An improved composition of Gongjingyan Kang and a preparation method thereof

Abstract

This invention discloses an improved cervicitis treatment composition and its preparation method, made from the following raw materials in parts by weight: 13-20 parts of Sophora flavescens, 0.3-0.8 parts of alum, 0.4-0.8 parts of bitter almond, and 0.02-0.04 parts of borneol. The improved cervicitis treatment composition of this invention has been formulated by adjusting the proportions of Sophora flavescens, alum, and bitter almond. While maintaining its basic efficacy, the dosage of the drugs has been reduced, improving the therapeutic effect and resulting in better economic value.

Description

Technical Field

[0001] This application relates to the field of traditional Chinese medicine technology, specifically to an improved cervicitis treatment composition and its preparation method. Background Technology

[0002] Cervicitis Suppositories are a traditional Chinese medicine specifically for cervicitis, composed of Sophora flavescens, alum, bitter almond, and borneol. They have the effects of clearing heat and drying dampness, promoting tissue regeneration. They are used to treat chronic cervical erosion belonging to the damp-heat syndrome of leukorrhea, with symptoms such as: profuse, yellow, purulent leukorrhea, sometimes with blood streaks and a foul odor, lower back pain, lower abdominal distension, bitter taste in the mouth, dry mouth, yellow urine, constipation, and vaginal itching. Since its market launch many years ago, it has shown good efficacy in treating cervicitis and has a high patient acceptance rate.

[0003] During their in-depth research on the cervicitis suppository, the inventors discovered the possibility of further optimizing its formula and conducted in-depth research accordingly, resulting in the technical solution of this invention. Summary of the Invention

[0004] This invention provides an improved cervicitis relief composition and its preparation method. The improved cervicitis relief composition has an adjusted formula. By adjusting the dosage ratio of Sophora flavescens, alum, and bitter almond, the dosage of the drugs is reduced while maintaining the basic efficacy, thereby improving the therapeutic effect and having better economic value.

[0005] To achieve the above objectives, the technical solution of the present invention is as follows: The improved cervicitis treatment composition is made from the following raw materials in parts by weight: Sophora flavescens 13-20 parts, alum 0.3-0.8 parts, bitter almond 0.4-0.8 parts, borneol 0.02-0.04 parts.

[0006] Preferably, it is made from the following raw materials in parts by weight: Sophora flavescens 15-18 parts, alum 0.4-0.6 parts, bitter almond 0.5-0.7 parts, borneol 0.02-0.04 parts.

[0007] The improved cervicitis treatment composition described above includes the following steps in its preparation method of active ingredients: Sophora flavescens is crushed into coarse powder, and then soaked in a 1% hydrochloric acid aqueous solution (6-10 times the weight of the coarse powder) at 40-60℃ for 0.5-1h under sealed conditions. After reflux extraction for 2-3h, the mixture is filtered, and the filtrate is selectively adsorbed through a pre-treated cation exchange resin. The filtrate is then washed with purified water and eluted with a 0.01% sodium hydroxide solution and a 60-70% ethanol solution. The eluent is collected, and the ethanol is recovered under reduced pressure at 50-60℃. Finally, the mixture is concentrated at 55-65℃ to a specific gravity of 1.01-1.20 to obtain Sophora flavescens extract. Take the alum and grind it into ultrafine powder for later use; after blanching the bitter almonds in hot water to remove the skin, air dry them at 40-50℃, and then grind them into fine powder; grind the borneol into fine powder in a light-proof and airtight container. The active ingredients are Sophora flavescens extract, alum ultrafine powder, bitter almond fine powder, and borneol fine powder.

[0008] The aforementioned alum ultrafine powder is a fine powder that has passed through a 120-mesh sieve.

[0009] The cation exchange resin is 732 cation exchange resin.

[0010] When washing the cation exchange resin, use 5-10 times the column volume of purified water; when eluting, use 2-8 times the column volume of a 0.01% sodium hydroxide 60-70% ethanol solution.

[0011] The improved cervicitis relief composition described above, the preparation method of its suppository includes the following steps: Using 5-12 parts by weight of fatty acid glycerides and 0.5-1 parts by weight of lanolin as the matrix, the fatty acid glycerides and lanolin are first heated and mixed at 50-60℃ to prepare a compound matrix. Then, Sophora flavescens extract is added to fully emulsify and make it compatible. Then, bitter almond powder, alum powder and borneol powder are added in batches and mixed evenly. Then, the mixture is repeatedly ground by a colloid mill, poured into a fixed quantity at constant temperature and pressure, cooled and solidified at low temperature, and sealed to obtain the final product.

[0012] The advantages of this invention are as follows: This invention reduces the amount of potentially irritating medicinal materials used by adjusting the ratio of Sophora flavescens, alum, and bitter almond, particularly by reducing the dosage of alum and bitter almond. Pharmacodynamic experiments have demonstrated that the improved formula, compared to the positive control drug compound metronidazole vaginal suppositories, has a significant advantage in treating cervicitis. Furthermore, while such a ratio adjustment is generally understood to reduce therapeutic efficacy, pharmacodynamic experiments have shown that this improvement actually demonstrates a certain therapeutic advantage over the original formulation in terms of therapeutic indicators.

[0013] This invention also investigated the mechanism of improved efficacy in the low-dose group. Pathological histological observation revealed that the drug of this invention can form a drug film on the vagina or cervix, and drug films were observed on the vagina or cervix of some samples in the positive control group (Baofukang suppositories) and each treatment group. This drug film formation not only prolongs the local residence time of the drug but also achieves sustained release of the drug components, enabling the suppositories of this invention to be administered every other day, resulting in higher efficacy and potential safety.

[0014] The improved formulation of this invention overcomes the shortcomings of existing technologies, reduces formulation costs, and has good therapeutic effects, thus showing promising application prospects. Attached Figure Description

[0015] Figure 1 This is a comparison chart of vulvar inflammation in rats of different groups after the last administration in Example 6; Figure 2 These are photographs of the vagina and uterus of rats in each group of Example 6. Detailed Implementation

[0016] The present invention will now be described in detail through specific embodiments. Example 1

[0017] The improved cervicitis treatment composition is made from the following ingredients: 13 kg of Sophora flavescens, 0.3 kg of alum, 0.4 kg of bitter almond, and 0.02 kg of borneol.

[0018] The preparation method of its active ingredient is as follows: Sophora flavescens was crushed into coarse powder, and then soaked in a 1% hydrochloric acid aqueous solution (6 times the weight of the coarse powder) at 40°C for 0.5 hours in a sealed container. After reflux extraction for 2 hours, the mixture was filtered, and the filtrate was selectively adsorbed through a pre-treated 732 cation exchange resin. The resin was then washed with 5 times the column volume of purified water, followed by elution with 2 times the column volume of a 0.01% sodium hydroxide 60% ethanol solution. The eluent was collected, and the ethanol was recovered under reduced pressure at 50°C. The solution was then concentrated at 55°C to a specific gravity of 1.01 to obtain Sophora flavescens extract. Take alum and pulverize it through a 120-mesh sieve for later use; after blanching bitter almonds in hot water to remove the skin, air dry them at 40℃ and then pulverize them into fine bitter almond powder; pulverize borneol in a dark and sealed environment into fine borneol powder. The active ingredients are Sophora flavescens extract, alum ultrafine powder, bitter almond fine powder, and borneol fine powder.

[0019] The preparation method of the suppository includes the following steps: Using 5 kg of fatty acid glycerides and 0.5 kg of lanolin as the matrix, the fatty acid glycerides and lanolin are first heated and mixed at 50°C to prepare a compound matrix. Then, Sophora flavescens extract is added to fully emulsify and make it compatible. Then, bitter almond powder, alum powder and borneol powder are added in batches and mixed evenly. Then, the mixture is repeatedly ground by a colloid mill, poured into a fixed quantity at constant temperature and pressure, cooled and solidified at low temperature, and sealed to obtain the final product. Example 2

[0020] The improved cervicitis treatment composition is made from the following ingredients: Sophora flavescens 20kg, alum 0.8kg, bitter almond 0.8kg, borneol 0.04kg.

[0021] The preparation method of its active ingredient is as follows: Sophora flavescens was crushed into coarse powder, and then soaked in a 1% hydrochloric acid aqueous solution (equivalent to 10 times the weight of the coarse powder) at 60°C for 1 hour in a sealed container. After reflux extraction for 3 hours, the mixture was filtered, and the filtrate was selectively adsorbed through a pre-treated 732 cation exchange resin. The resin was then washed with 10 times the column volume of purified water, and then eluted with 8 times the column volume of a 0.01% sodium hydroxide 70% ethanol solution. The eluent was collected, and the ethanol was recovered under reduced pressure at 60°C. The solution was then concentrated at 65°C to a specific gravity of 1.20 to obtain Sophora flavescens extract. Take alum and pulverize it through a 120-mesh sieve for later use; after blanching bitter almonds in hot water to remove the skin, air dry them at 50℃ and then pulverize them into fine bitter almond powder; pulverize borneol in a dark and sealed environment into fine borneol powder. The active ingredients are Sophora flavescens extract, alum ultrafine powder, bitter almond fine powder, and borneol fine powder.

[0022] The preparation method of the suppository includes the following steps: Using 12 kg of fatty acid glycerides and 0.1 kg of lanolin as the matrix, the fatty acid glycerides and lanolin are first heated and mixed at 60°C to prepare a compound matrix. Then, Sophora flavescens extract is added to fully emulsify and make it compatible. Then, bitter almond powder, alum powder and borneol powder are added in batches and mixed evenly. Then, the mixture is repeatedly ground by a colloid mill, poured into a fixed quantity at constant temperature and pressure, cooled and solidified at low temperature, and sealed to obtain the final product. Example 3

[0023] The improved cervicitis treatment composition is made from the following ingredients: 17 kg of Sophora flavescens, 0.5 kg of alum, 0.6 kg of bitter almond, and 0.03 kg of borneol.

[0024] The preparation method of its active ingredient is as follows: Sophora flavescens was crushed into coarse powder, and then soaked in a 1% hydrochloric acid aqueous solution (8 times the weight of the coarse powder) at 50°C for 0.7 h in a sealed container. After reflux extraction for 2.5 h, the mixture was filtered, and the filtrate was selectively adsorbed through a pre-treated 732 cation exchange resin. The resin was then washed with 7 times the column volume of purified water, and then eluted with 5 times the column volume of a 0.01% sodium hydroxide 65% ethanol solution. The eluent was collected, and the ethanol was recovered under reduced pressure at 55°C. The solution was then concentrated at 60°C to a specific gravity of 1.10 to obtain Sophora flavescens extract. Take alum and pulverize it through a 120-mesh sieve for later use; after blanching bitter almonds in hot water to remove the skin, air dry them at 45℃ and then pulverize them into fine bitter almond powder; pulverize borneol in a dark and sealed environment into fine borneol powder. The active ingredients are Sophora flavescens extract, alum ultrafine powder, bitter almond fine powder, and borneol fine powder.

[0025] The preparation method of the suppository includes the following steps: Using 88 kg of fatty acid glycerides and 0.7 kg of lanolin as the matrix, the fatty acid glycerides and lanolin are first heated and mixed at 55°C to prepare a compound matrix. Then, Sophora flavescens extract is added to fully emulsify and make it compatible. Then, bitter almond powder, alum powder and borneol powder are added in batches and mixed evenly. Then, the mixture is repeatedly ground by a colloid mill, poured into a fixed quantity at constant temperature and pressure, cooled and solidified at low temperature, and sealed to obtain the final product. Example 4

[0026] The improved cervicitis treatment composition is made from the following ingredients: 15kg of Sophora flavescens, 0.4kg of alum, 0.5kg of bitter almond, and 0.02kg of borneol.

[0027] The preparation method of its active ingredient is as follows: Sophora flavescens was crushed into coarse powder, and then soaked in a 1% hydrochloric acid aqueous solution (7 times the weight of the coarse powder) at 45°C for 0.8 hours in a sealed container. After reflux extraction for 2.3 hours, the mixture was filtered. The filtrate was selectively adsorbed through a pre-treated 732 cation exchange resin, washed with 6 times the column volume of purified water, and then eluted with 4 times the column volume of a 0.01% sodium hydroxide 63% ethanol solution. The eluent was collected, and the ethanol was recovered under reduced pressure at 52°C. The solution was then concentrated at 58°C to a specific gravity of 1.07 to obtain Sophora flavescens extract. Take alum and pulverize it through a 120-mesh sieve for later use; after blanching bitter almonds in hot water to remove the skin, air dry them at 43℃ and then pulverize them into fine bitter almond powder; pulverize borneol in a dark and sealed environment into fine borneol powder. The active ingredients are Sophora flavescens extract, alum ultrafine powder, bitter almond fine powder, and borneol fine powder.

[0028] The improved cervicitis relief composition described above, the preparation method of its suppository includes the following steps: Using 9 kg of fatty acid glycerides and 0.6 kg of lanolin as the matrix, the fatty acid glycerides and lanolin are first heated and mixed at 53°C to prepare a compound matrix. Then, Sophora flavescens extract is added to fully emulsify and make it compatible. Then, bitter almond powder, alum powder and borneol powder are added in batches and mixed evenly. Then, the mixture is repeatedly ground by a colloid mill, poured into a fixed quantity at constant temperature and pressure, cooled and solidified at low temperature, and sealed to obtain the final product. Example 5

[0029] The improved cervicitis treatment composition is made from the following ingredients: 18 kg of Sophora flavescens, 0.6 kg of alum, 0.7 kg of bitter almond, and 0.04 kg of borneol.

[0030] The preparation method of its active ingredient is as follows: Sophora flavescens was crushed into coarse powder, and then soaked in a 1% hydrochloric acid aqueous solution (equivalent to 9 times the weight of the coarse powder) at 56°C for 0.9 hours in a sealed container. After extraction by reflux for 2.7 hours, the mixture was filtered. The filtrate was selectively adsorbed through a pre-treated 732 cation exchange resin, washed with 9 times the column volume of purified water, and then eluted with 7 times the column volume of a 0.01% sodium hydroxide and 61% ethanol solution. The eluent was collected, and the ethanol was recovered under reduced pressure at 58°C. The solution was then concentrated at 63°C to a specific gravity of 1.15 to obtain Sophora flavescens extract. Take alum and pulverize it through a 120-mesh sieve for later use; after blanching bitter almonds in hot water to remove the skin, air dry them at 48℃ and then pulverize them into fine bitter almond powder; pulverize borneol in a light-proof and airtight container into fine borneol powder. The active ingredients are Sophora flavescens extract, alum ultrafine powder, bitter almond fine powder, and borneol fine powder.

[0031] The preparation method of the suppository includes the following steps: Using 11 kg of fatty acid glycerides and 0.7 kg of lanolin as the matrix, the fatty acid glycerides and lanolin are first heated and mixed at 57°C to prepare a compound matrix. Then, Sophora flavescens extract is added to fully emulsify and make it compatible. Then, bitter almond powder, alum powder and borneol powder are added in batches and mixed evenly. Then, the mixture is repeatedly ground by a colloid mill, poured into a fixed quantity at constant temperature and pressure, cooled and solidified at low temperature, and sealed to obtain the final product.

[0032] Example 6 Pharmacodynamic Experiment: I. Information regarding the test substance and reference standard: 1. Test substance information: (1) Cervicitis suppositories prepared in Example 3; Specification: 1.2 grams per suppository.

[0033] (2) Original formula for Cervicitis Suppository, batch number: 20240101, production date: 2024.1.24, manufacturer: Guangxi Zhuang Autonomous Region Huahong Jinrui Pharmaceutical Co., Ltd.; dosage form: suppository; specification: 1.2 grams per suppository.

[0034] 2. Positive control information: (1) Compound Metronidazole Vaginal Suppositories; Batch No.: 09241020; Production Date: 2024.10.20; Manufacturer: Hebei Jinniu Pharmaceutical Technology Co., Ltd.; Dosage Form: Suppository; Specification: 3g / suppository × 6 suppositories / box. Main Ingredients: Metronidazole, Tetracycline, Nystatin.

[0035] (2) Baofukang Suppository; Batch No.: 20241140; Production Date: 2024.11.27; Manufacturer: Hainan Bikai Pharmaceutical Co., Ltd.; Dosage Form: Suppository; Specification: 1.74g per suppository; Main Ingredients: Each suppository contains 82mg of Curcuma zedoaria oil, 75mg of borneol, and excipients are ethanol, poly(40) stearate, polyethylene glycol-4000, polyethylene glycol-400, and lauryl ketone.

[0036] 3. Preparation of the test substance solution: No preparation is required; the dosage is calculated based on the rat's body weight at a dose of 0.124 g / kg.

[0037] 4. Preparation of positive control solution: Positive control compound metronidazole vaginal suppositories: No preparation is required. The dosage is calculated based on the rat's body weight, using the positive control group dose of 0.313 g / kg.

[0038] Positive control product Baofukang suppositories: No preparation is required. The dosage is calculated based on the rat's body weight, using the positive control group dose of 0.181 g / kg.

[0039] II. Main experimental instruments and reagents: Main testing instruments: The main instruments required for the experiment are shown in Table 1.

[0040] .

[0041] III. Main Test Reagents 1. Test solution Name: Physiological saline; Batch number: H24111105B; Source: Sichuan Kelun Pharmaceutical Co., Ltd.; Specification: 250mL: 2.25g; Production date: 2024.11.11; Storage conditions and stability: Store at room temperature in a sealed container, shelf life until August 2026.

[0042] 2. Information on modeling drugs (1) Name: Solid phenol Manufacturer: Tianjin Damao Chemical Reagent Factory; Batch Number: 20250315; Production Date: March 15, 2025; Storage Conditions: Store in a sealed container away from light.

[0043] (2) Name: Astragalus membranaceus gelatin Manufacturer: Shanghai E. En Chemical Technology Co., Ltd.; Batch Number: RH791847; Storage Conditions: Store in a sealed container at room temperature; Production Date: March 11, 2025; (3) Name: Glycerol Manufacturer: Tianjin Damao Chemical Reagent Factory; Batch No.: 20250301; Production Date: March 1, 2025; Storage Conditions: Store in a sealed container at room temperature.

[0044] (4) Preparation of molding agent (10% phenol paste) (taking 50mL as an example) Weigh 5g of phenol and heat it to melt at 50℃. Add 4 mL of glycerin and stir well. Add 1g of scutellaria gum and slowly add purified water while stirring continuously until the total volume reaches 50mL. This gives you the molding reagent (10% phenol paste).

[0045] (5) ELISA kit Name: Rat IL-1β ELISA KIT, Rat TNF-α ELISA KIT, Rat IL-6 ELISA KIT, RatCP ELISA KIT, Rat CRP ELISA KIT; Batch Number: 202511; Source: Jiangsu Enzyme Immunoassay Co., Ltd.; Specification: 96T; Production Date: November 14, 2025; Storage Conditions and Stability: Store at 2~8 ℃, shelf life until May 2026.

[0046] (6) Biochemical kit; Name: Rat SOD Biochemical KIT; Batch number: 20251112, 20251107; Source: Nanjing Jiancheng Bioengineering Institute; Specification: 100 tubes / 96 samples, 50 tubes / 48 samples; Production date: 2025.11.12, 2025.11.07; Storage conditions and stability: Store at 2~8 ℃, shelf life until May 2026.

[0047] (7) Biochemical reagent kit Name: Rat MDA Biochemical KIT; Batch Number: 20251117, 20251111; Source: Nanjing Jiancheng Biotechnology Institute; Specifications: 100 tubes / 96 samples, 50 tubes / 48 samples; Production Date: 2025.11.17, 2025.11.11; Storage Conditions and Stability: Store at 2~8 ℃, shelf life until May 2026.

[0048] (8) Biochemical reagent kit Name: Rat TP Biochemical KIT; Batch Number: 20251113, 20251114; Source: Nanjing Jiancheng Bioengineering Institute; Specifications: 96T, 48T; Production Date: 2025.11.13, 2025.11.14; Storage Conditions and Stability: Store at 2~8℃, shelf life until May 2026.

[0049] 3. Anesthetics Name: Isoflurane; Batch number: 2024120901; Source: Shandong Ant牧业Science and Technology Co., Ltd.; Specification: 100 mL / bottle; Production date: December 9, 2024; Storage conditions and stability: Store in the dark, sealed, in a cool place, and can be stable until December 8, 2026 IV. Experimental system 1. Experimental system and reasons for selection The histological structure of the cervix of SD rats (such as stratified squamous epithelium) is comparable to that of humans, can simulate the pathological process of cervicitis, and has a mature modeling method, a moderate body size for easy operation and drug administration, low cost, fast reproduction, and a clear genetic background. It is suitable for large-sample research and is a commonly used model for studying the mechanism of non-specific cervicitis and drug evaluation.

[0050] 2. Experimental animals (1) Pharmacodynamic study on SD rats with cervicitis Strain and grade: SD rats, SPF grade.

[0051] [[ID=1,6]]Number and sex of animals: 75 females were selected for the experiment.

[0052] Age of animals: 42 - 49 days old when received; 49 - 56 days old at the start of the experiment.

[0053] Weight range of animals: The weight range of SD rats when received was 172.5 - 207.3 g, and the weight range at the start of the experiment was 198.5 - 240.6 g, both within ±20% of the average weight.

[0054] Source of animals: Guangdong Provincial Center for Laboratory Animals; Production license number of experimental animals: SCXK (Guangdong) 2022 - 0002; Issuing unit: Guangdong Provincial Department of Science and Technology. Animal certificate number: No.SCXK(Guangdong)2022 - 00022025527927.<6000188>

[0055] (2) Comparative study on drug film shedding Strain and grade: SD rats, SPF grade.

[0056] Number and sex of animals: 45 females were selected for the experiment.

[0057] Age of animals: 42 - 49 days old when received; 49 - 56 days old at the start of the experiment.

[0058] Weight range of animals: The weight range of SD rats when received was 187.9 - 208.9 g, and the weight range at the start of the experiment was 187.9 - 208.9 g, both within ±20% of the average weight.

[0059] Animal source: Miluo Branch of Hunan Silek Jingda Laboratory Animal Co., Ltd.; Laboratory Animal Production License No.: SCXK (Xiang) 2025-0004; Issuing Authority: Hunan Provincial Department of Science and Technology. Animal Qualification Certificate No.: No. 430806261100083115.

[0060] V. Animal Grouping and Identification 1. Animal grouping (1) Pharmacodynamic study of SD rats with cervicitis Group design: This experiment consists of 5 groups, namely blank control group, model control group, positive control group, sample group of Example 3, and sample group of cervicitis sedative formula.

[0061] Number of animals: 15 per group, female.

[0062] Grouping method: Stratified randomization was used for grouping. Fifteen SD rats that had passed the adaptive feeding were randomly selected as the blank control group; 60 SD rats that successfully established the model were randomly divided into 5 groups: model control group, positive control group, sample group of Example 3, and cervicitis suppository formula sample group, with 15 rats in each group.

[0063] (2) Comparative study on drug film shedding Group design: This experiment has 3 groups, namely the positive control group, the sample group of Example 3, and the sample group of the cervicitis suppository formula.

[0064] Number of animals: 15 per group, female.

[0065] Grouping method: The animals were divided into 3 groups using a stratified random grouping method: positive control group, sample group of Example 3, and sample group of cervicitis suppository formula, with 15 animals in each group.

[0066] VI. Dosage Design 1. Clinically intended use information Indications: Clears heat and dries dampness, removes necrotic tissue and promotes tissue regeneration. Used for leukorrhea due to damp-heat, characterized by profuse, yellow, purulent discharge, sometimes with blood streaks and a foul odor, lower back pain, lower abdominal distension, bitter taste in the mouth, dry mouth, yellow urine, constipation, and vaginal itching; also for chronic cervical erosion with the above symptoms.

[0067] Dosage and administration: Vaginal administration, one capsule every other day, for 10 consecutive times as one course of treatment.

[0068] 2. Dosage design Test substance dosage design: Referring to the clinical dosage of Cervicitis Suppository, the clinical dosage of the sample in Example 3 and the original formula sample of Cervicitis Suppository was calculated based on 1.2g per day for adults weighing 60 kg, which is 0.02g / kg; the equivalent dose for rats is 0.124g / kg (calculated at 6.2 times the clinical dosage). Dosage design for the positive control compound metronidazole vaginal suppositories: Referencing the clinical dosage of the positive control compound metronidazole vaginal suppositories, one suppository once daily, each suppository weighing 3g. Based on an adult daily dose of 3g and a body weight of 60kg, the proposed clinical dose is 0.05g / kg; the equivalent rat dose is 0.313g / kg (calculated at 6.25 times the proposed clinical dose).

[0069] Dosage design for the positive control product, Baofukang suppositories: Referencing the clinical dosage of the positive control product, Baofukang suppositories, is one suppository once daily, with each suppository weighing 1.74g. Based on an adult daily dose of 1.74g and a body weight of 60kg, the proposed clinical dose is 0.029g / kg; the equivalent rat dose is 0.181g / kg (calculated at 6.25 times the proposed clinical dose).

[0070] VII. Test Methods 1. Pharmacodynamic study of SD rats with cervicitis (1) Experimental grouping: Grouping shall be carried out in accordance with the provisions of Article 5.

[0071] (2) Modeling: Modeling method: Rats were anesthetized with isoflurane. Except for the blank control group, 0.2 mL of 10% phenol gel was slowly injected into the cervical fornix through a blunt needle via gavage in each group. After injection, the vaginal opening was plugged with cotton, and the rats were inverted with their heads lower than their tails for 2 minutes. The drug was administered once every other day for a total of 5 times. The blank control group was given an equal volume of physiological saline.

[0072] (3) Modeling effect check: Before and after modeling, observe whether there is redness, swelling, congestion and white secretion in the vagina and cervix of the rats (take pictures), and take uterine tissue from several rats for pathological analysis. If there is mucosal inflammatory cell infiltration or epithelial cell necrosis and shedding, the modeling is considered successful.

[0073] (3) Route of administration: vaginal administration.

[0074] (4) Administration method: After successful modeling, the positive control group was given compound metronidazole vaginal suppositories once a day for 10 consecutive days; each dose group was given the corresponding dose of the test substance vaginally once every other day for 10 consecutive days; the blank control group and the model control group were given physiological saline.

[0075] (5) Dosage frequency and duration: Dosage is administered every other day during the dosing period. The dosage is adjusted once a week according to changes in body weight, and the administration is continued for 10 consecutive weeks.

[0076] (6) The day of the first administration is recorded as D0, the day before the first administration is recorded as D-1, the day after the first administration is recorded as D1, and so on.

[0077] 2. Comparative Study on Drug Film Shedding (1) Experimental grouping: Grouping shall be carried out in accordance with the provisions of Article 5.

[0078] (2) Route of administration: vaginal administration.

[0079] (3) Administration method: Forty-five rats were randomly divided into a positive control group (Baofukang suppository, 0.181 g / kg), a sample group of Example 3 (0.124 g / kg), and a sample group of the original formula of cervicitis suppository (0.124 g / kg), with 15 rats in each group. The positive control group was given Baofukang suppository vaginally once a day for 10 consecutive days; each dose group was given the corresponding dose of the test substance vaginally once every other day for 10 consecutive days.

[0080] (4) Dosage frequency and duration: Dosage is administered every other day during the dosing period. The dosage is adjusted once a week according to changes in body weight, and the administration is continued for 10 consecutive weeks.

[0081] (5) The day of the first administration is recorded as D0, the day before the first administration is recorded as D-1, the day after the first administration is recorded as D1, and so on.

[0082] VIII. Detection Frequency and Methods for Various Indicators 1. Clinical symptom observation The condition of the vagina and secretions in rats of each group was observed before and after modeling and before and after drug administration, noting the presence of dryness, erythema, swelling, congestion, fluid discharge, and secretions. Vulvar inflammation response was also scored; the scoring criteria are shown in Table 2, and the grading criteria are shown in Table 3.

[0083] ; .

[0084] 2. Weight measurement Record the body weight of rats before and after modeling and before and after drug administration. Measure the body weight of fasted rats on the day of dissection to calculate the anesthetic dosage and organ coefficients.

[0085] 3. Determination of the organ indices of rat immune organs, uterus, and vagina. Twenty-four hours after the last administration, spleen, thymus, uterus, and vaginal tissues were collected. After rinsing with physiological saline, the tissues were blotted dry with absorbent paper, weighed, and the organ index (organ weight / body weight) was calculated. A photograph of the entire uterus was also taken.

[0086] 4. Detection of inflammatory factors and related indicators in rat uterine and vaginal tissues Tissue samples from the vagina and cervix of 10 rats in each group were collected and added to ice-cold saline at a weight-to-volume ratio (tissue: physiological saline = 1:9). The samples were then chopped, homogenized on ice, and centrifuged at 3000 r / min for 10 min to prepare a 10% tissue homogenate. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), ceruloplasmin (CP), and C-reactive protein (CRP) in the rat vaginal and cervical tissues were measured using ELISA. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected using biochemical methods.

[0087] Observation of pathological changes and drug film thickness in rat uterine and vaginal tissues. 5. Observation of pathological changes in uterine and vaginal tissues and thickness of the drug film. 24 hours after the drug administration, the vaginal to uterine horn tissue / entire uterus and vagina of 5 rats in each group were completely harvested. After washing with physiological saline, the tissue was fixed with 4% paraformaldehyde solution. After dehydration, embedding, sectioning and other treatments, the tissue was stained with HE and examined under a light microscope for histopathological examination to observe the amelioration effect on uterine tissue inflammation and the film formation in the uterus, and to compare the thickness of the drug film.

[0088] Comparative observation of drug film detachment Twenty-four hours, forty-eight hours, and seventy-two hours after drug administration, tissue samples from the vagina to the uterine horn of five rats in each group were collected, cleaned with physiological saline, fixed with 4% paraformaldehyde solution, and after routine tissue dehydration, paraffin embedding, sectioning, etc., stained with hematoxylin and eosin (HE) and examined under a light microscope for histopathological examination to observe the film-forming status of the drug in the uterus and to compare the thickness and shedding of the drug film.

[0089] IX. Results Analysis 1. Clinical symptom observation Before modeling, there were no differences in mental state, activity level, coat color, and responsiveness among the rats in each group. After modeling, compared with the blank control group, the rats in the model control group showed reduced food intake, curling up, lethargy, body tremors, decreased activity, slow response, irritability, obvious redness and swelling of the vulva and cervix, accompanied by a small amount of discharge. After the last administration, compared with the model control group, the symptoms of the rats in the positive control group and the different dose groups were improved to varying degrees.

[0090] 2. Effects on vulvar inflammatory response in rats The condition of the rat vagina and secretions was observed and recorded before and after modeling and before and after drug administration. As shown in Table 4, before modeling, the vagina and cervix of rats in each group were normal and without inflammation; after modeling, the modeling group rats showed mild erythema, mild edema and a small amount of secretions in the vagina and cervix, indicating mild inflammation. Compared with the blank control group, the vulvar inflammation score of the model control group was significantly increased (P<0.01), showing mild inflammation; compared with the model control group, the vulvar inflammation score of the positive control group was significantly decreased (P<0.01). The vulvar inflammation scores of the sample group of Example 3 and the original formula of Cervicitis Kang Suppository showed a decreasing trend, and the erythema, edema and other conditions improved. The vulva was dry and no obvious secretions were observed. The differences were not statistically significant. The vulvar inflammation of rats in each group after the last drug administration is shown in Table 4. Figure 1 As shown.

[0091] ; Note: For data that do not conform to normality and homogeneity of variance, non-parametric tests were used for two independent samples comparisons. * indicates a statistically significant difference compared to the blank control group. P <0.05, ** indicates a statistically significant difference ( P <0.01). Compared with the model control group, # indicates a statistically significant difference ( P <0.05), ## indicates a statistically significant difference ( P <0.01).

[0092] 3. Effects on rat body weight Table 5 shows the changes in rat body weight before and after modeling and before and after drug administration. After drug administration, the body weight of rats in all groups increased compared to after modeling. Compared with the blank control group, the body weight of the model control group was significantly lower after modeling (…). P <0.05%. After administration, the body weight of the model control group tended to decrease compared to the blank control group, but the difference was not statistically significant; compared to the model control group, the body weight of the positive control group was significantly reduced (…). P <0.05), with no statistically significant differences in the remaining groups. While the positive control group exerts its therapeutic effect, it may also be accompanied by side effects such as increased energy expenditure or decreased appetite, leading to slower weight gain or even weight loss. Alternatively, the smaller individual differences within the positive control group may make the effect more statistically significant. When evaluating drug efficacy, weight is only one indicator; it is necessary to combine it with other physiological and biochemical indicators and histopathological results for a comprehensive judgment.

[0093] ; Note: For pre- and post-modeling body weight data, one-way ANOVA was used for inter-group comparisons to test for normality and homogeneity of variance; for post-drug-administered body weight data, non-parametric tests were used for two independent samples comparisons to test for non-normality and homogeneity of variance. Compared with the blank control group, * indicates a statistically significant difference. P <0.05, ** indicates a statistically significant difference ( P <0.01). Compared with the model control group, # indicates a statistically significant difference ( P <0.05), ## indicates a statistically significant difference ( P <0.01).

[0094] 4. Observation of vaginal and uterine morphology The morphology of the vagina and uterus of rats in each group was observed by dissection, and the results are as follows: Figure 2 As shown, the vaginal and uterine tissues of the rats in the blank control group were normal in morphology, with full tissues and relatively small uterine cavities, and no obvious abnormal changes such as congestion, edema, or atrophy were observed. The uterus of the rats in the model control group showed varying degrees of congestion and swelling, with the cavity filled with tissue fluid, and exhibiting dilation and tortuosity. After administration of the positive control drug, the sample group of Example 3, and the original formula sample group of the cervicitis suppository, the above symptoms improved to varying degrees. The vaginal and uterine morphology of the rats in the positive control group was close to that of the blank control group.

[0095] 5. Effects on organ indices of the thymus, spleen, ovaries, uterus, and vagina. As shown in Table 6, compared with the blank control group, the thymus index of the model control group was significantly reduced ( P <0.01), the spleen index and the ovarian, uterine, and vaginal indices showed an increasing trend, but the differences were not statistically significant. Compared with the model control group, the thymus index in each treatment group showed an increasing trend, while the spleen index and the ovarian, uterine, and vaginal indices showed a decreasing trend, with no statistically significant differences. Among them, the spleen index in the positive control group was significantly decreased ( P <0.01).

[0096]

[0097] Note: For data that do not conform to normality and homogeneity of variance, non-parametric tests were used for two independent samples comparisons. * indicates a statistically significant difference compared to the blank control group. P <0.05, ** indicates a statistically significant difference ( P <0.01). Compared with the model control group, # indicates a statistically significant difference ( P <0.05), ## indicates a statistically significant difference ( P <0.01).

[0098] 6. Effects on the levels of IL-1β, IL-6, and TNF-α in rat uterine and vaginal tissues As shown in Table 7, compared with the blank control group, the levels of IL-1β in the uterine and vaginal tissues of rats in the model control group were significantly increased ( P <0.01), compared with the model control group, the IL-1β content in the positive control group, the sample group of Example 3, and the original formula sample group of Cervicitis Kang Suppository was significantly reduced ( P <0.01), but there was no significant difference ( P >0.05), indicating that the IL-1β reduction effect of the Example 3 sample group and the Cervicitis Kang Suppository Original Formula sample group was comparable to that of the positive control group. The TNF-α content in the uterine and vaginal tissues of rats in the Example 3 sample was significantly reduced ( P <0.01), showing a more significant advantage compared to the positive control group.

[0099]

[0100] Note: For IL-1β data, one-way ANOVA was used for inter-group comparisons to test for normality and homogeneity of variance; for IL-6 and TNF-α data, non-parametric tests were used for two independent samples comparisons to test for non-normality and homogeneity of variance. * indicates a statistically significant difference compared to the blank control group. P <0.05, ** indicates a statistically significant difference ( P <0.01). Compared with the model control group, # indicates a statistically significant difference ( P <0.05), ## indicates a statistically significant difference ( P <0.01).

[0101] 7. Effects on the levels of CP, CRP, SOD, and MDA in rat uterine and vaginal tissues As shown in Table 8, compared with the blank control group, the CP content in the uterine and vaginal tissues of rats in the model control group was significantly increased ( P <0.01%, SOD content decreased significantly ( P <0.01), CRP and MDA levels showed an increasing trend, but the differences were not statistically significant. Compared with the model control group, the positive control group significantly reduced the levels of CP and CRP in the uterine and vaginal tissues of rats ( P <0.01, P <0.05), the sample group in Example 3 significantly reduced the content of CP, CRP, and MDA in the uterine and vaginal tissues of rats. P<0.01). It is evident that the sample group in Example 3 was superior to the positive control compound metronidazole vaginal suppositories in reducing CP, CRP, and MDA levels, suggesting a more comprehensive anti-inflammatory and antioxidant stress-reducing effect. The original formula of the cervicitis suppository significantly reduced the CP and MDA content in the uterine and vaginal tissues of rats (…). P <0.05, P <0.01. Both the sample group in Example 3 and the sample group containing the original formula for cervicitis suppositories showed a trend of increasing SOD levels, but the difference was not statistically significant.

[0102]

[0103] Note: For SOD data, one-way ANOVA was used for inter-group comparisons to test for normality and homogeneity of variance; for CP, CRP, and MDA data, non-parametric tests were used for two independent samples comparisons to test for normality and homogeneity of variance. * indicates a statistically significant difference compared to the blank control group. P <0.05, ** indicates a statistically significant difference ( P <0.01). Compared with the model control group, # indicates a statistically significant difference ( P <0.05), ## indicates a statistically significant difference ( P <0.01).

[0104] 8. Effects on the histopathology of rat uterine tissue (1) Effects on pathological changes and drug film thickness in rat uterine and vaginal tissues At the end of the experiment, rats were euthanized, and five rats from each group underwent histopathological examination. No abnormalities were observed under the microscope in the blank control group. In the model control group, significant epithelial cell necrosis and shedding, along with extensive mucosal inflammatory cell infiltration, were observed in the vagina and cervix. Compared with the model control group, the lesions in all treatment groups and the positive control group (compound metronidazole vaginal suppositories) showed improvement, specifically a significant reduction in necrosis and shedding, a decrease in mucosal inflammatory cell infiltration, and a certain degree of restoration of epithelial continuity. A dose-dependent effect was observed in the improvement of lesions across the treatment groups; higher doses resulted in more pronounced inflammation resolution and epithelial repair. Drug film thickness results showed that some samples in the positive control group (compound metronidazole vaginal suppositories) and all treatment groups had drug film adhering to the vagina or cervix, while no drug film was observed in the uterus, indicating significant retention or adsorption of the drug on the vaginal and cervical mucosa. At the same time, the drug film attached to the surface of the vaginal and cervical mucosa forms a physical protective layer, reducing the further damage to the already damaged epithelium caused by external stimuli or pathogens. The drug components can also be continuously and slowly released at the lesion site, promoting the regeneration and healing of epithelial cells.

[0105] (2) Comparison of drug film shedding results Pathological histological observation revealed that in both the positive control group (Baofukang suppositories) and each treatment group, some samples showed drug film adhesion in the vagina or cervix, while no drug film adhesion was observed in the uterus. Twenty-four hours after administration, the drug film adhesion in the Example 3 sample group was more pronounced than in the positive control group. In the positive control group (Baofukang suppositories), the drug film adhered only to the vagina, while in the Example 3 sample group, the drug film adhered to both the vagina and uterus. In summary, compared with Baofukang suppositories, the drug film adhesion in the Example 3 sample group was more pronounced after administration, mainly manifested in a greater number of cases with drug film coverage, more complete drug film coverage, and a longer duration of adhesion.

[0106] 10. Discussion 1. Criteria for selecting positive control drugs This study used a rat model of cervicitis induced by phenol gel. The mechanism involved chemical burns leading to degeneration, necrosis, and shedding of cervical mucosal epithelial cells, subsequently inducing severe local congestion, edema, and inflammatory cell infiltration. This pathological change primarily mimics the mucosal barrier disruption and local inflammatory cascade response caused by physical and chemical damage or pathogen invasion during the acute phase of clinical cervicitis. Compound metronidazole vaginal suppositories were used as a positive control because they are currently recognized as a first-line, broad-spectrum, and potent drug for treating infectious cervicitis and vaginitis. Their formulation not only covers common pathogens but also rapidly controls local symptoms by inhibiting the release of inflammatory mediators induced by pathogens. [1] Although this modeling method involves chemical injury, its core pathological features (tissue edema, leukocyte infiltration, and high expression of inflammatory factors IL-1β and TNF-α) are consistent with the end-stage inflammatory effects of clinical cervicitis. Experimental results showed that the positive control drug significantly reduced the levels of inflammatory factors and improved pathological changes in the model animals, confirming its ameliorative effect on this type of non-specific inflammatory environment. Therefore, using this as a control aims to verify the efficacy of the test substance in inhibiting severe inflammatory responses and promoting epithelialization of damaged mucosa, clarifying its potential for clinical substitution or combination therapy.

[0107] 2. Effects on immune organs, ovaries, uterus, and vaginal index Cervicitis can cause immune dysregulation, suppressing thymus function and resulting in decreased thymus weight and index. The spleen, as an important organ for blood filtration and immunity, experiences increased workload under inflammatory conditions, leading to physiological or pathological hyperplasia and enlargement, thus significantly increasing the spleen index. This is a typical marker of activated immune system activity. Under chemical stimulation, inflammation causes local tissue congestion, edema, and extensive infiltration of inflammatory cells; these pathological changes directly lead to increased uterine and vaginal weight. This study found that the thymus index was significantly decreased in the model control group rats, while the spleen index and ovarian, uterine, and vaginal indices were increased. The test substance showed an increasing trend in the thymus index and a decreasing trend in the spleen, ovarian, uterine, and vaginal indices. This suggests that it may play a role by regulating immune function and reducing local inflammatory edema.

[0108] 3. Effects on inflammatory markers in rat uterine and vaginal tissues Studies have shown that cervicitis infection is closely related to dysregulation of inflammatory factor levels. [2-3] TNF-α, as an important initiator of the inflammatory response cascade, participates in the immune response; elevated levels can disrupt the body's immune balance and lead to pathological damage. Cytokines IL-1β and IL-6 are activated after the onset of inflammation, which can exacerbate cell degeneration and necrosis, as well as the inflammatory response, and suppress immune function. All three are important indicators reflecting the degree of inflammation. [4] In this study, the IL-1β level was significantly increased in the model control group, and significantly decreased in the positive control group, the sample group of Example 3, and the cervicitis suppository formula sample group. The TNF-α content was significantly reduced in the low-dose group, indicating that inflammatory damage to the cervix and vaginal tissues can be alleviated by downregulating the expression of inflammatory factors, and the low-dose group showed a more significant anti-inflammatory advantage compared to the positive control group.

[0109] The levels of IL-6 and TNF-α in the model control group were lower than those in the blank control group, possibly due to the sampling time point lagging behind the peak secretion of inflammatory factors. IL-6 and TNF-α are typical early, acute inflammatory factors. They are rapidly produced in large quantities upon initial stimulation of the vaginal mucosa by phenol gel, typically reaching their peak within a few hours to 24 hours after stimulation and then rapidly declining. However, when sampling was performed after the last administration, the measured values ​​in the model group may have already decreased. Repeated stimulation with phenol gel establishes a chronic inflammation model. In the chronic phase, the core driving factors of inflammation may have shifted from the early TNF-α and IL-6 to IL-1β, IL-17, chemokines, or growth factors, leading to a decrease in TNF-α and IL-6 levels in the model group.

[0110] 4. Effects on acute-reactive proteins and oxidative stress in rats CP, also known as ferrooxidase, is a copper-containing α2-glycoprotein. As an acute-reactive protein, it can be elevated in the early stages of inflammation, reflecting the state of inflammation and infection earlier than traditional indicators. [5] CRP is a sensitive cytokine in the body's inflammatory response. IL-6 can induce CRP secretion, causing inflammation to spread rapidly and increasing damage. [6] Acute inflammatory markers (CP) and cytoreactive protein (CRP) are important biomarkers for inflammatory responses and have been widely used in basic research and clinical testing. In this study, after inflammation occurred, the activity of acute-reactive proteins increased, and the levels of CP and CRP in the vaginal and uterine tissues of rats in the model group increased. The levels of CP and CRP in each dose group and the positive control group decreased to varying degrees, suggesting that the CP and CRP levels can be reduced in rats with cervicitis, and the anti-inflammatory effect of the low-dose group was better than that of the positive control group.

[0111] Oxidative stress imbalance is a significant pathogenic factor initiating or promoting female reproductive diseases. IL-1β can stimulate cells to produce more free radicals, thereby increasing lipid peroxidation and leading to elevated MDA levels. MDA is one of the end products of lipid peroxidation. MDA levels directly reflect the degree of lipid peroxidation and indirectly reflect the degree of cellular damage; its content is related to inflammation in the body, and detecting MDA is of great significance for assessing inflammation. [11-12] Superoxide dismutase (SOD) can scavenge oxygen free radicals in the body and plays a key role in maintaining the body's oxidation and antioxidant balance. SOD activity represents the body's ability to resist free radical damage.

[13] During oxidative stress, antioxidant enzymes such as SOD are activated and expressed, accelerating the removal of excess ROS and MDA from the body, promoting the production of SOD and other antioxidant enzymes, and enhancing the body's overall antioxidant capacity, thus providing a protective effect. [14-15] This study used 10% phenol gel to replicate a rat model of cervicitis. The results showed that treatment effectively repaired cervical tissue damage, reduced tissue congestion and edema, increased SOD activity, and decreased MDA content. All dosage groups showed better inhibition of lipid peroxidation than the positive control group. This indicates that the treatment can improve the antioxidant capacity of rats with cervicitis, effectively resist oxidative stress damage to uterine tissue, and thus improve tissue morphology.

[0112] 5. Effects on rat uterine histopathology Pathological histological observation revealed no abnormalities in the blank control group samples. The lesions in the model control group, positive control group (compound metronidazole vaginal suppositories), and the sample group of Example 3 and the original formula sample group of the cervicitis suppository mainly manifested as inflammatory changes in the vagina, cervix, or uterus, including mucosal inflammatory cell infiltration or epithelial cell necrosis and shedding. The lesions in the positive control group (compound metronidazole vaginal suppositories) and each treatment group showed improvement compared to the model control group. A certain dose-related correlation was observed in the improvement of lesions in each treatment group, suggesting that it can reduce local inflammatory response and promote epithelial cell repair.

[0113] In this study, 24 hours after the last administration, the drug film adhesion in the Example 3 sample group was significantly better than that of the Baofukang suppository, exhibiting a wider drug film coverage (obvious drug film adhesion was visible on both the vaginal and cervical mucosa surfaces), a greater number of adhered samples, and a more pronounced adhesion effect with increasing dosage. 48 hours after the end of administration, a significant number of samples in the Example 3 sample group still showed drug film coverage, while the number of samples with drug film adhesion using the Baofukang suppository decreased. It is noteworthy that the Example 3 sample group was administered every other day, while the positive controls, compound metronidazole vaginal suppositories and Baofukang suppositories, were administered daily; pathological results showed comparable or superior inflammation improvement effects. This indicates that after the suppository matrix melts at body temperature, it can form a high-viscosity drug film through bioadhesion on the cervical folds and damaged mucosa, not only prolonging the local drug residence time but also achieving sustained release of the drug components, thus providing a basis for the "every other day" clinical dosing regimen. In the cervicitis model induced by phenol adhesive, chemical corrosion and sloughing of the mucosa and exposure of the wound are common. The drug film observed in this study not only acts as a drug carrier but also serves as a physical barrier covering the cervical surface, isolating the wound from secondary irritation caused by the acidic environment and inflammatory secretions within the vagina. This "isolation-protection-repair" effect provides a stable microenvironment for epithelial regeneration and may be one of the important mechanisms behind the outstanding pathological histological performance of this product.

[0114] 6. Demonstrates advantages in the treatment of cervicitis through multi-target anti-inflammatory and antioxidant effects. In inhibiting key pro-inflammatory factors, it significantly reduced IL-1β and TNF-α levels. In particular, the anti-inflammatory effect of the sample group in Example 3 was superior to that of the first-line clinical drug, compound metronidazole vaginal suppositories, suggesting that it may exert its therapeutic effect on cervicitis by downregulating inflammatory factors such as IL-1β and TNF-α. Regarding uterine and vaginal tissue repair, the sample group in Example 3 showed better reduction of inflammation-related proteins CP and CRP than compound metronidazole vaginal suppositories, and also showed more significant improvement in the oxidative stress damage marker MDA, indicating that it possesses both anti-inflammatory and antioxidant protective effects. In terms of effective dosage, the sample group in Example 3 surpassed the efficacy of compound metronidazole vaginal suppositories in several core indicators, suggesting higher potency and potential safety. Regarding the drug film, the formed film not only has long-lasting sustained-release properties but also isolates and protects the wound, continuously exerting a repairing effect. In summary, the sample group in Example 3 demonstrated a comprehensive therapeutic advantage over compound metronidazole vaginal suppositories in terms of anti-inflammatory and tissue repair effects.

[0115] XI. Conclusion Under the conditions of this experiment, the test substance was able to alleviate vulvar inflammation in SD rats with cervicitis, increase the thymus index, decrease the spleen index and the indices of the ovary, uterus and vagina, reduce the levels of TNF-α, IL-1β, IL-6, CP, CRP and MDA in the vaginal and uterine tissues of rats, increase the SOD content, reduce inflammatory cell infiltration and epithelial cell necrosis and shedding in the vaginal, cervical and uterine mucosa / endometrium, promote epithelial cell repair, and improve cervical congestion and edema. The drug film mainly adhered tightly to the vaginal and cervical os mucosa, indicating that the test substance has a therapeutic effect on SD rats with cervicitis. Moreover, the sample group in Example 3 showed that its anti-inflammatory effect was superior to compound metronidazole vaginal suppositories in multiple inflammation-related indicators. Compared with Baofukang suppositories, the drug film adhesion was more obvious and the adhesion time was longer. Its good film-forming properties also had better sustained-release characteristics and wound protection.

Claims

1. An improved cervicitis treatment composition, characterized in that, Made from the following parts by weight of raw materials: Sophora flavescens 13-20 parts, alum 0.3-0.8 parts, bitter almond 0.4-0.8 parts, borneol 0.02-0.04 parts.

2. The improved cervicitis treatment composition according to claim 1, characterized in that, Made from the following parts by weight of raw materials: Sophora flavescens 15-18 parts, alum 0.4-0.6 parts, bitter almond 0.5-0.7 parts, borneol 0.02-0.04 parts.

3. The improved cervicitis treatment composition according to claim 1 or 2, characterized in that, The preparation method of its active ingredient includes the following steps: Sophora flavescens is crushed into coarse powder, and then soaked in a 1% hydrochloric acid aqueous solution (6-10 times the weight of the coarse powder) at 40-60℃ for 0.5-1h under sealed conditions. After reflux extraction for 2-3h, the mixture is filtered, and the filtrate is selectively adsorbed through a pre-treated cation exchange resin. The filtrate is then washed with purified water and eluted with a 0.01% sodium hydroxide solution and a 60-70% ethanol solution. The eluent is collected, and the ethanol is recovered under reduced pressure at 50-60℃. Finally, the mixture is concentrated at 55-65℃ to a specific gravity of 1.01-1.20 to obtain Sophora flavescens extract. Take the alum and grind it into ultrafine powder for later use; after blanching the bitter almonds in hot water to remove the skin, air dry them at 40-50℃, and then grind them into fine powder; grind the borneol into fine powder in a light-proof and airtight container. The active ingredients are Sophora flavescens extract, alum ultrafine powder, bitter almond fine powder, and borneol fine powder.

4. The improved cervicitis treatment composition according to claim 3, characterized in that: The aforementioned alum ultrafine powder is a fine powder that has passed through a 120-mesh sieve.

5. The improved cervicitis treatment composition according to claim 3, characterized in that: The cation exchange resin is 732 cation exchange resin.

6. The improved cervicitis treatment composition according to claim 3, characterized in that: When washing the cation exchange resin, use 5-10 times the column volume of purified water; when eluting, use 2-8 times the column volume of a 0.01% sodium hydroxide 60-70% ethanol solution.

7. The improved cervicitis treatment composition according to claim 3, characterized in that, The preparation method of the suppository includes the following steps: Using 5-12 parts by weight of fatty acid glycerides and 0.5-1 parts by weight of lanolin as the matrix, the fatty acid glycerides and lanolin are first heated and mixed at 50-60℃ to prepare a compound matrix. Then, Sophora flavescens extract is added to fully emulsify and make it compatible. Then, bitter almond powder, alum powder and borneol powder are added in batches and mixed evenly. Then, the mixture is repeatedly ground by a colloid mill, poured into a fixed quantity at constant temperature and pressure, cooled and solidified at low temperature, and sealed to obtain the final product.

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