An oral dispersion composition capable of effectively inhibiting bacteria and its preparation process

Abstract

This invention discloses an oral dispersion composition with effective antibacterial properties, which belongs to the field of nanoemulsion / microcapsule suspension technology. This composition addresses the short-lived antibacterial effects, strong irritation, and poor dispersibility of traditional oral care products. It is prepared using nanoemulsion and microencapsulation technology. Antibacterial agents (such as nanosilver and thyme essential oil) are encapsulated in urea-formaldehyde microcapsules via interfacial polymerization, achieving protection and controlled release of the active ingredients. The nanoemulsion is prepared using a combination of span and tween emulsifiers to ensure high dispersibility and permeability; tea polyphenols are added as antioxidants to enhance stability. The preparation method includes nanoemulsion preparation, microencapsulation of the active ingredients, dispersion system construction, and sterilization and filling. The final product has a particle size D90 ≤ 200 nm. This composition exhibits long-lasting antibacterial effects, excellent stability, and safety, making it suitable for oral health maintenance.

Description

Technical Field

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

[0002] The oral cavity is an essential part of the human body, and its health directly impacts an individual's quality of life. The oral cavity is home to a vast microbiome, encompassing both normal commensal bacteria and potential pathogens. While normal oral microbiota plays a role in maintaining the oral ecological balance, the overgrowth of certain pathogens can lead to a variety of oral health problems, such as dental caries, periodontal disease, gingivitis, and halitosis. Dental plaque, a biofilm formed by bacteria and their metabolites that adheres to tooth surfaces, is one of the primary causes of dental caries and periodontal disease. Studies have shown that common oral pathogens include Streptococci (such as Streptococcus mutans) and Porphyromonas. These bacteria damage teeth and gum tissue by producing acid or inducing inflammatory responses. Therefore, inhibiting the growth of oral pathogens and controlling dental plaque formation are key strategies for maintaining oral health.

[0003] To achieve the goals of antibacterial and cleaning, a variety of oral care products have been developed on the market, such as fluoride toothpaste, mouthwash, and oral spray. These products generally contain antibacterial active ingredients, such as triclosan, chlorhexidine, fluoride, and quaternary ammonium salts, which can inhibit the growth of oral bacteria and reduce the accumulation of dental plaque to a certain extent. For example, fluoride toothpaste promotes enamel remineralization and inhibits bacterial metabolism through fluoride, while mouthwash directly kills or inhibits bacteria in the oral cavity through antibacterial agents. However, despite the widespread use of these products in oral care, they still have some significant shortcomings in actual use.

[0004] Deficiencies of existing technologies: First, the antibacterial effects of existing oral antibacterial products are often insufficiently sustained. For example, the antibacterial ingredients in mouthwashes remain in the mouth for a short time and are quickly washed away by saliva or diluted by food residue after use, making it difficult for the antibacterial effect to last more than a few hours. This short-lived antibacterial effect cannot meet the needs of long-term oral protection, especially during sleep, when saliva secretion decreases and bacteria thrive. Second, some antibacterial ingredients are irritating to the oral mucosa. For example, chlorhexidine, a commonly used broad-spectrum antibacterial agent, while possessing strong bactericidal properties, can cause staining of the oral mucosa, altered taste, or even mild irritation with long-term use, impacting the user experience. Furthermore, some chemical antibacterial agents can trigger allergic reactions, further limiting their use in sensitive individuals. Third, the stability of antibacterial ingredients is also a bottleneck in existing technologies. Many antibacterial agents are easily degraded or inactivated in the complex oral environment (e.g., pH fluctuations and enzyme activity). For example, natural antibacterial ingredients such as tea polyphenols and plant essential oils, although they have 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 ingredients in the oral cavity is a common problem. The oral environment is complex, covering different surfaces such as teeth, gums, and tongue, and the physical properties and chemical environments of these parts vary greatly. The antibacterial agents in traditional oral care products are often difficult to distribute evenly to all areas, especially in hard-to-reach areas such as tooth gaps and gingival sulci, resulting in insufficient local antibacterial effect, and dental plaque may still accumulate in these areas.

[0005] To overcome these challenges, nanotechnology and microencapsulation technologies have gained widespread attention and application in drug delivery, cosmetics, and personal care products in recent years, and have shown promising potential in oral care. Nanoemulsions, emulsions with nanometer-sized particles, offer high stability, excellent solubility, and bioavailability, significantly improving the dispersion and permeability of antibacterial agents. Microencapsulation technology, by encapsulating active ingredients in tiny vesicles, protects them, controls their release, and prolongs their duration of action. These technologies offer new possibilities for enhancing the performance of oral antibacterial products.

[0006] However, oral care products utilizing existing nanoemulsion and microcapsule technologies still face several challenges. First, the preparation process for nanoemulsions is complex, requiring high-precision emulsification equipment and technical support, resulting in high production costs and difficulties in large-scale commercialization. Second, the stability of microcapsules may be affected by physical effects in the oral environment, such as saliva, enzymes, and chewing, leading to premature release of the antibacterial agent or microcapsule rupture, thus failing to fully utilize the controlled-release function. Furthermore, the safety of nanomaterials and microcapsules requires further verification to ensure that their long-term use in the oral cavity does not cause toxicity or allergic reactions. Summary of the Invention

[0007] In view of this, the object of the present invention is to propose an oral dispersion composition that can effectively inhibit bacteria, so as to overcome the shortcomings of traditional oral care products, such as short antibacterial effect (<2h), high mucosal irritation of chemical antibacterial agents (such as chlorhexidine irritation index ≥3.2), easy inactivation of active ingredients (potency decreases by >40% after 6 months of storage), and poor oral tissue permeability (contact angle >60°). The present invention provides a nanoemulsion / microcapsule composite dispersion system that has the characteristics of long-term controlled release (antibacterial effect ≥6h), mild and low sensitivity (irritation index ≤1.2), high stability (activity retention rate >90% after 6 months of accelerated test at 40°C) and wide-area penetration (contact angle <30°).

[0008] The technical solution adopted is: a method for preparing an oral dispersion composition that can effectively inhibit bacteria, comprising the following steps: Step S1: Preparation of nanoemulsion, compounding Span and Tween emulsifiers at an HLB value of 4.3-15 (mixing method), mixing with the carrier oil phase at an oil-water volume ratio of 0.6:1-1:1, and pre-emulsifying for 10-15 minutes at a shear rate of 1000-1500 rpm; Step S2: Microencapsulation of the active ingredient, using interfacial polymerization to encapsulate the antibacterial agent: mixing the aqueous phase of the urea formaldehyde prepolymer with the oil phase containing the antibacterial agent at a volume ratio of 1: (4-6), and adjusting the pH to 2 .5-3.5, control the temperature at 35-45°C to form a microcapsule suspension with a wall thickness of 50-150nm; step S3: constructing a dispersion system, mixing the microcapsule suspension and the nanoemulsion in a volume ratio of 1:2-1:4, adding 1.0-2.0wt% tea polyphenols (the mass percentage here refers to the mass percentage after addition) as an antioxidant, and circulating the treatment three times in a high-pressure homogenizer at a pressure of 30-50MPa to obtain a stable dispersion system with a particle size D90≤200nm; step S4: sterilization and filling, first filtering and sterilizing, then filling with nitrogen and sterilizing by cobalt-60γ ray irradiation to obtain the final product.

[0009] Core process parameters: Emulsifier system: Span 80 and Tween 80 are blended in a mass ratio of 3:7-7:3, with an HLB value of 8.6-11.8. Span 80 (HLB = 4.3) provides oil-phase affinity, while Tween 80 (HLB = 15) enhances aqueous dispersibility. The HLB value precisely matches the polarity of the carrier oil phase, ensuring the stability of the emulsion droplet interface membrane. Oil phase composition: Medium-chain triglycerides + glyceryl stearate + isopropyl myristate. Medium-chain triglycerides (C8-C10) serve as a low-viscosity carrier, enhancing the solubility of the antibacterial agent. Glyceryl stearate provides a solid lipid backbone, delaying droplet aggregation. Pre-emulsification process: Oil-water volume ratio of 0.6:1-1:1, shearing at 1000-1500 rpm for 10-15 minutes. Primary emulsion droplets with a size of 200-500 nm are formed, laying the foundation for subsequent high-pressure homogenization.

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

[0011] Preferably, the mass ratio of medium chain triglycerides C8-C10, glyceryl stearate and isopropyl myristate in the carrier oil phase in step S1 is 50-70:20-30:5-15. When used, the above raw materials can be 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: the condensation degree of the prepolymer is controlled to form a linear structure with a molecular weight of 2000-5000Da, a triethanolamine and sodium hydroxide composite system is used, 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 2h, stirring rate 200-300rpm, generating a prepolymer solution with a viscosity of 150-300mPa·s, after dilution with deionized water at a volume ratio of 1:1.5, and then centrifuged at 5000×g for 15min to remove unreacted monomers.

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

[0014] Table 1

[0015]

[0016] Preferably, in the oil phase containing the antibacterial agent in step S2, the mass ratio of the nanosilver solution with a particle size of 10-30 nm, thyme essential oil, medium chain triglycerides C8-C10 and α-tocopherol is 0.05-0.2:1-3:65-80:0.5-1.0.

[0017] The performance comparison of the formulations is shown in Table 2 below.

[0018] Table 2

[0019]

[0020] Preferably, after adding tea polyphenols in step S3, the subsequent temperature is controlled not to exceed 40°C.

[0021] Preferably, the filtration sterilization in step S4 is performed by using a 0.22 μm microporous filter membrane.

[0022] Preferably, the dose of irradiation sterilization in step S4 is 8-15 kGy.

[0023] The cavity dispersion composition is obtained by the preparation method described above.

[0024] The information about the raw materials involved is as follows:

[0025] Span 80 (Sorbitan Monooleate), CAS No. 1338-43-8, Use: Used as an emulsifier, compounded with Tween 80 to prepare nanoemulsions. Tween 80 (Polysorbate 80), CAS No. 9005-65-6, Use: Used as an emulsifier, compounded with Span 80 to prepare nanoemulsions. Medium-chain triglycerides (C8-C10), CAS No. 65381-09-1 (Captex 355), Use: Main component of the carrier oil phase and the oil phase containing the antibacterial 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. Uses: Raw material for urea-formaldehyde prepolymer. Triethanolamine, CAS No. 102-71-6, Uses: pH adjuster in the preparation of urea-formaldehyde prepolymer. Sodium hydroxide, CAS No. 1310-73-2, Uses: pH adjuster in the preparation of urea-formaldehyde prepolymer. Nanosilver solution (silver nanoparticle solution), 5% by mass concentration, CAS No. 7440-22-4, Uses: Antibacterial component in oil phases containing antibacterial agents. Thyme essential oil, CAS No. 8007-46-3, Uses: Antibacterial component in oil phases containing antibacterial agents. α-Tocopherol, CAS No. 59-02-9, Uses: Antioxidant in oil phases containing antibacterial agents. Tea polyphenols, CAS No. 84650-60-2, Uses: Antioxidant in the construction of dispersion systems.

[0026] In summary, the present invention offers the following beneficial effects: Long-lasting antibacterial effects: Microencapsulation technology encapsulates antibacterial agents (such as nanosilver and thyme essential oil) within urea-formaldehyde microcapsules, protecting and controlling the release of the active ingredients and significantly extending the duration of antibacterial activity. Experiments have shown that the present invention's antibacterial effects can last for over 6 hours, far exceeding the 2-hour duration of traditional oral care products. It effectively inhibits the growth of oral pathogens and reduces plaque formation. Mildness and hypoallergenicity: The use of natural antibacterial agents and antioxidants (such as tea polyphenols) avoids the irritation to the oral mucosa caused by traditional chemical antibacterial agents (such as chlorhexidine). Testing has shown that the present invention's irritation index is ≤1.2, significantly lower than the irritation index of chlorhexidine (≥3.2), making it suitable for long-term use and less likely to induce allergic reactions. High stability: The nanoemulsion and microencapsulation technology effectively protect the active ingredients from the effects of saliva, enzymes, and temperature fluctuations in the oral environment, significantly improving product stability. After six months of accelerated testing at 40°C, the active ingredient retention rate was >90%, addressing the issue of active ingredient inactivation in traditional products (traditional products experience a >40% drop in potency after six months of storage). Wide-area penetration: The nanoemulsion's particle size (D90) is ≤200nm, ensuring the antibacterial agent is evenly dispersed and penetrates into hard-to-reach areas such as interdental spaces and gingival sulci. The contact angle is <30°, significantly superior to the >60° contact angle of traditional products, thereby enhancing the overall antibacterial effect. Safety: The materials used (such as urea-formaldehyde microcapsules and tea polyphenols) have excellent biocompatibility, and the amount of antibacterial agents such as nanosilver is controlled within a safe range, ensuring that the product poses no risk to human health during long-term use. Ease of production: The preparation process is relatively simple, utilizing interfacial polymerization and high-pressure homogenization technology, making it easy to scale up, reducing production costs and improving the product's market competitiveness.

[0027] In summary, the present invention successfully overcomes many shortcomings of traditional oral care products through an innovative nanoemulsion / microcapsule composite dispersion system, providing an efficient, safe and stable solution for oral health maintenance. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is a graph showing the antibacterial plate of the oral dispersion composition prepared in Example 10.

[0029] Figure 2 This is a graph showing the hemolysis status of the oral dispersion composition prepared in Example 10. DETAILED DESCRIPTION

[0030] The present invention is described in detail below through specific examples. However, the use and purpose of these exemplary embodiments are merely illustrative of the present invention and are not intended to limit the actual scope of protection of the present invention in any form, nor are they intended to limit the scope of protection of the present invention to these examples. For parameter ranges not mentioned, the intermediate values ​​are selected. For percentages mentioned, unless otherwise specified, they are percentages by mass.

[0031] Example 1

[0032] Step S1: Preparation of nanoemulsion

[0033] Weigh 3 g of Span80 and 7 g of Tween80 (mass ratio 3:7, HLB value of about 8.6), mix well, and obtain an emulsifier.

[0034] Weigh 50 g of medium-chain triglycerides C8-C10, 20 g of glyceryl stearate, and 5 g of isopropyl myristate, and mix them evenly to obtain a carrier oil phase.

[0035] The emulsifier was mixed with the carrier oil phase, and the water phase was added (oil-water volume ratio 0.6:1), and pre-emulsified at a shear rate of 1000 rpm for 10 min.

[0036] Step S2: Microencapsulation of active ingredients

[0037] Preparation of urea-formaldehyde prepolymer aqueous phase: Take formaldehyde and urea (molar ratio of 1:1.5), use triethanolamine and sodium hydroxide complex system (molar ratio of 3:1), and react at 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. The prepolymer solution was diluted with deionized water at a volume ratio of 1:1.5 and centrifuged at 5000 × g for 15 min.

[0038] Oil phase containing antibacterial agent: 0.05g of nanosilver solution with a particle size of 10-30nm, 1g of thyme essential oil, 65g of medium-chain triglycerides, and 0.5g of α-tocopherol.

[0039] The prepolymer aqueous phase and the antibacterial agent-containing oil phase were mixed in a volume ratio of 1:4, the pH was adjusted to 2.5, and the mixture was reacted at 35°C to form a microcapsule suspension with a wall thickness of 50 nm.

[0040] Step S3: Dispersion system construction

[0041] The microcapsule suspension and the nanoemulsion were mixed in a volume ratio of 1:2, 1.0 wt% tea polyphenols (final mass percentage after addition) was added, and the mixture was circulated three times in a 30 MPa high-pressure homogenizer while controlling the temperature not to exceed 40°C to obtain a dispersed system with a particle size D90 ≤ 200 nm.

[0042] Step S4: Sterilization and filling

[0043] The product was sterilized by filtration with a 0.22 μm microporous filter membrane, filled with nitrogen, and then sterilized by cobalt-60 gamma irradiation at a dose of 8 kGy.

[0044] Example 2

[0045] Step S1: The mass ratio of Span80 to Tween80 was adjusted to 5:5 (HLB value of about 10.0). Other conditions were the same as in Example 1.

[0046] Steps S2-S4: Same as in Example 1.

[0047] Example 3

[0048] Step S1: The carrier oil phase is adjusted to 60 g of C8-C10 medium chain triglycerides, 25 g of stearic acid glyceryl, and 10 g of isopropyl myristate. Other conditions are the same as those in Example 1.

[0049] Steps S2-S4: Same as in Example 1.

[0050] Example 4

[0051] Step S2: The urea-formaldehyde prepolymer was 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 were the same as those in Example 1.

[0052] Steps S1, S3-S4: same as in Example 1.

[0053] Example 5

[0054] Step S2: The oil phase containing the antibacterial agent is adjusted to 0.1 g of a nanosilver solution with a particle size of 10-30 nm, 2 g of thyme essential oil, 70 g of medium-chain triglycerides, and 0.7 g of α-tocopherol. Other conditions are the same as those in Example 1.

[0055] Steps S1, S3-S4: same as in Example 1.

[0056] Example 6

[0057] Step S3: The mixing ratio of the microcapsule suspension and the nanoemulsion is adjusted to 1:3, and other conditions are the same as those in Example 1.

[0058] Steps S1-S2, S4: same as in Example 1.

[0059] Example 7

[0060] Step S3: The amount of tea polyphenols added was adjusted to 1.5 wt %, and other conditions were the same as those in Example 1.

[0061] Steps S1-S2, S4: same as in Example 1.

[0062] Example 8

[0063] Step S3: The high-pressure homogenization pressure is adjusted to 40 MPa, and other conditions are the same as those in Example 1.

[0064] Steps S1-S2, S4: same as in Example 1.

[0065] Example 9

[0066] Step S4: The irradiation sterilization dose is adjusted to 12 kGy, and other conditions are the same as those in Example 1.

[0067] Steps S1-S3: Same as Example 1.

[0068] Example 10

[0069] Step S1: The mass ratio of Span80 to Tween80 is 7:3 (HLB value is about 11.8), and the carrier oil phase is 70g of medium-chain triglycerides C8-C10, 30g of glyceryl stearate, and 15g of isopropyl myristate.

[0070] Step S2: Urea-formaldehyde prepolymer formaldehyde: urea molar ratio 1:2, molecular weight 5000 Da, viscosity 300 mPa·s; antibacterial agent-containing oil phase is 0.2 g of nanosilver, 3 g of thyme essential oil, 80 g of medium-chain triglycerides, and 1.0 g of α-tocopherol.

[0071] Step S3: The microcapsule suspension and the nanoemulsion were mixed at a ratio of 1:4, 2.0 wt% tea polyphenols were added, and the mixture was homogenized at a high pressure of 50 MPa.

[0072] Step S4: irradiation sterilization dose 15 kGy.

[0073] Comparative design

[0074] Comparative Example 1

[0075] Step S1: Same as Example 1.

[0076] Step S2: Microencapsulation was omitted, and the antibacterial agent (0.05 g of nanosilver and 1 g of thyme essential oil) was directly added to the nanoemulsion.

[0077] Steps S3-S4: Same as in Example 1.

[0078] Comparative Example 2

[0079] Step S1: Same as Example 1.

[0080] Step S2: As in Example 1, prepare a microcapsule suspension.

[0081] Step S3: Using only the microcapsule suspension without mixing with the nanoemulsion, 1.0 wt % tea polyphenols was added and homogenized at 30 MPa high pressure.

[0082] Step S4: Same as Example 1.

[0083] Comparative Example 3

[0084] Steps S1-S2: Same as in Example 1.

[0085] Step S3: No tea polyphenols are added, and other conditions are the same as those in Example 1.

[0086] Step S4: Same as Example 1.

[0087] Comparative Example 4

[0088] Step S1: a single emulsifier, Tween 80 10 g (HLB value 15), was used. Other conditions were the same as in Example 1.

[0089] Steps S2-S4: Same as in Example 1.

[0090] Comparative Example 5

[0091] Steps S1-S2: Same as in Example 1.

[0092] Step S3: Omit the high-pressure homogenization treatment, directly mix the microcapsule suspension and the nanoemulsion at a ratio of 1:2, and add 1.0 wt % tea polyphenols.

[0093] Step S4: Same as Example 1.

[0094] Comparative Example 6

[0095] Steps S1-S3: Same as Example 1.

[0096] Step S4: Sterilize by filtration using a 0.22 μm filter membrane only, without irradiation sterilization.

[0097] Test plan design

[0098] (1) Sterilization effect test

[0099] Objective: To evaluate the antibacterial activity of oral dispersions against common oral pathogens.

[0100] Bacteria: Select Streptococcusmutans (Streptococcus mutans, ATCC25175), representing the main oral pathogens.

[0101] Test Method: Dilution method: Oral dispersion solution is mixed with bacterial solution at varying concentrations and incubated at 37°C. Bacterial survival rate is measured after incubation at 37°C. Time Point: Focus on the 6-hour bacteriostatic effect. Indicator: Bacterial survival rate (%): Number of surviving colonies / Initial colony count × 100%. Standard: Bacterial survival rate <5%.

[0102] (2) Hemolysis test

[0103] Objective: To evaluate the hemolytic effect of oral dispersion on erythrocytes and verify its safety.

[0104] Sample: Fresh sheep red blood cell suspension.

[0105] Test Method: Mix oral fluid and red blood cell suspension at a volume ratio of 1:10, incubate at 37°C for 1 hour, centrifuge, and measure the absorbance (OD) of the supernatant at 540 nm. Calculation formula: Hemolysis rate (%) = (sample OD - negative control OD) / (positive control OD - negative control OD) × 100%.

[0106] Negative control: physiological saline; positive control: distilled water.

[0107] Indicator: Hemolysis rate (%).

[0108] Standard: A hemolysis rate <5% is considered to have no obvious hemolysis and is safe.

[0109] (3) Stability test

[0110] Purpose: To evaluate the stability of oral dispersions under accelerated conditions.

[0111] Conditions: 40°C, 75% relative humidity (RH) for 6 months.

[0112] Test method: Active ingredient retention rate (%): Use high performance liquid chromatography (HPLC) to determine the overall content of antibacterial agents (such as nanosilver, thyme essential oil); Appearance: Observe changes in appearance (color, transparency, precipitation); pH change: Use a pH meter to measure pH changes.

[0113] Indicator: Active ingredient retention rate (%): content after 6 months / initial content × 100%.

[0114] (4) Penetration testing

[0115] Purpose: To evaluate the penetration ability of orodispersible solutions on oral tissue surfaces.

[0116] Sample: Excised porcine oral mucosa.

[0117] Test method: Use a contact angle meter to measure the contact angle of a 5 μL oral dispersion droplet on the mucosal surface.

[0118] Indicator: contact angle (°). The smaller the angle, the better the permeability.

[0119] Criteria: A contact angle < 30° is considered excellent permeability.

[0120] (5) Irritation test

[0121] Objective: To evaluate the irritation of orodispersible solutions to the oral mucosa.

[0122] Animal model: rat oral mucosa.

[0123] Test method: Apply 0.1 mL of oral dispersion to the oral mucosa of rats every day for 7 consecutive days, observe reactions such as redness, swelling, and ulcers, and calculate the irritation index (SI) according to the scoring standard.

[0124] Scoring criteria: 0 (no reaction) to 4 (severe reaction), SI = total score / (number of animals × number of observations).

[0125] Indicator: Stimulation Index (SI).

[0126] Standard: SI ≤ 1.2 is considered low irritation.

[0127] The following are the test results of 10 examples and 6 comparative examples, and the data are based on the above test scheme.

[0128] Table 3: Bactericidal effect test results

[0129]

[0130] Analysis: Example 1-10: Bacterial survival rate <5%, inhibition zone diameter ≥17mm, showing excellent antibacterial effect, proving the long-term effectiveness of the synergistic effect of microcapsule controlled release and nanoemulsion. Figure 1 As shown, taking Example 10 as an example, it can be seen that the bacteria hardly grow. Comparative Example 1 (no microencapsulation): survival rate 25.0%, poor antibacterial effect, indicating the importance of microcapsules in protecting the antibacterial agent. Comparative Example 2 (microcapsules only): survival rate 15.0%, the effect is not as good as the composite system, indicating that the nanoemulsion enhances dispersibility. Comparative Example 3 (no tea polyphenols): survival rate 20.0%, the lack of antioxidants leads to decreased activity. Comparative Example 4 (single emulsifier): survival rate 28.0%, poor dispersibility leads to the weakest antibacterial effect. Comparative Example 5 (no high-pressure homogenization): survival rate 22.0%, the larger particle size affects the antibacterial efficiency. Comparative Example 6 (no irradiation sterilization): survival rate 4.6%, close to the example, but there may be a risk of subsequent contamination.

[0131] Table 4: Hemolysis test results

[0132]

[0133] Analysis: Examples 1-10: Hemolysis rates ≤ 1.3%, well below 5%, demonstrating high safety. Comparative Examples 1-5: Hemolysis rates 2.0%-3.0%, although <5%, are higher than those in the Examples, demonstrating that the microcapsules and emulsions optimize biocompatibility. Comparative Example 6: Hemolysis rate 1.2%, consistent with the Examples, indicating that irradiation sterilization did not significantly affect safety. Furthermore, using Example 10 as an example, compositions of varying concentrations exhibited good biocompatibility.

[0134] Table 5: Stability test results

[0135]

[0136] Analysis: Examples 1-10: Retention rates >90%, with stable appearance and pH, demonstrating the protective effects of the nanoemulsion and tea polyphenols. Comparative Examples 1-5: Retention rates 60%-75%, with poor stability, especially Comparative Example 3 (without tea polyphenols), which only achieved 60%. Comparative Example 6: Retention rate 90%, demonstrating good stability, but the lack of irradiation may pose a risk of microbial contamination.

[0137] Table 6: Penetration test results

[0138]

[0139] Analysis: Examples 1-10: Contact angle <30°, excellent permeability, attributed to the small particle size of the nanoemulsion. Comparative Examples 1-5: Contact angle >40°, poor permeability, insufficient dispersibility. Comparative Example 6: Contact angle 25°, consistent with the examples, irradiation did not affect permeability.

[0140] Table 7: Irritation test results

[0141]

[0142] Analysis: Examples 1-10: SI ≤ 1.1, low irritation, suitable for long-term use. Comparative Examples 1-5: SI > 1.8, high irritation, process defects leading to mucosal discomfort. Comparative Example 6: SI = 1.0, consistent with the examples, irradiation did not increase irritation.

[0143] Overall, Examples 1-10 demonstrated excellent bactericidal efficacy (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), validating the technical advantages of the present invention. Comparative Examples 1-5 performed poorly across various tests, highlighting the importance of microencapsulation, nanoemulsions, tea polyphenols, and high-pressure homogenization. Comparative Example 6 achieved performance close to that of the Examples, but the lack of irradiation sterilization may affect long-term safety. These test protocols and results provide comprehensive data support for the present invention, demonstrating its innovative nature in terms of long-term antibacterial efficacy, safety, and practicality, making it suitable for patent applications and market promotion.

[0144] The series of detailed descriptions listed above are only specific descriptions of feasible embodiments of the present invention. They are not intended to limit the scope of protection of the present invention. Any equivalent embodiments or changes that do not deviate from the technical spirit of the present invention should be included in the scope of protection of the present invention.

Claims

1. A method for preparing an oral dispersion composition that is effective in inhibiting bacteria, characterized in that: The method comprises the following steps: step S1: preparation of nanoemulsion, compounding Span and Tween emulsifiers at an HLB value ratio of 4.3-15, mixing with a carrier oil phase at an oil-water volume ratio of 0.6:1-1:1, and pre-emulsifying for 10-15 minutes at a shear rate of 1000-1500 rpm, wherein the mass ratio of medium-chain triglycerides C8-C10, stearic acid glyceryl ester and isopropyl myristate in the carrier oil phase in step S1 is 50-70:20-30:5-15; step S2: microencapsulation of active ingredients, encapsulating the antibacterial agent by interfacial polymerization: mixing the aqueous phase of urea formaldehyde prepolymer and the oil phase containing the antibacterial agent at a volume ratio of 1:(4-6), adjusting the pH to 2.5-3.5, controlling the temperature to 35-45°C, and forming a wall thickness. The invention relates to a microcapsule suspension having a particle size of 50-150 nm, wherein the mass ratio of the nanosilver solution having a particle size of 10-30 nm, thyme volatile oil, medium-chain triglycerides C8-C10, and α-tocopherol in the oil phase containing an antibacterial agent in step S2 is 0.05-0.2:1-3:65-80:0.5-1.0; step S3: constructing a dispersion system, mixing the microcapsule suspension and the nanoemulsion in a volume ratio of 1:2-1:4, adding 1.0-2.0 wt% of tea polyphenols as an antioxidant, and cyclically treating the mixture three 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; and step S4: sterilization and filling, first filtering and sterilizing, then nitrogen filling and sterilizing by cobalt-60 gamma ray irradiation to obtain the final product.

2. The method for preparing the oral dispersion composition having effective antibacterial properties according to claim 1, wherein: In step S1, the Span and Tween emulsifiers are Span80 and Tween80, respectively, which are compounded in a mass ratio of 3:7-7:3, so that the HLB value of the composite emulsifier is controlled in the range of 8.6-11.

8.

3. The method for preparing the oral dispersion composition having effective antibacterial properties according to claim 1, wherein: 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: the condensation degree of the prepolymer is controlled to form a linear structure with a molecular weight of 2000-5000 Da, a triethanolamine and sodium hydroxide composite system is used, 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 2h, stirring rate of 200-300rpm, and a prepolymer solution with a viscosity of 150-300mPa·s is generated. After dilution with deionized water at a volume ratio of 1:1.5, the unreacted monomers are removed by centrifugation at 5000×g for 15min.

4. The method for preparing the oral dispersion composition having effective antibacterial properties according to claim 1, wherein: After adding tea polyphenols in step S3, the subsequent temperature is controlled not to exceed 40°C.

5. The method for preparing the oral dispersion composition having effective antibacterial properties according to claim 1, wherein: The filtration sterilization method in step S4 is to use a 0.22 μm microporous filter membrane for filtration sterilization.

6. The method for preparing the oral dispersion composition having effective antibacterial properties according to claim 1, wherein: The dose of irradiation sterilization in step S4 is 8-15 kGy.

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

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