A pharmaceutical composition for treating periodontitis and its preparation method

Abstract

This invention relates to the field of biomedical technology, and more particularly to a pharmaceutical composition for treating periodontitis and its preparation method. The pharmaceutical composition comprises the following raw materials in parts by weight: 4-8% *Ipomoea aquatica* extract, 0.5-1% propolis extract, 0.8-1.2% vitamin B2, 0.6-0.8% vitamin C, 4-8% carboxymethyl chitosan, 0.3-0.5% gelatin, 0.1-0.3% modified silica, 0.25-0.3% costone lactone, and the balance being deionized water. This pharmaceutical composition exhibits stable efficacy and excellent therapeutic effect on periodontitis.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to a pharmaceutical composition for treating periodontitis and its preparation method. Background Technology

[0002] Periodontitis is a chronic inflammatory disease mediated by dental plaque biofilm and has become the leading cause of tooth loss in adults. This disease not only severely damages oral health but also has a clear bidirectional link with various systemic diseases such as diabetes, cardiovascular disease, and rheumatoid arthritis, thus posing a significant public health challenge.

[0003] Currently, clinical intervention for periodontitis primarily involves mechanical debridement, supplemented by antibiotic treatment. While these methods can control infection to some extent, they generally face problems such as high recurrence rates, easy induction of antibiotic resistance, and difficulty in effectively regulating excessive host immune responses. Therefore, developing comprehensive treatment strategies that can simultaneously target pathogenic bacteria and their virulence factors while modulating host immune inflammatory pathways has become a key focus and challenge in this field of research.

[0004] The pathogenesis of periodontitis involves a series of complex steps, the core of which includes the establishment of pathogenic bacterial biofilms and an excessive immune response in the host. During biofilm formation, glucosyltransferase (GTF) catalyzes the synthesis of extracellular glucans, providing adhesion sites for pathogenic bacteria and promoting biofilm maturation. On the host side, bacterial components such as lipopolysaccharide (LPS) can activate the NF-κB signaling pathway in macrophages, leading to the massive release of inflammatory cytokines, which in turn triggers alveolar bone resorption and connective tissue degradation.

[0005] Against this backdrop, current treatment approaches are gradually shifting towards dual-target intervention: on the one hand, it is necessary to precisely block the pathogenic behavior of pathogenic bacteria, such as by inhibiting GTF activity to reduce bacterial attachment sites and disrupt their biofilm microenvironment; on the other hand, it is essential to intelligently regulate the host's immune response, such as by inhibiting the NF-κB pathway to reduce the secretion of inflammatory factors by macrophages, thereby controlling the tissue destruction process. Integrating these two mechanisms into a single treatment system holds promise for achieving a more fundamental and systematic treatment of periodontitis. Based on this, the present invention provides a pharmaceutical composition for treating periodontitis and its preparation method. Summary of the Invention

[0006] In order to overcome the shortcomings of the prior art, the primary objective of the present invention is to provide a pharmaceutical composition for treating periodontitis that can improve the treatment effect of periodontitis.

[0007] Another objective of this invention is to provide a method for preparing a pharmaceutical composition for treating periodontitis, which is simple to operate.

[0008] The objective of this invention is achieved through the following technical solution: A pharmaceutical composition for treating periodontitis comprises the following raw materials in parts by weight: 4-8% of *Lysimachia christinae* extract, 0.5-1% of propolis extract, 0.8-1.2% of vitamin B2, 0.6-0.8% of vitamin C, 4-8% of carboxymethyl chitosan, 0.3-0.5% of gelatin, 0.1-0.3% of modified silica, 0.25-0.3% of costus lactone, and the balance being deionized water; The preparation process of the modified silica is as follows: S1. Add silica nanoparticles to toluene, then add silane coupling agent, stir and react to obtain silica nanoparticles modified with silane coupling agent; S2. The silica nanoparticles modified with the silane coupling agent are added to N,N-dimethylformamide, followed by sophorolipid and an initiator. The mixture is heated to react and obtain the modified silica.

[0009] Preferably, the mass ratio of silica nanoparticles to silane coupling agent in step S1 is 10:(1-1.5).

[0010] Preferably, the silane coupling agent is vinyltriethoxysilane.

[0011] Preferably, the temperature of the stirring reaction in step S1 is 55-65°C and the time is 5-6 hours.

[0012] Preferably, the mass ratio of the silane coupling agent-modified silica nanoparticles, sophorolipid, and initiator in step S2 is 100:(12-15):(0.5-1.5).

[0013] Preferably, the initiator is azobisisobutyronitrile.

[0014] Preferably, the heating reaction in step S2 is carried out at a temperature of 85-95°C for 3.5-5 hours.

[0015] The preparation method of the above-mentioned pharmaceutical composition for treating periodontitis includes the following steps: (a) Weigh each raw material according to the stated weight parts, add carboxymethyl chitosan to half of the deionized water to obtain a carboxymethyl chitosan solution; (b) Add gelatin to the remaining deionized water to obtain a gelatin solution, and then add modified silica, costus lactone, propolis extract, blue cloth extract, vitamin B2 and vitamin C in sequence to obtain a mixture. (c) Add the carboxymethyl chitosan solution to the mixture and mix by ultrasonication.

[0016] Preferably, the ultrasonic mixing time in step (c) is 10-15 min.

[0017] The present invention has the following advantages over the prior art: The pharmaceutical composition of this invention comprises the following ingredients: modified silica, costunolide, carboxymethyl chitosan, gelatin, propolis extract, blue basil extract, vitamin B2, and vitamin C. The combination of these components provides a stable and effective treatment for periodontitis. Specifically, costunolide can inhibit the secretion of LPS-stimulated inflammatory cytokines by inhibiting the NF-κB pathway, while the silica modified with sophorolipids can inhibit the activity of glucosyltransferase, thereby inhibiting glucan production, reducing attachment sites for pathogenic bacteria on teeth, and contributing to the treatment and recovery of periodontitis. Attached Figure Description

[0018] Figure 1 This is a SEM image of the modified silica prepared in Example 1 of the present invention; Figure 2 This is a graph showing the cytotoxicity of the modified silica prepared in Example 1; Figure 3 This is a diagram showing the cytotoxicity of costunolactone. Detailed Implementation

[0019] The present invention will be further described in detail below with reference to embodiments, but the implementation of the present invention is not limited thereto. Unless otherwise specified, the reagents, methods, and equipment used in the present invention are conventional reagents, methods, and equipment in this technical field. Test methods in the following embodiments that do not specify specific experimental conditions are generally performed according to conventional experimental conditions or experimental conditions recommended by the manufacturer. Unless otherwise specified, the reagents and raw materials used in the present invention are commercially available.

[0020] Example 1 Example 1 provides a modified silica, the preparation process of which is as follows: S1. With silica nanoparticles, vinyltriethoxysilane, and toluene in a ratio of 10g:1.2g:170mL, silica nanoparticles were added to toluene, followed by vinyltriethoxysilane. The mixture was stirred at 60℃ for 5.5h. After the reaction was completed, the mixture was filtered, washed, and dried to obtain silica nanoparticles modified with silane coupling agent. S2. The ratio of silane coupling agent-modified silica nanoparticles, sophorolipid, azobisisobutyronitrile, and N,N-dimethylformamide is 100g:14g:1g:1100mL. The silane coupling agent-modified silica nanoparticles are added to N,N-dimethylformamide (DMF), followed by sophorolipid and azobisisobutyronitrile. The mixture is reacted at 90℃ for 4 hours. After the reaction is complete, the mixture is filtered, washed, and dried to obtain the modified silica. The SEM image of the modified silica is shown below. Figure 1 As shown.

[0021] Example 2 Example 2 provides a modified silica, the preparation process of which is as follows: S1. With silica nanoparticles, vinyltriethoxysilane, and toluene in a ratio of 10g:1.5g:200mL, silica nanoparticles were added to toluene, followed by vinyltriethoxysilane. The mixture was stirred at 65℃ for 5 hours. After the reaction was completed, the mixture was filtered, washed, and dried to obtain silica nanoparticles modified with silane coupling agent. S2. The ratio of silica nanoparticles modified with silane coupling agent, sophorolipid, azobisisobutyronitrile, and DMF is 100g:15g:1.5g:1200mL. The silica nanoparticles modified with silane coupling agent are added to DMF, followed by sophorolipid and azobisisobutyronitrile. The mixture is reacted at 95℃ for 3.5h. After the reaction is completed, the mixture is filtered, washed, and dried to obtain the modified silica.

[0022] Example 3 Example 3 provides a modified silica, the preparation process of which is as follows: S1. With a ratio of 10g:1g:150mL for silica nanoparticles, vinyltriethoxysilane, and toluene, silica nanoparticles were added to toluene, followed by vinyltriethoxysilane. The mixture was stirred at 55℃ for 6 hours. After the reaction was completed, the mixture was filtered, washed, and dried to obtain silica nanoparticles modified with silane coupling agent. S2. The ratio of silica nanoparticles modified with silane coupling agent, sophorolipid, azobisisobutyronitrile, and DMF is 100g:12g:0.5g:1000mL. The silica nanoparticles modified with silane coupling agent are added to DMF, followed by sophorolipid and azobisisobutyronitrile. The mixture is reacted at 85℃ for 5h. After the reaction is completed, the mixture is filtered, washed, and dried to obtain the modified silica.

[0023] Example 4 Example 4 provides a pharmaceutical composition for treating periodontitis, comprising the following raw materials in parts by weight: 6% of blue broccoli extract, 0.7% of propolis extract, 1% of vitamin B2, 0.7% of vitamin C, 5% of carboxymethyl chitosan, 0.4% of gelatin, 0.2% of modified silica prepared in Example 1, 0.28% of costus lactone, and the balance being deionized water.

[0024] Example 4 also provides a method for preparing the above-mentioned pharmaceutical composition for treating periodontitis, comprising the following steps: (a) Weigh each raw material according to the stated weight parts, add carboxymethyl chitosan to half of the deionized water to obtain a carboxymethyl chitosan solution; (b) Add gelatin to the remaining deionized water to obtain a gelatin solution, and then add modified silica, costus lactone, propolis extract, blue cloth extract, vitamin C, and vitamin B2 in sequence to obtain a mixture. (c) Add the carboxymethyl chitosan solution to the mixture and sonicate for 12 minutes.

[0025] Example 5 Example 5 provides a pharmaceutical composition for treating periodontitis, comprising the following raw materials in parts by weight: 4% of blue broccoli extract, 0.5% of propolis extract, 0.8% of vitamin B2, 0.6% of vitamin C, 4% of carboxymethyl chitosan, 0.3% of gelatin, 0.1% of the modified silica prepared in Example 2, 0.25% of costunolide, and the balance being deionized water.

[0026] Example 5 also provides a method for preparing the above-mentioned pharmaceutical composition for treating periodontitis, comprising the following steps: (a) Weigh each raw material according to the stated weight parts, add carboxymethyl chitosan to half of the deionized water to obtain a carboxymethyl chitosan solution; (b) Add gelatin to the remaining deionized water to obtain a gelatin solution, and then add modified silica, costus lactone, propolis extract, blue cloth extract, vitamin C, and vitamin B2 in sequence to obtain a mixture. (c) Add the carboxymethyl chitosan solution to the mixture and sonicate for 15 minutes.

[0027] Example 6 Example 6 provides a pharmaceutical composition for treating periodontitis, comprising the following raw materials in parts by weight: 8% of blue broccoli extract, 1% of propolis extract, 1.2% of vitamin B2, 0.8% of vitamin C, 8% of carboxymethyl chitosan, 0.5% of gelatin, 0.3% of modified silica obtained in Example 3, 0.3% of costus lactone, and the balance being deionized water.

[0028] Example 6 also provides a method for preparing the above-mentioned pharmaceutical composition for treating periodontitis, comprising the following steps: (a) Weigh each raw material according to the stated weight parts, add carboxymethyl chitosan to half of the deionized water to obtain a carboxymethyl chitosan solution; (b) Add gelatin to the remaining deionized water to obtain a gelatin solution, and then add modified silica, costus lactone, propolis extract, blue cloth extract, vitamin C, and vitamin B2 in sequence to obtain a mixture. (c) Add the carboxymethyl chitosan solution to the mixture and sonicate for 10 minutes.

[0029] Comparative Example 1 Comparative Example 1 provides a pharmaceutical composition comprising the following raw materials in parts by weight: 6% blue cloth extract, 0.7% propolis extract, 1% vitamin B2, 0.7% vitamin C, 5% carboxymethyl chitosan, 0.4% gelatin, 0.2% modified silica prepared in Example 1, and the balance being deionized water.

[0030] Comparative Example 1 also provides a method for preparing the above-mentioned pharmaceutical composition, comprising the following steps: (a) Weigh each raw material according to the stated weight parts, add carboxymethyl chitosan to half of the deionized water to obtain a carboxymethyl chitosan solution; (b) Add gelatin to the remaining deionized water to obtain a gelatin solution, then add modified silica, propolis extract, blue cloth extract, vitamin C, and vitamin B2 to obtain a mixture; (c) Add the carboxymethyl chitosan solution to the mixture and sonicate for 12 minutes.

[0031] Comparative Example 2 Comparative Example 2 provides a pharmaceutical composition comprising the following raw materials in parts by weight: 6% of blue broccoli extract, 0.7% of propolis extract, 1% of vitamin B2, 0.7% of vitamin C, 5% of carboxymethyl chitosan, 0.4% of gelatin, 0.2% of silica nanoparticles, 0.28% of costunolide, and the balance being deionized water.

[0032] Comparative Example 2 also provides a method for preparing the above-mentioned pharmaceutical composition, comprising the following steps: (a) Weigh each raw material according to the stated weight parts, add carboxymethyl chitosan to half of the deionized water to obtain a carboxymethyl chitosan solution; (b) Add gelatin to the remaining deionized water to obtain a gelatin solution, and then add silica nanoparticles, costus lactone, propolis extract, blue cloth extract, vitamin C, and vitamin B2 in sequence to obtain a mixture. (c) Add the carboxymethyl chitosan solution to the mixture and sonicate for 12 minutes.

[0033] Experimental Example 1 Experiment 1 uses L929 fibroblasts to detect the cytotoxicity of modified silica and costus lactone prepared in Example 1. The specific detection process is as follows: Cytotoxicity of modified silica The concentration of L929 fibroblasts was adjusted to 1×10⁻⁶ using DMEM complete medium. 4Fibroblasts were cultured at a concentration of 100 μL / mL in 96-well plates. The plates were then transferred to a 37°C, 5% CO2 cell culture incubator for 14 h. After discarding the culture medium, 100 μL of DMEM complete medium containing 55 μg / mL modified silica (prepared in Example 1) was added to each well, and the plates were cultured for another 24 h. The growth morphology of fibroblasts in each well was observed under a microscope. This experiment also included blank control wells containing only DMEM serum-free medium and positive control wells containing DMEM complete medium supplemented with 5% phenol. The results are shown in [Figure number missing]. Figure 2 As shown.

[0034] Cytotoxicity of costus lactone The concentration of L929 fibroblasts was adjusted to 1×10⁻⁶ using DMEM complete medium. 4 Fibroblasts were cultured at a concentration of 100 μL / mL in 96-well plates. The plates were then transferred to a 37°C, 5% CO2 incubator and cultured for 14 h. After discarding the culture medium, 100 μL of DMEM complete medium containing 50 μg / mL costone was added to each well, and the plates were cultured for another 24 h. The growth morphology of fibroblasts in each well was observed under a microscope. This experiment also included blank control wells containing only DMEM serum-free medium and positive control wells containing DMEM complete medium supplemented with 5% phenol. The results are shown below. Figure 3 As shown.

[0035] Figure 2 This is a diagram showing the cytotoxicity of the modified silica prepared in Example 1. In the diagram, (1) is a diagram showing the cytotoxicity of the blank control well, (2) is a diagram showing the cytotoxicity of the modified silica prepared in Example 1, and (3) is a diagram showing the cytotoxicity of the positive control well. Figure 3 This is a graph showing the cytotoxicity of costunolide. In the graph, (1) shows the cytotoxicity of the blank control wells, (2) shows the cytotoxicity of costunolide, and (3) shows the cytotoxicity of the positive control wells. Figure 2-3 It is known that the modified silica and costus lactone provided by this invention have no obvious cytotoxicity and can be used for subsequent experiments.

[0036] Experimental Example 2 Experiment 2 used RAW264.7 cells to detect the effect of costunolide on inhibiting macrophage inflammatory response. The specific detection process is as follows: 2.1 Grouping Group 1: RAW264.7 cells were cultured in DMEM medium; Group 2: RAW264.7 cells were cultured in DMEM medium and treated with 100 ng / mL lipopolysaccharide (LPS) for 30 min. Group 3: RAW264.7 cells were cultured in DMEM medium and pre-cultured with 8 μmol / L costunol for 2 h, and then treated with 100 ng / mL LPS for 30 min.

[0037] 2.2 Indicator Testing Cell lysis buffer was added to each well, and total protein was extracted using a protein extraction kit. The protein concentration in the lysis buffer was then detected using a protein analysis kit. The protein was transferred to a polyvinylidene fluoride membrane by 10% sodium dodecyl sulfate polyacrylamide gel electrophoresis. The membrane was blocked in 10% skim milk at room temperature for 2 hours. Specific antibodies were added, and the membrane was detected using a chemiluminescent reagent. GAPDH protein was used as an internal control. The experimental results are shown in Table 1.

[0038] Table 1 Table 1 shows that, compared to the first group, the second group exhibited a significant increase in the release of inflammatory cytokines IL-6 and TNF-α due to LPS stimulation, indicating the successful establishment of an inflammation model. Compared to the second group, the third group, pretreatment of RAW264.7 cells with costunolide reduced the release of IL-6 and TNF-α inflammatory cytokines, as well as decreased the expression levels of p-IKBα and p-p65. These results indicate that costunolide alleviates LPS-induced macrophage inflammation by inhibiting the NF-κB signaling pathway, demonstrating its anti-inflammatory effect.

[0039] Experimental Example 3 Experiment 3 tested the inhibition rate of the compositions of Examples 4-6 and Comparative Examples 1-2 against glucosyltransferase (GTF). The specific testing process is as follows: 3.1 Extraction of glucose transferase In a clean bench, 3.75 mL of *Streptococcus brevis* culture was added to 15 mL of BHI medium and anaerobically cultured at 37°C for 1 day. 5 mL of the bacterial culture was added to THB medium, sealed, and anaerobically cultured at 37°C for 20 h. The culture was then centrifuged at 4°C and 4000 rpm for 15 min. The cell pellet was collected and washed with PBS buffer (pH 6). The mixture was then centrifuged again at 4°C and 4000 rpm for 15 min, and the cell pellet was collected. The collected cell pellet was added to 50 mL of 8 mol / L urea solution and shaken at 20°C for 1 h. It was then centrifuged at 4°C and 15000 rpm for 8 min, and the supernatant containing glucosyltransferase was collected. The supernatant was filtered through a 0.8 μm syringe bacterial filter and dialyzed continuously with PBS buffer (pH 6) for 1 day (using a 20000 MW biodialysis membrane) to obtain the crude glucosyltransferase solution.

[0040] 3.2 Preliminary Experiment 0.05 mL, 0.1 mL, 0.15 mL, and 0.2 mL of crude glucosyltransferase enzyme solution were mixed with 0.6 mL of PBS solution, and the volume was adjusted to 3 mL with distilled water. After incubation at 37 °C for 3 h, the absorbance was measured at 550 nm. The amount of enzyme solution corresponding to an absorbance of 1.0 was used as the enzyme solution volume for subsequent inhibition experiments. The results showed that when the crude glucosyltransferase enzyme solution was 0.15 mL, the absorbance was 1.0. Therefore, this invention uses 0.15 mL of crude glucosyltransferase enzyme solution as the enzyme solution volume for subsequent inhibition experiments.

[0041] 3.3 Detection of inhibition rate 0.15 mL of crude glucosyltransferase was mixed with 0.6 mL of PBS solution, and 2 mg of the compositions from Examples 4-6 and Comparative Examples 1-2 were added respectively. The volume was brought up to 3 mL with distilled water, and the mixture was incubated at 37 °C for 3 h. The absorbance was measured at 550 nm. A blank control group with an equal amount of PBS was also included. The inhibition rate was calculated as: (OD value of blank control group - OD value of experimental group) / OD value of blank control group × 100%. The experimental results are shown in Table 2.

[0042] Table 2 As shown in Table 2, compared with the composition prepared by silica nanoparticles in Comparative Example 2, the composition prepared by the modified silica of this invention can effectively inhibit the activity of GTF, thereby inhibiting the production of dextran, reducing the attachment sites of pathogenic bacteria on teeth, and helping the treatment and recovery of periodontitis.

[0043] Experiment Example 4 Experiment 4 tested the therapeutic effects of the compositions of Examples 4-6 and Comparative Examples 1-2 on periodontitis. The specific testing process is as follows: 4.1 Laboratory Animals Forty 6-week-old male SD rats were acclimatized for one week. After one week, five rats were randomly selected as the normal control group.

[0044] 4.2 Modeling Except for the normal group, the other rats were anesthetized by intraperitoneal injection of sodium pentobarbital solution. A 0.2 mm orthodontic ligature wire was used to ligate the interproximal spaces between the first and second molars in the right maxilla, with the wire being pressed as close to the gingiva as possible. The rats were fed a high-sugar diet (high-sugar periodontitis diet composition: 30g skim milk powder, 5g flour, 55g sucrose, 3g yeast powder, 1.5g liver powder, a small amount of salt, and fresh vegetables). The ligature wires were observed every week for detachment; if detachment was observed, the ligatures were re-ligated. After 3 weeks, the periodontal condition of each rat was observed: gingival redness and swelling, bleeding on probing, and increased exposure of the tooth root neck indicated successful establishment of the periodontitis model.

[0045] 4.3 Administration Rats that successfully modeled the disease were randomly divided into the following 6 groups: model group, Examples 4-6, and Comparative Examples 1-2, with 5 rats in each group. Drug administration was performed as follows: Model group: 20 μL of sterile water was injected into the periodontal pocket. Example 4 group: 20 μL of the drug composition of Example 4 was injected into the periodontal pocket once a week for 4 weeks; Example 5 group: 20 μL of the drug composition of Example 5 was injected into the periodontal pocket once a week for 4 weeks; Example 6 group: 20 μL of the drug composition of Example 6 was injected into the periodontal pocket once a week for 4 weeks; Comparative Example 1: 20 μL of the drug composition of Comparative Example 1 was injected into the periodontal pocket once a week for 4 weeks; Comparative Example 2: 20 μL of the drug composition of Comparative Example 2 was injected into the periodontal pocket once a week for 4 weeks.

[0046] 4.4 Indicator Testing 4.4.1 Imaging examinations Four weeks after treatment, rats in each group were euthanized under anesthesia, and specimens of the right maxillary molar, alveolar bone, and jawbone were collected. The maxilla of the rats was scanned and three-dimensional images were reconstructed. In order to assess the alveolar bone damage in each treatment group, the distance from the cementum-enamel junction (CEJ) to the alveolar crest (ABC) of the mesial, distal, and central parts of the first molar of each rat was measured, and the average value of the three was calculated. The experimental results are shown in Table 3.

[0047] 4.4.2 Inflammatory Factors The expression of TNF-α and IL-6 in the periodontal tissues of various rats was detected, and the experimental results are shown in Table 3.

[0048] Table 3 As shown in Table 3, compared with Comparative Examples 1-2, the pharmaceutical composition prepared in Example 1 of this invention has a better therapeutic effect on periodontitis. The above results indicate that the combined use of modified silica and costunolide can enhance the therapeutic effect on periodontitis.

[0049] The above embodiments are merely preferred embodiments of the present invention and should not be construed as limiting the scope of protection of the present invention. Any non-substantial changes and substitutions made by those skilled in the art based on the present invention shall fall within the scope of protection claimed by the present invention.

Claims

1. A pharmaceutical composition for treating periodontitis, characterized in that, The raw materials include the following parts by weight: 4-8% blue cloth extract, 0.5-1% propolis extract, 0.8-1.2% vitamin B2, 0.6-0.8% vitamin C, 4-8% carboxymethyl chitosan, 0.3-0.5% gelatin, 0.1-0.3% modified silica, 0.25-0.3% costus lactone, and the balance being deionized water; The preparation process of the modified silica is as follows: S1. Add silica nanoparticles to toluene, then add silane coupling agent, stir and react to obtain silica nanoparticles modified with silane coupling agent; S2. The silica nanoparticles modified with the silane coupling agent are added to N,N-dimethylformamide, followed by sophorolipid and an initiator. The mixture is heated to react and obtain the modified silica.

2. The pharmaceutical composition for treating periodontitis according to claim 1, characterized in that, The mass ratio of silica nanoparticles to silane coupling agent in step S1 is 10:(1-1.5).

3. The pharmaceutical composition for treating periodontitis according to claim 2, characterized in that, The silane coupling agent is vinyltriethoxysilane.

4. The pharmaceutical composition for treating periodontitis according to claim 1, characterized in that, The stirring reaction in step S1 is carried out at a temperature of 55-65℃ for 5-6 hours.

5. The pharmaceutical composition for treating periodontitis according to claim 1, characterized in that, The mass ratio of the silane coupling agent-modified silica nanoparticles, sophorolipids, and initiator in step S2 is 100:(12-15):(0.5-1.5).

6. The pharmaceutical composition for treating periodontitis according to claim 5, characterized in that, The initiator is azobisisobutyronitrile.

7. The pharmaceutical composition for treating periodontitis according to claim 1, characterized in that, The heating reaction in step S2 is carried out at a temperature of 85-95°C for 3.5-5 hours.

8. A method for preparing a pharmaceutical composition for treating periodontitis according to any one of claims 1-7, characterized in that, Includes the following steps: (a) Weigh each raw material according to the stated weight parts, add carboxymethyl chitosan to half of the deionized water to obtain a carboxymethyl chitosan solution; (b) Add gelatin to the remaining deionized water to obtain a gelatin solution, and then add modified silica, costus lactone, propolis extract, blue cloth extract, vitamin B2 and vitamin C in sequence to obtain a mixture. (c) Add the carboxymethyl chitosan solution to the mixture and mix by ultrasonication.

9. The method for preparing the pharmaceutical composition for treating periodontitis according to claim 8, characterized in that, The ultrasonic mixing time in step (c) is 10-15 min.

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