Medical-grade high-crosslinking polyurethane sponge as well as preparation method and application thereof

Abstract

The invention relates to the field of sponges, and discloses a medical-grade highly-crosslinked polyurethane sponge and a preparation method and application thereof.The medical-grade highly-crosslinked polyurethane sponge is prepared from, by weight, 58-62 parts of polyether polyol, 31-35 parts of 4, 4 '-dihydroxy-4, 4'-dihydroxy-4, 4 '-dihydroxy-4, 4'-dihydroxy-4, 4 '-dihydroxy-4, 4'-dihydroxy-4, 4 '-dihydroxy-4, 4' The invention relates to a polyurethane elastomer which is prepared from the following raw materials in parts by weight: 50-70 parts of polyurethane, 5-10 parts of 4, 4 '-diphenylmethane diisocyanate, 3.5-4.5 parts of trimethylolpropane, 4-5 parts of dichloromethane, 0.15-0.25 part of stannous octoate and 0.25-0.35 part of Through the technical combination of the high-crosslinking component design and the gradient foaming process, the comprehensive performance breakthrough that the sponge is reliable in physical barrier, high and stable in drug loading efficiency and safe and durable in structure is achieved.

Description

Technical Field

[0001] This invention relates to the field of sponges, and particularly to a medical-grade highly cross-linked polyurethane sponge, its preparation method, and its application. Background Technology

[0002] In the field of reproductive health protection, the safety, effectiveness, and comfort of use are core indicators for evaluating the performance of contraceptive products. Currently, common female contraceptive methods include intrauterine devices (IUDs), oral contraceptives, condoms, and external contraceptive devices. Among these, external contraceptive devices occupy an important position in clinical application due to their flexibility, lack of implantation or oral medication, and avoidance of potential risks associated with hormonal intervention or intrauterine procedures. Contraceptive sponges, as a typical external physical-chemical combined contraceptive device, work by physically blocking sperm from entering the uterus through the sponge substrate, while simultaneously using a spermicide loaded on the sponge to kill any sperm that comes into contact with it, thus achieving a dual contraceptive effect. However, existing contraceptive sponge products still face many technical bottlenecks in practical applications, making it difficult to fully meet clinical needs. The main problems are as follows: 1. Unstable physical barrier performance: Some products have unreasonable three-dimensional porous structure design of sponge substrate, with uneven pore size distribution. There are cases where the pore diameter is larger than the length of sperm (50-60μm), which makes it easy for sperm to penetrate the pores and lose the physical barrier function. At the same time, some products excessively reduce the pore diameter in pursuit of high barrier performance, resulting in poor pore connectivity and insufficient sponge breathability. Long-term use can easily cause local vaginal dampness and stuffiness, increasing the risk of infection.

[0003] 2. Low loading efficiency and poor stability of spermicides: In existing preparation processes, the binding of spermicides (such as nonyl alcohol ether-9, N-9) to the sponge substrate is mostly through simple soaking and adsorption, which has problems such as insufficient loading (below the effective spermicide concentration) and uneven loading (local spermicide deficiency), resulting in unstable spermicide effect. In addition, some sponge substrates have chemical interactions with spermicides. For example, the amino groups in polyurethane sponge react with the ether bonds of N-9, which destroys the molecular structure of spermicide, reduces spermicide activity, and affects the contraceptive effect.

[0004] 3. Insufficient structural stability and biocompatibility: The vaginal environment is complex, containing weak acids (pH 3.8-4.5), proteins (such as mucin), and various enzymes (such as lysozyme). Existing sponge substrates are prone to swelling, degradation, or fragmentation in this environment. For example, some modified polyurethane sponges undergo ester bond hydrolysis under acidic conditions, leading to structural collapse. This not only results in the loss of their barrier function but may also leave fragments in the vagina, triggering inflammatory reactions. Simultaneously, components released by some products (such as residual sponge monomers and spermicide excipients) can inhibit the growth of beneficial vaginal bacteria (such as lactobacilli), disrupting the vaginal microecological balance and increasing the risk of bacterial vaginosis.

[0005] Therefore, the prior art remains to be improved and developed. SUMMARY

[0006] In view of the deficiencies of the prior art described above, the purpose of the present application is to provide a medical grade high cross-linked polyurethane sponge and its preparation method and application, aiming to solve the problems of poor physical barrier effect, low spermicide loading efficiency, poor structural stability and poor biocompatibility of existing sponges in the preparation of contraceptive products.

[0007] In order to achieve the above purpose, the present application adopts the following technical scheme: A medical grade high cross-linked polyurethane sponge, wherein the medical grade high cross-linked polyurethane sponge comprises the following components by weight: 58-62 parts of polyether polyol, 31-35 parts of 4,4'-diphenyl methane diisocyanate, 3.5-4.5 parts of trimethylolpropane, 4-5 parts of dichloromethane, 0.15-0.25 parts of stannous octoate, and 0.25-0.35 parts of polydimethylsiloxane.

[0008] The medical grade high cross-linked polyurethane sponge, wherein the polyether polyol is a propylene oxide type polyether polyol, and the number average molecular weight of the propylene oxide type polyether polyol is 2000-3000 and the functionality is 3.

[0009] The medical grade high cross-linked polyurethane sponge, wherein it further comprises 0.08-0.12 parts of disodium ethylenediaminetetraacetate.

[0010] A preparation method of a medical grade high cross-linked polyurethane sponge as described in the present application, comprising the following steps: The polyether polyol and trimethylolpropane are added to a vacuum drying tank in advance, dried at 80-85℃ and a vacuum degree of-0.09MPa to-0.1MPa for 2-3 hours to remove the water in the raw materials, and a polyether polyol-TMP mixture is obtained; The 4,4'-diphenyl methane diisocyanate is heated to 40-45℃ and stirred at a speed of 50-80rpm to obtain MDI in a molten state; The dried polyether polyol-TMP mixture is transferred into a prepolymerization kettle, protected by nitrogen, heated to 65-70℃, and the molten state MDI is added dropwise under stirring, after the dropwise addition is completed, the temperature is kept at 70-75℃ for 1.5-2 hours to form a polyurethane prepolymer; The polyurethane prepolymer is transferred into a foaming kettle, cooled to 50-55℃, and the stannous octoate, polydimethylsiloxane and dichloromethane are added under stirring to form a uniform foaming slurry; The foaming slurry is quickly injected into a customized stainless steel mold, after the mold is closed, it is transferred into a constant temperature foaming box, and a temperature gradient is set: the first stage is set to 35-40 DEG C, and is maintained for 1-5 minutes; the second stage is set to 55-60 DEG C, and is maintained for 5-15 minutes; the third stage is set to 70-75 DEG C, and is maintained for 15-30 minutes; during the foaming process, the cavity pressure is monitored through the pressure sensor on the mold, and the pressure is controlled to be maintained at 0.12-0.15 MPa; After the foaming is completed, the stainless steel mold is transferred into a curing furnace, and is maintained at 85-90 DEG C for 4-6 hours for deep curing, the sponge block after curing is taken out of the mold, is placed into a vacuum defoaming tank, and is treated at 25-30 DEG C for 1-2 hours under the condition that the pressure is maintained at-0.08 to-0.09 MPa, so that the micro closed bubbles existing in the sponge block are removed, the pores are ensured to be interconnected, and a medical grade high crosslinking polyurethane sponge precursor is obtained; The medical grade high crosslinking polyurethane sponge precursor is soaked in an ethanol solution, the residual release agent and unreacted monomers on the surface are removed, and then is dried in a clean drying room until the water content is less than or equal to 3%; The dried medical grade high crosslinking polyurethane sponge precursor is immersed in a 3-aminopropyl triethoxysilane solution, and is soaked at 25-30 DEG C for 1-2 hours, so that the hydroxyl groups on the sponge surface and the-Si-OH of the silane are subjected to condensation reaction to form a-Si-O- covalent bond, and an inert silane film with a thickness of 50-100 nm is constructed on the sponge surface; The sponge with the inert silane film generated on the surface is placed into an oven at 80-85 DEG C and is dried for 2-3 hours, so that the inert silane film is completely cured to form a tightly adhered inert layer, and thus a medical grade high crosslinking polyurethane sponge is prepared.

[0011] The application of a medical grade high crosslinking polyurethane sponge as described in the application, wherein the medical grade high crosslinking polyurethane sponge is used for preparing a contraceptive sponge.

[0012] The application, wherein the contraceptive sponge is composed of the medical grade high crosslinking polyurethane sponge and a spermicide liquid loaded in the medical grade high crosslinking polyurethane sponge, and the spermicide liquid is composed of an auxiliary material solution and nonoxynol-9 dissolved in the auxiliary material solution.

[0013] The application, wherein the auxiliary material solution is composed of glycerol, citric acid, hydroxyphenyl ethyl ester and pure water.

[0014] The application, wherein the preparation of the contraceptive sponge comprises the following steps: Put the medical grade high cross-linked polyurethane sponge body into purified water and soak for 20-30 minutes, then use a reciprocating extruder to extrude, expel the air and residual small molecular impurities in the sponge pores, repeat the soaking-extruding operation 3-5 times, put the pretreated sponge block into a clean drying room, dry at 40-50°C and relative humidity ≤40% for 8-10 hours until the water content of the sponge is ≤3%, to obtain a dry sponge body; According to the design specifications of the contraceptive product, use a numerical control laser cutting machine to cut the dry sponge body, and obtain a contraceptive sponge body; Put glycerol, citric acid, and hydroxyphenyl ethyl ester into purified water, stir at 25-30°C for 15-20 minutes to form a uniform auxiliary solution; add nonoxynol-9 to the auxiliary solution and continue stirring for 30-60 minutes, with ultrasonic assistance during stirring until the liquid is clear and free of precipitates. Filter the prepared liquid through a 0.22 μm polyether sulfone microporous filter membrane to remove particulate impurities in the liquid, and obtain a spermicide liquid. Put the contraceptive sponge body into a sterile tray and sterilize it with ultraviolet light. Put the sterilized contraceptive sponge body into a sterile drug soaking tank, close the tank cover, start the vacuum system, and draw the tank pressure to -0.08 to -0.09 MPa, maintain the vacuum state for 10-15 minutes to remove the air in the sponge pores; then inject the prepared spermicide liquid into the drug soaking tank through a peristaltic pump, the liquid level should completely cover the contraceptive sponge body, close the vacuum system, restore normal pressure, and allow the liquid to fully penetrate into the pores of the contraceptive sponge body under the action of pressure difference, soak the sponge for 10-15 minutes, and gently shake the tank every 5 minutes during this period to promote uniform distribution of the liquid in the sponge pores and ensure saturation adsorption of the sponge. Remove the spermicide-adsorbed contraceptive sponge body from the soaking tank and place it in a sterile centrifuge basket, then use a low-speed centrifuge with a speed of 500-800 rpm to centrifuge for 1-2 minutes to remove residual liquid on the surface of the sponge; In a clean drying room, the contraceptive sponge body after soaking is subjected to low-temperature drying and shaping, and finally packaged in a sterile operation table to obtain the contraceptive sponge.

[0015] Beneficial effects: The medical grade high crosslinking polyurethane sponge provided by the application realizes multi-dimensional performance optimization through precise component proportion design: in terms of physical barrier performance, the high crosslinking structure constructed by the proportion can precisely control the sponge pores, the ratio of polyether polyol and 4,4'-diphenyl methane diisocyanate is adapted, combined with the crosslinking action of trimethylolpropane, a three-dimensional porous structure with uniform pore size (20-40 um) and excellent connectivity can be formed, the pore size is smaller than the length of sperm (50-60 um), which can effectively block the penetration of sperm, and the physical barrier rate is more than 99%; at the same time, the pore connectivity is good, avoiding the contradiction between high barrier and low permeability of traditional sponge, the air permeability is significantly improved compared with ordinary polyurethane sponge, reducing the problem of vaginal damp and hot, reducing the risk of infection.

[0016] In terms of structural stability, high proportion of 4,4'-diphenyl methane diisocyanate and trimethylolpropane synergistically enhance the crosslinking density, so that the tensile strength of the sponge reaches 1.6-2.0 MPa, and the tear strength reaches 0.5-0.65 kN / m, which is 40%-50% higher than that of sponge without trimethylolpropane; in the daily scene of repeated extrusion of vagina, the deformation recovery rate is more than 88%, without fragmentation and deformation, ensuring that the physical barrier structure does not fail during use; In terms of process adaptability and safety, dichloromethane as a foaming agent, with the reasonable dosage ratio of stannous octoate (catalyst) and polydimethylsiloxane (foaming agent), can form a uniform and stable foam system during foaming process, avoiding pore defects caused by uneven bubble size; and under this component combination, the residual amount of unreacted monomer in the sponge after forming is low, the residual amount of 4,4'-diphenyl methane diisocyanate can be controlled below 0.02%, which meets the safety standards of medical grade, reduces the risk of vaginal mucosa irritation, and lays a foundation for subsequent loading of spermicide and preparation of safe and effective contraceptive sponge. BRIEF DESCRIPTION OF DRAWINGS

[0017] Figure 1 The preparation method flow chart of the medical grade high crosslinking polyurethane sponge of the application. DETAILED DESCRIPTION

[0018] The application provides a medical grade high crosslinking polyurethane sponge and a preparation method and application thereof, in order to make the purpose, technical scheme and effect of the application more clear and explicit, the following examples are used to further illustrate the application. It should be understood that the specific examples described herein are only used to explain the application, and do not limit the protection scope of the application.

[0019] The application provides a medical grade high cross-linking polyurethane sponge, wherein the medical grade high cross-linking polyurethane sponge comprises the following components by weight parts: 58-62 parts of polyether polyol, 31-35 parts of 4,4'-diphenyl methane diisocyanate, 3.5-4.5 parts of trimethylolpropane, 4-5 parts of dichloromethane, 0.15-0.25 parts of stannous octoate and 0.25-0.35 parts of polydimethylsiloxane, wherein the polyether polyol is a propylene oxide type polyether polyol, the number average molecular weight of the propylene oxide type polyether polyol is 2000-3000, and the functionality is 3.

[0020] Specifically, the polyether polyol used in the application is a propylene oxide type polyether polyol rather than an ethylene oxide type polyether polyol, because the adjacent carbon atoms of the ether bond (-O-) in the molecular chain of the propylene oxide type polyether polyol have a methyl group (-CH3), which has a large steric hindrance and can hinder the active site of the enzyme (such as esterase) from combining with the ether bond, thereby avoiding the hydrolysis of the ether bond. At the same time, the design of the number average molecular weight of 2000-3000 makes the length of the polyether polyol molecular chain moderate, which can avoid the problems of too small molecular weight leading to too dense cross-linking network and sponge being brittle and hard, and too large molecular weight leading to decreased reaction activity and uneven cross-linking. The ether bond of the propylene oxide segment has good flexibility, which can give the sponge a certain elasticity and ensure the deformation recovery ability in the vaginal extrusion scene. The functionality of 3 means that each polyether polyol molecule contains 3 reactive hydroxyl groups, which can form 3 cross-linking bonds with the isocyanate groups (-NCO) of 4,4'-diphenyl methane diisocyanate (MDI), which can significantly improve the cross-linking node density compared with the polyether polyol with a functionality of 2, and avoid the problem of loose structure caused by linear polymerization of molecular chains.

[0021] In the application, 31-35 parts of MDI (containing 2 -NCO groups) are used as a cross-linking agent, the -NCO groups of which gradually polymerize with the -OH groups of the polyether polyol to generate the urethane bond (-NH-CO-O-) characteristic of polyurethane, thereby forming a preliminary cross-linking framework. The aromatic ring structure (diphenyl methane) of MDI has high rigidity, which can enhance the mechanical strength of the cross-linking framework and provide a structure basis for the sponge to resist tearing and stretching. 3.5-4.5 parts of trimethylolpropane (TMP, containing 3 -OH groups) are used as an auxiliary cross-linking agent, the multi-functional group characteristics of which can further react with the -NCO groups of MDI to introduce branched cross-linking points in the preliminary cross-linking framework. Each TMP molecule can simultaneously connect 3 MDI molecules, thereby connecting multiple polyether polyol molecular chains to form a “three-dimensional network structure” and significantly improve the cross-linking density. This structure can reduce the slippage between molecular chains and reduce the risk of swelling and hydrolysis of the sponge in the acidic environment (pH 3.8-4.5) of the vagina (the ester bond hydrolysis site is wrapped by the cross-linking network, reducing the contact with acidic substances).

[0022] In this invention, 4-5 parts of dichloromethane are used as a physical foaming agent, and its mechanism of action directly determines the pore structure of the sponge. In the foaming mixing tank, dichloromethane is heated and vaporized to produce gas. Under the action of polydimethylsiloxane (foaming agent), the gas is uniformly dispersed in the polyurethane prepolymer in the form of tiny bubbles (nucleation process). The amount of dichloromethane (4-5 parts) is precisely calculated to ensure that enough gas is generated to form a porous structure, while avoiding excessive dosage that would lead to bubble coalescence and increased pore size. The vaporization rate of dichloromethane works synergistically with the mold pressure (0.12-0.15 MPa) and temperature gradient (35-40℃→55-60℃→70-75℃): in the low-temperature stage (35-40℃), it vaporizes slowly, forming small bubbles (initial pore size 20-30μm); in the medium-temperature stage (55-60℃), vaporization accelerates, and the bubbles expand moderately (final pore size 20-40μm); in the high-temperature stage (70-75℃), the bubble walls solidify and take shape; at the same time, the bubbles compress each other during expansion, and the bubble walls partially fuse to form interconnected pores, avoiding the problem of insufficient air permeability caused by closed bubbles, and finally achieving the dual effect of pore size blocking sperm + interconnectivity ensuring air permeability.

[0023] In this invention, 0.25-0.35 parts of polydimethylsiloxane (PDMS) are used as a foam stabilizer, and its mechanism of action ensures uniform pore distribution. PDMS has low surface tension, which can reduce the interfacial tension between the polyurethane prepolymer and the bubbles, allowing the bubbles to be uniformly dispersed during the nucleation stage and preventing local bubble aggregation that forms large pores (>50μm). PDMS molecular chains can also be adsorbed onto the bubble surface to form a protective film, preventing bubbles from merging or rupturing during foaming, ensuring the stability of each bubble size, and ultimately forming a uniform pore structure, thus guaranteeing the stability of the physical barrier.

[0024] In this invention, 0.15-0.25 parts of stannous octoate are used as a catalyst for the polyurethane polymerization reaction. The mechanism is to regulate the reaction rate between -NCO and -OH. Stannous octoate exhibits high catalytic activity for the formation of urethane bonds. In the prepolymerization reactor (65-70℃), it can accelerate the reaction of polyether polyol, TMP, and MDI, ensuring the formation of a stable polyurethane prepolymer within 1.5-2 hours. During the foaming stage (50-55℃), its catalytic activity is moderately reduced to avoid excessively rapid bubble expansion and pore size control issues. The 0.15-0.25 parts dosage design ensures a moderate reaction rate, avoiding both incomplete reaction (residual unreacted monomers) due to insufficient dosage and localized overheating and uneven crosslinking due to excessive dosage, ultimately reducing the residual MDI content in the sponge (≤0.01%), meeting medical safety standards.

[0025] The components mentioned above in this invention do not act independently, but rather through the synergy of molecular reactions, structural construction, and process adaptation, ultimately achieving the following core technical effects: Structural stability and environmental resistance: The flexible segments of polyether polyol, the rigid skeleton of MDI, and the three-dimensional crosslinking of TMP form a crosslinked network that combines rigidity and flexibility, giving the sponge high tensile strength (1.8-2.2MPa) and hydrolysis resistance. Balance between physical barrier and breathability: The precise foaming of dichloromethane and the uniform foaming effect of PDMS form a pore structure with uniform pore size (20-40μm) and high connectivity (>95%), which both blocks sperm penetration and ensures breathability. Process controllability and safety: The catalytic regulation of stannous octoate and the proportion of each component ensure the stability of the reaction process, reduce small molecule residues, and lay a high-quality substrate foundation for the subsequent loading of spermicide (nonoxynol-9) and preparation of contraceptive sponges, avoiding problems such as uneven loading or decreased activity of spermicide due to substrate defects.

[0026] In some embodiments, the medical-grade highly cross-linked polyurethane foam further includes 0.08-0.12 parts of disodium ethylenediaminetetraacetate. In this invention, disodium ethylenediaminetetraacetate acts as a metal ion chelating agent, its function being to remove trace metal ions (such as Fe) that may be present in the raw materials. 3+ Cu 2+ This avoids side reactions (such as trimerization) catalyzed by metal ions in MDI, ensures that the direction of polymerization is controllable, and maintains the stability of the crosslinked structure.

[0027] In some embodiments, a method for preparing medical-grade highly cross-linked polyurethane foam as described in this invention is also provided, such as... Figure 1 As shown, it includes the following steps: S10. Add polyether polyol and trimethylolpropane to a vacuum drying tank and dry at 80-85℃ and -0.09MPa to -0.1MPa vacuum for 2-3 hours to remove moisture from the raw materials and obtain polyether polyol-TMP mixture. S20. Heat 4,4'-diphenylmethane diisocyanate to 40-45°C and stir at 50-80 rpm to obtain molten MDI. S30. Transfer the dried polyether polyol-TMP mixture into a prepolymer reactor, purge with nitrogen for protection, heat to 65-70°C, and add the molten MDI dropwise under stirring. After the addition is complete, keep the temperature at 70-75°C and continue the reaction for 1.5-2 hours to form a polyurethane prepolymer. S40. The polyurethane prepolymer is transferred to a foaming mixing tank and cooled to 50-55°C. Stannous octoate, polydimethylsiloxane, and dichloromethane are added sequentially under stirring to form a uniform foaming slurry. S50. Quickly inject the foaming slurry into the customized stainless steel mold. After the mold is closed, transfer it to a constant temperature foaming chamber and set the temperature gradient: the first stage is set at 35-40℃ and held for 1-5 minutes; the second stage is set at 55-60℃ and held for 5-15 minutes; the third stage is set at 70-75℃ and held for 15-30 minutes. During the foaming process, the pressure in the cavity is monitored by the pressure sensor on the mold and the pressure is controlled to be maintained at 0.12-0.15MPa. S60. After foaming, the stainless steel mold is transferred to a curing oven and kept at 85-90℃ for 4-6 hours for deep curing. The cured sponge block is removed from the mold and placed in a vacuum degassing tank at -0.08 to -0.09MPa and 25-30℃ for 1-2 hours to remove the tiny closed air bubbles inside the sponge block and ensure that the pores are interconnected, thus obtaining a medical-grade highly cross-linked polyurethane sponge precursor. S70. Immerse the medical-grade highly cross-linked polyurethane foam precursor in an ethanol solution to remove residual release agent and unreacted monomers from the surface, and then dry it in a clean drying room until the moisture content is ≤3%; S80. Immerse the dried medical-grade highly cross-linked polyurethane sponge precursor in a 3-aminopropyltriethoxysilane solution at 25-30°C for 1-2 hours to allow the hydroxyl groups on the sponge surface to undergo a condensation reaction with the -Si-OH groups of the silane, forming -Si-O-covalent bonds, and constructing an inert silane film with a thickness of 50-100nm on the sponge surface. S90. Place the sponge with the inert silane film formed on its surface into an oven at 80-85℃ and dry it for 2-3 hours to completely cure the inert silane film and form a tightly adhered inert layer, thereby obtaining a medical-grade highly cross-linked polyurethane sponge.

[0028] Specifically, in the polyurethane polymerization reaction of step S10, moisture will undergo a side reaction with the isocyanate groups (-NCO) of 4,4'-diphenylmethane diisocyanate (MDI) (generating urea bonds and CO2). If the raw material contains moisture, it will lead to two key problems: first, it will consume MDI, reduce the effective crosslinking agent concentration, and form incomplete crosslinking regions, resulting in a decrease in the mechanical strength of the sponge; second, the CO2 generated by the side reaction will mix with the bubbles generated by the foaming agent (dichloromethane), forming pores of uneven size (some pores may exceed 50μm in diameter, which cannot block sperm). The combination of temperature of 80-85℃ and high vacuum (-0.09MPa to -0.1MPa) in step S10 can accelerate the evaporation of moisture and remove it in time, reducing the moisture content of the raw material to below 0.05%, avoiding side reactions from the source, and ensuring the uniformity of the subsequent crosslinking reaction.

[0029] In step S20, the parameters for heating 4,4'-diphenylmethane diisocyanate to 40-45°C and stirring at 50-80 rpm are designed to ensure that MDI reaches a stable molten state, thereby ensuring that the subsequent reaction with the polyether polyol-TMP mixture is controllable.

[0030] In step S30, the process design of nitrogen protection, dropwise addition at 65-70℃, and holding at 70-75℃ for 1.5-2 hours aims to construct a polyurethane prepolymer with uniform molecular weight through stepwise temperature control and an inert environment, laying the crosslinking foundation for subsequent foaming and molding. Specifically, because the urethane bonds (-NH-CO-O-) in the polyurethane prepolymer are easily oxidized by oxygen at high temperatures, generating carbonyl-containing degradation products, which leads to a decrease in the stability of the subsequent sponge structure, the introduction of nitrogen gas creates an inert atmosphere, isolating oxygen and ensuring the purity of the prepolymer molecular chains without oxidation defects. Dropping stage at 65-70℃: At this temperature, the reactivity of the -NCO group of MDI with the -OH group of polyether polyol / TMP is moderate. During the dropping process, a prepolymer with terminal -NCO groups can be gradually formed. If the temperature is too high (e.g., >70℃), the reaction will accelerate rapidly, which may cause the prepolymer to gel prematurely (excessive cross-linking of molecular chains, making subsequent foaming impossible). Heating stage at 70-75℃: Heating for 1.5-2 hours allows the reaction to proceed fully, ensuring a uniform molecular weight distribution of the prepolymer and avoiding low molecular weight fragments caused by incomplete reaction. A uniform molecular weight of the prepolymer is a prerequisite for the subsequent formation of a uniform porous structure. Excessive molecular weight differences will lead to different viscosities in different areas during foaming, uneven bubble growth rates, and the formation of large-pore defects.

[0031] In step S40, after cooling to 50-55℃, the viscosity of the polyurethane prepolymer is increased, which can maintain good fluidity and provide a suspension and dispersion environment for stannous octoate (catalyst), polydimethylsiloxane (foaming agent), and dichloromethane (foaming agent), thus avoiding sedimentation or local aggregation of the additives.

[0032] In step S50, the temperature gradient (35-40℃→55-60℃→70-75℃) and pressure control (0.12-0.15MPa) are the core processes. The mechanism is to precisely control the nucleation, growth, and shaping of bubbles through the synergy of temperature and pressure, forming a porous structure with a pore size of 20-40μm and a connectivity rate of >95%. The first stage (35-40℃, 1-5 minutes) is for low-temperature nucleation to ensure bubble density: at this temperature, dichloromethane slowly vaporizes, forming a large number of tiny bubble nuclei (5-10μm in diameter). If the initial temperature is too high, the foaming agent will vaporize rapidly, reducing the number of bubble nuclei and making them prone to merging into large bubbles (pore size exceeding 50μm, which cannot prevent imperfection). The 1-5 minute holding time ensures that the bubble nuclei are evenly distributed in the slurry, laying a high-density and uniform foundation for subsequent growth. The second stage (55-60℃, 5-15 minutes) involves medium-temperature growth and control of pore size: after heating to 55-60℃, the bubble nuclei expand rapidly, and the prepolymer begins to crosslink under the action of the catalyst (forming a preliminary three-dimensional network). The temperature and time design at this stage can precisely control the bubble expansion range, so that the bubble diameter reaches 20-40μm (smaller than the sperm length of 50-60μm, meeting the requirements for sperm inhibition), while avoiding the bubble not expanding sufficiently due to excessively rapid crosslinking (poor pore size and poor air permeability). The third stage (70-75℃, 15-30 minutes) serves to set the shape at high temperature and ensure pore connectivity: the high temperature of 70-75℃ can accelerate the complete cross-linking of the prepolymer, solidify and set the bubble walls, and prevent pore collapse during subsequent demolding; at the same time, the viscosity of the bubble walls decreases at high temperature, and adjacent bubble walls will partially fuse to form interconnected channels (pore connectivity rate of over 95%), which solves the contradiction of high resistance and low air permeability in traditional sponges. The interconnected channels can achieve smooth flow of gas and liquid, reducing the problem of dampness and stuffiness after long-term use of the vagina.

[0033] The function of pressure control (0.12-0.15MPa) is to suppress excessive bubble expansion and ensure a dense structure: the mold cavity pressure is maintained at 0.12-0.15MPa (slightly higher than atmospheric pressure), which can form moderate resistance to bubble expansion, avoid excessive expansion of bubbles due to low pressure (pore size exceeding 40μm) or rupture (forming irregular pores), and at the same time promote the tight arrangement of bubble walls, thereby improving the mechanical strength of the sponge (tensile strength reaches 1.8-2.2MPa).

[0034] In step S60, the high temperature of 85-90℃ allows unreacted -NCO and -OH in the polyurethane molecular chain to react further, increasing the crosslinking density from 2.0-2.5 mmol / g in the prepolymer stage to 3.2-3.8 mmol / g. The high crosslinking density reduces the exposure of easily hydrolyzed ester bonds in the molecular chain (ester bonds are wrapped by the crosslinking network), resulting in a weight loss rate of only 2%-3% for the sponge after soaking in the acidic environment of the vagina (pH 3.8-4.5) for 30 days (far lower than the 10%-15% of traditional sponges), thus avoiding structural collapse or fragment residue.

[0035] During the foaming process, a small number of closed air bubbles that are not connected to the outside may exist. These air bubbles can cause poor local air permeability of the sponge and may rupture due to pressure changes in the vaginal environment (releasing tiny particles and causing inflammation). However, a vacuum of -0.08 to -0.09 MPa can cause the gas inside the closed air bubbles to expand and break through the bubble walls, merging with the connected channels, ultimately achieving a sponge structure without closed air bubbles, ensuring both air permeability and safety.

[0036] In step S70, ethanol, as a polar solvent, effectively dissolves the release agent on the surface of the sponge and unreacted small molecule monomers (MDI, polyether polyol fragments) inside. Unreacted MDI monomers are cytotoxic (inhibiting the growth of vaginal lactobacilli). After ethanol soaking, the residual MDI content in the sponge is ≤0.01% (far lower than the 0.1% standard of GB / T16886.1-2011 for medical use). Excessive moisture content in the sponge will provide a breeding environment for microorganisms (such as bacteria and fungi), leading to product deterioration during storage. Drying to a moisture content of ≤3% ensures the sponge is in a dry state while avoiding over-drying that could cause the sponge to become brittle, thus ensuring structural integrity during subsequent surface modification.

[0037] In steps S80-S90, an inert silane membrane is constructed to address the stability and biocompatibility issues of the spermicide. The condensation reaction in S80 forms a covalently bonded silane membrane, isolating chemical interactions: the polyurethane molecular chains on the sponge surface contain hydroxyl groups (-OH), and 3-aminopropyltriethoxysilane (APTES) hydrolyzes in aqueous solution to generate -Si-OH groups. These two groups undergo a condensation reaction at 25-30°C (generating -Si-O- covalent bonds). This covalent bonding allows the silane membrane to adhere tightly to the sponge surface, preventing it from detaching due to vaginal friction or liquid rinsing. The core function of the silane membrane is to isolate the chemical interaction between the sponge and the spermicide (nonoxynol-9): in traditional sponges, the amino groups of the polyurethane react with the ether bonds of nonoxynol-9, disrupting the spermicide's molecular structure and leading to decreased activity; however, the inert silane membrane (containing a -Si-O-Si- backbone) is chemically stable and does not react with the spermicide, thus improving the retention rate of spermicide activity.

[0038] The drying and curing process in S90 optimizes the silane membrane structure, improving biocompatibility and environmental resistance: drying at 80-85℃ for 2-3 hours allows unreacted -Si-OH groups in the silane membrane to further condense, forming a dense three-dimensional -Si-O-Si- network. The membrane thickness is controlled at 50-100nm, a thickness that neither clogs the sponge pores (ensuring breathability and spermicide penetration) nor obstructs them, while completely covering the active groups (such as amino and carboxyl groups) on the sponge surface. Simultaneously, the dense silane membrane reduces the adsorption of vaginal mucosal cells on the sponge surface (reducing irritation), lowering the skin sensitization rate to 0, and inhibiting the adhesion of harmful vaginal bacteria, thus maintaining the balance of the vaginal microecology.

[0039] The steps described above in this invention do not act independently, but rather work synergistically across the entire chain of raw material purification, reaction regulation, structural molding, and surface optimization, ultimately resulting in medical-grade highly cross-linked polyurethane foam with excellent physical barrier properties, spermicide compatibility, and structural and biological safety.

[0040] In some embodiments, an application of the medical-grade highly cross-linked polyurethane sponge as described in this invention is also provided, wherein the medical-grade highly cross-linked polyurethane sponge is used to prepare a contraceptive sponge; the contraceptive sponge is composed of the medical-grade highly cross-linked polyurethane sponge and a spermicide solution loaded in the medical-grade highly cross-linked polyurethane sponge, the spermicide solution being composed of an excipient solution and nonoxynol-9 dissolved in the excipient solution; the excipient solution being composed of glycerol, citric acid, ethylparaben, and purified water.

[0041] In this embodiment, the excipient solution (composed of glycerin, citric acid, ethylparaben, and purified water) is not a simple solvent carrier, but rather provides crucial support for the stability, sponge loading adaptability, and safety of use of the spermicide (nonoxynol-9) through the synergistic function of each component. The specific functions and mechanisms of each component are as follows: In excipient solutions, glycerin primarily serves a dual role as a humectant and compatibility modifier. From the perspective of drug stability, the glycerin molecule contains three hydroxyl groups (-OH), which can form hydrogen bonds with the ether bond (-O-) of nonoxynol-9 and water molecules, constructing a stable intermolecular force network and preventing crystallization of nonoxynol-9 during storage due to temperature fluctuations or moisture evaporation. Simultaneously, glycerin reduces the overall surface tension of the drug solution, allowing nonoxynol-9 to be more evenly dispersed in pure water, preventing turbidity caused by excessively high local concentrations. From the perspective of sponge compatibility and biocompatibility, glycerin possesses excellent hydrophilicity and bioinertness. During vacuum impregnation, it can penetrate deep into the pores of the sponge along with the drug solution, adhering to the inner wall of the sponge to form a moisturizing film. This film reduces direct contact between nonoxynol-9 and the sponge substrate (helping maintain spermicide activity) and also reduces the coefficient of friction between the sponge and the vaginal mucosa during use, preventing mucosal irritation caused by a dry sponge and improving user comfort.

[0042] Citric acid, as an acid regulator, plays a crucial role in precisely controlling the pH of the medication solution to within the physiological range of the vagina: the vaginal environment is generally weakly acidic (pH 3.8-4.5), and citric acid releases H+ through ionization. + It can stabilize the pH value of the excipient solution and the final spermicide solution at 4.0-4.5. This pH range has two key significances: on the one hand, matching the weakly acidic environment of the vagina can avoid vaginal microecological imbalance caused by pH deviation of the solution; on the other hand, this pH value can significantly enhance the spermicidal activity of nonoxynol-9: the spermicidal mechanism of nonoxynol-9 is to destroy the sperm cell membrane. Its molecules are more likely to maintain an amphiphilic structure in a weakly acidic environment, which can quickly penetrate to the surface of the sperm cell membrane, reduce the membrane potential and cause the membrane to rupture.

[0043] Ethylparaben, as a pharmaceutical-grade preservative, effectively inhibits the growth of microorganisms in the drug solution and the pores of the sponge. Spermicidal solutions contain nutrients such as glycerin and nonoxynol-9, and the porous structure of the sponge easily adsorbs bacteria and fungi (such as Escherichia coli and Candida albicans) from the air. Without preservatives, the product is prone to microbial contamination during storage. Ethylparaben kills bacteria and fungi broadly by disrupting the integrity of microbial cell membranes and inhibiting their respiratory enzymes and dehydrogenase activities. It has high biocompatibility; it is hardly absorbed in the vagina and is mainly excreted with secretions, without irritating the vaginal mucosa, meeting medical material safety standards.

[0044] Pure water serves as the basic solvent carrier in excipient solutions, and its core function is to provide a uniform dissolution and dispersion medium for glycerol, citric acid, ethylparaben, and nonylphenyl alcohol ether-9.

[0045] In some embodiments, the preparation of the contraceptive sponge includes the steps of: S1. The medical-grade highly cross-linked polyurethane sponge body is immersed in purified water for 20-30 minutes, and then squeezed using a reciprocating extruder to remove air and residual small molecule impurities from the sponge pores. The immersion-squeezing operation is repeated 3-5 times. The pretreated sponge block is placed in a clean drying room and dried for 8-10 hours at 40-50℃ and relative humidity ≤40% until the sponge moisture content is ≤3%, thus obtaining the dried sponge body. This step, through repeated immersion-squeezing, can effectively remove small molecule impurities remaining during the sponge production process, avoiding the release of these impurities during use and preventing vaginal mucosal irritation or allergic reactions. Low-temperature drying can maintain the original three-dimensional porous structure of the sponge, ensuring that the pore size and connectivity meet the design requirements, laying the foundation for subsequent spermicide loading and physical barrier. The soaking time should be controlled between 20 and 30 minutes. If the time is too short, the impurities in the sponge pores will not dissolve completely; if the time is too long, the sponge may absorb too much water, increasing the subsequent drying time. The extrusion pressure should be controlled between 0.1 and 0.2 MPa. If the pressure is too low, the impurities will not be completely discharged; if the pressure is too high, it may damage the porous structure of the sponge. The drying temperature should be controlled between 40 and 50°C. Low-temperature drying can avoid thermal aging of the sponge polymer chains caused by high temperatures, which can damage the three-dimensional porous structure (such as pore collapse and pore size shrinkage), thus ensuring the structural stability of the sponge.

[0046] S2. According to the design specifications of the contraceptive product, the dried sponge body is cut using a CNC laser cutting machine to obtain the contraceptive sponge body. For example, according to the product design specifications (e.g., diameter 5-7cm, thickness 2-3cm, with a central depression of 0.5-1cm depth for easy insertion and fixation in the vagina), a CNC laser cutting machine is selected for cutting: a carbon dioxide laser cutting machine is used, with a laser power of 50-80W, a cutting speed of 10-15mm / s, and a focused spot diameter of 0.1mm. Inert gas (nitrogen) is used for protection during the cutting process to prevent the sponge edges from carbonizing or becoming fuzzy due to high temperature.

[0047] S3. Add glycerin, citric acid, and ethylparaben to purified water and stir for 15-20 minutes at 25-30℃ to form a homogeneous excipient solution. Add nonoxynol-9 to the excipient solution and continue stirring for 30-60 minutes, using ultrasonic assistance during stirring, until the solution is clear and free of precipitate. Filter the prepared solution through a 0.22μm polyethersulfone microporous membrane to remove particulate impurities, obtaining the spermicide solution. For example, in a Class 1,000 sterile preparation room, prepare the spermicide solution according to the following formula and process: Add glycerin (5%-10% of the total mass of the solution), citric acid (0.1%-0.2% of the total mass of the solution), and ethylparaben (0.05%-...). Add 0.1% of the excipient to purified water, turn on the stirrer (paddle stirrer, speed 100-200 rpm), and stir for 15-20 minutes at 25-30℃ until the excipient is completely dissolved and a uniform excipient solution is formed; slowly add nonoxynol-9 (accounting for 5%-10% of the total mass of the drug solution) to the excipient solution, and continue stirring for 30-60 minutes. During the stirring process, use ultrasonic assistance (power 100-200W, frequency 20-30kHz) to promote uniform dispersion of N-9 until the drug solution is clear and free of precipitate; filter the prepared drug solution through a 0.22μm polyethersulfone (PES) microporous filter membrane at a filtration pressure of 0.1-0.2MPa to remove any particulate impurities that may be present in the drug solution, and obtain the spermicide drug solution.

[0048] In this step, the stirring speed should be controlled at 100-200 rpm. If the speed is too low, the excipients and spermicide will not dissolve and disperse evenly; if the speed is too high, the solution will easily generate bubbles, affecting the subsequent filtration effect. The stirring temperature should be controlled at 25-30℃. If the temperature is too low, the solubility of N-9 will decrease, and precipitation will easily occur; if the temperature is too high, it may cause ethylparaben to decompose and lose its preservative effect. The ultrasonic power and frequency need to be moderate. If the power is too high, it may damage the molecular structure of N-9 and reduce spermicidal activity; if the power is too low, the auxiliary dispersion effect will be poor.

[0049] S4. Place the contraceptive sponge body into a sterile tray and sterilize it using ultraviolet irradiation. Place the sterilized contraceptive sponge body into a sterile soaking tank, close the soaking tank cover, start the vacuum system, and pump the pressure inside the tank to -0.08 to -0.09 MPa. Maintain the vacuum state for 10-15 minutes to remove air from the sponge pores. Then, inject the prepared spermicide solution into the soaking tank using a peristaltic pump. The solution level should completely cover the contraceptive sponge body. Close the vacuum system and restore normal pressure, allowing the solution to fully penetrate into the pores of the contraceptive sponge body under the action of pressure difference. After soaking, keep the contraceptive sponge body in the solution for 10-15 minutes. During this period, gently shake the soaking tank once every 5 minutes to promote the uniform distribution of the solution in the sponge pores and ensure that the sponge is saturated with adsorption. As an example, in a Class 1,000 cleanroom, the vacuum adsorption method is used for sponge impregnation with medication. The specific procedure is as follows: The selected qualified sponge preforms were placed in a sterile tray and sterilized by ultraviolet (UV) irradiation (wavelength 254nm, irradiation intensity 100-200μW / cm²). 2 Irradiation time is 30-60 minutes to kill any microorganisms that may remain on the sponge surface. The pretreated sponge blank is then placed in a sterile soaking tank, the tank lid is closed, and the vacuum system is activated to reduce the pressure inside the tank to -0.08 to -0.09 MPa. This vacuum is maintained for 10-15 minutes to remove air from the sponge pores (to prevent air from hindering the penetration of the drug solution). Subsequently, the prepared spermicide solution is slowly injected into the soaking tank using a peristaltic pump (flow rate 50-100 mL / min). The solution level must completely cover the sponge blank (the liquid level should be 2-3 cm above the sponge surface). The vacuum system is then closed, and atmospheric pressure is restored, allowing the solution to fully penetrate the sponge pores under the pressure difference. After soaking, the sponge blank is left to stand in the solution for 10-15 minutes, during which the soaking tank is gently shaken every 5 minutes to promote uniform distribution of the solution in the sponge pores and ensure saturated adsorption.

[0050] In this step, the vacuum level is controlled between -0.08 and -0.09 MPa. If the vacuum is too low (too small in absolute value), air cannot be completely expelled from the sponge pores, resulting in insufficient drug penetration and insufficient adsorption. If the vacuum is too high (too large in absolute value), the sponge structure may be compressed, reducing the pore size and affecting subsequent drug penetration. The vacuum holding time is controlled between 10 and 15 minutes. If the time is too short, air will not be completely expelled; if the time is too long, production efficiency will decrease. The drug injection flow rate is controlled between 50 and 100 mL / min. If the flow rate is too fast, bubbles are easily generated in the drug, affecting the penetration effect; if the flow rate is too slow, production efficiency will be low.

[0051] S5. Remove the contraceptive sponge body after absorbing the drug solution from the soaking tank, place it in a sterile centrifuge basket, and centrifuge it for 1-2 minutes using a low-speed centrifuge at 500-800 rpm to remove the residual drug solution on the surface of the sponge. In this step, the centrifugation speed should be controlled at 500-800 rpm. If the speed is too low, the residual drug solution on the surface will not be completely removed, resulting in a large deviation in product weight. If the speed is too high, the drug solution absorbed inside the sponge may be thrown out, resulting in insufficient adsorption.

[0052] S6. In a clean drying room, the contraceptive sponge body after being soaked in medicine is dried and shaped at low temperature, and finally packaged in a sterile operating table to obtain the contraceptive sponge.

[0053] As an example, in a Class 10,000 clean drying room (temperature 35-45℃, relative humidity ≤40%, wind speed 0.5-1m / s), the soaked sponge is dried and shaped at low temperature: The molding mold is made of medical-grade silicone material (matching the size of the sponge blank, with a smooth inner wall). The surface of the mold is sterilized by gamma rays (dose 25-30kGy) to ensure sterility. Place the soaked sponge blank into the shaping mold and press gently to ensure a tight fit between the sponge and the inner wall of the mold, preventing shrinkage and deformation during drying. Place the shaping mold containing the sponge into a drying rack with a multi-layer structure to ensure uniform airflow. Dry for 8-12 hours at a temperature of 35-45℃, relative humidity ≤40%, and wind speed of 0.5-1m / s. Record the temperature and humidity of the drying room every 2 hours to ensure stable parameters. After drying, remove the sponge from the shaping mold.

[0054] In this step, the drying temperature is controlled between 35-45℃. Too low a temperature results in excessively long drying times, which can easily lead to microbial growth; too high a temperature may cause N-9 to decompose (N-9's thermal decomposition temperature is approximately 60℃, and it exhibits good thermal stability at 35-45℃), reducing its spermicidal activity. The relative humidity is controlled at ≤40%. Excessive humidity leads to low drying efficiency, making it difficult to achieve the required moisture content in the sponge. The air velocity is controlled between 0.5-1m / s. Too low a velocity results in poor air circulation in the drying chamber, uneven temperature and humidity distribution, and uneven drying of the sponge; too high a velocity may cause excessively rapid evaporation of moisture from the sponge surface, forming a hard shell that hinders internal moisture evaporation, leading to incomplete drying. The drying time is controlled between 8-12 hours. Too short a time results in excessively high moisture content, while too long a time makes the sponge brittle.

[0055] The present invention will be further explained and illustrated below through specific embodiments: All raw materials used in the examples and comparative examples were commercially available medical-grade products, including: propylene oxide polyol (number average molecular weight 2000-3000, functionality 3, purchased from BASF); 4,4'-diphenylmethane diisocyanate (MDI, purchased from Wanhua Chemical); trimethylolpropane (TMP, purchased from Sinopharm Group); stannous octoate (purchased from Aladdin); polydimethylsiloxane (purchased from Dow Corning); disodium ethylenediaminetetraacetate (EDTA-2Na, purchased from Sigma); 3-aminopropyltriethoxysilane (purchased from Bailingwei); nonoxynol-9 (purchased from Jiangsu Chenxing Pharmaceutical); glycerol, citric acid, and ethylparaben (all medical-grade, purchased from Shanghai Maclean).

[0056] Example 1 Preparation of medical-grade highly cross-linked polyurethane foam: The raw material proportions by weight include: 60 parts polyether polyol, 33 parts 4,4'-diphenylmethane diisocyanate, 4 parts trimethylolpropane, 4.5 parts dichloromethane, 0.2 parts stannous octoate, and 0.3 parts polydimethylsiloxane.

[0057] Preparation steps Drying treatment: The polyether polyol and trimethylolpropane were added to a vacuum drying tank and dried at 82°C and -0.095 MPa vacuum for 2.5 hours to obtain a polyether polyol-TMP mixture.

[0058] MDI melting: 4,4'-diphenylmethane diisocyanate was heated to 42°C and stirred at 65 rpm to obtain molten MDI.

[0059] Prepolymerization reaction: The polyether polyol-TMP mixture is transferred into a prepolymerization reactor, protected by nitrogen gas, heated to 68°C, and molten MDI is added dropwise with stirring. After the addition is complete, the mixture is kept at 72°C for 1.8 hours to form a polyurethane prepolymer.

[0060] Preparation of foaming slurry: The polyurethane prepolymer is transferred to a foaming mixing tank, cooled to 52°C, and stannous octoate, polydimethylsiloxane and dichloromethane are added in sequence under stirring. Stir for 15 minutes to form a uniform foaming slurry.

[0061] Gradient foaming: The foaming slurry is quickly injected into a stainless steel mold, and after the mold is closed, it is transferred to a constant temperature foaming chamber. The temperature gradient is set as follows: the first stage is 38℃ for 3 minutes, the second stage is 58℃ for 10 minutes, and the third stage is 72℃ for 22 minutes. During the foaming process, the cavity pressure is controlled to be 0.13MPa by a pressure sensor.

[0062] Deep curing and degassing: After foaming, the mold is transferred to a curing oven and kept at 88°C for 5 hours; after curing, the sponge block is taken out and placed in a vacuum degassing tank and treated at -0.085MPa and 28°C for 1.5 hours to obtain the sponge precursor.

[0063] Purification and drying: Soak the sponge precursor in 75% ethanol solution for 2 hours to remove residual impurities; then transfer it to a clean drying room and dry it at 50°C until the moisture content is 2.5%.

[0064] Surface modification: The dried sponge precursor was immersed in a 5% (mass concentration) 3-aminopropyltriethoxysilane ethanol solution and soaked at 28°C for 1.5 hours; then it was dried in an oven at 82°C for 2.5 hours to obtain medical-grade highly cross-linked polyurethane sponge.

[0065] Preparation of contraceptive sponges Preparation of spermicide solution: Add 5 parts glycerin, 0.3 parts citric acid, and 0.1 parts ethylparaben to 94.6 parts purified water, stir at 28°C for 18 minutes to form an excipient solution; add 98 parts nonoxynol ether, and continue stirring for 45 minutes (ultrasonic aid, power 300W). Filter the solution through a 0.22μm polyethersulfone membrane to obtain the spermicide solution.

[0066] Sponge pretreatment: The above-mentioned medical-grade highly cross-linked polyurethane sponge body was soaked in purified water for 25 minutes and extruded using a reciprocating extruder (pressure 0.3MPa), and the soaking-extrusion was repeated 4 times; then it was transferred to a clean drying room and dried at 45℃ and RH 35% for 9 hours to obtain a dry sponge body with a water content of 2.8%.

[0067] Cutting and sterilization: The sponge body is cut according to product specifications (50mm diameter, 15mm thickness) using a CNC laser cutting machine (50W power), placed in a sterile tray, and sterilized by ultraviolet irradiation for 30 minutes (wavelength 254nm, intensity 100μW / cm²). 2 ).

[0068] Vacuum impregnation: Place the sterilized sponge body into a sterile impregnation tank, close the tank cover, evacuate to -0.085MPa, and maintain for 12 minutes; inject spermicide solution through a peristaltic pump (liquid level covering the sponge 5mm), restore normal pressure, and let stand for 12 minutes, shaking the impregnation tank once every 5 minutes during this period.

[0069] Centrifugation and drying: After soaking in the drug, the sponge was taken out and placed in a sterile centrifuge basket and centrifuged at 700 rpm for 1.5 minutes; then transferred to a clean drying room and dried at 35℃ for 4 hours (moisture content controlled at 8%-10%). Finally, it was packaged on a sterile operating table to obtain the contraceptive sponge.

[0070] Example 2 Preparation of medical-grade highly cross-linked polyurethane foam Raw material ratio (by weight): 58 parts polyether polyol, 35 parts 4,4'-diphenylmethane diisocyanate, 4.5 parts trimethylolpropane, 5 parts dichloromethane, 0.25 parts stannous octoate, 0.35 parts polydimethylsiloxane, and 0.12 parts disodium ethylenediaminetetraacetate.

[0071] Preparation steps Drying treatment: The polyether polyol and trimethylolpropane were added to a vacuum drying tank and dried at 85°C and -0.1MPa vacuum for 3 hours to obtain a polyether polyol-TMP mixture.

[0072] MDI melting: 4,4'-diphenylmethane diisocyanate was heated to 45°C and stirred at 80 rpm to obtain molten MDI.

[0073] Prepolymerization reaction: The polyether polyol-TMP mixture is transferred into a prepolymerization reactor, protected by nitrogen gas, heated to 70°C, and molten MDI is added dropwise with stirring. After the addition is complete, the mixture is kept at 75°C for 2 hours to form a polyurethane prepolymer.

[0074] Preparation of foaming slurry: The polyurethane prepolymer is transferred to a foaming mixing tank and cooled to 55°C. Stannous octoate, polydimethylsiloxane, dichloromethane, and disodium ethylenediaminetetraacetate are added sequentially under stirring. The mixture is stirred for 20 minutes to form a uniform foaming slurry.

[0075] Gradient foaming: The foaming slurry is quickly injected into a stainless steel mold, and after the mold is closed, it is transferred to a constant temperature foaming chamber. The temperature gradient is set as follows: the first stage is 40℃ for 5 minutes, the second stage is 60℃ for 15 minutes, and the third stage is 75℃ for 30 minutes. During the foaming process, the cavity pressure is controlled to be 0.15MPa by a pressure sensor.

[0076] Deep curing and degassing: After foaming, the mold is transferred to a curing oven and kept at 90°C for 6 hours; after curing, the sponge block is taken out and placed in a vacuum degassing tank and treated at -0.09MPa and 30°C for 2 hours to obtain the sponge precursor.

[0077] Purification and drying: Soak the sponge precursor in 80% ethanol solution for 2.5 hours to remove residual impurities; then transfer it to a clean drying room and dry it at 55°C until the moisture content is 2%.

[0078] Surface modification: The dried sponge precursor was immersed in a 6% (mass concentration) 3-aminopropyltriethoxysilane ethanol solution and soaked at 30°C for 2 hours; then it was dried in an 85°C oven for 3 hours to obtain medical-grade highly cross-linked polyurethane sponge.

[0079] Preparation of contraceptive sponges Preparation of spermicide solution: Add 6 parts glycerin, 0.4 parts citric acid, and 0.15 parts ethylparaben to 93.45 parts purified water, stir at 30°C for 20 minutes to form an excipient solution; add 10 parts nonoxynol-9, and continue stirring for 60 minutes (ultrasonic aid, power 350W). Filter the solution through a 0.22μm polyethersulfone membrane to obtain the spermicide solution.

[0080] Sponge pretreatment: The above-mentioned medical-grade highly cross-linked polyurethane sponge body was soaked in purified water for 30 minutes and extruded using a reciprocating extruder (pressure 0.4MPa), and the soaking-extrusion was repeated 5 times; then it was transferred to a clean drying room and dried at 50℃ and RH38% for 10 hours to obtain a dry sponge body with a water content of 2.5%.

[0081] Cutting and sterilization: The sponge body is cut according to product specifications (55mm diameter, 16mm thickness) using a CNC laser cutting machine (60W power), placed in a sterile tray, and sterilized by ultraviolet irradiation for 40 minutes (wavelength 254nm, intensity 120μW / cm²). 2 ).

[0082] Vacuum impregnation: Place the sterilized sponge body into a sterile impregnation tank, close the tank cover, evacuate to -0.09MPa, and maintain for 15 minutes; inject spermicide solution through a peristaltic pump (liquid level covering the sponge 6mm), restore normal pressure, and let stand for 15 minutes, shaking the impregnation tank once every 5 minutes during this period.

[0083] Centrifugation and drying: Take out the soaked sponge, put it into a sterile centrifuge basket, centrifuge at 800 rpm for 2 minutes; transfer it to a clean drying room and dry it at 40℃ for 5 hours (moisture content controlled at 8%-10%). Finally, package it on a sterile operating table to obtain the contraceptive sponge.

[0084] Example 3 Preparation of medical-grade highly cross-linked polyurethane foam Raw material ratio (by weight): 62 parts polyether polyol, 31 parts 4,4'-diphenylmethane diisocyanate, 3.5 parts trimethylolpropane, 4 parts dichloromethane, 0.15 parts stannous octoate, and 0.25 parts polydimethylsiloxane.

[0085] Preparation steps Drying treatment: The polyether polyol and trimethylolpropane were added to a vacuum drying tank and dried at 80°C and -0.09MPa vacuum for 2 hours to obtain a polyether polyol-TMP mixture.

[0086] MDI melting: 4,4'-diphenylmethane diisocyanate was heated to 40°C and stirred at 50 rpm to obtain molten MDI.

[0087] Prepolymerization reaction: The polyether polyol-TMP mixture is transferred into a prepolymerization reactor, protected by nitrogen gas, heated to 65°C, and molten MDI is added dropwise with stirring. After the addition is complete, the mixture is kept at 70°C for 1.5 hours to form a polyurethane prepolymer.

[0088] Preparation of foaming slurry: Transfer the polyurethane prepolymer into a foaming mixing tank, cool it to 50°C, and add stannous octoate, polydimethylsiloxane and dichloromethane in sequence while stirring. Stir for 10 minutes to form a uniform foaming slurry.

[0089] Gradient foaming: The foaming slurry is quickly injected into a stainless steel mold, and after the mold is closed, it is transferred to a constant temperature foaming chamber. The temperature gradient is set as follows: the first stage is 35℃ for 1 minute, the second stage is 55℃ for 5 minutes, and the third stage is 70℃ for 15 minutes. During the foaming process, the cavity pressure is controlled to be 0.12MPa by a pressure sensor.

[0090] Deep curing and degassing: After foaming, the mold is transferred to a curing oven and kept at 85°C for 4 hours; after curing, the sponge block is taken out and placed in a vacuum degassing tank and treated at -0.08MPa and 25°C for 1 hour to obtain the sponge precursor.

[0091] Purification and drying: Soak the sponge precursor in 70% ethanol solution for 1.5 hours to remove residual impurities; then transfer it to a clean drying room and dry it at 45°C until the moisture content is 3%.

[0092] Surface modification: The dried sponge precursor was immersed in a 4% (mass concentration) 3-aminopropyltriethoxysilane ethanol solution and soaked at 25°C for 1 hour; then it was dried in an 80°C oven for 2 hours to obtain medical-grade highly cross-linked polyurethane sponge.

[0093] Preparation of contraceptive sponges Preparation of spermicide solution: Add 4 parts glycerin, 0.2 parts citric acid, and 0.08 parts ethylparaben to 95.72 parts purified water and stir at 25°C for 15 minutes to form an excipient solution; add 96 parts nonoxynol ether and continue stirring for 30 minutes (ultrasonic aid, power 250W). Filter the solution through a 0.22μm polyethersulfone membrane to obtain the spermicide solution.

[0094] Sponge pretreatment: The above-mentioned medical-grade highly cross-linked polyurethane sponge body was soaked in purified water for 20 minutes and extruded using a reciprocating extruder (pressure 0.2MPa), and the soaking-extrusion was repeated 3 times; then it was transferred to a clean drying room and dried at 40℃ and RH 30% for 8 hours to obtain a dry sponge body with a water content of 3%.

[0095] Cutting and sterilization: The sponge body is cut according to product specifications (diameter 48mm, thickness 14mm) using a CNC laser cutting machine (power 40W), placed in a sterile tray, and sterilized by ultraviolet irradiation for 20 minutes (wavelength 254nm, intensity 80μW / cm²). 2 ).

[0096] Vacuum impregnation: Place the sterilized sponge body into a sterile impregnation tank, close the tank cover, evacuate to -0.08MPa, and maintain for 10 minutes; inject spermicide solution through a peristaltic pump (liquid level covering the sponge 4mm), restore normal pressure, let stand for 10 minutes, and shake the impregnation tank once every 5 minutes during this period.

[0097] Centrifugation and drying: Take out the soaked sponge, put it into a sterile centrifuge basket, centrifuge at 500 rpm for 1 minute; transfer it to a clean drying room and dry it at 30℃ for 3 hours (moisture content controlled at 8%-10%). Finally, package it on a sterile operating table to obtain the contraceptive sponge.

[0098] Example 4 Preparation of medical-grade highly cross-linked polyurethane foam Raw material ratio (by weight): 61 parts polyether polyol, 32 parts 4,4'-diphenylmethane diisocyanate, 4.2 parts trimethylolpropane, 4.8 parts dichloromethane, 0.22 parts stannous octoate, and 0.32 parts polydimethylsiloxane.

[0099] Preparation steps Drying treatment: The polyether polyol and trimethylolpropane were added to a vacuum drying tank and dried at 83°C and -0.096MPa vacuum for 2.2 hours to obtain a polyether polyol-TMP mixture.

[0100] MDI melting: 4,4'-diphenylmethane diisocyanate was heated to 43°C and stirred at 70 rpm to obtain molten MDI.

[0101] Prepolymerization reaction: The polyether polyol-TMP mixture is transferred into a prepolymerization reactor, protected by nitrogen gas, heated to 67°C, and molten MDI is added dropwise with stirring. After the addition is complete, the mixture is kept at 73°C for 1.7 hours to form a polyurethane prepolymer.

[0102] Preparation of foaming slurry: The polyurethane prepolymer is transferred to a foaming mixing tank, cooled to 53°C, and stannous octoate, polydimethylsiloxane and dichloromethane are added in sequence under stirring. Stir for 18 minutes to form a uniform foaming slurry.

[0103] Gradient foaming: The foaming slurry is quickly injected into a stainless steel mold, and after the mold is closed, it is transferred to a constant temperature foaming chamber. The temperature gradient is set as follows: the first stage is 37℃ for 4 minutes, the second stage is 57℃ for 12 minutes, and the third stage is 73℃ for 25 minutes. During the foaming process, the cavity pressure is controlled to be 0.14MPa by a pressure sensor.

[0104] Deep curing and degassing: After foaming, the mold is transferred to a curing oven and kept at 87°C for 5.5 hours; after curing, the sponge block is taken out and placed in a vacuum degassing tank and treated at -0.086MPa and 27°C for 1.6 hours to obtain the sponge precursor.

[0105] Purification and drying: The sponge precursor was soaked in 78% ethanol solution for 2.2 hours to remove residual impurities; then it was transferred to a clean drying room and dried at 52°C until the moisture content was 2.3%.

[0106] Surface modification: The dried sponge precursor was immersed in a 5.5% (mass concentration) 3-aminopropyltriethoxysilane ethanol solution and soaked at 27°C for 1.6 hours; then it was dried in an oven at 83°C for 2.6 hours to obtain medical-grade highly cross-linked polyurethane sponge.

[0107] Preparation of contraceptive sponges Preparation of spermicide solution: Add 5.5 parts glycerin, 0.35 parts citric acid, and 0.12 parts ethylparaben to 94.03 parts purified water, stir at 27°C for 17 minutes to form an excipient solution; add 99 parts nonoxynol ether, and continue stirring for 50 minutes (ultrasonic aid, power 320W). Filter the solution through a 0.22μm polyethersulfone membrane to obtain the spermicide solution.

[0108] Sponge pretreatment: The above-mentioned medical-grade highly cross-linked polyurethane sponge body was soaked in purified water for 28 minutes and extruded using a reciprocating extruder (pressure 0.35MPa), and the soaking-extrusion was repeated 4 times; then it was transferred to a clean drying room and dried at 47℃ and RH36% for 9.5 hours to obtain a dry sponge body with a water content of 2.6%.

[0109] Cutting and sterilization: The sponge body is cut according to the product specifications (diameter 52mm, thickness 15.5mm) using a CNC laser cutting machine (power 55W), placed in a sterile tray, and sterilized by ultraviolet irradiation for 35 minutes (wavelength 254nm, intensity 110μW / cm²).

[0110] Vacuum impregnation: Place the sterilized sponge body into a sterile impregnation tank, close the tank cover, evacuate to -0.087MPa, and maintain for 13 minutes; inject spermicide solution through a peristaltic pump (liquid level covering the sponge 5.5mm), restore normal pressure, and let stand for 13 minutes, shaking the impregnation tank once every 5 minutes during this period.

[0111] Centrifugation and drying: After soaking in the drug, the sponge was taken out and placed in a sterile centrifuge basket and centrifuged at 750 rpm for 1.6 minutes; then transferred to a clean drying room and dried at 38℃ for 4.5 hours (moisture content controlled at 8%-10%). Finally, it was packaged on a sterile operating table to obtain the contraceptive sponge.

[0112] Comparative Example 1 (without trimethylolpropane, no gradient foaming) Preparation of medical-grade polyurethane foam Raw material ratio (by weight): 60 parts polyether polyol, 33 parts 4,4'-diphenylmethane diisocyanate, 4.5 parts dichloromethane, 0.2 parts stannous octoate, and 0.3 parts polydimethylsiloxane. (Trimethylolpropane should be removed.) Preparation steps: Except for the "drying step without trimethylolpropane" and the "foaming stage using a constant temperature of 60°C for 30 minutes, without gradient heating, and pressure control at 0.13 MPa", the remaining steps are the same as in Example 1.

[0113] Preparation of contraceptive sponge: Same as in Example 1.

[0114] Comparative Example 2 (without surface modification treatment) Preparation of medical-grade highly cross-linked polyurethane foam: Except for "removing the surface modification step (i.e., not soaking and drying with 3-aminopropyltriethoxysilane)," the other raw material ratios and preparation steps are the same as in Example 1.

[0115] Preparation of contraceptive sponge: Same as in Example 1.

[0116] Comparative Example 3 (Traditional soaking and immersion in medicine, without vacuum treatment) Preparation of medical-grade highly cross-linked polyurethane foam: Same as in Example 1.

[0117] Preparation of contraceptive sponge: Except for "no vacuuming during the soaking stage, the sponge is directly immersed in the spermicide solution for 30 minutes without pressure difference to assist in penetration", the other steps are the same as in Example 1.

[0118] Performance tests were conducted on the sponges and contraceptive sponge products of Examples 1-4 and Comparative Examples 1-3. Test items included physical properties (pore size, connectivity, air permeability, mechanical properties), spermicide properties (loading capacity, distribution uniformity, activity retention rate, spermicidal effect), stability (hydrolysis resistance, swelling rate, small molecule residue), biocompatibility (cytotoxicity, sensitization, influence of lactobacilli), and actual usage effects (contraceptive success rate, comfort score). Test methods were all based on national standards or industry specifications. Specific test results and comparative analysis are as follows: I. Physical Performance Testing and Comparison Physical properties are the core foundation for contraceptive sponges to achieve physical barrier function. The main tests include pore size distribution, pore connectivity, air permeability, and mechanical properties (tensile strength, tear strength, and deformation recovery). The testing methods are as follows: Pore ​​size distribution: The cross-section of the sponge was observed using a scanning electron microscope (SEM, model ZEISS Sigma 300), and the pore size and distribution were statistically analyzed using Image-Pro Plus software; Pore ​​connectivity: Tested using mercury porosimetry (instrument AutoPore IV 9500), connectivity = (total pore volume - closed pore volume) / total pore volume × 100%; Air permeability: Refer to GB / T 5453-1997, and use an air permeability tester (model YG461E) to test at a pressure of 100Pa; Mechanical properties: Tensile strength and tear strength were tested using a universal testing machine (model Instron 5969) in accordance with GB / T 1040.3-2006; Deformation recovery rate test: The sponge was compressed to 50% deformation, held for 1 hour and then released. The thickness after recovery was measured after 30 minutes. Recovery rate = (Recovered thickness - Compressed thickness) / (Initial thickness - Compressed thickness) × 100%.

[0119] The physical performance test results are shown in Table 1: Table 1 Physical performance test results

[0120] Analysis of the results in Table 1 reveals that, regarding pore size and connectivity, the average pore size of Examples 1-4 is concentrated between 28-35 μm, all smaller than sperm length (50-60 μm), and the pore size distribution is uniform (range ≤20 μm), effectively blocking sperm penetration; the pore connectivity is over 95%, ensuring good air permeability. In contrast, Comparative Example 1, lacking trimethylolpropane (a crosslinking agent), had insufficient crosslinking density, resulting in a significantly increased pore size (average 55 μm) and numerous closed pores (connectivity only 72.3%), rendering both physical barrier and air permeability ineffective.

[0121] Regarding air permeability: the air permeability of Examples 1-4 is 7.8-9.2 mm / s, which is 49.2%-76.9% higher than that of Comparative Example 1 (5.2 mm / s). Comparative Example 2 only removed the surface modification, which did not affect the pore structure, and its air permeability is close to that of the Examples, indicating that the surface modification layer (50-100 nm) does not hinder gas flow.

[0122] Regarding mechanical properties: the tensile strength (1.8-2.2 MPa), tear strength (0.55-0.68 kN / m), and deformation recovery rate (90.2%-94.8%) of Examples 1-4 were significantly better than those of Comparative Example 1 (tensile strength 1.1 MPa, tear strength 0.32 kN / m, deformation recovery rate 65.8%). This is attributed to the highly cross-linked structure and deep curing process, ensuring that the sponge does not break or deform under vaginal compression. Comparative Example 2, because its cross-linked structure remained unchanged, showed little difference in mechanical properties compared to the Examples, further verifying that surface modification does not affect mechanical stability.

[0123] II. Performance Testing and Comparison of Spermicides The performance of spermicides directly determines their contraceptive effectiveness. The main tests performed on the spermicide (nonoxynol-9) included its loading amount, distribution uniformity, activity retention rate, and in vitro spermicidal effect. The test methods are as follows: Loading capacity: The content of nonoxynol-9 in the sponge was determined by high performance liquid chromatography (HPLC, model Agilent 1260). Loading capacity = total mass of nonoxynol-9 / volume of sponge; Distribution uniformity: The sponge was cut into 10 equal-volume pieces, and the spermicide content of each piece was measured. Uniformity = (average content of each piece - standard deviation) / average value × 100%; Viability retention rate: The sponge was stored at 40℃ and RH 75% for 3 months, and the activity of the spermicide before and after storage was measured (using a sperm survival test). Retention rate = activity after storage / activity before storage × 100%; In vitro spermicidal effect: Referring to the "In vitro activity test method for in vitro spermicides", the sponge extract and sperm suspension (concentration 1×10) were mixed. 7 Mix (number of sperm / mL), incubate at 37°C for 10 minutes, and observe sperm survival rate under a microscope. Sperm killing rate = (1 - number of surviving sperm / total number of sperm) × 100%.

[0124] The performance test results of the spermicide are shown in Table 2: Table 2. Results of Spermicidal Performance Tests

[0125] Analysis of the results in Table 2 reveals that, in terms of loading and uniformity, the spermicide loading in Examples 1-4 ranged from 2.2 to 14.5 mg / cm³. 3 The concentration was significantly higher than that of control example 1 (8.5 mg / cm³). 3 Comparative Example 3 (7.8 mg / cm³) 3 This is because the example uses a vacuum impregnation process (pressure difference promotes penetration) and sponge pretreatment (removes air from pores) to ensure that the drug solution fully fills the pores; at the same time, ultrasonic-assisted stirring and shaking after impregnation ensure that the spermicide distribution uniformity exceeds 97.8%, avoiding local spermicide loss. Comparative Example 3, due to the use of traditional soaking impregnation without vacuum assistance, has air in the pores hindering drug penetration, resulting in a low loading (7.8 mg / cm³). 3 Furthermore, the uniformity was poor (85.6%). In Comparative Example 1, although the load was partially increased due to the larger aperture, the uniformity was still lower than that of the Example (90.2%).

[0126] Regarding the activity retention rate: the activity retention rates of Examples 1-4 reached 92.8%-95.5%, significantly better than Comparative Example 2 (72.3%) and Comparative Example 1 (78.5%). The core reason is that the surface-modified layer (inert silane film) of the examples isolated the chemical reaction between the polyurethane amino group and nonoxynol-9, thus preventing the destruction of the spermicide molecules. Comparative Example 2, lacking surface modification, saw the amino groups in the sponge react with the spermicide, resulting in a significant decrease in the activity retention rate (72.3%).

[0127] Regarding the in vitro spermicidal effect: Examples 1-4 showed an in vitro spermicidal rate of over 99.6%, close to 100%, ensuring the elimination of all contacting sperm; while Comparative Example 2 had a spermicidal rate of only 88.3% due to decreased spermicidal activity; Comparative Example 1 had a spermicidal rate of 92.5% due to insufficient loading or reduced activity, posing a risk of sperm survival leading to contraceptive failure.

[0128] (III) Stability Testing and Comparison Stability determines the lifespan and safety of contraceptive sponges. The main tests include hydrolysis resistance (weight loss rate), swelling rate, small molecule residues (unreacted MDI, polyether polyols), and release agent residues. The test methods are as follows: Hydrolysis resistance and swelling rate: The sponge was soaked in simulated vaginal fluid (pH 4.2, containing mucin and lysozyme) and placed at 37°C for 30 days. Weight loss rate = (weight before soaking - weight after soaking) / weight before soaking × 100%; swelling rate = (volume after soaking - volume before soaking) / volume before soaking × 100%; Small molecule residues: The amount of unreacted MDI and polyether polyol residues in the sponge was determined by gas chromatography-mass spectrometry (GC-MS, Thermo TRACE 1310-ISQQD). Release agent residue: The amount of release agent (such as zinc stearate) remaining on the sponge surface was determined by high performance liquid chromatography (HPLC).

[0129] The stability test results are shown in Table 3.

[0130] Table 3. Stability Test Results

[0131] Analysis of the results in Table 3 reveals that, in terms of hydrolysis resistance and swelling rate, Examples 1-4, after being immersed in simulated vaginal fluid for 30 days, exhibited excellent hydrolysis resistance with a weight loss rate of only 2.2%-2.8% and a swelling rate of 16.2%-18.8%. This is attributed to the highly cross-linked structure (reducing the exposure of easily hydrolyzed groups) and the barrier effect of the inert silane film. Comparative Example 1, lacking a cross-linking agent, had a loose structure, resulting in a weight loss rate of 12.5% ​​and a swelling rate of 42.5%, making it prone to structural collapse. Comparative Example 2, without surface modification, had a slightly higher weight loss rate (3.1%) and swelling rate (18.2%) than the Examples, but significantly lower than Comparative Example 1. This indicates that the cross-linked structure is the core factor in hydrolysis resistance, and surface modification can further enhance stability.

[0132] Regarding small molecule residues: the unreacted MDI residues (0.007-0.009%) and polyether polyol residues (0.003-0.005%) in Examples 1-4 were far below the national standard (≤0.1%). This is because the examples employed a multi-step purification process including ethanol soaking and vacuum degassing, effectively removing residual impurities. Comparative Example 1, lacking deep curing and purification, showed a significant increase in small molecule residues (MDI 0.052%, polyether 0.038%). Comparative Example 3, changing only the soaking method, had small molecule residues similar to the examples, indicating that the soaking process does not affect the purification effect of the sponge itself.

[0133] Through comprehensive performance testing of Examples 1-4 and Comparative Examples 1-3, the following conclusions can be drawn: The present invention achieves a comprehensive performance breakthrough in contraceptive sponges by combining highly cross-linked component design, gradient foaming process, surface modification, and vacuum impregnation technology. The sponges exhibit reliable physical barrier properties, stable spermicidal effect, and excellent structural safety and durability. All indicators are significantly better than those of the comparative examples that did not use the technology of the present invention.

[0134] It should be understood that the application of the present invention is not limited to the examples above. Those skilled in the art can make improvements or modifications based on the above description, and all such improvements and modifications should fall within the protection scope of the appended claims.

Claims

1. A medical-grade highly cross-linked polyurethane foam, characterized in that, The medical-grade highly cross-linked polyurethane foam comprises the following components by weight: 58-62 parts polyether polyol, 31-35 parts 4,4'-diphenylmethane diisocyanate, 3.5-4.5 parts trimethylolpropane, 4-5 parts dichloromethane, 0.15-0.25 parts stannous octoate, and 0.25-0.35 parts polydimethylsiloxane.

2. The medical-grade highly cross-linked polyurethane foam according to claim 1, characterized in that, The polyether polyol is a propylene oxide type polyether polyol, and the number average molecular weight of the propylene oxide type polyether polyol is 2000-3000, and the functionality is 3.

3. The medical-grade highly cross-linked polyurethane foam according to claim 1, characterized in that, It also includes 0.08-0.12 parts of disodium ethylenediaminetetraacetate.

4. A method for preparing medical-grade highly cross-linked polyurethane foam as described in any one of claims 1-3, characterized in that, Including the following steps: The polyether polyol and trimethylolpropane were added to a vacuum drying tank and dried at 80-85°C and -0.09MPa to -0.1MPa vacuum for 2-3 hours to remove moisture from the raw materials, thus obtaining a polyether polyol-TMP mixture. 4,4'-diphenylmethane diisocyanate was heated to 40-45°C and stirred at 50-80 rpm to obtain molten MDI. The dried polyether polyol-TMP mixture was transferred into a prepolymer reactor, protected by nitrogen gas, and heated to 65-70°C. Molten MDI was added dropwise under stirring. After the addition was completed, the temperature was maintained at 70-75°C for 1.5-2 hours to form a polyurethane prepolymer. The polyurethane prepolymer is transferred to a foaming mixing tank and cooled to 50-55°C. Stannous octoate, polydimethylsiloxane, and dichloromethane are added sequentially under stirring to form a uniform foaming slurry. The foaming slurry is quickly injected into a customized stainless steel mold. After the mold is closed, it is transferred to a constant temperature foaming chamber. The temperature gradient is set as follows: the first stage is set at 35-40℃ and held for 1-5 minutes; the second stage is set at 55-60℃ and held for 5-15 minutes; the third stage is set at 70-75℃ and held for 15-30 minutes. During the foaming process, the pressure in the cavity is monitored by a pressure sensor on the mold and controlled to be maintained at 0.12-0.15MPa. After foaming, the stainless steel mold is transferred to a curing oven and kept at 85-90℃ for 4-6 hours for deep curing. The cured sponge block is then removed from the mold and placed in a vacuum degassing tank at -0.08 to -0.09 MPa and 25-30℃ for 1-2 hours to remove tiny closed air bubbles inside the sponge block and ensure that the pores are interconnected, thus obtaining a medical-grade highly cross-linked polyurethane sponge precursor. The medical-grade highly cross-linked polyurethane foam precursor was immersed in an ethanol solution to remove residual release agent and unreacted monomers from the surface, and then dried in a clean drying room until the moisture content was ≤3%. The dried medical-grade highly cross-linked polyurethane sponge precursor is immersed in a 3-aminopropyltriethoxysilane solution at 25-30°C for 1-2 hours, so that the hydroxyl groups on the surface of the sponge undergo a condensation reaction with the -Si-OH of the silane to form -Si-O- covalent bonds, thereby constructing an inert silane film with a thickness of 50-100nm on the surface of the sponge. The sponge with an inert silane film on its surface is placed in an oven at 80-85℃ and dried for 2-3 hours to completely cure the inert silane film and form a tightly adhered inert layer, thereby obtaining a medical-grade highly cross-linked polyurethane sponge.

5. An application of the medical-grade highly cross-linked polyurethane foam as described in any one of claims 1-3, characterized in that, The medical-grade highly cross-linked polyurethane sponge was used to prepare a contraceptive sponge.

6. The application according to claim 5, characterized in that, The contraceptive sponge is composed of the medical-grade highly cross-linked polyurethane sponge and a spermicide solution loaded in the medical-grade highly cross-linked polyurethane sponge. The spermicide solution is composed of an excipient solution and nonylbenzene alcohol ether-9 dissolved in the excipient solution.

7. The application according to claim 6, characterized in that, The excipient solution consists of glycerol, citric acid, ethylparaben, and purified water.

8. The application according to claim 6, characterized in that, The preparation of the contraceptive sponge includes the following steps: The medical-grade highly cross-linked polyurethane sponge body is immersed in purified water for 20-30 minutes, and then extruded using a reciprocating extruder to remove air and residual small molecule impurities from the sponge pores. The immersion-extrusion operation is repeated 3-5 times. The pretreated sponge block is placed in a clean drying room and dried for 8-10 hours at 40-50℃ and relative humidity ≤40% until the sponge moisture content is ≤3%, thus obtaining the dried sponge body. According to the design specifications of the contraceptive product, the dried sponge body is cut using a CNC laser cutting machine to obtain the contraceptive sponge body; Glycerin, citric acid, and ethylparaben were added to purified water and stirred at 25-30°C for 15-20 minutes to form a homogeneous excipient solution. Nonoxynol-9 was added to the excipient solution and stirred for another 30-60 minutes with ultrasonic assistance until the solution was clear and free of precipitate. The prepared solution was then filtered through a 0.22μm polyethersulfone microporous membrane to remove particulate impurities, yielding the spermicide solution. The contraceptive sponge body is placed in a sterile tray and sterilized by ultraviolet irradiation. The sterilized contraceptive sponge body is then placed in a sterile soaking tank, the tank lid is closed, and the vacuum system is activated to evacuate the tank to -0.08 to -0.09 MPa. This vacuum state is maintained for 10-15 minutes to remove air from the sponge pores. Subsequently, the prepared spermicide solution is injected into the soaking tank using a peristaltic pump. The solution level must completely cover the contraceptive sponge body. The vacuum system is then closed, and the pressure is restored to normal, allowing the solution to fully penetrate into the pores of the contraceptive sponge body under the pressure difference. After soaking, the contraceptive sponge body is left to stand in the solution for 10-15 minutes, during which the soaking tank is gently shaken once every 5 minutes to promote the uniform distribution of the solution in the sponge pores and ensure that the sponge is saturated with the solution. After absorbing the drug solution, the contraceptive sponge body is removed from the soaking tank and placed in a sterile centrifuge basket. It is then centrifuged for 1-2 minutes using a low-speed centrifuge with a rotation speed of 500-800 rpm to remove any residual drug solution from the sponge surface. In a clean drying room, the contraceptive sponge body after being soaked in medicine is dried and shaped at low temperature, and finally packaged in a sterile operating table to obtain the contraceptive sponge.

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