Oral antibacterial paste for targeted inhibition of helicobacter pylori and preparation process of oral antibacterial paste

Abstract

The invention relates to the technical field of oral care, and discloses an oral antibacterial paste for targeted inhibition of helicobacter pylori and a preparation process thereof, the oral antibacterial paste comprises the following raw materials by mass: 3-10 parts of a targeted antibacterial component, 8-15 parts of a humectant, 1-3 parts of a thickener, 0.5-2 parts of a co-emulsifier, 1-2 parts of a surfactant, 0.1-0.5 part of essence, 0.1-0.3 part of a preservative, and 60-80 parts of deionized water; the targeted antibacterial component is composed of 40-60% of a plant extract, 20-30% of a probiotic metabolite, 10-20% of a composite targeted inhibitor and 5-10% of a targeted carrier. According to the invention, precise targeted inhibition of helicobacter pylori is realized, safety and use experience of the product are taken into account, and an efficient and practical technical scheme is provided for solving oral cavity helicobacter pylori related problems.

Description

Technical Field

[0001] This invention relates to the field of oral care technology, specifically to an oral antibacterial ointment that targets and inhibits Helicobacter pylori and its preparation process. Background Technology

[0002] Helicobacter pylori (Hp) is a Gram-negative bacillus that can colonize the oral cavity and gastric mucosa. It is a major pathogen causing chronic gastritis, peptic ulcers, and gastric cancer, and is highly contagious, primarily transmitted through oral-oral and fecal-oral routes, with the oral cavity being a key transmission medium and colonization site. Current interventions for Hp mainly involve quadruple therapy with oral antibiotics; however, long-term use can lead to intestinal flora imbalance and drug resistance, and it is ineffective in eradicating Hp from the oral cavity, resulting in a high recurrence rate.

[0003] Oral care products such as toothpaste and mouthwash are important carriers for daily prevention of oral pathogen colonization. However, most existing products use broad-spectrum antibacterial ingredients, which can inhibit oral bacteria to some extent, but their targeting is weak, easily disrupting the balance of normal oral flora, and their inhibitory effect on Helicobacter pylori is limited. Some products add single plant extracts, which have the problem of mild antibacterial effects and slow onset of action. Therefore, it is of great significance to develop an oral antibacterial paste that can precisely target and inhibit oral Helicobacter pylori and is friendly to the oral microecology. Summary of the Invention

[0004] (a) Technical problems to be solved

[0005] To address the shortcomings of existing technologies, this invention provides an oral antibacterial ointment that targets and inhibits Helicobacter pylori, along with its preparation process.

[0006] (II) Technical Solution

[0007] To achieve the above objectives, the present invention provides the following technical solution: an oral antibacterial ointment that targets and inhibits Helicobacter pylori, comprising the following raw materials in parts by weight:

[0008] The ingredients include 3-10 parts of targeted antibacterial ingredients, 8-15 parts of moisturizer, 1-3 parts of thickener, 0.5-2 parts of emulsifier, 1-2 parts of surfactant, 0.1-0.5 parts of fragrance, 0.1-0.3 parts of preservative, and 60-80 parts of deionized water.

[0009] The targeted antibacterial component consists of 40-60% plant extracts, 20-30% probiotic metabolites, 10-20% compound targeted inhibitors, and 5-10% targeted carriers.

[0010] The preparation method of the composite targeted inhibitor includes the following steps:

[0011] A1. Fucosylated flavonoid glycosides were dissolved in 0.01 mol / L phosphate buffer, trehalose and lipase were added, the temperature was raised to 38-40℃, after the reaction was completed, n-hexane was added, centrifuged, the aqueous phase was filtered through a 0.45 μm filter membrane, and freeze-dried to obtain fucosylated flavonoid glycosides-trehalose.

[0012] A2. Fucosylated flavonoid glycoside-trehalose was dissolved in 0.01 mol / L phosphate buffer, and 1-ethyl-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide were added to obtain the activation solution.

[0013] A3. Dissolve aminopolyethylene glycol in 0.01 mol / L phosphate buffer, and slowly add activation solution to form an intermediate solution; dissolve o-phthalaldehyde in 0.01 mol / L phosphate buffer, and slowly add it to the intermediate solution, add sodium borohydride, transfer the reaction solution to a dialysis bag, dialyze, and freeze-dry to obtain the composite inhibitor.

[0014] Furthermore, the preparation methods for plant extracts and probiotic metabolites are as follows:

[0015] Honeysuckle, dandelion, and peppermint were mixed in a mass ratio of 1.5–2:1.5–2:1, pulverized and passed through a 100–200 mesh sieve, and 10–15 times their volume of 70% ethanol solution were added. The mixture was refluxed for 1–1.5 hours and extracted 2–3 times. The extracts were combined. The extracts were concentrated under reduced pressure until no alcohol odor was detected. The mixture was then diluted with 3–5 times the volume of deionized water at 45–50°C and 0.08–0.1 MPa, and centrifuged at 8000–10000 r / min for 10–15 min. The supernatant was collected and adsorbed through D101 macroporous resin. The mixture was eluted with 70% ethanol and the eluent was collected. The eluent was freeze-dried at -20–-40°C and 6–10 Pa for 8–10 hours to obtain the plant extract.

[0016] Lactobacillus reuteri, Lactobacillus rhamnosus, and Lactobacillus plantarum were inoculated into MRS medium and anaerobically cultured at 37°C for 24–36 h to activate the bacteria for two generations. The activated bacterial solution was mixed at a volume ratio of 1:1:1 and inoculated into optimized MRS medium. 1–1.5% glucose and 0.5–0.8% yeast extract were added by weight of the medium. Anaerobic fermentation was carried out at 37°C for 24–36 h to obtain the fermentation broth. The fermentation broth was centrifuged at 8000–10000 r / min for 10–20 min. The supernatant was filtered through a 0.22 μm filter membrane to remove bacteria, concentrated under reduced pressure to 1 / 5 of the original volume, and freeze-dried at 38–40°C, 0.1–0.3 MPa, and then at -20–-40°C, 6–10 Pa for 8–10 h to obtain probiotic metabolites.

[0017] Furthermore, the method for preparing the target carrier includes the following steps:

[0018] B1. Add 80-100 parts of ethanol and 20-40 parts of deionized water to a three-necked flask. Add 1-3 parts of polyethylene glycol 4000 while stirring at 300-500 r / min. After dissolving, add 10-20 parts of tetraethyl orthosilicate dropwise. Stir for 10-15 min. Add ammonia dropwise to adjust the pH to 8.5-9.0. Heat to 35-40℃ and react at a constant temperature for 4-6 h. Centrifuge at 8000-10000 r / min for 10-15 min. Collect the precipitate. Wash with ethanol and deionized water 3 times each. Calcine in a muffle furnace at 500-550℃ for 1-2 h. After cooling, obtain porous nano-silica.

[0019] B2. Add 3-5 parts of porous activated carbon powder to 100-120 parts of 2-5% acetic acid solution, reflux and stir for 1-2 hours, centrifuge at 10000-12000 r / min, collect the activated carbon for 10-20 min, wash with deionized water until neutral, add 10-15 parts of polyethylene glycol 400 dispersion, polyethylene glycol 400 to deionized water mass ratio 1:6-9, ultrasonically disperse at 300-400W for 10-20 min to obtain activated carbon dispersion;

[0020] B3. Dissolve 5-10 parts of chitosan in 100-150 parts of 2-5% acetic acid solution to obtain a chitosan solution. Add the porous nano-silica from step B1 and stir at 600-800 r / min for 10-15 min. Then slowly add the activated carbon dispersion from step B2 and stir at 1000-1200 r / min for 10-15 min. Add 1 mol / L NaOH to adjust the pH to 5-5.5. Add 0.2-0.5 parts of 20-25% glutaraldehyde solution and stir at 30-35℃ for 1-2 h. Transfer to a freeze-drying mold and freeze-dry at -30 to -50℃ under a vacuum of 6-10 Pa for 12-24 h to obtain an activated carbon-chitosan-porous nano-silica carrier.

[0021] B4. Add 100-150 parts of deionized water to the activated carbon-chitosan-porous nano silica carrier from step B3, and ultrasonically disperse it at 200-300W for 10-15 min. Then add 5-10 parts of N,N-dimethylformamide and stir evenly. Then slowly add 0.5-1.5 parts of succinic anhydride and continue stirring for 5-10 min. Add triethylamine dropwise to adjust the pH of the system to 6.0-6.5, raise the temperature to 40-45℃, and stir for 2-3 h. After the reaction is complete, centrifuge at 10000-12000 r / min for 10-20 min, collect the precipitate, and wash it 3 times with deionized water to obtain the carboxylated carrier.

[0022] B5. Disperse the carboxylated carrier from step B4 in 120–160 parts of deionized water and sonicate at 200–300 W for 10–20 min to obtain a suspension. Add 10–20 parts of 0.05–0.1 mol / L FeCl3 aqueous solution dropwise to the suspension while stirring at 600–800 r / min. Adjust the pH to 4.0–4.5 with 1 mol / L NaOH and stir at 30–35 °C for 1–2 h. Centrifuge at 10000–12000 r / min for 10–20 min, wash three times with deionized water, and freeze-dry at -30–-50 °C and a vacuum of 6–10 Pa for 6–8 h to obtain the targeting carrier.

[0023] Furthermore, the moisturizer is one of glycerin, propylene glycol, or sodium hyaluronate.

[0024] Furthermore, the thickener is one of xanthan gum, hydroxypropyl methylcellulose, or carbomer.

[0025] Furthermore, the co-emulsifier is one of polyglycerol-4-isostearate, sorbitan monostearate, or potassium cetyl phosphate.

[0026] Furthermore, the surfactant is one of cocamidopropyl betaine, sodium lauroyl sarcosinate, or polyoxyethylene hydrogenated castor oil.

[0027] Furthermore, the flavoring is one of peppermint flavoring, lemon flavoring, and spearmint flavoring; wherein the peppermint flavoring contains ≥30% natural peppermint extract, the lemon flavoring contains ≥25% natural lemon extract, and the spearmint flavoring contains ≥35% natural spearmint extract.

[0028] Furthermore, the preservative is one of phenoxyethanol, methylparaben, or sodium dehydroacetate.

[0029] Furthermore, a method for preparing an oral antibacterial paste that targets and inhibits Helicobacter pylori includes the following steps:

[0030] S1. Take the formulated amount of the targeted carrier, add 5-8 times the volume of deionized water, stir for 5-10 min to form a carrier suspension; take the formulated amount of plant extract, probiotic metabolites, and compound targeted inhibitor, add 3-5 times the volume of deionized water, stir evenly, slowly add to the carrier suspension, stir at 35-37℃ and 400-600 r / min in the dark for 1-2 h, freeze dry at -30--40℃ and 6-10 Pa for 8-12 h to obtain the targeted antibacterial component;

[0031] S2. Take the prescribed amount of deionized water, add humectant, thickener, and preservative, stir to dissolve, and obtain the aqueous phase; take the targeted antibacterial ingredient powder, add emulsifier, stir evenly, add surfactant, stir and mix for 10-15 minutes, then slowly add to the aqueous phase at 10000-12000 r / min, emulsify for 10-20 minutes, after emulsification, homogenize 1-2 times under high pressure at 20-25 MPa, add fragrance, continue stirring at 400-600 r / min for 10-30 minutes, pour into a sterile ointment container, seal, and let stand at room temperature for 12-24 hours to obtain the oral antibacterial ointment that targets and inhibits Helicobacter pylori.

[0032] (III) Beneficial Technical Effects

[0033] This invention relates to an oral antibacterial ointment that targets and inhibits Helicobacter pylori. Through the fucose residues in the compound targeted inhibitor, it can specifically recognize the blood group antigens on the surface of Helicobacter pylori and bind to adhesins, competitively blocking the binding of bacteria to oral mucosal epithelial cells. Simultaneously, the phthalaldehyde in the inhibitor precisely targets urease, an enzyme essential for Helicobacter pylori survival. By chelating nickel ions at the enzyme's active center and forming covalent bonds with surrounding histidine residues, it irreversibly destroys enzyme activity, disrupting the bacteria's survival in the acidic oral environment and effectively avoiding the non-specific effects of traditional antibacterial ingredients on normal oral flora. Plant extracts and probiotic metabolites further enhance the direct inhibitory effect on Helicobacter pylori. The targeted carrier, modified with chitosan and activated carbon, not only enhances the loading and sustained-release capacity of active ingredients through surface amino and carboxyl groups but also improves the adhesion of the ingredients to the oral mucosa, prolonging the duration of action. This solves the problems of active ingredients being easily washed away by saliva and insufficient duration of action in traditional oral care products.

[0034] This invention achieves precise targeted inhibition of Helicobacter pylori while also ensuring product safety, providing an efficient and practical technical solution for addressing oral Helicobacter pylori-related problems. Detailed Implementation

[0035] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0036] Unless otherwise specified, all components of the oral antibacterial ointment formulation of this invention that target and inhibit Helicobacter pylori are commercially available.

[0037] The lipase used was Novozym 435, purchased from Novozymes, Denmark.

[0038] MRS medium formulation: glucose 20 g / L, yeast extract 10 g / L, peptone 10 g / L, beef extract 10 g / L, dipotassium hydrogen phosphate 2 g / L, diammonium citrate 2 g / L, sodium acetate 5 g / L, Tween-80 1 mL / L, magnesium sulfate 0.5 g / L, manganese sulfate 0.25 g / L;

[0039] The Helicobacter pylori strain used in the test was ATCC 43504 (standard pathogenic strain), purchased from the American Center for Type Culture Collection.

[0040] All parts used in this invention are parts by weight;

[0041] Example 1

[0042] An oral antibacterial cream that targets and inhibits Helicobacter pylori, comprising the following ingredients in parts by weight:

[0043] Targeted antibacterial ingredient 3 parts, moisturizer 8 parts, thickener 1 part, co-emulsifier 0.5 parts, surfactant 1 part, fragrance 0.1 parts, preservative 0.1 parts, deionized water 60 parts;

[0044] The targeted antibacterial component consists of 40% plant extracts, 30% probiotic metabolites, 20% compound targeted inhibitors, and 10% targeted carriers.

[0045] The moisturizer is glycerin.

[0046] The thickener is xanthan gum.

[0047] The co-emulsifier is polyglycerol-4-isostearate.

[0048] The surfactant is cocamidopropyl betaine.

[0049] The flavoring is peppermint flavoring; the peppermint flavoring contains ≥30% natural peppermint extract.

[0050] The preservative is phenoxyethanol.

[0051] The preparation method of the compound targeted inhibitor includes the following steps:

[0052] A1. Weigh 2 parts of fucoidylated flavonoid glycosides, dissolve them in 40 parts of 0.01mol / L phosphate buffer (pH 7.0), add 0.8 parts of trehalose, stir to dissolve, add 0.05 parts of lipase, heat to 38℃, stir at 300r / min for 4h, after the reaction is complete, add 20 parts of n-hexane, stir for 10min, centrifuge at 5000r / min for 10min, filter the aqueous phase through a 0.45μm filter membrane, and freeze-dry to obtain fucoidylated flavonoid glycosides-trehalose;

[0053] A2. Weigh 1 part of fucoidylated flavonoid glycoside-trehalose, dissolve it in 40 parts of 0.01mol / L phosphate buffer, pH 7.0, add 0.4 parts of 1-ethyl-(3-dimethylaminopropyl)carbodiimide and 0.1 parts of N-hydroxysuccinimide, stir at room temperature for 10 min to obtain the activation solution;

[0054] A3. Weigh 0.8 parts of amino polyethylene glycol and dissolve it in 20 parts of 0.01 mol / L phosphate buffer. Slowly add the activation solution and stir at 600 r / min in the dark for 2 h to form an intermediate solution. Dissolve 0.6 parts of o-phthalaldehyde in 5 parts of 0.01 mol / L phosphate buffer and slowly add it to the intermediate solution. Stir at 500 r / min in the dark for 1 h. Add 0.05 parts of sodium borohydride and stir at room temperature for 15 min. Transfer the reaction solution to a 5000 Da dialysis bag and dialyze for 24 h. After dialysis, freeze dry at -20℃ and 6 Pa for 8 h to obtain the composite inhibitor.

[0055] The preparation methods for plant extracts and probiotic metabolites are as follows:

[0056] Honeysuckle, dandelion, and peppermint were mixed in a mass ratio of 1.5:1.5:1, pulverized and passed through a 100-mesh sieve, and 10 times their volume of 70% ethanol solution were added. The mixture was refluxed for 1 hour and extracted twice. The extracts were combined. The extract was concentrated under reduced pressure until no alcohol odor was detected. The mixture was then diluted with 3 times the volume of deionized water at 45°C and 0.08 MPa, and centrifuged at 8000 r / min for 10 min. The supernatant was collected and adsorbed through a D101 macroporous resin. The mixture was eluted with 70% ethanol and the eluent was collected. The eluent was freeze-dried at -20°C and 6 Pa for 8 hours to obtain the plant extract.

[0057] Lactobacillus reuteri, Lactobacillus rhamnosus, and Lactobacillus plantarum were inoculated into MRS medium and anaerobically cultured at 37℃ for 24 h to activate the bacteria for two generations. The activated bacterial solution was mixed at a volume ratio of 1:1:1 and inoculated into optimized MRS medium. 1% glucose and 0.5% yeast extract (by weight of the medium) were added, and the mixture was anaerobically fermented at 37℃ for 24 h to obtain the fermentation broth. The fermentation broth was centrifuged at 8000 r / min for 10 min, and the supernatant was filtered through a 0.22 μm filter membrane for sterilization. The supernatant was concentrated to 1 / 5 of the original volume under reduced pressure, freeze-dried at 38℃ and 0.1 MPa, and then at -20℃ and 6 Pa for 8 h to obtain the probiotic metabolites.

[0058] The preparation method of the target carrier includes the following steps:

[0059] B1. Add 80 parts ethanol and 20 parts deionized water to a three-necked flask. Add 1 part polyethylene glycol 4000 while stirring at 300 r / min. After dissolving, add 10 parts tetraethyl orthosilicate dropwise and stir for 10 min. Add ammonia dropwise to adjust the pH to 8.5. Heat to 35℃ and react at a constant temperature for 4 h. Centrifuge at 8000 r / min for 10 min, collect the precipitate, wash 3 times each with ethanol and deionized water, calcine in a muffle furnace at 500℃ for 1 h, and obtain porous nano-silica after cooling.

[0060] B2. Add 3 parts of porous activated carbon powder to 100 parts of 2% acetic acid solution, reflux and stir for 1 hour, centrifuge at 10000 r / min, collect the activated carbon for 10 min, wash with deionized water until neutral, add 10 parts of polyethylene glycol 400 dispersion, polyethylene glycol 400 and deionized water mass ratio 1:6, ultrasonically disperse at 300W for 10 min to obtain activated carbon dispersion.

[0061] B3. Dissolve 5 parts of chitosan in 100 parts of 2% acetic acid solution to obtain a chitosan solution. Add the porous nano-silica from step B1 and stir at 600 r / min for 10 min. Then slowly add the activated carbon dispersion from step B2 and stir at 1000 r / min for 10 min. Add 1 mol / L NaOH to adjust the pH to 5. Add 0.2 parts of 20% glutaraldehyde solution and stir at 30℃ for 1 h. Transfer to a freeze-drying mold and freeze-dry at -30℃ and a vacuum of 6 Pa for 12 h to obtain an activated carbon-chitosan-porous nano-silica carrier.

[0062] B4. Add 100 parts of deionized water to the activated carbon-chitosan-porous nano silica carrier from step B3, and ultrasonically disperse it at 200W for 10 min. Then add 5 parts of N,N-dimethylformamide and stir evenly. Slowly add 0.5 parts of succinic anhydride and continue stirring for 5 min. Add triethylamine dropwise to adjust the pH of the system to 6.0, heat to 40℃, and stir for 2 h. After the reaction is complete, centrifuge at 10000 r / min for 10 min, collect the precipitate, and wash it 3 times with deionized water to obtain the carboxylated carrier.

[0063] B5. Disperse the carboxylated carrier from step B4 in 120 parts of deionized water and sonicate at 200W for 10 min to obtain a suspension. Add 10 parts of 0.05mol / L FeCl3 aqueous solution dropwise to the suspension while stirring at 600r / min. Adjust the pH to 4.0 with 1mol / L NaOH and stir at 30℃ for 1 h. Centrifuge at 10000r / min for 10 min, wash three times with deionized water, and freeze-dry at -30℃ and 6Pa vacuum for 6 h to obtain the targeting carrier.

[0064] A method for preparing an oral antibacterial ointment that targets and inhibits Helicobacter pylori includes the following steps:

[0065] S1. Take the formula amount of the targeted carrier, add 5 times the volume of deionized water, stir for 5 min to form a carrier suspension; take the formula amount of plant extract, probiotic metabolites, and compound targeted inhibitor, add 3 times the volume of deionized water, stir evenly, slowly add to the carrier suspension, stir at 35℃ and 400 r / min in the dark for 1 h, freeze dry at -30℃ and 6 Pa for 8 h to obtain the targeted antibacterial component.

[0066] S2. Take the prescribed amount of deionized water, add moisturizer, thickener, and preservative, stir to dissolve, and obtain the aqueous phase; take the targeted antibacterial ingredient powder, add emulsifier, stir evenly, add surfactant, stir and mix for 10 minutes, then slowly add to the aqueous phase, emulsify at 10000 r / min for 10 minutes. After emulsification, homogenize once under high pressure at 20 MPa, add fragrance, continue stirring at 400 r / min for 10 minutes, pour into a sterile ointment container, seal, and let stand at room temperature for 12 hours to obtain the oral antibacterial ointment that targets and inhibits Helicobacter pylori.

[0067] Example 2

[0068] An oral antibacterial cream that targets and inhibits Helicobacter pylori, comprising the following ingredients in parts by weight:

[0069] Targeted antibacterial ingredient 5 parts, moisturizer 10 parts, thickener 2 parts, emulsifier 1 part, surfactant 1.5 parts, fragrance 0.3 parts, preservative 0.2 parts, deionized water 70 parts;

[0070] The targeted antibacterial component consists of 60% plant extracts, 20% probiotic metabolites, 15% compound targeted inhibitors, and 5% targeted carriers.

[0071] The humectant is propylene glycol.

[0072] The thickener is hydroxypropyl methylcellulose.

[0073] The emulsifier is sorbitan monostearate.

[0074] The surfactant is sodium lauroyl sarcosinate.

[0075] The flavoring is lemon flavoring; the lemon flavoring contains ≥25% natural lemon extract.

[0076] The preservative is methylparaben.

[0077] The preparation method of the compound targeted inhibitor includes the following steps:

[0078] A1. Weigh 3 parts of fucoidylated flavonoid glycosides, dissolve them in 50 parts of 0.01mol / L phosphate buffer (pH 7.2), add 1 part of trehalose, stir to dissolve, add 0.08 parts of lipase, heat to 38℃, stir at 400r / min for 5h, after the reaction is complete, add 25 parts of n-hexane, stir for 10min, centrifuge at 6000r / min for 10min, filter the aqueous phase through a 0.45μm filter membrane, and freeze-dry to obtain fucoidylated flavonoid glycosides-trehalose;

[0079] A2. Weigh 2 parts of fucoidylated flavonoid glycoside-trehalose, dissolve them in 50 parts of 0.01mol / L phosphate buffer (pH 7.2), add 0.5 parts of 1-ethyl-(3-dimethylaminopropyl)carbodiimide and 0.2 parts of N-hydroxysuccinimide, stir at room temperature for 20 minutes to obtain the activation solution.

[0080] A3. Weigh 1 part of amino polyethylene glycol and dissolve it in 30 parts of 0.01 mol / L phosphate buffer. Slowly add the activation solution and stir at 700 r / min in the dark for 2 h to form an intermediate solution. Dissolve 0.7 parts of o-phthalaldehyde in 8 parts of 0.01 mol / L phosphate buffer and slowly add it to the intermediate solution. Stir at 550 r / min in the dark for 1 h. Add 0.08 parts of sodium borohydride and stir at room temperature for 20 min. Transfer the reaction solution to a 6000 Da dialysis bag and dialyze for 36 h. After dialysis, freeze dry at -30℃ and 8 Pa for 10 h to obtain the composite inhibitor.

[0081] The preparation methods for plant extracts and probiotic metabolites are as follows:

[0082] Honeysuckle, dandelion, and peppermint were mixed in a mass ratio of 1.8:1.8:1, pulverized and passed through a 150-mesh sieve, and 12 times the volume of 70% ethanol solution was added. The mixture was refluxed for 1 hour and extracted twice. The extracts were combined. The extract was concentrated under reduced pressure until no alcohol odor was detected. The mixture was then diluted with 4 times the volume of deionized water at 45°C and 0.09 MPa, and centrifuged at 9000 r / min for 10 min. The supernatant was collected and adsorbed through a D101 macroporous resin. The mixture was eluted with 70% ethanol and the eluent was collected. The eluent was freeze-dried at -30°C and 8 Pa for 9 hours to obtain the plant extract.

[0083] Lactobacillus reuteri, Lactobacillus rhamnosus, and Lactobacillus plantarum were inoculated into MRS medium and anaerobically cultured at 37℃ for 24 h to activate the bacteria for two generations. The activated bacterial solution was mixed at a volume ratio of 1:1:1 and inoculated into optimized MRS medium. 1.2% glucose and 0.6% yeast extract were added by weight of the medium. The mixture was anaerobically fermented at 37℃ for 30 h to obtain the fermentation broth. The fermentation broth was centrifuged at 9000 r / min for 15 min. The supernatant was filtered through a 0.22 μm filter membrane to remove bacteria. The supernatant was concentrated under reduced pressure to 1 / 5 of the original volume, freeze-dried at 38℃ and 0.2 MPa, and then freeze-dried at -30℃ and 8 Pa for 9 h to obtain the probiotic metabolites.

[0084] The preparation method of the target carrier includes the following steps:

[0085] B1. Add 90 parts ethanol and 30 parts deionized water to a three-necked flask. Add 2 parts polyethylene glycol 4000 while stirring at 400 r / min. After dissolving, add 15 parts tetraethyl orthosilicate dropwise and stir for 10 min. Add ammonia dropwise to adjust the pH to 8.8. Heat to 38℃ and react at a constant temperature for 5 h. Centrifuge at 9000 r / min for 10 min, collect the precipitate, wash 3 times each with ethanol and deionized water, calcine in a muffle furnace at 550℃ for 2 h, and obtain porous nano-silica after cooling.

[0086] B2. Add 4 parts of porous activated carbon powder to 110 parts of 3% acetic acid solution, reflux and stir for 1 hour, centrifuge at 11000 r / min for 15 min, collect the activated carbon, wash with deionized water until neutral, add 12 parts of polyethylene glycol 400 dispersion (polyethylene glycol 400 to deionized water mass ratio 1:8), and ultrasonically disperse at 350W for 10 min to obtain activated carbon dispersion.

[0087] B3. Dissolve 8 parts of chitosan in 120 parts of 3% acetic acid solution to obtain a chitosan solution. Add the porous nano-silica from step B1 and stir at 700 r / min for 10 min. Then slowly add the activated carbon dispersion from step B2 and stir at 1100 r / min for 10 min. Add 1 mol / L NaOH to adjust the pH to 5.2. Add 0.4 parts of 22% glutaraldehyde solution and stir at 32℃ for 1 h. Transfer to a freeze-drying mold and freeze-dry at -40℃ and 8 Pa for 18 h to obtain an activated carbon-chitosan-porous nano-silica carrier.

[0088] B4. Add 120 parts of deionized water to the activated carbon-chitosan-porous nano silica carrier from step B3, and ultrasonically disperse it at 250W for 10 min. Then add 8 parts of N,N-dimethylformamide, stir evenly, and slowly add 1 part of succinic anhydride. Continue stirring for 5 min, add triethylamine dropwise, adjust the pH of the system to 6.0, heat to 42℃, and stir for 2 h. After the reaction is complete, centrifuge at 11000 r / min for 15 min, collect the precipitate, and wash it 3 times with deionized water to obtain the carboxylated carrier.

[0089] B5. Disperse the carboxylated carrier from step B4 in 150 parts of deionized water and sonicate at 250W for 10 min to obtain a suspension. Add 15 parts of 0.08 mol / L FeCl3 aqueous solution dropwise to the suspension while stirring at 700 r / min. Adjust the pH to 4.0 with 1 mol / L NaOH and stir at 30℃ for 1 h. Centrifuge at 11000 r / min for 15 min, wash three times with deionized water, and freeze-dry at -40℃ and 8 Pa for 7 h to obtain the targeting carrier.

[0090] A method for preparing an oral antibacterial ointment that targets and inhibits Helicobacter pylori includes the following steps:

[0091] S1. Take the formula amount of the targeted carrier, add 6 times the volume of deionized water, stir for 10 min to form a carrier suspension; take the formula amount of plant extract, probiotic metabolites, and compound targeted inhibitor, add 4 times the volume of deionized water, stir evenly, slowly add to the carrier suspension, stir at 36℃ and 500 r / min in the dark for 1 h, freeze dry at -35℃ and 8 Pa for 10 h to obtain the targeted antibacterial component.

[0092] S2. Take the prescribed amount of deionized water, add moisturizer, thickener, and preservative, stir to dissolve, and obtain the aqueous phase; take the targeted antibacterial ingredient powder, add emulsifier, stir evenly, add surfactant, stir and mix for 10 minutes, then slowly add to the aqueous phase, emulsify at 11000 r / min for 15 minutes, after emulsification, homogenize once under high pressure with a homogenizer at 22 MPa, add fragrance, continue stirring at 500 r / min for 20 minutes, pour into a sterile ointment container, seal, and let stand at room temperature for 16 hours to obtain the oral antibacterial ointment that targets and inhibits Helicobacter pylori.

[0093] Example 3

[0094] An oral antibacterial cream that targets and inhibits Helicobacter pylori, comprising the following ingredients in parts by weight:

[0095] 10 parts targeted antibacterial ingredient, 15 parts moisturizer, 3 parts thickener, 2 parts emulsifier, 2 parts surfactant, 0.5 parts fragrance, 0.3 parts preservative, and 80 parts deionized water;

[0096] The targeted antibacterial component consists of 60% plant extracts, 20% probiotic metabolites, 15% compound targeted inhibitors, and 5% targeted carriers.

[0097] The moisturizer is sodium hyaluronate.

[0098] The thickener is carbomer.

[0099] The emulsifier is potassium cetyl phosphate.

[0100] The surfactant is polyoxyethylene hydrogenated castor oil.

[0101] The fragrance is spearmint fragrance; the content of natural spearmint extract in the spearmint fragrance is ≥35%.

[0102] The preservative is sodium dehydroacetate.

[0103] The preparation method of the compound targeted inhibitor includes the following steps:

[0104] A1. Weigh 5 parts of fucoidylated flavonoid glycosides, dissolve them in 60 parts of 0.01mol / L phosphate buffer (pH 7.4), add 1.5 parts of trehalose, stir to dissolve, add 0.1 parts of lipase, heat to 40℃, stir at 500r / min for 6h, after the reaction is complete, add 30 parts of n-hexane, stir for 15min, centrifuge at 8000r / min for 15min, filter the aqueous phase through a 0.45μm filter membrane, and freeze-dry to obtain fucoidylated flavonoid glycosides-trehalose;

[0105] A2. Weigh 3 parts of fucoidylated flavonoid glycoside-trehalose, dissolve in 60 parts of 0.01mol / L phosphate buffer, pH 7.4, add 0.7 parts of 1-ethyl-(3-dimethylaminopropyl)carbodiimide and 0.3 parts of N-hydroxysuccinimide, stir at room temperature for 10-30 min to obtain the activation solution;

[0106] A3. Weigh 1.2 parts of amino polyethylene glycol and dissolve it in 40 parts of 0.01 mol / L phosphate buffer. Slowly add the activation solution and stir at 800 r / min in the dark for 3 h to form an intermediate solution. Dissolve 0.8 parts of o-phthalaldehyde in 10 parts of 0.01 mol / L phosphate buffer and slowly add it to the intermediate solution. Stir at 600 r / min in the dark for 2 h. Add 0.1 parts of sodium borohydride and stir at room temperature for 30 min. Transfer the reaction solution to an 8000 Da dialysis bag and dialyze for 48 h. After dialysis, freeze dry at -40℃ and 10 Pa for 12 h to obtain the composite inhibitor.

[0107] The preparation methods for plant extracts and probiotic metabolites are as follows:

[0108] Honeysuckle, dandelion, and peppermint were mixed in a mass ratio of 2:2:1, pulverized and passed through a 200-mesh sieve, and 15 times their volume of 70% ethanol solution were added. The mixture was refluxed for 1.5 hours and extracted three times. The extracts were combined. The extracts were concentrated under reduced pressure until no alcohol odor was detected. The mixture was then diluted with 5 times the volume of deionized water at 50°C and 0.1 MPa, and centrifuged at 10,000 r / min for 15 minutes. The supernatant was collected and adsorbed through a D101 macroporous resin. The mixture was eluted with 70% ethanol and the eluent was collected. The eluent was freeze-dried at -40°C and 10 Pa for 10 hours to obtain the plant extract.

[0109] Lactobacillus reuteri, Lactobacillus rhamnosus, and Lactobacillus plantarum were inoculated into MRS medium and anaerobically cultured at 37°C for 36 h to activate the bacteria for two generations. The activated bacterial solution was mixed at a volume ratio of 1:1:1 and inoculated into optimized MRS medium. 1.5% glucose and 0.8% yeast extract were added by weight of the medium. The mixture was then anaerobically fermented at 37°C for 36 h to obtain the fermentation broth. The fermentation broth was centrifuged at 10,000 r / min for 20 min. The supernatant was filtered through a 0.22 μm filter membrane to remove bacteria. The supernatant was concentrated under reduced pressure to 1 / 5 of the original volume, freeze-dried at 40°C and 0.3 MPa, and then freeze-dried at -40°C and 10 Pa for 10 h to obtain the probiotic metabolites.

[0110] The preparation method of the target carrier includes the following steps:

[0111] B1. Add 100 parts ethanol and 40 parts deionized water to a three-necked flask. Add 3 parts polyethylene glycol 4000 while stirring at 500 r / min. After dissolving, add 20 parts tetraethyl orthosilicate dropwise and stir for 15 min. Add ammonia dropwise to adjust the pH to 9.0. Heat to 40℃ and react at a constant temperature for 6 h. Centrifuge at 10000 r / min for 15 min, collect the precipitate, wash 3 times each with ethanol and deionized water, calcine in a muffle furnace at 550℃ for 2 h, and obtain porous nano-silica after cooling.

[0112] B2. Add 5 parts of porous activated carbon powder to 120 parts of 5% acetic acid solution, reflux and stir for 2 hours, centrifuge at 12000 r / min for 20 min, collect the activated carbon, wash with deionized water until neutral, add 15 parts of polyethylene glycol 400 dispersion, polyethylene glycol 400 and deionized water mass ratio 1:9, ultrasonically disperse at 400W for 20 min to obtain activated carbon dispersion.

[0113] B3. Dissolve 10 parts of chitosan in 150 parts of 5% acetic acid solution to obtain a chitosan solution. Add the porous nano-silica from step B1 and stir at 800 r / min for 15 min. Then slowly add the activated carbon dispersion from step B2 and stir at 1200 r / min for 15 min. Add 1 mol / L NaOH to adjust the pH to 5.5. Add 0.5 parts of 25% glutaraldehyde solution and stir at 35℃ for 2 h. Transfer to a freeze-drying mold and freeze-dry at -50℃ and 10 Pa for 24 h to obtain an activated carbon-chitosan-porous nano-silica carrier.

[0114] B4. Add 150 parts of deionized water to the activated carbon-chitosan-porous nano silica carrier from step B3, and ultrasonically disperse it at 300W for 15 min. Then add 10 parts of N,N-dimethylformamide and stir evenly. Then slowly add 1.5 parts of succinic anhydride and continue stirring for 10 min. Add triethylamine dropwise to adjust the pH of the system to 6.5, heat to 45℃, and stir for 3 h. After the reaction is complete, centrifuge at 12000 r / min for 20 min, collect the precipitate, and wash it 3 times with deionized water to obtain the carboxylated carrier.

[0115] B5. Disperse the carboxylated carrier from step B4 in 160 parts of deionized water and sonicate at 300W for 20 min to obtain a suspension. Add 20 parts of 0.1 mol / L FeCl3 aqueous solution dropwise to the suspension while stirring at 800 r / min. Adjust the pH to 4.5 with 1 mol / L NaOH and stir at 35℃ for 2 h. Centrifuge at 12000 r / min for 20 min, wash three times with deionized water, and freeze-dry at -50℃ and 10 Pa for 8 h to obtain the targeting carrier.

[0116] A method for preparing an oral antibacterial ointment that targets and inhibits Helicobacter pylori includes the following steps:

[0117] S1. Take the formula amount of the targeted carrier, add 8 times the volume of deionized water, stir for 10 min to form a carrier suspension; take the formula amount of plant extract, probiotic metabolites, and compound targeted inhibitor, add 5 times the volume of deionized water, stir evenly, slowly add to the carrier suspension, stir at 37℃ and 600 r / min in the dark for 2 h, freeze dry at -40℃ and 10 Pa for 12 h to obtain the targeted antibacterial component.

[0118] S2. Take the prescribed amount of deionized water, add moisturizer, thickener, and preservative, stir to dissolve, and obtain the aqueous phase; take the targeted antibacterial ingredient powder, add emulsifier, stir evenly, add surfactant, stir and mix for 15 minutes, then slowly add to the aqueous phase, emulsify at 12000 r / min for 20 minutes, after emulsification, homogenize twice under high pressure at 25 MPa, add fragrance, continue stirring at 600 r / min for 30 minutes, pour into a sterile ointment container, seal, and let stand at room temperature for 24 hours to obtain the oral antibacterial ointment that targets and inhibits Helicobacter pylori.

[0119] The preparation method of fucoidylated flavonoid glycosides includes the following steps:

[0120] (1) Add 0.12 parts of magnesium chloride hexahydrate to 90 parts of Tris buffer solution, stir until completely dissolved, adjust the pH of the system to 7.3 with 1 mol / L hydrochloric acid, add deionized water to make up to 100 parts, and obtain Tris-magnesium ion buffer solution, which is stored at 4℃ for later use.

[0121] (2) Add 1.0 part of quercetin-3-O-glucoside to 50 parts of the above buffer solution, stir in a 30°C water bath for 30 min, add 1 part of uridine diphosphate fucose, stir for 5 min to form a uniform acceptor-donor mixture.

[0122] (3) Add 0.06 parts of α-L-fucosyltransferase, keep the reaction at 32℃ and stir at 450r / min in the dark for 10h, rapidly raise the temperature of the reaction solution to 70℃, keep it at 70℃ for 15min, cool it naturally to room temperature, centrifuge at 10000r / min for 10min, collect the supernatant, transfer it to a 5000Da dialysis bag, dialyze with deionized water for 20h, and collect the retentate after dialysis.

[0123] (4) 60 portions of Sephadex LH-20 gel column were packed into a chromatographic column with a diameter of 2.5 cm and a height of 60 cm. The column bed was equilibrated with methanol-water eluent at a volume ratio of 1:2. The retentate after dialysis was concentrated under reduced pressure at 40 °C and a vacuum of 0.081 MPa to 1 / 8 of the original volume. The sample was then slowly loaded onto the chromatographic column. Eluting was continued with methanol-water eluent at a flow rate of 0.8 mL / min. One tube of eluent was collected every 3 mL. The eluent was combined and concentrated again under reduced pressure until it became viscous. The eluent was then transferred to a lyophilized bottle and pre-frozen at -40 °C for 4 h. Subsequently, it was freeze-dried under a vacuum of 8 Pa for 10 h to obtain fucoidylated flavonoid glycosides.

[0124] Comparative Example 1: The compound targeted inhibitor was missing, and the other components and processes were the same as in Example 1.

[0125] Comparative Example 2: The targeting carrier was replaced with unmodified porous nano-silica, and the remaining components and processes were the same as in Example 1.

[0126] Comparative Example 3: Lacking the targeted antibacterial component, the remaining components and processes are the same as in Example 1.

[0127] Performance testing:

[0128] 1. Helicobacter pylori inhibition rate (%): 10 6 A CFU / mL Helicobacter pylori suspension was mixed with a sample diluted to 1% at a 1:1 ratio and anaerobically cultured at 37℃ for 24 h. The mixture was then serially diluted and spread onto MRS plates. After incubation, the number of colonies was counted. The inhibition rate (%) = (number of colonies in the blank group - number of colonies in the sample group) / number of colonies in the blank group × 100%.

[0129] 2. Helicobacter pylori adhesion blocking rate (%): Human oral mucosal epithelial cells (HOK cells) were seeded into 96-well plates (10... 4 Cells / well), cultured to the logarithmic phase, sample (1% concentration) mixed with Helicobacter pylori suspension (10 cells / well), 6 After incubation with CFU / mL for 30 min, the cells were added to a cell plate and incubated at 37°C for 2 h. The cells were washed three times with PBS to remove unadhered Helicobacter pylori. The number of Helicobacter pylori on the cell surface was detected by colony counting. Adhesion blocking rate (%) = (number of Helicobacter pylori adhering to the blank group - number of Helicobacter pylori adhering to the sample group) / number of Helicobacter pylori adhering to the blank group × 100%.

[0130] 3. Urease activity inhibition rate (%): Prepare a 0.1 U / mL Helicobacter pylori urease solution, mix it with a 1% concentration sample at a 1:1 ratio, incubate at 37℃ for 15 min, add 10 mmol / L urea substrate and react for 30 min, then add a colorimetric reagent and measure the absorbance at 420 nm. Activity inhibition rate (%) = (absorbance of blank group - absorbance of sample group) / absorbance of blank group × 100%;

[0131] 4. Antibacterial persistence (h): 1g of sample was applied to the oral cavity of volunteers, and oral mucosal swabs were collected at 0h, 2h, 4h, 6h and 8h. After the swabs were mixed with Helicobacter pylori suspension and cultured, the inhibition rate of Helicobacter pylori at each time point was detected. The longest time when the inhibition rate was still ≥80% was recorded as the antibacterial persistence.

[0132] Table 1

[0133]

[0134] Table 2

[0135] Group Urease activity inhibition rate (%) Antibacterial durability (h) Example 1 90.3 6.5 Example 2 94.5 8.2 Example 3 95.1 8.8 Comparative Example 1 48.7 3.0 Comparative Example 2 89.2 4.5 Comparative Example 3 5.2 0.5

[0136] As shown in Table 1, the inhibition rates of Examples 1-3 were above 95%, while those of Comparative Examples 1-3 were 72.3%, 85.7%, and 12.8%, respectively. The adhesion blocking rates of Examples 1-3 were 92.5-97.3%, while those of Comparative Examples 1-3 were 55.2%, 68.3%, and 8.6%, respectively. This indicates that the targeted antibacterial components can effectively inhibit Helicobacter pylori, and the targeted inhibitors can enhance the inhibitory effect and the adhesion blocking effect.

[0137] As shown in Table 2, the urease activity inhibition rate of Examples 1-3 was 90.3-95.1%, while that of Comparative Examples 1-3 was 48.7%, 89.2%, and 5.2%, respectively, indicating that the compound inhibitor can inhibit urease. The duration of action of Examples 1-3 was 6.5-8.8 h, while that of Comparative Examples 1-3 was 3.0 h, 4.5 h, and 0.5 h, respectively, indicating that the targeting carrier can prolong the antibacterial effect, improve adhesion, and release the active ingredient more persistently.

[0138] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. An oral antibacterial ointment that targets and inhibits Helicobacter pylori, characterized in that, Includes the following quantities of raw materials: The ingredients include 3-10 parts of targeted antibacterial ingredients, 8-15 parts of moisturizer, 1-3 parts of thickener, 0.5-2 parts of emulsifier, 1-2 parts of surfactant, 0.1-0.5 parts of fragrance, 0.1-0.3 parts of preservative, and 60-80 parts of deionized water. The targeted antibacterial component consists of 40-60% plant extracts, 20-30% probiotic metabolites, 10-20% compound targeted inhibitors, and 5-10% targeted carriers. The preparation method of the composite targeted inhibitor includes the following steps: A1. Fucosylated flavonoid glycosides were dissolved in 0.01 mol / L phosphate buffer, trehalose and lipase were added, the temperature was raised to 38-40℃, after the reaction was completed, n-hexane was added, centrifuged, the aqueous phase was filtered through a 0.45 μm filter membrane, and freeze-dried to obtain fucosylated flavonoid glycosides-trehalose. A2. Fucosylated flavonoid glycoside-trehalose was dissolved in 0.01 mol / L phosphate buffer, and 1-ethyl-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide were added to obtain the activation solution. A3. Dissolve aminopolyethylene glycol in 0.01 mol / L phosphate buffer, and slowly add activation solution to form an intermediate solution; dissolve o-phthalaldehyde in 0.01 mol / L phosphate buffer, and slowly add it to the intermediate solution, add sodium borohydride, transfer the reaction solution to a dialysis bag, dialyze, and freeze-dry to obtain the composite inhibitor.

2. The oral antibacterial ointment for targeting and inhibiting Helicobacter pylori according to claim 1, characterized in that, The preparation methods for plant extracts and probiotic metabolites are as follows: Honeysuckle, dandelion, and peppermint were mixed in a mass ratio of 1.5–2:1.5–2:1, pulverized and passed through a 100–200 mesh sieve, and 10–15 times their volume of 70% ethanol solution were added. The mixture was refluxed for 1–1.5 hours and extracted 2–3 times. The extracts were combined. The extracts were concentrated under reduced pressure until no alcohol odor was detected. The mixture was then diluted with 3–5 times the volume of deionized water at 45–50°C and 0.08–0.1 MPa, and centrifuged at 8000–10000 r / min for 10–15 min. The supernatant was collected and adsorbed through D101 macroporous resin. The mixture was eluted with 70% ethanol and the eluent was collected. The eluent was freeze-dried at -20–-40°C and 6–10 Pa for 8–10 hours to obtain the plant extract. Lactobacillus reuteri, Lactobacillus rhamnosus, and Lactobacillus plantarum were inoculated into MRS medium and anaerobically cultured at 37°C for 24–36 h to activate the bacteria for two generations. The activated bacterial solution was mixed at a volume ratio of 1:1:1 and inoculated into optimized MRS medium. 1–1.5% glucose and 0.5–0.8% yeast extract were added by weight of the medium. Anaerobic fermentation was carried out at 37°C for 24–36 h to obtain the fermentation broth. The fermentation broth was centrifuged at 8000–10000 r / min for 10–20 min. The supernatant was filtered through a 0.22 μm filter membrane to remove bacteria, concentrated under reduced pressure to 1 / 5 of the original volume, and freeze-dried at 38–40°C, 0.1–0.3 MPa, and then at -20–-40°C, 6–10 Pa for 8–10 h to obtain probiotic metabolites.

3. The oral antibacterial ointment for targeting and inhibiting Helicobacter pylori according to claim 1, characterized in that, The preparation method of the target carrier includes the following steps: B1. Add 80-100 parts of ethanol and 20-40 parts of deionized water to a three-necked flask. Add 1-3 parts of polyethylene glycol 4000 while stirring at 300-500 r / min. After dissolving, add 10-20 parts of tetraethyl orthosilicate dropwise. Stir for 10-15 min. Add ammonia dropwise to adjust the pH to 8.5-9.

0. Heat to 35-40℃ and react at a constant temperature for 4-6 h. Centrifuge at 8000-10000 r / min for 10-15 min. Collect the precipitate. Wash with ethanol and deionized water 3 times each. Calcine in a muffle furnace at 500-550℃ for 1-2 h. After cooling, obtain porous nano-silica. B2. Add 3-5 parts of porous activated carbon powder to 100-120 parts of 2-5% acetic acid solution, reflux and stir for 1-2 hours, centrifuge at 10000-12000 r / min, collect the activated carbon for 10-20 min, wash with deionized water until neutral, add 10-15 parts of polyethylene glycol 400 dispersion, polyethylene glycol 400 to deionized water mass ratio 1:6-9, ultrasonically disperse at 300-400W for 10-20 min to obtain activated carbon dispersion; B3. Dissolve 5-10 parts of chitosan in 100-150 parts of 2-5% acetic acid solution to obtain a chitosan solution. Add the porous nano-silica from step B1 and stir at 600-800 r / min for 10-15 min. Then slowly add the activated carbon dispersion from step B2 and stir at 1000-1200 r / min for 10-15 min. Add 1 mol / L NaOH to adjust the pH to 5-5.

5. Add 0.2-0.5 parts of 20-25% glutaraldehyde solution and stir at 30-35℃ for 1-2 h. Transfer to a freeze-drying mold and freeze-dry at -30 to -50℃ under a vacuum of 6-10 Pa for 12-24 h to obtain an activated carbon-chitosan-porous nano-silica carrier. B4. Add 100-150 parts of deionized water to the activated carbon-chitosan-porous nano silica carrier from step B3, and ultrasonically disperse it at 200-300W for 10-15 min. Then add 5-10 parts of N,N-dimethylformamide and stir evenly. Then slowly add 0.5-1.5 parts of succinic anhydride and continue stirring for 5-10 min. Add triethylamine dropwise to adjust the pH of the system to 6.0-6.5, raise the temperature to 40-45℃, and stir for 2-3 h. After the reaction is complete, centrifuge at 10000-12000 r / min for 10-20 min, collect the precipitate, and wash it 3 times with deionized water to obtain the carboxylated carrier. B5. Disperse the carboxylated carrier from step B4 in 120–160 parts of deionized water and sonicate at 200–300 W for 10–20 min to obtain a suspension. Add 10–20 parts of 0.05–0.1 mol / L FeCl3 aqueous solution dropwise to the suspension while stirring at 600–800 r / min. Adjust the pH to 4.0–4.5 with 1 mol / L NaOH and stir at 30–35 °C for 1–2 h. Centrifuge at 10000–12000 r / min for 10–20 min, wash three times with deionized water, and freeze-dry at -30–-50 °C and a vacuum of 6–10 Pa for 6–8 h to obtain the targeting carrier.

4. The oral antibacterial ointment for targeting and inhibiting Helicobacter pylori according to claim 1, characterized in that, The moisturizer is one of glycerin, propylene glycol, or sodium hyaluronate.

5. The oral antibacterial ointment for targeting and inhibiting Helicobacter pylori according to claim 1, characterized in that, The thickener is one of xanthan gum, hydroxypropyl methylcellulose, or carbomer.

6. The oral antibacterial ointment for targeting and inhibiting Helicobacter pylori according to claim 1, characterized in that, The co-emulsifier is one of polyglycerol-4-isostearate, sorbitan monostearate, or cetyl phosphate potassium.

7. The oral antibacterial ointment for targeting and inhibiting Helicobacter pylori according to claim 1, characterized in that, The surfactant is one of cocamidopropyl betaine, sodium lauroyl sarcosinate, or polyoxyethylene hydrogenated castor oil.

8. The oral antibacterial ointment for targeting and inhibiting Helicobacter pylori according to claim 1, characterized in that, The flavoring is one of peppermint flavoring, lemon flavoring, and spearmint flavoring; the peppermint flavoring contains ≥30% natural peppermint extract, the lemon flavoring contains ≥25% natural lemon extract, and the spearmint flavoring contains ≥35% natural spearmint extract.

9. The oral antibacterial ointment for targeting and inhibiting Helicobacter pylori according to claim 1, characterized in that, The preservative is one of phenoxyethanol, methylparaben, or sodium dehydroacetate.

10. A method for preparing an oral antibacterial ointment targeting and inhibiting Helicobacter pylori according to any one of claims 1 to 9, characterized in that, Includes the following steps: S1. Take the formulated amount of the targeted carrier, add 5-8 times the volume of deionized water, stir for 5-10 min to form a carrier suspension; take the formulated amount of plant extract, probiotic metabolites, and compound targeted inhibitor, add 3-5 times the volume of deionized water, stir evenly, slowly add to the carrier suspension, stir at 35-37℃ and 400-600 r / min in the dark for 1-2 h, freeze dry at -30--40℃ and 6-10 Pa for 8-12 h to obtain the targeted antibacterial component; S2. Take the prescribed amount of deionized water, add humectant, thickener, and preservative, stir to dissolve, and obtain the aqueous phase; take the targeted antibacterial ingredient powder, add emulsifier, stir evenly, add surfactant, stir and mix for 10-15 minutes, then slowly add to the aqueous phase at 10000-12000 r / min, emulsify for 10-20 minutes, after emulsification, homogenize 1-2 times under high pressure at 20-25 MPa, add fragrance, continue stirring at 400-600 r / min for 10-30 minutes, pour into a sterile ointment container, seal, and let stand at room temperature for 12-24 hours to obtain the oral antibacterial ointment that targets and inhibits Helicobacter pylori.

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