Mouthwash for treating oral ulcer caused by chemoradiotherapy

Abstract

The invention discloses mouthwash for treating oral ulcer caused by chemoradiotherapy, which is mainly prepared from the following raw materials in percentage by weight: 0.15 percent to 0.25 percent of chlorhexidine gluconate, 0.015 percent to 0.025 percent of polypeptide of which the amino acid sequence is RWRWRW, 0.05 percent to 0.15 percent of sodium hyaluronate, 0.05 percent to 0.15 percent of menthol, 2.8 percent to 3.2 percent of humectant, 0.45 percent to 0.55 percent of sodium ascorbyl phosphate, 0.5 percent to 1 percent of sodium bicarbonate and the balance of distilled water. The mouthwash for treating the oral ulcer caused by the chemoradiotherapy not only has antibacterial and moisturizing functions, but also can relieve the pain degree of the oral ulcer caused by the chemoradiotherapy, reduce the infection risk and promote ulcer healing, the technical problem that an existing product is single in function is solved, a patient does not need to alternately use multiple preparations, and the compliance is high.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical preparation technology, specifically relating to a mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy. Background Technology

[0002] Oral ulcers are highly common in cancer patients undergoing radiotherapy and chemotherapy. These ulcers manifest as mucosal erythema, erosion, ulceration, and severe pain, and in severe cases, can lead to treatment interruption and affect prognosis. Current clinical management strategies for this type of oral mucositis are mostly symptomatic, commonly including: basic cleaning and neutralization of the acidic environment using saline or sodium bicarbonate solution; temporary analgesia with mouthwash containing local anesthetics such as lidocaine; prevention of secondary infection with antibacterial mouthwashes such as chlorhexidine; topical application of corticosteroid mouthwashes (such as dexamethasone) to reduce inflammation; and promotion of repair using recombinant human epidermal growth factor (rhEGF) gel or sodium hyaluronate. In addition, supplementation with B vitamins and vitamin C is also considered to support mucosal health.

[0003] However, existing technologies have the following problems: (1) Existing mouthwashes are only developed for analgesia, anti-inflammation, or antibacterial purposes, with limited functions and a lack of integrated solutions for multiple pathological aspects such as pain, infection, inflammation, and repair obstacles. Patients often need to use multiple preparations alternately, resulting in poor compliance; (2) Some effective ingredients, such as vitamin C, are difficult to apply stably and gently in mouthwashes because their aqueous solutions are unstable and highly acidic, which can irritate damaged mucosa; (3) Existing solutions rarely include compound preparations of potent anti-inflammatory ingredients (such as hormones) and long-acting repair ingredients (such as cytokines), and often neglect the immediate protection and moisturizing of the local microenvironment of the oral mucosa. Therefore, it is urgent to develop a multifunctional compound mouthwash that is mild and stable and can synergistically act on all key aspects of oral ulcers caused by radiotherapy and chemotherapy. Summary of the Invention

[0004] The purpose of this invention is to provide a mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy, thereby solving the technical problems existing in the prior art.

[0005] According to a first aspect of the present invention, a mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy is provided, wherein the raw materials are mainly composed of the following components by weight percentage: chlorhexidine gluconate 0.15%-0.25%, polypeptide with amino acid sequence RWRWRW 0.015%-0.025%, sodium hyaluronate 0.05%-0.15%, menthol 0.05%-0.15%, sorbitol 2.8%-3.2%, sodium ascorbate phosphate 0.45%-0.55%, sodium bicarbonate 0.5%-1%, and the balance being distilled water.

[0006] This invention provides a mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy, offering a multi-target synergistic compound composition. Chlorhexidine gluconate possesses broad-spectrum antibacterial properties; sodium hyaluronate provides physical barrier protection and moisturizing repair; sodium ascorbate phosphate is stable and has antioxidant and wound-healing properties; and the polypeptide RWRWRW exhibits good antibacterial activity at weakly acidic radiotherapy and chemotherapy-induced oral ulcer sites. By using sodium ascorbate phosphate instead of traditional vitamin C, while retaining its collagen-promoting and antioxidant effects, it fundamentally overcomes the technical obstacles of unstable, highly acidic, and irritating ordinary vitamin C aqueous solutions, enabling its safe and stable application in treating radiotherapy and chemotherapy-induced oral ulcers. The mouthwash for radiotherapy and chemotherapy-induced oral ulcers is obtained by combining the polypeptide with the amino acid sequence RWRWRW with chlorhexidine gluconate, sodium ascorbate phosphate, and sodium hyaluronate. This compounding of raw materials improves product stability, and the components do not react with each other, thus preventing a decrease in the therapeutic effect of radiotherapy and chemotherapy-induced oral ulcers. At the same time, sodium bicarbonate is added to regulate the oral microenvironment. This mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy is mild and stable.

[0007] Among them, the polypeptide with the amino acid sequence RWRWRW and chlorhexidine gluconate are cationic antibacterial agents, and sodium ascorbate phosphate is negatively charged in solution. They all exist in their respective ionic forms in mouthwash and will not affect their respective chemical structural stability. Not only will the three not interact to reduce the therapeutic effect, but the coexistence of positive and negative ions of the raw materials can make the raw materials form salts in water, which will increase their solubility in water and be more beneficial to the overall stability of the product. Furthermore, the ionic state of polypeptide RWRWRW in solution may be beneficial to the physicochemical stability of the product.

[0008] In some embodiments, the raw materials, by weight percentage, mainly consist of the following components: 0.2% chlorhexidine gluconate, 0.02% polypeptide with the amino acid sequence RWRWRW, 0.1% sodium hyaluronate, 0.1% menthol, 3% sorbitol, 0.5% sodium ascorbate phosphate, 0.5%-1% sodium bicarbonate, with the balance being distilled water.

[0009] In some implementations, the mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy has a pH of 7.2-7.6.

[0010] In some embodiments, the polypeptide with the amino acid sequence RWRWRW is a synthetically produced cationic antimicrobial peptide with a purity of 95%-99%, and its amino acid sequence is arginine-tryptophan-arginine-tryptophan-arginine-tryptophan (Arg-Trp-Arg-Trp-Arg-Trp), with CAS number 359632-11-4.

[0011] In some embodiments, a polypeptide with the amino acid sequence RWRWRW is prepared by the following steps: Using the Fmoc solid-phase polypeptide synthesis method, 2-CTC resin is first fully swollen with DCM. 3.0 eq of Fmoc-Trp(Boc)-OH is dissolved in DMF and added to the resin, followed by the addition of DIPEA, HOBt, and HATU. After reacting at room temperature for 3 hours, the waste liquid is discarded, and the mixture is washed three times with DMF. Fmoc protection is removed using a PPD / DMF solution (20% v / v), followed by three more washes with DMF. 3 eq of Fmoc-Arg(Pbf)-OH is dissolved in DMF and added to the resin, followed by the addition of DIPEA, HOBt, and HATU. After coupling at room temperature for 3 hours, Fmoc is removed using a PPD / DMF solution (20% v / v). The above steps are repeated until a complete polypeptide sequence is synthesized. A 5% trifluoroacetic acid-dichloromethane (TFA-DCM) solution was added to the resin to lyse the peptides. The resulting lysate was concentrated under vacuum and purified by C18 reversed-phase silica gel column chromatography. Finally, the product was obtained by lyophilization.

[0012] This mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy is a weakly alkaline mouthwash. When used for oral ulcers caused by radiotherapy and chemotherapy, it can neutralize the acidic environment in the mouth, reduce chemical irritation to the damaged mucosa, and work with sodium hyaluronate to improve the overall gentleness and comfort of the product. It is especially suitable for radiotherapy and chemotherapy patients with fragile mucosa.

[0013] In some implementations, the humectant is sorbitol.

[0014] According to a second aspect of the present invention, a method for preparing a mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy is provided, comprising the following steps: (1) Add sodium hyaluronate to distilled water and stir to obtain solution A; (2) Add chlorhexidine gluconate, a polypeptide with the amino acid sequence RWRWRW, sodium ascorbate phosphate, humectant and sodium bicarbonate to distilled water in sequence, stir, and obtain solution B; (3) Add solution B slowly to solution A while stirring to obtain a mixed system; (4) Add menthol to the mixture and stir to obtain a mixture; (5) Adjust the pH of the mixture to 7.2-7.6 using a pH adjuster; (6) Add distilled water to the mixture and stir to obtain the final product.

[0015] In some embodiments, in step (4), menthol is added to the mixture at 25-30°C. The purpose of selecting the temperature of the mixture is to avoid loss of volatile components.

[0016] In some embodiments, step (6) further includes a step of filtering and retaining the filtrate after stirring. Step (6) further includes a step of filtering the filtrate through a 0.45 μm microporous membrane after stirring and retaining the filtrate.

[0017] In some embodiments, the pH adjuster is a 0.01-0.1 mol / L sodium bicarbonate solution or a 0.9-1.1 mol / L hydrochloric acid solution. Specifically, the pH adjuster is a 0.05 mol / L sodium bicarbonate solution or a 1 mol / L hydrochloric acid solution.

[0018] It should be noted that in step (5), when the pH value of the mixture does not meet the range of 7.2-7.6, a small amount of low-concentration pH adjuster is added to ensure that the mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy meets the pH range. When using the mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy, the adjustment of the oral pH environment mainly relies on the sodium bicarbonate added in step (2). In step (6), due to the low amount of distilled water added, the pH value of the mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy is 7.2-7.6.

[0019] According to a third aspect of the present invention, a mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy is provided for use in the preparation of a medicament for treating oral ulcers caused by radiotherapy and chemotherapy.

[0020] This mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy can be used to prepare medications for treating oral ulcers caused by radiotherapy and chemotherapy in cancer patients. It can effectively relieve pain, reduce the risk of infection, and accelerate ulcer healing.

[0021] The beneficial effects of this invention are as follows: (1) This invention uses chlorhexidine gluconate, a polypeptide with the amino acid sequence RWRWRW, and sodium ascorbate phosphate as raw materials to compound a solution targeting multiple key pathological links of oral ulcers caused by radiotherapy and chemotherapy. The resulting mouthwash not only has antibacterial and moisturizing functions, but also reduces the pain of oral ulcers caused by radiotherapy and chemotherapy, reduces the risk of infection, and promotes ulcer healing. It overcomes the technical problem of the single function of existing products. Patients do not need to use multiple preparations alternately, and the compliance is high. (2) The present invention uses sodium ascorbate phosphate as raw material, which has the effects of promoting collagen synthesis and anti-oxidation. It not only solves the technical problems of unstable vitamin C aqueous solution, strong acidity and great irritation to ulcer surface when vitamin C is used in mouthwash, but also can be safely and stably applied in mouthwash. In addition, it can synergistically promote mucosal repair with other raw materials. (3) The raw materials of the present invention can mutually enhance each other's solubility in water, thereby improving the overall stability of the product; (4) The mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy of the present invention is mild and stable. By adding sodium bicarbonate and adjusting the pH value to near neutral, it effectively neutralizes the acidic environment in the oral cavity and reduces the chemical stimulation to the damaged mucosa. Sodium bicarbonate can also work with sodium hyaluronate to improve the overall mildness and comfort of the product. It is especially suitable for patients with oral ulcers caused by radiotherapy and chemotherapy whose mucosa is fragile. Detailed Implementation

[0022] The present invention will be described in further detail below, but the embodiments of the present invention are not limited thereto. The raw materials and reagents involved in the following examples are all available from commercial sources.

[0023] In this invention, a polypeptide with the amino acid sequence RWRWRW is synthesized using conventional methods, including the following steps: Using the Fmoc solid-phase polypeptide synthesis method, firstly, 2-CTC resin is fully swollen with DCM. 3.0 eq of Fmoc-Trp(Boc)-OH is dissolved in DMF and added to the resin, followed by the addition of DIPEA, HOBt, and HATU. After reacting at room temperature for 3 hours, the waste liquid is discarded, and the mixture is washed three times with DMF. Fmoc protection is removed using a PPD / DMF solution (20% v / v), followed by three more washes with DMF. Then, 3 eq of Fmoc-Arg(Pbf)-OH is dissolved in DMF and added to the resin, followed by the addition of DIPEA, HOBt, and HATU. After coupling at room temperature for 3 hours, Fmoc is removed using a PPD / DMF solution (20% v / v). The above steps are repeated until a complete polypeptide sequence is synthesized. A 5% trifluoroacetic acid-dichloromethane (TFA / DCM) solution was added to the resin to lyse the peptides. The resulting lysate was concentrated under vacuum and purified by C18 reversed-phase silica gel column chromatography. Finally, the product was obtained by lyophilization.

[0024] It should be noted that peptides with the amino acid sequence RWRWRW can also be obtained by purchasing commercially available products.

[0025] Example 1 This embodiment provides a mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy, and a method for preparing the same.

[0026] The formula for a mouthwash to treat oral ulcers caused by radiotherapy and chemotherapy is as follows: chlorhexidine gluconate (0.2g), a polypeptide with the amino acid sequence RWRWRW (0.02g), sodium hyaluronate (0.1g), menthol (0.1g), sodium ascorbate phosphate (0.5g), sorbitol (3.0g), sodium bicarbonate (0.5g), and the remainder is distilled water.

[0027] The preparation method includes the following steps: (1) Add sodium hyaluronate slowly to distilled water that accounts for about 40% of the total water volume, and stir to make it fully swell and dissolve, to obtain a clear viscous liquid (solution A). (2) In another container, take about 50% of the total water volume of distilled water, and add chlorhexidine gluconate, a polypeptide with the amino acid sequence RWRWRW, sodium ascorbate phosphate, sorbitol and sodium bicarbonate to the distilled water in sequence, and stir until completely dissolved to obtain solution B; (3) Add solution B slowly to solution A while stirring to obtain a mixed system; (4) Control the temperature of the mixing system to 25-30℃, add menthol to the mixing system, stir evenly to obtain a mixture; (5) Adjust the pH of the mixture to 7.2-7.6 using 0.01M sodium bicarbonate aqueous solution or 0.1M dilute hydrochloric acid; (6) Add distilled water to the mixture until the total weight is 100g, stir evenly, filter through a 0.45 μm microporous membrane for sterilization, and then aseptically dispense into the final product.

[0028] Experimental Example 1 Twenty-four SD rats were randomly divided into four groups (n=6): a normal control group, a blank control group, a positive control group, and a treatment group. The normal control group received no treatment. For the other three groups, a rat oral ulcer model was established using a chemical cauterization method. Filter paper (5 mm in diameter, 1 mm thick) soaked in 90% phenol solution was applied to the buccal mucosa of the rats for 60 seconds, once daily for 7 days, successfully establishing the rat oral ulcer model. For the blank control group, sterile cotton swabs were used to apply physiological saline evenly to the ulcer surface and maintain contact for approximately 60 seconds. For the positive control group, sterile cotton swabs were used to apply commercially available recombinant human epidermal growth factor gel (purchased from Guilin Huanowei Gene Pharmaceutical Co., Ltd.) evenly to the ulcer surface and maintain contact for approximately 60 seconds. For the treatment group, sterile cotton swabs were used to apply the mouthwash for treating radiotherapy and chemotherapy-induced oral ulcers (Example 1) evenly to the ulcer surface and maintain contact for approximately 60 seconds. The drugs were administered twice daily for 7 days. On day 7, the number of times each animal wiped its mouth within 5 minutes was counted to reflect the pain level of the oral ulcers, and the area of ​​the oral ulcers was counted to reflect the treatment effect of different treatment methods. The results are shown in Table 1.

[0029] Table 1 shows that on day 7, the number of mouth wipings and the ulcer area in the treatment group and the positive control group were lower than those in the blank control group, indicating that both recombinant human epidermal growth factor gel and mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy had good relieving effects on pain and ulcer area. The number of mouth wipings in the treatment group was significantly lower than that in the positive control group, indicating that the mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy was more effective in relieving pain in rats with oral ulcers than recombinant human epidermal growth factor gel. The mean ulcer area in the treatment group was lower than that in the positive control group, indicating that the mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy was more beneficial for the treatment of radiotherapy-induced oral ulcers.

[0030] Table 1. Experimental results of the rat oral ulcer model established by chemical cauterization.

[0031] Experiment Example 2 Twenty-four SD rats were randomly divided into four groups (n=6): a normal control group, a blank control group, a positive control group, and a drug-treated group. The normal control group received no treatment. The other three groups were treated with cisplatin to establish a chemotherapy-induced rat oral ulcer model. Cisplatin (5 mg / L) was injected into the buccal mucosa of each rat, 50 μL per rat, once daily for 7 days, successfully establishing the chemotherapy-induced rat oral ulcer model.

[0032] For the blank control group, sterile cotton swabs were used to apply physiological saline evenly to the ulcer surface and maintain contact for approximately 60 seconds. For the positive control group, sterile cotton swabs were used to apply commercially available recombinant human epidermal growth factor gel evenly to the ulcer surface and maintain contact for approximately 60 seconds. For the treatment group, sterile cotton swabs were used to apply the mouthwash for treating radiotherapy and chemotherapy-induced oral ulcers (Example 1) evenly to the ulcer surface and maintain contact for approximately 60 seconds. Administered twice daily for 7 days. On day 7, the number of times each animal wiped its mouth within 5 minutes was counted to reflect the pain level of the oral ulcers, and the area of ​​the oral ulcers was counted to reflect the treatment effect of different treatment methods. The results are shown in Table 2.

[0033] As shown in Table 2, on day 7, the number of mouth wiping events in the treatment group was lower than that in the positive control group, indicating that the mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy was more effective than recombinant human epidermal growth factor gel in relieving the pain of chemotherapy-induced oral ulcers. Simultaneously, the ulcer area in the treatment group was significantly smaller than that in the blank control group, indicating that the mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy had a significant healing-promoting effect. The smaller ulcer area in the treatment group compared to the positive control group further demonstrates that the mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy is more effective than recombinant human epidermal growth factor gel in treating chemotherapy-induced oral ulcers.

[0034] Table 2. Therapeutic effects of chemotherapy-induced oral ulcer model in rats.

[0035] Comparative Example 1 This comparative example provides a mouthwash and its preparation method. The difference from Example 1 is that the mouthwash does not contain sodium ascorbate phosphate.

[0036] Comparative Example 2 This comparative example provides a mouthwash and its preparation method. The difference from Example 1 is that the mouthwash contains chlorhexidine gluconate.

[0037] Experimental Example 3 This experiment tested the product stability of the mouthwashes from Example 1 and Comparative Examples 1-2.

[0038] The test included: (1) placing the mouthwash at 4°C for 48 hours and observing the color change of the mouthwash; (2) placing the mouthwash under sunlight for 4 hours a day for a total of 5 days and observing the color change of the mouthwash.

[0039] After being placed at 4°C for 48 hours, a small amount of precipitate was observed in the mouthwash of Comparative Example 1, while the mouthwashes of Comparative Example 2 and Example 1 remained clear and transparent. Upon irradiation, the mouthwash of Comparative Example 2 changed from colorless to pale yellow, while the mouthwashes of Comparative Example 1 and Example 1 showed no significant color change. These results indicate that the combination of chlorhexidine gluconate, a peptide with the amino acid sequence RWRWRW, and sodium ascorbate phosphate is beneficial to improving the product stability of the mouthwash. It is speculated that this may be because the ionic state of the peptide with the amino acid sequence RWRWRW in solution is beneficial to the physicochemical stability of the product.

[0040] Experiment Example 4 This experiment investigated the minimum inhibitory concentration (MIC) of a peptide with the amino acid sequence RWRWRW against Streptococcus sanguinis, a common overproliferating bacterium in oral ulcers, under different pH conditions to verify its antibacterial activity.

[0041] The antimicrobial activity of the peptides was tested using the microdilution method. In short, a series of liquid culture media containing different concentrations of antimicrobial peptides and different pH values ​​were prepared and placed in bacterial culture tubes. An equal volume of bacterial suspension was added to each tube, and the tubes were incubated under suitable conditions for 24 hours. The growth of bacteria in the tubes was observed, and the lowest concentration of antimicrobial peptide at which bacterial growth was not visible to the naked eye was taken as the minimum inhibitory concentration (MIC).

[0042] At pH 7.2, the minimum inhibitory concentration (MIC) of peptide RWRWRW against *Streptococcus sanguinis* was 15.0 μg / mL, and at pH 4.5, the MIC was 3.4 μg / mL. The results indicate that peptide RWRWRW exhibits antibacterial activity at different pH values.

[0043] When used by patients with oral ulcers caused by radiotherapy and chemotherapy, the neutralizing effect of sodium bicarbonate creates a neutral or alkaline oral environment, limiting the spread of inflammatory mediators at the ulcer site and reducing their impact on surrounding normal tissues. However, due to the inflammatory response, the ulcer site remains slightly acidic. The peptide RWRWRW exerts its antibacterial activity at the ulcer site. Therefore, the antibacterial activity of the peptide RWRWRW at different pH levels is beneficial for its effectiveness in various pH environments within the oral cavity.

[0044] Comparative Example 3 This comparative example provides a mouthwash and its preparation method.

[0045] The mouthwash formula is as follows: chlorhexidine gluconate (0.1g), polypeptide with amino acid sequence RWRWRW (0.02g), sodium hyaluronate (0.1g), menthol (0.1g), sodium ascorbate phosphate (0.5g), sorbitol (3.0g), sodium bicarbonate (0.5g), and the remainder is distilled water.

[0046] The preparation method includes the following steps: (1) Add sodium hyaluronate slowly to distilled water that accounts for about 40% of the total water volume, and stir to make it fully swell and dissolve, to obtain a clear viscous liquid (solution A). (2) In another container, take about 50% of the total water volume of distilled water, and add chlorhexidine gluconate, a polypeptide with the amino acid sequence RWRWRW, sodium ascorbate phosphate, sorbitol and sodium bicarbonate to the distilled water in sequence, and stir until completely dissolved to obtain solution B; (3) Add solution B slowly to solution A while stirring to obtain a mixed system; (4) Control the temperature of the mixing system to 25-30℃, add menthol to the mixing system, stir evenly to obtain a mixture; (5) Adjust the pH of the mixture to 7.2-7.6 using 0.01M sodium bicarbonate aqueous solution or 0.1M dilute hydrochloric acid; (6) Add distilled water to the mixture until the total weight is 100g, stir evenly, filter through a 0.45 μm microporous membrane for sterilization, and then aseptically dispense into the final product.

[0047] Comparative Example 4 This comparative example provides a mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy, and its preparation method.

[0048] The formula for a mouthwash to treat oral ulcers caused by radiotherapy and chemotherapy is as follows: chlorhexidine gluconate (0.2g), a polypeptide with the amino acid sequence RWRWRW (0.02g), sodium hyaluronate (0.1g), menthol (0.1g), sodium ascorbate phosphate (0.2g), sorbitol (3.0g), sodium bicarbonate (0.5g), and the remainder is distilled water.

[0049] The preparation method includes the following steps: (1) Add sodium hyaluronate slowly to distilled water that accounts for about 40% of the total water volume, and stir to make it fully swell and dissolve, to obtain a clear viscous liquid (solution A). (2) In another container, take about 50% of the total water volume of distilled water, and add chlorhexidine gluconate, a polypeptide with the amino acid sequence RWRWRW, sodium ascorbate phosphate, sorbitol and sodium bicarbonate to the distilled water in sequence, and stir until completely dissolved to obtain solution B; (3) Add solution B slowly to solution A while stirring to obtain a mixed system; (4) Control the temperature of the mixing system to 25-30℃, add menthol to the mixing system, stir evenly to obtain a mixture; (5) Adjust the pH of the mixture to 7.2-7.6 using 0.01M sodium bicarbonate aqueous solution or 0.1M dilute hydrochloric acid; (6) Add distilled water to the mixture until the total weight is 100g, stir evenly, filter through a 0.45 μm microporous membrane for sterilization, and then aseptically dispense into the final product.

[0050] Experimental Example 5 The therapeutic effects of mouthwashes from Examples 1, 3, and 4 were verified using rat oral ulcer models constructed by chemical cauterization and those induced by chemotherapy drugs, respectively. The results are shown in Tables 3 and 4.

[0051] As shown in Tables 3 and 4, in both the rat oral ulcer model constructed by chemical cauterization and the rat oral ulcer model induced by chemotherapy drugs, the mouthwash of Example 1 was significantly better than Comparative Examples 3 and 4 in relieving both pain intensity and ulcer area. This indicates that the mouthwash formula of Example 1 had a much better therapeutic effect on the oral ulcer model than the formulas of Comparative Examples 3 and 4, and that the selection of the amount of raw materials used in the formula had a significant impact on the therapeutic effect of oral ulcers caused by radiotherapy and chemotherapy.

[0052] Table 3. Therapeutic effects of the rat oral ulcer model established by chemical cauterization.

[0053] Table 4. Therapeutic effects of chemotherapy-induced oral ulcer model in rats

[0054] The above descriptions are merely some embodiments of the present invention. Those skilled in the art can make various modifications and improvements without departing from the inventive concept of the present invention, and these all fall within the scope of protection of the present invention.

Claims

1. A mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy, characterized in that, By weight percentage, the raw materials mainly consist of the following components: chlorhexidine gluconate 0.15%-0.25%, polypeptide with amino acid sequence RWRWRW 0.015%-0.025%, sodium hyaluronate 0.05%-0.15%, menthol 0.05%-0.15%, humectant 2.8%-3.2%, sodium ascorbate phosphate 0.45%-0.55%, sodium bicarbonate 0.5%-1%, and the balance being distilled water.

2. The mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy according to claim 1, characterized in that, By weight percentage, the raw materials mainly consist of the following components: chlorhexidine gluconate 0.2%, polypeptide with amino acid sequence RWRWRW 0.02%, sodium hyaluronate 0.1%, menthol 0.1%, sorbitol 3%, sodium ascorbate phosphate 0.5%, sodium bicarbonate 0.5%-1%, and the balance being distilled water.

3. The mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy according to claim 1 or 2, characterized in that, The pH value of mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy is 7.2-7.

6.

4. The mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy according to claim 1, characterized in that, The humectant is sorbitol.

5. A method for preparing the mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy according to any one of claims 1-4, characterized in that, Includes the following steps: (1) Add sodium hyaluronate to distilled water and stir to obtain solution A; (2) Add chlorhexidine gluconate, a polypeptide with the amino acid sequence RWRWRW, sodium ascorbate phosphate, humectant and sodium bicarbonate to distilled water in sequence, stir, and obtain solution B; (3) Add solution B slowly to solution A while stirring to obtain a mixed system; (4) Add menthol to the mixture and stir to obtain a mixture; (5) Adjust the pH of the mixture to 7.2-7.6 using a pH adjuster; (6) Add distilled water to the mixture and stir to obtain the final product.

6. The preparation method according to claim 5, characterized in that, The pH adjuster is a 0.01-0.1 mol / L sodium bicarbonate solution or a 0.9-1.1 mol / L hydrochloric acid solution.

7. The preparation method according to claim 5, characterized in that, In step (4), menthol is added to the mixture at 25-30°C.

8. The preparation method according to claim 5, characterized in that, Step (6) also includes the step of filtering the solution through a 0.45 μm microporous membrane after stirring and retaining the filtrate.

9. The use of the mouthwash for treating oral ulcers caused by radiotherapy and chemotherapy according to any one of claims 1-4 in the preparation of a drug for treating oral ulcers caused by radiotherapy and chemotherapy.

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