A compound oral rinse composition and its preparation method

Abstract

This invention discloses a compound oral rinse composition and its preparation method, relating to the field of oral rinse technology. The compound oral rinse composition comprises the following components: a complex active ingredient, a mucosal repair agent, an anti-inflammatory synergist, a moisturizer, a solubilizer, a flavoring agent, a pH adjuster, and water, with the sum of all components being 100 wt%. The complex active ingredient is povidone-iodine and tinidazole, and the mucosal repair agent is at least one selected from chitosan, zinc hyaluronic acid, and silk fibroin. This invention enhances therapeutic efficacy through the synergistic effect of the complex active ingredient and the mucosal repair agent, effectively improving the oral environment and achieving anti-inflammatory and mucosal repair effects.

Description

Technical Field

[0001] This invention relates to the field of oral rinse solutions and related medical devices, specifically to a compound oral rinse solution composition and its preparation method. Background Technology

[0002] Oral diseases are a common problem affecting human health, including gingivitis, periodontitis, oral ulcers, and pericoronitis. These diseases not only cause discomfort such as pain, swelling, and bad breath, but can also affect normal daily functions such as eating and speaking, and in severe cases, even affect overall health. The oral cavity contains a complex microbial community, in which pathogens such as bacteria and fungi proliferate under suitable conditions, which is a significant factor in the development of oral diseases.

[0003] Currently, there are many types of mouthwashes on the market for treating oral diseases. However, existing mouthwashes have significant shortcomings in terms of the synergistic effect of active ingredients, mucosal repair function, and stability control: 1) Single active ingredient: Most commercially available mouthwashes use a single antibacterial ingredient (such as chlorhexidine, povidone-iodine, tinidazole, etc.), which has limited efficacy against complex oral infections (such as mixed infections of anaerobic bacteria and fungi), and long-term use can easily lead to drug resistance; 2) Lack of mucosal repair: Pathological conditions such as chemotherapy-induced oral mucositis and oral ulcers require synergistic repair ingredients, but traditional mouthwashes (such as sodium borate solution) only have basic cleaning functions and lack repair functions; 3) Ethanol dependence: Most mouthwashes need to add 15wt%-27wt% ethanol to dissolve fat-soluble ingredients, resulting in strong oral irritation and making them unsuitable for patients with mucosal damage. Summary of the Invention

[0004] This invention provides a compound oral rinse composition and its preparation method, which solves multiple technical problems in the prior art, such as poor synergy of active ingredients, poor mucosal repair function and poor stability.

[0005] The technical solution adopted in this invention is as follows:

[0006] A compound oral rinse composition, characterized in that it comprises the following components: a compound active ingredient, a mucosal repair agent, an anti-inflammatory synergist, a moisturizer, a solubilizer, a flavoring agent, a pH adjuster, and water, wherein the sum of the contents of each component is 100 wt%, wherein the compound active ingredient is povidone-iodine and tinidazole, and the mucosal repair agent is at least one of chitosan, zinc hyaluronic acid, and silk fibroin.

[0007] Preferably, the content of povidone-iodine in the composition is 0.4wt%~1wt%, and the content of tinidazole is 0.2wt%~1wt%.

[0008] Preferably, the chitosan content in the composition is 0 or 0.1wt%~1wt%, the zinc hyaluronic acid content is 0 or 0.01wt%~1wt%, and the silk fibroin content is 0 or 0.1wt%~1wt%.

[0009] Preferably, the anti-inflammatory synergist is at least one of the following plant extracts: baicalin, paeonol, zinc acetylsalicylate, flunixin meglumine, dipotassium glycyrrhizate, thymopentin, copper tripeptide-1, and liposomal curcumin, accounting for 0.01wt% to 0.3wt% of the composition.

[0010] Preferably, the moisturizer is one or more of glycerin, propylene glycol, sorbitol, and trehalose, accounting for 1 wt% to 5 wt% of the composition.

[0011] Preferably, the solubilizer is one or more of PEG 200, PEG 300, PEG 400, and PEG 600, accounting for 0.3wt% to 1.5wt% of the composition.

[0012] Preferably, the flavoring agent is any one of xylitol, erythritol, and isomalt, accounting for 0.5wt% to 4wt% of the composition.

[0013] Preferably, the pH adjuster is any one of a citric acid-sodium citrate buffer system, an acetate-sodium acetate buffer system, or a lactic acid-sodium lactate buffer system, accounting for 0.1wt% to 1wt% of the composition, and the pH adjuster adjusts the pH value of the composition to 5.5-6.5.

[0014] The preparation method of the composition described in any of the above schemes includes the following steps:

[0015] (1) Pre-dissolution in the dark: First, add water to dissolve the solubilizer, flavoring agent and humectant, then add the anti-inflammatory synergist and dissolve with ultrasonic assistance to obtain the solubilized phase; under the dark environment, add the compound active ingredients to water and stir to dissolve, then pass through a PVDF pre-filter membrane to obtain the active ingredient solution; under the dark environment, cool the solubilized phase to 25°C, slowly add the active ingredient solution, maintain pH 5.5–5.8, and obtain the main solution system;

[0016] (2) Mixing and volume adjustment: Under light-protected conditions, add the mucosal repair agent dropwise to the main solution system, add the pH adjuster to the above mixture, and adjust the pH of the solution to 5.8±0.1;

[0017] (3) In a light-proof environment, the above-mentioned composite liquid is filtered through multiple stages of sterilization, then aseptically filled and sterilized, and the filtrate is filled into a light-proof and heat-insulated liquid storage unit and sealed with nitrogen.

[0018] In summary, compared with the prior art, the present invention has the following advantages and beneficial effects:

[0019] 1. This invention enhances the therapeutic effect through the synergistic effect of compound active ingredients and mucosal repair agents, effectively improving the oral environment and playing a role in anti-inflammatory and mucosal repair.

[0020] 2. This invention solves the problem of poor stability in the prior art by dissolving the ingredients in steps, first adding solubilizing, moisturizing and anti-inflammatory components, then adding active ingredients, and adding povidone-iodine in the dark to avoid photolysis. The increased solubilizing agent solves the problem of tinidazole precipitation.

[0021] 3. By using mild solubilizing ingredients, this invention effectively avoids the irritation to the mucous membrane caused by the high concentration of ethanol in traditional mouthwashes; the pH buffer system simulates the oral physiological environment, avoiding large pH fluctuations in traditional mouthwashes, and further reducing mucous membrane irritation. Attached Figure Description

[0022] Figure 1 The flowchart illustrates the preparation process of the compound oral rinse composition provided by this invention. Detailed Implementation

[0023] The present invention will be described in detail below with reference to specific embodiments and examples, thereby making the advantages and various effects of the present invention more clearly apparent. Those skilled in the art should understand that these specific embodiments and examples are for illustrative purposes only and are not intended to limit the present invention.

[0024] Throughout this specification, unless otherwise specified, the terminology used herein should be understood to have the meaning commonly used in the art. Therefore, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. In the event of any conflict, this specification shall prevail.

[0025] Unless otherwise specified, all raw materials, reagents, instruments and equipment used in this invention can be purchased from the market or prepared by existing methods.

[0026] Example 1

[0027] The compound oral rinse composition provided in this embodiment has the following formula as shown in Table 1;

[0028] Table 1 Formulation ratio of Compound Oral Gargle Composition 1

[0029]

[0030] Its preparation process is as follows Figure 1 As shown, the specific preparation steps are as follows:

[0031] S1. Pre-dissolution (light-protected operation): Dissolve PEG 400, xylitol, and glycerin in 40°C water for injection by stirring. Add baicalin and sonicate for 20 minutes (300W). Separately, dissolve povidone-iodine and tinidazole in 25°C water for injection by stirring in the dark and pass through a 0.45μm PVDF membrane. Cool the solubilizing phase to 25°C and slowly add the active ingredient solution, maintaining the pH at 5.6±0.1.

[0032] S2. Mixing and adjusting volume: Add zinc hyaluronic acid to the main solution and stir at 200 rpm for 30 min; add citrate-sodium citrate buffer solution and adjust the pH to 5.8 ± 0.1.

[0033] S3. Sterile filling: After passing through a 0.22μm PES membrane for two-stage filtration, the contents are filled into the liquid storage unit of the quantitative spraying device (medical PP inner liner, 40ml) and sealed with nitrogen.

[0034] Example 2

[0035] The compound oral rinse composition provided in this embodiment has the formula shown in Table 2.

[0036] Table 2 Formulation ratio of compound oral rinse composition 2

[0037]

[0038] Its preparation process is as follows Figure 1 As shown, the specific preparation steps are as follows:

[0039] S1. Pre-dissolution (light-protected operation): Dissolve PEG 400, xylitol, and glycerin in 40°C water for injection by stirring. Add baicalin and sonicate for 20 minutes (300W). Separately, dissolve povidone-iodine and tinidazole in 25°C water for injection by stirring in the dark and pass through a 0.45μm PVDF membrane. Cool the solubilizing phase to 25°C and slowly add the active ingredient solution, maintaining the pH at 5.6±0.1.

[0040] S2. Mixing and Volume Adjustment: Add citrate-sodium citrate buffer solution to adjust the pH to 5.8±0.1.

[0041] S3. Sterile filling: After passing through a 0.22μm PES membrane for two-stage filtration, the contents are filled into the liquid storage unit of the quantitative spraying device (medical PP inner liner, 40ml) and sealed with nitrogen.

[0042] Example 3

[0043] The compound oral rinse composition provided in this embodiment has the formula shown in Table 3.

[0044] Table 3 Formulation ratio of compound oral rinse composition 3

[0045] Its preparation process is as follows Figure 1 As shown, the specific preparation steps are as follows:

[0046] S1. Pre-dissolution (light-protected operation): Add PEG 400, xylitol, and glycerin to 40℃ water for injection and stir to dissolve. Add baicalin and sonicate for 20 minutes (300W). Separately, dissolve povidone-iodine in 25℃ water for injection and stir in the dark. Filter through a 0.45μm PVDF membrane. Cool the solubilizing phase to 25℃ and slowly add the active ingredient solution, maintaining pH 5.6±0.1.

[0047] S2. Mixing and adjusting volume: Add zinc hyaluronic acid to the main solution and stir at 200 rpm for 30 min; add citrate-sodium citrate buffer solution and adjust the pH to 5.8 ± 0.1.

[0048] S3. Sterile filling: After passing through a 0.22μm PES membrane for two-stage filtration, the contents are filled into the liquid storage unit of the quantitative spraying device (medical PP inner liner, 40ml) and sealed with nitrogen.

[0049] Example 4

[0050] The compound oral rinse composition provided in this embodiment has the formula shown in Table 4.

[0051] Table 4 Formulation ratio of compound oral rinse composition 4

[0052]

[0053] Its preparation process is as follows Figure 1 As shown, the specific preparation steps are as follows:

[0054] S1. Pre-dissolution (light-protected operation): Add PEG 400, xylitol, and glycerin to 40℃ water for injection and stir to dissolve. Add baicalin and sonicate for 20 minutes (300W). Separately, dissolve tinidazole in 25℃ water for injection and stir in the dark, then pass it through a 0.45μm PVDF membrane. Cool the solubilizing phase to 25℃ and slowly add the active ingredient solution, maintaining the pH at 5.6±0.1.

[0055] S2. Mixing and adjusting volume: Add zinc hyaluronic acid to the main solution and stir at 200 rpm for 30 min; add citrate-sodium citrate buffer solution and adjust the pH to 5.8 ± 0.1.

[0056] S3. Sterile filling: After passing through a 0.22μm PES membrane for two-stage filtration, the contents are filled into the liquid storage unit of the quantitative spraying device (medical PP inner liner, 40ml) and sealed with nitrogen.

[0057] Example 5

[0058] The compound oral rinse composition provided in this embodiment has the same formulation as in Example 1;

[0059] The preparation method includes the following steps: mixing the compound active ingredients, mucosal repair agent, anti-inflammatory synergist, moisturizer, solubilizer, flavoring agent, pH adjuster and water to obtain composition 5.

[0060] Example 6

[0061] The compound oral rinse composition provided in this embodiment has the formula shown in Table 5.

[0062] Table 5 Formulation ratio of compound oral rinse composition 6

[0063]

[0064] Its preparation process is as follows Figure 1 As shown, the specific preparation steps are as follows:

[0065] S1. Pre-dissolution (light-protected operation): Dissolve PEG 400, xylitol, and glycerin in 40°C water for injection by stirring. Add baicalin and sonicate for 20 minutes (300W). Separately, dissolve povidone-iodine and tinidazole in 25°C water for injection by stirring in the dark and pass through a 0.45μm PVDF membrane. Cool the solubilizing phase to 25°C and slowly add the active ingredient solution, maintaining the pH at 5.6±0.1.

[0066] S2. Mixing and adjusting volume: Add chitosan to the main solution and stir at 200 rpm for 30 min; add citrate-sodium citrate buffer and adjust the pH to 5.8 ± 0.1.

[0067] S3. Sterile filling: After passing through a 0.22μm PES membrane for two-stage filtration, the contents are filled into the liquid storage unit of the quantitative spraying device (medical PP inner liner, 40ml) and sealed with nitrogen.

[0068] Example 7

[0069] The compound oral rinse composition provided in this embodiment has the formula shown in Table 6.

[0070] Table 6 Formulation ratio of compound oral rinse composition 7

[0071]

[0072] Its preparation process is as follows Figure 1 As shown, the specific preparation steps are as follows:

[0073] S1. Pre-dissolution (light-protected operation): Dissolve PEG 400, xylitol, and glycerin in 40°C water for injection by stirring. Add baicalin and sonicate for 20 minutes (300W). Separately, dissolve povidone-iodine and tinidazole in 25°C water for injection by stirring in the dark and pass through a 0.45μm PVDF membrane. Cool the solubilizing phase to 25°C and slowly add the active ingredient solution, maintaining the pH at 5.6±0.1.

[0074] S2. Mixing and adjusting volume: Add silk fibroin to the main solution and stir at 200 rpm for 30 min; add citrate-sodium citrate buffer and adjust the pH to 5.8±0.1.

[0075] S3. Sterile filling: After passing through a 0.22μm PES membrane for two-stage filtration, the contents are filled into the liquid storage unit of the quantitative spraying device (medical PP inner liner, 40ml) and sealed with nitrogen.

[0076] Example 8

[0077] The compound oral rinse composition provided in this embodiment is based on the formulation of Example 1, except that zinc hyaluronic acid is replaced with chitosan, zinc hyaluronic acid and silk fibroin in equal proportions by mass.

[0078] The compound oral rinse composition provided in this embodiment has the formula shown in Table 7.

[0079] Table 7 Formulation of Compound Oral Gargle Composition 8

[0080] Its preparation process is as follows Figure 1 As shown, the specific preparation steps are as follows:

[0081] S1. Pre-dissolution (light-protected operation): Dissolve PEG 400, xylitol, and glycerin in 40°C water for injection by stirring. Add baicalin and sonicate for 20 minutes (300W). Separately, dissolve povidone-iodine and tinidazole in 25°C water for injection by stirring in the dark and pass through a 0.45μm PVDF membrane. Cool the solubilizing phase to 25°C and slowly add the active ingredient solution, maintaining the pH at 5.6±0.1.

[0082] S2. Mixing and adjusting volume: Add zinc hyaluronic acid, silk fibroin and chitosan to the main solution and stir at 200 rpm for 30 min; add citrate-sodium citrate buffer and adjust the pH to 5.8±0.1.

[0083] S3. Sterile filling: After passing through a 0.22μm PES membrane for two-stage filtration, the contents are filled into the liquid storage unit of the quantitative spraying device (medical PP inner liner, 40ml) and sealed with nitrogen.

[0084] Test performance

[0085] 1. In vitro antibacterial efficacy test

[0086] The antibacterial activity of compound oral mouthwashes was evaluated by determining the minimum inhibitory concentration (MIC) and inhibition zone diameter of different concentrations of samples against *Porphyromonas gingivalis* and *Staphylococcus aureus* using the agar plate two-fold dilution method. In the experiment, bacterial suspensions were diluted with mouthwashes of different concentrations, spread on agar plates, and incubated in a constant temperature incubator. Bacterial growth was observed, and the lowest drug concentration at which no sterile growth occurred was defined as the MIC. Simultaneously, the antibacterial effects and synergistic effects of different formulations were compared by measuring the diameter of the inhibition zone, thus comprehensively evaluating their in vitro antibacterial capabilities.

[0087] Table 8 Results of in vitro antibacterial efficacy test

[0088] As shown in Table 8 of the test results, the composite active ingredients (povidone-iodine and tinidazole) in Example 1 provide the core antibacterial effect, while zinc hyaluronic acid, as a mucosal repair agent, enhances the synergistic antibacterial and diffusion effects. The preparation process, including ultrasound and filtration, ensures uniform dissolution and stability of the ingredients, thus exhibiting optimal antibacterial efficacy.

[0089] The MIC of Example 2 was slightly higher than that of Example 1, but the inhibition zone was significantly reduced (by about 22%). The absence of zinc hyaluronic acid reduced the mucosal repair and antibacterial synergy, resulting in weakened antibacterial diffusion ability (reduced inhibition zone), but the core active ingredients (povidone-iodine and tinidazole) still maintained basic antibacterial efficacy (small change in MIC).

[0090] In Example 3, the MIC was significantly increased (55% higher than in Example 1), and the inhibition zone was reduced. Tinidazole is a key active ingredient in the complex; its absence disrupts the synergistic antibacterial mechanism with povidone-iodine, leading to a decrease in overall antibacterial efficacy, especially against Porphyromonas gingivalis (with a significant increase in MIC), and its diffusion ability is weakened.

[0091] Example 4 showed a higher MIC (61% higher than Example 1) and a smaller inhibition zone. Povidone-iodine is a broad-spectrum antibacterial agent; its absence weakened its inhibition against Staphylococcus aureus (resulting in a smaller inhibition zone) and resulted in the loss of its synergistic effect with tinidazole, leading to a significant reduction in overall antibacterial efficacy, similar to Example 3. This highlights the necessity of the compound active ingredient.

[0092] The formulation of Example 5 was the same as that of Example 1, but the simplified process (direct miscibility) omitted key steps such as light-protection, sonication, and filtration, which resulted in the active ingredients (such as povidone-iodine and tinidazole) possibly not being fully dissolved or degraded. Therefore, the antibacterial efficacy decreased significantly: the MIC increased to 15.5 μg / mL (due to low drug dissolution, a higher concentration is required to inhibit bacteria), and the inhibition zone decreased to 17.0 mm (due to uneven component distribution, reducing antibacterial activity). The efficacy was worse than that of Example 4, indicating that the process had a greater impact on the overall quality than the absence of a single component.

[0093] In Example 6, chitosan, as a mucosal repair agent, exhibits inherent antibacterial properties (especially against Gram-positive bacteria such as Staphylococcus aureus). Compared to Example 3: the MIC was 8.4 μg / mL (slightly higher than Example 1, because chitosan has a weaker effect against Porphyromonas gingivalis, but tinidazole and povidone-iodine are still present), and the inhibition zone was 23.8 mm (significantly higher than 19.0 mm in Example 3, because chitosan partially replaces the synergistic antibacterial effect of zinc hyaluronic acid, especially enhancing the inhibition against Staphylococcus aureus).

[0094] In Example 7, silk fibroin mainly played a repair role, with weak antibacterial properties. Therefore, its effect was similar to that of Example 3: the MIC was 8.7 μg / mL (slightly higher than Example 1 due to the lack of antibacterial contribution), and the inhibition zone was 19.1 mm (comparable to Example 3, as silk fibroin could not provide additional antibacterial synergy).

[0095] The compound in Example 8 (chitosan, zinc hyaluronic acid, and silk fibroin in equal proportions) combines the antibacterial properties of chitosan with the synergistic repair effect of zinc hyaluronic acid. The MIC decreased to 7.9 μg / mL (slightly better than Example 1, due to the synergistic enhancement of inhibition against Porphyromonas gingivalis by chitosan and zinc hyaluronic acid), and the inhibition zone increased to 25.0 mm (better than Example 1, due to the enhanced inhibition against Staphylococcus aureus by chitosan, which has a synergistic effect with zinc hyaluronic acid).

[0096] 2. Evaluation of mucosal repair effect

[0097] A healthy SD rat model of oral ulcer was established using healthy SD rats (weighing 200-250g). Ulcers were created on the left cheek by cauterization with 40% glacial acetic acid. Rats were randomly divided into several groups, including a control group, a model group, and a mouthwash treatment group. Local administration of the mouthwash was performed daily for 7 consecutive days post-surgery. Experimental materials included prepared mouthwash (containing mucosal repair components such as zinc hyaluronic acid), sterile saline, hematoxylin and eosin (HE) staining reagents, and reagents for detecting inflammatory factors. The experimental procedures mainly included: ulcer area measurement, HE staining of tissue sections to observe epithelial regeneration, and detection of the expression levels of inflammatory factors (such as IL-1α and TNF-α). The promoting effect and mechanism of the mucosal repair components in the mouthwash were evaluated by comparing ulcer healing time, histological scores, and molecular biological indicators among different treatment groups.

[0098] The test results are shown in Table 9:

[0099] Table 9 Mucosal Repair Test Results

[0100] As can be seen from Table 9, Example 1 achieves efficient healing of oral ulcers through a triple synergistic effect of "antibacterial-anti-inflammatory-repair". This is because zinc hyaluronic acid forms a hydration membrane, reducing the resistance to epithelial cell migration, while baicalin inhibits inflammatory factors (TNF-α), reducing microenvironment interference. Povidone-iodine / tinidazole synergistically clears pathogens from the wound, blocks infectious inflammation, and prolongs the healing cycle. Zinc ions activate prolyl hydroxylase, promoting collagen cross-linking; tinidazole inhibits bacterial collagenase degradation.

[0101] The results of Example 2 indicate a decreased reepithelialization rate, prolonged ulcer healing time, and decreased collagen content, suggesting that the lack of hyaluronic acid for hydration and lubrication increases the resistance to epithelial cell migration, and zinc deficiency leads to a decrease in collagen synthase activity.

[0102] The results of Example 3 showed that the healing time increased by 21.0% (povidone-iodine alone was insufficient). Povidone-iodine is effective against aerobic bacteria, but it cannot penetrate the biofilm of anaerobic bacteria. Residual infection leads to repeated inflammation. Tinidazole's specific antibacterial properties against anaerobic bacteria are irreplaceable. Although it is better than the group without repair agent when it is missing, it is still weaker than the complete formula.

[0103] In Example 4, povidone-iodine (another antibacterial component) was missing, but the mucosal repair agent was intact, and the effect was similar to that of the group lacking tinidazole. The weakened antibacterial effect may have affected infection control, and the indicators were consistent with those in Example 3 (re-epithelialization 110.0 μm² / h, healing in 7.5 days), indicating the secondary effect of the lack of active ingredients.

[0104] The formulation of Example 5 was the same as that of Example 1, but the preparation process was simplified (direct miscibility, not stepwise dissolution). This may have led to component aggregation, degradation, or reduced bioavailability (e.g., insufficient sonication of baicalin), resulting in a significant deterioration in all parameters: re-epithelialization rate of 95.0 μm² / h (a 24% decrease compared to intact re-epithelialization), healing time of 8.5 days (a 37% increase), and collagen content of 35.0 μg / mg (a 17% decrease). Process optimization is crucial for stability (refer to steps S1-S3 of Example 1).

[0105] In Example 6, chitosan was used as a substitute for zinc hyaluronic acid as a mucosal repair agent. Chitosan has bioadhesive and healing-promoting effects, but it may not be as efficient as zinc hyaluronic acid (literature: zinc hyaluronic acid is superior in oral repair). Therefore, re-epithelialization was 115.0 μm² / h (8% lower than intact), healing time was 6.8 days (10% longer), and collagen was 40.0 μg / mg (slightly reduced). The data reflect the slight disadvantages of the alternative repair agent.

[0106] The silk fibroin in Example 7, as a repair agent, can promote cell migration, but its efficiency may be lower than that of zinc hyaluronic acid (especially collagen synthesis). Re-epithelialization rate was 110.0 μm² / h (a 12% decrease compared to intact cells), healing time was 7.0 days (a 13% increase), and collagen content was 39.0 μg / mg (a 7% decrease). Silk fibroin showed stable but slightly inferior effects in oral applications.

[0107] The compound in Example 8 (chitosan, zinc hyaluronic acid, and silk fibroin in equal proportions) may synergistically enhance repair through multiple mechanisms (such as zinc ions promoting collagen, chitosan's antibacterial properties, and silk fibroin's barrier function). Therefore, the indicators were slightly better than in Example 1: re-epithelialization 135.0 μm² / h (an 8% improvement), healing time 5.8 days (a 6% reduction), and collagen 45.0 μg / mg (a 7% improvement). The results show that compounding strategies are commonly used to improve therapeutic efficacy.

[0108] Finally, it should be noted that the terms "comprising," "including," or any other variations are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Although preferred embodiments of the invention have been described, those skilled in the art, upon learning the basic inventive concept, can make further changes and modifications to these embodiments. Therefore, the appended claims are intended to be interpreted as including both the preferred embodiments and all changes and modifications falling within the scope of the invention.

[0109] The embodiments described above merely illustrate specific implementation methods of this application, and while the descriptions are detailed, they should not be construed as limiting the scope of protection of this application. It should be noted that those skilled in the art can make various changes and improvements without departing from the concept of the technical solution of this application, and these all fall within the scope of protection of this application.

Claims

1. A compound oral rinse composition, characterized in that, The product comprises the following components: a compound active ingredient, a mucosal repair agent, an anti-inflammatory synergist, a moisturizer, a solubilizer, a flavoring agent, a pH adjuster, and water, with the total content of each component being 100 wt%. The anti-inflammatory synergist is at least one of the following plant extracts: baicalin, paeonol, zinc acetylsalicylate, flunixin meglumine, dipotassium glycyrrhizate, thymopentin, and copper tripeptide-1. The compound active ingredient is povidone-iodine and tinidazole, with the content of povidone-iodine being 0.4 wt% to 1 wt% and the content of tinidazole being 0.2 wt% to 1 wt%. The mucosal repair agent is composed of chitosan, zinc hyaluronic acid, and silk fibroin, wherein the chitosan accounts for 0.1 wt% to 1 wt% of the compound oral rinse composition, the zinc hyaluronic acid accounts for 0.01 wt% to 1 wt% of the compound oral rinse composition, and the silk fibroin accounts for 0.1 wt% to 1 wt% of the compound oral rinse composition. Its preparation process includes the following steps: (1) Pre-dissolution in the dark: First, add water to dissolve the solubilizer, flavoring agent and humectant, then add the anti-inflammatory synergist and dissolve with ultrasonic assistance to obtain the solubilized phase; under the dark environment, add the compound active ingredients to water and stir to dissolve, then pass through a PVDF pre-filter membrane to obtain the active ingredient solution; under the dark environment, cool the solubilized phase to 25°C, slowly add the active ingredient solution, maintain pH 5.5–5.8, and obtain the main solution system; (2) Mixing and volume adjustment: Under light-protected conditions, add the mucosal repair agent dropwise to the main solution system, add the pH adjuster to the above mixture, and adjust the pH of the solution to 5.8±0.1; (3) In a light-proof environment, the above-mentioned composite liquid is filtered through multiple stages of sterilization, then aseptically filled and sterilized, and the filtrate is filled into a light-proof and heat-insulated storage unit and sealed with nitrogen.

2. The composition according to claim 1, characterized in that, The anti-inflammatory synergist accounts for 0.01 wt% to 0.3 wt% of the composition.

3. The composition according to claim 1, characterized in that, The moisturizer is one or more of glycerin, propylene glycol, sorbitol, and trehalose, accounting for 1 wt% to 5 wt% of the composition.

4. The composition according to claim 1, characterized in that, The solubilizer is one or more of PEG 200, PEG 300, PEG 400, and PEG 600, accounting for 0.3wt% to 1.5wt% of the composition.

5. The composition according to claim 1, characterized in that, The flavoring agent is any one of xylitol, erythritol, and isomalt, accounting for 0.5wt% to 4wt% of the composition.

6. The composition according to claim 1, characterized in that, The pH adjuster is any one of the following: citric acid-sodium citrate buffer system, acetic acid-sodium acetate buffer system, and lactic acid-sodium lactate buffer system, accounting for 0.1wt% to 1wt% of the composition.

7. A method for preparing the composition according to any one of claims 1 to 6, characterized in that, Includes the following steps: (1) Light-protected pre-dissolution: First, add water to the solubilizer, flavoring agent and humectant and stir to dissolve. Then add the anti-inflammatory synergist and dissolve with ultrasound assistance to obtain the solubilized phase. Under light-protected conditions, add the compound active ingredients to water and stir to dissolve. Pass through a PVDF pre-filter membrane to obtain the active ingredient solution. In a light-protected environment, the solubilizing phase was cooled to 25°C, and the active ingredient solution was slowly added while maintaining the pH at 5.5–5.8 to obtain the main solution system. (2) Mixing and volume adjustment: Under light-protected conditions, add the mucosal repair agent dropwise to the main solution system, add the pH adjuster to the above mixture, and adjust the pH of the solution to 5.8±0.1; (3) In a light-proof environment, the above-mentioned composite liquid is filtered through multiple stages of sterilization, then aseptically filled and sterilized, and the filtrate is filled into a light-proof and heat-insulated liquid storage unit and sealed with nitrogen.

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