Anti-HPV contraceptive product and preparation process thereof

Abstract

The invention discloses an anti-HPV contraceptive product and a preparation process, and belongs to the technical field of contraceptive products. The latex base material is formed by vulcanizing and cross-linking natural latex and an epoxy chloropropane cross-linking agent; the composite lubricating liquid contains anhydridized bovine beta-lactoglobulin and beta-glucan, the anhydridized bovine beta-lactoglobulin and the beta-glucan form a synergistic anti-HPV system, and the combination of HPV virus L1 protein and a host cell surface receptor can be specifically blocked. The preparation process comprises the steps of raw material preparation, latex base material forming and vulcanization, demolding, lubricating liquid preparation, filling and sterilization. The product disclosed by the invention not only has a reliable physical contraception function, but also can efficiently and specifically inhibit HPV virus infection through the synergistic effect of specific active ingredients, and provides dual protection for a user.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of contraceptive products, in particular to an anti-HPV contraceptive product and a preparation process. BACKGROUND

[0002] Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections, and persistent infection of high-risk HPV is the main cause of diseases such as cervical cancer. The products such as condoms on the market mainly play a physical barrier role, and the blocking effect on sexually transmitted diseases, especially HPV virus, is limited. Although some products add bactericides (such as nano-silver), the specific inhibition effect of the bactericides on HPV, which is a non-enveloped virus, is not good, and may cause irritation or allergic reaction.

[0003] Therefore, there is an urgent need in the art to develop a product that can not only effectively prevent pregnancy, but also specifically block the transmission of HPV virus, while having good safety and use experience. SUMMARY

[0004] The present application aims to overcome the shortcomings of the prior art, and provides an anti-HPV contraceptive product and a preparation process. The product not only has reliable physical contraceptive function, but also can efficiently and specifically inhibit HPV virus infection through the synergistic effect of specific active ingredients, thereby providing double protection for the user.

[0005] To achieve the above-mentioned purpose, the technical scheme adopted by the present application is as follows: an anti-HPV contraceptive product, comprising a latex base material and a composite lubricating liquid; the latex base material is formed by vulcanization and cross-linking of natural latex and an epichlorohydrin cross-linking agent; the composite lubricating liquid comprises acid anhydride bovine beta-lactoglobulin and beta-glucan, and the acid anhydride bovine beta-lactoglobulin and the beta-glucan form a synergistic anti-HPV system, which can specifically block the binding of HPV virus L1 protein and host cell surface receptors.

[0006] Preferably, nano-silver particles are dispersed in the latex base material; and sodium hyaluronate and vitamin E are added to the composite lubricating liquid.

[0007] Preferably, the product is packaged with high barrier property, and has a virus inhibition effect on HPV16 / 18 type through in vitro test.

[0008] A process for preparing the anti-HPV contraceptive product described in any one of the above, comprising the following steps: S1, raw material preparation: preparing natural latex, epichlorohydrin cross-linking agent and components of lubricating liquid; S2, latex base material forming and vulcanization: coating the mixture of latex and cross-linking agent on a mold, and forming a latex base material through a vulcanization process; S3, demolding: demolding the vulcanized latex base material; S4, lubricating liquid preparation: mixing the components of the lubricating liquid to make it uniformly dispersed; S5, filling and sterilization: filling the latex substrate and the composite lubricating liquid into the package and performing sterilization treatment.

[0009] Preferably, the vulcanization process in step S2 is performed in a segmented heating manner.

[0010] Preferably, in step S2, when mixing the latex and the crosslinking agent, silver nanoparticles are also added to make them uniformly dispersed in the latex.

[0011] Preferably, step S3 further comprises: immersing the demolded latex substrate in a chitosan solution, and forming an antibacterial film on the surface of the latex substrate after treatment.

[0012] Preferably, the specific process of the lubricating liquid preparation in step S4 is: first, stirring and mixing glycerol, propylene glycol and part of purified water, then adding anhydride-modified bovine beta-lactoglobulin, beta-glucan, carbomer and sodium hyaluronate, heating and performing mechanical stirring and ultrasonic-assisted dispersion; finally, adding triethanolamine to adjust the pH, and stirring uniformly after adding vitamin E and preservatives; the ultrasonic-assisted dispersion treatment can break the agglomeration structure of beta-glucan, and improve the uniformity of dispersion of anhydride-modified bovine beta-lactoglobulin.

[0013] Further preferably, the preparation of the anhydride-modified bovine beta-lactoglobulin comprises extraction and anhydride modification of bovine beta-lactoglobulin: The extraction of bovine beta-lactoglobulin comprises adjusting whey to acidic pH to precipitate impurities, adding lectin to specifically co-precipitate bovine beta-lactoglobulin, dissolving and removing the lectin after separation, and then concentrating and drying to obtain protein powder; The anhydride modification is to react the obtained protein powder with an anhydride reagent under weak alkaline conditions, and to obtain anhydride-modified bovine beta-lactoglobulin after purification.

[0014] Preferably, the sterilization treatment in step S5 comprises: ultraviolet irradiation of the package, and filtration of the lubricating liquid.

[0015] As described above, due to the adoption of the above technical solutions, the present application has the following advantages: The present application forms a synergistic HPV system by compounding anhydride-modified bovine beta-lactoglobulin and beta-glucan, which can precisely block the binding of HPV virus and host cells, and has strong inhibitory effect and high specificity.

[0016] The product prepared by the present application has good physical properties such as high tensile strength and high elongation at break of the latex substrate, and by adding nano-silver, chitosan and other ingredients, the product is endowed with broad-spectrum antibacterial and moisturizing functions, and the safety and use comfort are improved.

[0017] This invention utilizes optimized preparation processes such as segmented vulcanization and ultrasonic dispersion, along with high-barrier packaging, to ensure the stability of the active ingredients during production and use, thus extending the product's shelf life. The selected active ingredients, such as β-glucan and sodium hyaluronate, possess excellent biocompatibility, avoiding the irritation or allergic risks that may arise from traditional chemical disinfectants. Attached Figure Description

[0018] Figure 1 This is a flowchart of the preparation process of the present invention; Detailed Implementation

[0019] To enable those skilled in the art to better understand the technical solution of the present invention, the present invention will be described in detail below. The description in this part is only exemplary and explanatory, and should not be used to limit the scope of protection of the present invention in any way.

[0020] This embodiment provides an anti-HPV contraceptive product, comprising a latex substrate, a composite lubricant, and high-barrier packaging; the latex substrate is formed by vulcanization crosslinking of natural latex and epichlorohydrin crosslinking agent in a mass ratio of 95:5-98:2, with a tensile strength ≥16MPa and an elongation at break ≥600%; the composite lubricant contains the following components in mass percentage: glycerol 15-25%, propylene glycol 10-18%, anhydride-modified bovine β-lactoglobulin 0.5-2%, β-glucan 1-3%, carbomer 0.3-0.8%, triethanolamine 0.2-0.5%, and purified water to 100%; wherein, the anhydride-modified bovine β-lactoglobulin and β-glucan form a synergistic anti-HPV system, which can specifically block the binding of HPV virus L1 protein to host cell surface receptors.

[0021] Furthermore, the latex substrate also contains 0.1-0.5% by mass of silver nanoparticles with a particle size of 20-50 nm; the composite lubricant also contains 0.5-1.5% by mass of sodium hyaluronate and 0.1-0.3% by mass of vitamin E, and its pH value is adjusted to 6.5-7.5.

[0022] Furthermore, the high-barrier packaging is an aluminum foil bag with an inner layer coated with an ethylene-vinyl alcohol copolymer (EVOH) film, whose oxygen permeability is ≤0.1cc / (m²). 2 • day • atm), water vapor transmission rate ≤ 0.1 g / (m 2 •day); This product has been tested in vitro and shows an inhibition rate of ≥85% against HPV16 / 18 types, with an effective period of up to 24 months.

[0023] like Figure 1 As shown, a process for preparing an anti-HPV contraceptive product as described in any of the above-mentioned claims includes the following steps: S1, raw material preparation: prepare the required natural latex, epoxy chloropropane crosslinking agent and lubricating liquid components; S2, latex substrate forming and vulcanization: after mixing the latex and crosslinking agent uniformly, coat it on the mold, and process it by staged temperature vulcanization process to form a latex substrate with a crosslinking degree of 75-85%; S3, demolding and post-processing: cool and demold the vulcanized latex substrate and perform surface finishing; S4, lubricating liquid preparation: mix the components of the lubricating liquid in proportion in steps, and use ultrasonic assisted stirring to make it uniformly dispersed; S5, filling and sterilization: fill the latex product and the composite lubricating liquid into the package in proportion, and perform composite sterilization treatment; S6, packaging and storage: package the qualified finished product and store it at 2-8℃.

[0024] Further, the staged temperature vulcanization process of step S1 is specifically: first, increase the temperature to 80℃ at a rate of 5℃ / min and keep it for 5min, then increase the temperature to 105-115℃ at a rate of 3℃ / min, and keep it for 15-25min under a pressure of 0.12-0.15MPa.

[0025] Further, in step S2, 0.1-0.5% of nano-silver particles by mass percentage are also added when mixing the latex and the crosslinking agent to make them uniformly dispersed in the latex.

[0026] Further, the post-processing of step S3 includes: soaking the finished latex product in a chitosan solution with a mass concentration of 0.5-1% at 30-35℃ for 10-15min, taking it out and drying it to form an antibacterial film on its surface.

[0027] Further, the specific process of lubricating liquid preparation in step S4 is: first, stir glycerol, propylene glycol and part of purified water at a speed of 300-500rpm for 10-15min, then add the remaining components of anhydride modified bovine beta-lactoglobulin, beta-glucan, carbomer and sodium hyaluronate, and heat to 40-45℃; while keeping mechanical stirring at 300-500rpm, open the ultrasonic auxiliary dispersion of 100-150W and process synchronously for 20-30min; finally, add triethanolamine to adjust the pH to 6.5-7.5, and add vitamin E and preservatives and stir uniformly. Among them, the ultrasonic auxiliary dispersion treatment can break the agglomeration structure of beta-glucan, improve the dispersion uniformity of anhydride modified bovine beta-lactoglobulin, and thus improve the synergistic HPV effect of the two by 10-15%; the preservative is preferably one or more of methylparaben and propylparaben.

[0028] Further, the preparation of the anhydride modified bovine beta-lactoglobulin includes the following steps: S41. Extraction of bovine beta-lactoglobulin, specifically comprising: S411. Pretreatment: the whey raw material is adjusted to pH 3.5-4.2 under low temperature conditions to cause the denaturation and precipitation of major impurities, and the precipitate is removed by centrifugation; S412. Specific affinity precipitation: a natural polysaccharide lectin rich in galactosyl is added to the supernatant, and gentle stirring is performed at 4-10°C to cause the specific binding and co-precipitation of bovine beta-lactoglobulin and the lectin; S413. Separation and resolution: the precipitate is collected and redissolved in a buffer solution at pH 7.5-8.5, and the macromolecular lectin is removed by an ultrafiltration device to obtain a high-purity bovine beta-lactoglobulin solution; S414. Concentration and drying: the solution is concentrated and freeze-dried to obtain a high-activity bovine beta-lactoglobulin powder; S42. Anhydride modification: the bovine beta-lactoglobulin obtained in step S41 is dissolved in a buffer solution at pH 8.0-9.0, maleic anhydride is slowly added under stirring conditions, and the reaction is performed at 25-35°C for 2-4 hours. After dialysis purification, a product with an anhydride modification degree of 60%-80% is obtained.

[0029] Further, the composite sterilization treatment in step S5 refers to first irradiating the aluminum foil bag filled with the product with ultraviolet light at a wavelength of 254 nm for 15-20 s, and then filtering the lubricating liquid through a 0.22 μm polyether sulfone filter membrane during the filling process to ensure that the microbial limit of the finished product is ≤10 CFU / mL. The finished product after filling needs to be subjected to negative pressure sealing test (-0.08 MPa, 5 min) and HPV activity test, and can be stored in the warehouse only after passing the tests.

[0030] The following provides specific examples, which can enable those skilled in the art to have a more comprehensive understanding of the present application, but do not limit the present application in any way.

[0031] Example 1: Preparation of a basic anti-HPV contraceptive product S1, Raw material preparation: prepare natural latex and epoxy chloropropane crosslinking agent meeting the quality requirements; prepare glycerol, propylene glycol, anhydride-modified bovine beta-lactoglobulin, beta-glucan, carbomer, triethanolamine, purified water, and other lubricating liquid components.

[0032] S2, Latex substrate forming and vulcanization: mix the natural latex and the epoxy chloropropane crosslinking agent uniformly at a mass ratio of 97:3. Dip the mixed latex into a glass mold, and then send it into a vulcanization oven for staged temperature increase vulcanization: first increase the temperature to 80°C at a rate of 5°C / min and maintain for 5 min, then increase the temperature to 110°C at a rate of 3°C / min, and maintain for 20 min under a pressure of 0.13 MPa to form a latex condom substrate with a crosslinking degree of about 80%.

[0033] S3, demolding and post-processing: cool the vulcanized latex substrate, demold using water washing method, and trim the edges of the demolded product.

[0034] S4, lubricating liquid preparation: take the components of the lubricating liquid by mass percentage: glycerol 20%, propylene glycol 15%, acid anhydride bovine beta-lactoglobulin 1.2%, beta-glucan 2%, carbomer 0.5%, triethanolamine 0.35%, and purified water to make up to 100%. First, stir glycerol, propylene glycol, and part of purified water at 400 rpm for 12 min, then add acid anhydride bovine beta-lactoglobulin, beta-glucan, and carbomer, and heat to 42°C; while maintaining mechanical stirring at 400 rpm, turn on 120W ultrasonic assisted dispersion, and process synchronously for 25 min; finally, add triethanolamine to adjust the pH to 7.0, and stir uniformly.

[0035] S5, filling and sterilization: fill the trimmed latex condom and the above-mentioned composite lubricating liquid into an aluminum foil packaging bag according to the predetermined proportion. First, irradiate the filled packaging bag with ultraviolet light at a wavelength of 254 nm for 18 s, and at the same time, make the lubricating liquid pass through a 0.22μm polyether sulfone filter membrane for filtration and sterilization in the filling pipeline.

[0036] S6, packaging and storage: test the filled finished product for negative pressure sealing (-0.08MPa, 5min) and rapid screening for HPV activity, package the qualified product, and store it in a 5°C refrigerator.

[0037] Example 2: Preparation of anti-HPV contraceptive products containing nano-silver and moisturizing ingredients S1, raw material preparation: additionally prepare nano-silver particles (particle size 30 nm), sodium hyaluronate, and vitamin E.

[0038] S2, latex substrate forming and vulcanization: when mixing the latex and the crosslinking agent, synchronously add 0.3% of the total mass of the latex nano-silver particles, and uniformly disperse them by high-speed stirring.

[0039] S4, lubricating liquid preparation: additionally add 1.0% of sodium hyaluronate and 0.2% of vitamin E to the lubricating liquid formula. Finally, adjust the pH of the lubricating liquid to 7.0.

[0040] The rest of the process is the same as Example 1.

[0041] Example 3: Preparation of anti-HPV contraceptive products with chitosan antibacterial film S3, demolding and post-processing: after completing demolding and trimming, add a post-processing step: immerse the trimmed latex product in a 0.8% chitosan acetic acid solution, treat it at 33°C for 12 min, take it out and dry it at 50°C, and form a dense antibacterial film on its surface.

[0042] The rest of the process is the same as Example 2.

[0043] Comparative Example 1: Contraceptive product without anti-HPV active ingredient S1, Raw material preparation: Prepare natural latex, epoxy chloropropane crosslinking agent; Prepare glycerol, propylene glycol, carbomer, triethanolamine, purified water and other ordinary lubricating liquid components.

[0044] S4, Lubricating liquid preparation: Prepare ordinary lubricating liquid without anti-HPV active ingredient, the composition is: glycerol 20%, propylene glycol 15%, carbomer 0.5%, triethanolamine 0.35%, purified water to 100%. Adjust pH to 7.0. Mix by mechanical stirring, without ultrasonic assisted dispersion.

[0045] The rest of the process is the same as Example 1.

[0046] Comparative Example 2: Contraceptive product with nano-silver but without synergistic anti-HPV system S1, Raw material preparation: Same as Comparative Example 1, additionally prepare nano-silver particles.

[0047] S2, Latex substrate forming and vulcanization: Process same as Example 2 (add 0.3% nano-silver).

[0048] S4, Lubricating liquid preparation: Process same as Comparative Example 1 (prepare ordinary lubricating liquid).

[0049] The rest of the process is the same as Example 1.

[0050] Effect verification experiment: The products prepared in Examples 1-3 and Comparative Examples 1-2 above were tested for performance: 1. Anti-HPV activity test: Refer to the standard ISO21702:2019 with slight modifications to determine the inhibition rate (%) of the product leaching solution on HPV16 Pseudovirus.

[0051] 2. Physical performance test: Test tensile strength (MPa) and elongation at break (%) according to GB / T7544 standard.

[0052] 3. Antibacterial test (on E. coli): Test the antibacterial rate (%) according to GB / T31402 standard.

[0053] 4. Storage stability: After storing the product at 5°C for 24 months, retest its anti-HPV activity and calculate the activity retention rate (%).

[0054] The test results are shown in the following table: Table 1: Comparison of product performance test results Test item Implementation Implementation Implementation Comparison Comparison HPV16 inhibition rate (%) 89.5 90.2 91.8 4.3 5.1 Tensile strength (MPa) 17.0 16.8 17.2 16.9 16.7 Elongation at break (%) 650 635 645 660 640 Antibacterial rate (%) (E. coli) 82.5 99.9 99.9 0 99.9 Activity retention rate (24 months, 5°C) 87.1% 88.5% 89.2% - - Result analysis: 1. Anti-HPV effect analysis: Examples 1-3 all showed extremely high inhibition rates (all higher than 89%) against HPV16 pseudovirus, which directly proved the effectiveness and necessity of the core of the present application - the synergistic anti-HPV system composed of acid anhydride- modified bovine beta-lactoglobulin and beta-glucan.

[0055] Comparative Example 1 (without any active ingredient) and Comparative Example 2 (containing only nano-silver) showed extremely low HPV inhibition rates (about 5%), indicating that ordinary lubricants and common broad-spectrum antibacterial agent nano-silver cannot provide effective anti-HPV protection. This comparison highlights the outstanding advantages and unpredictability of the specific antiviral strategy of the present application.

[0056] 2. Physical property analysis: The tensile strength and elongation at break of all groups of products met and were much higher than the basic requirements of the relevant standards, indicating that the formula improvement of the present application completely retained the core physical properties of the product as a contraceptive device while endowing it with excellent biological functions, without any negative effects.

[0057] 3. Anti-bacterial effect analysis: Example 1 (basic formula) showed certain antibacterial properties (82.5%), which was mainly due to the certain osmotic pressure and pH environment of the lubricating liquid itself.

[0058] Examples 2 (with nano-silver) and 3 (with nano-silver and chitosan film) both showed nearly 100% strong antibacterial effect, which was due to the broad-spectrum antibacterial effect of nano-silver and chitosan film.

[0059] Comparative Example 2 (only the substrate contained nano-silver) also showed strong antibacterial properties, proving the successful addition and effectiveness of nano-silver.

[0060] Comparative Example 1 had no antibacterial design, so the antibacterial rate was 0.

[0061] This result proves that the product of the present application can easily integrate additional antibacterial functions as needed to provide more comprehensive protection.

[0062] 4. Storage stability analysis: After 24 months of accelerated storage, the retention rates of the anti-HPV activity of the three example products were all higher than 87%, proving that the present application greatly guarantees the long-term stability of the core active ingredient through optimized formula and process (such as ultrasonic dispersion to ensure uniformity, high-barrier packaging), meeting the strict requirements of product commercialization on the shelf life.

[0063] Conclusion: Based on the above test results, the anti-HPV contraceptive product successfully combines specific anti-virus, reliable physical contraception, broad-spectrum antibacterial, and long-term stability and other advantages. The significant differences between the comparative examples and the examples irrefutably prove that the synergistic combination of anhydridized bovine beta-lactoglobulin and beta-glucan is the key and necessary technical feature to achieve high-efficiency anti-HPV function, rather than a simple superposition of conventional techniques in the art. The product provides a new solution for solving sexually transmitted diseases, especially HPV infection, which is efficient, safe, stable, and comfortable.

[0064] In summary, the anti-HPV contraceptive product and its preparation process successfully combine specific anti-virus, physical barrier contraception, broad-spectrum antibacterial moisturizing, and other functions, providing an efficient, safe, and stable dual protection solution.

[0065] The principles and implementation modes of the present application are described herein using specific examples, and the above examples are only used to help understand the method and core idea of the present application. The above is only a preferred embodiment of the present application, but the protection scope of the present application is not limited thereto. Any person skilled in the art can make equivalent substitutions or changes within the technical scope disclosed by the present application according to the technical solution and inventive concept of the present application, which should be within the protection scope of the present application.

Claims

1. An anti-HPV contraceptive product, characterized in that, The product includes a latex substrate and a composite lubricant; the latex substrate is formed by cross-linking natural latex with epichlorohydrin through vulcanization; the composite lubricant contains anhydride-modified bovine β-lactoglobulin and β-glucan, wherein the anhydride-modified bovine β-lactoglobulin and β-glucan form a synergistic anti-HPV system that can specifically block the binding of HPV virus L1 protein to host cell surface receptors.

2. The anti-HPV contraceptive product according to claim 1, characterized in that, The latex substrate also contains dispersed silver nanoparticles; the composite lubricant also contains sodium hyaluronate and vitamin E.

3. The anti-HPV contraceptive product according to claim 1 or 2, characterized in that, The product uses high-barrier packaging and has been tested in vitro to show antiviral effects against HPV types 16 / 18.

4. A process for preparing an anti-HPV contraceptive product as described in any one of claims 1-3, characterized in that, Includes the following steps: S1. Raw material preparation: Prepare natural latex, epichlorohydrin crosslinking agent and lubricant components; S2. Latex substrate molding and vulcanization: Latex and crosslinking agent are mixed and coated onto a mold, and then vulcanized to form a latex substrate. S3. Demolding: Demolding the vulcanized latex substrate; S4. Lubricant preparation: Mix the components of the lubricant to ensure they are evenly dispersed. S5. Filling and Sterilization: Fill the latex base material and composite lubricant into the packaging and sterilize them.

5. The preparation process according to claim 4, characterized in that, The vulcanization process described in step S2 is carried out using a segmented heating method.

6. The preparation process according to claim 4, characterized in that, In step S2, when mixing the latex and crosslinking agent, nano-silver particles are also added to ensure that they are uniformly dispersed in the latex.

7. The preparation process according to claim 4, characterized in that, Step S3 further includes: immersing the demolded latex substrate in a chitosan solution, and forming an antibacterial film on its surface after treatment.

8. The preparation process according to claim 4, characterized in that, The specific process for preparing the lubricant in step S4 is as follows: First, glycerol, propylene glycol, and a portion of purified water are stirred and mixed. Then, anhydride-modified bovine β-lactoglobulin, β-glucan, carbomer, and sodium hyaluronate are added. The mixture is heated and mechanically stirred and ultrasonically dispersed. Finally, triethanolamine is added to adjust the pH, and vitamin E and preservatives are added and stirred evenly. The ultrasonically assisted dispersion treatment can break the aggregated structure of β-glucan, thereby improving the dispersion uniformity of it and anhydride-modified bovine β-lactoglobulin.

9. The preparation process according to claim 8, characterized in that, The preparation of the anhydride-modified bovine β-lactoglobulin includes the extraction and anhydride modification of bovine β-lactoglobulin: The extraction of bovine β-lactoglobulin includes adjusting whey to an acidic pH to precipitate impurities, adding lectin to cause bovine β-lactoglobulin to be specifically co-precipitated, separating, dissolving and removing the lectin, and then concentrating and drying to obtain protein powder. The anhydride modification involves reacting the obtained protein powder with an anhydride reagent under weakly alkaline conditions, followed by purification to obtain anhydride-modified bovine β-lactoglobulin.

10. The preparation process according to claim 4, characterized in that, The sterilization process described in step S5 includes: irradiating the packaging with ultraviolet light and filtering the lubricant.

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