Nano-silver contraceptive gel for rapidly killing various venereal disease pathogens such as HPV (human papilloma virus)

Abstract

The invention relates to the technical field of sexual health, and discloses a nano-silver contraceptive gel for rapidly killing various venereal disease pathogens such as HPV (human papillomavirus), the nano-silver contraceptive gel comprises the following components by weight: 1.5-2.5 parts of nano-silver particles; 2.0 to 3.0 parts of nonoxynol ether; the invention further provides a preparation method of the nano-silver contraceptive gel capable of rapidly killing various venereal disease pathogens such as HPV, and the preparation method comprises the following steps: S1, preparing nano-silver particles: carrying out hyaluronic acid or chitosan surface modification on the nano-silver particles with the particle size of 10-30nm; s2, preparing active solutions, namely respectively preparing nonoxynol, green tea polyphenol and chitosan into solutions; by modifying the nano-silver particles, optimizing the active solution and adjusting the pH value of the gel, the comprehensive effects of uniform distribution of components, efficient virus resistance, contraception protection and mucous membrane friendliness are achieved.

Description

Technical Field

[0001] The invention relates to the technical field of sexual health, in particular to a nano silver contraceptive gel that can quickly kill various sexually transmitted disease pathogens such as HPV. Background Art

[0002] In modern society, sexual health issues are receiving more and more attention, among which the spread of human papillomavirus (HPV) and the need for contraception are particularly prominent. HPV is not only the main pathogen causing sexually transmitted diseases, but is also closely related to the occurrence of cervical cancer, which seriously threatens women's health. As a highly effective antibacterial material, nanosilver has gradually been used in health products due to its excellent safety and antibacterial effects. In particular, the innovative design of combining nanosilver with gel can meet the comprehensive needs of rapid sterilization, contraception and protection of mucous membranes, becoming a new trend of multifunctional protection.

[0003] In current technologies, nanosilver has been widely used in anti-infection products, which can effectively inhibit the activity of various pathogens and show good safety and applicability. At the same time, chemical contraceptives such as nonoxynol have become a mature choice among chemical contraceptive products by quickly destroying sperm cell membranes. These technologies solve single needs in some specific scenarios and have achieved certain results in their respective fields.

[0004] Although the existing technology has achieved certain results in some aspects, there are still some shortcomings. First, the unmodified nanosilver particles often lead to uneven distribution of activity due to the problem of agglomeration, which affects the stability of the antiviral performance. Second, although chemical contraceptives take effect quickly, they often cause mucosal irritation and even user discomfort during use due to unreasonable concentration distribution. In addition, the gel matrix with unadjusted pH does not match the natural microecology of the vagina, which not only reduces the antibacterial effect, but also may disrupt the balance of healthy flora. Summary of the invention

[0005] In view of the shortcomings of the prior art, the present invention provides a nanosilver contraceptive gel that can quickly kill HPV and other sexually transmitted disease pathogens, solving the problems of nanosilver agglomeration, contraceptive irritation, and the mismatch between gel pH and vaginal microecology in the prior art.

[0006] To achieve the above objectives, the present invention is implemented by the following technical scheme: a nanosilver contraceptive gel that quickly kills various sexually transmitted disease pathogens such as HPV, and the nanosilver contraceptive gel comprises the following components in parts by weight: Nanosilver particles: 1.5-2.5 parts. Nanosilver reacts with protein sulfhydryl groups to change the membrane structure of the virus, further inhibiting its ability to infect. In addition, nanosilver can also play a certain antibacterial role in contraceptive gels, reducing the risk of transmission of other STD pathogens (such as Neisseria gonorrhoeae and Candida albicans); Nonoxynol: 2.0-3.0 parts. Nonoxynol is a nonionic surfactant that destroys the lipid bilayer structure of sperm cell membrane, causing sperm inactivation. In the gel matrix, nonoxynol reduces local surface tension, improves the uniformity of contact between nanosilver particles and pathogens, and enhances the overall killing effect. Chitosan: 1.0-1.5 parts. Chitosan has cationic properties and can adsorb negatively charged pathogens such as viruses through electrostatic action, preventing them from attaching to the surface of host cells. At the same time, it combines with the vaginal mucosa to form a protective film, which helps to repair possible damaged epithelial tissue. Green tea polyphenols: 0.5-1.0 parts. Green tea polyphenols (the main component is EGCG) have broad-spectrum antiviral and antioxidant effects, which can inhibit the infection of HPV and other viruses. At the same time, it can reduce the oxidative damage of pathogens to cells by removing reactive oxygen species (ROS), and reduce the potential stimulation of nanosilver and nonoxynol to mucosa. Carbomer: 2.0-3.5 parts. Carbomer, as a hydrophobic polymer, forms a three-dimensional network structure to achieve long-lasting adhesion of the gel. It can also control the sustained release rate of nanosilver and other active ingredients, thus prolonging the action time of the gel. Polyethylene glycol (PEG): 3.0-5.0 parts. PEG improves the dispersion of nanosilver particles and nonoxynol ether in the matrix by increasing the hydrophilicity of the gel, avoiding aggregation of components, and also improves the lubricity of the gel and enhances comfort in use; Sodium hyaluronate: 1.0-1.5 parts. Sodium hyaluronate enhances the lubrication property of the gel by absorbing water, while promoting the repair of mucosal tissue and the restoration of barrier function; Lactic acid or citric acid: 0.5-1.0 parts, which reduces the proliferation of pathogens (especially bacteria and fungi) by acidifying the environment, while helping to maintain the balance of healthy flora; Glycerol: 2.5-3.5 parts. The high hydrophilicity of glycerol helps improve the uniformity and adhesion of the gel. Vitamin E: 0.5-1.0 parts. Vitamin E reduces inflammation by scavenging free radicals and works synergistically with green tea polyphenols to further improve tissue repair ability.

[0007] Preferably, the nanosilver particles include: Nanosilver particles with a particle size of 10-30nm can significantly increase the specific surface area of ​​nanosilver particles, increase the contact probability with HPV virus particles, and thus improve the inactivation efficiency. Nanosilver particles of this particle size can penetrate the HPV virus shell and directly interact with its internal genetic material (DNA or RNA) to inhibit viral replication; Surface-modified hyaluronic acid or chitosan. Surface modification can prevent the nanosilver particles from agglomerating in the gel matrix, ensuring that they are evenly dispersed and maintain high activity. Chitosan has cationic properties and can electrostatically adsorb to the negatively charged areas on the surface of HPV and other viruses, promoting the contact between nanosilver particles and viruses. Hyaluronic acid improves the binding efficiency of nanosilver particles with virus particles by enhancing the wettability of the particles. The concentration of the modification solution is 1.5-2.0%, which can form a uniform modification layer and enhance the stability of the nanosilver particles in the gel matrix.

[0008] Preferably, the nonoxynol ether comprises: Nonoxynol ether and warm water are mixed and dissolved in a ratio of 1:5. Nonoxynol ether has limited solubility in water. Mixing in a ratio of 1:5 can effectively reduce its surface tension and promote the formation of a stable dispersion system between its molecules. The mixed solution can be better compatible with the gel matrix, ensuring that nonoxynol ether is evenly distributed in the gel, avoiding excessive local concentration and causing irritation to the mucous membrane; The dissolving temperature is 40-50℃. The temperature range of 40-50℃ can reduce the viscosity of nonoxynol ether, enhance the molecular activity, and make it disperse faster and more stable in water. If the temperature is too high (>50℃), it is easy to cause the molecular structure of nonoxynol ether to change, affecting its surface activity; and below 40℃, the dissolving speed is slow and local aggregation is prone to occur. Therefore, this temperature range can make nonoxynol ether disperse faster and more evenly into the subsequent gel matrix, thereby improving the release efficiency of contraceptive and antiviral components; The dissolution time is 10-20 minutes. This range of dissolution time can ensure that the nonoxynol ether molecules are completely dissociated and evenly distributed in water to form a stable dispersed phase, thereby providing a high-quality basic solution for subsequent gel preparation.

[0009] Preferably, the chitosan comprises: The molecular weight of chitosan is 50-150 kDa. Chitosan with a molecular weight of 50-150 kDa has a moderate molecular chain length and a number of positively charged amino groups, which can electrostatically adsorb to the negatively charged surface of HPV and other viruses, interfering with the binding of viruses to host cells. The concentration of chitosan solution is 1.0-2.0%. When the concentration is lower than 1.0%, the chitosan solution may not form a complete modification layer, reducing the stability of the nanosilver particles; higher than 2.0% may cause the solution viscosity to be too high, affecting the dispersion and uniformity during the modification process. Therefore, the concentration in this range can ensure the effective exposure of the cationic amino group, maximize the electrostatic adsorption efficiency with HPV and other virus particles, and balance the biological function and safety. The modification time is 4-6 hours. If the modification time is too short (<4 hours), it may lead to incomplete chitosan adsorption and failure to form a stable modification layer. If the modification time is too long (>6 hours), it may cause excessive cross-linking of the chitosan molecular chains and reduce the uniformity of the modification. Therefore, this decoration time range can prevent the nanosilver particles from agglomerating in the gel matrix, ensuring the durability of their antiviral and antibacterial activity, while also improving their electrostatic adsorption capacity, so that the modified nanosilver particles can more efficiently capture HPV viruses and enhance the overall antiviral effect.

[0010] Preferably, the gel matrix comprises: Carbomer is dispersed in pure water at a stirring speed of 300-500rpm. Carbomer is a high molecular polymer. By being dispersed in water, its molecular chain can fully extend and form a hydrogen bond network with water molecules, thereby constructing a three-dimensional structure of the gel and providing a stable carrier for other functional ingredients. The stirring speed in this range can ensure the complete dispersion of carbomer and avoid introducing too many bubbles that affect the stability and uniformity of the gel, thereby ensuring that the functions of each ingredient can be fully exerted. Polyethylene glycol is added at a weight ratio of 1:2-1:3 between carbomer and PEG. PEG reduces the cohesion of the gel and improves solubility and dispersibility through interaction with the carbomer molecular chain, thereby enhancing the lubricity and ductility of the gel. Carbomer and PEG are mixed at a ratio of 1:2-1:3 to maintain the strength of the gel while improving its flexibility and user comfort. A ratio lower than 1:2 is likely to result in insufficient mechanical properties of the gel; a ratio higher than 1:3 is likely to result in the gel being too thin, reducing its carrying capacity for active components; The pH is adjusted to 3.5-4.5, and the dripping speed is 0.1-0.3 ml / min. The pH value of the gel matrix is ​​adjusted to 3.5-4.5, which is not only compatible with the vaginal environment, but also can enhance the anti-infection effect of the gel by inhibiting the activity of pathogens. The dripping speed in this range can ensure that the acid solution and the gel matrix are fully mixed, avoiding the breakage of the carbomer molecular chain or the destruction of the gel structure due to local over-acidity.

[0011] The present invention also provides a method for preparing a nano-silver contraceptive gel that can quickly kill various sexually transmitted disease pathogens such as HPV, comprising the following steps: S1, preparing nanosilver particles, modifying the surface of nanosilver particles with a particle size of 10-30 nm with hyaluronic acid or chitosan; S2, preparing an active solution, preparing nonoxynol, green tea polyphenols and chitosan into solutions respectively; S3, preparing a gel matrix, mixing carbomer and polyethylene glycol to prepare a matrix; S4, adding the components in S1, S2 and S3 to the gel matrix in sequence and stirring evenly; S5. Adjust the pH value to 3.5-4.5, cool and shape.

[0012] Preferably, the preparation of the nanosilver particles comprises: Preparation of silver nanoparticles by chemical reduction method. Chemical reduction principle: Ag in silver nitrate + Under the action of reducing agent, it is reduced to metallic silver (Ag 0 ), gradually aggregate to form nanoparticles. The particle size and distribution of nanosilver particles can be adjusted by controlling the reduction rate and reaction conditions; The concentration of the modification solution is controlled to 1.5-2.0%. A concentration range of 1.5-2.0% can form a moderate modification layer, which ensures the stability of the particles while not completely covering the active sites on the particle surface. The stirring speed is 500-700rpm and the modification time is 4-6 hours. The stirring speed in this range can provide sufficient shear force to make the chitosan or hyaluronic acid molecules in the modification liquid evenly adsorbed onto the surface of the nanosilver particles to form a stable protective layer. This decoration time range ensures the formation and stability of the modification layer.

[0013] Preferably, the preparation of the active solution comprises: Nonoxynol ether is mixed with warm water at a weight ratio of 1:5, and the mixing temperature is 40-50°C. The weight ratio of 1:5 can effectively reduce the surface tension of nonoxynol ether, ensure that it is evenly dissolved in water, and prevent poor dispersion or insufficient dilution effect caused by too low or too high a ratio. This temperature range can reduce the viscosity of nonoxynol ether, increase its molecular activity, make it easier to disperse in water, and form a uniform solution; Green tea polyphenols are extracted using an ethanol-water mixed solvent with an ethanol volume fraction of 70-80%, an extraction temperature of 60-70°C, and a time of 2-4 hours. This volume fraction can effectively dissolve the polyphenols in green tea. The polarity of ethanol and the polarity of water work synergistically to increase the solubility of the target ingredients (polyphenol compounds) and extract more active substances. This temperature and time range can accelerate the release of active substances from plant cells while avoiding oxidation or degradation of polyphenols caused by high temperatures.

[0014] Preferably, the preparation of the gel matrix comprises: Carbomer is dispersed in pure water at a concentration of 2.0-3.5%. This concentration range can balance mechanical strength and operability. When the carbomer concentration is lower than 2.0%, it cannot form a gel matrix of sufficient strength, affecting the dispersion and adhesion properties of other active ingredients. When the concentration exceeds 3.5%, the viscosity will increase, reducing the fluidity of the gel and user comfort. The stirring speed is 300-500rpm, and the dissolution time is 2-3 hours. This stirring speed range can provide moderate shear force to fully dissolve and evenly distribute the carbomer. At the same time, this dissolution time range can ensure that the carbomer molecular chain is fully unfolded and fully interacts with water molecules to establish a stable gel network. Polyethylene glycol and carbomer are mixed in a weight ratio of 1:2-1:3 and stirred for 1 hour. The weight ratio of 1:2-1:3 can significantly improve the fluidity and lubricity of the gel while maintaining the mechanical strength of the gel. This stirring can ensure that the PEG molecules are fully mixed with the carbomer network without destroying the three-dimensional structure of the carbomer, while improving the flexibility and biocompatibility of the matrix.

[0015] Preferably, the final mixing step comprises: Slowly adding the nanosilver dispersion into the gel matrix at a stirring speed of 400-600 rpm for 1-2 hours. The slow addition and stirring speed within this range can prevent the nanosilver particles from agglomerating due to excessive local concentration, thereby ensuring their uniform distribution in the gel matrix. The active solutions are added to the gel matrix in sequence and stirred for 30-60 minutes. The nonoxynol solution should be added first so that it can be evenly distributed in the matrix to form a contraceptive barrier. The green tea polyphenol solution is added subsequently to enhance the antioxidant and antiviral functions of the gel. The chitosan solution is added last to further stabilize the gel structure and enhance its ability to protect the mucosa. At the same time, the stirring time within this range allows the active ingredients to be fully combined in the gel matrix. The gel is allowed to stand for 12-24 hours to complete the gel formation. The standing time allows the bubbles generated during the mixing process to escape naturally, ensuring the uniformity and integrity of the gel appearance.

[0016] The present invention provides a nano-silver contraceptive gel that can quickly kill various sexually transmitted disease pathogens such as HPV. It has the following beneficial effects: 1. The present invention modifies the nanosilver particles with hyaluronic acid or chitosan, making the particles more stable and more evenly dispersed. The virus killing effect is thus significantly enhanced. Compared with traditional unmodified particles, the common problems of easy agglomeration and weakened activity are solved, while the antiviral durability is enhanced.

[0017] 2. The present invention achieves a perfect combination of the two functions of contraception and antiviral by precisely adjusting the ratio of nonoxynol and the extraction conditions of green tea polyphenols. The activity of green tea polyphenols is retained to the greatest extent and exerted synchronously with the effect of nonoxynol. Compared with the previous process, the problem of low solution activity and single function is solved.

[0018] 3. The present invention adjusts the pH value of the gel precisely to 4.2, which is highly compatible with the vaginal microecology and significantly enhances the inhibitory effect on pathogens. Compared with the solution without pH adjustment, this technology effectively solves the problems of insufficient antibacterial and potential irritation, and also maintains the natural acid barrier.

[0019] 4. The present invention adopts a process design of gradual dripping and sequential mixing to evenly distribute the nanosilver and active solution in the matrix. The result is higher consistency and more stable performance. Compared with the traditional rapid mixing method, this technology completely avoids local component deviation and unevenness. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 The present invention is a process flow chart of the preparation method. DETAILED DESCRIPTION

[0021] The following will be combined with the drawings in the specification of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0022] Please see attached Figure 1 : Example 1: Preparation of Nanosilver Contraceptive Gel for Rapid Killing of HPV step: Using silver nitrate (AgNO 3 , 0.1M) as the silver source, take 10mL of silver nitrate solution and mix it with an equal amount of 0.1M glucose solution. The reaction temperature is set to 60°C, the stirring speed is 600rpm, and the reaction is continued for 30 minutes. The particle size of the prepared nanosilver particles is controlled at about 20nm. Then 1.5% hyaluronic acid solution is added for modification, stirred for 4 hours at a speed of 500rpm to form a stable dispersion.

[0023] Nonoxynol was mixed with warm water at 45°C in a weight ratio of 1:5 and stirred to a transparent solution; green tea polyphenols were extracted by 70% ethanol at a temperature of 65°C for 3 hours; chitosan was dissolved in 1% acetic acid solution and the concentration was adjusted to 2.0%.

[0024] Carbomer was dispersed in pure water at a concentration of 3%, stirred at 400 rpm, and dissolved for 2.5 hours to form a colloidal liquid. Polyethylene glycol (PEG4000) was added and mixed at a weight ratio of 1:2 between carbomer and PEG, and stirred for another hour to form a matrix solution.

[0025] The nanosilver dispersion was slowly added to the matrix, with the stirring speed maintained at 500 rpm for 1.5 hours. Then, nonoxynol ether, green tea polyphenols and chitosan solution were added in sequence, and stirred for 40 minutes after each addition to ensure uniform dispersion. The pH value was adjusted to 4.0 and allowed to stand for 18 hours to complete the molding.

[0026] Example 2: Nanosilver gel with enhanced contraceptive and antiviral functions step: Using silver nitrate (AgNO 3 , 0.05M) and sodium citrate were used as raw materials, mixed in a volume ratio of 1:1, reaction temperature of 50°C, stirring speed of 700rpm. The average particle size of the generated silver particles was 15nm. 1.8% chitosan solution was added for modification, the modification time was 5 hours, and a uniform dispersion was prepared.

[0027] Nonoxynol was mixed with 50°C warm water at a weight ratio of 1:5 and stirred until transparent. Green tea polyphenols were extracted with 75% ethanol at a temperature of 70°C for 2 hours. Chitosan solution was prepared and the concentration was adjusted to 1.5%.

[0028] Carbomer was dispersed in pure water at a concentration of 2.5%, stirred at 500 rpm, and dissolved for 3 hours. PEG4000 was added and mixed at a weight ratio of 1:3 between carbomer and PEG, and stirred for 40 minutes to form a uniform matrix.

[0029] The nanosilver dispersion was slowly added to the matrix, with a stirring speed of 600 rpm for 1 hour. Then, the nonoxynol solution was added and stirred for 30 minutes; the green tea polyphenol solution was stirred for 40 minutes; and finally, the chitosan solution was added and stirred for another 50 minutes. The pH value was adjusted to 3.8 and the mixture was allowed to stand for 24 hours to form a finished gel.

[0030] Example 3: Nanosilver contraceptive gel for enhanced mucosal protection step: Take silver nitrate (AgNO 3 , 0.08M) was mixed with 1.5% hyaluronic acid solution at a ratio of 1:1. 0.1M glucosamine reducing agent was added, the reaction temperature was 65°C, the stirring speed was 450rpm, and the time was 45 minutes to prepare nanosilver particles with a particle size of 25nm.

[0031] The nonoxynol ether solution was mixed with 47°C warm water at a ratio of 1:5 and stirred evenly. Green tea polyphenols were extracted by 80% ethanol at a temperature of 60°C for 4 hours. Chitosan was dissolved in 1% acetic acid solution and the concentration was adjusted to 1.0%.

[0032] Carbomer concentration was 2.0%, dispersed in pure water, stirred at 350 rpm for 2 hours, PEG4000 was added at a ratio of 1:2, stirred for 40 minutes, and a matrix with good fluidity was formed.

[0033] The nanosilver dispersion was added dropwise to the matrix, with the stirring speed maintained at 500 rpm for 1.5 hours. Then the nonoxynol solution was added and stirred for 30 minutes; the green tea polyphenol solution was added and stirred for 40 minutes; finally, the chitosan solution was added and stirred for 50 minutes, the pH was adjusted to 4.5, and the mixture was allowed to stand for 12 hours to complete the molding.

[0034] Example 4: Long-acting antiviral nanosilver gel step: Silver nitrate (0.1M) and reducing agent (sodium citrate) were used at a reaction temperature of 55°C and a stirring speed of 500 rpm to generate particles with a particle size of 20 nm. 1.6% chitosan solution was added for modification for 6 hours.

[0035] Nonoxynol was mixed with warm water at a ratio of 1:5 at 45°C and stirred evenly. Green tea polyphenols were extracted with 75% ethanol at 70°C for 3 hours, and the chitosan concentration was 1.5%.

[0036] Carbomer concentration was 3.0%, dispersed in pure water, stirred at 400 rpm for 3 hours. PEG was added, carbomer and PEG were mixed at a weight ratio of 1:3, and stirred for 1 hour.

[0037] The nanosilver dispersion was slowly added to the matrix, with a stirring speed of 600 rpm for 1 hour. Then, nonoxynol solution, green tea polyphenol solution and chitosan solution were added in sequence, with each stirring time of 45 minutes. The pH was adjusted to 3.8 and the mixture was allowed to stand for 18 hours to form a finished gel.

[0038] Example 5: Multifunctional composite nanosilver gel step: Silver nitrate and 0.1M glucose were used as raw materials and reacted at 60°C for 30 minutes to prepare nanosilver particles with a particle size of 10 nm. Subsequently, 2.0% hyaluronic acid solution was added for modification and stirred for 5 hours.

[0039] Nonoxynol ether and water were mixed at a ratio of 1:5 at 50°C. Green tea polyphenols were extracted by 80% ethanol at 65°C for 3 hours. The concentration of chitosan solution was adjusted to 1.8%.

[0040] 3.5% carbomer was dispersed in pure water, stirred at 500 rpm for 2.5 hours. PEG was added at a ratio of 1:2 between carbomer and PEG, and stirred for 1 hour.

[0041] The nanosilver dispersion was added to the matrix and stirred at 600 rpm for 2 hours. The active solutions were added in sequence and stirred for 30, 45 and 50 minutes respectively. The pH was finally adjusted to 4.2 and the gel was formed after standing for 12 hours.

[0042] Comparative Example 1: Contraceptive gel with unmodified nanosilver particles (corresponding to Example 1) Unmodified silver nanoparticles were used directly, with a particle size range of 10-30 nm, prepared by chemical reduction method without modification with hyaluronic acid or chitosan.

[0043] The other steps are consistent with those in Example 1, including the preparation of nonoxynol and green tea polyphenol solutions, the preparation of the matrix and the mixing process.

[0044] Comparative Example 2: Contraceptive gel without optimizing the active solution ratio (corresponding to Example 2) Nonoxynol ether and warm water were mixed in a weight ratio of 1:3 at a temperature of 30°C; green tea polyphenols were extracted by 70% ethanol at a temperature of 50°C for 1 hour; the concentration of chitosan solution was 0.5%.

[0045] The other steps are consistent with those in Example 2, including the preparation of nanosilver particles and the formulation of the gel matrix.

[0046] Comparative Example 3: No polyethylene glycol was added to the gel matrix (corresponding to Example 3) Carbomer was dispersed in pure water at a concentration of 3.5%, with a stirring speed of 400 rpm and a dissolution time of 3 hours. No polyethylene glycol (PEG) was added.

[0047] The other steps are consistent with those in Example 3, including the preparation and mixing of nanosilver particles and active solution.

[0048] Comparative Example 4: Contraceptive gel without optimized mixing conditions (corresponding to Example 4) The nanosilver dispersion was added to the matrix all at once without stepwise addition, with a stirring speed of 200 rpm for 30 minutes. The active solution was added to the matrix at the same time with a stirring time of 15 minutes, without sequential addition.

[0049] The other steps are consistent with Example 4, including the preparation of nanosilver particles and active solution, and the preparation of the matrix.

[0050] Comparative Example 5: Contraceptive gel without pH adjustment (corresponding to Example 5) No lactic acid or citric acid was added, and the pH of the gel was kept neutral (about 7.0).

[0051] The other steps are consistent with those in Example 5, including the preparation of nanosilver particles and active solution, matrix mixing and molding.

[0052] Experiment 1: Verify the effect of silver nanoparticle modification on anti-HPV effect Experimental Description Experimental objectives: The difference in anti-HPV performance between Example 1 (modified nanosilver) and Comparative Example 1 (unmodified nanosilver) was compared to verify the effect of surface modification on the antiviral effect of nanosilver particles.

[0053] Experimental steps: Sample preparation: Example 1: A gel modified with nanosilver particles was prepared according to the method of Example 1, the particle size was controlled at 10-30 nm, and the surface was modified with hyaluronic acid (concentration 1.5%).

[0054] Comparative Example 1: Unmodified nanosilver particles were directly used for gel preparation, and the remaining steps were consistent with Example 1.

[0055] HPV pseudovirus preparation: Take HPV16 pseudovirus and adjust the concentration of virus suspension to 10 4 PFU / mL.

[0056] Virus sample mixing: The samples of Example 1 and Comparative Example 1 were mixed with the virus suspension at a ratio of 1: 1. Each group was tested 3 times in parallel.

[0057] Incubate at 37°C for 10 min.

[0058] Virus activity detection: The incubated samples were extracted and the viral gene copy number was detected by fluorescence quantitative PCR. The untreated virus suspension was used as the control group to calculate the virus inactivation rate.

[0059] Effect of modification of silver nanoparticles on anti-HPV effect The modified nanosilver particles showed a significant virus inactivation effect, which is a direct contribution of the hyaluronic acid modification layer. The modification layer not only stabilizes the dispersion of the particles, but also enhances the ability of the particles to bind to the viral coat protein, especially through the effect of the carboxyl group of hyaluronic acid on the viral envelope, making the viral structure more vulnerable to damage. Although the unmodified nanosilver particles still have a certain antiviral ability, they have a serious agglomeration phenomenon and a greatly reduced specific surface area, which greatly reduces the chance of contact with the virus. The inactivation efficiency of modified nanosilver against HPV was observed to be close to 90%, while that of unmodified particles was only about 68%. This difference is not only reflected in the inactivation rate, but also in the significant change in the number of viral copies. The surface modification of hyaluronic acid further enhances the capture ability of nanosilver particles through electrostatic interaction, changing the limitations of traditional unmodified particles in virus treatment.

[0060] Experiment 2: Verify the effect of active solution optimization on antiviral effect Experimental Description Experimental objectives: The anti-HPV performance of Example 2 (optimized active solution) and Comparative Example 2 (unoptimized active solution) was compared to verify the contribution of the optimized solution in enhancing the virus inactivation ability.

[0061] Experimental steps: Sample preparation: Example 2: According to the method of Example 2, an optimized nonoxynol solution (1:5 weight ratio, 40° C.) and a green tea polyphenol solution (70% ethanol extraction, extraction temperature 65° C., time 3 hours) were prepared, and finally a gel sample was obtained.

[0062] Comparative Example 2: Nonoxynol solutions were mixed in a weight ratio of 1:3 at a temperature of 30°C; green tea polyphenols were extracted under conditions of 50% ethanol, 50°C extraction temperature, and 1 hour to obtain a comparative example gel sample.

[0063] Virus Model: Take HPV18 pseudovirus suspension (concentration 10 4 PFU / mL). Three parallel experiments were set up for each sample, and the untreated virus group was used as a control.

[0064] Virus sample mixing: Each gel sample was mixed with the virus suspension in a 1:1 volume ratio and incubated at 37°C for 10 min.

[0065] Virus activity detection: After incubation, samples were extracted, and the residual viral infection capacity was determined using a cell infection experiment, and the viral inhibition rate was calculated.

[0066] Effect of active solution optimization on antiviral efficacy The optimized active solution significantly improved the antiviral performance, especially the extraction conditions of green tea polyphenols played a key role. In the experiment, the optimized nonoxynol ratio (1:5) was more conducive to uniform dispersion, increased the contact area with the virus, and further improved the inactivation efficiency. The optimization of the extraction temperature and ethanol concentration of green tea polyphenols significantly retained the activity of polyphenols. Its ability to bind to the viral capsid protein is enhanced, making the virus unable to infect cells. These optimization parameter details seem simple, but they show significant differences in actual effects; The experimental results showed that the virus inhibition rate of the optimized samples was close to 88%, while that of the non-optimized group was only 63%. This indicates that the extraction conditions and the ratio of nonoxynol ether have a direct impact on the antiviral effect. In particular, green tea polyphenols have stronger antioxidant capacity and more obvious virus destruction effect under optimized conditions. The low extraction efficiency of the non-optimized group resulted in insufficient polyphenol content, thus limiting the overall effect. It can also be observed from the data that the experimental deviation of the optimized group is smaller, indicating that the active solution is more evenly distributed and the synergistic effect between the components is more stable. This also confirms that under the optimized conditions, nonoxynol ether and green tea polyphenols can achieve the best combination, making it not only superior in antiviral performance, but also more reliable in preparation process and application effect.

[0067] Experiment 3: Verification of the effect of matrix optimization on gel physical properties Experimental Description Experimental objectives: The gel rheological properties and use comfort of Example 3 (optimized matrix) and Comparative Example 3 (no PEG added) were compared to verify the necessity of adding polyethylene glycol (PEG) in the matrix design and its contribution to the gel properties.

[0068] Experimental steps: Sample preparation: Example 3: A gel sample was prepared according to Example 3, with a carbomer concentration of 3%, and mixed with PEG in a ratio of 1:3 to form a gel.

[0069] Comparative Example 3: PEG addition was omitted, the carbomer concentration was 3%, and the other preparation processes were the same as those in Example 3.

[0070] Rheological properties test: The shear viscosity of the two samples was measured using a rotational rheometer (shear rate 10 s -1 Up to 100s -1 The test temperature was set at 25°C and each group was repeated 3 times.

[0071] User Experience Testing: 10 volunteers were recruited, each of whom applied the gel samples of the embodiment and the comparative example, and recorded the application experience, mainly including lubricity (1-5 points) and coating uniformity (1-5 points). The results were averaged.

[0072] Stability test: The samples were stored at room temperature (25°C) for 30 days and observed for any changes in physical state such as stratification and bubbles.

[0073] Effect of Gel Matrix Optimization on Physical Properties and User Experience The optimized matrix showed significant rheological advantages, especially the addition of PEG reduced the shear viscosity of the gel, making it easier to apply and more uniform during use. The PEG molecular chain not only improved the fluidity of the matrix through the synergistic effect with the three-dimensional network of carbomer, but also enhanced the lubrication performance. This change has a direct improvement in user experience. In actual operation, volunteers gave a more positive evaluation of the optimized matrix, while the samples without PEG addition appeared more viscous, difficult to apply evenly, and scored lower; The difference was also highlighted in the storage stability test. The unoptimized comparative sample showed stratification after 30 days, especially at high temperatures. This is because the internal structure of carbomer is relatively fragile and prone to phase separation when it does not work synergistically with PEG. The optimized matrix remained stable during long-term storage, and no significant changes in the physical state were observed. This shows that the addition of PEG not only improves the use characteristics, but also enhances the overall stability of the structure; From the rheological data, it can be seen that the viscosity of the unoptimized sample is high and the fluidity during shear is poor, which may lead to uneven distribution of ingredients. This physical property will limit the release efficiency of the active ingredients. The optimized matrix forms a system with better fluidity and uniform internal structure, ensuring the synergy and stability of the active components during use. The whole mechanism illustrates the key role of PEG, which is not only a lubricant, but also a dual role of stabilizer and dispersant.

[0074] Experiment 4: Verify the effect of mixing conditions on the uniformity of active components Experimental Description Experimental objectives: The uniformity of the active components of Example 4 (optimized mixing conditions) and Comparative Example 4 (unoptimized mixing conditions) was compared to verify the effect of the mixing process on the uniformity of the distribution of the gel components.

[0075] Experimental steps: Sample preparation: Example 4: The nanosilver dispersion was gradually added dropwise to the gel matrix, with a stirring speed of 600 rpm for 1 hour; the active solutions (nonoxynol, green tea polyphenols, chitosan) were added in sequence, with stirring for 40 minutes each time.

[0076] Comparative Example 4: The nanosilver dispersion was added quickly at one time, with a stirring speed of 200 rpm and a mixing time of 30 minutes; the active solution was added at the same time and the mixing time was 15 minutes.

[0077] Sampling and testing: Random sampling: 2 mL was sampled from 5 locations (top, middle, bottom, and both sides) of each gel sample.

[0078] Nanosilver content: The nanosilver particle content (unit: ppm) was detected using ICP-MS (inductively coupled plasma mass spectrometry).

[0079] Contents of nonoxynol and green tea polyphenols: determined by high performance liquid chromatography (HPLC), the units are μg / mL and mg / mL respectively.

[0080] Uniformity evaluation: The mean and relative standard deviation (RSD) of each group of samples were calculated. The lower the RSD, the more uniform the distribution.

[0081] Effect of mixing conditions on the uniformity of active components in gel The difference between the examples and the comparative examples is obvious in the uniformity test. The optimized mixing process ensures uniform distribution of the active components, which is manifested by low RSD (relative standard deviation). The gradual addition of the nanosilver dispersion avoids the problem of excessive local concentration, and the active solution is added sequentially to allow each component to have sufficient mixing time. This precise control directly reduces component deviation and ensures the overall performance of the gel. The comparative samples showed large fluctuations in the test, with local nanosilver content being significantly higher or lower, indicating that rapid addition leads to uneven particle distribution; The concentrations of nonoxynol and green tea polyphenols in the data also showed a similar trend. The optimized process allows the active solution added each time to fully combine with the matrix to form a stable distribution; while the unoptimized comparative samples have insufficient mixing time, resulting in too low concentrations in some areas and a significant decrease in activity. This uneven distribution may directly affect the antiviral effect and contraceptive ability of the gel; From a mechanistic point of view, the optimized stirring speed and mixing time of the embodiment provide sufficient physical interaction conditions for the components, especially the nanosilver particles can be better combined with the matrix and dispersed after being gradually added. In contrast, in the comparative example, the too fast addition and insufficient stirring intensity aggravate the particle agglomeration phenomenon, and the active solution is even more difficult to be completely integrated into the matrix. This process out of control has a fatal impact on the performance and stability of the final product.

[0082] Experiment 5: Verify the effect of pH adjustment on the antibacterial properties of gel Experimental Description Experimental objectives: The difference in antibacterial performance between Example 5 (pH adjusted to 4.2) and Comparative Example 5 (pH not adjusted, kept neutral) was compared to verify the key effect of the acidic environment on the gel function.

[0083] Experimental steps: Sample preparation: Example 5: A gel was prepared according to the method of Example 5, and the pH was adjusted to 4.2 using lactic acid.

[0084] Comparative Example 5: The gel was prepared according to the method of Comparative Example 5 without pH adjustment, and the final pH value was about 7.0.

[0085] Bacteria Model: Select common vaginal pathogens: Escherichia coli (E.coli) and Candida albicans (Candida albicans). Prepare bacterial liquids at a concentration of 10 5 CFU / mL.

[0086] Antibacterial test: Mix the gel sample with the bacterial solution in a 1:1 volume ratio.

[0087] Incubate at 37°C in a shaker for 1 hour.

[0088] After mixing, samples were taken, and after 10-fold gradient dilution, they were spread on LB medium (Escherichia coli) and PDA medium (Candida albicans), cultured at 37°C for 24 hours, and the number of colonies was counted.

[0089] Antimicrobial performance evaluation: The colony reduction rate (antibacterial rate) was calculated by the number of colonies. The untreated bacterial solution served as the control group.

[0090] Effect of pH adjustment on antibacterial properties of gel The experimental results show that pH adjustment has a decisive influence on the antibacterial properties of the gel. The gel adjusted to an acidic environment (pH 4.2) in the example showed a significant inhibitory effect on both Escherichia coli and Candida albicans. The acidic environment not only inhibits the growth of pathogens, but also enhances the overall antibacterial properties of the gel. This improvement stems from the inhibition of pathogen enzyme activity under acidic conditions and the release of component activity promoted by acidity. The unadjusted neutral gel showed a clear disadvantage, with a significantly lower colony reduction rate and large fluctuations, and was unable to stably inhibit pathogens; In both models, from Escherichia coli to Candida albicans, the samples after acid adjustment were able to maintain a high antibacterial rate, and the results were more stable. This effect is highly related to the acidic environment of the gel. pH 4.2 is the appropriate acidity for the natural vaginal microecology, and the presence of lactic acid further strengthens the simulation of this physiological environment, which is in sharp contrast to the unadjusted neutral gel. Neutral pH not only fails to inhibit bacteria, but may even destroy the stability of the vaginal microecology, making it easier for pathogens to grow; The experiment also revealed another meaning of the deviation data. The results of the unadjusted group fluctuated greatly, indicating that it has poor adaptability to the environment and pathogens, and its antibacterial properties are easily affected by external factors. The gel in an acidic environment showed stable functions, proving that pH adjustment optimizes the functional adaptability and antibacterial properties of the gel. Through the key step of adjusting the lactic acid to 4.2, the gel can not only inhibit pathogens, but also achieve a better match with the vaginal environment. This is precisely its mechanistic advantage.

[0091] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. Nanosilver contraceptive gel that quickly kills HPV and other sexually transmitted disease pathogens, characterized in that: The nano silver contraceptive gel comprises the following components in parts by weight: Nano silver particles: 1.5-2.5 parts; Nonoxynol: 2.0-3.0 parts; Chitosan: 1.0-1.5 parts; Green tea polyphenols: 0.5-1.0 parts; Carbomer: 2.0-3.5 parts; Polyethylene glycol: 3.0-5.0 parts; Sodium hyaluronate: 1.0-1.5 parts; Lactic acid or citric acid: 0.5-1.0 parts; Glycerin: 2.5-3.5 parts; Vitamin E: 0.5-1.0 parts.

2. The nanosilver contraceptive gel for rapidly killing various sexually transmitted disease pathogens such as HPV according to claim 1, characterized in that: The nano silver particles include: Nanosilver particles with a particle size of 10-30 nm; surface-modified hyaluronic acid or chitosan; The concentration of the modification solution is 1.5-2.0%.

3. The nanosilver contraceptive gel for rapidly killing various sexually transmitted disease pathogens such as HPV according to claim 1, characterized in that: The nonoxynol ether comprises: Mix nonoxynol ether and warm water in a ratio of 1:5 to dissolve; The dissolving temperature is 40-50°C; The dissolution time is 10-20 minutes.

4. The nanosilver contraceptive gel for rapidly killing various sexually transmitted disease pathogens such as HPV according to claim 1, characterized in that: The chitosan comprises: The molecular weight of chitosan is 50-150 kDa; The concentration of chitosan solution is 1.0-2.0%; The touch-up time is 4-6 hours.

5. The nanosilver contraceptive gel for rapidly killing various sexually transmitted disease pathogens such as HPV according to claim 1, characterized in that: The gel matrix comprises: Carbomer was dispersed in pure water with a stirring speed of 300-500 rpm; Polyethylene glycol is added at a weight ratio of carbomer to PEG of 1:2-1:3; The pH was adjusted to 3.5-4.5 and the dropping speed was 0.1-0.3 ml / min.

6. A method for preparing a nano-silver contraceptive gel that can quickly kill various sexually transmitted disease pathogens such as HPV, characterized in that: The use of the nanosilver contraceptive gel for rapidly killing multiple sexually transmitted disease pathogens such as HPV according to any one of claims 1 to 5 comprises the following steps: S1, preparing nanosilver particles, modifying the surface of nanosilver particles with a particle size of 10-30 nm with hyaluronic acid or chitosan; S2, preparing an active solution, preparing nonoxynol, green tea polyphenols and chitosan into solutions respectively; S3, preparing a gel matrix, mixing carbomer and polyethylene glycol to prepare a matrix; S4, adding the components in S1, S2 and S3 to the gel matrix in sequence and stirring evenly; S5. Adjust the pH value to 3.5-4.5, cool and shape.

7. The nanosilver contraceptive gel for rapidly killing various sexually transmitted disease pathogens such as HPV according to claim 6, characterized in that: The preparation of the nano silver particles comprises: Preparation of silver nanoparticles by chemical reduction method; Control the concentration of the modification solution to 1.5-2.0%; The stirring speed is 500-700 rpm and the modification time is 4-6 hours.

8. The nanosilver contraceptive gel for rapidly killing various sexually transmitted disease pathogens such as HPV according to claim 6, characterized in that: The preparation of the active solution comprises: Nonoxynol ether is mixed with warm water in a weight ratio of 1:5, and the mixing temperature is 40-50°C; Green tea polyphenols are extracted using an ethanol-water mixed solvent, with an ethanol volume fraction of 70-80%, an extraction temperature of 60-70°C, and a time of 2-4 hours.

9. The nanosilver contraceptive gel for rapidly killing various sexually transmitted disease pathogens such as HPV according to claim 6, characterized in that: The preparation of the gel matrix comprises: Carbomer is dispersed in pure water at a concentration of 2.0-3.5%; The stirring speed is 300-500rpm and the dissolution time is 2-3 hours; Polyethylene glycol and carbomer were mixed in a weight ratio of 1:2-1:3 and stirred for 1 hour.

10. The nanosilver contraceptive gel for rapidly killing various sexually transmitted disease pathogens such as HPV according to claim 6, characterized in that: The final mixing step includes: Slowly add the nanosilver dispersion into the gel matrix at a stirring speed of 400-600 rpm for 1-2 hours; The active solutions were added to the gel matrix in sequence and stirring was continued for 30-60 minutes; Let it sit for 12-24 hours to complete the gel formation.

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