Peristomal skin protection film, method of preparation and use thereof

Abstract

The application discloses a peristomal skin protection film, a preparation method and application thereof, and is characterized in that an acrylate-polyurethane copolymer is used as a film-forming matrix, surface-modified zinc oxide nanoparticles, vitamin E acetate and sodium hyaluronate are added, and an ethanol-ethyl acetate mixed solvent is used to prepare a coating solution, and the film is formed after 30-60 s of coating, the film thickness is 5-15 um, the water washing resistance is greater than 24 h, the excrement blocking rate is greater than 95%, the film has the functions of antibiosis, antioxidation and moisturizing repair, and the peristomal dermatitis incidence is effectively reduced.

Description

Technical Field

[0001] This invention belongs to the field of medical polymer materials and stoma care technology, specifically relating to a protective film composition for the skin around the stoma, a method for preparing the protective film, and its application in the protection of the skin around patients with enterostomies and urostomies. Background Technology

[0002] Enterostomy and urostomy are common surgical procedures in clinical practice, with approximately 2 million new stoma patients worldwide each year. After stoma surgery, the skin around the stoma is chronically exposed to the corrosive environment of fecal matter, urine, and other excrement. The digestive enzymes, bile salts, bacterial metabolites in these excrement, and ammonia produced from the decomposition of urea in urine, among other irritating substances, continuously damage the stratum corneum barrier function, leading to an incidence of irritant contact dermatitis as high as 30% to 40%. Furthermore, the mechanical damage caused by repeated application and removal of the ostomy bag baseplate, skin softening due to moisture maceration, and fungal infections further exacerbate the occurrence of peristomal skin complications.

[0003] Currently, commonly used methods for peristaltic skin protection in clinical practice mainly include three categories: petrolatum-based oily protective agents, hydrocolloid skin barrier powders, and alcohol-based skin protective films. While petrolatum and other oily protective agents have good moisturizing effects, their film-forming properties are poor, and the film adhesion is low, making them easily washed away by excrement. The actual protective duration is usually no more than 4 hours, which is insufficient to meet the long-term protection needs of ostomy patients. Hydrocolloid barrier powders can absorb small amounts of exudate and form a colloidal protective layer on the skin surface, but their water resistance is insufficient. They swell and fail rapidly when exposed to large amounts of fecal matter, and long-term use carries the risk of worsening local maceration. Existing alcohol-based skin protective films, although forming films relatively quickly, mostly use single polymers such as acrylic homopolymers or polyvinylpyrrolidone as the film-forming matrix. The resulting film has defects such as insufficient flexibility, poor skin adhesion, and weak water erosion resistance. Furthermore, high concentrations of ethanol cause significant irritation and burning sensations to the already damaged peristaltic skin, resulting in low patient compliance.

[0004] From the perspective of polymer materials science, the core bottleneck of existing skin protective films lies in the fact that the molecular structure design of the film-forming polymers fails to simultaneously meet the multiple conflicting performance requirements for peristomal skin protection. High water resistance requires polymers with high glass transition temperatures and dense chain segment stacking structures, but this inevitably leads to insufficient film flexibility and poor skin adhesion. High flexibility requires polymers with low glass transition temperatures and long flexible segments, but this reduces the film's water resistance and mechanical strength. Traditional acrylic homopolymers or copolymer systems struggle to reconcile these contradictions, as their linear chain structures cannot simultaneously provide both flexibility and water resistance—two opposing properties. Furthermore, most existing protective film products only possess physical barrier functions, lacking active protective functions such as antibacterial, anti-inflammatory, and repair-promoting effects tailored to the specific pathological environment of peristomal skin, making it difficult to fundamentally prevent and treat peristomal dermatitis.

[0005] In recent years, polyurethane polymers have attracted widespread attention in the field of medical dressings due to their excellent biocompatibility and tunable mechanical properties. However, a technical solution combining polyurethane and acrylate through copolymerization for rapid film formation and protection of the skin around stomas has not yet been reported. The urethane groups in the polyurethane segments can form a strong hydrogen bond network, endowing the film with high water resistance, while the designability of the acrylate segments allows for precise control of the film's flexibility and skin adhesion through monomer selection and ratio adjustment. Furthermore, the copolymerization of these two polymers can form a microphase-separated structure, achieving compatibility between flexibility and water resistance at the molecular level, providing a novel materials science approach to resolving the aforementioned technical contradictions.

[0006] Therefore, developing a protective film formulation that combines excellent film-forming properties, high water erosion resistance, good skin adhesion and flexibility, and no irritation to damaged skin around the stoma is of great clinical significance for reducing the incidence of peristomal dermatitis and improving the quality of life of stoma patients. Summary of the Invention

[0007] To address the technical problems of existing peristomal skin protection technologies, such as poor film-forming properties, insufficient water erosion resistance, poor flexibility and adhesion, and high irritation to damaged skin, the present invention aims to provide a peristomal skin protection film composition, its preparation method, and its application. This protective film uses acrylate-polyurethane copolymer as the film-forming matrix, and is combined with functional additives such as nano zinc oxide, vitamin E acetate, and sodium hyaluronate. It can quickly form a transparent, flexible, and highly water-resistant protective film layer on the peristomal skin surface, effectively blocking the erosion of excrement on the skin, while providing antibacterial, antioxidant, moisturizing, and repairing functions.

[0008] To achieve the above objectives, the present invention adopts the following technical solution: The first aspect of this invention provides a peristomal skin protective film, comprising a film-forming matrix and functional additives, wherein the film-forming matrix is ​​an acrylate-polyurethane copolymer with a weight-average molecular weight of 80,000 to 150,000 Da and a glass transition temperature of -10 to 5 °C; the functional additives comprise zinc oxide nanoparticles, vitamin E acetate, and sodium hyaluronate; based on the total mass of the coating liquid, the solid content of the acrylate-polyurethane copolymer is 15% to 25%, the content of zinc oxide nanoparticles is 3% to 8%, the content of vitamin E acetate is 0.5% to 2%, and the content of sodium hyaluronate is 0.1% to 0.5%; the solvent system of the coating liquid is a mixture of ethanol and ethyl acetate.

[0009] The second aspect of the present invention provides a method for preparing the above-mentioned peristomal skin protective film, comprising the following steps: adding an acrylate-polyurethane copolymer to a mixed solvent of ethanol and ethyl acetate, stirring and dissolving at 40 to 60 °C until completely transparent to obtain a film-forming matrix solution; dispersing zinc oxide nanoparticles, which have been pre-treated with a silane coupling agent for surface modification, in a small amount of ethanol to prepare a dispersion, adding it to the film-forming matrix solution for ultrasonic dispersion; sequentially adding vitamin E acetate and sodium hyaluronate, and continuing to stir until uniform to obtain a coating solution; and filling the coating solution into a brush-equipped applicator or a spray bottle.

[0010] A third aspect of the present invention provides the use of the above-mentioned peristomal skin protective film in the preparation of peristomal skin protective products.

[0011] The beneficial effects of this invention are as follows: Using an acrylate-polyurethane copolymer as the film-forming matrix, the acrylate segments provide flexibility and van der Waals adhesion to the stratum corneum of the skin, while the urethane groups in the polyurethane segments enhance the cohesive strength and water resistance of the film through hydrogen bonding. The microphase separation structure formed by the copolymerization of these two components gives the film both high flexibility and high water resistance. Nano-zinc oxide, after surface modification with a silane coupling agent, exhibits good interfacial compatibility with the copolymer matrix, providing antibacterial and astringent functions without affecting the film's transparency. Vitamin E acetate and sodium hyaluronate synergistically protect the damaged skin around the stoma from two dimensions: antioxidant repair and moisturizing and water-locking, respectively. The synergistic volatility of the ethanol and ethyl acetate mixed solvent system allows the coating solution to form and dry within 30 to 60 seconds after application. The resulting protective film has a thickness of 5 to 15 μm, a transparency greater than 90%, and withstands continuous flushing by fecal water and urine for more than 24 hours. It also exhibits a barrier rate of more than 95% against excrement. Clinical application can reduce the incidence of peristoma dermatitis from 35% to below 8%. Attached Figure Description

[0012] Figure 1 This is a scanning electron microscope image of the cross-section of the protective film in Embodiment 1 of the present invention.

[0013] Figure 2 This is a bar chart comparing the resistance of the protective films of various embodiments of the present invention to continuous flushing time with simulated sewage with those of the comparative examples.

[0014] Figure 3 This is a photograph of the inhibition zone test results of the protective film of Example 1 of the present invention against four pathogenic microorganisms.

[0015] Figure 4 Tensile stress-strain curves of acrylate-polyurethane copolymer protective films with different weight-average molecular weights.

[0016] Figure 5 This is a photograph of the static water contact angle measurement on the surface of the protective film in Embodiment 1 of the present invention.

[0017] Figure 6 This is a comparison chart of the incidence of peristomal dermatitis and DET scores between the experimental group and the control group in a clinical controlled study. Detailed Implementation

[0018] The technical solution of the present invention will be described in detail below with reference to specific embodiments. It should be understood that the following embodiments are for illustrative purposes only and are not intended to limit the scope of protection of the present invention. Unless otherwise stated, the reagents and materials used in the following embodiments are commercially available analytical grade or medical grade products.

[0019] The acrylate-polyurethane copolymer of this invention is prepared by a two-step method. The first step is the synthesis of the polyurethane prepolymer: polytetrahydrofuran diol (number average molecular weight 2000 Da) and isophorone diisocyanate are added to a four-necked flask equipped with a mechanical stirrer, thermometer, and nitrogen protection device at a molar ratio of 1:2, and reacted at 80 °C for 3 h to obtain an isocyanate-terminated polyurethane prepolymer. The second step is a free radical copolymerization reaction: butyl acrylate, methyl methacrylate, and hydroxyethyl acrylate are mixed at a mass ratio of 60:30:10, and then blended with the polyurethane prepolymer at a mass ratio of 70:30. Azobisisobutyronitrile (AIB) is used as an initiator (0.5% to 1.5% of the total monomer mass), and solution polymerization is carried out in ethyl acetate solvent at 70 to 75 °C for 6 to 8 h. After the reaction, the solvent is recovered by vacuum distillation to obtain the acrylate-polyurethane copolymer. By adjusting the feed ratio of polyurethane prepolymer to acrylate monomer and the amount of initiator, the weight-average molecular weight of the copolymer can be precisely controlled within the range of 80,000 to 150,000 Da, and the molecular weight distribution coefficient determined by gel permeation chromatography is 1.8 to 2.5. The glass transition temperature of the copolymer is determined by differential scanning calorimetry within the range of -10 to 5 °C. This temperature range allows the copolymer to remain in a highly elastic state at room temperature, enabling it to adhere closely to the skin's microstructure after application. This prevents the film from becoming brittle and cracking due to excessively low temperatures, nor from becoming excessively fluid due to excessively high temperatures.

[0020] The butyl acrylate component in the acrylate segments provides the membrane with the necessary flexibility and low-temperature suppleness. Its long side-chain structure imparts excellent internal plasticizing effect to the polymer, avoiding the potential skin irritation risk of external plasticizers. The introduction of the methyl methacrylate component enhances the mechanical strength and hardness of the membrane, preventing excessive deformation under the friction of the ostomy bag base. The hydroxyl side chains provided by the hydroxyl acrylate component serve as chemical linking points with the isocyanate groups at the ends of the polyurethane prepolymer, enabling block copolymerization. Furthermore, they enhance the hydrogen bonding interactions between the membrane and skin surface proteins and lipid molecules, improving the membrane's adhesion to the skin. The abundant urethane groups in the polyurethane segments form a physical cross-linking network through inter-segment hydrogen bonds. This cross-linking network endows the membrane with excellent cohesive strength and dimensional stability. Simultaneously, the polarity of the urethane groups provides a moderate surface energy (38 to 42 mN / m), allowing for sufficient contact with hydrophilic skin surfaces while also providing some repulsion against aqueous excretions. The thermodynamic incompatibility between the acrylate soft segments and the polyurethane hard segments in the copolymer drives the formation of microphase separation structures, such as Figure 1 As shown, the scanning electron microscope image of the protective film cross-section clearly shows the microstructure of nano-zinc oxide particles uniformly dispersed in the continuous polymer phase in the copolymer matrix. The film cross-section is dense without obvious pores and defects, and the thickness is uniform at about 10 μm. The soft segment enriched phase provides flexibility, while the hard segment enriched phase provides water resistance and mechanical strength. The two phases work together to enable the protective film to maintain high flexibility and adhesion while having excellent water erosion resistance.

[0021] Surface modification of zinc oxide nanoparticles is a crucial step in ensuring their uniform dispersion in organic solvent systems and their good interfacial bonding with the copolymer matrix. Medical-grade zinc oxide nanoparticles with an average particle size of 20 to 50 nm were selected. First, they were vacuum-dried at 110 °C for 2 h to remove surface adsorbed water. Then, the dried nanoparticles were dispersed in ethanol, and 2% to 5% (by mass) of gamma-methacryloyloxypropyltrimethoxysilane coupling agent was added. The mixture was stirred at 60 °C for 4 h, centrifuged, washed three times with anhydrous ethanol, and vacuum-dried at 60 °C to obtain surface-modified zinc oxide nanoparticles. The methoxysilane group at one end of the silane coupling agent molecule undergoes a condensation reaction with the hydroxyl groups on the zinc oxide surface to form a covalent bond, while the methacryloyl group at the other end can physically entangle or chemically graft with the acrylate segments during copolymer film formation. This achieves anchoring and dispersion of the nanoparticles in the polymer matrix, preventing agglomeration caused by van der Waals forces. The modified zinc oxide nanoparticles exhibited significantly improved dispersion stability in a mixed solvent of ethanol and ethyl acetate, with no obvious sedimentation observed after standing at room temperature for 72 h.

[0022] Zinc oxide nanoparticles perform multiple functions in the protective membrane: their antibacterial activity stems from the reactive oxygen species released by nano-zinc oxide in a slightly humid environment, which synergistically disrupt the integrity of bacterial cell membranes with zinc ions. The minimum inhibitory concentrations against Staphylococcus aureus and Candida albicans are 0.8 mg / mL and 1.2 mg / mL, respectively, effectively preventing infectious dermatitis around the stoma caused by bacterial and fungal infections. Their astringent function involves zinc ions reacting with skin surface proteins to form insoluble protein zinc salts, creating a dense protein coagulation layer on the surface of micro-damaged skin, reducing exudate production and promoting wound healing. While the refractive index of zinc oxide nanoparticles (2.0) differs from that of the copolymer matrix (1.48 to 1.52), the nanoparticle size is much smaller than the visible light wavelength (400 to 700 nm), resulting in extremely weak light scattering. When the content is controlled below 8%, the visible light transmittance of the protective membrane remains above 88%, without affecting clinical observation of the stoma and surrounding skin condition.

[0023] Vitamin E acetate, as a fat-soluble antioxidant, slowly releases active vitamin E (alpha-tocopherol) through hydrolysis by esterases on the skin surface after the protective film is applied. Alpha-tocopherol then quenches the free radical chain reaction induced by excretion stimulation, inhibiting lipid peroxidation damage to keratinocytes and maintaining cell membrane integrity. Simultaneously, vitamin E promotes the synthesis of collagen and elastin by dermal fibroblasts, accelerating the tissue repair process of damaged skin around the stoma. Vitamin E acetate exhibits good solubility in the copolymer matrix and does not affect the film's transparency or mechanical properties.

[0024] Sodium hyaluronate is a natural moisturizing factor analogue. Its molecular structure contains numerous carboxyl and N-acetyl groups that can bind to water molecules 500 to 1000 times their own mass via hydrogen bonding, creating a hydrating and moisturizing microenvironment between the protective film and the skin. This prevents dryness and cracking of the skin around the stoma due to compensatory transepidermal water loss caused by prolonged immersion in excrement. This invention uses medium molecular weight sodium hyaluronate with a molecular weight of 100,000 to 300,000 Da. Sodium hyaluronate in this molecular weight range can form an effective moisturizing film on the skin surface without causing excessive viscosity due to a high molecular weight, which would affect the spraying performance of the coating solution. The sodium hyaluronate content is controlled within the range of 0.1% to 0.5%. Below 0.1%, the moisturizing effect is not significant; above 0.5%, the viscosity of the coating solution increases, affecting the uniformity of film formation.

[0025] The design of the solvent system is a crucial factor determining the film-forming speed and final film quality of the coating solution. This invention employs a mixed solvent system of ethanol and ethyl acetate at a mass ratio of 50:50 to 70:30. Ethanol has a boiling point of 78.3 °C, and ethyl acetate has a boiling point of 77.1 °C. Their vapor pressures at room temperature are 5.95 kPa and 9.73 kPa, respectively. The synergistic evaporation effect of the mixture allows the coating solution to complete solvent evaporation and film drying within 30 to 60 seconds after application to the skin surface. Compared to a pure ethanol solvent system, the introduction of the mixed solvent offers the following technical advantages: ethyl acetate has a better solubility for acrylate-polyurethane copolymers than ethanol, allowing the coating solution to achieve the required film thickness with a lower solids content, thus reducing the skin irritation caused by ethanol; the higher vapor pressure of ethyl acetate accelerates solvent evaporation, shortening the time the skin is exposed to the solvent, further reducing the irritation caused by the solvent. The preferred mass ratio of ethanol to ethyl acetate is 60:40. Under this ratio, the viscosity of the coating solution is moderate (5 to 15 mPa·s), the coating uniformity is good, and the film formation time is about 40 to 50 s.

[0026] Example 1 provides a preferred embodiment of the present invention. The peristomal skin protective film coating solution was prepared according to the following steps: 20 g of acrylate-polyurethane copolymer (weight average molecular weight 120,000 Da, glass transition temperature -2 °C) was weighed and added to a mixed solvent consisting of 48 g of ethanol and 32 g of ethyl acetate. The mixture was magnetically stirred in a 50 °C water bath for 2 h until the copolymer was completely dissolved, forming a transparent and homogeneous film-forming matrix solution. Separately, 5 g of zinc oxide nanoparticles (average particle size 30 nm) modified with gamma-methacryloyloxypropyltrimethoxysilane were pre-dispersed in 10 g of anhydrous ethanol and ultrasonically treated for 15 min using a probe-type ultrasonic generator (power 200 W, frequency 20 kHz) to obtain a uniform nano-dispersion. This dispersion was slowly added to the above film-forming matrix solution, and ultrasonic dispersion treatment was continued for 10 min. Then, 1.0 g of vitamin E acetate and 0.3 g of sodium hyaluronate (molecular weight 200,000 Da) were added sequentially, and the mixture was stirred at room temperature for 30 min until completely dissolved and uniformly dispersed. The final coating solution has a solid content of approximately 20%, is a milky white semi-transparent liquid, and has a viscosity of approximately 10 mPa·s. After filtering the coating solution through a 0.45 μm filter membrane, it is filled into 50 mL application bottles equipped with brush heads and stored in a cool, dry place in a sealed container.

[0027] The protective film prepared in Example 1 was subjected to performance testing. The coating solution was uniformly applied to the inner forearm skin of healthy volunteers at a concentration of approximately 0.5 mg / cm², and allowed to dry naturally at 25 °C and 50% relative humidity. Film-forming time measurements showed that the film was no longer sticky to the touch after 42 seconds of application, and the complete drying time was 55 seconds. The thickness of the dried protective film, measured by a thin film thickness gauge, was 8 to 12 μm. It was transparent with a light transmittance of 92.3%. Mechanical property testing was performed on the protective film using a universal testing machine. The tensile strength was 18.5 MPa, and the elongation at break was 380%, indicating that the protective film possesses excellent flexibility and extensibility, capable of stretching and contracting synchronously with the natural movement and deformation of the skin without cracking or peeling.

[0028] The water erosion resistance test was conducted using a simulated stoma excrement erosion experiment. Simulated fecal solutions (containing 0.1% trypsin, 0.5% ox bile salts, and 0.9% sodium chloride, pH 7.8 to 8.2) and simulated urine solutions (containing 2% urea, 0.9% sodium chloride, and 0.1% creatinine, pH 5.5 to 6.5) were prepared and continuously rinsed onto detached pigskin samples coated with a protective film at a flow rate of 0.5 mL / min. The results of the simulated fecal erosion experiment showed that the protective film remained intact without peeling after 28 hours of continuous rinsing, with a film thickness retention rate of 82.7% and a 96.3% barrier rate against trypsin in the simulated fecal solution. The results of the simulated urine erosion experiment showed that the protective film remained intact after 36 hours of continuous rinsing, with a film thickness retention rate of 89.5% and a 95.8% barrier rate against urea. These results indicate that, as Figure 2 As shown, the water erosion resistance of the protective film of the present invention is far superior to that of traditional petrolatum-based protective agents (which are completely washed away after 4 hours) and existing acrylic homopolymer protective films (which show obvious peeling after 12 hours of washing). The erosion resistance times of Examples 1 to 3 are more than 28 hours, 24 hours and 36 hours, respectively, while that of Comparative Example 1 is only 8 hours.

[0029] Example 2 provides another implementation scheme to verify the effect of component ratio on the performance of the protective film. The preparation process is the same as in Example 1, but the amounts of each component are adjusted as follows: 15 g of acrylate-polyurethane copolymer (weight average molecular weight 100,000 Da, glass transition temperature 0 °C), 50 g of ethanol and 35 g of ethyl acetate in the mixed solvent, 3 g of modified zinc oxide nanoparticles, 0.5 g of vitamin E acetate, and 0.1 g of sodium hyaluronate. The liquid-solid content of the coating is approximately 15%, the film-forming time is 35 s, the protective film thickness is 5 to 8 μm, the light transmittance is 95.1%, the tensile strength is 12.8 MPa, the elongation at break is 450%, the simulated fecal flushing tolerance time is 24 h, and the barrier effect is 95.2%. The protective film formed by this implementation scheme is thinner and more transparent, suitable for patients with good periostomy skin who only require daily preventive protection.

[0030] Example 3 provides an implementation scheme for a high-concentration functional additive, suitable for reparative protection of the skin around the stoma with mild inflammation. The amounts of each component are as follows: 25 g of acrylate-polyurethane copolymer (weight average molecular weight 150,000 Da, glass transition temperature -5 °C), 42 g of ethanol and 28 g of ethyl acetate in the mixed solvent, 8 g of modified zinc oxide nanoparticles, 2.0 g of vitamin E acetate, 0.5 g of sodium hyaluronate, and 0.3 g of allantoin as an auxiliary repair component. The coating has a liquid-solid content of approximately 25%, a film-forming time of 58 s, a protective film thickness of 12 to 15 μm, a light transmittance of 88.2%, a tensile strength of 22.3 MPa, an elongation at break of 310%, a simulated fecal flushing tolerance time of more than 36 h, and a barrier efficiency of 97.8%. The high content of zinc oxide nanoparticles and vitamin E acetate in this solution significantly enhances antibacterial, anti-inflammatory, and skin repair functions. The addition of allantoin further promotes epithelial cell regeneration, making it suitable for therapeutic protection of the peristomal skin in patients with mild dermatitis symptoms such as erythema and erosion.

[0031] Comparative Example 1 used pure butyl acrylate homopolymer (molecular weight 100,000 Da) instead of acrylate-polyurethane copolymer as the film-forming matrix, with the remaining components and amounts the same as in Example 1. Test results showed that although the formed protective film had good flexibility (elongation at break 520%), its water erosion resistance was significantly reduced. Simulated sewage flushing resulted in large-area swelling and peeling of the film layer after only 8 hours, with the barrier efficiency dropping to 72.5%. This is because the butyl acrylate homopolymer lacks the hydrogen-bonded crosslinking network of polyurethane segments, resulting in insufficient cohesive strength within the film layer. Water molecules easily penetrate the membrane layer through the polymer's free volume, causing swelling.

[0032] Comparative Example 2 used unmodified zinc oxide nanoparticles instead of the modified nanoparticles, with all other conditions the same as in Example 1. Test results showed that a noticeable white precipitate appeared within 2 hours of coating preparation. The zinc oxide nanoparticles rapidly aggregated and settled due to incompatibility between their surface polarity and the organic solvent system. The protective film formed after a forced coating exhibited localized white spots and opaque areas, with a light transmittance of only 68.3%. Furthermore, the film's mechanical properties were uneven, and early cracking occurred in localized areas due to stress concentration points caused by nanoparticle agglomerates.

[0033] Comparative Example 3 used pure ethanol as the solvent instead of the ethanol-ethyl acetate mixed solvent system, with all other conditions the same as in Example 1. Because the acrylate-polyurethane copolymer has low solubility in pure ethanol, the solid content needed to be reduced to 10% to obtain a uniform solution, resulting in insufficient single-coat amount to form a film layer meeting the required protective thickness. To achieve the same film thickness, repeated coating 3 to 4 times was required, significantly prolonging the coating operation time and increasing the skin's exposure time to ethanol. Volunteers reported a significant increase in burning sensation scores during the coating process.

[0034] Example 4 provides an implementation scheme for a spray-type coating liquid. Based on Example 1, the solvent ratio and solid content were adjusted to meet the requirements of aerosol can spray packaging. The amounts of each component are as follows: 12 g of acrylate-polyurethane copolymer (weight average molecular weight 100,000 Da, glass transition temperature -3 °C), 56 g of ethanol and 32 g of ethyl acetate in the mixed solvent, 4 g of modified zinc oxide nanoparticles, 0.8 g of vitamin E acetate, and 0.2 g of sodium hyaluronate. The coating liquid has a solid content of approximately 12% and a viscosity reduced to 3 to 5 mPa·s, suitable for atomization and spraying through the valve system of the aerosol can. A butane-propane mixture is used as the propellant (propellant to coating liquid mass ratio of 30:70), and the coating liquid is filled into an aluminum aerosol can. When using, shake well and spray from a distance of 10 to 15 cm from the skin surface. The spray droplets automatically spread and converge to form a film on the skin surface, with a film formation time of 25 to 35 seconds. After drying, the film thickness is 5 to 8 μm. Spray-type protective film is particularly suitable for patients with deep stomas or skin folds and depressions around the stoma that make brush application inconvenient. The spray can evenly cover the irregular skin surface and avoids the risk of cross-contamination during the operation by eliminating the need for direct skin contact.

[0035] The antibacterial properties of the protective films of each embodiment were systematically evaluated. The antibacterial activity of the protective films against common pathogenic microorganisms of the peristomal skin was determined using the agar plate diffusion method and the minimum inhibitory concentration (MIC) method in liquid culture. Test strains included Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, and Candida albicans ATCC 10231. The coating solutions of each embodiment were aseptically spread onto 6 mm diameter filter paper discs, allowed to dry naturally, and then placed on Mueller-Hinton agar plates inoculated with 10⁸ CFU / mL bacterial suspension. After incubation at 37 °C for 24 h, the diameter of the inhibition zone was measured. The protective film of Example 1 showed an inhibition zone diameter of 15.3 mm against Staphylococcus aureus, 12.8 mm against Escherichia coli, 11.5 mm against Pseudomonas aeruginosa, and 13.2 mm against Candida albicans. Figure 3 As shown, all four strains formed well-defined, transparent inhibition zones on agar plates, demonstrating good broad-spectrum antibacterial activity. Example 3, containing a higher concentration of zinc oxide nanoparticles (8%), exhibited an even larger inhibition zone diameter of 18.7 mm (Staphylococcus aureus) and 16.5 mm (Candida albicans), making it more suitable for peristaltic skin protection in areas with a risk of microbial infection.

[0036] The skin compatibility and safety of the protective film were evaluated through in vitro cytotoxicity assays and human closed patch assays. In vitro experiments used the CCK-8 assay to evaluate the cytotoxicity of the film-forming solution to human immortalized keratinocytes (HaCaT). The film-forming solution was serially diluted with culture medium to 1:10, 1:50, 1:100, and 1:500 and then added to 96-well plates to co-culture with HaCaT cells for 48 h. Cell viability was measured at each concentration. The results showed that the cell viability of the film-forming solution in Example 1 was 93.7% at a 1:50 dilution and 97.2% at a 1:100 dilution, both significantly higher than the 70% biosafety threshold specified in ISO 10993-5, indicating that the protective film composition had no significant toxicity to skin cells. Human closed patch assays were performed on the inner forearm of 30 healthy volunteers. The film-forming solution was applied to a 2 cm diameter skin area and then sealed with a Finn Chamber for 48 h. Skin reactions were observed at 1 h, 24 h, and 48 h after removal. The results showed that no adverse reactions such as erythema, papules, or vesicles occurred in any of the subjects, and the skin irritation index was 0.03 (out of a maximum of 4.0), which is considered non-irritating. Individual analysis of 10 subjects with a history of sensitive skin also showed no significant adverse reactions, confirming that the protective film of this invention has good safety and tolerability for sensitive and damaged skin.

[0037] To verify the clinical efficacy of the protective film, a prospective controlled study was conducted at the stoma clinic of a tertiary hospital. 120 patients 3 to 12 months post-enterostomy were included and randomly assigned to an experimental group (n=60, using the protective film of Example 1 of this invention) and a control group (n=60, using a commercially available alcohol-based acrylic skin protective film). The observation period was 12 weeks. The primary endpoint was the incidence and severity score of peristomal dermatitis (using the DET score, a peristaltic skin assessment tool with a maximum score of 15, where higher scores indicated more severe skin lesions). Secondary endpoints included the duration of single-use of the protective film, patient comfort visual analog scale (VAS score, 0 to 10), and patient quality of life questionnaire score. Results showed that, as Figure 6 As shown, the total incidence of peristomal dermatitis in the experimental group at 12 weeks was 6.7% (4 / 60), significantly lower than 31.7% (19 / 60) in the control group, with a statistically significant difference (P < 0.01). The mean DET score in the experimental group was 1.2, while that in the control group was 4.8. Figure 6 The columnar contrast clearly reflects that the experimental group was significantly better than the control group in both the incidence of dermatitis and the severity of skin damage. Regarding the duration of a single application of the protective film, the experimental group averaged 28.5 hours, while the control group averaged 14.2 hours, meaning the experimental group's continuous protection time was approximately twice that of the control group. The patient comfort VAS score was 8.3 points in the experimental group and 5.7 points in the control group. Patients in the experimental group showed significantly higher satisfaction with the application and wearing comfort of the protective film compared to the control group. The main advantages were the absence of burning sensation during application, the soft and non-tight film layer, and the transparency, which did not interfere with stoma observation.

[0038] The controllable removability of the protective film is also an important factor affecting the convenience of clinical use. Although the protective film of this invention has excellent resistance to erosion by excrement, it can be gently dissolved and removed with a medical adhesive remover (the main components of which are isoparaffins or siloxane solvents). The removal process does not require vigorous wiping or tearing, and does not cause secondary damage to the already fragile skin around the stoma. There is no residue on the skin surface after removing the old film layer, allowing for direct reapplication of the new protective film or attachment of the ostomy bag baseplate without affecting the adhesion of the ostomy bag. The protective film can also be removed along with the baseplate when changing the ostomy bag, simplifying daily care procedures. In repeated application and removal cycle experiments, after 7 consecutive days of daily application-use-24 h-removal-reapplication cycles on the same skin area, there was no statistically significant difference in skin barrier function indicators (transepidermal water loss rate and stratum corneum moisture content) compared to baseline values, confirming that long-term repeated use of the protective film does not impair skin barrier function.

[0039] Accelerated and long-term stability tests were conducted on the coating solution. Accelerated stability testing was performed at 40 °C and 75% relative humidity for 6 months, while long-term stability testing was conducted at 25 °C and 60% relative humidity for 24 months. Sampling was taken at each time point to test key quality indicators of the coating solution, including appearance, viscosity, solid content, zinc oxide content, film-forming time, and mechanical properties of the protective film. The accelerated stability test results showed that after 6 months of storage at 40 °C, the coating solution showed no significant change in appearance, a viscosity change rate of less than 8%, a solid content change rate of less than 2%, and both film-forming time and tensile strength of the protective film were within the specified range. All indicators met the quality standards for medical coating solutions. The long-term stability test showed that all time points within the 24-month observation period met the quality standards, indicating that the coating solution has a shelf life of at least 24 months under normal temperature storage conditions. The coating solution exhibits better stability when stored at 2 to 8 °C, with all indicators showing lower change rates than under accelerated and normal temperature conditions. It is recommended to store the solution in a cool place after use for optimal user experience.

[0040] The compatibility between the protective film and the ostomy bag baseplate is a key factor affecting clinical usability. This invention systematically evaluates the adhesion compatibility of the protective film with commercially available ostomy bag baseplates from mainstream brands. Three representative ostomy bag baseplate products (hydrocolloid baseplate, microporous baseplate, and malleable baseplate) were selected, and their adhesion forces were compared on the surfaces of excised pigskin coated with the protective film of this invention and blank excised pigskin without the protective film. The adhesion force of the baseplate was measured using a universal testing machine at a peel angle of 180 degrees and a peel speed of 300 mm / min. The results showed that the adhesion force of the hydrocolloid baseplate on the skin surface coated with the protective film was 12.5 N / 25 mm, which was 9.4% lower than the adhesion force of 13.8 N / 25 mm on the blank skin surface, but still within the safe adhesion force range for normal use. The adhesion force change rate of the microporous baseplate was 7.2%, and the adhesion force change rate of the malleable baseplate was 5.8%, neither of which affected the normal wearing and use of the ostomy bag. The protective film's moderate surface energy (38 to 42 mN / m) ensures sufficient interfacial adhesion with the chassis adhesive while avoiding the risk of ineffective chassis adhesion due to excessively low surface energy. In dynamic wearing tests simulating daily activities (including walking, bending over, and alternating sitting and standing), the average wearing time of the ostomy bag after applying the protective film was 72 hours, which was not statistically significantly different from the average wearing time of 68 hours without the protective film.

[0041] The water vapor permeability of protective membranes is crucial for maintaining normal physiological function of the skin around the stoma. Too low a water vapor permeability can lead to impaired skin respiration and excessive local humidity, causing maceration damage, while too high a water vapor permeability indicates insufficient barrier capacity of the membrane against liquid excretions. This invention uses the permeabilization cup method to determine the water vapor permeability of the protective membranes in each embodiment according to GB / T 1037 standard. Measurements were taken for 24 h at 38 °C and a relative humidity gradient of 90% to 0%. The water vapor permeability of the protective membrane in Example 1 was 850 g / (m²·24h), in Example 2 it was 1050 g / (m²·24h), and in Example 3 it was 620 g / (m²·24h). For reference, the normal transepidermal water loss rate of healthy human skin is approximately 300 to 600 g / (m²·24h), and clinically, dressing materials with a water vapor permeability in the range of 500 to 2000 g / (m²·24h) are considered to maintain suitable skin microenvironment humidity. The water vapor permeability of the protective film in each embodiment of the present invention is within the above-mentioned suitable range, which allows normal transdermal water evaporation (respiratory function) of the skin, while effectively blocking the direct erosion of liquid feces and urine on the skin, thus achieving functional separation of selective permeability of gaseous water molecules and effective blocking of liquid excrement.

[0042] To elucidate the influence of copolymer molecular weight on the overall performance of the protective film, six acrylate-polyurethane copolymers with weight-average molecular weights of 60,000, 80,000, 100,000, 120,000, 150,000, and 180,000 Da were prepared. Coating solutions and protective films were prepared under the same conditions as in Example 1, with the remaining components and amounts identical. Various performance indicators were measured. When the molecular weight was 60,000 Da, the copolymer's chain entanglement density was insufficient, resulting in a protective film with a tensile strength of only 8.2 MPa and an elongation at break as high as 620%. Although the film was soft, it was excessively fluid, making it difficult to maintain a stable film morphology on the skin surface after coating, and its water rinsing resistance time was only 10 h. When the molecular weight increased from 80,000 Da to 150,000 Da, as... Figure 4As shown, the tensile stress-strain curve of the protective film exhibits a regular change with increasing molecular weight, showing an increase in yield strength and a decrease in elongation at break. The tensile strength increases linearly from 13.5 MPa to 23.8 MPa, and the water erosion resistance time increases from 24 h to 38 h, but the elongation at break gradually decreases from 450% to 290%, and the film-forming time extends from 35 s to 62 s. When the molecular weight further increases to 180,000 Da, the copolymer becomes difficult to dissolve in the mixed solvent, the viscosity of the coating solution increases sharply to 55 mPa·s, and uniform coating is difficult to achieve in both spraying and brushing operations. The film-forming time extends to 95 s, and the film thickness uniformity is poor. Therefore, considering the film-forming speed, film flexibility, mechanical strength, and water erosion resistance, this invention limits the copolymer molecular weight range to 80,000 to 150,000 Da, preferably 100,000 to 120,000 Da.

[0043] To determine the optimal content range of zinc oxide nanoparticles, six groups of protective film samples were prepared with content gradients of 1%, 3%, 5%, 8%, 10%, and 12% (based on the total mass of the coating solution), with the remaining components and amounts being the same as in Example 1. The antibacterial activity monotonically increased with increasing nanoparticle content. When the content increased from 1% to 8%, the diameter of the inhibition zone against Staphylococcus aureus increased from 9.2 mm to 17.8 mm, showing a significant improvement in antibacterial effect. However, when the content continued to increase to 10% and 12%, the diameter of the inhibition zone only increased slightly to 18.5 mm and 19.1 mm, respectively, indicating that the antibacterial activity plateaued, and the marginal contribution of further increasing the nanoparticle concentration to antibacterial performance was no longer significant. Simultaneously, the optical transparency and mechanical uniformity of the protective film decreased with increasing nanoparticle content. When the content was 10%, the transmittance dropped to 82.5%, and when the content was 12%, the transmittance further decreased to 76.3%, with visible white translucent spots appearing locally on the film layer, affecting clinical observation of the stoma. Regarding skin irritation, samples with concentrations of 10% and 12% showed mild erythema reactions in the closed patch test (skin irritation indices of 0.28 and 0.42, respectively). Although still considered mild irritation, this was significantly higher than the almost zero irritation response observed in samples with concentrations below 8%. Based on the combined experimental data on antibacterial efficacy, optical properties, and skin safety, this invention determines the zinc oxide nanoparticle content range to be 3% to 8%. Within this range, the protective film exhibits sufficient antibacterial activity, good transparency, and safety.

[0044] The method of using the protective film of this invention is as follows: First, use stoma-specific cleaning wipes or saline-soaked cotton balls to clean the skin surface around the stoma to remove residual excrement and grease. The cleaning area should cover a circular area with a radius of 5 to 8 cm centered on the stoma. After cleaning, gently absorb the moisture from the skin surface with non-woven gauze. After the skin surface is completely dry, use a brush-headed applicator to apply an appropriate amount of the film-forming solution in a circular motion outward from the stoma edge. The thickness of the application should be such that one application is sufficient (approximately 0.5 mg / cm²), avoiding repeated layering which would result in an excessively thick film layer that would affect breathability. After application, allow it to stand naturally for 30 to 60 seconds until the solvent in the film-forming solution has completely evaporated and the film layer is dry and no longer sticky to the touch, then attach the stoma bag base plate. If using a spray-type film-forming solution, shake well before use and spray evenly from a distance of 10 to 15 cm from the skin surface, covering the area to be protected in a circular scanning manner. Each time the ostomy bag is changed, a new protective film can be applied after removing the old baseplate. It is recommended to reapply every 24 to 48 hours to maintain the best protective effect. For patients with mild erythema or erosion around the stoma, a thin film can be applied first, allowed to dry, and then a second layer can be applied to enhance the protective thickness. The interval between the two applications should be 60 seconds.

[0045] The surface wetting properties of the protective film were characterized using the static contact angle method. The static contact angles of deionized water, simulated fecal solution, and simulated urine on the protective film surface were measured using a contact angle meter. In Example 1, the contact angle of deionized water on the protective film surface was 85.3°. Figure 5 As shown, the droplets exhibit an approximately hemispherical wetting state on the protective membrane surface. The simulated fecal contact angle is 82.7°, and the simulated urine contact angle is 79.5°, both close to the 90° hydrophobic-hydrophilic boundary but slightly biased towards the hydrophilic side. This contact angle value indicates that the protective membrane surface exhibits moderately weak hydrophobic properties towards liquid water: on the one hand, it prevents excrement from completely spreading and wetting the membrane surface, reducing the driving force for harmful substances in the excrement to penetrate into the membrane layer, thus prolonging the effective protection time of the protective membrane; on the other hand, the protective membrane surface is not excessively hydrophobic, thus avoiding loss of affinity with the skin and maintaining the adhesion stability between the membrane layer and the skin. In contrast, the water contact angle of the butyl acrylate homopolymer protective membrane in Comparative Example 1 is only 62.5°. Its high hydrophilicity causes excrement droplets to spread and penetrate rapidly on the membrane surface, leading to premature membrane failure. Further analysis revealed that the contact angle hysteresis (the difference between the advancing and retreating angles) on the protective membrane surface was 18.2°, which is at a low level. This indicates that the chemical composition and morphology of the protective membrane surface are relatively uniform, which is conducive to the autonomous flow and cleaning of excrement on the membrane surface and reduces the residual accumulation of excrement on the skin protective membrane surface around the stoma.

[0046] The environmental adaptability of the protective film was also systematically verified. Film formation time and mechanical properties of the protective film were measured under different temperature conditions (10 °C, 25 °C, 35 °C, and 40 °C) and different relative humidity conditions (30%, 50%, 70%, and 90%). The results showed that ambient temperature significantly affected the film formation rate; at 35 °C, the film formation time was shortened to 28 s, and at 10 °C, it was extended to 85 s, but the mechanical properties of the resulting protective films did not differ significantly. Under high humidity conditions (90% relative humidity), the film formation time was slightly extended but did not exceed 75 s, with no significant impact on film quality. These results confirm that the protective film of this invention can be used normally in indoor environments in most climatic regions of China. For use in cold regions during winter, it is recommended to warm the coating solution in the palm of your hand before application to accelerate film formation. In hot and sweaty summer environments, the protective film also maintains good adhesion stability; the weak acidity of sweat does not cause the film to dissolve or peel off.

[0047] Based on the results of the above embodiments and comparative examples, the synergistic mechanism among the various technical features of the present invention can be elucidated. The microphase separation structure of the acrylate soft segments and polyurethane hard segments in the acrylate-polyurethane copolymer is the structural basis for achieving a membrane with both high flexibility and high water resistance. The uniform anchoring and dispersion of nano-zinc oxide in the polymer matrix after modification with a silane coupling agent is a necessary condition to ensure the optical transparency and mechanical uniformity of the membrane. Vitamin E acetate and sodium hyaluronate synergistically protect damaged skin cells around the stoma through free radical scavenging and hydration, respectively, and their compatibility with the copolymer matrix ensures the uniform distribution and continuous release of functional components in the membrane. The ethanol and ethyl acetate mixed solvent system plays a synergistic role in improving copolymer solubility, accelerating film formation, and reducing skin irritation. The organic combination of the above-mentioned technical features produces a synergistic effect that goes beyond the simple superposition of the performance of a single component. As a result, the protective film of the present invention is significantly superior to the existing technology in terms of water erosion resistance (greater than 24 h), film formation speed (30 to 60 s), film flexibility (elongation at break 310% to 450%), and multifunctional properties (antibacterial, antioxidant, moisturizing and repairing).

[0048] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of the claims of the present invention.

Claims

1. A peristomal skin protective membrane, characterized in that, The protective film comprises a film-forming matrix and functional additives. The film-forming matrix is ​​an acrylate-polyurethane copolymer with a weight-average molecular weight of 80,000 to 150,000 Da and a glass transition temperature of -10 to 5 °C. The functional additives include zinc oxide nanoparticles, vitamin E acetate, and sodium hyaluronate. The coating solution of the protective film uses a mixed solvent of ethanol and ethyl acetate as the solvent system. Based on the total mass of the coating solution, the solid content of the acrylate-polyurethane copolymer is 15% to 25%, the content of the zinc oxide nanoparticles is 3% to 8%, the content of the vitamin E acetate is 0.5% to 2%, and the content of the sodium hyaluronate is 0.1% to 0.5%.

2. The peristomal skin protective membrane according to claim 1, characterized in that, The acrylate-polyurethane copolymer is prepared by free radical copolymerization of acrylate monomers and polyurethane prepolymer. The acrylate monomers include butyl acrylate, methyl methacrylate and hydroxyethyl acrylate, with a mass ratio of 60:30:

10. The mass ratio of acrylate monomers to polyurethane prepolymer is 70:

30.

3. The peristomal skin protective membrane according to claim 1, characterized in that, The zinc oxide nanoparticles have an average particle size of 20 to 50 nm. The zinc oxide nanoparticles are surface modified by a silane coupling agent, which is gamma-methacryloyloxypropyltrimethoxysilane, and its amount is 2% to 5% of the mass of the nanoparticles.

4. The peristomal skin protective membrane according to claim 1, characterized in that, The mass ratio of ethanol to ethyl acetate is 50:50 to 70:30, preferably 60:

40.

5. The peristomal skin protective membrane according to claim 1, characterized in that, The molecular weight of the sodium hyaluronate is between 100,000 and 300,000 Da.

6. A method for preparing the peristomal skin protective film according to any one of claims 1 to 5, characterized in that, Includes the following steps: Step 1: Add the acrylate-polyurethane copolymer to a mixed solvent of ethanol and ethyl acetate, and stir at 40 to 60 °C until completely transparent to obtain a film-forming matrix solution; Step 2: Disperse zinc oxide nanoparticles modified with silane coupling agent in ethanol to prepare a dispersion, and add it to the film-forming matrix solution obtained in Step 1 for ultrasonic dispersion treatment. Step 3: Add vitamin E acetate and sodium hyaluronate in sequence and stir well to obtain the coating solution; Step 4: Fill the coating solution into a brush-equipped application bottle or spray bottle.

7. The preparation method according to claim 6, characterized in that, The conditions for ultrasonic dispersion treatment in step two are: ultrasonic power 150 to 250 W, frequency 18 to 25 kHz, and treatment time 10 to 20 min.

8. The preparation method according to claim 6, characterized in that, Before step one, there is also a synthesis step of acrylate-polyurethane copolymer: polytetrahydrofuran diol is reacted with isophorone diisocyanate to obtain polyurethane prepolymer, which is then mixed with acrylate monomer and subjected to solution polymerization at 70 to 75 °C for 6 to 8 h using azobisisobutyronitrile as an initiator.

9. The use of the peristomal skin protective film according to any one of claims 1 to 5 in the preparation of peristomal skin protective articles.

10. The application according to claim 9, characterized in that, The stoma includes an enterostomy and a urostomy. The protective film is applied to the skin surface around the stoma and dries after 30 to 60 seconds to form a transparent protective film layer with a thickness of 5 to 15 μm. The protective film layer has a barrier rate of more than 95% against excrement and a water flushing time of more than 24 hours.

Images