Oral antibacterial composition synthesized from pseudo-ginseng and tea polyphenol and preparation method of oral antibacterial composition

Abstract

The invention discloses an oral antibacterial composition synthesized from pseudo-ginseng and tea polyphenol and a preparation method of the oral antibacterial composition, and relates to the technical field of nano modification. Specifically, a metal-polyphenol nano core is formed through metal ion coordination self-assembly, a tea polyphenol core component, namely gallocatechin gallate, is synergistically compounded with notoginsenoside R1, and a chitosan-sodium tripolyphosphate ionic gel crosslinking technology is adopted to construct nano particles of a core-shell structure. The composition realizes multi-target bacteriostasis (MIC 15.7-22.1 mu g / mL) and anti-inflammatory effect (TNF-alpha inhibition rate is 75.4-84.2%) on oral pathogens (such as streptococcus mutans and porphyromonas gingivalis), solves the problems that EGCG is easy to oxidize and degrade, the residence time is short, the permeability of a traditional preparation is poor and the like, and provides a green and efficient oral care solution.

Description

Technical Field

[0001] This invention relates to the field of nanotechnology, specifically to an oral antibacterial composition synthesized from Panax notoginseng and tea polyphenols, and its preparation method. Background Technology

[0002] Oral diseases, as a global public health issue, are showing a continuous upward trend in both incidence and pathogenic complexity. Imbalance of the oral microecology is a core mechanism leading to these diseases, with Streptococcus mutans (S. mutans) being a key factor. Streptococcus mutans ), Porphyromonas gingivalis ( Porphyromonas gingivalis Staphylococcus aureus ( Staphylococcus aureus Candida albicans ( Candida albicans Pathogenic microorganisms such as endotoxins and proteases multiply in the warm and humid environment of the oral cavity, forming a complex biofilm structure. This not only directly damages the host tissues but also produces virulence factors such as endotoxins and proteases, triggering local inflammatory reactions and tissue destruction.

[0003] Traditional oral antibacterial treatment mainly relies on chemically synthesized antibacterial agents, such as chlorhexidine, triclosan, and benzalkonium chloride. Although these compounds have broad-spectrum antibacterial activity, long-term use has significant drawbacks: First, bacteria easily develop resistance to chemical antibacterial agents, especially bacteria within biofilms, whose reduced metabolic activity and extracellular polymer protection significantly decrease their sensitivity to antibacterial drugs; second, chemical antibacterial agents lack selectivity, disrupting the normal oral flora while killing pathogenic bacteria, leading to dysbiosis and secondary infections; third, some chemical antibacterial agents are irritating to the oral mucosa, and long-term use may cause adverse reactions such as mucosal erosion, taste abnormalities, and tooth discoloration; finally, simple antibacterial treatment cannot address inflammatory damage and tissue repair issues, making it difficult to achieve comprehensive oral health management.

[0004] Tea polyphenols are the main active components in tea, with gallocatechin gallate (EGCG) being the most abundant, accounting for approximately 50-80% of the total. EGCG's molecular structure contains eight phenolic hydroxyl groups, exhibiting strong reducing and complexing abilities and demonstrating multiple biological activities. In terms of antibacterial activity, EGCG works through multiple targets: binding to bacterial cell wall peptidoglycans, disrupting cell wall integrity; inhibiting the activity of key enzymes such as DNA gyrase and RNA polymerase, interfering with genetic material replication and transcription; binding to cell membrane phospholipids, increasing membrane permeability and leading to extravasation of cell contents; and chelating essential metal ions for bacterial metabolism, such as Fe. 2+ Zn 2+EGCG can block energy metabolism pathways. In vitro antibacterial experiments have confirmed that the minimum inhibitory concentration (MIC) of EGCG against Streptococcus mutans, Staphylococcus aureus, and Escherichia coli is 12.5-100 μg / mL, and it is not prone to inducing bacterial resistance. In terms of anti-inflammation, EGCG can inhibit the activation of nuclear transcription factor NF-κB, downregulate the production of inflammatory mediators such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2), while activating the antioxidant enzyme system, scavenging reactive oxygen free radicals, and reducing oxidative stress damage. However, EGCG faces serious stability challenges in practical applications. The pyrogallol structure in the EGCG molecule is easily oxidized under neutral or alkaline conditions, forming quinone compounds and polymers, leading to loss of activity and solution discoloration. Studies have shown that the half-life of EGCG in phosphate buffer at pH 7.4 is only 30 min, while it is relatively stable below pH 6.0. Light, temperature, and metal ions can all accelerate the degradation process of EGCG. Furthermore, EGCG has an extremely short retention time in the oral environment. Due to physiological factors such as saliva dilution and swallowing, the effective concentration drops below the MIC within 10-15 minutes after rinsing, making it unable to maintain a sustained antibacterial effect. The strong bitter taste of EGCG also limits its application concentration in oral care products and its consumer acceptance.

[0005] Existing oral care formulations mainly include mouthwash, toothpaste, mouthwash tablets, sprays, and gels, but they generally suffer from technical defects. While traditional mouthwashes are convenient, the active ingredients have a short retention time in the oral cavity, typically maintaining an effective concentration for only 15-30 minutes, and require frequent use to achieve the desired effect. Most of the active ingredients in toothpaste are rinsed away during brushing, with very little actually penetrating the gingival sulcus and interdental spaces. Mouthwash tablets require complete dissolution to be effective, resulting in long dissolution times and uneven concentration distribution. Although sprays can quickly cover the oral surface, the lack of an adhesion mechanism means the drug is quickly diluted and removed by saliva. These formulations fail to effectively address the fundamental problems of poor drug stability, short retention time, and insufficient targeting. The rise of nanomedicine delivery technology has provided new opportunities for innovation in oral care formulations. Nanomedicine delivery systems, by encapsulating active ingredients in nanoscale carrier materials, can significantly improve the physicochemical properties and biological behavior of drugs. An ideal oral nanocarrier should possess the following characteristics: a particle size controlled within the range of 50-200 nm to ensure good dispersion stability and effective penetration into oral microfibers and biofilms; a positively charged surface to enhance electrostatic adsorption to negatively charged oral mucosa and bacterial surfaces; pH responsiveness and enzyme degradation to achieve controlled drug release under specific environmental conditions; and biocompatibility and biodegradability of the carrier material itself to avoid toxic reactions and tissue damage. Summary of the Invention

[0006] In view of this, the purpose of this invention is to propose an oral antibacterial composition synthesized from Panax notoginseng and tea polyphenols and its preparation method, in order to solve the problems of traditional chemical antibacterial agents easily inducing bacterial resistance, destroying normal flora and causing mucosal irritation; although tea polyphenols (EGCG) have multi-target antibacterial and anti-inflammatory activities, they have poor stability (half-life <30min under neutral conditions), are easily oxidized and degraded, have a short residence time in the oral environment (<15min) and a strong bitter taste, which makes it impossible to maintain an effective concentration and limits the application concentration; existing oral care preparations (such as mouthwash, toothpaste, and sprays) have poor penetration of active ingredients into the gingival sulcus and biofilm, uneven distribution, inconvenience of frequent use, and difficulty in achieving comprehensive management of inflammation suppression and tissue repair; although nano-drug delivery technology can improve drug behavior, existing systems (such as simple polyphenol complexes or emulsions) lack the synergistic effect of Panax notoginseng saponin R1, pH-responsive controlled release, targeted adsorption and biodegradability, resulting in technical bottlenecks such as low antibacterial efficiency, large purification loss, serious environmental pollution and high difficulty in industrialization.

[0007] The adopted technical solution is as follows: a method for preparing an oral antibacterial composition synthesized from Panax notoginseng and tea polyphenols, comprising the following steps: S1, dissolving 3-12 parts by mass of gallic catechin gallate (CAS No.: 989-51-5) in 200-600 parts by mass of purified water, adjusting the pH to 5.8-6.4 to obtain an adjusted solution; S2, adding 0.3-3 parts of Panax notoginseng saponin to the adjusted solution obtained in step S1 to obtain a coexisting solution; S3, adding... Ferric chloride solution was added dropwise to the coexisting liquid, and the molar ratio between the amount of iron ions added and gallocatechin gallate was controlled to be 1:(3-10). Then, metal-polyphenol nanonuclei were formed by self-assembly at room temperature. S4, the metal-polyphenol nanonuclei obtained in step S3 were cross-linked with 5-20 parts of chitosan solution and 1-4 parts of sodium tripolyphosphate solution to obtain a cross-linked product. S5, the cross-linked product obtained in step S4 was filtered and sterilized to obtain a dispersion. Then, the zeta potential was adjusted to obtain the final product.

[0008] Preferably, the reagent used to adjust the pH in step S1 is an aqueous solution of glacial acetic acid; the concentration of the aqueous solution of glacial acetic acid is 0.1-1.0 mol / L; the pH is adjusted by adding it dropwise at a rate of 0.5-2.0 mL / min, and the process is carried out under magnetic stirring at a speed of 200-400 rpm. After the pH value reaches the target value, stirring is continued for 3-5 min.

[0009] Preferably, the notoginsenoside component in step S2 is Notoginsenoside R1 (CAS No.: 80418-24-2); the addition method is as follows: first, Notoginsenoside R1 is dissolved in 5-20 parts of purified water to prepare a stock solution with a concentration of 5-20 mg / mL, and then, under stirring at 300-500 rpm, it is added dropwise to the solution in step S1 at a rate of 1-3 mL / min. After the addition is completed, stirring is continued at a temperature of 20-25℃ for 5-15 min to obtain a coexisting solution.

[0010] The preparation method of Notoginsenoside R1 is as follows: PPS (1500bp), UGT71A1 variant (1200bp), and XylT1 (900bp) genes were amplified by PCR from a Panax notoginseng root cDNA library. Codon optimization was performed using SnapGene software to construct the pETDuet-1 multi-gene expression vector. The expression cassette was integrated into the BL21(DE3) genome using a CRISPR / Cas9 system (vector pCas9, sgRNA targeting the lacZ site). Positive clones were screened and sequenced for verification. E. coli NR1-Engineered strain. Will E. coli A single colony of NR1-Engineered was inoculated into 5 mL of LB medium (containing 50 μg / mL ampicillin) and cultured at 30 °C and 200 rpm for 12 h; then transferred to 500 mL of optimized fermentation medium (10 g glucose, 5 g yeast extract, 2.5 g (NH4)2SO4, etc., pH 7.0) and cultured at 37 °C and 250 rpm until OD500. 600 =1.8, add 0.4mM IPTG for induction, continue culturing at 25℃ for 48h, supplement with 5g glucose and 1g yeast extract every 12h, final OD 600=15.2. Collect bacterial cells by centrifugation (5000 rpm, 15 min), resuspend in 50 mL phosphate buffer (pH 7.5), sonicate on ice (150 W, 5 s / 5 s, 15 min), and centrifuge at 12000 rpm to collect the supernatant (enzyme activity: PPS 25 U / mL, UGT 18 U / mL, XylT 12 U / mL); prepare nanoliposomes: dissolve 70 mg DSPC and 30 mg cholesterol in 5 mL chloroform, rotary evaporate to form a membrane, resuspend in PBS (pH 7.4), and sonicate to encapsulate 10 mL of crude enzyme solution (encapsulation rate 82%); react the encapsulated enzyme with 5 mM protopanaxadiol, 2 mM UDP-glucose, and 1 mM UDP-xylose in 100 mL Tris-HCl buffer, and incubate at 37℃ and 150 rpm for 24 h. TLC monitoring (Rf = 0.4, chloroform:methanol 4:1) indicates complete conversion. The reaction solution was extracted with ethyl acetate (3 × 100 mL), concentrated to dryness, and eluted on a silica gel column (chloroform:methanol:water = 65:35:5 to 65:35:10). The target fractions were combined. The solution was purified by HPLC (C18 column, 5 μm, 250 × 10 mm; mobile phase A: 0.1% formic acid water, B: acetonitrile; 0-10 min 0% B, 10-25 min 20-50% B, 25-30 min 50-60% B, flow rate 2 mL / min). The peak at 18.5 min was collected and freeze-dried to obtain 0.42 g of notoginsenoside R1 (purity 99.2%, yield 840 mg / L, MS confirmed m / z 955 [M+H]+).

[0011] Preferably, in step S3, the concentration of the ferric chloride solution is 0.01-0.1 mol / L, the dropping rate is controlled at 0.2-1.0 mL / min, and magnetic stirring is performed at 600-1000 rpm. After the dropping is completed, stirring continues for 10-30 min.

[0012] Preferably, the preparation method of chitosan solution in step S4 is as follows: Chitosan powder (CAS No.: 9012-76-4) with a degree of deacetylation ≥80% and a molecular weight of 50-300kDa is slowly added to a 1-2% (v / v) aqueous solution of acetic acid pre-cooled to 4-10℃ under nitrogen protection. The mixture is first stirred at low speed of 200rpm for 30min to fully wet the chitosan, and then heated to room temperature and the stirring speed is increased to 400-600rpm to continue dissolving for 2-4h. During the dissolution process, ultrasonic degassing is performed every 30min at an ultrasonic power of 40kHz for 3-5min, finally obtaining a clear chitosan solution with a mass-volume percentage of 0.5-1.0%. Then, the solution is filtered using a 0.45μm filter membrane to remove insoluble matter, and the pH is adjusted to 4.5-5.5. The pH adjustment is achieved by adding 0.1mol / L sodium hydroxide solution dropwise to make the protonation degree of the amino groups in the clear chitosan solution reach 60-80%.

[0013] Preferably, the preparation method of sodium tripolyphosphate solution in step S4 is as follows: sodium tripolyphosphate is dissolved in deionized water to prepare a solution with a mass-volume percentage of 0.05-0.50%, the dissolution temperature is controlled at 15-20℃, and a vortex shaker is used to shake at 2000 rpm for 3-5 minutes to ensure complete dissolution.

[0014] Preferably, the crosslinking method in step S4 is as follows: In the first stage, the metal-polyphenol nanocore suspension obtained in step S3 is slowly added to the chitosan solution under stirring at 400 rpm, with a volume ratio of 1:(2-4), and the mixing time is 5-10 min to form a pre-coating layer; In the second stage, the sodium tripolyphosphate solution is added dropwise at a rate of 0.05-0.2 mL / min using an injection pump. During the dropwise addition, the turbidity of the system is monitored. When the turbidity value reaches 0.8-1.2 NTU, it indicates that crosslinking has started. After the dropwise addition is completed, a variable speed stirring mode is adopted: first, the mixture is rapidly stirred at 600 rpm for 5 min to promote the uniformity of crosslinking, and then the stirring is reduced to 300 rpm for 10-25 min to complete the crosslinking and curing; The temperature is controlled at 20±2℃ and the pH is maintained at 5.5-6.0 throughout the crosslinking process, ultimately forming core-shell structured nanoparticles with a shell thickness of 15-30 nm.

[0015] Preferably, the filtration and sterilization method in step S5 is as follows: sterilization is performed by sequentially passing the material through a 0.45μm pre-filtration and a 0.22μm aseptic filtration, with a filtration pressure ≤0.2MPa.

[0016] Preferably, the dispersion in step S5 is obtained as follows: the crosslinked product after filtration and sterilization is subjected to pulsed ultrasonic treatment at 40 kHz for 3-10 min, the particle size is controlled at 80-180 nm, and PDI≤0.25.

[0017] Preferably, in step S5, the zeta potential of the dispersion is adjusted to +15 to +35 mV, and the pH is adjusted to 5.8-6.2.

[0018] The following steps list commonly used instrument models.

[0019] S1. Dissolution and pH Control: pH meter and electrode: Mettler Toledo SevenCompact S220 / SevenExcellence S400 with InLab Routine / Expert Pro combination electrode; or Thermo Orion StarA211 / STAR A221, or domestic options such as Leici PHS-3E (suitable for weakly acidic systems and samples with low ionic strength). Magnetic stirring / heating: IKA RCT basic, C-MAG HS 7 or Heidolph MR Hei-Standard; for higher viscosity, use IKA EUROSTAR 20 / 60 or Heidolph Hei-TORQUE Core top stirrer (for stable stirring at 200-400 rpm). Precision addition: Metrohm 905 / 907 automatic titrator for constant-rate, dropwise control; or Harvard Apparatus PHD Ultra, New Era NE-1000 syringe pump, or domestically produced Baoding Lange Longer Pump peristaltic / syringe pump (0.5-2.0 mL / min). Low temperature and protection from light: 4℃ refrigerator / ice bath and amber glassware to slow polyphenol oxidation; acetic acid preparation and storage follow chemical management regulations (acetic acid information supports the rationality of pH adjustment). S2, Panax notoginseng saponin stock solution preparation and addition: Quantitative pipetting: Eppendorf Research Plus or Rainin LTS multichannel pipette to ensure the quantitative accuracy of stock solution preparation and 1-3 mL / min addition. Addition and stirring: Same syringe / peristaltic pump as S1, stirring at 300-500 rpm to avoid local overconcentration; container recommended to be in a constant-temperature 20-25℃ water bath or constant-temperature stirring plate. S3. Ferric Chloride Dropping and Self-Assembly: Dropping Control: A constant drop rate of 0.2-1.0 mL / min is achieved using the same syringe pump as above. Corrosion-resistant PTFE tubing and a brown syringe are used to reduce the photosensitivity of Fe(III) / polyphenols. Stirring and Reaction Vessel: A high-speed magnetic stirrer (600-1000 rpm) and a baffled glass reaction vessel are used to promote uniform nucleation. If necessary, top stirring is used to improve shear mixing uniformity. Online / Offline Monitoring: A UV-Vis spectrophotometer (such as Shimadzu UV-2600i or Agilent Cary 60) is used to monitor changes in EGCG coordination absorption to determine the self-assembly process. S4. Chitosan Solution Preparation and TPP Crosslinking: Nitrogen Protection: High-purity nitrogen cylinders and a two-stage pressure reducing valve (Air Liquide / Linde) are used to suppress the risk of polyphenol oxidation and chitosan solution oxidation and discoloration under an inert atmosphere.Ultrasonic degassing / dispersion: 40kHz ultrasonic cleaning tank such as Branson 2510 / 3510, Elma S30H, or domestically produced Scientificz KQ series; for pulsed ultrasound and high-energy dispersion, use a probe-type Sonics Vibra-Cell VCX130 or Ningbo Scientificz JY92-IIN (meeting the requirement of 3-5 minutes of ultrasound every 30 minutes). Vortex mixing: Scientific Industries Vortex-Genie 2 or Thermo Vortex, at 2000rpm to promote rapid dissolution and uniform dispersion of TPP. Turbidity monitoring (NTU): Hach 2100Q / 2100N portable / desktop turbidimeter or ThermoOrion AQ4500, used to determine the crosslinking initiation window of 0.8-1.2 NTU. Temperature and pH control: Julabo / Lauda constant temperature water bath (20±2℃). For sodium hydroxide micro-titration, use an automatic titrator or syringe pump to precisely control the pH to 5.5-6.0. For chitosan solution, pH adjustment to 4.5-5.5 and amino protonation control rely on accurate pH measurement. S5, Filtration, Sterilization, Ultrasonic Granulation, and Zeta Adjustment: Aseptic filtration: 0.45μm pre-filtration + 0.22μm terminal aseptic filtration. Millipore Sigma Steritop / Stericup PES series or similar products from Pall / Sartorius are recommended. For vacuum source, select a KNF / LABOPORT diaphragm pump or a Rocker vacuum pump. If ≤0.2MPa pressure filtration is required, configure a Sartorius / Millipore 47mm stainless steel pressure filter and pressure gauge. Ultrasonic granulation: Using the same S4 ​​ultrasonic equipment, control the particle size to 80-180 nm and PDI ≤ 0.25 with pulse mode at 40 kHz for 3-10 min (processing basis derived from common ultrasonic dispersion practices of chitosan / TPP nanosystems). Zeta potential and particle size characterization: For DLS / electrophoretic light scattering, we recommend Malvern Zetasizer Ultra / Pro, HORIBA SZ-100V2, or Brookhaven NanoBrook Omni, which can simultaneously provide particle size, PDI, and Zeta to guide the adjustment of the +15~+35 mV window.

[0020] In summary, the beneficial effects of this invention are as follows: The oral antibacterial composition synthesized from Panax notoginseng and tea polyphenols, and its preparation method, described in this invention, possess significant technical innovation and practical value. Compared with existing technologies, it exhibits the following outstanding beneficial effects: High inventiveness and technological breakthrough: This invention is the first to synthesize notoginsenoside R1 and the core component of tea polyphenols, gallic catechin gallate (EGCG), through the use of metal ions (Fe... 3+Stable metal-polyphenol nanonuclei are formed through coordination self-assembly, and core-shell structured nanoparticles (shell thickness 15-30 nm, particle size 80-180 nm, PDI ≤ 0.25, Zeta potential +15 to +35 mV) are constructed using chitosan-sodium tripolyphosphate (TPP) ion gel crosslinking technology. This design not only solves the problems of easy oxidative degradation of EGCG (half-life < 30 min) and short oral retention time ( < 15 min), but also achieves a green and efficient supply of raw materials through the biosynthetic pathway of Panax notoginseng saponin R1 (CRISPR / Cas9 gene-edited E. coli cell factory, yield 840 mg / L, purity > 99%), avoiding the limitations of seasonality and low yield (< 100 mg / kg) of traditional plant extraction. Compared to existing polyphenol nanomedicines (such as the tea polyphenol complex recombinant nanosystem described in CN111888481B, which only involves simple mixing and assembly without the integration of Panax notoginseng saponins), this invention constructs a multi-target synergistic antibacterial mechanism: EGCG disrupts bacterial membranes and enzyme activity, Panax notoginseng saponins R1 enhance anti-inflammatory and vascular repair, and the core-shell structure enables pH-responsive controlled release (activity release >90% at oral pH 5.8-6.4), greatly enhancing the originality and functional complexity of the composition. Excellent antibacterial and anti-inflammatory properties: Test results show that the minimum inhibitory concentration (MIC) of the composition of this invention against Streptococcus mutans is 15.7-22.1 μg / mL, which is much lower than that of traditional chemical antibacterial agents (such as chlorhexidine MIC 50-100 μg / mL) and EGCG alone (MIC 12.5-100 μg / mL), making it less likely to induce drug resistance; the TNF-α inflammation inhibition rate reaches 75.4-84.2%, which is significantly better than existing tea polyphenol nanoemulsions (such as the tea polyphenol-silk protein system described in CN110075018A, with an inhibition rate of <60%). This performance originates from the chelation of Fe in the metal-polyphenol core. 3+It stabilizes EGCG activity and enhances the targeted adsorption of negatively charged bacterial biofilms through the positive charge of chitosan (adsorption rate >85%), achieving broad-spectrum antibacterial effects (covering Streptococcus mutans, Porphyromonas gingivalis, Staphylococcus aureus, and Candida albicans) and comprehensive anti-inflammatory effects, effectively addressing oral microecological imbalance and biofilm drug resistance. Excellent stability and biocompatibility: The composition has an absolute Zeta potential of 21.8-28.3 mV, ensuring long-term dispersion stability (particle size change rate <5% after 3 months of storage at 4℃), far superior to shell-less polyphenol nanoparticles (change rate >15%); the survival rate of human gingival epithelial cells (HGF-1) is >92.6%, with no mucosal irritation or taste interference, meeting the ISO 10993-5 biocompatibility standard. Compared to traditional mouthwashes or toothpastes (where active ingredients remain for <30 min), the core-shell nanostructure of this invention exhibits an adhesion rate of >70% in the saliva environment, extending the effective concentration maintenance time to 2-4 hours. This supports the development of various dosage forms (such as mouthwash, gel, and spray) and improves the safety of clinical applications. It is environmentally friendly and economically feasible: the preparation process is entirely aqueous, with no organic solvent residue, reducing the carbon footprint by >80%. The biosynthetic pathway of Panax notoginseng saponin R1 (enzyme cascade encapsulated in nanoliposomes, conversion rate >95%) reduces raw material costs to 1 / 5 of traditional extraction (<0.5 yuan / g). Process parameters (such as dropping speed 0.5-2.0 mL / min, stirring 200-1000 rpm) are easily scalable (suitable for industrial fermenters and continuous flow reactors). Compared to existing nano-drug delivery technologies (such as high-pressure homogenization, which is prone to clogging and has high energy consumption), this method is simple (completed in 5 steps, yield >85%), environmentally friendly, and conducive to the sustainable development of the oral care industry.

[0021] In summary, this invention achieves a breakthrough across the entire chain from raw material innovation to functional optimization through multidisciplinary collaboration (nano self-assembly, biosynthesis, and ion gelation). It not only fills the technological gap in the Panax notoginseng-tea polyphenol nano antibacterial composition, but also provides a new paradigm for nano-sized oral products of natural products, and has broad industrialization prospects and intellectual property value. Attached Figure Description

[0022] Figure 1 This is a hemolysis test diagram of the oral antibacterial composition prepared in Example 1 (hemolysis test at different mass percentages).

[0023] Figure 2 This is a photograph of the oral antibacterial composition prepared in Example 1. Detailed Implementation

[0024] The present invention will now be described in detail through specific embodiments. However, these exemplary embodiments are for illustrative purposes only and are not intended to limit the actual scope of protection of the present invention in any way, nor are they intended to restrict the scope of protection of the present invention to these embodiments. For parameter ranges not mentioned, intermediate values ​​are selected.

[0025] Example 1

[0026] The preparation method of the oral antibacterial composition synthesized by Panax notoginseng and tea polyphenols is as follows: Step S1: Dissolve 7.5g of gallic catechin gallate (CAS No.: 989-51-5) in 400g of purified water, and adjust the pH to 6.1 with 0.55mol / L glacial acetic acid aqueous solution. The pH is adjusted by adding dropwise at a rate of 1.25mL / min under magnetic stirring at a speed of 300rpm. After the pH value reaches the target value, continue stirring for 4min to obtain the adjusted solution. Step S2: Add 1.65g of Notoginsenoside R1 to the adjusted solution obtained in Step S1. The addition method is as follows: First, dissolve 1.65g of Notoginsenoside R1 in 12.5g of purified water to prepare a stock solution with a concentration of 12.5mg / mL. Then, under stirring at 400rpm, add it dropwise to the solution in Step S1 at a rate of 2mL / min. After the addition is complete, continue stirring at 22.5℃ for 10min to obtain a coexisting solution. Step S3: Add 0.055mol / L ferric chloride solution dropwise to the coexisting solution obtained in Step S2, controlling the molar ratio between the added iron ions and gallocatechin gallate to be 1:6.5, at a dropping rate of 0.6mL / min, while magnetically stirring at 800rpm. After the addition is complete, continue stirring for 20min. Then, at room temperature, metal-polyphenol nanonuclei are formed through self-assembly.Step S4: Crosslink the metal-polyphenol nanonucleus obtained in Step S3 with 12.5g chitosan solution and 2.5g sodium tripolyphosphate solution to obtain the crosslinked product. The chitosan solution is prepared as follows: 7.5g of chitosan powder (CAS No.: 9012-76-4) with a degree of deacetylation of 88% and a molecular weight of 175kDa is slowly added to 125g of 1.5% acetic acid aqueous solution pre-cooled to 7℃ under nitrogen protection. The mixture is first stirred at low speed of 200rpm for 30min to fully wet the chitosan, and then... The mixture was heated to room temperature and the stirring speed was increased to 500 rpm to continue dissolving for 3 hours. During the dissolution process, ultrasonic degassing was performed every 30 minutes at a power of 40 kHz for 4 minutes, resulting in a clear chitosan solution with a mass-volume percentage of 0.75%. Insoluble matter was then removed by filtration through a 0.45 μm filter membrane. The pH was adjusted to 5.0 by adding 0.1 mol / L sodium hydroxide solution dropwise to achieve a protonation degree of 70% for the amino groups in the clear chitosan solution. The preparation method of sodium tripolyphosphate solution is as follows: [The text abruptly ends here, likely due to an incomplete translation or a missing section.] Sodium phosphate (CAS No.: 7758-29-4) 1.65g was dissolved in 325g of deionized water to prepare a solution with a mass-volume percentage of 0.275%. The dissolution temperature was 17.5℃, and a vortex shaker was used to shake at 2000rpm for 4min to ensure complete dissolution. The cross-linking method was as follows: In the first stage, the metal-polyphenol nanonucleus suspension obtained in step S3 was slowly added to the chitosan solution at a volume ratio of 1:3 under stirring at 400rpm for 7.5min to form a pre-coating layer; In the second stage, the cross-linking was controlled... Sodium tripolyphosphate solution was added dropwise at a rate of 0.125 mL / min using a syringe pump. Turbidity changes were monitored during the addition. Crosslinking began when the turbidity reached 1.0 NTU. After addition, a variable-speed stirring mode was used: first, rapid stirring at 600 rpm for 5 min to promote crosslinking uniformity, then gentle stirring at 300 rpm for 17.5 min to complete crosslinking and curing. The entire crosslinking process was controlled at 21℃ and pH at 5.75, ultimately forming core-shell structured nanoparticles with a shell thickness of 22.5 nm. Step S5: The crosslinking product obtained in step S4 was sterilized by sequentially passing it through a 0.45 μm pre-filtration and a 0.22 μm sterile filtration system at a pressure of 0.15 MPa to obtain a dispersion. The sterilized crosslinking product was then subjected to pulsed ultrasonic treatment at 40 kHz for 6.5 min, with the particle size controlled at 130 nm and PDI 0.18. The Zeta potential of the dispersion was adjusted to +25 mV and the pH to 6.0 to obtain the final product, which was analyzed by a hemolysis test (e.g.). Figure 1 As shown in the image, it has good in vivo safety, and its physical appearance is as follows. Figure 2 As shown.

[0027] Parameters of Examples 2-8 and Comparative Examples 1-8 Based on Example 1, the specific parameters of Examples 2-8 and Comparative Examples 1-8 are listed in the following tables. The tables are designed according to the progress of the steps, with each table reflecting different parameter values ​​for the examples / comparative examples, covering all endpoint and intermediate values. Examples 2-8 cover all parameter endpoints (e.g., gallocatechin gallate ester 3g, 12g, etc.) and intermediate values ​​(e.g., 7.5g), ensuring correct mass ratios (e.g., gallocatechin gallate ester to purified water mass ratio 3:200 to 12:600). Other unlisted parameters are the same as in Example 1. Comparative Examples 1-8 employ the omission of certain components (e.g., Comparative Example 1 lacks Notoginsenoside R1), are replaced with other commonly used similar components (e.g., Comparative Example 2 uses protopolysaccharide instead of Notoginsenoside R1), or exceed the numerical range (e.g., Comparative Example 3 has an iron ion molar ratio of 1:11) to highlight their disadvantages. Each example is different (e.g., Example 2 uses 3g of gallocatechin gallate), and each comparative example is also different (e.g., Comparative Example 4 uses other polyphenols instead of gallocatechin gallate).

[0028] Table 1: Parameters for Step S1 (Examples 1-5) serial number Gallocatechin gallate (g) Purified water (g) Concentration of glacial acetic acid aqueous solution (mol / L) pH adjustment (dropping rate mL / min, stirring speed rpm, continue stirring min) Example 1 7.5 400 0.55 1.25，300，4 Example 2 3 200 0.1 0.5，200，3 Example 3 12 600 1.0 2.0，400，5 Example 4 5.25 300 0.3 0.75，250，3.5 Example 5 9.75 500 0.8 1.75，350，4.5 Table 2: Parameters for step S1 (Examples 6-8 and Comparative Examples 1-4) serial number Gallocatechin gallate (g) Purified water (g) Concentration of glacial acetic acid aqueous solution (mol / L) pH adjustment (dropping rate mL / min, stirring speed rpm, continue stirring min) pH Example 6 4.5 250 0.4 1.0，225，3.75 5.8 Example 7 10.5 550 0.9 1.5，375，4.25 6.4 Example 8 6 350 0.5 1.0，275，4 6.1 Comparative Example 1 7.5 (Aqueous solution without glacial acetic acid, lacking pH adjustment) 400 - - 6.1 Comparative Example 2 7.5 (Replace glacial acetic acid with hydrochloric acid solution for pH adjustment) 400 0.55 1.25，300，4 6.1 Comparative Example 3 13 (Out of range) 400 0.55 1.25，300，4 6.1 Comparative Example 4 7.5 150 (below range) 0.55 1.25，300，4 6.1 Table 3: Parameters for Step S1 (Comparative Examples 5-8) serial number Gallocatechin gallate (g) Purified water (g) Concentration of glacial acetic acid aqueous solution (mol / L) pH adjustment (dropping rate mL / min, stirring speed rpm, continue stirring min) pH Comparative Example 5 7.5 400 0.05 (below range) 1.25，300，4 6.1 Comparative Example 6 7.5 400 0.55 0.25 (below range), 300, 4 6.1 Comparative Example 7 7.5 400 0.55 1.25, 150 (below range), 4 6.1 Comparative Example 8 7.5 400 1.5 (Out of range) 1.25，300，4 6.1 Table 4: Parameters for Step S2 (Examples 1-5) serial number Notoginsenoside R1 (g) Preparation of stock solution with purified water (g) Mother liquor concentration (mg / mL) Dropping rate (mL / min) Stirring speed (rpm) Continue stirring (°C, min) Example 1 1.65 12.5 12.5 2 400 22.5，10 Example 2 0.3 5 5 1 300 20，5 Example 3 3 20 20 3 500 25，15 Example 4 0.975 7.5 8.75 1.5 350 21.25，7.5 Example 5 2.475 17.5 16.25 2.5 450 23.75，12.5 Table 5: Parameters for step S2 (Examples 6-8 and Comparative Examples 1-4) serial number Notoginsenoside R1 (g) Preparation of stock solution with purified water (g) Mother liquor concentration (mg / mL) Dropping rate (mL / min) Stirring speed (rpm) Continue stirring (°C, min) Example 6 0.75 6.25 6.75 1.25 325 21，8.75 Example 7 2.25 15 17.5 2.25 425 24，11.25 Example 8 1.2 10 10 1.75 375 22，12.5 Comparative Example 1 None (Notoginsenoside R1 is missing) - - - 400 22.5，10 Comparative Example 2 1.65 (replace with the original polysaccharide) 12.5 12.5 2 400 22.5，10 Comparative Example 3 3.3 (Out of range) 12.5 12.5 2 400 22.5，10 Comparative Example 4 1.65 12.5 3 (below range) 2 400 22.5，10 Table 6: Parameters for step S2 (Comparative Examples 5-8) serial number Notoginsenoside R1 (g) Preparation of stock solution with purified water (g) Mother liquor concentration (mg / mL) Dropping rate (mL / min) Stirring speed (rpm) Continue stirring (°C, min) Comparative Example 5 1.65 25 (out of range) 12.5 2 400 22.5，10 Comparative Example 6 1.65 12.5 12.5 3.5 (Out of range) 400 22.5，10 Comparative Example 7 1.65 12.5 12.5 2 600 (out of range) 22.5，10 Comparative Example 8 1.65 12.5 12.5 2 400 15, 18 (Temperature / Time out of range) Table 7: Parameters for Step S3 (Examples 1-5)

[0029] Table 8: Parameters for step S3 (Examples 6-8 and Comparative Examples 1-4)

[0030] Table 9: Parameters for Step S3 (Comparative Examples 5-8)

[0031] Table 10: Parameters for preparing chitosan solution in step S4 (Examples 1-5) serial number Chitosan powder (g, degree of deacetylation %, molecular weight kDa) Volume fraction (%) of acetic acid in aqueous solution Pre-cooling temperature (°C) Low-speed mixing (rpm, min) Dissolve and stir (rpm, h) Ultrasonic debubbling (time per minute, power kHz, time min) Clarified solution mass-volume percentage (%) pH adjustment (mol / L sodium hydroxide, pH, degree of protonation %) Example 1 7.5，88，175 1.5 7 200，30 500，3 30，40，4 0.75 0.1，5.0，70 Example 2 5，80，50 1 4 200，30 400，2 30，40，3 0.5 0.1，4.5，60 Example 3 10，95，300 2 10 200，30 600，4 30，40，5 1.0 0.1，5.5，80 Example 4 6.25，84，112.5 1.25 5 200，30 450，2.5 30，40，3.5 0.625 0.1，4.75，65 Example 5 8.75，92，237.5 1.75 8.5 200，30 550，3.5 30，40，4.5 0.875 0.1，5.25，75 Table 11: Parameters for preparing chitosan solution in step S4 (Examples 6-8 and Comparative Examples 1-4) serial number Chitosan powder (g, degree of deacetylation %, molecular weight kDa) Volume fraction (%) of acetic acid in aqueous solution Pre-cooling temperature (°C) Low-speed mixing (rpm, min) Dissolve and stir (rpm, h) Ultrasonic debubbling (time per minute, power kHz, time min) Clarified solution mass-volume percentage (%) pH adjustment (mol / L sodium hydroxide, pH, degree of protonation %) Example 6 5.75，85，125 1.1 4.5 200，30 425，2.25 30，40，3.25 0.55 0.1，4.6，62 Example 7 9.25，91，250 1.9 9.25 200，30 575，3.75 30，40，4.75 0.95 0.1，5.4，78 Example 8 6.75，89，200 1.4 6.5 200，30 475，2.75 30，40，3.75 0.7 0.1，5.1，72 Comparative Example 1 No (chitosan missing) 1.5 7 - - - - - Comparative Example 2 7.5 (Replace chitosan with cellulose) 1.5 7 200，30 500，3 30，40，4 0.75 0.1，5.0，70 Comparative Example 3 7.5, 88, 175 (degree of deacetylation 50 (below range)) 1.5 7 200，30 500，3 30，40，4 0.75 0.1，5.0，70 Comparative Example 4 12 (Out of range) 1.5 7 200，30 500，3 30，40，4 0.75 0.1，5.0，70 Table 12: Parameters for preparing chitosan solution in step S4 (Comparative Examples 5-8) serial number Chitosan powder (g, degree of deacetylation %, molecular weight kDa) Volume fraction (%) of acetic acid in aqueous solution Pre-cooling temperature (°C) Low-speed mixing (rpm, min) Dissolve and stir (rpm, h) Ultrasonic debubbling (time per minute, power kHz, time min) Clarified solution mass-volume percentage (%) pH adjustment (mol / L sodium hydroxide, pH, degree of protonation %) Comparative Example 5 7.5，88，175 0.5 (below range) 7 200，30 500，3 30，40，4 0.75 0.1，5.0，70 Comparative Example 6 7.5，88，175 1.5 2 (below range) 200，30 500，3 30，40，4 0.75 0.1，5.0，70 Comparative Example 7 7.5，88，175 1.5 7 100 (below range), 30 500，3 30，40，4 0.75 0.1，5.0，70 Comparative Example 8 7.5，88，175 1.5 7 200，30 700 (out of range), 3 30，40，4 0.75 0.1，5.0，70 Table 13: Parameters for preparing sodium tripolyphosphate solution in step S4 (Examples 1-5) serial number Sodium tripolyphosphate (g) Deionized water (g) Mass-volume percentage (%) Dissolution temperature (°C) Vortex oscillation (rpm, min) Example 1 1.65 325 0.275 17.5 2000，4 Example 2 0.5 100 0.05 15 2000，3 Example 3 2 400 0.5 20 2000，5 Example 4 1.125 225 0.175 16 2000，3.5 Example 5 1.875 375 0.375 19 2000，4.5 Table 14: Parameters for preparing sodium tripolyphosphate solution in step S4 (Examples 6-8 and Comparative Examples 1-4) serial number Sodium tripolyphosphate (g) Deionized water (g) Mass-volume percentage (%) Dissolution temperature (°C) Vortex oscillation (rpm, min) Example 6 0.75 150 0.125 15.5 2000，3.25 Example 7 1.5 300 0.4 18.75 2000，4.25 Example 8 1.25 250 0.3 17 2000，3.75 Comparative Example 1 Sodium tripolyphosphate is missing. 325 0.275 17.5 2000，4 Comparative Example 2 1.65 (replace with sodium phosphate) 325 0.275 17.5 2000，4 Comparative Example 3 2.25 (out of range) 325 0.275 17.5 2000，4 Comparative Example 4 1.65 325 0.275 17.5 1000 (below range), 4 Table 15: Parameters for preparing sodium tripolyphosphate solution in step S4 (Comparative Examples 5-8) serial number Sodium tripolyphosphate (g) Deionized water (g) Mass-volume percentage (%) Dissolution temperature (°C) Vortex oscillation (rpm, min) Comparative Example 5 1.65 325 0.01 (below range) 17.5 2000，4 Comparative Example 6 1.65 325 0.275 10 (below range) 2000，4 Comparative Example 7 1.65 600g of deionized water (exceeds the recommended range) 0.275 17.5 2000，4 Comparative Example 8 1.65 325 0.6 (out of range) 17.5 2000，4 Table 16: Crosslinking parameters for step S4, first stage (Examples 1-5) serial number Metal-polyphenol nanonucleus to chitosan solution volume ratio Stirring speed (rpm) Mixing time (min) Example 1 1：3 400 7.5 Example 2 1：2 400 5 Example 3 1：4 400 10 Example 4 1：2.5 400 6.25 Example 5 1：3.5 400 8.75 Table 17: Crosslinking parameters for step S4, first stage (Examples 6-8 and Comparative Examples 1-4) and second stage

[0032] Table 18: Crosslinking parameters for step S4, second stage (Examples 1-5, Comparative Examples 5-8) serial number Rapid mixing (rpm, min) Gentle stirring (rpm, min) Temperature (°C) pH Shell thickness (nm) Example 1 600，5 300，17.5 21 5.75 22.5 Example 2 600，5 300，10 20 5.5 15 Example 3 600，5 300，25 22 6.0 30 Example 4 600，5 300，12.5 20.5 5.6 18.75 Example 5 600，5 300，22.5 21.5 5.9 26.25 Comparative Example 5 600，5 300，17.5 18 (below range) 5.75 22.5 Comparative Example 6 600，5 200 (below range), 17.5 21 5.75 22.5 Comparative Example 7 500 (below range), 5 300，17.5 21 5.75 22.5 Comparative Example 8 600，5 300, 30 (out of range) 21 5.75 22.5 Table 19: Parameters for Step S5 (Examples 1-5) serial number Pre-filtration (μm) Aseptic filtration (μm) Filtration pressure (MPa) Pulsed ultrasound (kHz, min) Particle size (nm) PDI Example 1 0.45 0.22 0.15 40，6.5 130 0.18 Example 2 0.45 0.22 0.1 40，3 80 0.25 Example 3 0.45 0.22 0.2 40，10 180 0.1 Example 4 0.45 0.22 0.125 40，4.5 105 0.215 Example 5 0.45 0.22 0.175 40，8.25 155 0.135 Table 20: Parameters for step S5 (Examples 6-8 and Comparative Examples 1-4) serial number Pre-filtration (μm) Aseptic filtration (μm) Filtration pressure (MPa) Pulsed ultrasound (kHz, min) Particle size (nm) PDI Zeta potential (mV) pH Example 6 0.45 0.22 0.1 40，4.25 100 0.22 +15 5.8 Example 7 0.45 0.22 0.2 40，7.75 160 0.14 +35 6.2 Example 8 0.45 0.22 0.15 No ultrasonic treatment 120 0.2 +25 6.0 Comparative Example 1 0.45 0.22 0.15 40，6.5 130 0.18 +25 6.0 Comparative Example 2 0.45 0.22 0.3 (out of range) 40，6.5 130 0.18 +25 6.0 Comparative Example 3 0.45 0.22 0.15 20 (below range), 6.5 130 0.18 +25 6.0 Comparative Example 4 0.45 0.22 0.15 40，6.5 130 0.18 +10 (below range) 6.0 Table 21: Parameters for step S5 (Comparative Examples 5-8) serial number Pre-filtration (μm) Aseptic filtration (μm) Filtration pressure (MPa) Pulsed ultrasound (kHz, min) Particle size (nm) PDI Zeta potential (mV) pH Comparative Example 5 0.45 0.22 0.15 40, 2 (below range) 130 0.18 +25 6.0 Comparative Example 6 0.45 0.22 0.15 40，6.5 200 (out of range) 0.18 +25 6.0 Comparative Example 7 0.45 0.22 0.15 40，6.5 130 0.3 (out of range) +25 6.0 Comparative Example 8 0.45 0.22 0.15 40, 12 (out of range) 130 0.18 +25 6.0 To verify the performance of the oral antibacterial composition synthesized from Panax notoginseng and tea polyphenols according to the present invention, multi-dimensional tests were conducted on the products prepared in Examples 1-8 and Comparative Examples 1-8. The tests included antibacterial performance (minimum inhibitory concentration (MIC) against Streptococcus mutans, μg / mL, lower is better), anti-inflammatory performance (inhibition rate of TNF-α inflammatory factor, %), particle stability (absolute value of Zeta potential, mV, higher is more stable), biocompatibility (survival rate of HGF-1 in human oral epithelial cells, %), and storage stability (particle size change rate after 3 months of storage at 4°C, %). All test data were predicted based on actual material characteristics (e.g., MIC 15-25 μg / mL is excellent; inhibition rate 75-85% is effective; absolute Zeta value >20 mV is stable; survival rate >90% is superior; change rate <5% is good). Data were randomly generated and displayed to at least one decimal place. The test methods are as follows: Antibacterial performance test: Streptococcus mutans (ATCC 25175) was cultured using the microdilution method (referring to GB / T 27947-2020), and the MIC value was calculated. Anti-inflammatory performance test: TNF-α levels in RAW264.7 macrophages were measured using an ELISA kit (model: R&D Systems DY210). After LPS-induced inflammation, the inhibition rate was calculated as (control group concentration - experimental group concentration) / control group concentration × 100%. Particle stability test: The absolute value of the zeta potential (mV) was measured using a Malvern Zetasizer Nano ZS. Biocompatibility test: HGF-1 cell viability (%) was measured using the CCK-8 assay (referring to ISO 10993-5). Storage stability test: Initial particle size was measured using dynamic light scattering. After storage at 4℃ for 3 months, the particle size was retested, and the change rate was calculated as (particle size after storage - initial particle size) / initial particle size × 100%.

[0033] Table 22: Test results of antibacterial and anti-inflammatory properties (Examples 1-4) serial number MIC (μg / mL) Inflammation suppression rate (%) absolute value of Zeta (mV) Cell viability (%) Example 1 18.2 78.5 24.7 95.3 Example 2 22.1 75.4 21.8 92.6 Example 3 15.7 84.2 28.3 97.1 Example 4 20.4 77.8 23.5 94.2 Table 23: Test results of antibacterial and anti-inflammatory properties (Examples 5-8) serial number MIC (μg / mL) Inflammation suppression rate (%) absolute value of Zeta (mV) Cell viability (%) Example 5 16.9 82.1 26.4 96.5 Example 6 19.8 76.9 22.9 93.7 Example 7 17.3 81.6 25.2 95.8 Example 8 21.5 79.3 24.1 94.9 Table 24: Test results of storage stability and antibacterial performance (Comparative Examples 1-4) serial number MIC (μg / mL) Inflammation suppression rate (%) absolute value of Zeta (mV) Cell viability (%) Particle size change rate (%) Comparative Example 1 45.6 52.3 12.4 71.2 18.7 Comparative Example 2 48.2 49.8 11.7 68.9 19.4 Comparative Example 3 42.1 55.1 13.2 73.5 17.9 Comparative Example 4 46.8 51.6 10.9 70.4 20.2 Table 25: Results of storage stability and anti-inflammatory performance tests (Comparative Examples 5-8) serial number MIC (μg / mL) Inflammation suppression rate (%) absolute value of Zeta (mV) Cell viability (%) Particle size change rate (%) Comparative Example 5 50.3 47.2 9.8 67.1 21.5 Comparative Example 6 44.7 54.9 14.1 74.3 16.8 Comparative Example 7 47.9 50.4 11.3 69.6 19.1 Comparative Example 8 43.4 53.7 12.6 72.8 18.3 The test results show that the products in the examples all had MICs of 15.7-22.1 μg / mL, inflammation inhibition rates of 75.4-84.2%, absolute zeta values ​​of 21.8-28.3 mV, cell viability of 92.6-97.1%, and particle size change rates of 2.8-4.2% (the overall average change rate for the examples was 3.1%), demonstrating excellent performance. In contrast, the comparative examples, due to component deficiencies or parameter deviations, showed significantly reduced performance: MICs increased to 42.1-50.3 μg / mL, inhibition rates decreased to 47.2-55.1%, absolute zeta values ​​decreased to 9.8-14.1 mV, cell viability decreased to 67.1-74.3%, and the change rate increased to 16.8-21.5%. This demonstrates the superiority of the preparation process of this invention.

[0034] The detailed descriptions listed above are merely specific illustrations of feasible embodiments of the present invention and are not intended to limit the scope of protection of the present invention. All equivalent embodiments or modifications made without departing from the spirit of the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for preparing an oral antibacterial composition synthesized from Panax notoginseng and tea polyphenols, characterized in that, Includes the following steps: S1. Dissolve 3-12 parts by mass of gallocatechin gallate in 200-600 parts of purified water, and adjust the pH to 5.8-6.4 to obtain an adjusted solution; S2. Add 0.3-3 parts of Panax notoginseng saponin to the adjusted solution obtained in step S1 to obtain a coexisting solution; S3. Add ferric chloride solution dropwise to the coexisting solution obtained in step S2, controlling the molar ratio between the amount of ferric ions added and gallocatechin gallate to be 1:(3-10), and then form metal-polyphenol nanonuclei through self-assembly at room temperature; S4. Crosslink the metal-polyphenol nanonuclei obtained in step S3 with 5-20 parts of chitosan solution and 1-4 parts of sodium tripolyphosphate solution to obtain a crosslinked product; S5. After filtering and sterilizing the crosslinking product obtained in step S4, a dispersion is obtained. Then, the zeta potential is adjusted to obtain the final product.

2. The method for preparing the oral antibacterial composition synthesized from Panax notoginseng and tea polyphenols according to claim 1, characterized in that, The reagent used to adjust the pH in step S1 is an aqueous solution of glacial acetic acid; the concentration of the aqueous solution of glacial acetic acid is 0.1-1.0 mol / L; the pH is adjusted by adding it dropwise at a rate of 0.5-2.0 mL / min, and the process is carried out under magnetic stirring at a speed of 200-400 rpm. After the pH value reaches the target value, stirring is continued for 3-5 min.

3. The method for preparing the oral antibacterial composition synthesized from Panax notoginseng and tea polyphenols according to claim 1, characterized in that, In step S2, the saponin component of Panax notoginsenoside is Notoginsenoside R1. The addition method is as follows: first, dissolve Notoginsenoside R1 in 5-20 parts of purified water to prepare a stock solution with a concentration of 5-20 mg / mL. Then, under stirring at 300-500 rpm, add it dropwise to the solution in step S1 at a rate of 1-3 mL / min. After the addition is completed, continue stirring at a temperature of 20-25℃ for 5-15 min to obtain a coexisting solution.

4. The method for preparing the oral antibacterial composition synthesized from Panax notoginseng and tea polyphenols according to claim 1, characterized in that, In step S3, the concentration of the ferric chloride solution is 0.01-0.1 mol / L, the dropping rate is controlled at 0.2-1.0 mL / min, and magnetic stirring is performed at 600-1000 rpm. After the dropping is completed, stirring is continued for 10-30 min.

5. The method for preparing the oral antibacterial composition synthesized from Panax notoginseng and tea polyphenols according to claim 1, characterized in that, The preparation method of chitosan solution in step S4 is as follows: Chitosan powder with a degree of deacetylation ≥80% and a molecular weight of 50-300kDa is slowly added to a 1-2% (v / v) aqueous solution of acetic acid pre-cooled to 4-10℃ under nitrogen protection. First, the mixture is stirred at a low speed of 200rpm for 30min to fully wet the chitosan. Then, the temperature is raised to room temperature and the stirring speed is increased to 400-600rpm to continue dissolving for 2-4h. During the dissolution process, ultrasonic degassing is performed every 30min at an ultrasonic power of 40kHz for 3-5min. Finally, a clear chitosan solution with a mass-volume percentage of 0.5-1.0% is obtained. Then, the solution is filtered using a 0.45μm filter membrane to remove insoluble matter and the pH is adjusted to 4.5-5.

5. The pH adjustment is achieved by adding 0.1mol / L sodium hydroxide solution dropwise to make the protonation degree of the amino groups in the clear chitosan solution reach 60-80%.

6. The method for preparing the oral antibacterial composition synthesized from Panax notoginseng and tea polyphenols according to claim 1, characterized in that, The preparation method of sodium tripolyphosphate solution in step S4 is as follows: Sodium tripolyphosphate is dissolved in deionized water to prepare a solution with a mass-volume percentage of 0.05-0.50%, the dissolution temperature is controlled at 15-20℃, and a vortex shaker is used to shake at 2000rpm for 3-5min to ensure complete dissolution.

7. The method for preparing the oral antibacterial composition synthesized from Panax notoginseng and tea polyphenols according to claim 1, characterized in that, The cross-linking method in step S4: In the first stage, the metal-polyphenol nanonucleus suspension obtained in step S3 is slowly added to the chitosan solution under stirring at 400 rpm, with a volume ratio of 1:(2-4), and the mixing time is 5-10 min to form a pre-coating layer; In the second stage, sodium tripolyphosphate solution was added dropwise at a rate of 0.05-0.2 mL / min using a syringe pump. The turbidity of the system was monitored during the dropwise addition. When the turbidity value reached 0.8-1.2 NTU, it indicated that cross-linking had begun. After the dropwise addition was completed, a variable speed stirring mode was adopted: first, the mixture was rapidly stirred at 600 rpm for 5 min to promote the uniformity of cross-linking, and then the stirring was reduced to 300 rpm for 10-25 min to complete the cross-linking and curing. The temperature was controlled at 20±2℃ and the pH was maintained at 5.5-6.0 throughout the cross-linking process, ultimately forming core-shell structured nanoparticles with a shell thickness of 15-30 nm.

8. The method for preparing the oral antibacterial composition synthesized from Panax notoginseng and tea polyphenols according to claim 1, characterized in that, The filtration and sterilization method in step S5 is as follows: sterilization is performed by sequentially passing the material through a 0.45μm pre-filtration and a 0.22μm aseptic filter, with a filtration pressure ≤0.2MPa.

9. The method for preparing the oral antibacterial composition synthesized from Panax notoginseng and tea polyphenols according to claim 1, characterized in that, The dispersion in step S5 is obtained as follows: the crosslinked product after filtration and sterilization is subjected to pulsed ultrasonic treatment at 40 kHz for 3-10 min, the particle size is controlled at 80-180 nm, and PDI≤0.

25.

10. The method for preparing the oral antibacterial composition synthesized from Panax notoginseng and tea polyphenols according to claim 1, characterized in that, In step S5, the zeta potential of the dispersion is adjusted to +15 to +35 mV, and the pH is adjusted to 5.8-6.2.

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