Antioxidant polyphenol sustained-release ointment suitable for oral cavity as well as preparation method and application of antioxidant polyphenol sustained-release ointment

Abstract

The invention relates to the technical field of oral cavity medicines, and discloses an antioxidant polyphenol sustained-release ointment suitable for oral cavity and a preparation method and application thereof, the antioxidant polyphenol sustained-release ointment comprises the following raw materials by weight: 0.5%-5% of antioxidant polyphenol, 20%-45% of a drug solvent, 1%-10% of a water-soluble polymer substance, 15%-40% of a water-based thickener, 1%-10% of a hydrophobic polymer, and 15%-40% of an ester plasticizer. The natural polyphenol is used as a main medicine, and the natural polyphenol has multiple functions of oxidation resistance, inflammation resistance, bacterium resistance, metal ion chelation, biological adhesion and the like; the slow-release ointment is prepared from an antioxidant polyphenol substance, and a slow-release system does not contain antibiotics, has no bacterial drug resistance problem and has relatively high biological safety; the antioxidant polyphenol sustained-release ointment does not contain water, can absorb peripheral gingival crevicular fluid after being coated in a periodontal pocket, and is converted into gel with higher strength to be more stably released locally; the preparation process is simple, mild in condition and low in cost.

Description

Technical Field

[0001] The invention relates to the technical field of oral medicines, and in particular to an antioxidant polyphenol sustained-release ointment suitable for oral cavity and a preparation method and application thereof. Background Art

[0002] Oral inflammatory diseases are a common oral health problem, characterized by high incidence, easy recurrence, and significant impact on patients' daily lives, such as periodontitis, gingivitis, oral ulcers, periodontal abscesses, etc. At present, the treatment of such diseases mainly relies on antibiotics, anti-inflammatory drugs, mouthwashes, etc., but these treatments often have limited effects, easy to produce drug resistance, and poor patient compliance.

[0003] Antioxidant polyphenols have anti-inflammatory, antioxidant and tissue repair properties and are considered to be potential drugs for the treatment of oral inflammatory diseases. However, their application is limited due to their poor stability during storage and use and their susceptibility to oxidation and photolysis.

[0004] In order to solve these problems, it is particularly important to develop a topical preparation that can continuously release antioxidant polyphenols, is stable, efficient and easy to use. As a topical drug delivery system, sustained-release ointment can provide continuous drug release, reduce the frequency of administration, and directly act on the lesion site, reduce systemic side effects, and improve patient compliance and treatment effects.

[0005] The minocycline hydrochloride ointment prepared by US Patent US6566350B2 is a common clinical periodontal adjuvant drug, which has a good killing effect on periodontal pathogens, but its main drug ingredient is the antibiotic preparation minocycline hydrochloride, and long-term use is prone to cause bacterial resistance, oral flora imbalance and other problems. The sustained-release metronidazole ointment prepared by Chinese Patent CN104367547B has a good sustained release effect, but its effect is also mainly aimed at pathogens, and cannot effectively improve the oxidative stress problem caused by inflammation. The anti-inflammatory and antibacterial polyphenol gel prepared by Chinese Patent CN115487303A has the effect of killing common oral pathogens and treating rat periodontitis, but its polyphenol extraction uses an organic solvent that may irritate the skin, and there is no description of a local sustained release effect, which cannot guarantee the stable and continuous therapeutic effect of the polyphenol extract. Summary of the invention

[0006] The purpose of the present invention is to provide an antioxidant polyphenol sustained-release ointment suitable for oral cavity, a preparation method and an application thereof, so as to solve the technical problems in the prior art that the reaction activity of antioxidant polyphenol drugs is too large and thus they cannot play a role for a long time, and that too many antibiotics cause oral flora imbalance. Specifically, by constructing a sustained-release system loaded with antioxidant polyphenol drugs, long-term and safe antioxidant effects are achieved, the growth and proliferation of oral pathogenic bacteria are inhibited, the oxidative stress effect of local inflammation is improved, the balance of oral flora is adjusted, and the occurrence of drug resistance is avoided while treating diseases such as periodontitis, gingivitis, oral ulcers and periodontal abscesses.

[0007] To achieve the above object, the present invention provides the following technical solutions:

[0008] The invention provides an antioxidant polyphenol sustained-release ointment suitable for oral cavity. The raw materials thereof are composed of the following by weight: 0.5%-5% antioxidant polyphenol, 20%-45% drug solvent, 1%-10% water-soluble polymer, 15%-40% aqueous thickener, 1%-10% hydrophobic polymer and 15%-40% ester plasticizer.

[0009] Furthermore, the antioxidant polyphenols include tannic acid, gallic acid, propyl gallate, octyl gallate, and epigallocatechin gallate.

[0010] Furthermore, the drug solvent is one or more of ethanol, glycerol, propylene glycol, and polyethylene glycol.

[0011] Furthermore, the water-soluble polymer substance is one or more of Pluronic F127 and cyclodextrin; the hydrophobic polymer is one or more of ethyl cellulose and acrylic resin type I.

[0012] Furthermore, the ester plasticizer is one or more of triacetin, glyceryl mono- and distearate, and dimethyl silicone oil.

[0013] Furthermore, the aqueous thickener is one or more of carbomer P974, carbomer P941, and carbomer polyvinyl pyrrolidone.

[0014] In one aspect, the present invention also provides a method for preparing an antioxidant polyphenol sustained-release ointment suitable for oral cavity, comprising the following steps:

[0015] (1) fully dispersing antioxidant polyphenols weighed in proportion in a drug solvent at room temperature to form a polyphenol solution;

[0016] (2) The hydrophobic polymer and the ester plasticizer are fully dissolved and mixed in a water bath, and then the aqueous thickener is added. After being dissolved and mixed in a water bath at 50-70° C., the mixture is cooled to room temperature, and then the water-soluble polymer is added and mixed to form a sustained-release ointment base;

[0017] (3) The polyphenol solution in step (1) and the ointment base in step (2) are mixed and stirred in a mortar, followed by centrifugation and degassing to prepare an antioxidant polyphenol sustained-release ointment.

[0018] Furthermore, the water bath heating temperature of the hydrophobic polymer and the ester plasticizer is 80-100° C. for 20-40 min; the stirring time of the ointment base and the polyphenol solution is 20-30 min; and the centrifugal speed in (3) is 1000-2000 rad / min for 10-30 min.

[0019] On the other hand, the present invention also provides a use of a polyphenol sustained-release ointment in preventing / treating oral inflammatory diseases and in manufacturing a drug for preventing / treating oral inflammatory diseases, wherein the oral inflammatory diseases include periodontitis, gingivitis, oral ulcers and periodontal abscesses.

[0020] Based on the above technical solution, the embodiments of the present invention can at least produce the following technical effects:

[0021] The present invention uses polyphenol substances with antioxidant and antibacterial properties as materials, and directly mixes them by changing different temperatures through a simple preparation method to form an antioxidant polyphenol sustained-release ointment. The sustained-release system technology of the present invention can not only regulate the ability of antioxidant polyphenol drugs that are too reactive and thus unable to function for a long time, but also avoid the problem of oral flora imbalance caused by excessive use of antibiotics. The polyphenol substances used in the local sustained-release system technology of the present invention have antioxidant activity, can remove active oxygen free radicals, and inhibit the growth of pathogenic bacteria; the matrix synthesized by the water-soluble polymer, aqueous thickener, hydrophobic polymer, and ester plasticizer used has the functions of preventing and controlling excessive drug reaction and slow release.

[0022] (1) Polyphenols from natural sources are used as the main drugs, which have multiple functions such as antioxidant, anti-inflammatory, antibacterial, metal ion chelation, and bioadhesion;

[0023] (2) A sustained-release ointment is prepared using antioxidant polyphenols. The sustained-release system does not contain antibiotics, has no bacterial resistance problem, and has high biosafety;

[0024] (3) Antioxidant polyphenol sustained-release ointment does not contain water. When applied to the periodontal pocket, it absorbs the surrounding gingival sulcus fluid and then transforms into a gel with higher strength for more stable local release.

[0025] (4) The preparation process is simple, the conditions are mild, and the cost is low.

[0026] The present invention can locally slowly release antioxidant and antibacterial natural polyphenol components in the mouth for the treatment of oral inflammatory diseases, and can be applied to the field of biomedicine, providing a theoretical basis and technical support for the development of natural non-antibiotic drugs for the treatment of periodontitis, gingivitis, oral ulcers, periodontal abscesses and other diseases. Therefore, it has great development potential and prospects in the use of antioxidant polyphenol drugs for the prevention and treatment of related diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to more clearly illustrate the technical solutions in the present invention or the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the structures shown in these drawings without paying creative work.

[0028] Figure 1 The conventional state of the polyphenol sustained-release ointment of the present invention and the storage modulus and loss modulus measured by a rheometer;

[0029] Figure 2 The state of the polyphenol sustained-release ointment of the present invention after absorbing water for 2 days and the storage modulus and loss modulus measured by the rheometer;

[0030] Figure 3 is the release capacity of the polyphenol sustained-release ointment of the present invention;

[0031] Figure 4 is the clearance rate of ABTS by the polyphenol sustained-release ointment of the present invention;

[0032] Figure 5 NPN results of different experimental groups of the present invention;

[0033] Figure 6 The effects of different concentrations of ointment base and natural polyphenol periodontal sustained-release ointment on the survival rate of common oral pathogens;

[0034] Figure 7 The effects of different experimental groups of the present invention on the colony formation of common oral pathogens;

[0035] Figure 8 The toxicity of the polyphenol sustained-release ointment of the present invention to mouse embryonic fibroblasts and RAW264.7 cells;

[0036] Fig. 9 Confocal images and corresponding semi-quantitative analysis of the inhibitory effect of different experimental groups of the present invention on the production of ROS after LPS stimulation of RAW264.7;

[0037] Fig.10Confocal images and corresponding semi-quantitative analysis of the inhibitory effect of different experimental groups of the present invention on the production of ROS after H2O2 stimulation of RAW264.7;

[0038] Fig.11 The hemolytic property of the antioxidant polyphenol sustained-release ointment of the present invention;

[0039] Fig.12 The three-dimensional and two-dimensional Micro-CT images of the alveolar bones of rats with periodontitis after different treatments of the present invention;

[0040] Fig.13 is the CEJ-ABC distance of rats in different treatment groups obtained by CTAn software in the present invention;

[0041] Fig.14 is the BV / TV value of rats in different treatment groups obtained by CTVox software in the present invention;

[0042] Fig.15 These are microscopic images of H&E stained sections of periodontal tissues of rats with periodontitis in different treatment groups of the present invention;

[0043] Fig.16 DHE staining and corresponding fluorescence semi-quantitative analysis of gingival tissue of rats with periodontitis in different treatment groups of the present invention; DETAILED DESCRIPTION

[0044] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0045] It should be understood that the terms described in the present invention are only for describing special embodiments and are not intended to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that each intermediate value between the upper and lower limits of the scope is also specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the described range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0046] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art. Although the present invention describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0047] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments of the present invention description without departing from the scope or spirit of the present invention. Other embodiments derived from the present invention description will be apparent to the skilled artisan. The present invention description and examples are exemplary only.

[0048] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0049] The experimental methods without specific conditions in the examples are usually carried out according to conventional conditions and conditions described in the manual, or according to conditions recommended by the manufacturer; the general equipment, materials, reagents, etc. used can be obtained from commercial channels unless otherwise specified.

[0050] Example 1

[0051] composition:

[0052]

[0053] Preparation method:

[0054] (1) Construction and characterization of a periodontal sustained-release ointment of octyl gallate with antibacterial and antioxidant effects

[0055] ① Mix octyl gallate (OG), glycerol and carbomer P934 to form an OG solution

[0056] ② Heat and dissolve ethyl cellulose and triacetin, then cool and grind with Pluronic F127 to form an ointment base

[0057] ③ Evenly mix the ointment base and OG solution to form the final antioxidant polyphenol sustained-release ointment

[0058] Example 2

[0059] composition:

[0060]

[0061]

[0062] Preparation method: Same as Example 1

[0063] Embodiment 3 composition:

[0064]

[0065] Preparation method: Same as Example 1

[0066] Embodiment 4 composition:

[0067]

[0068]

[0069] Preparation method: Same as Example 1

[0070] Determination of rheological properties, in vitro sustained release capacity, rheological test using a hybrid rheometer, by scanning the oscillation frequency at room temperature, monitoring the storage modulus and loss modulus of ointments with different proportions to detect the viscoelastic properties of the material; by performing destructive shear and recovery scanning cycles, monitoring the storage modulus and loss modulus of ointments with different proportions to detect the self-healing properties of the material for comparison and evaluation of the rheological properties of ointments with different proportions. Figure 1 The sustained-release ointment has good solid rheological properties and good injectability. It can form a stable gel structure after absorbing water for 24 hours. Figure 2 This ensures that it can stably exist in the periodontal pocket or wisdom tooth blind pocket after contacting the gingival sulcus fluid or saliva.

[0071] The in vitro sustained-release capacity of the ointment system was tested using a modified Franz diffusion cell. First, the ultraviolet absorption peaks of polyphenol solutions of different concentrations were measured and a standard curve was drawn. Antioxidant polyphenol sustained-release ointments of different proportions were accurately weighed and placed in the supply pool. The receiving pool was PBS, and a semipermeable membrane was placed between the supply pool and the receiving pool of the diffusion pool. The temperature was set to 37±℃. The corresponding OD values ​​of polyphenols in the medium at different time points were measured for one week, and the drug concentration was calculated by substituting the standard curve, and the cumulative release percentage was calculated to examine the in vitro release level of the ointment. Figure 3 The preparation can stably release polyphenols in a dynamic liquid environment, with the release degree approaching 95% in 9 days.

[0072] ABTS + Free radical scavenging activity is often used as the total antioxidant capacity of an antioxidant. Mix equal volumes of ABTS solution and potassium persulfate solution to obtain green ABTS + Free radical solution, and store it in dark conditions at room temperature for 12 hours to fully react. Dilute with ultrapure water to a suitable absorbance. Add ABTS+ solution to the polyphenol sustained-release ointment solution of different concentrations, mix well, and react in the dark for 20 minutes. Measure the ultraviolet absorption spectrum of the solution after the reaction to calculate the antioxidant activity. Figure 4 The clearance rate of ABTS was concentration-dependent. When the ointment concentration reached 600 μg / mL, the clearance rate of ABTS reached 99%.

[0073] A common oral pathogen was cultured to an appropriate concentration and co-cultured with different concentrations of sustained-release ointment dilutions. After a certain period of time, the CCK-8 method was used to examine the inhibition of the pathogen. After the appropriate concentration of bacterial solution was co-incubated with different ointment groups for 3 hours, the in vitro antibacterial effect of the ointment system was verified by NPN permeation experiment under a fluorescence spectrophotometer. The killing effect of the sustained-release ointment on this type of common oral pathogens was examined. Figure 5 , NPN experiments have shown that antioxidant polyphenol sustained-release ointment has good bacterial membrane penetration effect; Figure 6 , 24-hour incubation experiments proved that the bactericidal effect of antioxidant polyphenol sustained-release ointment has a certain concentration dependence, such as Figure 7 The streaking plate cloning experiment can verify that the antioxidant polyphenol sustained-release ointment can effectively inhibit colony formation.

[0074] Cytotoxicity study: observe the growth state of cells under a microscope, use a cell live-dead staining kit to observe the ratio of live and dead cells after administration, use MTT experiment to observe the proliferation activity of cells, use flow cytometry to observe the changes of cell apoptosis and cell cycle, and comprehensively evaluate the in vitro toxicity. Figure 8 The CCK8 method was used to prove that the antioxidant polyphenol sustained-release ointment had no cytotoxicity to RAW264.8 and 3T3 cells.

[0075] The macrophages in the logarithmic growth phase were digested and resuspended, then inoculated in a 48-well plate and cultured for 24 hours. The cells were inoculated on a blank periodontal ointment matrix and an OG periodontal sustained-release ointment with a thickness of 1 mm as the cell protection group, and fresh culture medium was added to the control group. After incubation in the incubator for 24 hours, the supernatant was aspirated and washed with PBS. Except for the blank control group, H2O2 was added to the control injury group and the cell protection group, respectively. After stimulating the cells for 2 hours, the MTT test was used to detect the inhibitory effect of the antioxidant polyphenol sustained-release ointment and H2O2 co-incubated macrophage cells to detect the inhibitory effect of the drug on H2O2-induced oxidative overload and killing cells. In addition, the above-mentioned cell stimulation experiment was repeated and the fluorescence production of ROS was observed under a microscope after adding the DCFH-DA probe to detect the inhibitory effect of OG periodontal sustained-release ointment on cellular oxidative stress. The above experiment was repeated by replacing H2O2 with LPS, and LPS and H2O2 were used to stimulate macrophages to produce ROS in both endogenous and exogenous ways. The results showed that Fig. 9 , 10 antioxidant polyphenol sustained-release ointment has a certain inhibitory effect on ROS produced by H2O2 and LPS stimulation.

[0076] Hemolysis and coagulation test: refer to the hemolysis test method of the 2015 edition of the "Chinese Pharmacopoeia". Based on the principle that hemoglobin released after red blood cell rupture has maximum absorption in the visible light wavelength range, the hemolysis of the antioxidant polyphenol sustained-release ointment is detected by spectrophotometry to evaluate its blood compatibility. The drug is administered locally to the periodontium in the mouth. The behavior, state and death time of the mice are observed after administration. After killing, blood cell counts, blood biochemistry, immune response indicators, organ quality and histopathological examinations are performed to evaluate immunogenicity and in vivo toxicity. Fig.11 The hemolysis experiment proved that different concentrations of natural polyphenol periodontal sustained-release ointment had no hemolysis phenomenon.

[0077] An experimental rat periodontitis model was constructed, and different intervention measures including an antioxidant polyphenol sustained-release ointment group were given. ROS fluorescence staining, Micro-CT and histological staining were used to evaluate the therapeutic effect of the ointment system on the oral inflammatory disease - periodontitis.

[0078] A group of SD rats were randomly selected as the blank control group (healthy rat group), and the rest of the rats were ligated with orthodontic ligatures on the second molars on both sides of the maxilla to establish an experimental rat periodontitis model. The ligatures were removed after 4 weeks. The SD rats with periodontitis were randomly divided into different groups (blank control group, periodontitis negative control group, minocycline hydrochloride ointment group, blank ointment matrix group and antioxidant polyphenol sustained-release ointment group) and treated accordingly. Local administration was performed on the periodontium of the second molars on both sides of the maxilla of the rats once a week for a total of 2 weeks. The clinical score of periodontitis in rats was detected once a week. After the treatment, the inflammatory factors in the gingival crevicular fluid were detected again, and the local ROS fluorescence intensity in the mouth and the jaw bone Micro-CT were observed by small animal in vivo imaging after intravenous injection of DCFH-DA. After that, the peripheral blood, major organs (heart, liver, spleen, kidney, lung), gingival tissue and corresponding bone tissue of the rats were collected for the following examinations. The major organs and gingiva were embedded in paraffin, sectioned and stained with H&E. The expression level of ROS in gingival tissue was detected by DHE. CT was used to measure the distance from the alveolar spine to the cementoenamel junction before and after treatment, the bone volume fraction of the alveolar bone, the trabecular spacing, the trabecular thickness and the number of trabeculae, and statistical analysis was used to observe the treatment effect of periodontitis in rats in different groups before and after treatment.

[0079] like Fig.12 By performing CT scans on the periodontitis rats after treatment, it can be seen from the 3D reconstruction images and sagittal sections that compared with the periodontitis group, the antioxidant polyphenol sustained-release ointment group retained more alveolar bone, such as Fig.13 The same conclusion can be drawn from the distance between the buccal and lingual alveolar crest (ABC) and the cementoenamel junction (CEJ), and the effect is better than that of the positive treatment group (minocycline hydrochloride ointment group). Fig.14CTAn software was used to calculate the bone volume (BV), tissue volume (TV) and their ratio (BV / TV) around the ligated molars. Fig.15 H&E staining of gingival tissue sections of rats in each group showed that normal healthy rats had no periodontal inflammation, and the fibrous tissue was distributed normally. Fibroblasts were seen arranged in parallel along the long axis of the fibrous tissue. Rats in the positive control group had a small amount of bleeding, local tissue edema, loose and disordered tissue distribution, and inflammatory cell infiltration, indicating an acute and extensive inflammatory state of the gingival tissue. After different treatments, the antioxidant polyphenol sustained-release ointment had the best inhibitory effect on periodontitis. All layers of the gingiva were normal without obvious inflammatory cell infiltration, which was not significantly different from the positive treatment group. Fig.16 This is also confirmed by the DHE gingival fluorescence staining, which shows that the antioxidant polyphenol sustained-release ointment effectively removes ROS in periodontal soft tissue.

[0080] Although the present invention has been disclosed as above in the form of a preferred embodiment, it is not intended to limit the present invention. Anyone familiar with this technology can make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be based on the definition of the claims.

[0081] Finally, it should be noted that:

[0082] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that the technical solutions described in the above embodiments may still be modified, or some or all of the technical features may be replaced by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. An antioxidant polyphenol sustained-release ointment suitable for oral cavity, characterized in that: The raw materials are composed of 0.5%-5% antioxidant polyphenols, 20%-45% drug solvents, 1%-10% water-soluble polymers, 15%-40% aqueous thickeners, 1%-10% hydrophobic polymers, and 15%-40% ester plasticizers by weight.

2. The antioxidant polyphenol sustained-release ointment suitable for oral cavity according to claim 1, characterized in that: The antioxidant polyphenols include tannic acid, gallic acid, propyl gallate, octyl gallate, and epigallocatechin gallate.

3. The antioxidant polyphenol sustained-release ointment suitable for oral cavity according to claim 1, characterized in that: The drug solvent is one or more of ethanol, glycerol, propylene glycol, and polyethylene glycol.

4. The antioxidant polyphenol sustained-release ointment suitable for oral cavity according to claim 1, characterized in that: The water-soluble high molecular substance is one or more of Pluronic F127 and cyclodextrin; the hydrophobic polymer is one or more of ethyl cellulose and acrylic resin type I.

5. The antioxidant polyphenol sustained-release ointment suitable for oral cavity according to claim 1, characterized in that: The ester plasticizer is one or more of triacetin, mono- and distearic acid glyceryl, and dimethyl silicone oil.

6. The antioxidant polyphenol sustained-release ointment suitable for oral cavity according to claim 1, characterized in that: The aqueous thickener is one or more of carbomer P974, carbomer P941, and carbomer polyvinyl pyrrolidone.

7. The method for preparing the antioxidant polyphenol sustained-release ointment suitable for oral cavity according to any one of claims 1 to 6, characterized in that: The following steps are involved: (1) fully dispersing the antioxidant polyphenols weighed in proportion in a drug solvent at room temperature to form a polyphenol solution; (2) After the hydrophobic polymer and ester plasticizer are fully dissolved and mixed in a water bath, an aqueous thickener is added, and after the mixture is dissolved and mixed in a water bath at 50-70°C and cooled to room temperature, a water-soluble polymer is added and mixed to form a sustained-release ointment matrix; (3) The polyphenol solution in step (1) and the ointment base in step (2) are mixed and stirred in a mortar, and then centrifuged and degassed to prepare an antioxidant polyphenol sustained-release ointment.

8. The method for preparing the antioxidant polyphenol sustained-release ointment suitable for oral cavity according to claim 7, characterized in that: The water bath heating temperature of the hydrophobic polymer and the ester plasticizer is 80-100°C for 20-40 minutes; the stirring time of the ointment base and the polyphenol solution is 20-30 minutes; the centrifugal speed in (3) is 1000-2000 rad / min for 10-30 minutes.

9. Use of a polyphenol sustained-release ointment in preventing / treating oral inflammatory diseases and in manufacturing a medicament for preventing / treating oral inflammatory diseases, characterized in that: The oral inflammatory diseases include periodontitis, gingivitis, oral ulcers and periodontal abscesses.

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