Oral care composition for inhibiting helicobacter pylori and preparation method thereof

Abstract

The invention provides an oral care composition for inhibiting helicobacter pylori and a preparation method of the oral care composition. The oral care composition comprises glycerin, xylitol, erythritol, thymol clathrate, garlic extract clathrate, propolis extract, lactoferrin, disodium ethylene diamine tetraacetate, menthol, potassium sorbate and purified water. The thymol clathrate compound is obtained by carrying out clathration on thymol through beta-cyclodextrin. The garlic extract clathrate compound is obtained by clathrating a garlic extract with beta-cyclodextrin. According to the oral care composition provided by the invention, the helicobacter pylori in the oral cavity can be effectively inhibited through reasonable proportioning of various components, so that the risks of ozostomia and stomach reinfection are reduced.

Description

Technical Field

[0001] This invention belongs to the field of oral care technology and relates to an oral care composition for inhibiting Helicobacter pylori and its preparation method. Background Technology

[0002] Helicobacter pylori, a pathogen closely associated with chronic gastritis, peptic ulcers, and even gastric cancer, has a global reach and is easily transmitted within families via oral-oral and fecal-oral routes. Studies have shown that the oral cavity, particularly dental plaque and periodontal pockets, is an important reservoir for Helicobacter pylori outside the stomach. Oral Helicobacter pylori not only causes persistent halitosis but also serves as a potential source of recurrent gastric infections. Even after eradication treatment of Helicobacter pylori in the stomach, oral Helicobacter pylori can re-colonize the gastric mucosa through swallowing, leading to reinfection. Therefore, controlling Helicobacter pylori in the oral cavity is crucial for blocking bacterial transmission, reducing the risk of gastric reinfection, and improving bad breath.

[0003] Currently, conventional treatment for Helicobacter pylori primarily focuses on the stomach, employing triple or quadruple therapy with bismuth-containing agents and antibiotics. However, these systemic medication regimens often have limited effectiveness in eradicating Helicobacter pylori in the oral cavity. In the oral care field, some products claiming to inhibit Helicobacter pylori exist, such as toothpastes or mouthwashes containing fucoidan and lactoferrin, or mouthwashes using specific plant extracts. However, these existing technologies still have some shortcomings. For example, some products have relatively simple antibacterial ingredients, leading to drug resistance with long-term use; some chemical antibacterial agents, while effective, can irritate the oral mucosa or cause tooth discoloration and altered taste with long-term use; and some natural extracts suffer from poor water solubility, chemical instability, strong odor, or low bioavailability, affecting their stability and ultimate antibacterial effect in products.

[0004] Therefore, there is an urgent need in the field to develop a novel oral care composition that can effectively inhibit Helicobacter pylori in the oral cavity. Summary of the Invention

[0005] In view of the shortcomings of the existing technology, the purpose of this invention is to provide an oral care composition for inhibiting Helicobacter pylori and its preparation method. The oral care composition provided by this invention can effectively inhibit Helicobacter pylori in the oral cavity through the reasonable ratio of various components, thereby reducing halitosis and the risk of gastric reinfection.

[0006] To achieve this objective, the present invention adopts the following technical solution: In a first aspect, the present invention provides an oral care composition for inhibiting Helicobacter pylori, the oral care composition comprising glycerin, xylitol, erythritol, thymol inclusion complex, garlic extract inclusion complex, propolis extract, lactoferrin, disodium EDTA, menthol, potassium sorbate and purified water; The thymol inclusion complex was obtained by including thymol with β-cyclodextrin. The garlic extract inclusion complex was obtained by incorporating garlic extract with β-cyclodextrin.

[0007] The oral care composition provided by this invention, through a rational formulation of multiple components, can effectively inhibit Helicobacter pylori in the oral cavity, thereby reducing halitosis and the risk of gastric reinfection. Xylitol and erythritol interfere with bacterial metabolism, lactoferrin inhibits bacterial growth by depriving the body of iron ions, and disodium EDTA disrupts bacterial cell membranes by chelating metal ions, thus enhancing the penetration of other antibacterial ingredients. Furthermore, this invention effectively solves the problems of chemical instability, poor water solubility, noticeable odor, and irritation to the oral mucosa that exist when thymol and garlic extract are used directly by encapsulating them with β-cyclodextrin. Encapsulation not only improves the stability and bioavailability of the active ingredients but also enables slow release and prolongs the duration of action.

[0008] Glycerin, as a humectant and solvent, helps maintain oral moisture and ensures even dispersion of other ingredients. Xylitol and erythritol are common sweeteners that inhibit bacterial sugar metabolism, reduce plaque formation, and weaken the survival environment of Helicobacter pylori. Thymol is a natural antibacterial agent that inhibits various bacteria, including Helicobacter pylori, but it is volatile and highly irritating when used directly. Garlic extract contains active ingredients such as allicin and has broad-spectrum antibacterial properties, but it has poor water solubility and a noticeable odor. Encapsulation with β-cyclodextrin encapsulates thymol and garlic extract within the cyclodextrin molecule cavity, improving their stability and bioavailability and preventing irritation from direct contact with the oral mucosa. Propolis extract, as a natural antibacterial agent, enhances the overall antibacterial effect and has some anti-inflammatory properties. Lactoferrin is an iron-binding protein that removes iron ions needed for bacterial growth, thereby inhibiting the reproduction of Helicobacter pylori. Disodium EDTA, as a chelating agent, binds to metal ions on bacterial cell membranes, disrupting membrane structure and enhancing the permeability of other antibacterial ingredients. Menthol primarily provides a cooling sensation and improves the user experience. Potassium sorbate, as a preservative, ensures that the product is not contaminated by microorganisms during storage.

[0009] Helicobacter pylori exists in dental plaque and other biofilms in the oral cavity, and single components are often insufficient for complete eradication. The oral care composition provided by this invention significantly improves the inhibition rate of Helicobacter pylori through the synergistic effect of its components. Specifically: Xylitol and erythritol work synergistically in oral care compositions, interfering with the metabolism and survival environment of oral pathogens. Xylitol, a pentose sugar alcohol, cannot be effectively metabolized and utilized by most oral bacteria. When bacteria ingest xylitol, toxic metabolic intermediates accumulate within their cells, interfering with normal glycolysis and energy metabolism, thereby inhibiting bacterial growth and reducing plaque formation. Erythritol, a tetraose sugar alcohol, has a smaller molecule and more easily penetrates bacterial cells. It not only interferes with bacterial sugar metabolism but also causes cell dehydration through osmotic pressure, further weakening bacterial activity. When xylitol and erythritol are used together, they disrupt bacterial metabolic stability from different angles. Xylitol primarily interferes with energy production internally, while erythritol enhances external osmotic pressure stress, jointly exacerbating the physiological burden on bacteria. Furthermore, both can inhibit the formation of plaque biofilms that Helicobacter pylori can adhere to.

[0010] Lactoferrin and disodium EDTA work synergistically in oral care compositions to weaken the survival ability of Helicobacter pylori. Lactoferrin is an iron-binding protein whose mechanism of action is to strongly bind to iron ions in the environment, depriving bacteria of the iron necessary for growth and reproduction, thereby inhibiting their metabolic activities. Disodium EDTA, as a metal ion chelating agent, mainly acts on the bacterial cell membrane by chelating calcium and magnesium ions that maintain the structural integrity and stability of the cell membrane, thus disrupting the permeability of the cell membrane. When lactoferrin and disodium EDTA are used together, disodium EDTA first disrupts the structural integrity of the bacterial cell membrane, increasing its permeability and facilitating faster entry of lactoferrin into the bacterial cell. Once inside the bacterial cell, lactoferrin binds to iron ions necessary for bacterial growth and reproduction, thereby inhibiting bacterial metabolic activities and limiting bacterial growth and reproduction.

[0011] Thymol inclusion complexes and garlic extract inclusion complexes, as natural antibacterial agents, work synergistically with propolis extract. The main active ingredient in garlic extract is allicin, which increases bacterial permeability by disrupting the integrity of bacterial cell membranes, leading to leakage of cell contents. Thymol interferes with bacterial enzyme systems and energy metabolism, inhibiting bacterial growth and reproduction. Propolis extract contains various flavonoids, which not only have broad-spectrum antibacterial activity but also inhibit bacterial biofilm formation. When thymol inclusion complexes, garlic extract, and propolis extract are used in combination, garlic extract first disrupts the bacterial cell membrane structure, facilitating the entry of active molecules from thymol and propolis extract into the bacterial cell. Once inside the cell, thymol interferes with normal bacterial physiological functions, while propolis extract inhibits bacterial aggregation and the formation of a protective biofilm, preventing bacterial attachment and growth.

[0012] While thymol possesses antibacterial properties, it is easily oxidized and volatilized, and direct addition can affect product shelf life and antibacterial efficacy. Garlic extract contains unstable components such as allicin, and its strong odor can negatively impact user experience. By encapsulating these active molecules with β-cyclodextrin, they are embedded within the hydrophobic cavities of the cyclodextrin, forming inclusion complexes. This reduces contact with light, oxygen, or moisture, weakening the influence of the external environment, slowing degradation, and improving water solubility and stability. In the oral cavity, these inclusion complexes can slowly release the active ingredients through saliva, achieving localized and sustained antibacterial action while masking odors and improving taste.

[0013] As a preferred embodiment of the present invention, the oral care composition comprises, in parts by weight of 100, the following components: 5-10 parts glycerin; 3-5 parts xylitol; Erythritol 3-5 parts; 0.1-0.3 parts of thymol inclusion complex; Garlic extract inclusion complex, 0.5-1.5 parts; 1-2 parts of propolis extract; Lactoferrin 0.3-0.5 parts; Disodium ethylenediaminetetraacetate 0.1~0.3 parts; Menthol 0.1~0.3 parts; Potassium sorbate 0.1~0.2 parts; The remainder is purified water.

[0014] The weight parts of glycerol can be 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, or 10.0 parts; the weight parts of xylitol can be 3.0, 3.2, 3.4, 3.6, 3.8, 4.0, 4.2, 4.4, 4.6, 4.8, or 5.0 parts; and the weight parts of erythritol can be 3.0, 3.2, 3.4, 3.6, 3.8, 4.0, 4.2, 4.4, or 4. The weight parts of thymol inclusion complex can be 0.1, 0.12, 0.14, 0.16, 0.18, 0.2, 0.22, 0.24, 0.26, 0.28, or 0.3 parts; the weight parts of garlic extract inclusion complex can be 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, or 1.5 parts; and the weight parts of propolis extract can be 1.0, 1.1, 1.2, or 1.5 parts. The weight percentages of lactoferrin can be 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, or 2.0 parts; the weight percentages of lactoferrin can be 0.3, 0.32, 0.34, 0.36, 0.38, 0.4, 0.42, 0.44, 0.46, 0.48, or 0.5 parts; and the weight percentages of disodium EDTA can be 0.1, 0.12, 0.14, 0.16, 0.18, 0.2, 0.22, 0.24, 0.26, or 0.28 parts. The weight of menthol can be 0.1, 0.12, 0.14, 0.16, 0.18, 0.2, 0.22, 0.24, 0.26, 0.28, or 0.3 parts, and the weight of potassium sorbate can be 0.1, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, 0.19, or 0.2 parts, but is not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0015] This invention specifically limits the addition amount of thymol inclusion complex to 0.1-0.3 parts. Thymol is the core natural antibacterial component, and its main function is to inhibit Helicobacter pylori by disrupting the bacterial cell membrane structure and interfering with its energy metabolism. After inclusion with β-cyclodextrin, its stability and water solubility are improved, and its irritation is reduced. Within the addition range specified in this invention, the thymol inclusion complex can slowly release an effective concentration of thymol in the oral environment, which is sufficient to inhibit Helicobacter pylori.

[0016] When the amount of thymol inclusion complex added is less than 0.1 parts, the effective concentration of thymol in the composition is low, and the ideal antibacterial effect cannot be achieved. When the amount of thymol inclusion complex added exceeds 0.3 parts, the excessive amount of thymol, even after inclusion treatment, will still cause some irritation and burning sensation to the user's oral mucosa, affecting the user experience.

[0017] This invention specifically limits the addition amount of the garlic extract inclusion complex to 0.5-1.5 parts. Garlic extract is a key natural antibacterial component in the composition, and its core active substance, allicin, can effectively disrupt the cell membrane structure of Helicobacter pylori. After inclusion with β-cyclodextrin, the stability, water solubility, and taste of the garlic extract are significantly improved. Within the addition range specified in this invention, the garlic extract inclusion complex can continuously release a sufficient concentration of active antibacterial components.

[0018] When the amount of garlic extract inclusion complex added is less than 0.5 parts, the effective concentration of garlic extract in the composition is low, and the antibacterial effect is poor. When the amount of garlic extract inclusion complex added exceeds 1.5 parts, the excessive garlic extract will escape due to its inherent strong sulfide odor, affecting the aroma and taste of the product, and will also irritate the oral mucosa of the user.

[0019] This invention specifically limits the addition amount of propolis extract to 1-2 parts. Propolis extract is rich in flavonoids and other active ingredients, which not only have a direct inhibitory effect on Helicobacter pylori but also effectively interfere with bacterial biofilm formation, reducing bacterial adhesion and aggregation in dental plaque biofilm. Within the addition range specified in this invention, the propolis extract can provide a sufficient effective concentration to achieve the above-mentioned effects.

[0020] When the amount of propolis extract added is less than 1 part, the effective concentration of propolis extract in the composition is too low, making it difficult to effectively remove existing dental plaque biofilm. This reduces the ability of the antibacterial components in the composition to remove bacteria adsorbed on the plaque biofilm. When the amount of propolis extract added exceeds 2 parts, due to the viscosity and special resinous odor of propolis extract, excessive addition will affect the fluidity and taste of the composition, ultimately resulting in an overly viscous product texture and negatively impacting the user experience.

[0021] This invention specifically limits the addition amount of lactoferrin to 0.3-0.5 parts. Lactoferrin is a natural iron-binding protein whose core antibacterial mechanism is the competitive and tight binding of free iron ions in the environment. Iron ions are a trace element essential for the growth and reproduction of many pathogenic bacteria, such as Helicobacter pylori. By depriving bacteria of the iron source necessary for growth and reproduction, its metabolic activity can be effectively inhibited. Within the addition range specified in this invention, lactoferrin can effectively reduce the concentration of iron ions available for bacterial use in the oral environment, thereby significantly inhibiting the growth and reproduction of Helicobacter pylori.

[0022] When the amount of lactoferrin added is less than 0.3 parts, its concentration is insufficient to effectively chelate iron ions in the oral cavity, and it cannot significantly inhibit the growth and reproduction of Helicobacter pylori. Conversely, when the amount of lactoferrin added exceeds 0.5 parts, the iron ions in the oral cavity are already saturated with chelation, and further increasing the amount of lactoferrin will not chelate more iron ions, resulting in waste of raw materials and increased production costs.

[0023] This invention specifically limits the addition amount of disodium EDTA to 0.1-0.3 parts. As a metal ion chelating agent, disodium EDTA's core function is to strongly bind to metal ions such as calcium and magnesium, essential for maintaining the structural stability and function of bacterial cell membranes, thereby disrupting the cell membrane's integrity and increasing its permeability. Within the addition range specified in this invention, disodium EDTA can effectively weaken the cell membrane barrier of Helicobacter pylori, facilitating the smoother passage of other antibacterial components in the formulation (lactoferrin, thymol, garlic extract, etc.) into the bacterial cell.

[0024] When the amount of disodium EDTA added is less than 0.1 parts, its concentration in the oral cavity is insufficient to effectively chelate metal ions on bacterial cell membranes and to adequately disrupt the bacterial cell membrane structure. Conversely, when the amount of disodium EDTA added exceeds 0.3 parts, excessive disodium EDTA will over-chelate metal ions in the oral cavity, causing mild irritation to the oral mucosa.

[0025] In a second aspect, the present invention provides a method for preparing the oral care composition for inhibiting Helicobacter pylori as described in the first aspect, the method comprising: (I) Thymol was encapsulated with β-cyclodextrin to obtain thymol inclusion complex; garlic extract was encapsulated with β-cyclodextrin to obtain garlic extract inclusion complex; (II) Glycerin, xylitol, erythritol, thymol inclusion complex, garlic extract inclusion complex, propolis extract, lactoferrin, disodium EDTA, menthol, potassium sorbate and purified water are mixed evenly to obtain the oral care composition.

[0026] As a preferred technical solution of the present invention, in step (I), the thymol inclusion complex is prepared by the following method: β-Cyclodextrin was dissolved in hot water, mixed, stirred, and heated to obtain a cyclodextrin solution; thymol was heated and melted to obtain a thymol melt. Under stirring and heating conditions, the molten thymol was added dropwise to the cyclodextrin solution. After all the solution was added, stirring and heating continued to obtain a thymol inclusion solution. The thymol inclusion solution was placed in a low-temperature environment to cool and crystallize, and then filtered to obtain the inclusion complex. The inclusion complex was washed and dried to obtain the thymol inclusion complex.

[0027] This invention utilizes the cavity structure of β-cyclodextrin molecules to encapsulate thymol molecules, forming a stable thymol inclusion complex, thereby significantly improving the problems of thymol's poor water solubility, easy volatility, unstable chemical properties, and strong irritation to the oral mucosa.

[0028] In the preparation process, β-cyclodextrin was first dissolved in hot water and stirred until fully dissolved. Thymol was then heated to a molten state, enhancing its molecular fluidity and facilitating thorough contact with cyclodextrin molecules during subsequent dropwise addition. Under stirring and heating conditions, the molten thymol was slowly added dropwise to the cyclodextrin solution. By controlling the dropping rate, thymol molecules were able to orderly enter the hydrophobic cavities of β-cyclodextrin, forming an inclusion structure through intermolecular forces. Continuous stirring and heating promoted the inclusion reaction and ensured complete inclusion. Subsequently, the resulting inclusion solution was placed in a low-temperature environment. Utilizing the principle that solubility decreases with decreasing temperature, the inclusion compound crystallized out. After filtration, washing, and drying, a pure inclusion compound powder was finally obtained.

[0029] The resulting thymol inclusion complex not only improved the solubility and stability of thymol in aqueous systems and masked its original odor, but also reduced its direct irritation to oral tissues through sustained-release action, thereby enhancing its suitability and safety in oral care compositions.

[0030] As a preferred technical solution of the present invention, β-cyclodextrin is dissolved in hot water at 50~60℃, for example, 50℃, 51℃, 52℃, 53℃, 54℃, 55℃, 56℃, 57℃, 58℃, 59℃ or 60℃, and mixed and heated at 50~60℃ for 30~40 minutes to obtain the cyclodextrin solution, for example, for 30 minutes, 31 minutes, 32 minutes, 33 minutes, 34 minutes, 35 minutes, 36 minutes, 37 minutes, 38 minutes, 39 minutes or 40 minutes, but is not limited to the listed values, and other unlisted values ​​within this range are also applicable.

[0031] In some optional instances, the mass fraction of β-cyclodextrin in the cyclodextrin solution is 10 to 15 wt%, for example, it can be 10 wt%, 10.5 wt%, 11 wt%, 11.5 wt%, 12 wt%, 12.5 wt%, 13 wt%, 13.5 wt%, 14 wt%, 14.5 wt%, or 15 wt%, but is not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0032] In some alternative examples, the heating and melting temperature of the thymol is 50-60°C, for example, 50°C, 51°C, 52°C, 53°C, 54°C, 55°C, 56°C, 57°C, 58°C, 59°C or 60°C, but is not limited to the listed values, and other unlisted values ​​within this range are also applicable.

[0033] In some alternative examples, the heating and melting time of the thymol is 5 to 10 min, for example, 5.0 min, 5.5 min, 6.0 min, 6.5 min, 7.0 min, 7.5 min, 8.0 min, 8.5 min, 9.0 min, 9.5 min or 10.0 min, but is not limited to the listed values, and other unlisted values ​​within this range are also applicable.

[0034] In some optional examples, the stirring speed is 300-500 rpm and the heating temperature is 50-60°C, wherein the stirring speed can be 300 rpm, 320 rpm, 340 rpm, 360 rpm, 380 rpm, 400 rpm, 420 rpm, 440 rpm, 460 rpm, 480 rpm, or 500 rpm, and the heating temperature can be 50°C, 51°C, 52°C, 53°C, 54°C, 55°C, or 500°C. The molten thymol solution is added dropwise to the cyclodextrin solution at 6℃, 57℃, 58℃, 59℃, or 60℃. After all the solution has been added, the mixture is stirred and heated for 2-4 hours to obtain a thymol inclusion solution. For example, the time can be 2.0h, 2.2h, 2.4h, 2.6h, 2.8h, 3.0h, 3.2h, 3.4h, 3.6h, 3.8h, or 4.0h, but it is not limited to the listed values. Other unlisted values ​​within this range are also applicable.

[0035] In some alternative examples, the dripping rate of the thymol melt is 1 to 3 mL / min, for example, 1.0 mL / min, 1.2 mL / min, 1.4 mL / min, 1.6 mL / min, 1.8 mL / min, 2.0 mL / min, 2.2 mL / min, 2.4 mL / min, 2.6 mL / min, 2.8 mL / min or 3.0 mL / min, but is not limited to the listed values, and other unlisted values ​​within this range are also applicable.

[0036] In some alternative instances, the mass ratio of the thymol melt to the β-cyclodextrin in the cyclodextrin solution is 1:(4~6), for example, it can be 1:4.0, 1:4.2, 1:4.4, 1:4.6, 1:4.8, 1:5.0, 1:5.2, 1:5.4, 1:5.6, 1:5.8 or 1:6.0, but is not limited to the listed values, other unlisted values ​​within this range are also applicable.

[0037] In some alternative examples, the cooling temperature for crystallization of the thymol inclusion solution is 3 to 5°C, for example, 3.0°C, 3.2°C, 3.4°C, 3.6°C, 3.8°C, 4.0°C, 4.2°C, 4.4°C, 4.6°C, 4.8°C, or 5.0°C, but is not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0038] In some optional instances, the cooling and crystallization time of the thymol inclusion solution is 12 to 24 hours, for example, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, or 24 hours, but is not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0039] In some alternative instances, the inclusion complex is washed with purified water at 3–5°C, for example, at 3.0°C, 3.2°C, 3.4°C, 3.6°C, 3.8°C, 4.0°C, 4.2°C, 4.4°C, 4.6°C, 4.8°C, or 5.0°C, but not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0040] In some optional instances, the drying temperature of the inclusion compound is 40 to 50°C, for example, 40°C, 41°C, 42°C, 43°C, 44°C, 45°C, 46°C, 47°C, 48°C, 49°C or 50°C, but is not limited to the listed values, and other unlisted values ​​within this range are also applicable.

[0041] In some alternative instances, the drying time of the inclusion compound is 4 to 8 hours, for example, 4.0 hours, 4.5 hours, 5.0 hours, 5.5 hours, 6.0 hours, 6.5 hours, 7.0 hours, 7.5 hours, or 8.0 hours, but is not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0042] As a preferred technical solution of the present invention, in step (I), the garlic extract inclusion complex is prepared by the following method: β-Cyclodextrin was dissolved in hot water, mixed, stirred, and heated to obtain a cyclodextrin solution; garlic extract was mixed evenly with anhydrous ethanol to obtain a garlic extract solution. Under heating and high-speed stirring conditions, the garlic extract solution was added dropwise to the cyclodextrin solution. After all the solution was added, stirring and heating continued to obtain a garlic extract inclusion solution. The garlic extract inclusion solution was placed in a low-temperature environment to cool and crystallize, and then filtered to obtain the inclusion complex. The inclusion complex was washed and dried to obtain the garlic extract inclusion complex.

[0043] This invention utilizes the hollow structure of β-cyclodextrin to effectively encapsulate allicin, the active ingredient in garlic extract, forming a stable inclusion complex. This solves the problems of poor water solubility, unstable chemical properties, volatility, strong irritation, and obvious odor that exist when garlic extract is used directly.

[0044] In the preparation process, β-cyclodextrin was first dissolved in hot water and stirred until fully dissolved. Garlic extract was then mixed with anhydrous ethanol to fully disperse the lipid-soluble active ingredients in the garlic extract, forming a homogeneous garlic extract solution to promote sufficient contact between the garlic extract and cyclodextrin molecules. Under heating and high-speed stirring conditions, the garlic extract solution was slowly added dropwise to the cyclodextrin solution. The strong shear force generated by high-speed stirring broke the garlic extract solution into micron- or even nano-sized droplets, greatly increasing the contact area with the cyclodextrin molecules and thus significantly improving the inclusion efficiency and uniformity. After all the droplets were added, the stirring speed was reduced to ensure a more thorough inclusion reaction and the formation of a stable inclusion structure. Subsequently, the inclusion complex was allowed to crystallize by low-temperature standing, followed by filtration, washing, and drying to finally obtain the garlic extract inclusion complex.

[0045] The resulting garlic extract inclusion complex not only improved its solubility and stability in aqueous systems, but also effectively masked its strong sulfide odor, reduced mucosal irritation from direct use, and prolonged its antibacterial effect through sustained release, making it more suitable for use in oral care compositions.

[0046] As a preferred technical solution of the present invention, β-cyclodextrin is dissolved in hot water at 50~60℃, for example, 50℃, 51℃, 52℃, 53℃, 54℃, 55℃, 56℃, 57℃, 58℃, 59℃ or 60℃, and mixed and heated at 50~60℃ for 30~40 minutes to obtain the cyclodextrin solution, for example, for 30 minutes, 31 minutes, 32 minutes, 33 minutes, 34 minutes, 35 minutes, 36 minutes, 37 minutes, 38 minutes, 39 minutes or 40 minutes, but is not limited to the listed values, and other unlisted values ​​within this range are also applicable.

[0047] In some optional instances, the mass fraction of β-cyclodextrin in the cyclodextrin solution is 10 to 15 wt%, for example, it can be 10 wt%, 10.5 wt%, 11 wt%, 11.5 wt%, 12 wt%, 12.5 wt%, 13 wt%, 13.5 wt%, 14 wt%, 14.5 wt%, or 15 wt%, but is not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0048] In some optional instances, the garlic extract is in a 1:1 mass ratio to the anhydrous ethanol.

[0049] In some optional examples, the garlic extract solution is added dropwise to the cyclodextrin solution at a heating temperature of 30-40°C and a stirring speed of 10,000-12,000 rpm, wherein the heating temperature can be 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, 36°C, 37°C, 38°C, 39°C, or 40°C, and the stirring speed can be 10,000 rpm, 10,200 rpm, 10,400 rpm, 10,600 rpm, 10,800 rpm, 11,000 rpm, 11,200 rpm, 11,400 rpm, 11,600 rpm, 11,800 rpm, or 12,000 rpm. After all the solution has been added, the garlic extract solution is added dropwise to the cyclodextrin solution. The stirring speed is reduced to 200-400 rpm, for example, 200 rpm, 220 rpm, 240 rpm, 260 rpm, 280 rpm, 300 rpm, 320 rpm, 340 rpm, 360 rpm, 380 rpm, or 400 rpm, and stirring and heating are continued at a heating temperature of 30-40°C for 2-3 hours to obtain the garlic extract inclusion solution, for example, 2.0h, 2.1h, 2.2h, 2.3h, 2.4h, 2.5h, 2.6h, 2.7h, 2.8h, 2.9h, or 3.0h, but not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0050] In some alternative examples, the drip rate of the garlic extract solution is 1 to 3 mL / min, for example, 1.0 mL / min, 1.2 mL / min, 1.4 mL / min, 1.6 mL / min, 1.8 mL / min, 2.0 mL / min, 2.2 mL / min, 2.4 mL / min, 2.6 mL / min, 2.8 mL / min or 3.0 mL / min, but is not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0051] In some optional instances, the mass ratio of garlic extract in the garlic extract solution to β-cyclodextrin in the cyclodextrin solution is 1:(3~5), for example, it can be 1:3.0, 1:3.2, 1:3.4, 1:3.6, 1:3.8, 1:4.0, 1:4.2, 1:4.4, 1:4.6, 1:4.8 or 1:5.0, but is not limited to the listed values, other unlisted values ​​within this range are also applicable.

[0052] In some alternative instances, the cooling crystallization temperature of the garlic extract inclusion solution is 3 to 5°C, for example, 3.0°C, 3.2°C, 3.4°C, 3.6°C, 3.8°C, 4.0°C, 4.2°C, 4.4°C, 4.6°C, 4.8°C, or 5.0°C, but is not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0053] In some optional instances, the cooling crystallization time of the garlic extract inclusion solution is 12 to 24 hours, for example, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, or 24 hours, but is not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0054] In some alternative instances, the inclusion complex is washed with purified water at 3–5°C, for example, at 3.0°C, 3.2°C, 3.4°C, 3.6°C, 3.8°C, 4.0°C, 4.2°C, 4.4°C, 4.6°C, 4.8°C, or 5.0°C, but not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0055] In some optional instances, the drying temperature of the inclusion compound is 40 to 50°C, for example, 40°C, 41°C, 42°C, 43°C, 44°C, 45°C, 46°C, 47°C, 48°C, 49°C or 50°C, but is not limited to the listed values, and other unlisted values ​​within this range are also applicable.

[0056] In some alternative instances, the drying time of the inclusion compound is 4 to 8 hours, for example, 4.0 hours, 4.5 hours, 5.0 hours, 5.5 hours, 6.0 hours, 6.5 hours, 7.0 hours, 7.5 hours, or 8.0 hours, but is not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0057] As a preferred technical solution of the present invention, step (II) specifically includes the following steps: (1) Add purified water to the mixing tank and stir and heat it. Under stirring and high temperature heating conditions, add disodium ethylenediaminetetraacetate, xylitol, erythritol and glycerol to the mixing tank and continue stirring and heating until completely dissolved to obtain an intermediate solution. (2) After the intermediate solution is cooled to room temperature, lactoferrin, thymol inclusion complex, garlic extract inclusion complex, propolis extract, potassium sorbate and menthol are added to the mixing tank in sequence under stirring and room temperature conditions. Each component is stirred for a period of time after being added, and then the next component is added. After all components are added, stirring is continued, and then the mixture is sent to a homogenizer for high-pressure homogenization to obtain a composite emulsion. A pH adjuster is added to the composite emulsion to adjust the pH value to obtain the oral care composition.

[0058] In the formulation of the oral care composition, water-soluble components such as disodium EDTA, xylitol, erythritol, and glycerin are first dissolved under heating conditions. Heating and stirring at 60-70°C accelerates the dissolution and diffusion of these components, forming a homogeneous base solution. Subsequently, after the solution cools to room temperature, heat-sensitive components such as lactoferrin, inclusion complexes, and propolis extract are added sequentially. This avoids denaturation of lactoferrin and destruction of the inclusion structure caused by high temperatures, ensuring the bioactivity of the core antibacterial substances. Subsequent high-pressure homogenization further breaks down particles and reduces particle size through strong shear force, allowing the hydrophobic inclusion complexes to better compatibility with the aqueous system, forming a stable composite emulsion and improving the product's physical homogeneity and storage stability. Finally, the pH is adjusted to 6-7, which meets the physiological requirements of the oral environment, reduces mucosal irritation, and avoids degradation or precipitation of certain components in excessively acidic or alkaline environments.

[0059] As a preferred technical solution of the present invention, in step (1), the stirring speed is 300~500 rpm and the heating temperature is 60~70℃, wherein the stirring speed can be 300 rpm, 320 rpm, 340 rpm, 360 rpm, 380 rpm, 400 rpm, 420 rpm, 440 rpm, 460 rpm, 480 rpm or 500 rpm, and the heating temperature can be 60℃, 61℃, 62℃, 63℃, 64℃, 65℃, 66℃, 67℃. Add disodium ethylenediaminetetraacetate, xylitol, erythritol, and glycerol to the mixing tank at ℃, 68℃, 69℃, or 70℃, and continue stirring and heating for 30-40 minutes until completely dissolved to obtain the intermediate solution. For example, the time may be 30 minutes, 31 minutes, 32 minutes, 33 minutes, 34 minutes, 35 minutes, 36 minutes, 37 minutes, 38 minutes, 39 minutes, or 40 minutes, but it is not limited to the listed values. Other unlisted values ​​within this range are also applicable.

[0060] As a preferred technical solution of the present invention, in step (2), under the conditions of a stirring speed of 200~300 rpm and room temperature, for example, 200 rpm, 210 rpm, 220 rpm, 230 rpm, 240 rpm, 250 rpm, 260 rpm, 270 rpm, 280 rpm, 290 rpm or 300 rpm, lactoferrin, thymol inclusion complex, garlic extract inclusion complex, propolis extract, potassium sorbate and menthol are added sequentially to the mixing tank. After each component is added, the mixture is stirred for 5~10 minutes before adding the next component. For example, it can be... Stirring can be performed for 5.0 min, 5.5 min, 6.0 min, 6.5 min, 7.0 min, 7.5 min, 8.0 min, 8.5 min, 9.0 min, 9.5 min, or 10.0 min. After all components have been added, continue stirring for 20 to 30 min, for example, 20 min, 21 min, 22 min, 23 min, 24 min, 25 min, 26 min, 27 min, 28 min, 29 min, or 30 min. However, it is not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0061] In some optional instances, the pressure of the high-pressure homogenization is 30 to 40 MPa, for example, it can be 30 MPa, 31 MPa, 32 MPa, 33 MPa, 34 MPa, 35 MPa, 36 MPa, 37 MPa, 38 MPa, 39 MPa or 40 MPa, but is not limited to the listed values, other unlisted values ​​within this range are also applicable.

[0062] In some optional instances, the high-pressure homogenization is performed 2 to 3 times.

[0063] In some optional instances, a pH adjuster is added to the composite emulsion to adjust its pH value to 6-7, for example, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9 or 7.0, but not limited to the listed values, other unlisted values ​​within this range are also applicable.

[0064] Compared with the prior art, the beneficial effects of the present invention are as follows: The oral care composition provided by this invention, through a rational formulation of multiple components, can effectively inhibit Helicobacter pylori in the oral cavity, thereby reducing halitosis and the risk of gastric reinfection. Xylitol and erythritol interfere with bacterial metabolism, lactoferrin inhibits bacterial growth by depriving the body of iron ions, and disodium EDTA disrupts bacterial cell membranes by chelating metal ions, thus enhancing the penetration of other antibacterial ingredients. Furthermore, this invention effectively solves the problems of chemical instability, poor water solubility, noticeable odor, and irritation to the oral mucosa that exist when thymol and garlic extract are used directly by encapsulating them with β-cyclodextrin. Encapsulation not only improves the stability and bioavailability of the active ingredients but also enables slow release and prolongs the duration of action. Attached Figure Description

[0065] Figure 1 Optical micrographs of Helicobacter pylori in the blank control group (without oral care composition) and the experimental group (with oral care composition). Detailed Implementation

[0066] The technical solutions of the present invention will be described in detail below with reference to specific embodiments and accompanying drawings. The embodiments described herein are specific implementations of the present invention, used to illustrate the concept of the present invention; these descriptions are explanatory and exemplary, and should not be construed as limiting the implementation methods or the scope of protection of the present invention. In addition to the embodiments described herein, those skilled in the art can employ other obvious technical solutions based on the content disclosed in the claims and specification of this application. These technical solutions include those that make any obvious substitutions and modifications to the embodiments described herein.

[0067] Example 1 This embodiment provides an oral care composition for inhibiting Helicobacter pylori. Based on 100 parts by weight of the oral care composition, it comprises the following components in parts by weight: 5 parts glycerin; 4 parts xylitol; 5 parts erythritol; 0.3 parts of thymol inclusion complex; 1.5 parts of garlic extract inclusion complex; 2 parts propolis extract; Lactoferrin 0.5 parts; 0.1 parts of disodium ethylenediaminetetraacetate; 0.1 part menthol; 0.1 parts potassium sorbate; The remainder is purified water.

[0068] This embodiment also provides a method for preparing the above-mentioned oral care composition for inhibiting Helicobacter pylori, the preparation method specifically including the following steps: (1) Dissolve β-cyclodextrin in hot water at 50°C, mix and heat at 50°C for 40 min to obtain a cyclodextrin solution with a β-cyclodextrin mass fraction of 10 wt%; heat thymol at 50°C for 10 min to obtain a thymol melt; add the thymol melt to the cyclodextrin solution at a stirring speed of 300 rpm and a heating temperature of 50°C at a rate of 1 mL / min, with a mass ratio of thymol melt to β-cyclodextrin in the cyclodextrin solution of 1:4. After all the thymol melt is added, continue stirring and heating for 4 h to obtain a thymol inclusion solution; place the thymol inclusion solution in a low temperature environment of 3°C for 12 h, then filter to obtain the inclusion complex, wash the inclusion complex with purified water at 3°C, and then dry at 40°C for 8 h to obtain the thymol inclusion complex; (2) Dissolve β-cyclodextrin in hot water at 50°C, mix and heat at 50°C for 40 min to obtain a cyclodextrin solution with a β-cyclodextrin mass fraction of 10 wt%; mix garlic extract and anhydrous ethanol at a mass ratio of 1:1 to obtain a garlic extract solution; add garlic extract solution dropwise to cyclodextrin solution at a stirring speed of 10000 rpm and a heating temperature of 30°C at a rate of 1 mL / min, with a mass ratio of garlic extract to β-cyclodextrin in the cyclodextrin solution of 1:3. After all the solution is added, reduce the stirring speed to 200 rpm and heat at 30°C for 3 h to obtain a garlic extract inclusion solution; place the garlic extract inclusion solution in a low temperature environment of 3°C and let it stand for 12 h, then filter it to obtain the inclusion complex, wash the inclusion complex with purified water at 3°C, and then dry it at 40°C for 8 h to obtain the garlic extract inclusion complex. (3) At a stirring speed of 300 rpm and a heating temperature of 60°C, disodium EDTA, xylitol, erythritol and glycerol were added to the mixing tank and stirred and heated for 40 min until completely dissolved to obtain an intermediate solution. After the intermediate solution cooled to room temperature, lactoferrin, thymol inclusion complex, garlic extract inclusion complex, propolis extract, potassium sorbate and menthol were added to the mixing tank in sequence at a stirring speed of 200 rpm and room temperature. After each component was added, the mixture was stirred for 10 min and then the next component was added. After all components were added, the mixture was stirred for another 30 min. Then it was sent to a homogenizer and homogenized three times under a pressure of 30 MPa to obtain a composite emulsion. 1 wt% citric acid solution or 1 wt% sodium hydroxide solution was added to the composite emulsion to adjust its pH value to 6 to obtain the oral care composition.

[0069] Example 2 This embodiment provides an oral care composition for inhibiting Helicobacter pylori. Based on 100 parts by weight of the oral care composition, it comprises the following components in parts by weight: 6 parts glycerin; 4.5 parts xylitol; Erythritol 3.5 parts; 0.3 parts of thymol inclusion complex; One part of garlic extract inclusion complex; 2 parts propolis extract; Lactoferrin 0.5 parts; 0.3 parts of disodium ethylenediaminetetraacetate; 0.3 parts menthol; Potassium sorbate 0.2 parts; The remainder is purified water.

[0070] This embodiment also provides a method for preparing the above-mentioned oral care composition for inhibiting Helicobacter pylori, the preparation method specifically including the following steps: (1) Dissolve β-cyclodextrin in hot water at 52℃, mix and heat at 52℃ for 38 min to obtain cyclodextrin solution, the mass fraction of β-cyclodextrin in cyclodextrin solution is 11wt%; heat thymol at 52℃ for 8 min to obtain thymol melt; at a stirring speed of 350 rpm and a heating temperature of 52℃, add thymol melt dropwise to cyclodextrin solution at a rate of 1.5 mL / min, the mass ratio of thymol melt to β-cyclodextrin in cyclodextrin solution is 1:4.5, after all the thymol is added, continue stirring and heating for 3.5 h to obtain thymol inclusion solution; place thymol inclusion solution in a low temperature environment of 3.5℃ for 15 h, then filter to obtain inclusion complex, wash the inclusion complex with purified water at 3.5℃, and then dry at 42℃ for 7 h to obtain thymol inclusion complex; (2) Dissolve β-cyclodextrin in hot water at 52℃, mix and heat at 52℃ for 38 min to obtain cyclodextrin solution, the mass fraction of β-cyclodextrin in cyclodextrin solution is 11wt%; mix garlic extract and anhydrous ethanol at a mass ratio of 1:1 to obtain garlic extract solution; at a stirring speed of 10500 rpm and a heating temperature of 32℃, add garlic extract solution dropwise to cyclodextrin solution at a rate of 1.5 mL / min, the mass ratio of garlic extract in garlic extract solution to β-cyclodextrin in cyclodextrin solution is 1:3.5. After all the solution is added, reduce the stirring speed to 250 rpm and heat at 32℃ for 2.8 h to obtain garlic extract inclusion solution; place garlic extract inclusion solution in a low temperature environment of 3.5℃ for 15 h, then filter to obtain inclusion complex, wash the inclusion complex with purified water at 3.5℃, and then dry at 42℃ for 7 h to obtain garlic extract inclusion complex; (3) At a stirring speed of 350 rpm and a heating temperature of 62°C, disodium EDTA, xylitol, erythritol and glycerol were added to the mixing tank and stirred and heated for 38 min until completely dissolved to obtain an intermediate solution. After the intermediate solution cooled to room temperature, lactoferrin, thymol inclusion complex, garlic extract inclusion complex, propolis extract, potassium sorbate and menthol were added to the mixing tank in sequence at a stirring speed of 220 rpm and room temperature. Each component was stirred for 8 min after addition and then the next component was added. After all components were added, stirring was continued for 28 min. Then the mixture was sent to a homogenizer and homogenized three times under a pressure of 32 MPa to obtain a composite emulsion. 1 wt% citric acid solution or 1 wt% sodium hydroxide solution was added to the composite emulsion to adjust its pH value to 6.2 to obtain the oral care composition.

[0071] Example 3 This embodiment provides an oral care composition for inhibiting Helicobacter pylori. Based on 100 parts by weight of the oral care composition, it comprises the following components in parts by weight: 7 parts glycerin; 4 parts xylitol; 4 parts erythritol; 0.15 parts of thymol inclusion complex; 1.2 parts of garlic extract inclusion complex; 1.5 parts of propolis extract; Lactoferrin 0.3 parts; 0.2 parts of disodium ethylenediaminetetraacetate; 0.1 part menthol; Potassium sorbate 0.15 parts; The remainder is purified water.

[0072] This embodiment also provides a method for preparing the above-mentioned oral care composition for inhibiting Helicobacter pylori, the preparation method specifically including the following steps: (1) Dissolve β-cyclodextrin in hot water at 55°C, mix and heat at 55°C for 35 min to obtain a cyclodextrin solution with a β-cyclodextrin mass fraction of 12 wt%; heat thymol at 55°C for 7 min to obtain a thymol melt; add the thymol melt to the cyclodextrin solution at a stirring speed of 400 rpm and a heating temperature of 55°C at a rate of 2 mL / min, with a mass ratio of thymol melt to β-cyclodextrin in the cyclodextrin solution of 1:5. After all the thymol melt is added, continue stirring and heating for 3 h to obtain a thymol inclusion solution; place the thymol inclusion solution in a low temperature environment of 4°C for 18 h, then filter to obtain the inclusion complex, wash the inclusion complex with purified water at 4°C, and then dry at 45°C for 6 h to obtain the thymol inclusion complex; (2) Dissolve β-cyclodextrin in hot water at 55°C, mix and heat at 55°C for 35 min to obtain a cyclodextrin solution with a β-cyclodextrin mass fraction of 12 wt%; mix garlic extract and anhydrous ethanol at a mass ratio of 1:1 to obtain a garlic extract solution; add garlic extract solution dropwise to cyclodextrin solution at a stirring speed of 11000 rpm and a heating temperature of 35°C at a rate of 2 mL / min, with a mass ratio of garlic extract to β-cyclodextrin in the cyclodextrin solution of 1:4. After all the solution is added, reduce the stirring speed to 300 rpm and heat at 35°C for 2.5 h to obtain a garlic extract inclusion solution; place the garlic extract inclusion solution in a low temperature environment of 4°C for 18 h, then filter to obtain the inclusion complex, wash the inclusion complex with purified water at 4°C, and then dry at 45°C for 6 h to obtain the garlic extract inclusion complex. (3) At a stirring speed of 400 rpm and a heating temperature of 65°C, disodium EDTA, xylitol, erythritol and glycerol were added to the mixing tank and stirred and heated for 35 min until completely dissolved to obtain an intermediate solution. After the intermediate solution cooled to room temperature, lactoferrin, thymol inclusion complex, garlic extract inclusion complex, propolis extract, potassium sorbate and menthol were added to the mixing tank in sequence at a stirring speed of 250 rpm and room temperature. Each component was stirred for 7 min after addition and then the next component was added. After all components were added, stirring was continued for 25 min. Then the mixture was sent to a homogenizer and homogenized twice under high pressure of 35 MPa to obtain a composite emulsion. 1 wt% citric acid solution or 1 wt% sodium hydroxide solution was added to the composite emulsion to adjust its pH value to 6.5 to obtain the oral care composition.

[0073] Example 4 This embodiment provides an oral care composition for inhibiting Helicobacter pylori. Based on 100 parts by weight of the oral care composition, it comprises the following components in parts by weight: 8 parts glycerin; 3.5 parts xylitol; Erythritol 4.5 parts; 0.2 parts of thymol inclusion complex; 0.8 parts of garlic extract inclusion complex; 1 part propolis extract; Lactoferrin 0.3 parts; 0.1 parts of disodium ethylenediaminetetraacetate; 0.1 part menthol; 0.1 parts potassium sorbate; The remainder is purified water.

[0074] This embodiment also provides a method for preparing the above-mentioned oral care composition for inhibiting Helicobacter pylori, the preparation method specifically including the following steps: (1) Dissolve β-cyclodextrin in hot water at 58°C, mix and heat at 58°C for 32 min to obtain a cyclodextrin solution with a β-cyclodextrin mass fraction of 13 wt%; heat thymol at 58°C for 6 min to obtain a thymol melt; add the thymol melt to the cyclodextrin solution at a stirring speed of 450 rpm and a heating temperature of 58°C at a rate of 2.5 mL / min, with a mass ratio of thymol melt to β-cyclodextrin in the cyclodextrin solution of 1:5.5. After all the thymol melt is added, continue stirring and heating for 2.5 h to obtain a thymol inclusion solution; place the thymol inclusion solution in a low temperature environment of 4.5°C for 21 h, then filter to obtain the inclusion complex, wash the inclusion complex with purified water at 4.5°C, and then dry at 48°C for 5 h to obtain the thymol inclusion complex; (2) Dissolve β-cyclodextrin in hot water at 58°C, mix and heat at 58°C for 32 min to obtain a cyclodextrin solution with a β-cyclodextrin mass fraction of 13 wt%; mix garlic extract and anhydrous ethanol at a mass ratio of 1:1 to obtain a garlic extract solution; add garlic extract solution dropwise to cyclodextrin solution at a stirring speed of 11500 rpm and a heating temperature of 38°C at a rate of 2.5 mL / min, with a mass ratio of garlic extract to β-cyclodextrin in the cyclodextrin solution of 1:4.5. After all the solution is added, reduce the stirring speed to 350 rpm and heat at 38°C for 2.2 h to obtain a garlic extract inclusion solution; place the garlic extract inclusion solution in a low temperature environment of 4.5°C and let it stand for 21 h, then filter to obtain the inclusion complex, wash the inclusion complex with purified water at 4.5°C, and then dry it at 48°C for 5 h to obtain the garlic extract inclusion complex; (3) At a stirring speed of 450 rpm and a heating temperature of 68°C, disodium EDTA, xylitol, erythritol and glycerol were added to the mixing tank and stirred and heated for 32 min until completely dissolved to obtain an intermediate solution. After the intermediate solution cooled to room temperature, lactoferrin, thymol inclusion complex, garlic extract inclusion complex, propolis extract, potassium sorbate and menthol were added to the mixing tank in sequence at a stirring speed of 280 rpm and room temperature. Each component was stirred for 6 min after addition and then the next component was added. After all components were added, stirring was continued for 22 min. Then the mixture was sent to a homogenizer and homogenized twice under high pressure of 38 MPa to obtain a composite emulsion. 1 wt% citric acid solution or 1 wt% sodium hydroxide solution was added to the composite emulsion to adjust its pH value to 6.8 to obtain the oral care composition.

[0075] Example 5 This embodiment provides an oral care composition for inhibiting Helicobacter pylori. Based on 100 parts by weight of the oral care composition, it comprises the following components in parts by weight: 10 parts glycerin; 3 parts xylitol; Erythritol 3 parts; 0.1 part of thymol inclusion complex; 0.5 parts of garlic extract inclusion complex; 1 part propolis extract; Lactoferrin 0.4 parts; 0.2 parts of disodium ethylenediaminetetraacetate; 0.2 parts menthol; Potassium sorbate 0.2 parts; The remainder is purified water.

[0076] This embodiment also provides a method for preparing the above-mentioned oral care composition for inhibiting Helicobacter pylori, the preparation method specifically including the following steps: (1) Dissolve β-cyclodextrin in hot water at 60°C, mix and heat at 60°C for 30 min to obtain a cyclodextrin solution, the mass fraction of β-cyclodextrin in the cyclodextrin solution is 15 wt%; heat thymol at 60°C for 5 min to obtain thymol melt; at a stirring speed of 500 rpm and a heating temperature of 60°C, add thymol melt dropwise to the cyclodextrin solution at a rate of 3 mL / min, the mass ratio of thymol melt to β-cyclodextrin in the cyclodextrin solution is 1:6, after all the melt is added, continue stirring and heating for 2 h to obtain a thymol inclusion solution; place the thymol inclusion solution in a low temperature environment of 5°C for 24 h, then filter to obtain the inclusion complex, wash the inclusion complex with purified water at 5°C, and then dry at 50°C for 4 h to obtain the thymol inclusion complex; (2) Dissolve β-cyclodextrin in hot water at 60°C, mix and heat at 60°C for 30 min to obtain a cyclodextrin solution with a β-cyclodextrin mass fraction of 15 wt%; mix garlic extract and anhydrous ethanol at a mass ratio of 1:1 to obtain a garlic extract solution; add garlic extract solution dropwise to cyclodextrin solution at a stirring speed of 12000 rpm and a heating temperature of 40°C at a rate of 3 mL / min, with a mass ratio of garlic extract to β-cyclodextrin in the cyclodextrin solution of 1:5. After all the solution is added, reduce the stirring speed to 400 rpm and heat at 40°C for 2 h to obtain a garlic extract inclusion solution; place the garlic extract inclusion solution in a low temperature environment of 5°C for 24 h, then filter to obtain the inclusion complex, wash the inclusion complex with purified water at 5°C, and then dry at 50°C for 4 h to obtain the garlic extract inclusion complex. (3) At a stirring speed of 500 rpm and a heating temperature of 70°C, disodium EDTA, xylitol, erythritol and glycerol were added to the mixing tank and stirred and heated for 30 min until completely dissolved to obtain an intermediate solution. After the intermediate solution cooled to room temperature, lactoferrin, thymol inclusion complex, garlic extract inclusion complex, propolis extract, potassium sorbate and menthol were added to the mixing tank in sequence at a stirring speed of 300 rpm and room temperature. Each component was stirred for 5 min after addition and then the next component was added. After all components were added, stirring was continued for 20 min. Then the mixture was sent to a homogenizer and homogenized twice under high pressure of 40 MPa to obtain a composite emulsion. 1 wt% citric acid solution or 1 wt% sodium hydroxide solution was added to the composite emulsion to adjust its pH value to 7 to obtain the oral care composition.

[0077] Example 6 This embodiment provides an oral care composition for inhibiting Helicobacter pylori. The difference from Example 1 is that the amount of thymol inclusion complex added is adjusted to 0.05 parts, while the other components and their amounts are exactly the same as in Example 1. The remaining amount is made up to 100 parts by deionized water.

[0078] Example 7 This embodiment provides an oral care composition for inhibiting Helicobacter pylori. The difference from Example 1 is that the amount of thymol inclusion complex added is adjusted to 0.5 parts, while the other components and their amounts are exactly the same as in Example 1. The remaining amount is made up to 100 parts by deionized water.

[0079] Example 8 This embodiment provides an oral care composition for inhibiting Helicobacter pylori. The difference from Example 1 is that the amount of garlic extract inclusion complex added is adjusted to 0.1 parts, while the other components and their amounts are exactly the same as in Example 1. The remaining amount is made up to 100 parts by deionized water.

[0080] Example 9 This embodiment provides an oral care composition for inhibiting Helicobacter pylori. The difference from Example 1 is that the amount of garlic extract inclusion complex added is adjusted to 2 parts, while the other components and their amounts are exactly the same as in Example 1. The remaining amount is made up to 100 parts by deionized water.

[0081] Example 10 This embodiment provides an oral care composition for inhibiting Helicobacter pylori. The difference from Example 1 is that the amount of propolis extract added is adjusted to 0.5 parts, while the other components and their amounts are exactly the same as in Example 1. The remaining amount is made up to 100 parts by deionized water.

[0082] Example 11 This embodiment provides an oral care composition for inhibiting Helicobacter pylori. The difference from Example 1 is that the amount of propolis extract added is adjusted to 3 parts, while the other components and their amounts are exactly the same as in Example 1. The remaining amount is made up to 100 parts by deionized water.

[0083] Example 12 This embodiment provides an oral care composition for inhibiting Helicobacter pylori. The difference from Example 1 is that the amount of lactoferrin added is adjusted to 0.1 parts, while the other components and their amounts are exactly the same as in Example 1. The remaining amount is made up to 100 parts by deionized water.

[0084] Example 13 This embodiment provides an oral care composition for inhibiting Helicobacter pylori. The difference from Example 1 is that the amount of lactoferrin added is adjusted to 1 part, while the other components and their amounts are exactly the same as in Example 1. The remaining amount is made up to 100 parts by deionized water.

[0085] Example 14 This embodiment provides an oral care composition for inhibiting Helicobacter pylori. The difference from Example 1 is that the amount of disodium EDTA added is adjusted to 0.05 parts, while the other components and their amounts are exactly the same as in Example 1. The remaining amount is made up to 100 parts by deionized water.

[0086] Example 15 This embodiment provides an oral care composition for inhibiting Helicobacter pylori. The difference from Example 1 is that the amount of disodium EDTA added is adjusted to 0.5 parts, while the other components and their amounts are exactly the same as in Example 1. The remaining amount is made up to 100 parts by deionized water.

[0087] Comparative Example 1 This comparative example provides an oral care composition for inhibiting Helicobacter pylori. The difference from Example 1 is that the thymol inclusion complex is omitted, while the other components and their amounts are exactly the same as in Example 1. The remaining amount is made up to 100 parts by deionized water.

[0088] Comparative Example 2 This comparative example provides an oral care composition for inhibiting Helicobacter pylori. The difference from Example 1 is that the garlic extract inclusion complex is omitted, while the other components and their amounts are exactly the same as in Example 1. The remaining amount is made up to 100 parts by deionized water.

[0089] Comparative Example 3 This comparative example provides an oral care composition for inhibiting Helicobacter pylori. The difference from Example 1 is that the propolis extract is omitted, while the other components and their amounts are exactly the same as in Example 1, with the remainder made up to 100 parts by deionized water.

[0090] Comparative Example 4 This comparative example provides an oral care composition for inhibiting Helicobacter pylori. The difference from Example 1 is that lactoferrin is omitted, while the other components and their amounts are exactly the same as in Example 1. The remaining amount is made up to 100 parts by deionized water.

[0091] Comparative Example 5 This comparative example provides an oral care composition for inhibiting Helicobacter pylori. The difference from Example 1 is that disodium EDTA is omitted, while the other components and their amounts are exactly the same as in Example 1. The remaining amount is made up to 100 parts by deionized water.

[0092] Application examples The oral care composition provided by this invention can be used as a mouthwash for daily care. Its usage is similar to that of regular mouthwash, and the method of use is as follows: Take 10-15 ml of this product each time, after brushing your teeth in the morning and evening, or when you need fresh breath. Hold the product in your mouth, close your lips tightly, and move your cheeks and lips to allow the oral care composition to fully contact the teeth, gums, and all mucous membrane surfaces in your mouth. Rinse all parts of your mouth repeatedly with water for 30 seconds to 1 minute. Spit it out after use. There is no need to rinse your mouth with water again to retain the continuous effect of the active ingredients in the mouth. It is recommended to use it twice a day (once in the morning and once in the evening) and continue to use it.

[0093] The properties of the oral care compositions provided in Examples 1-15 and Comparative Examples 1-5 were tested, and the specific test steps are as follows: (1) Minimum inhibitory concentration and inhibition rate of Helicobacter pylori Prepare 10 sterile test tubes. Add 1.8 mL of Brucella broth to tube 1. Add 1 mL of Brucella broth to each of tubes 2 through 10. Add 0.2 mL of the oral care composition sample to tube 1 and mix well. Tube 1 is now a 1:10 dilution. Add 1 mL of the liquid from tube 1 to tube 2 and mix well. Tube 2 is now a 1:20 dilution. Continue this serial dilution up to tube 9. Discard 1 mL of the liquid from tube 9, ensuring all tubes have a final volume of 1 mL. The dilution factors for tubes 1 through 9 are 10, 20, 40, 80, 160, 320, 640, 1280, and 2560, respectively. Tube 10 is a blank control containing only Brucella broth and no oral care composition sample.

[0094] The standard strain of Helicobacter pylori (ATCC 43504) was streaked onto Brucella blood agar plates and incubated at 37°C for 3-5 days under microaerophilic conditions (85% N2, 10% CO2, 5% O2) until distinct colonies formed. Fresh colonies were scraped off, suspended in Brucella broth, and the bacterial concentration was adjusted to approximately 0.5 McFarland turbidity standard. This bacterial suspension was further diluted 100-fold with Brucella broth to prepare a concentration of approximately 1.5 × 10⁻⁶. 6 Working bacterial solution at CFU / mL.

[0095] Add 0.1 mL of the prepared working bacterial solution to each of the diluted test tubes (tubes 1 to 10), mix well, and place all test tubes in a microaerophilic flask. Incubate at 37°C for 72 hours under microaerophilic conditions (85% N2, 10% CO2, 5% O2). After incubation, visually observe the turbidity of each test tube. The blank control tube (tube 10) is significantly turbid, indicating normal bacterial growth. The concentration of the oral care composition sample in tubes 1 to 9 gradually decreases, and the corresponding turbidity gradually increases. Find the first test tube that becomes clear from tubes 1 to 9; the dilution factor of this test tube is D. Calculate the minimum inhibitory concentration (μg / mL) of Helicobacter pylori using the following formula: Minimum inhibitory concentration (μg / mL) = C / D Wherein, C is the baseline concentration of the oral care composition sample stock solution, set at 1000 μg / mL.

[0096] The first turbid test tube adjacent to the MIC tube was used as the experimental group, and the 10th tube as the blank control group. A certain amount of bacterial suspension was taken from each tube, serially diluted, and then spread onto Brucella blood agar plates. After incubation, the number of colonies on each plate was counted, and the original bacterial concentration was calculated. These concentrations represent the CFU in the experimental group and the CFU in the blank control group. The inhibition rate (%) was calculated using the following formula: Antibacterial rate (%) = [(CFU of blank control group - CFU of experimental group) / average CFU of blank control group] × 100%.

[0097] The microstructure of Helicobacter pylori in the blank control group and the experimental group was observed using an optical microscope, such as... Figure 1 As shown in the figure, in the blank control group, Helicobacter pylori exhibits a complete and clear typical spiral structure, indicating that it is in a normal active state. In the experimental group, after treatment with the oral care composition provided in Example 1 of this invention, the bacterial morphology underwent a fundamental change. The bacteria swelled and became enlarged, the original spiral structure disappeared, becoming rounded or even ruptured, and the internal structure of some bacteria became blurred, showing signs of dissolution and death. This indicates that the oral care composition provided by this invention can effectively destroy the cell structure of Helicobacter pylori, thereby causing its death or loss of normal function.

[0098] (2) Turesky Plaque Index This randomized, double-blind, controlled clinical trial recruited eligible participants (adults with plaque problems). Before the trial began, all participants underwent professional teeth cleaning by a dentist to ensure an initial plaque level of zero. Subsequently, participants used the product twice daily for eight weeks, following the instructions provided in the application guide.

[0099] After the experiment, the plaque on individual tooth surfaces of the subjects was scored using the Quigley-Hein modified Turesky plaque index to obtain the Turesky plaque index.

[0100] The test data is shown in Table 1.

[0101] Table 1

[0102] As can be seen from the test data provided in Table 1, the content and synergistic effect of each component have a crucial impact on the efficacy of the oral care composition in inhibiting Helicobacter pylori and controlling dental plaque. Key components such as thymol, garlic extract, propolis extract, lactoferrin, and disodium EDTA, when used within the dosage range specified in this invention, can produce synergistic effects through multiple mechanisms, including disrupting bacterial cell membranes, chelating iron ions, and interfering with metabolism. The complete absence of any component leads to a significant decrease in antibacterial performance.

[0103] The applicant declares that the above description is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention fall within the protection and disclosure scope of the present invention.

Claims

1. An oral care composition for inhibiting Helicobacter pylori, characterized in that, The oral care composition comprises glycerin, xylitol, erythritol, thymol inclusion compound, garlic extract inclusion compound, propolis extract, lactoferrin, disodium ethylenediaminetetraacetate, menthol, potassium sorbate and purified water; The thymol inclusion compound is obtained by inclusion of thymol by β-cyclodextrin; The garlic extract inclusion compound is obtained by inclusion of garlic extract by β-cyclodextrin.

2. The oral care composition of claim 1, wherein, The oral care composition comprises the following components by weight parts, taking 100 parts of the oral care composition as 100 parts: Glycerin 5-10 parts; Xylitol 3-5 parts; Erythritol 3-5 parts; Thymol inclusion compound 0.1-0.3 parts; Garlic extract inclusion compound 0.5-1.5 parts; Propolis extract 1-2 parts; Lactoferrin 0.3-0.5 parts; Disodium ethylenediaminetetraacetate 0.1-0.3 parts; Menthol 0.1-0.3 parts; Potassium sorbate 0.1-0.2 parts; The balance is purified water.

3. A method of preparing an oral care composition for inhibiting H. pylori according to claim 1 or 2, characterized in that, The preparation method comprises: (I) Inclusion of thymol by β-cyclodextrin to obtain thymol inclusion compound; Inclusion of garlic extract by β-cyclodextrin to obtain garlic extract inclusion compound; (II) Mixing glycerin, xylitol, erythritol, thymol inclusion compound, garlic extract inclusion compound, propolis extract, lactoferrin, disodium ethylenediaminetetraacetate, menthol, potassium sorbate and purified water uniformly to obtain the oral care composition.

4. The production method according to claim 3, characterized by, In step (I), the thymol inclusion compound is prepared by the following method: Dissolve β-cyclodextrin in hot water, mix and stir to heat to obtain a cyclodextrin solution; Heat and melt thymol to obtain a thymol melt solution; Under the conditions of stirring and heating, drop the thymol melt solution into the cyclodextrin solution, continue to stir and heat after all the thymol melt solution is dropped, to obtain a thymol inclusion solution; Cool and crystallize the thymol inclusion solution in a low temperature environment, then filter to obtain an inclusion compound, wash and dry the inclusion compound to obtain the thymol inclusion compound.

5. The preparation method according to claim 4, characterized in that, Dissolve β-cyclodextrin in hot water at 50-60°C, mix and stir to heat at 50-60°C for 30-40 min to obtain the cyclodextrin solution; The mass fraction of β-cyclodextrin in the cyclodextrin solution is 10-15 wt%; The heating and melting temperature of thymol is 50-60°C; The heating and melting time of thymol is 5-10 min; Drop the thymol melt solution into the cyclodextrin solution at a stirring speed of 300-500 rpm and a heating temperature of 50-60°C, continue to stir and heat for 2-4 h after all the thymol melt solution is dropped to obtain a thymol inclusion solution; The dropping speed of the thymol melt solution is 1-3 mL / min; The mass ratio of the thymol melt solution to β-cyclodextrin in the cyclodextrin solution is 1:(4-6); The cooling and crystallization temperature of the thymol inclusion solution is 3-5°C; The cooling and crystallization time of the thymol inclusion solution is 12-24 h; Wash the inclusion compound with purified water at 3-5°C; The drying temperature of the inclusion compound is 40-50°C; The drying time of the inclusion compound is 4-8 h.

6. The preparation method according to claim 3, characterized in that, In step (I), the garlic extract inclusion compound is prepared by the following method: Dissolve β-cyclodextrin in hot water, mix and stir to heat, and obtain a cyclodextrin solution; uniformly mix garlic extract and anhydrous ethanol to obtain a garlic extract solution; Under the conditions of heating and high-speed stirring, drop the garlic extract solution into the cyclodextrin solution, continue to stir and heat after all is dropped, and obtain a garlic extract inclusion solution; Place the garlic extract inclusion solution in a low-temperature environment to cool and crystallize, then filter to obtain an inclusion compound, wash and dry the inclusion compound, and obtain the garlic extract inclusion compound.

7. The preparation method according to claim 6, characterized in that, Dissolve β-cyclodextrin in hot water at 50-60°C, mix and stir to heat at 50-60°C for 30-40 min, and obtain the cyclodextrin solution; The mass fraction of β-cyclodextrin in the cyclodextrin solution is 10-15 wt%; Under the conditions of a heating temperature of 30-40°C and a stirring speed of 10,000-12,000 rpm, drop the garlic extract solution into the cyclodextrin solution, reduce the stirring speed to 200-400 rpm after all is dropped, and continue to stir and heat at a heating temperature of 30-40°C for 2-3 h to obtain the garlic extract inclusion solution; The dropping speed of the garlic extract solution is 1-3 mL / min; The mass ratio of garlic extract in the garlic extract solution to β-cyclodextrin in the cyclodextrin solution is 1:(3-5); The temperature for cooling and crystallization of the garlic extract inclusion solution is 3-5°C; The time for cooling and crystallization of the garlic extract inclusion solution is 12-24 h; Wash the inclusion compound with purified water at 3-5°C; The drying temperature of the inclusion compound is 40-50°C; The drying time of the inclusion compound is 4-8 h.

8. The preparation method according to claim 3, characterized in that, Step (II) specifically comprises the following steps: (1) Add purified water into a batching tank and stir to heat, under the conditions of stirring and high-temperature heating, add disodium ethylenediaminetetraacetate, xylitol, erythritol, and glycerol into the batching tank, continuously stir to heat until completely dissolved, and obtain an intermediate solution; (2) After the intermediate solution is cooled to room temperature, under the conditions of stirring and room temperature, sequentially add lactoferrin, thymol inclusion compound, garlic extract inclusion compound, propolis extract, potassium sorbate, and menthol into the batching tank, stir for a period of time after each component is added, then add the next component, continue to stir after all components are added, and then send into a homogenizer for high-pressure homogenization to obtain a composite emulsion; Add a pH adjuster to the composite emulsion to adjust the pH value, and obtain the oral care composition.

9. The production method according to claim 8, characterized by, In step (1), under the conditions of a stirring speed of 300-500 rpm and a heating temperature of 60-70°C, add disodium ethylenediaminetetraacetate, xylitol, erythritol, and glycerol into the batching tank, continuously stir to heat for 30-40 min until completely dissolved, and obtain the intermediate solution.

10. The method of claim 8, wherein, In step (2), the ingredients are sequentially added to the mixing tank under stirring at a speed of 200-300 rpm and room temperature, and after each ingredient is added, the mixture is stirred for 5-10 min before the next ingredient is added. After all the ingredients are added, the mixture is stirred for another 20-30 min; The pressure of the high-pressure homogenization is 30-40 MPa; The number of times of the high-pressure homogenization is 2-3 times; A pH regulator is added to the compound emulsion to adjust the pH value to 6-7.

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