Oral dispersion liquid composition capable of effectively inhibiting bacteria and preparation process thereof

Abstract

The invention discloses an oral dispersion liquid composition capable of effectively inhibiting bacteria, and relates to the technical field of nano-emulsion / micro-capsule suspension liquid. Aiming at the problems of transient antibacterial effect, strong irritation and poor dispersibility of the traditional oral care product, the composition is prepared by adopting a nano-emulsion and micro-capsule technology. A bacteriostatic agent (such as nano-silver and thyme volatile oil) is wrapped in urea formaldehyde microcapsules through an interfacial polymerization method, and protection and controlled release of active ingredients are achieved. The nano-emulsion is prepared by compounding Span and Tween emulsifiers, so that high dispersity and permeability are ensured; tea polyphenol is added as an antioxidant, so that the stability is enhanced. The preparation method comprises the steps of nano-emulsion preparation, active ingredient microencapsulation, disperse system construction and sterilization filling, and the particle size D90 of a final product is smaller than or equal to 200 nm. The composition has a lasting antibacterial effect, good stability and safety, and is suitable for oral health maintenance.

Description

Technical Field

[0001] The present invention relates to the technical field of nanoemulsion / microcapsule suspension, and particularly relates to an oral dispersible composition capable of effectively inhibiting bacteria. Background Art

[0002] The oral cavity is an important part of the human body, and its health status directly affects the quality of life of an individual. A large number of microbiota inhabit the oral cavity, including normal commensal flora and potential pathogenic bacteria. The normal oral flora plays a certain role in maintaining the oral ecological balance. However, when certain pathogenic bacteria overgrow, various oral health problems may be caused, such as dental caries, periodontal disease, gingivitis, and bad breath. Among them, dental plaque, as a biofilm formed by bacteria and their metabolites, adheres to the tooth surface and is one of the main causes of dental caries and periodontal disease. Research shows that common pathogenic bacteria in the oral cavity include streptococci (such as Streptococcus mutans), Porphyromonas, etc. These bacteria damage tooth and gum tissues by producing acids or triggering inflammatory reactions. Therefore, inhibiting the growth of pathogenic bacteria in the oral cavity and controlling the formation of dental plaque are key strategies for maintaining oral health.

[0003] To achieve the purpose of inhibiting bacteria and cleaning, a variety of oral care products have been developed on the market, such as fluoride toothpaste, mouthwash, oral sprays, etc. These products usually contain antibacterial active ingredients, such as triclosan, chlorhexidine, fluoride, quaternary ammonium salts, etc., which can inhibit the reproduction of oral bacteria to a certain extent and reduce the accumulation of dental plaque. For example, fluoride toothpaste promotes the remineralization of tooth enamel and inhibits bacterial metabolism through fluoride, while mouthwash directly kills or inhibits bacteria in the oral cavity through antibacterial agents. However, although these products are widely used in oral care, there are still some significant deficiencies in their actual use.

[0004] Deficiencies of the prior art: First, the antibacterial effects of existing oral antibacterial products are often not persistent enough. Take mouthwash as an example. The antibacterial components in it stay in the oral cavity for a short time and are quickly washed away by saliva or diluted by food residues after use, resulting in the antibacterial effect being difficult to last for more than a few hours. Such a short-term antibacterial effect cannot meet the needs of long-term oral protection, especially during nighttime sleep when saliva secretion decreases and bacteria are prone to multiply. Second, some antibacterial components have certain irritations to oral mucosa. For example, chlorhexidine, a commonly used broad-spectrum antibacterial agent, although having strong bactericidal ability, may cause oral mucosa staining, taste changes, or even slight irritation after long-term use, affecting the user experience. In addition, certain chemical antibacterial agents may cause allergic reactions, further limiting their application in sensitive populations. Third, the stability problem of antibacterial components is also a bottleneck in the prior art. Many antibacterial agents are prone to decomposition or inactivation in the complex oral environment (such as changes in pH and the action of enzymes). For example, natural antibacterial components such as tea polyphenols and plant essential oils, although having good biocompatibility and antibacterial activity, are easily oxidized or degraded in aqueous solutions and are difficult to maintain long-term stability. This not only reduces the antibacterial efficacy of the product but also increases the difficulty of production and storage. Finally, the poor dispersion of antibacterial components in the oral cavity is a common problem. The oral environment is complex, covering different surfaces such as teeth, gums, and tongue, and there are significant differences in the physical properties and chemical environments of these parts. The antibacterial agents in traditional oral care products are often difficult to be evenly distributed to all areas, especially hard-to-reach areas such as dental floss and gingival sulcus, resulting in insufficient local antibacterial effects, and dental plaque may still accumulate in these areas.

[0005] To overcome the above problems, in recent years, nanotechnology and microencapsulation technology have received extensive attention and application in the fields of drug delivery, cosmetics, and personal care products, and have shown certain potential in the field of oral care. Nanoemulsion is an emulsion with a particle size in the nanometer range, having high stability, good solubility, and bioavailability, and can significantly improve the dispersion and permeability of antibacterial agents. Microencapsulation technology, on the other hand, realizes the protection, controlled release, and extended action time of active ingredients by encapsulating the active ingredients in tiny vesicles. These technologies provide new possibilities for improving the performance of oral antibacterial products.

[0006] However, oral care products applying nanoemulsion and microencapsulation technology in the prior art still face some challenges. First, the preparation process of nanoemulsion is relatively complex and requires high-precision emulsification equipment and technical support, resulting in high production costs and being difficult to achieve large-scale commercialization. Second, the stability of microcapsules may be affected by saliva, enzymes, and physical actions such as chewing in the oral environment, leading to premature release of antibacterial agents or rupture of microcapsules, and the controlled release function cannot be fully exerted. In addition, the safety of nanomaterials and microcapsule materials also needs to be further verified to ensure that their long-term use in the oral cavity will not cause toxicity or allergic reactions. Summary of the Invention

[0007] In view of this, the object of the present invention is to provide an oral dispersion composition with effective antibacterial properties, so as to overcome the deficiencies of traditional oral care products, such as short antibacterial duration (<2 h), high mucosal irritation of chemical antibacterial agents (e.g., the irritation index of chlorhexidine ≥ 3.2), easy inactivation of active ingredients (the titer decreases by >40% after 6 months of storage), and poor oral tissue permeability (contact angle >60°). A nanoemulsion / microcapsule composite dispersion system with long-acting controlled release (antibacterial duration ≥ 6 h), mild and low sensitivity (irritation index ≤ 1.2), high stability (the activity retention rate >90% after 6 months of accelerated test at 40°C), and wide-range penetration (contact angle <30°) is provided.

[0008] The technical solution adopted is as follows: A preparation method of an oral dispersion composition with effective antibacterial properties, comprising the following steps: Step S1: Preparation of nanoemulsion. The Span and Tween emulsifiers are compounded according to the HLB value of 4.3 - 15 (mixing method), and mixed with the carrier oil phase at an oil-water volume ratio of 0.6:1 - 1:1, and pre-emulsified for 10 - 15 min at a shear rate of 1000 - 1500 rpm; Step S2: Microencapsulation of active ingredients. The interfacial polymerization method is used to encapsulate the antibacterial agent: The aqueous phase of urea formaldehyde prepolymer and the oil phase containing the antibacterial agent are mixed at a volume ratio of 1:(4 - 6), the pH is adjusted to 2.5 - 3.5, and the temperature is controlled at 35 - 45°C to form a microcapsule suspension with a wall thickness of 50 - 150 nm; Step S3: Construction of the dispersion system. The microcapsule suspension and the nanoemulsion are mixed at a volume ratio of 1:2 - 1:4, and 1.0 - 2.0 wt% tea polyphenol (here the mass percentage refers to the mass percentage after addition) is added as an antioxidant, and the mixture is circulated and treated 3 times at a pressure of 30 - 50 MPa in a high-pressure homogenizer to obtain a stable dispersion system with a particle size D90 ≤ 200 nm; Step S4: Sterilization and filling. First, filter and sterilize, then fill with nitrogen and sterilize by cobalt-60 γ-ray irradiation to obtain the final product.

[0009] Core process parameters: Emulsifier system: Span80 and Tween80 are compounded according to a mass ratio of 3:7 - 7:3, controlling the HLB value to be 8.6 - 11.8. Span80 (HLB = 4.3) provides oil phase affinity, and Tween80 (HLB = 15) enhances the water phase dispersibility. The HLB value is precisely matched with the polarity of the carrier oil phase to ensure the stability of the emulsion droplet interfacial film. Oil phase composition: Medium-chain triglycerides + glyceryl stearate + isopropyl myristate. Medium-chain triglycerides (C8 - C10) act as a low-viscosity carrier to enhance the solubility of the bacteriostatic agent. Glyceryl stearate provides a solid lipid skeleton to delay the aggregation of emulsion droplets. Pre-emulsification process: The oil-water volume ratio is 0.6:1 - 1:1, shearing at 1000 - 1500 rpm for 10 - 15 min. Primary emulsion droplets with a particle size of 200 - 500 nm are formed, laying the foundation for subsequent high-pressure homogenization.

[0010] Preferably, in step S1, the Span-type and Tween-type emulsifiers are Span80 and Tween80 respectively, compounded according to a mass ratio of 3:7 - 7:3, so that the HLB value of the composite emulsifier is controlled within the range of 8.6 - 11.8.

[0011] Preferably, in step S1, the mass ratio among medium-chain triglycerides C8 - C10, glyceryl stearate, and isopropyl myristate in the carrier oil phase is 50 - 70:20 - 30:5 - 15. When in use, the above raw materials are evenly mixed.

[0012] Preferably, the aqueous phase of the urea-formaldehyde prepolymer in step S2 is prepared by the following process: The molar ratio of formaldehyde to urea is 1:1.5 - 1:2; controlling the degree of prepolymer condensation to form a linear structure with a molecular weight of 2000 - 5000 Da, using a compound system of triethanolamine and sodium hydroxide, and the molar ratio between triethanolamine and sodium hydroxide is 3:1 - 5:1. Reaction conditions: Constant temperature reaction at 70 ± 2 °C for 2 h, stirring rate 200 - 300 rpm, generating a prepolymer solution with a viscosity of 150 - 300 mPa·s, diluting with deionized water according to a volume ratio of 1:1.5, and centrifuging at 5000×g for 15 min to remove unreacted monomers.

[0013] The following Table 1 shows that through precise material balance and process control, this process realizes the designability of the prepolymer structure, providing an ideal wall material precursor for subsequent microcapsule interfacial polymerization.

[0014] Table 1 Preferably, in step S2, the mass ratio among the nano-silver solution with a particle size of 10 - 30 nm, thyme volatile oil, medium-chain triglycerides C8 - C10, and α-tocopherol in the oil phase containing the bacteriostatic agent is 0.05 - 0.2:1 - 3:65 - 80:0.5 - 1.0.

[0015] As shown in Table 2 below, the formulation performance is compared.

[0016] Table 2 Preferably, after adding tea polyphenols in step S3, the subsequent temperature is controlled not to exceed 40°C.

[0017] Preferably, the method of filtration and sterilization in step S4 is to use a 0.22 μm microporous membrane for filtration and sterilization.

[0018] Preferably, the dose of irradiation sterilization in step S4 is a dose of 8 - 15 kGy.

[0019] The cavity dispersion composition obtained by the preparation method as described above.

[0020] Regarding the raw material information involved, as follows: Span80 (sorbitan monooleate), CAS No.: 1338 - 43 - 8, Use: Used as an emulsifier, and compounded with Tween80 to prepare nanoemulsion. Tween80 (polysorbate 80), CAS No.: 9005 - 65 - 6, Use: Used as an emulsifier, and compounded with Span80 to prepare nanoemulsion. Medium-chain triglycerides C8 - C10, CAS No.: 65381 - 09 - 1 (Captex355) Use: The main component of the carrier oil phase and the oil phase containing bacteriostatic agent. Glyceryl stearate, CAS No.: 555 - 43 - 1, Use: Component of the carrier oil phase. Isopropyl myristate, CAS No.: 110 - 27 - 0, Use: Component of the carrier oil phase. Formaldehyde, CAS No.: 50 - 00 - 0, Use: Raw material for urea formaldehyde prepolymer. Urea, CAS No.: 57 - 13 - 6. Use: Raw material for urea formaldehyde prepolymer. Triethanolamine, CAS No.: 102 - 71 - 6, Use: pH regulator in the preparation of urea formaldehyde prepolymer. Sodium hydroxide, CAS No.: 1310 - 73 - 2, Use: pH regulator in the preparation of urea formaldehyde prepolymer. Nano silver solution (silver nanoparticle solution), mass concentration is 5%, CAS No.: 7440 - 22 - 4, Use: Bacteriostatic component in the oil phase containing bacteriostatic agent. Thyme volatile oil, CAS No.: 8007 - 46 - 3, Use: Bacteriostatic component in the oil phase containing bacteriostatic agent. α-Tocopherol, CAS No.: 59 - 02 - 9, Use: Antioxidant in the oil phase containing bacteriostatic agent. Tea polyphenols, CAS No.: 84650 - 60 - 2, Use: Antioxidant in the construction of the dispersion system.

[0021] In summary, the beneficial effects of the present invention are as follows: Long-acting antibacterial: By encapsulating antibacterial agents (such as nano silver and thyme volatile oil) in urea-formaldehyde microcapsules through microencapsulation technology, the protection and controlled release of active ingredients are achieved, significantly prolonging the antibacterial time. Experiments show that the antibacterial time of the product of the present invention can reach more than 6 hours, far exceeding the 2-hour antibacterial time of traditional oral care products, effectively inhibiting the growth of oral pathogenic bacteria and reducing the formation of dental plaque. Mild and hypoallergenic: Natural antibacterial agents and antioxidants (such as tea polyphenols) are used, avoiding the irritation of traditional chemical antibacterial agents (such as chlorhexidine) to the oral mucosa. After testing, the irritation index of the product of the present invention is ≤1.2, far lower than the irritation index of chlorhexidine ≥3.2, suitable for long-term use and not likely to cause allergic reactions. High stability: The nanoemulsion and microencapsulation technology effectively protect the active ingredients from the effects of saliva, enzymes and temperature changes in the oral environment, significantly improving the stability of the product. After 6 months of accelerated testing at 40°C, the retention rate of the active ingredient is >90%, solving the problem that the active ingredient in traditional products is easily inactivated (the titer of traditional products decreases by >40% after 6 months of storage). Wide-area penetration: The particle size D90 of the nanoemulsion is ≤200 nm, ensuring that the antibacterial agent can be evenly dispersed and penetrate into difficult-to-reach areas such as dental floss and gingival sulcus, with a contact angle <30°, significantly better than the contact angle of traditional products >60°, thus improving the overall antibacterial effect. Safety: The materials used (such as urea-formaldehyde microcapsules and tea polyphenols) have good biocompatibility, and the usage amount of antibacterial agents such as nano silver is controlled within a safe range, ensuring that the product will not cause harm to human health during long-term use. Easy to produce: The preparation process is relatively simple, using the interfacial polymerization method and high-pressure homogenization technology, which is easy to achieve large-scale production, reducing production costs and improving the market competitiveness of the product.

[0022] In summary, through the innovative nanoemulsion / microcapsule composite dispersion system, the present invention has successfully overcome multiple deficiencies of traditional oral care products, providing an efficient, safe and stable solution for oral health maintenance. Brief Description of the Drawings

[0023] Figure 1 It is the antibacterial plate diagram of the oral dispersion composition prepared in Example 10.

[0024] Figure 2 It is the hemolysis condition diagram of the oral dispersion composition prepared in Example 10. Detailed Description of the Invention

[0025] The present invention will be described in detail below through specific examples. However, the uses and purposes of these exemplary embodiments are only used to illustrate the present invention, and do not constitute any form of limitation to the actual protection scope of the present invention, nor will the protection scope of the present invention be limited thereto. For parameter ranges not mentioned, intermediate values are selected. For percentages involved, if not otherwise specified, they are mass percentages.

[0026] Example 1 Step S1: Preparation of nanoemulsion Weigh 3 g of Span80 and 7 g of Tween80 (mass ratio 3:7, HLB value about 8.6), mix them evenly to obtain an emulsifier.

[0027] Weigh 50 g of medium-chain triglyceride C8-C10, 20 g of glyceryl stearate, and 5 g of isopropyl myristate, mix them evenly to obtain a carrier oil phase.

[0028] Mix the emulsifier with the carrier oil phase, add the aqueous phase (oil-water volume ratio 0.6:1), and pre-emulsify for 10 min at a shear rate of 1000 rpm.

[0029] Step S2: Microencapsulation of active ingredients Prepare the urea-formaldehyde prepolymer aqueous phase: Take formaldehyde and urea (molar ratio 1:1.5), use a complex system of triethanolamine and sodium hydroxide (molar ratio 3:1), react at a constant temperature of 70 °C for 2 h with a stirring rate of 200 rpm to generate a prepolymer solution with a molecular weight of 2000 Da and a viscosity of 150 mPa·s, dilute it with deionized water at a volume ratio of 1:1.5, and centrifuge at 5000×g for 15 min.

[0030] Oil phase containing bacteriostatic agent: 0.05 g of silver nanosol with a particle size of 10-30 nm, 1 g of thyme volatile oil, 65 g of medium-chain triglyceride, 0.5 g of α-tocopherol.

[0031] Mix the prepolymer aqueous phase with the oil phase containing bacteriostatic agent at a volume ratio of 1:4, adjust the pH to 2.5, and react at 35 °C to form a microcapsule suspension with a wall thickness of 50 nm.

[0032] Step S3: Construction of dispersion system Mix the microcapsule suspension with the nanoemulsion at a volume ratio of 1:2, add 1.0 wt% of tea polyphenol (final mass percentage after addition), and circulate and process 3 times in a high-pressure homogenizer at 30 MPa, controlling the temperature not to exceed 40 °C to obtain a dispersion system with a particle size D90≤200 nm.

[0033] Step S4: Sterilization and filling Filter and sterilize with a 0.22 μm microporous membrane, fill with nitrogen, and then irradiate with cobalt-60 γ-rays at a dose of 8 kGy for sterilization.

[0034] Example 2 Step S1: Adjust the mass ratio of Span80 to Tween80 to 5:5 (HLB value about 10.0), and other conditions are the same as in Example 1.

[0035] Steps S2-S4: The same as in Example 1.

[0036] Example 3 Step S1: The carrier oil phase is adjusted to 60 g of medium-chain triglyceride C8-C10, 25 g of glyceryl stearate, and 10 g of isopropyl myristate. Other conditions are the same as in Example 1.

[0037] Steps S2 - S4: The same as in Example 1.

[0038] Example 4 Step S2: The urea formaldehyde prepolymer is adjusted to a formaldehyde:urea molar ratio of 1:1.8, a molecular weight of 3500 Da, and a viscosity of 200 mPa·s. Other conditions are the same as in Example 1.

[0039] Steps S1, S3 - S4: The same as in Example 1.

[0040] Example 5 Step S2: The oil phase containing the bacteriostatic agent is adjusted to 0.1 g of silver nanosol with a particle size of 10 - 30 nm, 2 g of thyme volatile oil, 70 g of medium-chain triglyceride, and 0.7 g of α-tocopherol. Other conditions are the same as in Example 1.

[0041] Steps S1, S3 - S4: The same as in Example 1.

[0042] Example 6 Step S3: The mixing ratio of the microcapsule suspension and the nanoemulsion is adjusted to 1:3. Other conditions are the same as in Example 1.

[0043] Steps S1 - S2, S4: The same as in Example 1.

[0044] Example 7 Step S3: The addition amount of tea polyphenols is adjusted to 1.5 wt%. Other conditions are the same as in Example 1.

[0045] Steps S1 - S2, S4: The same as in Example 1.

[0046] Example 8 Step S3: The high-pressure homogenization pressure is adjusted to 40 MPa. Other conditions are the same as in Example 1.

[0047] Steps S1 - S2, S4: The same as in Example 1.

[0048] Example 9 Step S4: The irradiation sterilization dose is adjusted to 12 kGy. Other conditions are the same as in Example 1.

[0049] Steps S1 - S3: The same as in Example 1.

[0050] Example 10 Step S1: The mass ratio of Span80 to Tween80 is 7:3 (HLB value is about 11.8). The carrier oil phase consists of 70 g of medium-chain triglyceride C8-C10, 30 g of glyceryl stearate, and 15 g of isopropyl myristate.

[0051] Step S2: The molar ratio of formaldehyde to urea in the urea-formaldehyde prepolymer is 1:2, with a molecular weight of 5000 Da and a viscosity of 300 mPa·s. The oil phase containing the bacteriostatic agent consists of 0.2 g of nano-silver, 3 g of thyme volatile oil, 80 g of medium-chain triglyceride, and 1.0 g of α-tocopherol.

[0052] Step S3: The microcapsule suspension and the nanoemulsion are mixed at a ratio of 1:4, and 2.0 wt% of tea polyphenols is added, followed by high-pressure homogenization at 50 MPa.

[0053] Step S4: The irradiation sterilization dose is 15 kGy.

[0054] Design of comparative examples Comparative example 1 Step S1: The same as in Example 1.

[0055] Step S2: Omit microencapsulation and directly add the bacteriostatic agent (0.05 g of nano-silver and 1 g of thyme volatile oil) to the nanoemulsion.

[0056] Steps S3-S4: The same as in Example 1.

[0057] Comparative example 2 Step S1: The same as in Example 1.

[0058] Step S2: The same as in Example 1 to prepare the microcapsule suspension.

[0059] Step S3: Only use the microcapsule suspension, do not mix it with the nanoemulsion, add 1.0 wt% of tea polyphenols, and perform high-pressure homogenization at 30 MPa.

[0060] Steps S4: The same as in Example 1.

[0061] Comparative example 3 Steps S1-S2: The same as in Example 1.

[0062] Step S3: Do not add tea polyphenols, and keep other conditions the same as in Example 1.

[0063] Steps S4: The same as in Example 1.

[0064] Comparative example 4 Step S1: Use a single emulsifier, 10 g of Tween80 (HLB value 15), and keep other conditions the same as in Example 1.

[0065] Steps S2-S4: The same as in Example 1.

[0066] Comparative example 5 Steps S1 - S2: The same as in Example 1.

[0067] Step S3: Omit the high - pressure homogenization treatment, directly mix the microcapsule suspension and the nano - emulsion at a ratio of 1:2, and add 1.0 wt% of tea polyphenols.

[0068] Steps S4: The same as in Example 1.

[0069] Comparative Example 6 Steps S1 - S3: The same as in Example 1.

[0070] Step S4: Only filter and sterilize with a 0.22 - μm filter membrane, without irradiation sterilization.

[0071] Test Scheme Design (1) Bactericidal Effect Test Purpose: To evaluate the antibacterial ability of the oral dispersion against common oral pathogenic bacteria.

[0072] Bacterial strain: Select Streptococcus mutans (Streptococcus mutans, ATCC25175), representing the main oral pathogenic bacteria.

[0073] Test method: Dilution method: Mix the oral dispersion with the bacterial suspension at different concentrations, and measure the bacterial survival rate after culturing at 37°C. Time point: Focus on the antibacterial effect at 6 h. Index: Bacterial survival rate (%) = (number of surviving colonies / initial number of colonies) × 100%. Standard: Bacterial survival rate < 5%.

[0074] (2) Hemolysis Test Purpose: To evaluate the hemolytic effect of the oral dispersion on red blood cells and verify its safety.

[0075] Sample: Fresh sheep blood red blood cell suspension.

[0076] Test method: Mix the oral dispersion and the red blood cell suspension at a volume ratio of 1:10, incubate at 37°C for 1 h, and measure the absorbance (OD) of the supernatant at 540 nm after centrifugation. Calculation formula: Hemolysis rate (%) = (OD of sample - OD of negative control) / (OD of positive control - OD of negative control) × 100%.

[0077] Negative control: Normal saline; Positive control: Distilled water.

[0078] Index: Hemolysis rate (%).

[0079] Standard: A hemolysis rate < 5% is considered to have no obvious hemolytic effect and is safe.

[0080] (3) Stability Test Purpose: To evaluate the stability of the oral dispersion under accelerated conditions.

[0081] Condition: 40 °C, 75% relative humidity (RH), lasting for 6 months.

[0082] Test method: Retention rate of active ingredient (%): Use high performance liquid chromatography (HPLC) to determine the overall content of bacteriostatic agents (such as nano silver, thyme volatile oil); Appearance: Observe the appearance changes (color, transparency, precipitation); pH change: Measure the pH value change with a pH meter.

[0083] Index: Retention rate of active ingredient (%): Content after 6 months / Initial content × 100%.

[0084] (4) Permeability test Purpose: To evaluate the penetration ability of the oral dispersion on the surface of oral tissues.

[0085] Sample: Ex vivo porcine oral mucosa.

[0086] Test method: Use a contact angle meter to measure the contact angle of a 5 μL oral dispersion droplet on the mucosal surface.

[0087] Index: Contact angle (°), the smaller the angle, the better the permeability.

[0088] Standard: A contact angle < 30° is considered excellent permeability.

[0089] (5) Irritation test Purpose: To evaluate the irritation of the oral dispersion to the oral mucosa.

[0090] Animal model: Rat oral mucosa.

[0091] Test method: Apply 0.1 mL of the oral dispersion to the rat oral mucosa every day for 7 consecutive days, observe reactions such as redness and ulceration, and calculate the irritation index (SI) according to the scoring standard.

[0092] Scoring standard: 0 (no reaction) to 4 (severe reaction), SI = Total score / (Number of animals × Number of observations).

[0093] Index: Irritation index (SI).

[0094] Standard: SI ≤ 1.2 is considered low irritation.

[0095] The following are the test results of 10 examples and 6 comparative examples, and the data are based on the above test scheme.

[0096] Table 3: Test results of bactericidal effect Analysis: Examples 1 - 10: Bacterial survival rate < 5%, diameter of inhibition zone ≥ 17 mm, showing excellent bacteriostatic effect, proving the long - term effect of the synergistic action of microcapsule controlled release and nanoemulsion. As Figure 1As shown, taking Example 10 as an example, it can be seen that the bacteria hardly grow. Comparative Example 1 (without microencapsulation): survival rate of 25.0%, poor antibacterial effect, indicating the importance of microcapsules in protecting antibacterial agents. Comparative Example 2 (only microcapsules): survival rate of 15.0%, the effect is not as good as the composite system, indicating that nanoemulsion enhances dispersibility. Comparative Example 3 (without tea polyphenols): survival rate of 20.0%, the lack of antioxidant leads to a decrease in activity. Comparative Example 4 (single emulsifier): survival rate of 28.0%, poor dispersibility results in the weakest antibacterial effect. Comparative Example 5 (without high-pressure homogenization): survival rate of 22.0%, larger particle size affects the antibacterial efficiency. Comparative Example 6 (without irradiation sterilization): survival rate of 4.6%, close to the example, but there may be a risk of subsequent contamination.

[0097] Table 4: Hemolysis test results Analysis: Examples 1 - 10: hemolysis rate ≤ 1.3%, far lower than 5%, high safety. Comparative Examples 1 - 5: hemolysis rate of 2.0% - 3.0%, although < 5%, but higher than the examples, indicating that microcapsules and emulsions optimize biocompatibility. Comparative Example 6: hemolysis rate of 1.2%, consistent with the examples, irradiation sterilization did not significantly affect safety. In addition, taking Example 10 as an example, compositions with different concentrations all show good biocompatibility.

[0098] Table 5: Stability test results Analysis: Examples 1 - 10: retention rate > 90%, appearance and pH are stable, proving the protective effect of nanoemulsion and tea polyphenols. Comparative Examples 1 - 5: retention rate of 60% - 75%, poor stability, especially Comparative Example 3 (without tea polyphenols) is only 60%. Comparative Example 6: retention rate of 90%, good stability, but no irradiation may lead to the risk of microbial contamination.

[0099] Table 6: Permeability test results Analysis: Examples 1 - 10: contact angle < 30°, excellent permeability, due to the small particle size of nanoemulsion. Comparative Examples 1 - 5: contact angle > 40°, poor permeability, insufficient dispersibility. Comparative Example 6: contact angle of 25°, consistent with the examples, irradiation does not affect permeability.

[0100] Table 7: Irritation test results Analysis: Examples 1 - 10: SI ≤ 1.1, low irritation, suitable for long-term use. Comparative Examples 1 - 5: SI > 1.8, higher irritation, process defects lead to mucosal discomfort. Comparative Example 6: SI = 1.0, consistent with the examples, irradiation did not increase irritation.

[0101] Generally speaking, Examples 1 - 10: They perform excellently in terms of bactericidal effect (survival rate < 5%, inhibition zone > 17 mm), safety (hemolysis rate < 1.3%), stability (retention rate > 90%), permeability (contact angle < 30°), and low irritation (SI ≤ 1.1), verifying the technical advantages of the present invention. Comparative Examples 1 - 5: They perform poorly in different tests, highlighting the importance of microencapsulation, nanoemulsion, tea polyphenols, and high-pressure homogenization. Comparative Example 6: Its performance is close to that of the examples, but the lack of irradiation sterilization may affect long-term safety. These test schemes and results provide comprehensive data support for the present invention, proving its innovation in long-acting antibacterial, safety, and practicality, and are applicable to patent applications and market promotion.

[0102] The series of detailed descriptions listed above are only specific descriptions of the feasible embodiments of the present invention, and they are not intended to limit the protection scope of the present invention. Any equivalent embodiments or changes made without departing from the spirit of the art of the present invention should be included in the protection scope of the present invention.

Claims

1. A preparation method of an oral dispersion composition with effective antibacterial properties, characterized in that, It includes the following steps: Step S1: Preparation of nanoemulsion. Mix Span and Tween emulsifiers according to the HLB value of 4.3 - 15 ratio, and mix with the carrier oil phase according to the oil - water volume ratio of 0.6:1 - 1:1, and pre - emulsify for 10 - 15 min at a shear rate of 1000 - 1500 rpm; Step S2: Microencapsulation of active ingredients. Use the interfacial polymerization method to encapsulate the bacteriostatic agent: Mix the aqueous phase of urea - formaldehyde prepolymer and the oil phase containing the bacteriostatic agent according to the volume ratio of 1:(4 - 6), adjust the pH to 2.5 - 3.5, control the temperature at 35 - 45 °C to form a microcapsule suspension with a wall thickness of 50 - 150 nm; Step S3: Construction of the dispersion system. Mix the microcapsule suspension and the nanoemulsion according to the volume ratio of 1:2 - 1:4, add 1.0 - 2.0 wt% tea polyphenols as an antioxidant, and circulate and process 3 times in a high - pressure homogenizer at a pressure of 30 - 50 MPa to obtain a stable dispersion system with a particle size D90 ≤ 200 nm; Step S4: Sterilization and filling. First, filter and sterilize, then fill with nitrogen and irradiate with cobalt - 60 γ - rays for sterilization to obtain the final product.

2. The preparation method of the oral dispersion composition with effective antibacterial property according to claim 1, characterized in that In step S1, the Span and Tween emulsifiers are Span80 and Tween80 respectively, and are mixed according to the mass ratio of 3:7 - 7:3 to control the HLB value of the composite emulsifier in the range of 8.6 - 11.

8.

3. The preparation method of the oral dispersion composition capable of effectively inhibiting bacteria according to claim 1, characterized in that, In step S1, the mass ratio among medium - chain triglycerides C8 - C10, glyceryl stearate and isopropyl myristate in the carrier oil phase is 50 - 70:20 - 30:5 - 15.

4. The preparation method of the orally-dispersible composition capable of effectively inhibiting bacteria according to claim 1, characterized in that, In step S2, the aqueous phase of urea - formaldehyde prepolymer is prepared by the following process: The molar ratio of formaldehyde to urea is 1:1.5 - 1:

2. Control the degree of prepolymer condensation to form a linear structure with a molecular weight of 2000 - 5000 Da. Use a compound system of triethanolamine and sodium hydroxide, and the molar ratio between triethanolamine and sodium hydroxide is 3:1 - 5:

1. The reaction conditions are: constant - temperature reaction at 70 ± 2 °C for 2 h, stirring rate of 200 - 300 rpm to generate a prepolymer solution with a viscosity of 150 - 300 mPa·s. Dilute with deionized water according to the volume ratio of 1:1.5, and centrifuge at 5000×g for 15 min to remove unreacted monomers.

5. The preparation method of the oral dispersion composition with effective antibacterial property according to claim 1, characterized in that, In step S2, the mass ratio among nano - silver solution with a particle size of 10 - 30 nm, thyme volatile oil, medium - chain triglycerides C8 - C10 and α - tocopherol in the oil phase containing the bacteriostatic agent is 0.05 - 0.2:1 - 3:65 - 80:0.5 - 1.

0.

6. The preparation method of the oral dispersion composition capable of effectively inhibiting bacteria according to claim 1, wherein, In step S3, after adding tea polyphenols, control the subsequent temperature not to exceed 40 °C.

7. The preparation method of the oral dispersion composition capable of effectively inhibiting bacteria according to claim 1, characterized in that, In step S4, the method of filter sterilization is to filter and sterilize using a 0.22 - μm microporous membrane.

8. The preparation method of the oral dispersion composition capable of effectively inhibiting bacteria according to claim 1, wherein, In step S4, the dose of irradiation sterilization is 8 - 15 kGy.

9. The cavity dispersion liquid composition obtained by the preparation method according to claim 1.

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