Vagina foaming agent with antibacterial effect and preparation method thereof

Abstract

The invention relates to the field of medicines, in particular to a vagina foaming agent with an antibacterial effect and a preparation method thereof. The vagina foaming agent with the antibacterial effect comprises a drug matrix and a propellant, and the drug matrix comprises the following raw materials in parts by mass: 20-40 parts of an antibacterial carrier, 40-70 parts of an emulsifier, 70-130 parts of a co-emulsifier, 8-20 parts of a foaming agent, 4-9 parts of a foam stabilizer and the balance of purified water, totaling 1000 parts; the antibacterial carrier comprises an antibacterial active substance, phospholipid and a carrier base material; the carrier base material is prepared from polylactic acid microspheres and water-soluble chitosan. The foaming agent obtained by the invention can effectively overcome the influence of a pathogenic bacteria biological membrane on the drug effect, improves the drug concentration under the biological membrane, is excellent in curative effect, and has the effects of durably resisting bacteria, regulating the vagina microenvironment for a long time, effectively relieving uncomfortable symptoms of patients, being high in safety and the like.

Description

Technical Field

[0001] This application relates to the pharmaceutical field, specifically to a vaginal foam with antibacterial properties and its preparation method. Background Technology

[0002] Vaginitis is a common gynecological disease in women, mainly manifested as abnormal changes in the color, odor, or amount of vaginal discharge, accompanied by vaginal dryness, itching, or burning sensations, seriously affecting women's physical and mental health. The main causes are bacterial and fungal infections, and it may also be related to poor hygiene habits and hormonal changes.

[0003] In postmenopausal women, the decline in estrogen levels and the weakening or even disappearance of estrogen receptor effects lead to corresponding clinical symptoms and signs. Normally, vaginal epithelial cells shed and release glycogen, which is converted into lactic acid by beneficial bacteria in the vagina. With weakened receptor effects, the vaginal epithelium thins, cell shedding decreases, and vaginal pH increases, causing excessive growth of pathogens and a reduction in normal flora, leading to inflammation and infection.

[0004] As pathogens overgrow in the vagina, biofilms form. Biofilms are an adhesive form of survival that fungi or bacteria develop to adapt to their environment. In vaginal biofilms, microorganisms adhere tightly to vaginal epithelial cells. Biofilms not only allow pathogens to evade clearance by the host's immune cells but also act as a barrier, blocking the penetration of antimicrobial drugs. This reduces the drug concentration of pathogens beneath the biofilm, leading to stronger drug resistance, increased susceptibility to recurrent infections, and prolonged treatment cycles.

[0005] Foaming formulations are a new type of vaginal medication, characterized by good dispersibility and a large surface area. After being sprayed into the vagina, they can distribute evenly and penetrate deep into the folds of the vaginal mucosa, the fornix, and the cervix—areas that are difficult for conventional medications to reach. They also have good adsorption properties, adhering tightly to the vaginal wall mucosa. Using a foaming formulation as a carrier, it can fully contact the lesion after being sprayed into the vagina, resulting in more thorough sterilization and anti-inflammatory effects, longer-lasting action, and a soft, delicate foam that is comfortable for patients, making it an ideal external medication.

[0006] However, there are currently few foaming agents developed for treating pathogenic biofilms, which leads to problems such as poor efficacy, long treatment cycles, and high recurrence rates in the treatment of vaginitis. Therefore, it is necessary to develop a vaginal foaming agent with excellent efficacy against pathogenic biofilms. Summary of the Invention

[0007] In order to develop a vaginal foam agent with excellent efficacy against pathogenic bacterial biofilms, this application provides a vaginal foam agent with antibacterial effects and its preparation method.

[0008] In a first aspect, this application provides a vaginal foam with antibacterial properties, employing the following technical solution: A vaginal foaming agent with antibacterial properties includes a pharmaceutical matrix and a propellant. The pharmaceutical matrix comprises the following raw materials in parts by weight: 20-40 parts antibacterial carrier, 40-70 parts emulsifier, 70-130 parts co-emulsifier, 8-20 parts foaming agent, 4-9 parts foam stabilizer, and purified water to a total of 1000 parts. The antibacterial carrier includes antibacterial active substances, phospholipids, and a carrier substrate; The carrier substrate is prepared from polylactic acid microspheres and water-soluble chitosan; The method for preparing the antibacterial carrier is as follows: first, antibacterial active substances are coated with phospholipids to obtain a coating, and then the coating is loaded onto a carrier substrate to obtain the antibacterial carrier.

[0009] By adopting the above technical solution, firstly, the active ingredients in the drug matrix exist in the form of antibacterial carriers, which is beneficial to improve the stability of antibacterial active substances during storage, and also helps to achieve a long-term sustained-release effect after medication.

[0010] Meanwhile, since phospholipids have good compatibility with biofilms formed by pathogen infection, antibacterial active substances coated with phospholipids in the antibacterial carrier can easily pass through the biofilms formed by pathogen infection, allowing the antibacterial active substances to directly act on pathogens under the biofilm barrier and improve antibacterial efficacy.

[0011] After medication, the antibacterial carrier adheres tightly to the vaginal wall, forming a drug film. This film essentially adheres to the biofilm formed by the pathogen infection in the infected area. Due to the good biocompatibility between the drug film and the biofilm, as the antibacterial active substance passes through the biofilm, the encapsulation bodies bound to the biofilm act as anchor points between the drug film and the biofilm, forming a more stable three-dimensional network structure. This results in better adhesion stability of the drug film in the infected area, thus contributing to a longer-lasting antibacterial effect and effectively reducing leakage after medication.

[0012] In addition, the phospholipids in the antibacterial carrier have excellent moisturizing effects. During the process of the coating acting on pathogens through the biomembrane, it can effectively relieve symptoms of vaginal dryness and itching. Furthermore, the acetyl groups contained in the phospholipids enter the intercellular space and bind with choline to form the signaling molecule acetylcholine, which can effectively activate cells, promote epithelial cell growth, thereby improving the vaginal microenvironment, enhancing therapeutic efficacy, and reducing the probability of recurrence.

[0013] A carrier substrate was prepared using polylactic acid (PLA) microspheres and water-soluble chitosan. PLA microspheres, with their porous hydrophobic structure and good mechanical strength, resulted in excellent loading capacity and superior drug film adhesion stability after application. This effectively counteracted the effects of vaginal secretions or urine on drug film adhesion, further improving the long-lasting antibacterial effect of the foaming agent. Simultaneously, PLA microspheres exhibited good biocompatibility, being non-toxic, harmless, and non-irritating. They can naturally degrade within the human body, and the lactic acid formed during degradation can regulate vaginal pH, effectively improving the vaginal microenvironment and achieving long-lasting regulation. Water-soluble chitosan possesses antibacterial, hemostatic, analgesic, and tissue-repair-promoting effects, effectively relieving patient discomfort after application. Furthermore, the excellent water solubility of chitosan allowed for the preparation of the carrier substrate in a purified water system, without the introduction of other organic solvents, resulting in higher safety for the foaming agent. The process was also relatively simple, facilitating large-scale industrial production.

[0014] In summary, the foaming agent obtained in this application can effectively overcome the influence of pathogenic biofilm on drug efficacy, increase the drug concentration under the biofilm, and exhibit excellent therapeutic effects. It also has positive effects such as long-lasting antibacterial properties, long-term regulation of the vaginal microenvironment, effective relief of patient discomfort symptoms, and high safety. It effectively solves the problems of poor efficacy, long treatment cycle, and high recurrence rate that are common in the treatment of vaginitis.

[0015] Preferably, the antibacterial active substance includes at least one of miconazole nitrate, econazole nitrate, sertaconazole nitrate, isoconazole nitrate, clotrimazole, metronidazole, polycresolsulfonate, nifuratel, nystatin, metronidazole, and ornidazole.

[0016] Preferably, the water-soluble chitosan includes at least one of carboxymethylated chitosan and oligochitosan.

[0017] By adopting the above technical solutions, both carboxymethyl chitosan and oligochitosan have good water solubility, which facilitates the preparation of carrier substrates; they also have high biological activity, exhibiting excellent antibacterial, hemostatic, analgesic, and tissue repair-promoting effects, and can effectively relieve patients' discomfort symptoms after administration; at the same time, they are easily absorbed by the human body, have high biological safety, and have good practical application effects.

[0018] Preferably, the phospholipid includes at least one of lecithin, dipalmitoylphosphatidylcholine, and distearate phosphatidylcholine.

[0019] Preferably, the carrier substrate is prepared as follows: water-soluble chitosan is dissolved in purified water, polylactic acid microspheres are added, the mixture is thoroughly mixed, the purified water is distilled off, and then the substrate is dried and pulverized to obtain the carrier substrate.

[0020] Preferably, the particle size of the antibacterial carrier is 30–100 μm.

[0021] Preferably, the foaming agent includes at least one of sodium dodecyl sulfate, sodium fatty alcohol polyoxyethylene ether sulfate, and nonylphenol polyoxyethylene ether.

[0022] Preferably, the antibacterial carrier further includes polyglutamic acid, and the preparation method of the antibacterial carrier is as follows: first, mix polyglutamic acid and phospholipids, and use the resulting mixture to coat the antibacterial active substance to obtain a coating; then load the coating onto a carrier substrate to obtain the antibacterial carrier.

[0023] By adopting the above technical solution, polyglutamic acid exhibits good biodegradability, is non-toxic and harmless, and has high biosafety. Due to its excellent adsorption capacity for antibacterial active substances, polyglutamic acid achieves even better encapsulation of these substances when mixed with phospholipids, resulting in more stable properties of the antibacterial active substances within the encapsulated form. Simultaneously, polyglutamic acid possesses excellent moisturizing effects; when the encapsulated form fuses with the biofilm formed by pathogens, it can further alleviate symptoms of vaginal dryness and itching, with a rapid onset of action, which helps increase patients' willingness to use the medication.

[0024] Furthermore, polyglutamic acid carries a negative charge during the preparation of the antibacterial carrier, causing the coating to tend to exhibit a negative charge. Meanwhile, the carrier substrate, influenced by water-soluble chitosan, tends to exhibit a positive charge. Therefore, under the influence of this charge, the carrier substrate has a higher loading rate for the coating and greater loading stability during storage. After medication, under the influence of the acidic vaginal environment, polyglutamic acid tends to exhibit a positive charge. Under this charge, the coating tends to move away from the carrier substrate, thereby promoting the fusion of the coating with the biofilm formed by the pathogen. This, in turn, improves the rate at which the antibacterial active substance acts on the pathogen through the biofilm, resulting in faster onset of action.

[0025] Preferably, the ratio of polyglutamic acid to phospholipid is 1:(7-13) by mass.

[0026] Secondly, this application provides a method for preparing a vaginal foam with antibacterial properties, using the following technical solution: A method for preparing a vaginal foam with antibacterial properties includes the following steps: dissolving an emulsifier and a foaming agent in purified water to obtain an aqueous phase; mixing an antibacterial carrier, a co-emulsifier, and a foam stabilizer to obtain an alcohol phase; adding the alcohol phase to the aqueous phase and emulsifying it to obtain a drug matrix; dispensing the drug matrix and pressing it with a propellant to obtain the finished vaginal foam.

[0027] In summary, this application has the following beneficial effects: 1. The antibacterial active substances coated with phospholipids in the antibacterial carrier of this application can easily pass through the biofilm formed by pathogen infection, so that the antibacterial active substances can directly act on the pathogens under the biofilm barrier and improve the antibacterial efficacy. At the same time, phospholipids have good moisturizing effect, which can effectively relieve the symptoms of vaginal dryness and itching, and can promote the growth of epithelial cells, thereby improving the vaginal microenvironment, which is conducive to enhancing the therapeutic effect and reducing the probability of disease recurrence.

[0028] 2. After application, the foaming agent of this application can form a stable and adherent film in the infected area, which is conducive to achieving a long-lasting antibacterial effect and effectively reduces leakage after application.

[0029] 3. This application uses polylactic acid microspheres as one of the raw materials to prepare the carrier substrate. Based on the good mechanical strength and hydrophobicity of polylactic acid microspheres, the adhesion stability of the drug film is better, which can effectively resist the influence of vaginal secretions or urine on the adhesion of the drug film. At the same time, the lactic acid formed by polylactic acid microspheres during natural degradation can regulate the vaginal pH, effectively improve the vaginal microenvironment, and thus achieve long-term regulation.

[0030] 4. The preparation of the carrier substrate of this application can be carried out in a purified water system without the introduction of other organic solvents, which makes the foaming agent safer and the process is relatively simple, making it easy for industrial-scale production.

[0031] 5. The phospholipids, water-soluble chitosan, polylactic acid microspheres and polyglutamic acid in this application all have good biocompatibility, are non-toxic and harmless, and can be naturally degraded or absorbed by tissues in the human body, thus having high biological safety. Detailed Implementation

[0032] The emulsifier in this embodiment includes at least one of Tween-20, Tween-40, Tween-60, Tween-80, poloxamer 407, and carbomer 934, with Tween-80 being preferred as the emulsifier; the co-emulsifier includes at least one of ethanol, glycerin, and propylene glycol, with glycerin being preferred as the co-emulsifier; the foaming agent includes at least one of sodium dodecyl sulfate, sodium fatty alcohol polyoxyethylene ether sulfate, and nonylphenol polyoxyethylene ether, with sodium dodecyl sulfonate being preferred as the foaming agent; the foam stabilizer includes at least one of stearic acid, stearyl alcohol, and lauric acid, with stearic acid being preferred as the foam stabilizer; and the propellant includes at least one of hydrofluoroalkane, hydrocarbon, and compressed gas, with tetrafluoroethane being preferred as the propellant. In this application, the mass of the drug matrix in each bottle of vaginal foam can be 20-80g, preferably 40g in this embodiment; the amount of propellant filled in each bottle of vaginal foam can be 3-6g, preferably 5g in this embodiment; the internal pressure of each bottle of vaginal foam is 3.5-4 bar; in the preparation of the carrier substrate, the mass ratio of water-soluble chitosan to polylactic acid microspheres can be 1:(1-2.5), preferably 1:1.8 in this embodiment; All the raw materials involved in this application are commercially available, including Tween-80 (CAS number 9005-65-6), sodium dodecyl sulfate (CAS number 2386-53-0), stearic acid (CAS number 57-11-4), distearylphosphatidylcholine (CAS number 816-94-4), lecithin (CAS number 8002-43-5), carboxymethyl chitosan (CAS number 83512-85-0), and polyglutamic acid (CAS number 25513-46-6). The present application will be further described in detail below with reference to preparation examples, embodiments and comparative examples.

[0033] Preparation Example 1 A method for preparing an antibacterial carrier includes the following steps: S1. Dissolve 100g of water-soluble chitosan in 1L of purified water and stir until there is no obvious solid to obtain a mixture. Add 180g of polylactic acid microspheres to the mixture and stir at 800rpm for 30min. Then, evaporate the purified water and dry and pulverize the mixture to obtain a carrier substrate with a particle size of 30μm. S2. Dissolve 100g of phospholipids and 10g of antibacterial active substance in 1L of anhydrous ethanol, and sonicate for 10min to obtain a homogeneous oil phase. Slowly drop the homogeneous oil phase into purified water while stirring at 600rpm and 45℃. After the addition is complete, sonicate in an ice-water bath for 5min to obtain a coating solution. Add 200g of carrier substrate to the coating solution and stir at 600rpm for 1h. Then, evaporate the purified water and residual ethanol, and then dry and pulverize to obtain an antibacterial carrier with a particle size of 50μm. The water-soluble chitosan is carboxymethyl chitosan with a degree of substitution ≥90%; the polylactic acid microspheres are racemic polylactic acid microspheres with a porous structure and a particle size of 20 μm; the antibacterial active substance is composed of metronidazole and nystatin in a mass ratio of 1.5:1; and the phospholipid is composed of distearylphosphatidylcholine and lecithin in a mass ratio of 1:1.

[0034] Preparation Example 2 The difference between this preparation example and preparation example 1 is that in step S1, the amount of polylactic acid microspheres added is 250g.

[0035] Preparation Example 3 The difference between this preparation example and Preparation Example 1 is that in step S1, the amount of polylactic acid microspheres added is 100g.

[0036] Preparation Example 4 The difference between this preparation example and Preparation Example 1 is that, in step S1, the water-soluble chitosan is oligochitosan with a degree of deacetylation ≥85% and a molecular weight ≤3200 Da.

[0037] Preparation Example 5 The difference between this preparation example and preparation example 1 is that, in step S2, an antibacterial carrier with a particle size of 30 μm is obtained.

[0038] Preparation Example 6 The difference between this preparation example and preparation example 1 is that, in step S2, an antibacterial carrier with a particle size of 100 μm is obtained.

[0039] Preparation Example 7 The difference between this preparation example and preparation example 1 is that in step S2, 90g of phospholipid and 10g of polyglutamic acid are dissolved in 1L of 90% ethanol solution, mixed and stirred for 15min, and then the antibacterial active substance is added. The mixture is then sonicated for 10min to obtain a homogeneous oil phase. The remaining steps remain unchanged. The molecular weight of polyglutamic acid is 700-1000kDa.

[0040] Preparation Example 8 The difference between this preparation example and preparation example 7 is that in step S2, the amount of phospholipid added is 87.5g and the amount of polyglutamic acid added is 12.5g.

[0041] Preparation Example 9 The difference between this preparation example and preparation example 7 is that in step S2, the amount of phospholipid added is 92.8g and the amount of polyglutamic acid added is 7.2g.

[0042] Comparative Preparation Example 1 The difference between this comparative preparation example and preparation example 1 is that the antibacterial carrier does not include phospholipids, that is, no phospholipids are added in step S2, and the amount of carrier substrate added is 300g.

[0043] Comparative Preparation Example 2 The difference between this comparative preparation example and preparation example 1 is that the antibacterial carrier does not include a carrier substrate. The preparation method includes the following steps: 100g of phospholipid and 10g of antibacterial active substance are dissolved in 1L of anhydrous ethanol and ultrasonically treated for 10min to obtain a homogeneous oil phase; the homogeneous oil phase is slowly dripped into purified water under stirring at a stirring speed of 600rpm and a purified water temperature of 45℃. After the dripping is completed, the mixture is ultrasonically treated in an ice-water bath for 5min to obtain a coating solution. The purified water and residual ethanol are evaporated, and the mixture is then dried and pulverized to obtain an antibacterial carrier with a particle size of 50μm.

[0044] Comparative preparation example 3 The difference between this comparative preparation example and preparation example 1 is that the carrier substrate does not include water-soluble chitosan, that is, polylactic acid microspheres with a particle size of 30 μm are selected as the carrier substrate.

[0045] Comparative preparation example 4 The difference between this comparative preparation example and preparation example 1 is that the carrier substrate does not include polylactic acid microspheres. Step S1 is as follows: 280g of water-soluble chitosan is dissolved in 1L of purified water, mixed and stirred until there is no obvious solid, and a mixture is obtained. The purified water is evaporated, and then dried and pulverized to obtain a carrier substrate with a particle size of 30μm.

[0046] Comparative preparation example 5 The difference between this comparative preparation example and preparation example 1 is that an equal amount of insoluble chitosan was used to replace the water-soluble chitosan. The insoluble chitosan had a degree of deacetylation of 70% and a molecular weight of 300-600 kDa. Step S1 is as follows: 100 g of insoluble chitosan was dissolved in 1 L of 10% glacial acetic acid solution and stirred until no obvious solid was obtained. 180 g of polylactic acid microspheres were added to the mixture and stirred at 800 rpm for 30 min. The glacial acetic acid was then evaporated and dried and pulverized to obtain a carrier substrate with a particle size of 30 μm.

[0047] Example 1 A vaginal foam with antibacterial properties includes a pharmaceutical matrix and a propellant. The pharmaceutical matrix comprises the following raw materials by weight: 32g of antibacterial carrier, 58g of emulsifier, 100g of co-emulsifier, 14g of foaming agent, 6g of foam stabilizer, and 790g of purified water. The propellant is tetrafluoroethane; the antibacterial carrier is the one prepared in Preparation Example 1; the emulsifier is Tween-80; the co-emulsifier is glycerin; the foaming agent is sodium dodecyl sulfonate; and the foam stabilizer is stearic acid. The preparation method includes the following steps: Aqueous phase preparation: Dissolve the emulsifier and foaming agent in purified water at 70℃, mix and stir for 10 min to obtain the aqueous phase; Preparation of alcohol phase: Mix antibacterial carrier, co-emulsifier and foam stabilizer, heat to 45℃ and stir for 15 min to obtain alcohol phase; Homogenization: The alcohol phase was added to the aqueous phase, and then homogenized and emulsified at 5000 rpm for 10 min to obtain the drug matrix; Filling and pressurizing: After the drug matrix cools to room temperature, the drug matrix is ​​dispensed according to the dosage, then placed into aluminum cans, filled with propellant, and sealed to obtain the finished vaginal foam product.

[0048] The difference between Examples 2-5 and Example 1 lies in the different raw material ratios of the drug matrix, as shown in the table below.

[0049] Table 1. Proportioning of Drug Matrix Raw Materials The difference between Examples 6-13 and Example 1 is that the antibacterial carriers were prepared using different preparation methods. The specific correspondences are as follows: The antibacterial carrier in Example 6 was prepared in Preparation Example 2; the antibacterial carrier in Example 7 was prepared in Preparation Example 3; the antibacterial carrier in Example 8 was prepared in Preparation Example 4; the antibacterial carrier in Example 9 was prepared in Preparation Example 5; the antibacterial carrier in Example 10 was prepared in Preparation Example 6; the antibacterial carrier in Example 11 was prepared in Preparation Example 7; the antibacterial carrier in Example 12 was prepared in Preparation Example 8; and the antibacterial carrier in Example 13 was prepared in Preparation Example 9.

[0050] Comparative Example 1 The difference between this comparative example and Example 1 is that the antibacterial carrier was prepared in Comparative Preparation Example 1.

[0051] Comparative Example 2 The difference between this comparative example and Example 1 is that the antibacterial carrier was prepared in Comparative Preparation Example 2.

[0052] Comparative Example 3 The difference between this comparative example and Example 1 is that the antibacterial carrier was prepared in Comparative Preparation Example 3.

[0053] Comparative Example 4 The difference between this comparative example and Example 1 is that the antibacterial carrier was prepared in Comparative Preparation Example 4.

[0054] Comparative Example 5 The difference between this comparative example and Example 1 is that the antibacterial carrier was prepared in Comparative Preparation Example 5.

[0055] Performance testing methods 1. The foaming agents in Examples 1-13 were used as test samples for foam appearance evaluation. The judgment criteria for each index of foam appearance evaluation are as follows: Foam resilience: When rubbed by hand, foam that is dry and easily breaks is poor; foam that is slightly moist and increases in diameter without breaking after prolonged rubbing is average; and foam that is moist and does not change shape significantly after prolonged rubbing is good. Foam fineness: Individual bubbles that are clearly visible and have a large diameter are poor; individual bubbles that are slightly smaller in diameter but still distinguishable are average; individual bubbles that are difficult to distinguish and whose diameter cannot be visually estimated are good. Foam stability: Foam lasting less than 10 minutes is poor, 10-30 minutes is average, and more than 30 minutes is good.

[0056] The results showed that the vaginal foaming agents in Examples 1 to 13 were rated as good in terms of foam toughness, foam fineness, and foam stability. That is, the foam was moist, the foam shape did not change much after prolonged rubbing, the foam was fine and intact, and the defoaming time could be maintained at more than 30 minutes.

[0057] 2. Therapeutic efficacy trials Bacterial culture: Using Staphylococcus aureus, Escherichia coli, and Candida albicans as pathogenic bacteria, pure cultures of Staphylococcus aureus + Escherichia coli were prepared and passaged to produce 1×10⁻⁶ cultures. 9 CFU / ml bacterial suspension and pure culture of Candida albicans were used to prepare 1×10 9 CFU / ml bacterial suspension for later use; Experimental subjects: young adult female non-pregnant New Zealand experimental rabbits, weighing 2-3 kg, acclimatized for 7 days before the experiment; Establishing a vaginitis model: (1) After rinsing the vagina of experimental rabbits three times with sterile phosphate buffer at pH 8 (5 min interval each time), 0.2 ml of 1×10⁻⁶ solution was used. 9 A suspension of Staphylococcus aureus and Escherichia coli at CFU / ml was injected into the cervix of experimental rabbits once a day for three consecutive days. After that, the redness and swelling of the vulva and vagina, as well as the presence of secretions, were examined. Vaginal swabs were taken from vaginal and cervical secretions for smear staining and microscopic examination. If the vulva and vagina of the experimental rabbits showed obvious edema, and the vaginal and cervical secretions contained a large number of pathogenic bacteria, it indicated that the bacterial vaginosis model had been successfully established. (2) Rinse the vagina of the experimental rabbits three times with sterile phosphate buffer at pH 8, with a 5-minute interval between each rinse, and then rinse with 0.2 ml of 1×10⁻⁶ solution. 9 A CFU / ml Candida albicans suspension was injected into the cervix of experimental rabbits via a catheter once a day for three consecutive days. After that, vaginal secretions were collected by vaginal swabs for microbial examination. When the experimental rabbit's vagina was obviously congested, red and swollen, and accompanied by a large amount of purulent secretions, and a large number of infectious bacteria were visible under a microscope, it was considered that the rabbit fungal vaginitis model had been successfully prepared. Grouping and Treatment Observation: Rabbits without established vaginitis models were used as a blank control group. The rabbits with established vaginitis models were divided into a model group and 18 sample groups, with 10 rabbits in each group. Each group consisted of half bacterial vaginitis models and half fungal vaginitis models. The 18 sample groups were treated with the vaginal foam agents described in Examples 1-13 and Comparative Examples 1-5 of this application. Each rabbit in each group was given the corresponding drug once a day for 6 consecutive days. The dosage was determined by filling the vagina, reaching the cervix, and applying it around the vulva. The model group and the blank control group were given sterile saline. Scoring criteria: Observe vaginal secretions 24 hours after the last administration, then sacrifice the rabbits using the air embolization method. Obtain vaginal tissue, fix it in 10% neutral formaldehyde, paraffin-embedded it, section it, and stain it with hematoxylin and eosin (HE) for pathological examination. The pathological scoring and grading criteria for vaginal tissue biopsy are as follows: 0 points: No congestion, edema, erosion, or obvious discharge; 1 point: Mild congestion, edema, erosion, and a small amount of discharge; 2 points: Moderate congestion, edema, erosion, and copious discharge; 3 points: Severe congestion, edema, erosion, and copious secretions; The average score of vaginal tissue biopsy pathology in each group of experimental rabbits was calculated. The experimental samples with a score of 0 were recorded as cured samples, and the experimental samples with a score of 1 were recorded as improved samples. The cure rate and improvement rate of each group were calculated respectively. The specific experimental data are shown in the table below.

[0058] Table 2 Experimental Data Based on the experimental data in Table 2, the vaginal foam agent of this application, when used to treat bacterial vaginosis and fungal vaginitis, maintained an average pathological score of less than 0.6 in vaginal tissue biopsies from experimental rabbits, with a cure rate exceeding 50%, an improvement rate exceeding 30%, and an overall effective rate of 100%. Therefore, the vaginal foam agent of this application demonstrates excellent efficacy against both the BV biofilm present in bacterial vaginosis and the VVC biofilm present in fungal vaginitis.

[0059] Based on the experimental data from Examples 1 and 11, while both examples had an efficacy rate of 100%, Example 11 showed a higher cure rate. This may be because the antibacterial carrier in Example 11 was further supplemented with polyglutamic acid during the preparation process. Polyglutamic acid has excellent moisturizing effects and works better with phospholipids to encapsulate antibacterial active substances. Furthermore, the positive charge property of polyglutamic acid in an acidic environment is conducive to promoting the fusion of the coating with the pathogen biofilm, resulting in a better bactericidal effect.

[0060] Based on the experimental data from Example 1 and Comparative Example 1, the average score of vaginal tissue biopsy pathology in Comparative Example 1 was significantly higher than that in Example 1, with an improvement rate of only 10% and a cure rate of 0%. This means that 90% of the rabbits in Comparative Example 1 exhibited moderate to severe symptoms of vaginal congestion, edema, and erosion, accompanied by significant discharge. This may be because the antibacterial carrier in Comparative Example 1 does not contain phospholipids. Antibacterial active substances directly loaded onto the carrier substrate have difficulty crossing the pathogen biofilm barrier and cannot fully exert their efficacy. Furthermore, under the influence of vaginal secretions and urine from the rabbits, the adhesion of the phospholipid-free antibacterial carrier to the pathogen biofilm is generally poor, leading to a decrease in therapeutic efficacy.

[0061] Based on the experimental data from Example 1 and Comparative Example 2, the average pathological score of vaginal tissue biopsies from rabbits in Comparative Example 2 was significantly higher than that in Example 1, with an improvement rate of only 20% and a cure rate of 0%. This may be because the antibacterial carrier in Comparative Example 2 did not include a carrier substrate; that is, the antibacterial active substance was directly coated with phospholipids as the antibacterial carrier. Such antibacterial carriers may have problems with poor stability and drug efficacy loss. In addition, in the absence of polylactic acid microspheres and water-soluble chitosan, the mechanical strength, hydrophobicity, and adhesion of the drug film decreased significantly, and vaginal secretions and urine had a significant impact on the stability of the drug film. Furthermore, the degradation products of polylactic acid microspheres can regulate vaginal pH and effectively improve the vaginal microenvironment, while water-soluble chitosan has antibacterial, hemostatic, analgesic, and tissue repair-promoting effects. Therefore, in the absence of a carrier substrate, the vaginal foam in Comparative Example 2 had poor efficacy.

[0062] Based on the experimental data from Examples 1 and Comparative Examples 3-5, the treatment performance of the vaginal foams in Comparative Examples 3 and 4 was worse than that in Example 1. This may be because the carrier substrates of both examples did not contain water-soluble chitosan and polylactic acid microspheres, respectively. In Comparative Example 3, without water-soluble chitosan, the use of polylactic acid microspheres as the carrier substrate may have resulted in poor loading of the encapsulation, leading to lower adhesion of the drug film after application and thus poorer efficacy. While Comparative Example 5, which used an equal amount of insoluble chitosan instead of water-soluble chitosan, showed a significant improvement in efficacy, it still lagged behind Example 1. This may be because water-soluble chitosan binds more stably to polylactic acid microspheres than insoluble chitosan, resulting in better loading of the encapsulation and more effective release of the encapsulation after application.

[0063] In Comparative Example 4, only water-soluble chitosan was used as the carrier substrate. Compared with the carrier substrate in Example 1, it may have problems with poor loading effect and poor drug film stability, resulting in poor efficacy.

[0064] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.

Claims

1. A vaginal foam with antibacterial properties, characterized in that, It includes a drug matrix and a propellant, wherein the drug matrix comprises the following raw materials in parts by weight: 20-40 parts of antibacterial carrier, 40-70 parts of emulsifier, 70-130 parts of co-emulsifier, 8-20 parts of foaming agent, 4-9 parts of foam stabilizer, and purified water to make up to 1000 parts. The antibacterial carrier includes antibacterial active substances, phospholipids, and a carrier substrate; The carrier substrate is prepared from polylactic acid microspheres and water-soluble chitosan; The method for preparing the antibacterial carrier is as follows: first, antibacterial active substances are coated with phospholipids to obtain a coating, and then the coating is loaded onto a carrier substrate to obtain the antibacterial carrier.

2. The vaginal foaming agent with antibacterial effect according to claim 1, characterized in that, The antibacterial active substance includes at least one of miconazole nitrate, econazole nitrate, sertaconazole nitrate, isoconazole nitrate, clotrimazole, metronidazole, polycresolsulfonate, nifuratel, nystatin, metronidazole, and ornidazole.

3. The vaginal foaming agent with antibacterial effect according to claim 1, characterized in that, The water-soluble chitosan includes at least one of carboxymethylated chitosan and oligochitosan.

4. The vaginal foaming agent with antibacterial effect according to claim 1, characterized in that, The phospholipids include at least one of lecithin, dipalmitoylphosphatidylcholine, and distearate phosphatidylcholine.

5. A vaginal foaming agent with antibacterial properties according to claim 1, characterized in that, The carrier substrate is prepared as follows: water-soluble chitosan is dissolved in purified water, polylactic acid microspheres are added, the mixture is thoroughly mixed, the purified water is distilled off, and then the substrate is dried and pulverized to obtain the carrier substrate.

6. A vaginal foaming agent with antibacterial properties according to claim 1, characterized in that, The particle size of the antibacterial carrier is 30–100 μm.

7. The vaginal foaming agent with antibacterial effect according to claim 1, characterized in that, The foaming agent includes at least one of sodium dodecyl sulfate, sodium fatty alcohol polyoxyethylene ether sulfate, and nonylphenol polyoxyethylene ether.

8. A vaginal foaming agent with antibacterial properties according to claim 1, characterized in that, The antibacterial carrier also includes polyglutamic acid. The preparation method of the antibacterial carrier is as follows: first, mix polyglutamic acid and phospholipids, and use the resulting mixture to coat the antibacterial active substance to obtain a coating; then load the coating onto a carrier substrate to obtain the antibacterial carrier.

9. A vaginal foaming agent with antibacterial properties according to claim 8, characterized in that, The ratio of polyglutamic acid to phospholipid by mass is 1:(7-13).

10. A method for preparing a vaginal foam with antibacterial properties as described in any one of claims 1 to 9, characterized in that, Includes the following steps: Emulsifier and foaming agent are dissolved in purified water to obtain an aqueous phase; antibacterial carrier, co-emulsifier and foam stabilizer are mixed to obtain an alcohol phase; the alcohol phase is added to the aqueous phase and emulsified to obtain a drug matrix; the drug matrix is ​​dispensed and then injected with a propellant to obtain the finished vaginal foam product.

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