plant polyphenol extract obtained in S2 was slowly added first, and the reaction was carried out at 37°C and 500 rpm for 1 hour to form a zinc-polyphenol complex dispersion. Then, the N-trimethyl chitosan solution prepared in S1 was slowly added dropwise under continuous stirring. After the addition was completed, the reaction was continued at a constant temperature for 0.5 hours, so that the strongly positively charged N-trimethyl chitosan and the negatively charged zinc-polyphenol complex formed a stable ternary complex system through electrostatic interaction, and the complex dispersion was obtained.

[0043] S4: Mixing and preparation: Add glycerin, azone, peppermint flavoring and the remaining 4 parts of deionized water to the complex dispersion obtained in S3 in sequence. After stirring evenly, filter through a 0.22μm microporous membrane for sterilization and fill into the container to obtain the highly effective antibacterial oral care solution.

[0044] Comparative Example 1: The difference between this comparative example and Example 2 is that the raw materials used in this example use ordinary chitosan in equal parts by weight instead of N-trimethyl chitosan. That is, the raw materials are: 0.25 parts zinc lactate, 1.0 part grape seed polyphenol extract, 0.15 parts ordinary chitosan, 1.0 part citrate-sodium citrate buffer, 10 parts sorbitol, 0.1 parts azone, 0.05 parts peppermint flavor, and 87.45 parts deionized water. The preparation step of N-trimethyl chitosan is omitted in the preparation method. Ordinary chitosan is used directly in step S1, and ordinary chitosan solution is directly mixed with zinc-polyphenol complex to obtain complex dispersion in step S3. The remaining steps are unchanged.

[0045] Comparative Example 2: The difference between this comparative example and Example 2 is that zinc chloride is used in place of zinc lactate in equal parts by weight in the raw materials. The raw materials are: 0.25 parts zinc chloride, 1.0 part grape seed polyphenol extract, 0.15 parts N-trimethyl chitosan, 1.0 part citric acid-sodium citrate buffer, 10 parts sorbitol, 0.1 parts azone, 0.05 parts peppermint flavor, and 87.45 parts deionized water. The S3 step in the preparation method is modified to: zinc chloride is directly mixed and reacted with the plant polyphenol extract, while the other steps remain unchanged.

[0046] Experimental methods:

[0047] Antibacterial performance test: Referring to the "Disinfection Technical Specifications", the inhibition zone method was used to test the antibacterial effect against Staphylococcus aureus, Escherichia coli and Candida albicans respectively. At the same time, the antibacterial rate was determined by the colony counting method.

[0048] Stability test: The sample was placed in a 40℃ constant temperature chamber for accelerated testing for 3 months. The properties, pH value and antibacterial activity were observed and measured at 0, 1, 2 and 3 months.

[0049] Table 1. Results of antibacterial performance test

[0050]

[0051] Table 2 Stability Test Results

[0052]

[0053] As can be seen from the data in Table 1, the inhibition zone diameter and antibacterial rate of all embodiments were significantly higher than those of the comparative examples. This proves that the ternary complex system obtained by mixing zinc lactate, plant polyphenol extracts, and N-trimethyl chitosan in this invention has excellent synergistic antibacterial effects. Table 2 shows that all embodiments remained stable after accelerated testing, while the comparative examples showed varying degrees of morphological changes and a decrease in antibacterial activity. This indicates that the ternary complex system of this invention significantly improves product stability.

[0054] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

[0055] The present invention and its embodiments have been described above. This description is not restrictive, and the accompanying drawings are only one embodiment of the present invention. The actual application is not limited to this. In conclusion, if those skilled in the art are inspired by this description and design similar methods and embodiments without departing from the spirit of the present invention, they should all fall within the protection scope of the present invention.

Claims

1. A highly effective antibacterial oral care solution, characterized in that, Composed of the following parts by weight: The ingredients include: 0.01-0.5 parts zinc lactate, 0.1-2 parts plant polyphenol extract, 0.05-0.3 parts N-trimethyl chitosan, 0.5-2 parts buffer, 5-15 parts humectant, 0.05-0.2 parts azone, 0.01-0.1 parts peppermint flavor, and 80-94 parts deionized water; the plant polyphenol extract is any one of green tea polyphenols, grape seed polyphenols, or olive leaf polyphenols, wherein the polyphenol content is 78%-90%; the N-trimethyl chitosan... The preparation method of the sugar is as follows: (1) weigh chitosan, disperse it in isopropanol, add sodium hydroxide solution under stirring, and carry out alkalization and activation; (2) after alkalization and activation, cool the reaction system, and then add iodomethane dropwise under nitrogen protection. After the addition is complete, heat the reaction; (3) after the reaction is completed, cool to room temperature, filter and collect the solid, wash with ethanol solution, vacuum dry, pulverize and sieve to obtain the N-trimethyl chitosan; the preparation method of the high-efficiency antibacterial oral care solution includes the following steps: S1: Preparation of N-trimethyl chitosan solution: First, divide the deionized water into four parts, then weigh N-trimethyl chitosan and slowly add it to the preheated first part of deionized water, stir to dissolve and prepare N-trimethyl chitosan solution for later use; S2: Preparation of plant polyphenol extract: Mix the plant polyphenol extract with the second part of deionized water according to the material-liquid ratio, add cellulase for enzymatic hydrolysis, and filter to obtain a clear plant polyphenol extract; S3: Complexation and compounding reaction: Dissolve zinc lactate in deionized water in the third part, then add buffer to adjust the pH to 5.8-6.2, then slowly add the plant polyphenol extract obtained in S2 and stir the reaction, and finally slowly add the N-trimethyl chitosan solution prepared in S1. After the addition is complete, continue the reaction at a constant temperature to obtain a complex dispersion. S4: Mixing and preparation: Add humectant, azone, peppermint flavoring and the remaining deionized water from the fourth part to the complex dispersion obtained in S3 in sequence. After stirring evenly, filter to remove bacteria and fill to obtain the highly effective antibacterial oral care solution.

2. The highly effective antibacterial oral care solution according to claim 1, characterized in that, The buffer is a citric acid-sodium citrate buffer system.

3. The highly effective antibacterial oral care solution according to claim 1, characterized in that, The moisturizer is glycerin or sorbitol.

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