A method for preparing a composite gel, products thereof and use in the preparation of a medicament for treating dry socket

Abstract

This invention discloses a method for preparing a composite gel, its product, and its application in the preparation of drugs for treating dry socket. Carboxymethyl chitosan and oat β-glucan are weighed and dissolved in deionized water, heated until completely dissolved, yielding carboxymethyl chitosan aqueous solution and oat β-glucan aqueous solution, respectively. Carbomer is weighed and placed in deionized water, allowed to swell at room temperature, yielding a carbomer aqueous solution. While stirring, carboxymethyl chitosan aqueous solution is added to the carbomer aqueous solution to adjust the pH to neutral. Then, oat β-glucan aqueous solution is added and mixed thoroughly to obtain the composite gel. The composite gel promotes the healing of dry socket, achieving rapid elimination of inflammation and accelerated wound and bone healing, providing a faster, more effective, and safer solution for the clinical prevention and treatment of dry socket.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of dry socket treatment drugs, and particularly relates to a preparation method of a composite gel and application of the composite gel in preparation of a dry socket treatment drug. BACKGROUND

[0002] Dry socket is one of the most common complications after oral tooth socket surgery. Dry socket is mostly seen after extraction of mandibular impacted wisdom tooth, and the incidence rate thereof is as high as 15%. Clinical manifestations of dry socket are bone wound infection caused by oral bacteria after tooth extraction and severe pain caused by exposure of nerve endings in the tooth socket and stimulation by various reasons.

[0003] At present, the method for treating dry socket in the clinic is to repeatedly flush with 3% hydrogen peroxide solution and normal saline under block anesthesia, and to wipe the tooth socket with a small cotton ball to remove the decayed and necrotic substances, and then to place an iodoform gauze in the tooth socket to prevent wound infection, but there are problems such as slow wound healing and the need to remove the gauze again. SUMMARY

[0004] This section aims to summarize some aspects of the embodiments of the application and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section and the abstract and title of the specification to avoid obscuring the purpose of this section, the abstract and the title, and such simplifications or omissions cannot be used to limit the scope of the application.

[0005] As one aspect of the application, the application provides a preparation method of a composite gel, which consists of the following steps,

[0006] Carboxymethyl chitosan and oat beta-glucan are weighed and dissolved in deionized water, heated to complete dissolution, and carboxymethyl chitosan and oat beta-glucan aqueous solutions are obtained, respectively. Carbopol is weighed and placed in deionized water, and is left to swell at room temperature to obtain a carbopol aqueous solution. While stirring, carboxymethyl chitosan aqueous solution is added to the carbopol aqueous solution, the pH is adjusted to neutral, and then oat beta-glucan aqueous solution is added, and the mixture is uniformly mixed to obtain a composite gel. In the composite gel, the mass concentration of carboxymethyl chitosan is 0.5-1.5%, the mass concentration of oat beta-glucan is 0.5-1.5%, and the mass concentration of carbopol is 0.4-0.6%.

[0007] As a preferred scheme of the preparation method of the composite gel, the carbopol is carbopol 940.

[0008] As a preferred embodiment of the preparation method of the composite gel described in this invention: the mass concentration of the carboxymethyl chitosan aqueous solution is 4-6%, the mass concentration of the oat β-glucan aqueous solution is 4-6%, and the mass concentration of the carbomer aqueous solution is 1-2%.

[0009] As a preferred embodiment of the preparation method of the composite gel described in this invention: the heating to complete dissolution, wherein the heating temperature is 80-85°C.

[0010] As a preferred embodiment of the preparation method of the composite gel described in this invention: the gel is allowed to swell at room temperature for 24 hours.

[0011] As a preferred embodiment of the preparation method of the composite gel described in this invention: in the composite gel, the mass concentration of carboxymethyl chitosan is 1%, the mass concentration of oat β-glucan is 1%, and the mass concentration of carbomer is 0.5%.

[0012] As a preferred embodiment of the preparation method of the composite gel described in this invention, the molecular weight of the carboxymethyl chitosan is 3KD.

[0013] The present invention also provides the application of the composite gel in the preparation of a drug for treating dry socket, wherein the composite gel can promote wound healing and osteoblast migration and eliminate inflammation.

[0014] The beneficial effects of this invention are as follows: This study discovered and utilized the antibacterial, hemostatic, and osteogenic properties of carboxymethyl chitosan (CMCS) and the wound-healing effects of β-Dex. Furthermore, Carbomer 940 was added to improve the viscosity and consistency of the gel, meeting the requirements for alveolar filling in dry socket treatment. The composite gel, blended with the aforementioned polymeric materials and Carbomer 940, promotes dry socket healing, rapidly eliminating inflammation and accelerating wound and bone healing, providing a faster, more effective, and safer solution for the clinical prevention and treatment of dry socket. In addition, both CMCS and β-Dex have good biodegradability, making the treatment procedure more convenient compared to the need for secondary removal of iodoform gauze strips. Attached Figure Description

[0015] To more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort. Wherein:

[0016] Figure 1 The results are for screening composite gel formulations.

[0017] Figure 2 The effect of temperature and humidity on the viscosity of the composite gel.

[0018] Figure 3 To investigate the effect of β-Dex on promoting osteoblast migration using a scratch assay.

[0019] Figure 4 The migration rate statistics for each group in the scratch test are presented.

[0020] Figure 5 For the Oxford Cup antibacterial test.

[0021] Figure 6 The image shows the alveolar socket wound observed and stained with hematoxylin and eosin (HE) on the 4th day after tooth extraction.

[0022] Figure 7 This study compares the soft tissue recovery at 7 and 14 days among the blank control group, CMCS / β-Dex composite gel group, CMCS gel group, and iodoform gauze group.

[0023] Figure 8 HE staining results at 7d, 14d, and 28d for the blank control group, CMCS / β-Dex composite gel group, and iodoform gauze group.

[0024] Figure 9 The expression of IL-6 in rats of each group was detected by immunofluorescence assay.

[0025] Figure 10 The expression of IL-10 in rats of each group was detected by immunofluorescence. Detailed Implementation

[0026] To make the above-mentioned objectives, features and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention will be described in detail below with reference to specific examples.

[0027] Many specific details are set forth in the following description in order to provide a full understanding of the invention. However, the invention may also be practiced in other ways different from those described herein, and those skilled in the art can make similar extensions without departing from the spirit of the invention. Therefore, the invention is not limited to the specific embodiments disclosed below.

[0028] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in different places in this specification does not necessarily refer to the same embodiment, nor is it a single or selective embodiment that is mutually exclusive with other embodiments.

[0029] Example 1:

[0030] 1. Experimental materials:

[0031] Instruments: DF-101S thermostatic magnetic stirrer (Gongyi Yuhua Instrument Co., Ltd.); SB-5200D ultrasonic cleaner (Ningbo Xinzhi Biotechnology Co., Ltd.); GZX-9023 electric thermostatic drying oven (Shanghai Hede Experimental Equipment Co., Ltd.); MYX-15013 mold incubator (Tianjin Saidelis Experimental Analytical Instrument Manufacturing Plant); ACE600 vacuum spraying machine (Leica, EM, Germany); RX 50 biological microscope (Ningbo Sunny Instrument Co., Ltd.); clean bench (Suzhou Purification Equipment Co., Ltd.).

[0032] Reagents: Carbomer 940 (Shanghai Maclean Biochemical Co., Ltd.), 0.9% sodium chloride injection (Jiangsu Huai'an Shuanghe Pharmaceutical Co., Ltd.), carboxymethyl chitosan (CMCS, Xi'an Tianguangyuan Biotechnology Co., Ltd., 3KD), oat β-glucan (β-Dex, Xi'an Tianguangyuan Biotechnology Co., Ltd.), chloral hydrate (grade: AR, Sinopharm Chemical Reagent Co., Ltd.), 3% hydrogen peroxide disinfectant (Shandong Anjie Gaoke Disinfection Technology Co., Ltd.), epinephrine hydrochloride (Shanhai Hefeng Pharmaceutical Co., Ltd.), iodoform gauze strips (Xinxiang Huaxi Medical Supplies Co., Ltd.).

[0033] Animals: Female SD rats, weighing approximately 150g, were provided by the Animal Experiment Center of Xuzhou Medical University. They were kept in clean-grade and standard housing conditions. This experimental protocol was approved by the Animal Ethics Committee of Xuzhou Medical University.

[0034] Experimental methods:

[0035] Preparation and formulation screening of carboxymethyl chitosan / oat β-glucan composite gel:

[0036] Preparation method of composite gel: Weigh appropriate amounts of CMCS and β-Dex and add them to deionized water. Stir thoroughly with a magnetic stirrer at 80℃ until completely dissolved, preparing 4% (w / w) CMCS solution and 4% (w / w) β-Dex solution respectively. Weigh an appropriate amount of Carbomer 940 and place it in deionized water, allowing it to stand at room temperature for 24 hours to swell, preparing a 1.5% (w / w) Carbomer 940 sol. Slowly add CMCS sol to the Carbomer 940 sol while stirring. Adjust the pH to 7.0 with 4% NaOH solution, then add the β-Dex solution and continue stirring until homogeneous to obtain the composite gel.

[0037] Screening of Carbomer 940 Addition Amount: With the mass fractions of CMCS and β-Dex in the composite gel fixed at 1.0%, Carbomer 940 sol was added at mass fractions of 0.25%, 0.5%, and 0.75%, respectively, to prepare three experimental composite gel formulations according to method 2.1.1 (see Table 1). The color, odor, consistency, uniformity, gloss, and spreading properties of each formulation composite gel were observed, and the results were evaluated using an NDJ-1 rotational viscometer (rotor #4, rotation speed 6 r·min). -1 Test the viscosity of each formulation to screen for the optimal amount of Carbomer 940 to be added.

[0038] Table 1. Content (%) of each component in the experimental prescription

[0039] Experiment No. Carbomer 940 Carboxymethyl chitosan Oat beta-glucan 1 0.25 1.00 1.00 2 0.50 1.00 1.00 3 1.00 1.00 1.00

[0040] Figure 1 The results of the composite gel formulation screening are as follows. Figure 1 (A) Comparison of results for each formulation of compound gel after tilting at 45° and standing for 1 minute. Figure 1 (B) shows the viscosity test results of the composite gel, and Table 2 shows the sensory evaluation results of the composite gel. As can be seen from the various tables, the viscosity of the composite gel increases with the increase of the Carbomer 940 mass fraction. The composite gel prepared with a Carbomer 940 mass fraction of 0.25% has an uneven texture and low viscosity, making it difficult to remain in the dry socket wound due to excessive gel flow. The composite gel prepared with a Carbomer 940 mass fraction of 0.75% has a uniform texture but high viscosity, resulting in insufficient gel flow and poor filling performance. The composite gel prepared with a mass fraction of 0.5% has a uniform texture and moderate consistency, filling the dry socket wound well without causing discomfort to the patient's mouth. Based on a comprehensive evaluation including sensory evaluation and viscosity testing, the optimal formulation for the composite gel was determined to be: 0.5% Carbomer 940, 1.0% CMCS, and 1.0% β-Dex. This ratio was used in the following experiments.

[0041] Table 2 Sensory evaluation of the composite gel

[0042]

[0043] Effects of temperature and humidity on the viscosity of the composite gel: CMCS / β-Dex composite gels (1.0% CMCS, 1.0% β-Dex, 0.5% Carbomer 940) were prepared and placed at 25℃ and 37℃, and at relative humidity of 50% and 95%, respectively. The viscosity was tested using an NDJ-1 rotational viscometer (rotor #4, speed 6 r·min⁻¹). Figure 2As shown, in the test simulating oral temperature and humidity, the viscosity of the composite gel did not change much over time, indicating that the composite gel is not affected by temperature or humidity and can still maintain its good adhesion and filling properties under the special environment of the oral cavity, ensuring the effectiveness of dry socket treatment.

[0044] Example 2:

[0045] CMCS / β-Dex composite gel assay for promoting osteoblast proliferation: Mouse-derived pre-MC3T3-E1 osteoblasts were cultured in DMEM medium containing 10% fetal bovine serum and 3% penicillin-streptomycin antibiotics. The cells were incubated at 37°C with 5% CO2 and saturated humidity. Cell experiments were performed at passage 3. MC3T3-E1 cells in logarithmic growth phase were cultured at 2 × 10⁻⁶ cells / cells. 5 Cells were seeded at a density of / well in 6-well plates. Once the cell monolayer had reached confluence, a sterile 200 μL pipette tip was used to vertically scratch the cell layer, followed by rinsing with PBS to remove any remaining cells in the scratched area. Then, DMEM medium containing 0.5% β-Dex, 1% β-Dex, a mixture of 1% CMCS and 1.0% β-Dex, and a serum-free DMEM control were added, respectively. Cells were incubated at 37°C and 5% CO2 for 24 h. At 0 h and 24 h, cells from each experimental group were photographed using an imaging microscope, and the migration rate of each group was calculated as (initial scratch distance - current scratch distance) / initial scratch distance × 100%.

[0046] The results showed that, compared with the blank control group, both the 0.5% β-Dex group (P<0.001) and the 1.0% β-Dex group (P<0.001) significantly promoted osteoblast migration, and the higher the β-Dex concentration, the stronger the ability to promote osteoblast migration (compared to the 0.5% β-Dex group, the higher the concentration of β-Dex). ### P<0.001); the osteocyte proliferation-promoting effect of the 1% CMCS and 1.0% β-Dex mixture was similar to that of 1.0% β-Dex (P>0.05). Figure 3 To investigate the effect of β-Dex on promoting osteoblast migration using a scratch assay. Figure 4 The migration rate statistics for each group in the scratch test are as follows (compared with the blank group, ***P<0.001; compared with the 0.5% β-Dex group, ###P<0.001).

[0047] Example 3:

[0048] Antibacterial test: Agar was boiled and dissolved, then poured onto plates and placed in a constant temperature incubator until solidified. Staphylococcus aureus (CMCC(B)26003) bacterial suspension was evenly poured onto the plates and allowed to stand until solidification, thus preparing bacterial plates. Four sterilized Oxford cups were placed vertically on the surface of the culture medium, and gentle pressure was applied to ensure seamless contact between the cup and the medium. Oxford cup #1 contained no additives; Oxford cup #2 contained 100 μL of deionized water; Oxford cup #3 contained 100 μL of 1.0% CMCS solution; and Oxford cup #4 contained 100 μL of a mixed solution of 1% CMCS and 1.0% β-Dex. The culture medium was incubated at 37°C for 24 hours. The presence and diameter of inhibition zones were observed and measured.

[0049] Figure 5 The results of the Staphylococcus aureus inhibition test show that no inhibition zones appeared around Oxford cups 1 and 2, while clear inhibition zones appeared around cups 3 and 4. The outer diameter of the inhibition zone around Oxford cup 3 (1.0% CMCS solution) was 11 mm; subtracting the inner diameter, the result was 6.5 mm, indicating a good antibacterial effect of CMCS. The outer diameter of the inhibition zone around Oxford cup 4 (1% CMCS + 1.0% β-Dex mixed solution) was 13 mm; subtracting the inner diameter, the result was 8.5 mm, indicating that the composite gel showed the best antibacterial effect, more significant than CMCS alone.

[0050] Example 4:

[0051] Pharmacodynamic study:

[0052] Establishment of a rat dry socket model:

[0053] SD rats were anesthetized via intraperitoneal injection using a 4% chloral hydrate solution (1 mL / 100 g). After complete anesthesia, the gingiva was separated using a probe, and the maxillary first molar was extracted. The alveolar bone wall was continuously scraped to damage the wound. A cotton ball soaked in 1000-fold diluted epinephrine hydrochloride was inserted into the alveolar socket for 1–2 minutes to constrict blood vessels. After bleeding stopped, a cotton ball saturated with Staphylococcus aureus was placed in the extraction wound for 2 minutes to achieve bacterial infection. After the rats recovered, they were returned to the animal room, deprived of water for 2 hours, and then fed as usual. Four days later, the oral infection status of the rats was observed, and the maxilla and gingiva were collected for HE staining.

[0054] On the 4th day after tooth extraction, by Figure 6 As can be seen, there was obvious pale yellow, viscous purulent discharge in the rat's alveolar socket, accompanied by a slight odor. The gingiva around the alveolar socket was obviously red and swollen. Gently scraping the swollen gingiva with a probe revealed a small amount of bleeding, and the area of ​​the alveolar socket wound did not shrink significantly. At the same time, HE staining showed infection in the extraction socket, indicating that the rat dry socket model was successfully established.

[0055] Treatment plan: On the 4th day after tooth extraction, SD rats were randomly divided into four groups: a blank control group, a CMCS / β-Dex group, a CMCS gel group, and an iodoform gauze group, with 7 rats in each group. The blank control group received no treatment and their natural healing was observed. After the rats were completely anesthetized, a probe was used to remove purulent exudate and bacteria-laden cotton balls from the infected alveolar socket. The infected alveolar socket was cleaned alternately with cotton swabs soaked in 3% hydrogen peroxide solution and 0.9% physiological saline, respectively, and the residual cleaning solution in the alveolar socket was then absorbed with sterile cotton swabs. According to the same operation, CMCS / β-Dex composite gel and CMCS gel were injected into the alveolar sockets of the rats in the group, and iodoform gauze strips were packed into the alveolar sockets of the rats in the iodoform gauze group. The healing of the alveolar socket wounds of the rats was recorded. All rats were kept under the same conditions, such as temperature, feed, water, living environment, and sunlight, and were kept in accordance with the prescribed feeding and uniformity.

[0056] Measurement of extraction wounds: On days 4, 7, 10, and 14 after treatment, rats were anesthetized, and the healing of the alveolar socket wounds was observed and recorded by the naked eye. The maximum length (L) and width (W) of the alveolar socket wounds were measured using a ruler and compass. The initial length was recorded as L0 and the initial width as W0. The measurements were taken three times and the average value was recorded. The area of ​​the alveolar socket wounds was calculated and recorded to compare the soft tissue recovery of rats in each group.

[0057] Depend on Figure 7 As observed by the naked eye and as shown in Table 3 (extraction wound area measurement results), 7 days after treatment, the alveolar sockets of rats in the blank control group healed slowly, with large wounds remaining. The inflammation in the wounds of the CMCS / β-Dex composite gel group, CMCS gel group, and iodoform gauze group all significantly decreased, and the wound area shrank and gradually healed over time. The healing rate among the three treatment groups was: CMCS / β-Dex composite gel group > CMCS gel group ≈ iodoform gauze group. At 14 days after treatment, the blank control group still had noticeable wounds, while the CMCS / β-Dex composite gel group showed near-complete healing, with granulation tissue visible within the extraction wound. The healing effect was significantly better than that of the CMCS gel group and the iodoform gauze group.

[0058] Table 3 shows the measurement results of extraction wounds at various time points after treatment in the blank control group, CMCS / β-Dex composite gel group, CMCS gel group, and iodoform gauze group. On day 4 post-treatment, the wounds of rats in the blank control group healed slowly. The wound areas of rats in the CMCS / β-Dex composite gel group, CMCS gel group, and iodoform gauze group decreased significantly, and the wound healing speed was faster. Among them, the CMCS / β-Dex composite gel group showed the most significant healing effect, with more than half of the wound healed and the fastest healing speed. On day 7 post-treatment, the wounds of rats in the blank control group still did not show significant reduction. The extraction wound area of ​​the CMCS / β-Dex composite gel group further decreased, and the healing speed and effect were significantly better than those of the CMCS gel group and iodoform gauze group. On day 10 post-treatment, the wounds of rats in the blank control group had just healed more than half. On day 14 post-treatment, wounds were still visible in the blank control group. The wounds of rats in the CMCS gel group and iodoform gauze group were basically completely healed, with only some rats having minor wounds. The CMCS / β-Dex composite gel group showed the most significant healing effect, with a wound area of ​​only (0.6% ± 0.3). Table 3. Measurement of extraction wound area in the blank control group, CMCS / β-Dex composite gel group, CMCS gel group, and iodoform gauze group (n=3)

[0059]

[0060] Statistical results: Throughout the healing process, the CMCS / β-Dex composite gel group prepared in Example 1 showed a statistically significant difference compared to the blank control group (P < 0.01), and the CMCS gel group and iodoform gauze group also showed statistically significant differences compared to the blank control group (P < 0.05). Furthermore, there was no statistically significant difference between the CMCS gel group and the iodoform gauze group throughout the healing process (P > 0.05), indicating that the therapeutic effect of the gel prepared with CMCS alone is similar to that of the iodoform gauze. However, there was a statistically significant difference between the CMCS / β-Dex composite gel group and both the CMCS gel group and the iodoform gauze group (P < 0.05). These results indicate that the CMCS / β-Dex composite gel prepared in this invention, compared to the CMCS gel group, exhibits a significant synergistic effect with β-Dex through the interaction of CMCS and β-Dex.

[0061] Table 4. Evaluation of the synergistic therapeutic effect of CMCS / β-Dex composite gel on the healing of extraction wounds in rats with dry socket (14 days, n=3)

[0062]

[0063]

[0064] Note: +++ indicates strong synergy; ++ indicates moderate synergy.

[0065] Synergistic Evaluation: To evaluate the combined effect of CMCS and β-Dex, the combined effect index (CI) values ​​of CMCS and β-Dex (mass ratio 1:1) at 0.125 IC50, 0.25 IC50, 0.5 IC50, and 1.0 IC50 were obtained using the Chou-Talalay combination drug index method and CompuSy software (Table 4). The obtained IC values ​​were all less than 1, indicating that the combined effect of CMCS and β-Dex (mass ratio 1:1) has a synergistic effect, and the CI value is the smallest at the individual IC50 concentrations, indicating the best synergistic therapeutic effect for dry socket.

[0066] Example 5:

[0067] HE staining: Rats were sacrificed on days 1 and 14 post-treatment, and the maxilla and gingiva were harvested. The specimens were fixed in 4% paraformaldehyde solution, with the solution changed every 3 days, and then left to be processed. Seven days after fixation, the specimens were decalcified with 10% EDTA decalcification solution at room temperature, with the solution changed every 2 days until the bone softened. Afterward, the specimens were rinsed clean and dehydrated. The rat maxilla and gingiva tissues were routinely embedded in paraffin, cut into 5 μm thick sections, and stained with HE. The histological changes in the alveolar sockets were observed under a biological microscope. Figure 8 HE staining results at 7, 14, and 28 days for the blank control group, CMCS / β-Dex composite gel group, and iodoform gauze group. Figure 8 It was observed that after 7 days of treatment, the wounds of rats in the control group showed extensive infiltration of inflammatory cells (such as lymphocytes and neutrophils), indicating a severe inflammatory response. The inflammatory response in the CMCS / β-Dex composite gel group and the iodoform gauze group was milder than that in the control group, with localized neutrophil infiltration. After 14 days of treatment, the control group still had a severe inflammatory response and no epithelial continuity was observed. The inflammatory response in both the CMCS / β-Dex composite gel group and the iodoform gauze group was significantly reduced compared to 7 days, with inflammatory cell infiltration scattered. Furthermore, the epithelial continuity was restored significantly better and more completely in the CMCS / β-Dex composite gel group than in the iodoform gauze group. After 28 days of treatment, the granulation tissue in the extraction wounds of the control group was replaced by fibrous tissue. New bone remodeling occurred in both the CMCS / β-Dex composite gel group and the iodoform gauze group, with a higher degree of new bone remodeling in the CMCS / β-Dex composite gel group than in the iodoform gauze group.

[0068] Example 6:

[0069] Immunofluorescence detection of IL-6 and IL-10: On days 7 and 14, intact maxillae and gingival tissues from rats were harvested. After fixation in 4% paraformaldehyde, routine dehydration, embedding, sectioning, dewaxing, and antigen retrieval, the following procedures were performed: Newborn calf serum blocking solution was added and incubated at room temperature for 30 min; primary antibodies (IL-6 and IL-10) were added and incubated overnight at 4°C; secondary fluorescent antibody was added and incubated at 37°C for 30 min; DAPI was added for counterstaining and incubated at room temperature for 10 min; the sections were mounted with anti-fluorescence attenuation mounting medium, and the sections were observed and images acquired under a fluorescence microscope. The immunofluorescence results of inflammatory factors IL-6 and IL-10 in gingival tissues from different groups on days 7 and 14 are shown below. Figure 9 , Figure 10 Regarding the expression of the pro-inflammatory cytokine IL-6, at 7 and 14 days post-treatment, the fluorescence intensity of IL-6 in the blank group was significantly higher than that in the CMCS / β-Dex composite gel group and the iodoform gauze group, with no significant difference between the two groups. However, for the anti-inflammatory cytokine IL-10, with the extension of treatment time, the positive expression of IL-10 in both the CMCS / β-Dex composite gel group and the iodoform gauze group significantly increased. Furthermore, the positive expression of IL-10 in the CMCS / β-Dex composite gel group was significantly higher than that in the iodoform gauze group at 7 days post-treatment. At both 7 and 14 days post-treatment, the positive fluorescence expression of IL-10 in both the CMCS / β-Dex composite gel group and the iodoform gauze group was significantly higher than that in group A.

[0070] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.

Claims

1. The application of a composite gel in the preparation of a drug for treating dry socket, characterized in that: The preparation method of the composite gel consists of the following steps: Carboxymethyl chitosan and oat β-glucan were weighed and dissolved in deionized water, heated until completely dissolved, to obtain carboxymethyl chitosan aqueous solution and oat β-glucan aqueous solution, respectively. Carbomer 940 was weighed and placed in deionized water, and allowed to swell at room temperature to obtain carbomer 940 aqueous solution. While stirring, carboxymethyl chitosan aqueous solution was added to carbomer 940 aqueous solution to adjust the pH to neutral, and then oat β-glucan aqueous solution was added and mixed evenly to obtain composite gel. In the composite gel, the mass concentration of carboxymethyl chitosan was 1%, the mass concentration of oat β-glucan was 1%, and the mass concentration of carbomer 940 was 0.5%. The molecular weight of the carboxymethyl chitosan is 3 kDa.

2. The application according to claim 1, characterized in that: The process of heating until completely dissolved involves heating at a temperature of 80–85°C.

3. The application according to claim 1 or 2, characterized in that: The swelling is allowed to occur at room temperature, and the standing time is 24 hours.

4. The application according to claim 1 or 2, characterized in that: The composite gel can promote wound healing and bone cell migration, and eliminate inflammation.

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