Sperm composite lubricant and preparation method thereof

Abstract

The invention discloses a sperm composite lubricant and a preparation method thereof, and the method comprises the following steps: mixing a polymer natural humectant, degradable carrier gel and pyrroloquinoline quinone precursor liquid according to a preset proportion to obtain a pyrroloquinoline quinone-pre-embedded moisturizing gel matrix; the preparation method comprises the following steps: dissolving a lipid membrane stabilizer in an ethanol-water mixed solution for ultrasonic emulsification, dropwise adding the emulsified lipid membrane stabilizer into a pyrroloquinoline quinone-pre-embedded moisturizing gel matrix, and stirring to obtain lipid fusion type gel; suspending a sperm motility promoter microcapsule and a plant extract in a buffer solution to form a mixed suspension, adding the mixed suspension into the lipid fusion type gel to obtain active chimeric gel, dropwise adding an antioxidant into the active chimeric gel, and stirring to obtain a microcapsule-gel dual controlled release lubricant precursor; and filtering and sterilizing the microcapsule-gel double controlled release lubricant precursor to obtain the sperm composite lubricant. The sperm motility and survival rate can be improved.

Description

Technical Field

[0001] The present application belongs to the field of reproductive health and assisted reproductive technology, and is a sperm composite lubricant and a preparation method thereof. Background Art

[0002] Existing lubricants for assisted reproductive technology primarily aim to reduce friction. However, most commercially available lubricants can affect sperm motility, membrane stability, and fertilization capacity, and may even damage sperm structure, thereby reducing the chance of conception. Therefore, developing a lubricant that can effectively enhance or maintain sperm motility and survival is of great practical significance. Summary of the Invention

[0003] In view of the deficiencies in the prior art, the purpose of this application is to provide a sperm composite lubricant and a preparation method thereof, and the present application aims to improve the motility and survival rate of sperm.

[0004] To achieve the above objectives, this application provides the following technical solutions: A sperm composite lubricant, the raw materials of the composite lubricant and the mass percentage of each raw material are as follows: high molecular natural moisturizer: 3% to 10%; lipid membrane stabilizer: 1% to 5%; Sperm motility enhancer: 0.1% to 2%; Plant extract: 1% to 3%; Antioxidant: 0.01% to 1%; Biodegradable carrier gel: 80% to 90%.

[0005] The present application also provides a method for preparing a sperm composite lubricant, the method comprising: A preset proportion of a high-molecular natural moisturizer is dispersed in deionized water and mixed with a biodegradable carrier gel, and then a pyrroloquinoline quinone precursor liquid is added, stirred evenly, and cooled to room temperature to obtain a pyrroloquinoline quinone-pre-chimeric moisturizing gel matrix; a lipid membrane stabilizer is dissolved in an ethanol-water mixture and ultrasonically emulsified, and under constant temperature conditions, the emulsified lipid membrane stabilizer is dropwise added to the pyrroloquinoline quinone-pre-chimeric moisturizing gel matrix, and stirred to obtain a lipid fusion gel; sperm motility promoter microcapsules and plant extracts are suspended in a buffer solution to form a mixed suspension, and the mixed suspension is added to the lipid fusion gel to obtain an active chimeric gel, and an antioxidant is dropwise added to the active chimeric gel, and stirred in the dark to obtain a microcapsule-gel dual-controlled-release lubricant precursor; the microcapsule-gel dual-controlled-release lubricant precursor is filtered and sterilized to obtain a sperm composite lubricant.

[0006] Preferably, after dispersing a preset proportion of the high molecular weight natural moisturizing agent in deionized water, the method further comprises: heating the deionized water in which the high molecular weight natural moisturizing agent is dispersed and keeping the temperature high.

[0007] Preferably, the step of dissolving the lipid membrane stabilizer in an ethanol-water mixture and performing ultrasonic emulsification comprises: preliminarily emulsifying the lipid membrane stabilizer to form large emulsion droplets with a particle size of 200 nm to 500 nm; and refining the large emulsion droplets into small emulsion droplets with a particle size of 50 nm to 150 nm.

[0008] Preferably, the step of adding the emulsified lipid membrane stabilizer dropwise into the pyrroloquinoline quinone-pre-chimeric moisturizing gel matrix comprises: slowly adding the emulsified lipid membrane stabilizer dropwise into the pyrroloquinoline quinone-pre-chimeric moisturizing gel matrix.

[0009] Preferably, the droplet addition rate of the emulsified lipid membrane stabilizer is 0.5 mL / min to 0.8 mL / min.

[0010] Preferably, after obtaining the microcapsule-gel dual controlled-release lubricant precursor, the method further comprises: adjusting the pH of the microcapsule-gel dual controlled-release lubricant precursor.

[0011] Preferably, after adjusting the pH of the microcapsule-gel dual controlled-release lubricant precursor, the method further comprises: regulating the osmotic pressure of the microcapsule-gel dual controlled-release lubricant precursor.

[0012] Preferably, before filtering and sterilizing the microcapsule-gel dual controlled-release lubricant precursor, the method further comprises: vacuum defoaming the microcapsule-gel dual controlled-release lubricant precursor.

[0013] Preferably, after the sperm composite lubricant is prepared, the method further comprises: performing plasma surface treatment on the sperm composite lubricant.

[0014] Compared with the prior art, the present invention has the following beneficial effects: This application significantly enhances the performance of lubricants in reproductive applications through the integration of multiple structural designs and a progressive controlled-release strategy. By optimizing the encapsulation structure and release pathway, it achieves stable delivery and sustained action of the active ingredients, enhancing the lubricant's adaptability and support for the reproductive microenvironment, thereby effectively improving its overall effectiveness and application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 This is a schematic flow chart of a method for preparing a sperm composite lubricant provided in one embodiment of the present application; Figure 2 It is a macroscopic diagram of existing lubricants; Figure 3 This is a macroscopic schematic diagram of a composite lubricant prepared based on the present application, provided in another embodiment of the present application; Figure 4 This is the SEM electron microscope image of the existing lubricant; Figure 5 This is a SEM electron microscope image of the composite lubricant prepared based on the present application, provided in another embodiment of the present application. DETAILED DESCRIPTION

[0016] Specific embodiments of the present application will be described in detail below with reference to the accompanying drawings. Although specific embodiments of the present application are shown in the accompanying drawings, it should be understood that the present application can be implemented in various forms and should not be limited by the embodiments described herein. Rather, these embodiments are provided to enable a more thorough understanding of the present application and to fully convey the scope of the present application to those skilled in the art.

[0017] It should be noted that certain words are used in the specification and claims to refer to specific components. Those skilled in the art should understand that technicians may use different nouns to refer to the same component. This specification and claims do not use the difference in nouns as a way to distinguish components, but use the difference in the functions of the components as the criterion for distinction. As mentioned throughout the specification and claims, "including" or "comprising" is an open term, so it should be interpreted as "including but not limited to". The subsequent description of the specification is a preferred embodiment of the present application, but the description is based on the general principles of the specification and is not intended to limit the scope of the present application. The scope of protection of this application shall be as defined by the attached claims.

[0018] To facilitate understanding of the embodiments of the present application, further explanation will be given below using specific embodiments as examples in conjunction with the accompanying drawings, and the various drawings do not constitute a limitation on the embodiments of the present application.

[0019] In one exemplary embodiment, the present application provides a sperm composite lubricant. The raw materials and the weight percentages of the raw materials of the composite lubricant are as follows: polymer natural moisturizer: 3% to 10%; lipid membrane stabilizer: 1% to 5%; sperm motility enhancer: 0.1% to 2%; plant extract: 1% to 3%; antioxidant: 0.01% to 1%; pyrroloquinoline quinone precursor solution: 0.1% to 0.5%; biodegradable carrier gel: 79.5% to 94.79%. Preferably, the components of the composite lubricant and the weight percentages of the raw materials are as follows: polymer natural moisturizer: 5%; lipid membrane stabilizer: 2%; sperm motility enhancer: 0.8%; plant extract: 2%; antioxidant: 0.3%; pyrroloquinoline quinone precursor solution: 0.2%; biodegradable carrier gel: 89.7%.

[0020] Figure 1 A method for preparing a sperm composite lubricant proposed in an exemplary embodiment of the present application includes the following steps: S100: A predetermined ratio of a high molecular weight natural moisturizer is dispersed in deionized water and mixed with a biodegradable carrier gel. A pyrroloquinoline quinone precursor solution (obtained by dissolving pyrroloquinoline quinone disodium salt in a phosphate buffer solution having a pH of 6.2 to 6.8) is then added. The mixture is stirred evenly and then cooled to room temperature to obtain a pyrroloquinoline quinone-pre-embedded moisturizing gel matrix. S200: dissolving a lipid membrane stabilizer in an ethanol-water mixture and performing ultrasonic emulsification, and adding the emulsified lipid membrane stabilizer dropwise to the pyrroloquinoline quinone-pre-chimeric moisturizing gel matrix under constant temperature conditions, and stirring to obtain a lipid fusion gel; S300: suspending sperm motility promoter microcapsules and plant extracts in a pH buffer solution to form a mixed suspension, injecting the mixed suspension into a lipid fusion gel to obtain an active chimeric gel, adding an antioxidant dropwise into the active chimeric gel, and stirring in the dark to obtain a microcapsule-gel dual controlled-release lubricant precursor; S400: pH adjustment and osmotic pressure control are performed on the microcapsule-gel dual controlled-release lubricant precursor, and after vacuum defoaming, filtration and sterilization are performed to obtain a sperm composite lubricant.

[0021] Below, this application describes the above preparation method in detail through specific examples.

[0022] Example 1 1. Disperse 89.7 g of trehalose-gelatin complex powder in deionized water, heat to 40°C and maintain constant temperature, stir until completely dissolved, slowly add 5 g of poly(N-isopropylacrylamide)-gelatin copolymer, magnetically stir (300 rpm) for 30 minutes, then add 0.2 g of pyrroloquinoline quinone precursor solution (obtained by dissolving pyrroloquinoline quinone disodium salt in PBS at pH 6.5), and cool to room temperature (25°C) to obtain a pyrroloquinoline quinone-pre-chimeric moisturizing gel matrix; 2. Dissolve 2 g of phosphatidylcholine in an ethanol-water mixture (volume ratio of 1:1) and use an ultrasonic emulsifier (power 200 W, frequency 20 kHz) for 20 minutes to form a nano-emulsion. Slowly add the emulsion at a rate of 0.5 mL / min to the pyrroloquinoline quinone-pre-chimeric moisturizing gel matrix at a constant temperature of 35°C. Stir magnetically (200 rpm) for 1 hour to obtain a lipid fusion gel.

[0023] 3. 0.8 g of L-carnitine and 2 g of ginseng extract (the main components include ginsenosides, polysaccharides, amino acids, minerals and vitamins) were co-encapsulated in gelatin-esterase-responsive polylactic acid (PLA) double-shell microcapsules. The microcapsules were prepared by spray drying and dispersed in pre-cooled phosphate buffer (4°C). The mixture was magnetically stirred (150 rpm) for 30 minutes to uniformly suspend the microcapsule powder to obtain a mixed suspension containing L-carnitine and ginseng extract microcapsules; the mixed suspension was slowly added to the lipid fusion gel and magnetic stirring was continued (150 rpm) for 30 minutes to obtain an active chimeric gel containing L-carnitine and ginseng extract; subsequently, 0.3 g of astaxanthin nanoemulsion was added dropwise to the active chimeric gel containing L-carnitine and ginseng extract at a rate of 0.1 mL / min and stirred simultaneously (200 rpm) for 30 minutes in the dark to obtain a microcapsule-gel dual controlled-release lubricant precursor.

[0024] In this step, 0.8g of L-carnitine and 2g of ginseng extract (primarily composed of ginsenosides, polysaccharides, amino acids, minerals, and vitamins) were co-encapsulated in gelatin-esterase-responsive polylactic acid (PLA) double-shell microcapsules, aiming to achieve stable protection and on-demand release of key active ingredients. The gelatin inner shell provides initial encapsulation and water-solubility regulation, while the outer PLA shell, sensitive to esterase degradation, allows for responsive release of the active ingredients within the specific enzymatic environment of the female reproductive tract, preventing rapid release or degradation of the ingredients during initial administration and enhancing their bioavailability. L-carnitine, as a promoter of mitochondrial energy metabolism, helps improve sperm motility. The ginsenosides and polysaccharides in ginseng extract, possess anti-fatigue and antioxidant properties, synergistically protecting sperm membrane stability and cell viability. This double-shell microcapsule structure not only ensures stable encapsulation of the ingredients but also, through precise design of enzyme responsiveness, enhances the lubricant's intelligent release and long-lasting action within the complex reproductive microenvironment.

[0025] 4. Use 0.1M NaOH / HCl to adjust the pH value of the microcapsule-gel dual controlled-release lubricant precursor to 7.3, and add NaCl to adjust the osmotic pressure of the microcapsule-gel dual controlled-release lubricant precursor to 290 mOsm / kg. After vacuum defoaming, filter and sterilize the adjusted microcapsule-gel dual controlled-release lubricant precursor through a 0.22μm microporous filter membrane under sterile conditions to obtain a sperm composite lubricant.

[0026] Example 2 1. Disperse 97.79 g of sodium carboxymethyl cellulose in deionized water, heat to 45°C and maintain constant temperature, stir until completely dissolved, slowly add 3 g of chitosan powder, magnetically stir (250 rpm) for 20 minutes, add 0.1 g of pyrroloquinoline quinone precursor solution, and cool to room temperature to obtain a pyrroloquinoline quinone-pre-chimeric moisturizing gel matrix; 2. Dissolve 3 g of lecithin in an ethanol-water mixture (volume ratio 2:1) and perform ultrasonic emulsification for 25 minutes using an ultrasonic emulsifier (power 150 W, 25 kHz) to form a nanoscale emulsion. Slowly add the emulsion dropwise to the pyrroloquinoline quinone-pre-embedded moisturizing gel matrix at a rate of 0.8 mL / min at a constant temperature of 38°C. Magnetic stirring (180 rpm) was performed for 1.5 hours to obtain a lipid fusion gel. 3. Dissolve 1.2 g of taurine and 1 g of L-arginine in Tris-HCl buffer (pH 7.4) and ultrasonicate (power 120 W) for 10 min to obtain a mixed suspension containing taurine and L-arginine. Add the mixed suspension to a lipid fusion gel and stir magnetically (200 rpm) for 20 min to obtain an active chimeric gel containing taurine and L-arginine. Subsequently, add 1 g of glutathione-SH-modified gold nanoparticles to the active chimeric gel containing taurine and L-arginine and stir magnetically (220 rpm) for 40 min to obtain a microcapsule-gel dual controlled-release lubricant precursor.

[0027] 4. The pH of the microcapsule-gel dual controlled-release lubricant precursor was adjusted to 7.2 using 0.05 M HCl, and the osmotic pressure of the microcapsule-gel dual controlled-release lubricant precursor was adjusted to 285 mOsm / kg using trehalose. After vacuum degassing, the mixture was sterilized by γ-ray irradiation to obtain a sperm composite lubricant.

[0028] Example 3 1. Disperse 79.5 g of agarose-gelatin complex in deionized water, heat to 50°C and maintain constant temperature, stir until completely dissolved, slowly add 10 g of polyglutamic acid powder, magnetically stir (300 rpm) for 15 minutes, then add 0.5 g of pyrroloquinoline quinone precursor solution, and cool to room temperature to obtain a pyrroloquinoline quinone-pre-chimeric moisturizing gel matrix; 2. Dissolve 5 g of soybean lecithin in a chloroform-methanol mixture (volume ratio 3:1). After removing the solvent by rotary evaporation, use an ultrasonic emulsifier (power 250 W) for 30 minutes to form a nano-emulsion. Slowly add the emulsion at a rate of 0.6 mL / min to the pyrroloquinoline quinone-pre-chimeric moisturizing gel matrix at a constant temperature of 37°C. Stir magnetically (150 rpm) for 2 hours to obtain a lipid fusion gel.

[0029] 3. Dissolve 0.8 g of L-carnitine, 0.7 g of taurine, and 3 g of grape seed extract in HEPES buffer (pH 7.4). At low temperature (4°C), use an ultrasonic disperser (power 100 W) to treat for 20 minutes to obtain a mixed suspension containing L-carnitine, taurine, and grape seed extract. Slowly add the mixed suspension to the lipid fusion gel and magnetically stir (180 rpm) for 30 minutes to obtain an active chimeric gel containing L-carnitine, taurine, and grape seed extract. Subsequently, 0.5 g of coenzyme Q10 nanoemulsion was slowly added dropwise to the active chimeric gel containing L-carnitine, taurine, and grape seed extract at a rate of 0.2 mL / min and magnetically stirred (200 rpm) for 25 minutes to obtain a microcapsule-gel dual controlled-release lubricant precursor.

[0030] 4. Use 0.1 M NaOH to adjust the pH of the microcapsule-gel dual controlled-release lubricant precursor to 7.4, and adjust the osmotic pressure of the microcapsule-gel dual controlled-release lubricant precursor to 300 mOsm / kg by adding trehalose. After vacuum degassing, sterilize with high-pressure steam (121°C, 15 minutes) and cool to obtain the sperm composite lubricant.

[0031] Based on the above embodiments, the reason for heating and heat preservation in step 1 of each embodiment is that, for example, in Example 1, the solubility of powders such as sodium hyaluronate and trehalose-gelatin complex in water is affected by temperature. Heating to 40°C to 50°C can accelerate the dissolution of these ingredients in water, avoid the formation of particulate matter or uneven dispersion, and ensure a uniform solution or colloidal matrix. If heated at lower temperatures, the dissolution rate is slower, which will affect the quality of the final product. In addition, when heated, the molecules of trehalose and gelatin undergo structural changes, making them easier to disperse in deionized water, which is particularly important for subsequent gel formation. Polymer materials such as sodium hyaluronate need to be dissolved at an appropriate temperature to achieve their desired effect. Furthermore, if the poly(N-isopropylacrylamide)-gelatin copolymer is added at too low a temperature, the powder will clump in the solution, making it difficult to completely dissolve or evenly disperse. Heating to 40°C to 50°C helps prevent caking and ensure the uniformity of the solution or colloid.

[0032] Based on the above examples, in step 2 of each example, the emulsion contains numerous tiny particles. If the emulsion is added too quickly, these particles tend to aggregate or precipitate, leading to emulsion instability. Slow addition ensures that the particles remain evenly dispersed within the emulsion, maintaining its stability. Furthermore, if the emulsion is added at an excessively rapid rate (e.g., 1 mL / min), bubbles can be easily introduced during mixing, which can affect the physical properties and appearance of the final gel. Slow addition reduces bubble formation, resulting in a smoother, bubble-free gel.

[0033] Based on the above examples, in step 4 of each example, the pH of the microcapsule-gel dual controlled-release lubricant precursor is adjusted because a pH close to the physiological range is crucial for the biocompatibility of the lubricant. Human physiological fluids (such as semen and blood) typically have a pH between 7.2 and 7.4. Therefore, adjusting the pH of the microcapsule-gel dual controlled-release lubricant precursor ensures the lubricant's compatibility with the in vivo environment, reduces irritation or damage to sperm, cells, and tissues, and ensures its safety and effectiveness. Furthermore, polymers (such as gelatin and sodium hyaluronate) are highly sensitive to pH, and their solubility and gelation ability vary at different pH values. Excessively high or low pH can lead to gel structure instability, thereby affecting the lubricant's physical properties (such as viscosity and durability). Adjusting the pH within the physiological range helps ensure the stability and durability of the gel and microcapsule structures.

[0034] In addition, by regulating the osmotic pressure of the microcapsule-gel dual-controlled release lubricant precursor, the lubricant can be matched to the osmotic properties of body fluids, thereby reducing possible osmotic damage or excessive hydration, and thus avoiding adverse reactions such as cell edema or atrophy due to osmotic pressure differences. If the osmotic pressure of the lubricant is too high or too low, it will cause osmotic imbalance in the sperm cell membrane, affecting sperm motility and survival rate. For example, too high an osmotic pressure may cause sperm cells to dehydrate, while too low an osmotic pressure may cause sperm cells to swell and lose activity. By regulating the osmotic pressure to near physiological levels, the structure and function of sperm can be protected to the greatest extent possible.

[0035] Based on the above embodiments, the present application proposes an inventive emulsification method, which specifically includes the following steps: Step 1: The lipid membrane stabilizer is initially emulsified using high shear stirring or a homogenizer to form large emulsion droplets with a particle size of 200 nm to 500 nm to construct a primary lipid structure with strong encapsulation capacity and fast release rate; Step 2: Ultrasound or high-pressure microfluidization is used to further refine the large droplets into small droplets of 50 nm to 150 nm, thereby obtaining a nanoemulsion system with uniform particle size and higher dispersion stability.

[0036] In summary, in the first stage, high-speed shearing forms larger primary emulsion droplets, enabling efficient encapsulation of active ingredients and providing a foundation for rapid release of the lubricant. In the second stage, ultrasound or high-pressure homogenization further refines the droplets to the nanoscale, forming a uniform, highly stable microemulsion structure that slows the release rate of the ingredients and avoids an initial burst. This coarse-grained, double-emulsification strategy not only achieves progressive, controlled release, but also improves the uniformity of the lipid system's distribution within the gel and the overall biocompatibility of the lubricant, thereby enhancing the ability to maintain sperm motility and stabilize the reproductive microenvironment. Based on the above embodiments, the present application proposes a vacuum degassing method, which specifically includes the following steps: Step 1: Place the microcapsule-gel dual controlled-release lubricant precursor after pH adjustment and osmotic pressure regulation in an ultrasonic tank and use multi-frequency ultrasonic waves (20 to 100 kHz) at room temperature for pretreatment, with the frequency alternating over time, for example, switching once every 30 seconds.

[0037] In this step, multi-frequency ultrasound is used to generate acoustic pressure cavitation of varying sizes, causing tiny bubbles to resonate and aggregate into larger ones while avoiding the localized overheating caused by a single frequency. This helps break the bubbles from their stable dispersion, making them easier to release in the subsequent vacuum environment.

[0038] Step 2: The pretreated microcapsule-gel dual controlled-release lubricant precursor is transferred into a vacuum chamber and an initial low vacuum environment (e.g., 0.2 bar) is set. At the same time, the microcapsule-gel dual controlled-release lubricant precursor is heated to a moderate temperature (e.g., 35-40°C) through a temperature control system to promote bubble separation.

[0039] Step 3: When the bubbles begin to expand under low vacuum, start the vacuum system so that the vacuum pressure changes in pulses (for example, 0.2 bar → 0.05 bar → 0.15 bar → 0.02 bar, cycle 5 times), with each pulse period of 2 minutes.

[0040] In this step, dynamic pressure pulses rapidly change the air pressure, causing the bubbles to experience repeated expansion and contraction mechanical stress, accelerating the rupture of the bubble walls. Simultaneously, the pressure gradient changes drive the bubbles toward the surface, preventing them from residing deep within the bubble layer.

[0041] Step 4: During the pulsed vacuum stage, low-frequency ultrasonic waves (25 kHz, 50 W) were applied synchronously until the vacuum pressure stabilized at 0.02 bar.

[0042] In this step, ultrasonic vibrations enhance the Brownian motion of bubbles in a vacuum environment, driving them toward the liquid surface and merging into larger bubbles. Furthermore, the shear force of the ultrasound breaks down the interfacial tension between the pyrroloquinoline quinone-pre-embedded moisturizing gel matrix and the bubbles, thereby improving desorption efficiency.

[0043] After the lubricant is prepared based on the above embodiment, the present application further performs plasma surface treatment on the lubricant, specifically comprising the following steps: Step 1: Deposit an ultrathin (5-10 nm) titanium dioxide / graphene heterojunction photocatalytic layer on the lubricant surface by magnetron sputtering; In this step, the conductivity of graphene accelerates the migration of plasma electrons, and the photocatalytic activity of titanium dioxide can continuously decompose residual organic matter in subsequent treatments to form a self-cleaning surface.

[0044] Step 2: treating the lubricant with the photocatalytic layer deposited thereon with a pulsed gradient plasma; In this step, a helium-oxygen mixture (9:1 by volume) was used, with a dynamic plasma power gradient (50 W → 150 W → 50 W, 30 seconds per stage). The pulse frequency was simultaneously increased from 1 kHz to 5 kHz and then decreased. This gradient power and frequency control the penetration depth of plasma-active particles (such as O⁃ and O⁺), achieving a gradient distribution of surface hydrophilicity from the outside to the inside (contact angle gradually changes from 20° to 50°). This ensures lubricant adhesion while preventing lubricant loss due to excessive hydrophilicity.

[0045] Step 3: Immediately after the plasma treatment, the lubricant surface was irradiated with a UV LED (wavelength 365 nm, intensity 10 mW / cm²) for 5 minutes to activate the photocatalytic reaction of the titanium dioxide / graphene layer.

[0046] In this step, ultraviolet light can excite titanium dioxide to produce electron-hole pairs, and graphene acts as an electron transmission channel to inhibit recombination. The two can synergistically decompose residual bubble film and organic pollutants on the surface, while releasing trace reactive oxygen species (ROS) to enhance bactericidal performance.

[0047] Step 4: At the end of the plasma treatment, an aerosol containing phosphorylcholine (PC) monomer is introduced into the chamber, and the free radicals generated by the plasma are used to initiate surface graft polymerization to form a cell membrane-mimicking structure.

[0048] In this step, the phosphorylcholine layer can simulate the hydrophilic-hydrophobic microregions of the biological membrane, which is beneficial to reducing the friction coefficient between the lubricant and the biological tissue, while improving the stability of the sperm membrane.

[0049] In summary, the present application can form a self-cleaning surface by depositing an ultra-thin titanium dioxide / graphene photocatalytic layer on the surface of the lubricant. The gradient distribution of the hydrophilicity of the lubricant surface can be achieved through pulse gradient plasma treatment, which can not only ensure the adhesion of the lubricant, but also avoid excessive hydrophilization. By activating the photocatalytic reaction by ultraviolet LED, the generation of electron-hole pairs and the decomposition of residual bubble film and organic pollutants on the surface can be achieved, while at the same time, trace amounts of active oxygen can be released to enhance the bactericidal effect. Finally, the surface grafting polymerization of phosphorylcholine monomers is initiated by plasma to form a cell membrane-like structure, simulating the hydrophilic-hydrophobic microregions of the biological membrane, effectively reducing the friction coefficient between the lubricant and the biological tissue, and improving the stability of the sperm membrane, thereby improving the overall lubrication performance and biocompatibility.

[0050] Next, the present application conducts a comparison and testing of the lubricants prepared in Examples 1 to 3 through specific experiments.

[0051] Experiment 1: Sperm motility and survival rate test First, healthy male sperm (WHO standard, motility>50%) was mixed with the lubricants prepared based on Examples 1 to 3 at a volume ratio of 1:1, and the control group was physiological saline.

[0052] Next, the mixed lubricant and saline were incubated in a 37°C, 5% CO2 incubator for 1 hour.

[0053] Finally, the total motility (TM) and progressive motility (PM) were assessed using the computer-assisted sperm analysis system (CASA). The specific results are shown in Table 1: Table 1

[0054] As shown in Table 1, the total sperm motility of Example 1 (65.3%) after 6 hours was significantly higher than that of Examples 2 (58.1%) and 3 (60.9%), indicating that the synergistic effect of L-carnitine and vitamin E is superior. Furthermore, a comparison of forward motility (PM) showed that the sustained release of the active ingredient in Example 1 is more conducive to maintaining directional sperm motility.

[0055] Experiment 2: Physical and Chemical Properties Test First, measure the pH (pH meter) and osmotic pressure (freezing point osmometer) of the lubricant.

[0056] Secondly, the dynamic viscosity of the lubricant was measured using a rotational viscometer (25°C, shear rate 10 s⁻¹).

[0057] The test results are shown in Table 2: Table 2

[0058] In Table 2, Example 1's pH (7.3) and osmotic pressure (290 mOsm / kg) are closest to physiological conditions, minimizing osmotic damage to sperm. Furthermore, Example 1's viscosity (1250 mPa·s) is moderate, balancing lubricity and structural support, and is superior to Example 2 (too thin) and Example 3 (too thick).

[0059] Experiment 3: Active ingredient release characteristics The lubricant was placed in simulated vaginal fluid (pH 7.4, 37°C), and samples were taken regularly to detect the cumulative release rates of L-carnitine (HPLC) and vitamin E (UV spectrophotometry).

[0060] The test results are shown in Table 3: Table 3

[0061] In Table 3, Example 1 shows sustained-release characteristics for L-carnitine and vitamin E (82.1% and 65.8% released in 12 hours), respectively, consistent with a dual-controlled-release design. Example 2 exhibits rapid taurine release (95% in 12 hours), resulting in a short lubricant duration. Example 3 also exhibits a low coenzyme Q10 release rate (45.6%).

[0062] Experiment 4: Comparison of active ingredient retention rates before and after sterilization by HPLC.

[0063] The test results are shown in Table 4: Table 4

[0064] In Table 4, the filtration sterilization of Example 1 caused the least damage to the active ingredients (retention rate>97%), which was significantly better than that of Example 2 and Example 3.

[0065] In summary, through systematic experimental comparisons, this application found that the lubricant prepared based on Example 1 maintained a total activity of 65.3% after 6 hours, significantly higher than that of other groups. The physical compatibility of the lubricant prepared based on Example 1 was closest to physiological requirements. The active ingredient retention rate of the lubricant prepared based on Example 1 was >97%, and it had the highest sterilization stability. Therefore, this application adopts Example 1 as the best example.

[0066] Figure 2 It is a macroscopic diagram of existing lubricants. Figure 2The lubricant in question appears as a transparent, homogeneous liquid or gel, with strong fluidity but a loose structure. It primarily provides physical lubrication and lacks structural support. Existing lubricants are clear, uniform, and light, primarily reflecting their auxiliary properties of physical lubrication and short-term moisturizing, lacking any evidence of biological regulatory effects.

[0067] Figure 3 This is a macroscopic schematic diagram of the composite lubricant prepared based on this application. Figure 3 The lubricant shown has a thicker texture, a translucent gel-like substance that is soft, moist, and slightly viscoelastic. It has a delicate and smooth appearance, is colorless or slightly milky white to the naked eye, feels soft and non-greasy, and is easy to spread and apply. Figure 2 Lubricants shown, Figure 3 The lubricant shown has enhanced moisturizing, adhesion and reproductive compatibility, and contains effective active ingredients and controlled release mechanisms, suitable for improving sperm motility and survival rate.

[0068] Figure 4 This is the SEM electron microscope image of the existing lubricant. Figure 4 The structure shown exhibits a low-density, hydrogel-like pore structure. These lubricant pores have a uniform pore size distribution and a relatively loose structure. Existing surface lubricants primarily provide lubrication, but their simple microstructures prevent them from providing long-term support and effectively protecting the sperm microenvironment. Figure 5 This is a SEM electron microscope image of the composite lubricant prepared based on this application. Figure 5 The structure shown is relatively dense, showing a multi-level pore size distribution, and the pore walls are continuous and smooth, forming a three-dimensional bionic network. This structure has the following significant advantages: 1. Multi-level pore size structure: can accommodate microcapsules and nano-antioxidant particles to build an efficient controlled release system; 2. Thicker pore walls and tough mesh support: can provide good gel elasticity and lubrication ductility; 3. Continuous porous network: can enhance hydration and osmotic regulation, and avoid damage to sperm caused by osmotic pressure shock. In summary, Figure 5 The lubricant shown has a more complex microstructure, which can provide better sperm survival support, activity maintenance and structural protection, making it more advantageous for use in reproductive health. Figure 4 Existing lubricants are more likely to appear as simple hydrogel structures at the microscopic level, without obvious structural networks. Their main functions are limited to surface lubrication and short-term moisturizing, and they lack structural support and protection mechanisms for the sperm microenvironment.

[0069] In summary, from the microstructural level, the lubricant prepared in this application not only improves the ability to support sperm survival and maintain activity, but also provides a reliable basis for its efficient application in scenarios such as natural assisted conception, artificial insemination, in vitro fertilization and male reproductive intervention through three-dimensional structure synergistic lubrication, sustained release and simulated ecological environment reconstruction.

Claims

1. A sperm composite lubricant, characterized in that: The raw materials of the composite lubricant and the mass percentage of each raw material are: High molecular weight natural moisturizer: 3% to 10%; Lipid membrane stabilizers: 1% to 5%; Sperm motility enhancers: 0.1% to 2%; Plant extracts: 1% to 3%; Antioxidants: 0.01% to 1%; Pyrroloquinoline quinone precursor solution: 0.1% to 0.5%; Biodegradable carrier gel: 79.5% to 94.79%.

2. A method for preparing a sperm composite lubricant, characterized in that: The method comprises: A predetermined ratio of high molecular weight natural moisturizer is dispersed in deionized water and mixed with a biodegradable carrier gel, followed by addition of a pyrroloquinoline quinone precursor solution, stirring evenly and cooling to room temperature to obtain a pyrroloquinoline quinone-pre-embedded moisturizing gel matrix; The lipid membrane stabilizer is dissolved in an ethanol-water mixture and ultrasonically emulsified. Under constant temperature conditions, the emulsified lipid membrane stabilizer is added dropwise to the pyrroloquinoline quinone-pre-embedded moisturizing gel matrix, and the lipid fusion gel is obtained after stirring. Suspending sperm motility promoter microcapsules and plant extracts in a buffer solution to form a mixed suspension, adding the mixed suspension to the lipid fusion gel to obtain an active chimeric gel, adding an antioxidant dropwise to the active chimeric gel, and stirring in the dark to obtain a microcapsule-gel dual controlled-release lubricant precursor; The microcapsule-gel dual controlled-release lubricant precursor is subjected to filtration sterilization to obtain a sperm composite lubricant.

3. The method according to claim 2, characterized in that After dispersing a preset ratio of a high molecular weight natural moisturizing agent in deionized water, the method further comprises: Deionized water dispersed with a high molecular weight natural moisturizing agent is heated and kept warm.

4. The method according to claim 2, characterized in that The method of dissolving the lipid membrane stabilizer in an ethanol-water mixture for ultrasonic emulsification comprises: Preliminary emulsification of the lipid membrane stabilizer to form large emulsion droplets with a particle size of 200 nm to 500 nm; The large emulsion droplets are refined into small droplets of 50nm to 150nm.

5. The method according to claim 2, characterized in that The method of adding the emulsified lipid membrane stabilizer dropwise into the pyrroloquinoline quinone-pre-embedded moisturizing gel matrix comprises: The emulsified lipid membrane stabilizer is slowly added dropwise into the pyrroloquinoline quinone-pre-embedded moisturizing gel matrix.

6. The method according to claim 5, characterized in that The dropwise addition rate of the emulsified lipid membrane stabilizer is 0.5 mL / min to 0.8 mL / min.

7. The method according to claim 2, characterized in that After obtaining the microcapsule-gel dual controlled-release lubricant precursor, the method further comprises: The pH of the microcapsule-gel dual controlled-release lubricant precursor is adjusted.

8. The method according to claim 7, characterized in that After adjusting the pH of the microcapsule-gel dual controlled-release lubricant precursor, the method further comprises: The microcapsule-gel dual controlled-release lubricant precursor is subjected to osmotic pressure regulation.

9. The method according to claim 2, characterized in that Before filtering and sterilizing the microcapsule-gel dual controlled-release lubricant precursor, the method further comprises: The microcapsule-gel dual controlled-release lubricant precursor is subjected to vacuum degassing.

10. The method according to claim 2, characterized in that After the sperm composite lubricant is prepared, the method further comprises: Plasma surface treatment of sperm composite lubricant.

Images