Oral anti-inflammatory and chronic disease nursing method for inhibiting porphyromonas gingivalis

Through the combination of propolis microcapsule sustained-release system, zinc lactobacillus and lactoferrin-sodium hyaluronate, the bad breath and inflammation problems caused by Porphyromonas gingivalis are solved, multiple functions of oral health management and chronic disease prevention are achieved, and the quality of life of patients is significantly improved.

CN120605320AInactive Publication Date: 2025-09-09ZIYI (SHANGHAI) IND CO LTD
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Patent Information

Application Number
CN202510769721.7
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2025-06-10
Publication Date
2025-09-09
Estimated Expiration
Not applicable · inactive patent

AI Technical Summary

Technical Problem

Existing technologies have failed to effectively address the relationship between bad breath, inflammation, and chronic diseases caused by Porphyromonas gingivalis, and are unable to achieve multiple functions such as odor elimination, anti-inflammation, and tissue regeneration, resulting in insufficient attention to the relationship between oral health and chronic diseases.

Method used

A composition of propolis microcapsules, zinc lactobacillus, lactoferrin and sodium hyaluronate is used to neutralize volatile sulfur compounds through the propolis microcapsule sustained-release system. Zinc ions precisely chelate cystathionine β-lyase to inhibit HS production, lactoferrin blocks the NF-κB pathway, and sodium hyaluronate promotes epithelial cell migration and proliferation to form a protective film.

Benefits of technology

It achieves dual control of bad breath, significantly reduces the release of inflammatory factors, accelerates tissue repair, enhances chewing and language functions, improves social functions, and has potential value in chronic disease management.

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Abstract

The invention provides an oral cavity anti-inflammatory and chronic disease nursing method for inhibiting porphyromonas gingivalis, and relates to the technical field of oral cavity anti-inflammatory of porphyromonas gingivalis in stomatology, the oral cavity anti-inflammatory and chronic disease nursing method comprises propolis microcapsules, zinc lactein, lactoferrin, sodium hyaluronate and pharmaceutic adjuvants, the propolis microcapsules account for 5%, ethyl cellulose serves as a wrapping material of the propolis microcapsules, and the zinc lactein is added into the zinc lactein, the lactoferrin, the sodium hyaluronate and the pharmaceutic adjuvants. The zinc lactein sustained-release tablet is characterized in that artepillin C is slowly released inside the zinc lactein sustained-release tablet, the content of zinc lactein is 0.5%, zinc ions in the zinc lactein can precisely chelate an active center of cystathionine beta-lyase of Pg bacteria, the proportion of lactoferrin is 0.3%, the lactoferrin can specifically block combination of LPS and TLR4 of the Pg bacteria so as to inhibit activation of an NF-kB pathway, and the content of sodium hyaluronate is 0.5%. The problems that in the prior art, the correlation between oral health and chronic diseases is insufficiently emphasized, a scheme capable of treating the oral diseases and effectively predicting and intervening the chronic diseases cannot be developed, and then ozostomia cannot be fundamentally solved are solved.
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Description

Technical Field

[0001] The present invention relates to the technical field of oral anti-inflammatory of Porphyromonas gingivalis in oral medicine, and in particular to an oral anti-inflammatory and chronic disease nursing method for inhibiting Porphyromonas gingivalis. Background Art

[0002] Porphyromonas gingivalis (Pg), a key pathogenic factor in the oral microbiome, poses a multidimensional and systemic threat to human health. Within the oral environment, the metabolic activity of Pg is the primary source of malodor. It metabolizes volatile sulfur compounds (VSCs) such as hydrogen sulfide (HS), which have a pungent odor and cause bad breath, severely impacting patients' social experiences. From a physiological perspective, the lipopolysaccharide (LPS) produced by Pg is a key trigger for inflammatory responses. LPS activates the NF-κB pathway, triggering a series of cascades that lead to the release of inflammatory factors, disrupting the integrity of the oral mucosal barrier and making oral tissues more susceptible to invasion by external pathogens, leading to diseases such as periodontitis and oral ulcers. Furthermore, the harm posed by Pg extends to the social and psychological realm. Problems such as bad breath and dysphagia can significantly reduce patients' quality of life. Studies have shown that these patients often experience negative emotions such as low self-esteem and anxiety during social interactions, resulting in diminished social confidence and reduced life satisfaction. Crucially, numerous medical studies in recent years have found a close association between oral Pg bacteria infection and various systemic chronic diseases, such as cardiovascular disease and diabetes. Pg bacteria and their metabolites can enter the bloodstream through the oral mucosa, triggering systemic inflammatory responses and contributing to the development and progression of chronic diseases. This further highlights the importance of controlling Pg bacteria in maintaining overall health, a common practice in dentistry.

[0003] Prior art includes an invention with publication number CN110237251B, which discloses a composite specific egg yolk antibody oral spray and its preparation method. The patent comprises composite specific egg yolk antibodies against Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans, sorbitol, hydrogenated castor oil, sucralose, borneol, menthol, watermelon frost, and purified water. The oral spray of this invention has simple and safe ingredients, is non-toxic and non-irritating, contains no alcohol, and exhibits a strong antibacterial effect against the specific bacteria Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans. It can effectively inhibit biofilm formation, reduce the formation and development of dental plaque, and has a good preventive effect on gingivitis and periodontitis. The oral spray is simple and easy to prepare, has low production costs, and exhibits excellent product stability.

[0004] In oral medicine, it has been found that in terms of antibacterial ingredients, the functions of traditional single antibacterial ingredients are relatively limited. They can often only play a role in a certain link of bacterial growth, and cannot simultaneously achieve multiple functions such as odor elimination, anti-inflammation and tissue regeneration. It is difficult to meet the needs of comprehensive treatment of oral diseases. The balance of oral flora is an important basis for maintaining oral health. Imbalance of flora will lead to a decrease in the number of beneficial bacteria and excessive reproduction of harmful bacteria, thereby delaying the healing speed of wounds and may even cause new oral health conditions. Existing technologies do not pay enough attention to the relationship between oral health and chronic diseases, and have failed to develop solutions that can not only treat oral diseases but also effectively predict and intervene in chronic diseases, which in turn leads to the inability to fundamentally solve the problem of bad breath. Summary of the Invention

[0005] The purpose of the present invention is to address the shortcomings of the prior art, which is that the prior art does not pay enough attention to the relationship between oral health and chronic diseases, fails to develop solutions that can both treat oral diseases and effectively predict and intervene in chronic diseases, thereby resulting in the inability to fundamentally solve the problem of bad breath.

[0006] In order to achieve the above-mentioned purpose, the present invention adopts the following technical scheme: an oral anti-inflammatory and chronic disease care method for inhibiting Porphyromonas gingivalis, comprising propolis microcapsules, zinc lactic acid bacteria, lactoferrin, sodium hyaluronate and pharmaceutical excipients, wherein the propolis microcapsules account for 5%, and the propolis microcapsules are wrapped with ethyl cellulose and slowly release aspirin C inside. The zinc lactic acid bacteria content is 0.5%, and the zinc ions in the zinc lactic acid bacteria can accurately chelate the active center of Pg bacteria cystathionine β-lyase. The lactoferrin accounts for 0.3%, and lactoferrin can specifically block the binding of Pg bacteria LPS with TLR4, thereby inhibiting the activation of the NF-κB pathway. The sodium hyaluronate content is 0.5%, and sodium hyaluronate can activate CD44 receptors and promote epithelial cell migration and proliferation. The balance of the pharmaceutical excipient is hydroxypropyl methylcellulose, and as a film-forming matrix, it can form a uniform and tough protective film on the surface of the oral cavity.

[0007] Preferably, the ethyl cellulose wall thickness of the propolis microcapsules is 1.5-2.5 μm, and under oral pH triggering conditions, the release rate is ≥60% within 30 minutes.

[0008] Preferably, the preparation of the propolis microcapsules includes: an inclusion process and a release test. In the inclusion process, the propolis ethanol extract and ethyl cellulose are mixed in a ratio of core material:wall material = 1:3.

[0009] Preferably, the propolis microcapsule preparation and inclusion process includes: high-pressure homogenization emulsification and spray drying process, and the moisture content of the final product is ≤3%.

[0010] Preferably, the pressure range of the high-pressure homogenization emulsification is 14000-16000 psi.

[0011] Preferably, the inlet air temperature of the spray drying process is 175-185°C.

[0012] Preferably, the release test of the propolis microcapsule preparation includes: an in vitro release experiment and a verification of the neutralization effect of VSCs. The in vitro release experiment includes: simulation conditions and a detection method. The simulation conditions include: artificial saliva (pH = 5.5, containing 0.1% Tween 80); temperature: 37°C, oscillation rate 100 rpm; the detection method includes: timed sampling (5, 15, 30 minutes), HPLC analysis of the release amount of aspirin C (C18 chromatographic column, mobile phase acetonitrile-water = 60:40, detection wavelength 280 nm).

[0013] Preferably, the oral anti-inflammatory composition comprises: a propolis microcapsule sustained-release system, zinc lactobacillus synergistic antibacterial effect, and lactoferrin-sodium hyaluronate synergistic repair effect.

[0014] Preferably, the propolis microcapsule sustained-release system: uses ethyl cellulose to wrap propolis to form a microcapsule structure with a wall thickness of 2 μm; the zinc lactic acid bacteria synergistic antibacterial: the zinc ions in zinc lactic acid bacteria chelate with the CBL active center to block the key link of HS generation at the molecular level; the lactoferrin-sodium hyaluronate synergistic repair: lactoferrin reduces oral inflammatory response by inhibiting the expression of inflammatory factors, thereby creating a favorable microenvironment for oral tissue repair.

[0015] Preferably, the method for preparing the propolis microcapsules is as follows:

[0016] (1) First, extract the propolis ethanol extract to ensure that the purity of aspirin C is ≥90%;

[0017] (2) accurately weighing and mixing the propolis ethanol extract and ethyl cellulose in a ratio of core material to wall material = 1:3;

[0018] (3) Using high-pressure homogenization technology, the mixture forms a stable W / O emulsion under high pressure conditions of 15,000 psi. The high-pressure homogenization process can evenly disperse the core material in the wall material to form tiny droplets;

[0019] (4) The W / O emulsion was treated by a spray drying process with the inlet air temperature set at 180°C;

[0020] (5) During the spray drying process, the solvent in the emulsion evaporates rapidly, and ethyl cellulose forms a solid wall film on the surface of the propolis ethanol extract, ultimately obtaining propolis microcapsules with a particle size between 50 and 100 μm.

[0021] Compared with the prior art, the advantages and positive effects of the present invention are:

[0022] In the present invention, 1. Highly effective in neutralizing bad breath and precise in inhibiting bacteria

[0023] Propolis microcapsule sustained-release system:

[0024] pH-responsive release: Ethylcellulose microcapsules (wall thickness 2 μm) trigger release at oral pH = 5.5, with a cumulative release rate of 62% of aspirin C within 30 minutes (HPLC verification), accurately neutralizing volatile sulfur compounds (VSCs). Testing showed that the concentration of VSCs decreased by 63% (250 ppb → 93 ppb);

[0025] Antibacterial synergy: The binding energy of aspirin C in propolis and VSCs is ΔG = -7.2 kcal / mol (determined by XRD). The binding force is strong and synergistic with the anti-inflammatory properties of propolis itself to inhibit the growth of Pg bacteria.

[0026] Zinc lactic acid bacteria antibacterial mechanism:

[0027] Targeted binding of zinc ions: Molecular docking revealed that zinc ions bind to the active center of Pg bacterium cystathionine β-lyase (CBL) Inhibits HS generation rate ≥90% (GC-MS verified), eliminating bad breath from the source;

[0028] Microbial flora regulation: Lactobacillus promotes the colonization of beneficial bacteria and forms a dual antibacterial mechanism with zinc ions, significantly inhibiting the proliferation of Pg bacteria.

[0029] 2. Synergistic effect of anti-inflammation and tissue repair

[0030] Lactoferrin anti-inflammatory pathway blockade: Inhibition of the NF-κB pathway: Western blot showed that the level of p65 phosphorylation decreased by 82%, the secretion of the inflammatory factor IL-6 decreased by 70% (350→105pg / mL), and TNF-α decreased by 65%;

[0031] Antibacterial enhancement: Lactoferrin inhibits Pg bacteria by chelating iron ions and enhances the antibacterial effect of zinc lactobacillus.

[0032] Sodium hyaluronate promotes repair:

[0033] Accelerate epithelial regeneration: Scratch tests showed that the healing rate of oral epithelial cells increased from 30% to 75%. Western blot confirmed that Integrinβ1 expression was upregulated, promoting cell migration and adhesion.

[0034] Moisturizing and microenvironment optimization: Sodium hyaluronate maintains the moisture of the oral mucosa, synergizes with lactoferrin to inhibit inflammation, and creates favorable conditions for repair.

[0035] 3. Clinical efficacy is significantly better than traditional treatments

[0036] Bad breath control: treatment group The readings decreased by 63%, which was significantly better than the chlorhexidine control group (25%, p < 0.001);

[0037] Functional recovery: Chewing efficiency: The amount of peanut particles remaining was reduced from 35% to 8% (22% in the control group), improving oral mechanical function;

[0038] Speech clarity: Spectrogram analysis showed an improvement of 72% (31% in the control group), improving pronunciation disorders caused by inflammation.

[0039] Improvement of systemic inflammation: After long-term use, the patient's systemic inflammatory indicators (such as CRP, IL-6) decreased significantly, suggesting the management value of potential chronic diseases (such as cardiovascular disease, diabetes).

[0040] 4. Sustained-release system and process advantages

[0041] Precise controlled release and long-lasting effect: The propolis microcapsule sustained-release system prolongs the drug's duration of action (1-2 times a day) and increases bioavailability by 40%; the pharmaceutical excipient hydroxypropyl methylcellulose forms a film, prolongs the retention time of the ingredients and isolates them from external stimuli.

[0042] Process stability: high pressure homogenization (14000-16000psi) and spray drying (175-185℃) ensure uniform microcapsule particle size (50-100μm) and moisture ≤3%; double verification (HPLC release rate + Functional effect) ensures the consistency of process and efficacy.

[0043] First, odor source control: The composition of this invention achieves a 63% neutralization rate for VSCs and a 90% or higher inhibition rate for HS, effectively controlling the source of oral odor. Compared to existing technologies, this invention utilizes a synergistic effect of multiple ingredients to not only neutralize existing VSCs but also inhibit the formation of HS, achieving dual control of oral odor and fundamentally resolving the problem of bad breath.

[0044] Inflammation-Regeneration Synergy: In terms of inflammation suppression, it can inhibit NF-κB activity by 82%, significantly reducing the release of inflammatory factors and effectively alleviating oral inflammatory responses. In terms of tissue regeneration, it promotes a 45% increase in epithelial healing rate, accelerating the repair and regeneration of oral tissue. This invention achieves a synergistic effect of inflammation suppression and tissue regeneration, breaking the limitations of the single function of existing technologies and providing a more comprehensive and efficient solution for the treatment of oral diseases.

[0045] 3. Social Function Restoration: Clinical validation has shown that after using the composition of the present invention, patients' chewing efficiency increased by 4.4 times, and the speech clarity reached 92%. This demonstrates that the composition of the present invention can effectively improve patients' chewing and speech dysfunction caused by oral diseases, significantly enhance their social function, improve their quality of life, and enable them to participate in social activities with greater confidence.

[0046] IV. Potential for Chronic Disease Care: Since oral health is closely related to systemic chronic diseases, this invention provides a new approach for the prediction and management of chronic diseases by effectively inhibiting the pathogenicity of Pg bacteria, improving the oral microenvironment, and reducing systemic inflammatory responses. Clinical observations have shown improvements in systemic inflammatory markers in patients using the composition of this invention, suggesting its potential value in the prevention and adjunctive treatment of chronic diseases, and could provide beneficial assistance for the health management of patients with chronic diseases. DETAILED DESCRIPTION

[0047] In order to more clearly understand the above-mentioned objects, features and advantages of the present invention, the present invention is further described below in conjunction with the embodiments. It should be noted that, in the absence of conflict, the embodiments of the present application and the features therein can be combined with each other.

[0048] In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention may also be implemented in other ways than those described herein. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0049] Example 1. The present invention provides an oral anti-inflammatory and chronic disease care method for inhibiting Porphyromonas gingivalis, comprising propolis microcapsules, zinc lactic acid bacteria, lactoferrin, sodium hyaluronate and pharmaceutical excipients, wherein the propolis microcapsules account for 5%, and the propolis microcapsules are wrapped with ethyl cellulose, and the internal sustained-release aspirin C, the zinc lactic acid bacteria content is 0.5%, and the zinc ions in the zinc lactic acid bacteria can accurately chelate the active center of the Pg bacteria cystathionine β-lyase, the lactoferrin accounts for 0.3%, and lactoferrin can specifically block the binding of Pg bacteria LPS with TLR4, thereby inhibiting the activation of the NF-κB pathway, the sodium hyaluronate content is 0.5%, and sodium hyaluronate can activate the CD44 receptor and promote epithelial cell migration and proliferation. The balance of the pharmaceutical excipient is hydroxypropyl methylcellulose, and as a film-forming matrix, it can form a uniform and tough protective film on the surface of the oral cavity.

[0050] In propolis microcapsules, aspirin C specifically binds to VSCs. X-ray diffraction (XRD) analysis shows a binding energy of -7.2 kcal / mol. This strong binding force enables aspirin C to efficiently capture and neutralize VSCs, eliminating bad breath at its source. Furthermore, propolis itself possesses antibacterial and anti-inflammatory properties, which can synergize with other ingredients to inhibit the growth of Pg bacteria.

[0051] In zinc lactic acid bacteria, molecular docking analysis shows that its root mean square deviation This indicates a high degree of binding compatibility between zinc ions and the CBL active center. CBL is a key enzyme in the production of HS. Inhibiting its activity can achieve an HS production inhibition rate of ≥90% (measured by gas chromatography-mass spectrometry (GC-MS)), effectively reducing the production of oral odor substances. Furthermore, lactobacilli can regulate the balance of oral flora, promote the growth of beneficial bacteria, and enhance the stability of the oral microbiome.

[0052] Experimental tests have shown that the addition of lactoferrin reduced p65 phosphorylation levels by 82% (using Western blot technology), significantly reducing the release of inflammatory factors, such as IL-6 by 70% and TNF-α by 65%, effectively alleviating oral inflammation. Lactoferrin also has multiple biological activities, such as antibacterial and antiviral activities, which can enhance local oral immune defense capabilities.

[0053] In vitro studies have shown that sodium hyaluronate can improve wound healing rates by 45%. Furthermore, sodium hyaluronate has excellent moisturizing properties, maintaining a moist environment in the oral mucosa and providing favorable conditions for epithelial cell repair and regeneration. It also synergizes with other ingredients to enhance the overall efficacy of the composition.

[0054] In pharmaceutical excipients, the film formed can not only prolong the residence time of the active ingredients in the composition in the oral cavity, allowing them to fully exert their effects, but also isolate external stimuli, reduce damage to oral tissues, and create a good environment for the repair of oral tissues.

[0055] The ethyl cellulose wall thickness of the propolis microcapsules is 1.5-2.5 μm, and under oral pH triggering conditions, the release rate is ≥60% within 30 minutes. The preparation of the propolis microcapsules includes: an inclusion process and a release test. In the inclusion process, the propolis ethanol extract and ethyl cellulose are mixed in a core material: wall material ratio of 1:3, and a high-pressure homogenization emulsification and spray drying process is performed. The moisture content of the final product is ≤3%. The pressure range of the high-pressure homogenization emulsification is 14,000-16,000 psi, and the inlet air temperature of the spray drying process is 175-185°C. The release test of the propolis microcapsules includes: an in vitro release experiment and verification of the neutralization effect of VSCs. The in vitro release experiment includes: simulation conditions and detection methods. The simulation conditions are artificial saliva (pH = 5.5, containing 0.1% Tween 80); temperature: 37°C, oscillation rate 100 rpm, detection method: timed sampling (5, 15, and 30 minutes), HPLC analysis of aspirin C release (C18 column, mobile phase acetonitrile-water = 60:40, detection wavelength 280 nm), oral anti-inflammatory composition comprising: propolis microcapsule sustained-release system, zinc lactic acid bacteria synergistic antibacterial and lactoferrin-sodium hyaluronate synergistic repair;

[0056] Propolis microcapsule sustained-release system: Ethyl cellulose is used to wrap propolis to form a microcapsule structure with a wall thickness of 2μm. This microcapsule has a unique pH response characteristic. When the oral pH is 5.5, the molecular structure of ethyl cellulose will change, thereby triggering the release mechanism. The test found that within 30 minutes, the concentration of VSCs in the oral cavity decreased by 63%, effectively eliminating bad breath. At the same time, high-performance liquid chromatography (HPLC) technology was used to test the release of the microcapsules. The results showed that in an in vitro simulated saliva environment (pH = 5.5), the cumulative release rate in 30 minutes was 62%, ensuring that Acetylated C can continuously and stably play a role in neutralizing VSCs. This sustained-release system can not only accurately control drug release, but also improve the bioavailability of the drug, reduce the dosage and frequency of drug use, and reduce potential side effects.

[0057] Synergistic antibacterial effect of zinc lactic acid bacteria: The chelation effect of zinc ions in zinc lactic acid bacteria and the CBL active center blocks the key link of HS production at the molecular level. The molecular docking model clearly shows the binding mode and binding site of zinc ions and the CBL active center, providing an intuitive theoretical basis for this antibacterial mechanism. The HS production inhibition rate was detected by GC-MS, and the results showed that its inhibition rate was ≥90%, which can effectively control the generation of oral odor from the source. In addition, the lactic acid bacteria component in zinc lactic acid bacteria can regulate the balance of oral flora, and synergize with the antibacterial effect of zinc ions to form a dual antibacterial mechanism, which more effectively inhibits the growth and reproduction of Pg bacteria;

[0058] Lactoferrin-sodium hyaluronate synergistic repair: Lactoferrin reduces oral inflammatory responses by inhibiting the expression of inflammatory factors, thereby creating a favorable microenvironment for oral tissue repair. Sodium hyaluronate promotes epithelial cell migration and proliferation by activating CD44 receptors, accelerating wound healing. Western blot verification results show that sodium hyaluronate can upregulate the expression of Integrinβ1. Integrinβ1 is a cell adhesion molecule. Its upregulation helps the migration and adhesion of epithelial cells, thereby promoting tissue repair. The synergistic effect of the two realizes the organic combination of inflammation inhibition and tissue regeneration, and can more efficiently promote the repair and regeneration of oral tissues compared to a single component;

[0059] Propolis microcapsule sustained-release system: Ethyl cellulose is used to wrap propolis to form a microcapsule structure with a wall thickness of 2μm. Zinc lactic acid bacteria synergistic antibacterial: The zinc ions in zinc lactic acid bacteria chelate with the CBL active center, blocking the key link of HS production at the molecular level. Lactoferrin-sodium hyaluronate synergistic repair: Lactoferrin reduces oral inflammatory response by inhibiting the expression of inflammatory factors, creating a favorable microenvironment for oral tissue repair.

[0060] The method for preparing propolis microcapsules is specifically as follows:

[0061] (1) First, extract the propolis ethanol extract to ensure that the purity of aspirin C is ≥90%;

[0062] (2) accurately weighing and mixing the propolis ethanol extract and ethyl cellulose in a ratio of core material to wall material = 1:3;

[0063] (3) Using high-pressure homogenization technology, the mixture forms a stable W / O emulsion under high pressure conditions of 15,000 psi. The high-pressure homogenization process can evenly disperse the core material in the wall material to form tiny droplets;

[0064] (4) The W / O emulsion was treated by a spray drying process with the inlet air temperature set at 180°C;

[0065] (5) During the spray drying process, the solvent in the emulsion evaporates rapidly, and ethyl cellulose forms a solid wall film on the surface of the propolis ethanol extract, ultimately obtaining propolis microcapsules with a particle size between 50 and 100 μm.

[0066] Example 2, based on Example 1, verification of anti-inflammatory and regenerative functions

[0067] In vitro anti-inflammatory experiment: Human gingival fibroblasts (HGFs) were selected as the research subjects, and they were co-cultured with Pg bacteria LPS to construct an in vitro inflammatory cell model. In this model, Pg bacteria LPS can activate the NF-κB pathway in HGFs and induce an inflammatory response. The composition of the present invention was then added to the model, and after culturing for a certain period of time under suitable culture conditions, the phosphorylation level of NF-κBp65 was detected by Western blot technology. The results showed that its phosphorylation level decreased by 82%. At the same time, the secretion of the inflammatory factor IL-6 was detected by ELISA, and it was found that the secretion of IL-6 decreased from 350pg / mL to 105pg / mL. These experimental results fully demonstrate that the composition of the present invention can effectively inhibit the activation of the NF-κB pathway, reduce the release of inflammatory factors, and has a significant anti-inflammatory effect.

[0068] Scratch repair experiment: A human oral epithelial cell (OEC) scratch model was constructed to simulate oral epithelial damage. A sterile gun tip was used to make vertical scratches on the OEC monolayer in the culture dish to create a cell-free area of ​​a certain width. The composition of the present invention was then added to the scratched area and cultured under suitable culture conditions for 24 hours. The scratch healing was observed and measured under a microscope, and the results showed that the wound healing rate increased from 30% to 75%. The experimental results show that the composition of the present invention can promote the migration and proliferation of OEC, accelerate the repair of oral epithelial tissue, and verify its effectiveness in tissue regeneration.

[0069] Example 3: Clinical effect evaluation

[0070] Study subjects: 60 patients with moderate periodontitis who met the clinical diagnostic criteria for moderate periodontitis were selected. The patients were randomly divided into a treatment group (using the composition of the present invention) and a control group (using chlorhexidine). The two groups were comparable in age, gender, and disease severity.

[0071] result:

[0072] Bad breath value: Use The halitosis values ​​of the two groups of patients were tested. After the treatment group used the composition of the present invention for a period of time, The readings decreased by 63%, while the control group only decreased by 25% after using chlorhexidine. The two groups of data showed a significant difference (p<0.001). This shows that the composition of the present invention is significantly more effective than chlorhexidine in eliminating bad breath.

[0073] Chewing efficiency: The amount of peanut particles remaining in the mouth was measured to assess the patient's chewing efficiency. After using the composition of the present invention, the amount of peanut particles remaining in the treatment group decreased from 35% to 8%, while in the control group, it decreased to 22%. The improvement in chewing efficiency in the treatment group was significantly greater than in the control group, indicating that the composition of the present invention can better promote the recovery of oral function.

[0074] Speech clarity: Spectrogram analysis was used to assess the patients' speech clarity. Results showed that after using the composition of the present invention, the treatment group experienced a 72% improvement in speech clarity, while the control group experienced only a 31% improvement. This demonstrates that the composition of the present invention can effectively improve speech disorders caused by oral diseases and enhance their quality of life. Furthermore, long-term clinical observations revealed that systemic inflammatory markers in the treatment group also improved to a certain extent, further suggesting the potential value of the composition of the present invention in chronic disease care.

[0075] The present invention systematically verifies the synergistic effect and clinical efficacy of the propolis microcapsule sustained-release system, anti-inflammatory and regenerative components through Examples 1-3:

[0076] Preparation and functional verification of propolis microcapsules: Using propolis ethanol extract (acetylspirin C purity ≥90%) as the core material and ethyl cellulose as the wall material (core-wall ratio 1:3), 50-100 μm microcapsules were prepared by high-pressure homogenization (15000 psi) and spray drying (180°C). In vitro, acetylspirin C was released by 62% (HPLC) in simulated saliva (pH = 5.5) within 30 minutes. Testing showed a 63% neutralization rate of VSCs (250 ppb → 93 ppb), confirming its precise release and ability to eliminate bad breath;

[0077] Anti-inflammatory and regenerative mechanisms: In a Pg bacteria LPS-induced human gingival fibroblast (HGFs) inflammation model, the combination reduced NF-κB p65 phosphorylation by 82% (Western blot) and IL-6 secretion by 70% (350→105 pg / mL, ELISA). A wound healing assay also showed an increase in the healing rate of oral epithelial cells (OECs) from 30% to 75%, demonstrating that the combination achieves a synergistic anti-inflammatory and regenerative effect by inhibiting inflammatory pathways (NF-κB) and promoting epithelial migration (integrinβ1 upregulation).

[0078] Clinical efficacy evaluation: After use in 60 patients with moderate periodontitis, the bad breath value of the treatment group The decrease was 63% (25% in the control group, p<0.001), and the chewing efficiency (peanut residue 8% vs 22%) and speech clarity (increased 72% vs 31%) were significantly better than those in the chlorhexidine control group, and systemic inflammatory indicators improved, suggesting its potential value in the treatment of oral diseases and chronic disease management.

[0079] The above description is merely a preferred embodiment of the present invention and does not constitute any other form of limitation to the present invention. Any person skilled in the art may utilize the technical contents disclosed above to change or modify them into equivalent embodiments with equivalent changes for application in other fields. However, any simple modification, equivalent change, and modification of the above embodiments made in accordance with the technical essence of the present invention without departing from the technical solution of the present invention shall still fall within the scope of protection of the technical solution of the present invention.

Claims

1. A method for oral anti-inflammatory and chronic disease care for inhibiting Porphyromonas gingivalis, comprising propolis microcapsules, zinc lactobacillus, lactoferrin, sodium hyaluronate, and pharmaceutical excipients, characterized in that: The propolis microcapsules account for 5%, and the propolis microcapsules are wrapped with ethyl cellulose, and slowly release aspirin C inside. The zinc lactic acid bacteria content is 0.5%, and the zinc ions in the zinc lactic acid bacteria can accurately chelate the active center of the Pg bacteria cystathionine β-lyase. The lactoferrin accounts for 0.3%, and lactoferrin can specifically block the binding of Pg bacteria LPS and TLR4, thereby inhibiting the activation of the NF-κB pathway. The sodium hyaluronate content is 0.5%, and sodium hyaluronate can activate the CD44 receptor and promote epithelial cell migration and proliferation. The remainder of the pharmaceutical excipient is hydroxypropyl methylcellulose, which acts as a film-forming matrix and can form a uniform and tough protective film on the surface of the oral cavity.

2. The oral anti-inflammatory and chronic disease nursing method for inhibiting Porphyromonas gingivalis according to claim 1, characterized in that: The ethyl cellulose wall thickness of the propolis microcapsule is 1.5-2.5 μm, and under the pH triggering condition of the oral cavity, the release rate within 30 minutes is greater than or equal to 60%.

3. The oral anti-inflammatory and chronic disease nursing method for inhibiting Porphyromonas gingivalis according to claim 2, characterized in that: The preparation of the propolis microcapsules includes: inclusion process and release test. In the inclusion process, the propolis ethanol extract and ethyl cellulose are mixed in a ratio of core material to wall material of 1:

3.

4. The oral anti-inflammatory and chronic disease nursing method for inhibiting Porphyromonas gingivalis according to claim 3, characterized in that: The propolis microcapsule preparation and inclusion process includes: high-pressure homogenization emulsification and spray drying processes, and the moisture content of the final product is ≤3%.

5. The oral anti-inflammatory and chronic disease nursing method for inhibiting Porphyromonas gingivalis according to claim 4, characterized in that: The pressure range of the high-pressure homogenization emulsification is 14000-16000 psi.

6. The oral anti-inflammatory and chronic disease nursing method for inhibiting Porphyromonas gingivalis according to claim 5, characterized in that: The inlet air temperature of the spray drying process is 175-185°C.

7. The oral anti-inflammatory and chronic disease nursing method for inhibiting Porphyromonas gingivalis according to claim 6, characterized in that: The release test of the propolis microcapsule preparation includes: an in vitro release experiment and a verification of the neutralization effect of VSCs. The in vitro release experiment includes: simulation conditions and a detection method. The simulation conditions include: artificial saliva (pH = 5.5, containing 0.1% Tween 80); temperature: 37°C, oscillation rate 100 rpm; the detection method includes: timed sampling (5, 15, 30 minutes), and HPLC analysis of the release amount of aspirin C (C18 chromatographic column, mobile phase acetonitrile-water = 60:40, detection wavelength 280 nm).

8. The oral anti-inflammatory and chronic disease nursing method for inhibiting Porphyromonas gingivalis according to claim 7, characterized in that: The oral anti-inflammatory composition comprises: a propolis microcapsule sustained-release system, zinc lactobacillus synergistic bacteriostasis and lactoferrin-sodium hyaluronate synergistic repair.

9. The oral anti-inflammatory and chronic disease nursing method for inhibiting Porphyromonas gingivalis according to claim 8, characterized in that: The propolis microcapsule sustained-release system uses ethyl cellulose to wrap propolis to form a microcapsule structure with a wall thickness of 2 μm. The zinc lactic acid bacteria synergistic antibacterial effect: the zinc ions in zinc lactic acid bacteria chelate with the CBL active center to block the key link in the formation of HS at the molecular level. The lactoferrin-sodium hyaluronate synergistic repair effect: lactoferrin reduces oral inflammatory reactions by inhibiting the expression of inflammatory factors, thereby creating a favorable microenvironment for oral tissue repair.

10. The oral anti-inflammatory and chronic disease nursing method for inhibiting Porphyromonas gingivalis according to claim 9, characterized in that: The method for preparing the propolis microcapsules is specifically as follows: (1) First, extract the propolis ethanol extract to ensure that the purity of aspirin C is ≥90%; (2) accurately weighing and mixing the propolis ethanol extract and ethyl cellulose in a ratio of core material to wall material = 1:3; (3) Using high-pressure homogenization technology, the mixture forms a stable W / O emulsion under high pressure conditions of 15,000 psi. The high-pressure homogenization process can evenly disperse the core material in the wall material to form tiny droplets; (4) The W / O emulsion was treated by a spray drying process with the inlet air temperature set at 180°C; (5) During the spray drying process, the solvent in the emulsion evaporates rapidly, and ethyl cellulose forms a solid wall film on the surface of the propolis ethanol extract, ultimately obtaining propolis microcapsules with a particle size between 50 and 100 μm.

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