Compound antibacterial powder for inhibiting gynecological infection and preparation method thereof

Abstract

The invention provides compound antibacterial powder for inhibiting gynecological infection and a preparation method, and relates to the technical field of gynecological infection disease treatment, the compound antibacterial powder comprises 15%-25% of pomegranate flower extract, 15%-25% of pomegranate peel extract, 10%-20% of nutgall extract, 10%-20% of rose extract, 5%-10% of chlorhexidine acetate, 2%-5% of chitosan, 18%-45% of starch, and 0.5%-1% of microcrystalline cellulose. According to the compound antibacterial powder for inhibiting gynecological infection, the traditional Uygur medicine materials and the modern compound PCSB-1 are adopted, so that the antibacterial powder formula with multiple effects in one dose is realized. In the components, pomegranate flower, pomegranate peel and nutgall extract synergistically destroy pathogenic biomembranes and provide powerful antibacterial, antifungal and antiamebic activity, rose extract has the effects of soothing liver-qi stagnation, promoting blood circulation and repairing mucous membranes, and medicine-grade chlorhexidine acetate and chitosan are added, so that the bacterium loading capacity can be rapidly reduced, a protective film is formed on the vaginal mucous membranes, and the effects of preventing and treating the vaginal mucous membranes are achieved. The drug effect retention time is prolonged.

Description

Technical Field

[0001] The present invention relates to the technical field of gynecological infectious disease treatment, in particular to a compound antibacterial powder for inhibiting gynecological infections and a preparation method thereof. Background Art

[0002] Gynecological infectious diseases primarily include trichomonas, fungal, and bacterial vaginosis, as well as cervicitis, cervical erosion, and pelvic inflammatory disease, which severely impact women's reproductive health and quality of life. Common clinical treatments include: vaginal douching: using washes containing chemicals such as chlorhexidine and povidone-iodine to directly cleanse and eliminate bacteria; oral antibiotics: such as metronidazole and clindamycin, administered systemically for up to four to six weeks; vaginal suppositories / gels: delivering antimicrobial agents topically, but with limited effective coverage and duration; and physical / surgical treatments: laser, cryosurgery, or surgical excision of diseased tissue can remove the lesion but can damage the normal mucosa and lead to complications during recovery.

[0003] Although chemical washes can temporarily inhibit bacteria, long-term use will destroy the normal vaginal flora. Studies have shown that about 60% of women experience vaginal microecological imbalance after long-term douching, and 30% of them are reinfected within half a year; although oral antibiotics are effective, they require continuous use for several weeks, and about 40% of patients experience systemic side effects such as nausea and vomiting, which are more likely to lead to drug resistance; after vaginal suppositories are used to treat candidal vaginitis, about 45% of patients relapse within three months of stopping the drug; the release rate of active ingredients in commercially available gynecological gels is only about 60%, which is difficult to meet the needs of continuous antibacterial treatment; although physical and surgical methods can remove lesions, they are accompanied by mechanical damage and postoperative adhesion and infection risks, with a long recovery period and a potential threat to reproductive safety.

[0004] Existing products mostly target a single or limited number of pathogens (e.g., only antifungals or only antibacterials), making it difficult to treat multiple infections with a single dose, including trichomonas, fungi, bacteria, and viruses. While chemical lotions and broad-spectrum antibiotics can provide short-term antibacterial effects, they often lead to imbalances in the normal bacterial flora, causing itching, odor, and high recurrence rates. Traditional suppositories / gels release the drug slowly, have limited coverage, and cannot fundamentally restore microbial balance. Traditional manual grinding and decoction extraction methods result in significant loss of active ingredients, resulting in coarse particles that are difficult to absorb through the mucosa, long treatment courses, and slow onset of effect. Summary of the Invention

[0005] In response to the shortcomings of the existing technology, the present invention provides a compound antibacterial powder for inhibiting gynecological infections and a preparation method. The technical problem to be solved by this invention is: how to combine multiple traditional Uyghur medical extracts with effective compounds to prepare a multi-effect synergistic, controlled-release repairing gynecological antibacterial powder through modern technology.

[0006] To achieve the above objectives, the present invention is implemented through the following technical solutions: a compound antibacterial powder for inhibiting gynecological infections and a preparation method thereof, comprising: Pomegranate flower extract: 15%–25%; Pomegranate peel extract: 15%–25%; Gallic acid extract: 10%–20%; Rose flower extract: 10%–20%; Chlorhexidine acetate: 5%–10%; Chitosan: 2%–5%; Starch: 18%–45%; Microcrystalline cellulose: 0.5%–1%; N-(-deoxy-2-amino-β-D-glucosyl) punica granatum imine derivative: 2%-5%; Silicon dioxide: 1% to enhance moisture resistance.

[0007] Preferably, the tannin content in the pomegranate peel extract is ≥15%, and the gallic acid content in the gallic fruit extract is ≥20%.

[0008] Preferably, the chlorhexidine acetate is of pharmaceutical grade, and the chitosan has a molecular weight of 10,000-50,000 and a degree of deacetylation of 80%-95%.

[0009] Preferably, the particle size of the microcrystalline cellulose is ≤100 mesh, and the average particle size of the compound antibacterial powder is 50-80 μm.

[0010] Preferably, the starch is corn starch.

[0011] A method for preparing a compound antibacterial powder for inhibiting gynecological infections, comprising the following steps: S1. crushing raw materials, adding them to ethanol aqueous solution for ultrasonic or reflux extraction, extracting each medicinal material 2-3 times, filtering, and combining the extracts; S2. The extract is concentrated under reduced pressure to 1 / 5–1 / 10 of its original volume, the pH is adjusted to 2.0–4.0, and the extract is passed through a macroporous adsorption resin column for adsorption. After adsorption, the extract is washed with water and then the polyphenols are eluted with 60–80% ethanol. The eluate is collected and concentrated under reduced pressure to dryness to obtain a high-purity plant polyphenol extract powder. S3. N-(-deoxy-2-amino-β-D-glucosyl) punica granatum imine derivative was mixed with pomegranate flower extract, pomegranate peel extract, gallic acid fruit extract, and rose flower extract in a mass ratio of 1:2–4:2–4:0.5–2:0.5–2. Water was added to form a suspension. The pH of the mixture was adjusted to 4.0–4.5. The mixture was sheared and homogenized at 5000–10000 rpm at 50–65°C for 10–20 minutes to fully disperse the components. S4. spray drying the homogenized mixture to obtain a dry powder, grinding the resulting coarse powder and sieving it with a 50-100 mesh sieve so that 80% of the final powder has a particle size distribution within the range of 20-100 μm; S5. Prepare the obtained powder into a solution with purified water and adjust the pH to 3.8–4.5. Fill the powder into a disposable vaginal propeller in a clean, constant-temperature workshop at 20–25°C and a relative humidity of <60%, and sterilize it by high-pressure steam at 121°C for 30 minutes or by gamma ray sterilization to obtain a sterile product.

[0012] Preferably, the volume fraction of the ethanol solution in S1 is 60-65%, the mass ratio of the raw material to the solvent is about 1:20, g:mL, the extraction temperature is 50±5°C, and the extraction time is 60 minutes.

[0013] Preferably, the process conditions of the spray drying in S4 are: air inlet temperature 150-180°C, air outlet temperature 80-90°C, and the moisture content of the coarse powder obtained after spray drying is less than 5%.

[0014] Preferably, the N-(-deoxy-2-amino-β-D-glucosyl) punicic acid imine derivative is referred to as PCSB-1. The preparation of PCSB-1 comprises: a. Purified pomegranate bitters were subjected to TEMPO-mediated oxidation to obtain 6-aldehyde pomegranate bitters; b. 6-aldehyde punicic acid was reacted with 2-deoxy-2-amino-β-D-glucose at pH 5.0 and room temperature for 12 h to generate a Schiff base; c. PCSB-1 was obtained by vacuum concentration, pretreatment and dissolution, column preparative separation and spray drying.

[0015] Preferably, the specific steps of purifying the pomegranate bitter element are: Ingredients: 500g pomegranate peel powder Solvent: 70% ethanol aqueous solution 5L Extraction: Mix the powder and solvent and reflux for 2 hours, let it stand and cool at room temperature, and filter to obtain the filtrate; Concentration: Reduce pressure until ethanol is almost completely evaporated to obtain a concentrated aqueous phase; Separation: add an equal volume of ethyl acetate to the concentrate, separate the liquid once, and collect the aqueous phase; Ion exchange: The aqueous phase was adsorbed on D-101 resin and eluted with ethanol, concentrated and dried under vacuum to obtain pure pomegranate bitter element, 5 g, with a yield of ≈1%.

[0016] The present invention provides a compound antibacterial powder for inhibiting gynecological infections and a preparation method thereof. It has the following beneficial effects: This compound antibacterial powder for gynecological infections combines traditional Uyghur medicinal herbs with the modern compound PCSB-1, achieving a "one-dose, multi-effect" antibacterial powder formula. Its ingredients, pomegranate flower, pomegranate peel, and gall nut extracts, synergistically disrupt pathogenic biofilms and provide potent antibacterial, antifungal, and anti-amoebic activity. Rose extract soothes the liver, relieves depression, activates blood circulation, and repairs mucosal membranes. The addition of pharmaceutical-grade chlorhexidine acetate and chitosan not only rapidly reduces bacterial load but also forms a protective film on the vaginal mucosa, prolonging the drug's effectiveness. PCSB-1's pH-responsive C=N imine bond enables controlled release in weakly acidic environments, precisely triggering the release of active ingredients and ultimately creating a weakly acidic microbiome-friendly environment. This combination offers the advantages of rapid onset and long-lasting repair.

[0017] At the same time, this solution incorporates a complete industrial mass production process: from ultrasonic / reflux extraction and TEMPO-mediated oxidation to high-shear homogenization, spray drying, jet milling, and multi-stage screening. Strict control of particle size, moisture content, content uniformity, and sterility ensures batch-to-batch consistency and quality traceability. This not only ensures high recovery and stability of the active ingredients in traditional Chinese herbal medicines, but also meets the large-scale, standardized production requirements of modern pharmaceutical manufacturing. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 A schematic diagram of the structure of an N-(-deoxy-2-amino-β-D-glucosyl) punica granatum imine derivative for realizing the invention; Figure 2 The present invention is a flowchart for implementing the present invention. DETAILED DESCRIPTION

[0019] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. All other embodiments obtained by ordinary technicians in this field based on the embodiments of the present invention without making any creative efforts shall fall within the scope of protection of the present invention. Example

[0020] like Figure 1-2 As shown, an embodiment of the present invention provides a compound antibacterial powder for inhibiting gynecological infections, comprising: 15% pomegranate flower extract, which is rich in polyphenols and volatile oils and has heat-clearing and blood-cooling, astringent and hemostatic, and anti-inflammatory effects. The polyphenol components can inhibit the growth of fungi and bacteria in the vagina and relieve itching and redness caused by inflammation; Pomegranate peel extract: 15%, the tannin content in pomegranate peel extract is ≥15%, and the gallic acid content in gallic acid extract is ≥20%; it is mainly composed of high content of tannins, with astringent, antiparasitic and anti-leukorrhea effects; its molecules can destroy the biofilm of pathogens and significantly enhance antibacterial, anti-amoebic and antiviral activities.

[0021] Gallic acid extract: 10%; mainly contains gallic acid, which has strong astringent, hemostatic, antibacterial and anti-inflammatory activities; it can synergize with pomegranate polyphenols to further destroy the cell walls of pathogens and inhibit the release of inflammatory mediators.

[0022] Rose extract: 10%; rich in flavonoids and volatile aroma components, it has the effects of soothing the liver and relieving depression, promoting blood circulation and regulating menstruation; its aromatic substances can improve local microcirculation and enhance mucosal barrier repair, while bringing a sense of pleasure.

[0023] Chlorhexidine acetate: 5%, pharmaceutical grade chlorhexidine acetate; has a killing effect on Gram-positive / negative bacteria and fungi, rapidly reducing the pathogen load and creating a good environment for natural medicinal ingredients.

[0024] Chitosan: 2%. Chitosan has a molecular weight of 10,000–50,000 and a degree of deacetylation of 80%. It is a natural polysaccharide with excellent mucosal adhesion and biocompatibility. It forms a protective film on the vaginal mucosa, prolongs the retention time of active substances, and has certain antibacterial activity.

[0025] Starch: 39.5%, corn starch; pharmaceutical-grade filling excipient used to adjust powder viscosity and disintegration, making the powder easy to disperse and dissolve quickly, thereby promoting the release of active ingredients.

[0026] Microcrystalline cellulose: 0.5%, microcrystalline cellulose particle size ≤100 mesh; used as an anti-caking agent and flow improver to prevent powder from agglomerating during production and storage, ensuring dosage form stability.

[0027] N-(-deoxy-2-amino-β-D-glucosyl) punicic acid imine derivative: 2%; it has the dual functions of punicic acid's strong anti-biofilm damage and glucosamine's mucosal repair; its C=N imine bond can be controllably hydrolyzed in a weakly acidic environment to achieve pH-triggered sustained release.

[0028] Silicon dioxide: 1% to enhance moisture resistance. The average particle size of the compound antibacterial powder is 50–80 μm. Food-grade adsorbents enhance the powder’s moisture resistance and fluidity, extending the product’s storage stability in high humidity environments.

[0029] A method for preparing a compound antibacterial powder for inhibiting gynecological infections comprises the following steps: S1. After the raw materials were ground, they were added to ethanol-water solutions for ultrasonic or reflux extraction. Each herb was extracted twice, filtered, and the extracts were combined. The volume fraction of the ethanol solution was 65%, the mass ratio of the raw material to the solvent was approximately 1:20, g:mL, the extraction temperature was 50±5°C, and the extraction time was 60 minutes; S2. The extract is concentrated under reduced pressure to 1 / 5–1 / 10 of its original volume, the pH is adjusted to 2.0, and the extract is passed through a macroporous adsorption resin column for adsorption. After adsorption, the extract is washed with water and then the polyphenols are eluted with 80% ethanol. The eluate is collected and concentrated under reduced pressure to dryness to obtain a high-purity plant polyphenol extract powder. S3. N-(-deoxy-2-amino-β-D-glucosyl) punicic acid imine derivative was mixed with pomegranate flower extract, pomegranate peel extract, gallic acid fruit extract, and rose flower extract in a mass ratio of 1:2:2:0.5:0.5. Water was added to form a suspension. The pH of the mixture was adjusted to 4.5. The mixture was sheared and homogenized at 5000 rpm at 65°C for 20 minutes to fully disperse the components. The N-(-deoxy-2-amino-β-D-glucosyl) punicic acid imine derivative was referred to as PCSB-1. The preparation of PCSB-1 includes the following steps: a. Purified pomegranate bitters were subjected to TEMPO-mediated oxidation to obtain 6-aldehyde pomegranate bitters; The specific steps are: a1. Dissolve 100 g of punicic acid, 0.50 g of 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxide, 1.00 g of KBr, and 14 mL of NaClO solution in 2 L of ethanol:deionized water (1:4 v / v) total solvent volume. a2 Stir under ice bath to keep the mixed solution temperature at 5°C; a3 Slowly add NaClO solution dropwise at a rate of 1 mL / min; simultaneously, automatically maintain the pH at 10.0 with 1 M NaHCO3 solution; After the addition of a4 is completed, continue stirring in an ice bath for 2 h. During this period, monitor the consumption of raw materials and the formation of new sites at a time interval (20 min). a5 When the reaction is finished, stop with 200 mL of ethanol and dilute to pH 7; a6 Filtration was performed to remove the generated NaBr precipitate and a small amount of solids, and dialysis was performed to remove small molecular impurities and inorganic salts. The dialysis water was changed three times a day for a total of 24 hours; a7 was transferred to a rotary evaporator and concentrated to dryness under reduced pressure at 40°C and 200 mbar to obtain a yellow-brown solid, i.e., 6-aldehyde punicic acid, about 85 g; b. 6-aldehyde punicic acid was reacted with 2-deoxy-2-amino-β-D-glucose at pH 5.0 and room temperature for 12 h to generate a Schiff base; c. PCSB-1 was obtained by concentration under reduced pressure, pretreatment and dissolution, column preparative separation and spray drying; The specific steps for purifying pomegranate bitters are as follows: Ingredients: 500g pomegranate peel powder Solvent: 70% ethanol aqueous solution 5L Extraction: Mix the powder and solvent and reflux for 2 hours, let it stand and cool at room temperature, and filter to obtain the filtrate; Concentration: Reduce pressure until ethanol is almost completely evaporated to obtain a concentrated aqueous phase; Separation: add an equal volume of ethyl acetate to the concentrate, separate the liquid once, and collect the aqueous phase; Ion exchange: The aqueous phase was adsorbed on D-101 resin and eluted with ethanol, concentrated and dried under vacuum to obtain pure pomegranate bitter element, 5 g, with a yield of ≈1%.

[0030] S4. The homogenized mixture is spray-dried to obtain a dry powder. The resulting coarse powder is ground and sieved using a 50–100 mesh screen such that 80% of the final powder has a particle size distribution within the range of 20–100 μm. The spray drying process conditions in S4 are: an inlet air temperature of 180°C, an outlet air temperature of 90°C, and a moisture content of less than 5% in the coarse powder obtained after spray drying. Dry powder collection and pretreatment are specifically as follows: The dry powder in the spraying area flows into the cyclone separator and is recovered by the bag dust collector; Primary dry powder moisture content determination ≤4%; Initial screening: Use a 50-mesh vibrating screen to remove oversized aggregates; Fine grinding and classification Grinding equipment: air jet mill (pressure 0.8 MPa), circulation grinding for 2 hours, inlet temperature ≤ 50°C; Grading screening: First, sieve with 100 mesh (150 μm) to remove ≤2% of super coarse particles; Then sieve with 200 mesh (75 μm), the lower cut powder accounts for 80%, and the laser particle size analyzer is used to confirm D = 50–80 μm; Final dry powder moisture: ≤5%.

[0031] S5. Prepare the obtained powder into a solution with purified water and adjust the pH to 4.5. Fill the powder into a disposable vaginal propeller in a clean constant temperature workshop at 25°C and relative humidity <60%, and sterilize it with high-pressure steam at 121°C for 30 minutes or with gamma rays to obtain a sterile finished product.

[0032] The pH of the suspension was measured using a calibrated online pH electrode; If the pH is > 4.5, slowly add 0.5% (w / v) lactic acid solution dropwise to pH 4.5; If the pH is less than 3.8, add 0.1M NaOH solution dropwise to 4.5; After the titration, stir for another 5 minutes and re-test the pH to ensure that it is stable within ±0.05 units.

[0033] Example 2 like Figure 1-2As shown, an embodiment of the present invention provides a compound antibacterial powder for inhibiting gynecological infections, comprising: pomegranate flower extract: 17%, rich in polyphenols and volatile oils, with heat-clearing and blood-cooling, astringent and hemostatic, and anti-inflammatory effects. The polyphenol components can inhibit the growth of fungi and bacteria in the vagina, and relieve itching and redness caused by inflammation; Pomegranate peel extract 17%, pomegranate peel extract tannin content ≥15%, gallic acid content in gallic acid extract ≥20%; mainly composed of high content of tannins, it has astringent, antiparasitic and anti-leukorrhea effects; its molecules can destroy the biofilm of pathogens and significantly enhance the antibacterial, anti-amoebic and antiviral activities.

[0034] Gallic acid extract: 12%; mainly contains gallic acid, which has strong astringent, hemostatic, antibacterial and anti-inflammatory activities; it can synergize with pomegranate polyphenols to further destroy the cell walls of pathogens and inhibit the release of inflammatory mediators.

[0035] Rose extract: 12%; rich in flavonoids and volatile aroma components, it has the effects of soothing the liver and relieving depression, promoting blood circulation and regulating menstruation; its aromatic substances can improve local microcirculation and enhance mucosal barrier repair, while bringing a sense of pleasure.

[0036] Chlorhexidine acetate: 7%, chlorhexidine acetate is pharmaceutical grade; it has a killing effect on Gram-positive / negative bacteria and fungi, quickly reducing the pathogen load and creating a good environment for natural medicinal ingredients.

[0037] Chitosan: 3%. Chitosan has a molecular weight of 10,000–50,000 and a degree of deacetylation of 80%–95%. It is a natural polysaccharide with excellent mucosal adhesion and biocompatibility. It forms a protective film on the vaginal mucosa, prolongs the retention time of active substances, and has certain antibacterial activity.

[0038] Starch: 27%, corn starch; pharmaceutical-grade filling excipient used to adjust powder viscosity and disintegration, making the powder easy to disperse and dissolve quickly, thereby promoting the release of active ingredients.

[0039] Microcrystalline cellulose: 1%, microcrystalline cellulose particle size ≤100 mesh; used as an anti-caking agent and flow improver to prevent powder from agglomerating during production and storage, ensuring dosage form stability.

[0040] N-(-deoxy-2-amino-β-D-glucosyl) punicic acid imine derivative: 3%; it has the dual functions of punicic acid's strong anti-biofilm damage and glucosamine's mucosal repair; its C=N imine bond can be controllably hydrolyzed in a weakly acidic environment to achieve pH-triggered sustained release.

[0041] Silicon dioxide: 1% to enhance moisture resistance. The average particle size of the compound antibacterial powder is 50–80 μm. Food-grade adsorbents enhance the powder’s moisture resistance and fluidity, extending the product’s storage stability in high humidity environments.

[0042] A method for preparing a compound antibacterial powder for inhibiting gynecological infections comprises the following steps: S1. Grind the raw materials and extract them separately with ethanol-water for ultrasonic or reflux extraction. Extract each herb 2–3 times, filter, and combine the extracts. The volume fraction of ethanol solution is 60%, the mass ratio of raw material to solvent is approximately 1:20 (g:mL), the extraction temperature is 50 ± 5°C, and the extraction time is 60 minutes. S2. The extract was concentrated under reduced pressure to 1 / 10 of its original volume, the pH was adjusted to 4.0, and the mixture was passed through a macroporous adsorption resin column for adsorption; after adsorption, the polyphenols were washed with water and then eluted with 80% ethanol. The eluate was collected and concentrated under reduced pressure to dryness to obtain a high-purity plant polyphenol extract powder; S3. An N-(-deoxy-2-amino-β-D-glucosyl) punicic acid imine derivative was mixed with pomegranate flower extract, pomegranate peel extract, gallic acid fruit extract, and rose flower extract in a mass ratio of 1:4:2:2:2. Water was added to form a suspension. The pH of the mixture was adjusted to 4.5. The mixture was sheared and homogenized at 10,000 rpm for 15 minutes at 65°C to fully disperse the components. The N-(-deoxy-2-amino-β-D-glucosyl) punicic acid imine derivative was referred to as PCSB-1. The preparation of PCSB-1 includes the following steps: a. Purified pomegranate bitters were subjected to TEMPO-mediated oxidation to obtain 6-aldehyde pomegranate bitters; The specific steps are: a1. Dissolve 100 g of punicic acid, 0.50 g of 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxide, 1.00 g of KBr, and 14 mL of NaClO solution in 2 L of ethanol:deionized water (1:4 v / v) total solvent volume. a2 Stir under ice bath to keep the mixed solution temperature at 5°C; a3 Slowly add NaClO solution dropwise at a rate of 1 mL / min; simultaneously, automatically maintain the pH at 10.0 with 1 M NaHCO3 solution; After the addition of a4 is completed, continue stirring in an ice bath for 2 h. During this period, monitor the consumption of raw materials and the formation of new sites at a time interval (20 min). a5 When the reaction is finished, stop with 200 mL of ethanol and dilute to pH 7; a6 Filtration was performed to remove the generated NaBr precipitate and a small amount of solids, and dialysis was performed to remove small molecular impurities and inorganic salts. The dialysis water was changed three times a day for a total of 24 hours; a7 was transferred to a rotary evaporator and concentrated to dryness under reduced pressure at 40°C and 200 mbar to obtain a yellow-brown solid, i.e., 6-aldehyde punicic acid, about 85 g; b. 6-aldehyde punicic acid was reacted with 2-deoxy-2-amino-β-D-glucose at pH 5.0 and room temperature for 12 h to generate a Schiff base; c. PCSB-1 was obtained by concentration under reduced pressure, pretreatment and dissolution, column preparative separation and spray drying; The specific steps for purifying pomegranate bitters are as follows: Ingredients: 500g pomegranate peel powder Solvent: 70% ethanol aqueous solution 5L Extraction: Mix the powder and solvent and reflux for 2 hours, let it stand and cool at room temperature, and filter to obtain the filtrate; Concentration: Reduce pressure until ethanol is almost completely evaporated to obtain a concentrated aqueous phase; Separation: add an equal volume of ethyl acetate to the concentrate, separate the liquid once, and collect the aqueous phase; Ion exchange: The aqueous phase was adsorbed on D-101 resin and eluted with ethanol, concentrated and dried under vacuum to obtain pure pomegranate bitter element, 5 g, with a yield of ≈1%.

[0043] S4. The homogenized mixture was spray-dried to obtain a dry powder. The resulting coarse powder was ground and sieved through a 100-mesh sieve so that 80% of the final powder had a particle size distribution within the 100-μm range. The spray drying process conditions in S4 were: an inlet air temperature of 180°C, an outlet air temperature of 90°C, and a moisture content of less than 5% in the coarse powder obtained after spray drying. Dry powder collection and pretreatment are specifically as follows: The dry powder in the spraying area flows into the cyclone separator and is recovered by the bag dust collector; Primary dry powder moisture content determination ≤4%; Initial screening: Use a 50-mesh vibrating screen to remove oversized aggregates; Fine grinding and classification Grinding equipment: air jet mill (pressure 0.8 MPa), circulation grinding for 2 hours, inlet temperature ≤ 50°C; Grading screening: First, sieve with 100 mesh (150 μm) to remove ≤2% of super coarse particles; Then sieve with 200 mesh (75 μm), the lower cut powder accounts for 80%, and the laser particle size analyzer is used to confirm D = 50–80 μm; Final dry powder moisture: ≤5%.

[0044] S5. Prepare the obtained powder into a solution with purified water and adjust the pH to 4.5. Fill the powder into a disposable vaginal propeller in a clean constant temperature workshop at 25°C and relative humidity <60%, and sterilize it with high-pressure steam at 121°C for 30 minutes or with gamma rays to obtain a sterile finished product.

[0045] The pH of the suspension was measured using a calibrated online pH electrode; If the pH is > 4.5, slowly add 0.5% (w / v) lactic acid solution dropwise to pH 4.5; If the pH is less than 3.8, add 0.1M NaOH solution dropwise to 4.5; After the titration, stir for another 5 minutes and re-test the pH to ensure that it is stable within ±0.05 units.

[0046] Example 3 like Figure 1-2 As shown, an embodiment of the present invention provides a compound antibacterial powder for inhibiting gynecological infections, comprising 23% pomegranate flower extract, which is rich in polyphenols and volatile oils and has heat-clearing and blood-cooling, astringent and hemostatic, and anti-inflammatory effects. The polyphenol components can inhibit the growth of fungi and bacteria in the vagina and relieve itching and redness caused by inflammation. Pomegranate peel extract: 15%, the tannin content in pomegranate peel extract is ≥15%, and the gallic acid content in gallic acid extract is ≥20%; it is mainly composed of high content of tannins, with astringent, antiparasitic and anti-leukorrhea effects; its molecules can destroy the biofilm of pathogens and significantly enhance antibacterial, anti-amoebic and antiviral activities.

[0047] Gallic acid extract: 20%; mainly contains gallic acid, which has strong astringent, hemostatic, antibacterial and anti-inflammatory activities; it can synergize with pomegranate polyphenols to further destroy the cell walls of pathogens and inhibit the release of inflammatory mediators.

[0048] Rose extract: 10%; rich in flavonoids and volatile aroma components, it has the effects of soothing the liver and relieving depression, promoting blood circulation and regulating menstruation; its aromatic substances can improve local microcirculation and enhance mucosal barrier repair, while bringing a sense of pleasure.

[0049] Chlorhexidine acetate: 5%, pharmaceutical grade chlorhexidine acetate; has a killing effect on Gram-positive / negative bacteria and fungi, rapidly reducing the pathogen load and creating a good environment for natural medicinal ingredients.

[0050] Chitosan: 5%, chitosan has a molecular weight of 50,000 and a degree of deacetylation of 95%; it is a natural polysaccharide with excellent mucosal adhesion and biocompatibility; it forms a protective film on the vaginal mucosa, prolongs the retention time of active substances, and has certain antibacterial activity.

[0051] Starch: 18%, corn starch; pharmaceutical-grade filling excipient used to adjust powder viscosity and disintegration, making the powder easy to disperse and dissolve quickly, thereby promoting the release of active ingredients.

[0052] Microcrystalline cellulose: 1%, microcrystalline cellulose particle size ≤100 mesh; used as an anti-caking agent and flow improver to prevent powder from agglomerating during production and storage, ensuring dosage form stability.

[0053] N-(-deoxy-2-amino-β-D-glucosyl) punicic acid imine derivative: 2%; it has the dual functions of punicic acid's strong anti-biofilm damage and glucosamine's mucosal repair; its C=N imine bond can be controllably hydrolyzed in a weakly acidic environment to achieve pH-triggered sustained release.

[0054] Silicon dioxide: 1% to enhance moisture resistance. The average particle size of the compound antibacterial powder is 80μm. Food-grade adsorbent enhances the powder's moisture resistance and fluidity, extending the product's storage stability in high humidity environments.

[0055] A method for preparing a compound antibacterial powder for inhibiting gynecological infections comprises the following steps: S1. Grind the raw materials and extract them separately with ethanol-water for ultrasonic or reflux extraction. Extract each herb 2–3 times, filter, and combine the extracts. The volume fraction of the ethanol solution is 65%, the mass ratio of raw material to solvent is approximately 1:20 (g:mL), the extraction temperature is 50 ± 5°C, and the extraction time is 60 minutes. S2. The extract was concentrated under reduced pressure to 1 / 10 of its original volume, the pH was adjusted to 4.0, and the extract was passed through a macroporous adsorption resin column for adsorption. After adsorption, the extract was washed with water and then the polyphenols were eluted with 60–80% ethanol. The eluate was collected and concentrated under reduced pressure to dryness to obtain a high-purity plant polyphenol extract powder. S3. N-(-deoxy-2-amino-β-D-glucosyl) punicic acid imine derivative was mixed with pomegranate flower extract, pomegranate peel extract, gallic acid fruit extract, and rose flower extract in a mass ratio of 1:4:2:0.5:0.5. Water was added to form a suspension. The pH of the mixture was adjusted to 4.0. The mixture was sheared and homogenized at 10,000 rpm at 50°C for 10 minutes to fully disperse the components. The N-(-deoxy-2-amino-β-D-glucosyl) punicic acid imine derivative was referred to as PCSB-1. The preparation of PCSB-1 includes the following steps: a. Purified pomegranate bitters were subjected to TEMPO-mediated oxidation to obtain 6-aldehyde pomegranate bitters; The specific steps are: a1. Dissolve 100 g of punicic acid, 0.50 g of 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxide, 1.00 g of KBr, and 14 mL of NaClO solution in 2 L of ethanol:deionized water (1:4 v / v) total solvent volume. a2 Stir under ice bath to keep the mixed solution temperature at 0–5°C; a3 Slowly add NaClO solution dropwise at a rate of 1 mL / min; simultaneously, automatically maintain the pH at 9.5 with 1 M NaHCO3 solution; After the addition of a4 is completed, continue stirring in an ice bath for 2 h. During this period, monitor the consumption of raw materials and the formation of new sites at a time interval (20 min). a5 When the reaction is finished, stop with 200 mL of ethanol and dilute to pH 7; a6 Filtration was performed to remove the generated NaBr precipitate and a small amount of solids, and dialysis was performed to remove small molecular impurities and inorganic salts. The dialysis water was changed three times a day for a total of 24 hours; a7 was transferred to a rotary evaporator and concentrated to dryness under reduced pressure at 40°C and 200 mbar to obtain a yellow-brown solid, i.e., 6-aldehyde punicic acid, about 85 g; b. 6-aldehyde punicic acid was reacted with 2-deoxy-2-amino-β-D-glucose at pH 5.0 and room temperature for 12 h to generate a Schiff base; c. PCSB-1 was obtained by concentration under reduced pressure, pretreatment and dissolution, column preparative separation and spray drying; The specific steps for purifying pomegranate bitters are as follows: Ingredients: 500g pomegranate peel powder Solvent: 70% ethanol aqueous solution 5L Extraction: Mix the powder and solvent and reflux for 2 hours, let it stand and cool at room temperature, and filter to obtain the filtrate; Concentration: Reduce pressure until ethanol is almost completely evaporated to obtain a concentrated aqueous phase; Separation: add an equal volume of ethyl acetate to the concentrate, separate the liquid once, and collect the aqueous phase; Ion exchange: The aqueous phase was adsorbed on D-101 resin and eluted with ethanol, concentrated and dried under vacuum to obtain pure pomegranate bitter element, 5 g, with a yield of ≈1%.

[0056] S4. The homogenized mixture is spray-dried to obtain a dry powder. The resulting coarse powder is ground and sieved through a 50-mesh sieve such that 80% of the final powder has a particle size distribution within the range of 20–100 μm. The spray drying process conditions in S4 are: an inlet air temperature of 150–180°C, an outlet air temperature of 80°C, and a moisture content of less than 5% in the coarse powder obtained after spray drying. Dry powder collection and pretreatment are specifically as follows: The dry powder in the spraying area flows into the cyclone separator and is recovered by the bag dust collector; Primary dry powder moisture content determination ≤4%; Initial screening: Use a 50-mesh vibrating screen to remove oversized aggregates; Fine grinding and classification Grinding equipment: air jet mill (pressure 0.8 MPa), circulation grinding for 2 hours, inlet temperature ≤ 50°C; Grading screening: First, sieve with 100 mesh (150 μm) to remove ≤2% of super coarse particles; Then sieve with 200 mesh (75 μm), the lower cut powder accounts for 80%, and the laser particle size analyzer is used to confirm D = 50–80 μm; Final dry powder moisture: ≤5%.

[0057] S5. Prepare the obtained powder into a solution with purified water and adjust the pH to 3.8. Fill the powder into a disposable vaginal propeller in a clean, constant-temperature workshop at 20–25°C and a relative humidity of <60%, and sterilize it by high-pressure steam at 121°C for 30 minutes or by gamma ray sterilization to obtain a sterile product.

[0058] The pH of the suspension was measured using a calibrated online pH electrode; If the pH is > 4.5, slowly add 0.5% (w / v) lactic acid solution dropwise to pH 4.5; If the pH is less than 3.8, add 0.1M NaOH solution dropwise to 4.5; After the titration, stir for another 5 minutes and re-test the pH to ensure that it is stable within ±0.05 units.

[0059] Table 1: Comparison of key quality indicators and in vitro antibacterial performance of Examples 1-3 to evaluate the comprehensive performance of compound antibacterial powders under different formulations: index Example 1 Example 2 Example 3 Dry powder yield 92% 90% 88% <![CDATA[Average particle size D 50 > 65μm 70μm 75μm RSD (content uniformity) 3% 4% 5% Moisture content 4.2% 4.0% 3.8% pH (aqueous suspension) 4.2 4.1 3.9 Disintegration time 1.5min 1.8min 2.0min Candida inhibition rate 95% 93% 96% Antibacterial rate against Escherichia coli 92% 90% 94% Antibacterial rate against Staphylococcus aureus 94% 92% 95% Storage stability (30°C / 75%RH, 3 months) No caking, no activity drop ≤ 2% Slight agglomeration, activity decreased by ≈3% Mild hardening, activity decreased by ≈4% Comparative Analysis Example 1 has the highest dry powder yield (92%) and the finest particle size (D = 65 μm), which is conducive to propeller administration and rapid release of active ingredients.

[0060] Example 3 had the coarsest particle size (75 μm) but the strongest antibacterial effect because it had a higher content of pomegranate flower / gallic acid extract.

[0061] Uniformity and disintegration The content uniformity fluctuated slightly with changes in PCSB-1 or natural extract content; Example 1 was the most stable. The disintegration time was less than 2 minutes, meeting the requirement for rapid drug delivery.

[0062] In vitro antibacterial effect Example 3 is slightly better in the three major indicators (96% inhibition rate against Candida, 94% inhibition rate against Escherichia coli, and 95% inhibition rate against Staphylococcus aureus), mainly due to the higher content of pomegranate flowers (23%) and gallic acid fruits (20%).

[0063] Example 2 has slightly lower overall antibacterial effect, but its PCSB-1 content is the highest (3%), and it has greater potential in long-term controlled release.

[0064] Stability investigation All formulations showed no fatal deterioration after storage at 30°C / 75%RH for 3 months, with only Example 3 showing slight hardening.

[0065] Silica has good moisture resistance and almost no caking.

[0066] in conclusion Example 1 takes into account the yield, particle size and uniformity, and is suitable for large-scale industrial rapid preparation.

[0067] Example 2 PCSB-1 has a slightly higher ratio, and is predicted to have greater advantages in weak acid controlled release and microecological restoration.

[0068] Example 3: The natural extract has the highest content and the strongest antibacterial effect, but its particle size is larger and its stability is slightly lower. The stability can be taken into account by optimizing the screening parameters or fine-tuning the excipients.

[0069] Although the embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that these embodiments may be modified without departing from the principles and spirit of the present invention. Numerous changes, modifications, substitutions, and variations are possible, and the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A compound antibacterial powder for inhibiting gynecological infections, characterized in that: include: Pomegranate flower extract: 15%–25%; Pomegranate peel extract: 15%–25%; Gallic acid extract: 10%–20%; Rose flower extract: 10%–20%; Chlorhexidine acetate: 5%–10%; Chitosan: 2%–5%; Starch: 18%–45%; Microcrystalline cellulose: 0.5%–1%; N-(-deoxy-2-amino-β-D-glucosyl) punica granatum imine derivative: 2%-5%; Silicon dioxide: 1% to enhance moisture resistance.

2. The compound antibacterial powder for inhibiting gynecological infections according to claim 1, characterized in that: The tannin content in the pomegranate peel extract is ≥15%, and the gallic acid content in the gallic fruit extract is ≥20%.

3. The compound antibacterial powder for inhibiting gynecological infections according to claim 1, characterized in that: The chlorhexidine acetate is of pharmaceutical grade, and the chitosan has a molecular weight of 10,000-50,000 and a deacetylation degree of 80%-95%.

4. The compound antibacterial powder for inhibiting gynecological infections according to claim 1, characterized in that: The particle size of the microcrystalline cellulose is ≤100 mesh, and the average particle size of the compound antibacterial powder is 50-80 μm.

5. The compound antibacterial powder for inhibiting gynecological infections according to claim 1, characterized in that: The starch is corn starch.

6. A method for preparing a compound antibacterial powder for inhibiting gynecological infections, characterized in that: The following steps are involved: S1. Grind the raw materials and add them to ethanol-water solution for ultrasonic or reflux extraction. Extract each herb 2–3 times, then filter and combine the extracts. S2. The extract is concentrated under reduced pressure to 1 / 5–1 / 10 of its original volume, the pH is adjusted to 2.0–4.0, and the extract is passed through a macroporous adsorption resin column for adsorption. After adsorption, the extract is washed with water and then the polyphenols are eluted with 60–80% ethanol. The eluate is collected and concentrated under reduced pressure to dryness to obtain a high-purity plant polyphenol extract powder. S3. N-(-deoxy-2-amino-β-D-glucosyl) punica granatum imine derivative was mixed with pomegranate flower extract, pomegranate peel extract, gallic acid fruit extract, and rose flower extract in a mass ratio of 1:2–4:2–4:0.5–2:0.5–2. Water was added to form a suspension. The pH of the mixture was adjusted to 4.0–4.

5. The mixture was sheared and homogenized at 5000–10000 rpm at 50–65°C for 10–20 minutes to fully disperse the components. S4. spray drying the homogenized mixture to obtain a dry powder, grinding the resulting coarse powder and sieving it with a 50-100 mesh sieve so that 80% of the final powder has a particle size distribution within the range of 20-100 μm; S5. Prepare the obtained powder into a solution with purified water and adjust the pH to 3.8–4.

5. Fill the powder into a disposable vaginal propeller in a clean, constant-temperature workshop at 20–25°C and a relative humidity of <60%, and sterilize it by high-pressure steam at 121°C for 30 minutes or by gamma ray sterilization to obtain a sterile product.

7. The method for preparing a compound antibacterial powder for inhibiting gynecological infections according to claim 6, characterized in that: The volume fraction of the ethanol solution in S1 is 60-65%, the mass ratio of the raw material to the solvent is about 1:20, g:mL, the extraction temperature is 50±5°C, and the extraction time is 60 minutes.

8. The method for preparing a compound antibacterial powder for inhibiting gynecological infections according to claim 6, characterized in that: The process conditions of the spray drying in S4 are: an air inlet temperature of 150-180°C, an air outlet temperature of 80-90°C, and a moisture content of the coarse powder obtained after spray drying of less than 5%.

9. The method for preparing a compound antibacterial powder for inhibiting gynecological infections according to claim 6, characterized in that: The N-(-deoxy-2-amino-β-D-glucosyl) punicic acid imine derivative is referred to as PCSB-1. The preparation of PCSB-1 includes: a. Purified pomegranate bitters were subjected to TEMPO-mediated oxidation to obtain 6-aldehyde pomegranate bitters; b. 6-aldehyde punicic acid was reacted with 2-deoxy-2-amino-β-D-glucose at pH 5.0 and room temperature for 12 h to generate a Schiff base; c. PCSB-1 was obtained by vacuum concentration, pretreatment and dissolution, column preparative separation and spray drying.

10. The method for preparing a compound antibacterial powder for inhibiting gynecological infections according to claim 6, characterized in that: The specific steps of purifying the pomegranate bitter element are as follows: Ingredients: 500g pomegranate peel powder Solvent: 70% ethanol aqueous solution 5L Extraction: Mix the powder and solvent and reflux for 2 hours, let it stand and cool at room temperature, and filter to obtain the filtrate; Concentration: Reduce pressure until ethanol is almost completely evaporated to obtain a concentrated aqueous phase; Separation: add an equal volume of ethyl acetate to the concentrate, separate the liquid once, and collect the aqueous phase; Ion exchange: The aqueous phase was adsorbed on D-101 resin and eluted with ethanol, concentrated and dried under vacuum to obtain pure pomegranate bitter element, 5 g, with a yield of ≈1%.

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