A hard plaster substrate for a compress and a method for preparing the same

Abstract

This invention provides a breathable plaster matrix for application and its preparation method, belonging to the field of polymeric dressings and plasters. The plaster matrix raw materials include terpene-modified rosin beeswax, hydrogenated rosin glyceryl ester, camellia oil, castor oil, stearic acid hydrophobically modified microcrystalline cellulose, zinc oxide, glycerin, coated citric acid, sodium bicarbonate, polyethylene glycol, camphor, and menthol. The terpene-modified rosin beeswax is prepared by reacting rosin and α-pinene in the presence of di-tert-butylperoxyisopropylbenzene, followed by the addition of white beeswax and maleic anhydride, and then the addition of trimethylolpropane. The stearic acid hydrophobically modified microcrystalline cellulose is microcrystalline cellulose coated with stearic acid. The coated citric acid is citric acid coated with hydrogenated castor oil. This invention's plaster matrix significantly improves skin breathability, application comfort, and biocompatibility while ensuring sufficient adhesion, formability, and drug loading capacity.

Description

Technical Field

[0001] This invention pertains to the field of polymeric dressings and ointments, specifically relating to a breathable plaster matrix for application and its preparation method. Background Technology

[0002] Plasters are topical preparations with a long history of clinical application, representing a typical example of external treatments in Traditional Chinese Medicine. They are still widely used in the treatment of bone injuries, rheumatism, and pain. Modern plasters mainly involve mixing the medication with a viscous base, spreading it onto a backing material such as cloth or paper, and then applying it to the skin to deliver the medication locally. Through skin penetration, the medication directly reaches the affected area, exerting effects such as promoting blood circulation, reducing swelling and pain, and clearing the meridians. They also offer advantages such as convenient use, long-lasting efficacy, and avoiding gastrointestinal irritation associated with oral medications.

[0003] Currently, common plasters on the market are mainly divided into three categories: traditional lead plasters, rubber plasters, and hot-melt pressure-sensitive adhesive plasters. Traditional black plasters are made from vegetable oils and lead oxide, with strong adhesion and a large drug loading capacity, but the preparation process is complicated and has problems such as heavy metal residues and high skin irritation. Rubber plasters use rubber as the core matrix, have good formability and are easy to apply, and were once the mainstream plaster products, but their matrix is ​​mostly a dense polymer network structure, and organic solvents are often added during the preparation process, which can easily cause skin allergies. Although hot-melt pressure-sensitive adhesive plasters have optimized the irritation problem by using a solvent-free hot-melt process, they still retain the dense characteristics of the traditional plaster matrix.

[0004] Existing plasters present several intractable problems in clinical application: First, the dense matrix of conventional plasters completely blocks the skin from air circulation, hindering normal sweat evaporation and gas exchange. This leads to discomfort such as stuffiness, dampness, and itching at the application site. Prolonged use can also cause skin maceration, redness, and rashes, severely impacting patient compliance. Second, traditional matrices suffer from an imbalance between flexibility and breathability. Some matrices are excessively hardened to ensure adhesion, resulting in poor extensibility when applied to the skin. They cannot adapt to joints and other active areas, easily curling or falling off. Softened matrices, on the other hand, are highly sticky, easily staining clothing and exhibiting unstable drug release efficiency. Third, some matrices contain highly irritating components, and their lack of breathability weakens the skin barrier function, further exacerbating adverse reactions such as allergies and redness.

[0005] Furthermore, existing plaster bases struggle to balance adhesion and breathability, failing to meet the demands for long-term, safe, and comfortable application. Therefore, it is necessary to develop novel breathable plaster bases. By optimizing the base formulation and structure and creating breathable channels, these bases can improve skin breathability and compatibility while ensuring the plaster's adhesion, drug loading capacity, and formability, thereby enhancing application comfort and reducing adverse reactions. Summary of the Invention

[0006] To address the challenge of balancing adhesion and breathability in existing plaster bases, this invention provides a breathable plaster base for application and its preparation method. The plaster is prepared by compounding terpene-modified rosin beeswax, hydrogenated rosin glyceryl ester, camellia oil, castor oil, stearic acid hydrophobically modified microcrystalline cellulose, coated citrate, sodium bicarbonate, and other raw materials. While ensuring sufficient adhesion, formability, and drug loading capacity, it significantly improves skin breathability, application comfort, and biocompatibility, making it suitable for prolonged application. The specific technical solution is as follows: A breathable plaster base for application is prepared from the following raw materials in parts by weight: 26-34 parts of terpene-modified rosin beeswax, 18-23 parts of hydrogenated rosin glyceryl ester, 8-12 parts of camellia oil, 8-12 parts of castor oil, 4-6 parts of stearic acid hydrophobically modified microcrystalline cellulose, 3-5 parts of zinc oxide, 1-3 parts of glycerin, 1.5-2.5 parts of coated citric acid, 3-4 parts of sodium bicarbonate, 2-3 parts of polyethylene glycol, 7-11 parts of camphor, 2-5 parts of menthol, and 0.2-0.5 parts of 2,6-di-tert-butyl-4-methylphenol; The terpene-modified rosin beeswax is prepared by reacting rosin and α-pinene in the presence of bis(tert-butylperoxyisopropylbenzene), followed by the addition of white beeswax and maleic anhydride, and then the addition of trimethylolpropane. The stearic acid hydrophobically modified microcrystalline cellulose is prepared by coating microcrystalline cellulose with stearic acid. The coated citric acid is prepared by coating citric acid with hydrogenated castor oil.

[0007] Furthermore, the mass ratio of rosin, white beeswax, α-pinene, bis(tert-butylperoxyisopropylbenzene), maleic anhydride, and trimethylolpropane is (20-23):(12-15):(1.0-1.5):(0.16-0.25):(0.15-0.25):(0.1-0.2).

[0008] Furthermore, the rosin, α-pinene, and bis-tert-butylperoxyisopropylbenzene are reacted at 190–198°C, white beeswax and maleic anhydride are added and reacted at 160–170°C, and trimethylolpropane is added and reacted at 185–195°C.

[0009] Furthermore, the preparation method of the terpene-modified rosin beeswax includes: heating rosin to 175-185°C to melt it, adding α-pinene and bis-tert-butylperoxyisopropylbenzene, stirring and reacting at 190-198°C, cooling to 160-170°C, adding white beeswax and maleic anhydride, stirring and reacting at 160-170°C; heating to 185-195°C, adding trimethylolpropane and stirring for crosslinking reaction, removing low-boiling substances, unreacted monomers and low-molecular-weight byproducts under reduced pressure; cooling to obtain terpene-modified rosin beeswax.

[0010] Furthermore, the preparation method of the stearic acid hydrophobically modified microcrystalline cellulose includes: uniformly mixing microcrystalline cellulose and stearic acid at a mass ratio of 100:(3-5) in a temperature range of 80-85℃, cooling and sieving to obtain stearic acid hydrophobically modified microcrystalline cellulose.

[0011] Furthermore, the preparation method of the coated citric acid includes: pulverizing citric acid through a 200-250 mesh sieve, and heating the hydrogenated castor oil to 90-95°C to melt it, adding citric acid, stirring and dispersing it evenly in a sealed manner, cooling and solidifying it, and pulverizing it through a 200-250 mesh sieve to obtain coated citric acid.

[0012] Furthermore, the polyethylene glycol is PEG-400 or PEG-600.

[0013] The preparation method of the above-mentioned breathable plaster matrix for application includes the following steps: S1: Mix camellia oil and castor oil, and refine them until the acid value is <8mg KOH / g, the peroxide value is <5meq / kg, water droplets form beads without stickiness, and there is no oil residue or odor, to obtain refined oil; S2: At 155-165℃, terpene-modified rosin beeswax and hydrogenated rosin glycerol esters are added to refined oil and stirred to obtain a melt; S3: Cool the melt to 70-75℃, add polyethylene glycol, glycerin, 2,6-di-tert-butyl-4-methylphenol, stearic acid hydrophobically modified microcrystalline cellulose, and coated citric acid in sequence, and stir until uniform; cool to 55-60℃, add zinc oxide, sodium bicarbonate, camphor, and menthol, and stir until uniform to obtain the matrix; S4: The matrix is ​​roller-coated onto a medical pure cotton backing at 58-65℃, and immediately covered with a release film to obtain the coated blank; S5: The coated blank is pore-forming, held at 91-96℃ for 3-5 minutes, at 98-102℃ for 2-3 minutes, and at 30-38℃ for 3-5 minutes to obtain a sheet; S6: Remove the release film, let the sheet stand, and obtain the breathable plaster matrix.

[0014] In step S4 of the above preparation method, the thickness of the substrate coated by roller is 0.9 to 1.2 mm.

[0015] In step S6 of the above preparation method, the standing is carried out in a closed clean environment at 20-28°C and 40-55% relative humidity for 22-26 hours, with the final setting point being that the substrate surface is no longer sticky to the touch, the shape is unchanged, and there is no residue after peeling.

[0016] The present invention provides a breathable plaster matrix for application and its preparation method, the beneficial effects of which include: I. This invention's plaster fundamentally solves the pain points of traditional plasters, such as the difficulty in simultaneously achieving breathability, adhesion, and flexibility, by constructing a stable skeletal structure that combines chemical cross-linking and physical entanglement, and forming continuous, interconnected, breathable microporous channels within the matrix. While ensuring sufficient adhesion, shape retention, and drug loading capacity, it significantly improves skin breathability, application comfort, and biocompatibility, making it suitable for long-term safe application, especially for use on active areas such as joints. Overall, it achieves a synergistic improvement in five key properties: breathability, adhesion, shape retention, low irritation, and drug loading.

[0017] II. Terpene-modified rosin beeswax uses rosin as a matrix, which is modified by α-pinene grafting, functionalized with maleic anhydride, and cross-linked with trimethylolpropane to form a stable double-network structure. This provides sufficient rigidity and structural strength to ensure the molding and cohesiveness of the paste, while also improving compatibility with other components, reducing raw material irritation, and balancing the hardness and ductility of the paste, making the hard paste neither brittle nor overly soft and deformable.

[0018] III. Stearic acid-modified hydrophobic microcrystalline cellulose improves its dispersibility in oily matrices by coating the surface of microcrystalline cellulose with stearic acid, avoiding localized defects caused by the aggregation of hydrophilic particles. After modification, it can form a uniform rigid support framework inside the paste, which can not only inhibit flow deformation during high-temperature coating, but also stabilize the microporous structure after curing, improve the paste's creep resistance, and reduce moisture absorption and stickiness, thus improving the refreshing feeling after application.

[0019] IV. Coated citric acid is produced by coating citric acid with hydrogenated castor oil, achieving a temperature-triggered, point-based release control mechanism. At room temperature, citric acid and sodium bicarbonate are completely isolated to prevent premature reaction and failure; during high-temperature coating, the coating layer melts, and the citric acid is activated to participate in foaming, ensuring a stable and controllable pore-forming process and a uniform and complete pore structure.

[0020] V. In the preparation of hard plaster sheets, camellia oil and castor oil are dehydrated, impurity removed, and their acid and peroxide values ​​are controlled to reduce the risk of oil oxidation and rancidity, reduce irritating impurities, and improve the long-term stability and skin compatibility of the plaster. A three-stage gradient pore-forming and shaping process is designed. Through a temperature-controlled process of low-temperature foaming, medium-temperature penetration, and cooling locking, closed pores are first formed by acid-base reaction, then polyethylene glycol and cooling ingredients are used to open the pores, and finally rapid cooling is used to fix the micropore morphology, ultimately forming a continuous, uniform, and stable breathable network, which significantly improves breathability without weakening the adhesion performance.

[0021] VI. Terpene-modified rosin beeswax and hydrogenated rosin glyceryl esters jointly construct a strong and tough adhesion system, balancing initial tack, peel strength, and holding power; camellia oil and castor oil synergistically soften and toughen, improving spreadability and skin feel, and reducing the hardness and brittleness of the plaster; modified microcrystalline cellulose and zinc oxide provide rigid reinforcement and structural stability, while soothing the skin and reducing the risk of irritation; encapsulated citric acid, sodium bicarbonate, polyethylene glycol, camphor, and menthol together form a controllable pore-forming system, synergistically forming interconnected micropores, improving breathability and a cooling and comfortable feel; the overall formula achieves a holistic effect of structural stability, reliable adhesion, breathability and comfort, hypoallergenic safety, and controllable drug loading, significantly improving the overall quality of the plaster. Detailed Implementation

[0022] The present invention will be further described below with reference to specific implementation examples, but the present invention is not limited to these implementation examples.

[0023] Example 1 A breathable plaster base for application, the base being prepared from the following raw materials in parts by weight: 30 parts terpene-modified rosin beeswax, 20 parts hydrogenated rosin glyceryl ester, 10 parts camellia oil, 10 parts castor oil, 5 parts stearic acid hydrophobically modified microcrystalline cellulose, 4 parts zinc oxide, 2 parts glycerin, 2 parts coated citric acid, 3.5 parts sodium bicarbonate, 2.5 parts polyethylene glycol (PEG-400), 9 parts camphor, 3.5 parts menthol, and 0.3 parts 2,6-di-tert-butyl-4-methylphenol.

[0024] Zinc oxide and sodium bicarbonate passed through a 200-mesh sieve. Camphor and menthol passed through a 150-mesh sieve.

[0025] The preparation method of terpene-modified rosin beeswax includes: preparing materials according to the mass ratio of rosin: white beeswax: α-pinene: di-tert-butylperoxyisopropylbenzene: maleic anhydride: trimethylolpropane = 21:13:1.2:0.2:0.2:0.15; adding rosin into a high-pressure reactor equipped with a reflux condenser and a pressure relief valve, purging the reactor with nitrogen three times to replace the air inside, and heating to a temperature range of 175-185℃ to completely melt the rosin; adding α-pinene and di-tert-butylperoxyisopropylbenzene, sealing the reactor, maintaining a positive nitrogen pressure, controlling the temperature range of 190-198℃, and stirring at 280 r / min. The reaction was stirred for 3 hours, with reflux condensation running throughout to recover volatile terpenes. The temperature was lowered to 165°C, and the mixture was fed under nitrogen positive pressure in a sealed environment. White beeswax and maleic anhydride were added, and the mixture was stirred at 160–170°C for 2 hours. The temperature was then raised to 185–195°C, and trimethylolpropane was added and stirred for crosslinking reaction for 1.5 hours. Low-boiling substances were pre-removed under vacuum of -0.06–-0.07 MPa for 35 minutes, and then distilled under reduced pressure of -0.085–-0.095 MPa for 1.5 hours to remove unreacted monomers and low-molecular-weight byproducts. The mixture was then naturally cooled to room temperature to obtain terpene-modified rosin beeswax.

[0026] The preparation method of stearic acid hydrophobically modified microcrystalline cellulose includes: microcrystalline cellulose and stearic acid are uniformly mixed at a mass ratio of 100:4 in a temperature range of 80-85℃ to ensure uniform coating of stearic acid, and after cooling, the mixture is passed through a 100-mesh sieve to obtain stearic acid hydrophobically modified microcrystalline cellulose.

[0027] The preparation method of coated citric acid includes: pulverizing citric acid through a 200-mesh sieve, and mixing it with hydrogenated castor oil at a mass ratio of citric acid:hydrogenated castor oil = 100:8; heating the hydrogenated castor oil to a temperature range of 90-95℃ to melt it, adding citric acid, stirring and dispersing it evenly in a sealed environment to ensure that the coating material is completely melted and evenly coats the citric acid particles, cooling and solidifying it, and pulverizing it through a 200-mesh sieve to obtain coated citric acid.

[0028] The preparation method of the above-mentioned breathable plaster matrix for application includes the following steps: S1 Oil Refining: Camellia oil and castor oil are mixed, and nitrogen gas (0.7L / min) is introduced into a sealed refining pot. The temperature is raised to 115-125℃ and dehydrated for 30 minutes. Then the temperature is raised to 185-195℃ and refined for 30 minutes (acid value <8mg KOH / g, peroxide value <5meq / kg, water droplets form beads and do not stick to the hand, no oil residue and no odor), to obtain refined oil. S2 resin melt homogenization: The refined oil is cooled to a temperature range of 155-165℃, and terpene-modified rosin beeswax and hydrogenated rosin glycerol ester are added. The mixture is stirred at 200 r / min for 18 min to obtain a melt. S3 Low-Temperature Stepwise Feeding: The melt is cooled to 70–75°C, and polyethylene glycol (PEG-400), glycerol, 2,6-di-tert-butyl-4-methylphenol, stearic acid hydrophobically modified microcrystalline cellulose, and coated citric acid are added sequentially. The mixture is stirred at 180 rpm for 6 minutes and then at 80 rpm for 8 minutes to ensure uniform dispersion. The temperature is then lowered to 55–60°C, and zinc oxide, sodium bicarbonate, camphor, and menthol are added under nitrogen positive pressure in a closed system. The mixture is stirred at 120 rpm for 6 minutes, and the entire process is kept closed to reduce sublimation loss, thus obtaining the matrix. S4 constant temperature coating molding: The substrate is roller-coated onto a medical pure cotton backing at a temperature range of 58–65℃ to a thickness of 1 mm. Immediately afterward, a release film is applied to prevent cooling and skin formation and loss of volatile components, thus obtaining the coated blank. S5 Three-Segment Gradient Hole Shaping: The coated preform is placed in a tunnel oven with condensation recovery, with the medical-grade pure cotton backing side facing upwards (to facilitate gas dissipation through the cotton backing). Zone 1 (foaming zone): temperature 94℃, hold for 4 minutes, the hydrogenated castor oil coating melts and unseales, citric acid comes into contact with sodium bicarbonate, releasing carbon dioxide and forming closed-cell cavities; Zone 2 (through zone): temperature 100℃, hold for 2 minutes; Zone 3 (shaping zone): temperature 35℃, hold for 4 minutes, rapid cooling locks in the pore structure, resulting in a sheet material; S6 Sealed Moisture-proof Curing and Shaping: Remove the release film and place the sheet in a closed clean environment with a temperature range of 20-28℃ and a relative humidity range of 40-55% for 24 hours. The final setting point is when the substrate surface is no longer sticky to the touch, the shape is unchanged, and there is no residue after peeling, thus obtaining a breathable hard plaster substrate.

[0029] Example 2 A breathable plaster base for application, the base being prepared from the following raw materials in parts by weight: 26 parts terpene-modified rosin beeswax, 18 parts hydrogenated rosin glyceryl ester, 8 parts camellia oil, 8 parts castor oil, 4 parts stearic acid hydrophobically modified microcrystalline cellulose, 3 parts zinc oxide, 1 part glycerin, 1.5 parts coated citric acid, 3 parts sodium bicarbonate, 2 parts polyethylene glycol (PEG-600), 7 parts camphor, 2 parts menthol, and 0.2 parts 2,6-di-tert-butyl-4-methylphenol.

[0030] Zinc oxide and sodium bicarbonate passed through a 200-mesh sieve. Camphor and menthol passed through a 100-mesh sieve.

[0031] The preparation method of terpene-modified rosin beeswax includes: preparing materials according to the mass ratio of rosin: white beeswax: α-pinene: di-tert-butylperoxyisopropylbenzene: maleic anhydride: trimethylolpropane = 20:12:1.0:0.16:0.15:0.1; adding rosin into a high-pressure reactor equipped with a reflux condenser and a pressure relief valve, purging the reactor with nitrogen twice to replace the air inside, and heating to a temperature range of 175-185℃ to completely melt the rosin; adding α-pinene and di-tert-butylperoxyisopropylbenzene, sealing the reactor, maintaining positive nitrogen pressure, controlling the temperature range of 190-198℃, and operating at 250 rpm. The mixture was stirred for 3.5 hours, with reflux condensation running throughout to recover volatile terpenes. The temperature was lowered to 160°C, and the mixture was fed under nitrogen pressure in a sealed environment. White beeswax and maleic anhydride were added, and the mixture was stirred at 160–170°C for 1.5 hours. The temperature was then raised to 185–195°C, and trimethylolpropane was added and stirred for crosslinking reaction for 1 hour. Low-boiling-point substances were pre-removed under vacuum of -0.06–-0.07 MPa for 30 minutes, followed by vacuum distillation at -0.085–-0.095 MPa for 1 hour to remove unreacted monomers and low-molecular-weight byproducts. The mixture was then naturally cooled to room temperature to obtain terpene-modified rosin beeswax.

[0032] The preparation method of stearic acid hydrophobically modified microcrystalline cellulose includes: microcrystalline cellulose and stearic acid are uniformly mixed at a mass ratio of 100:3 in a temperature range of 80-85℃ to ensure uniform coating of stearic acid, and after cooling, the mixture is passed through a 100-mesh sieve to obtain stearic acid hydrophobically modified microcrystalline cellulose.

[0033] The preparation method of coated citric acid includes: pulverizing citric acid through a 200-mesh sieve, and mixing it with hydrogenated castor oil at a mass ratio of citric acid:hydrogenated castor oil = 100:5; heating the hydrogenated castor oil to a temperature range of 90-95℃ to melt it, adding citric acid, stirring and dispersing it evenly in a sealed environment to ensure that the coating material is completely melted and evenly coats the citric acid particles, cooling and solidifying it, and pulverizing it through a 200-mesh sieve to obtain coated citric acid.

[0034] The preparation method of the above-mentioned breathable plaster matrix for application includes the following steps: S1 Oil Refining: Camellia oil and castor oil are mixed, and nitrogen gas (0.6 L / min) is introduced into a sealed refining pot. The temperature is raised to 115-125℃ and dehydrated for 25 minutes. Then the temperature is raised to 185-195℃ and refined for 25 minutes (acid value < 8 mg KOH / g, peroxide value < 5 meq / kg, water droplets form beads and do not stick to the hand, no oil residue and no odor), to obtain refined oil. S2 resin melt homogenization: The refined oil is cooled to a temperature range of 155-165℃, and terpene-modified rosin beeswax and hydrogenated rosin glycerol ester are added. The mixture is stirred at 150 r / min for 20 min to obtain a melt. S3 Low-Temperature Stepwise Feeding: The melt is cooled to 70–75°C, and polyethylene glycol (PEG-600), glycerol, 2,6-di-tert-butyl-4-methylphenol, stearic acid hydrophobically modified microcrystalline cellulose, and coated citric acid are added sequentially. The mixture is stirred at 150 rpm for 8 minutes and then at 70 rpm for 10 minutes to ensure uniform dispersion. The temperature is then lowered to 55–60°C, and zinc oxide, sodium bicarbonate, camphor, and menthol are added under nitrogen positive pressure in a closed system. The mixture is stirred at 100 rpm for 8 minutes, and the entire process is kept closed to reduce sublimation loss, thus obtaining the matrix. S4 constant temperature coating molding: The substrate is roller-coated onto a medical pure cotton backing at a temperature range of 58–65°C to a thickness of 0.9 mm. Immediately afterward, a release film is applied to prevent cooling and skin formation and loss of volatile components, thus obtaining the coated preform. S5 Three-Segment Gradient Hole Shaping: The coated preform is placed in a tunnel oven with condensation recovery, with the medical-grade pure cotton backing side facing upwards (to facilitate gas dissipation through the cotton backing). Zone 1 (foaming zone): temperature 91℃, hold for 5 minutes, the hydrogenated castor oil coating melts and unseales, citric acid comes into contact with sodium bicarbonate, releasing carbon dioxide and forming closed-cell cavities; Zone 2 (through zone): temperature 98℃, hold for 3 minutes; Zone 3 (shaping zone): temperature 30℃, hold for 5 minutes, rapid cooling locks in the pore structure, resulting in a sheet material; S6 Sealed Moisture-proof Curing and Shaping: Remove the release film and place the sheet in a closed clean environment with a temperature range of 20-28℃ and a relative humidity range of 40-55% for 22 hours. The final setting point is when the substrate surface is no longer sticky to the touch, the shape is unchanged, and there is no residue after peeling. This yields a breathable hard plaster substrate.

[0035] Example 3 A breathable plaster base for application, the base being prepared from the following raw materials in parts by weight: 34 parts terpene-modified rosin beeswax, 23 parts hydrogenated rosin glyceryl ester, 12 parts camellia oil, 12 parts castor oil, 6 parts stearic acid hydrophobically modified microcrystalline cellulose, 5 parts zinc oxide, 3 parts glycerin, 2.5 parts coated citric acid, 4 parts sodium bicarbonate, 3 parts polyethylene glycol (PEG-400), 11 parts camphor, 5 parts menthol, and 0.5 parts 2,6-di-tert-butyl-4-methylphenol.

[0036] Zinc oxide and sodium bicarbonate passed through a 250-mesh sieve. Camphor and menthol passed through a 150-mesh sieve.

[0037] The preparation method of terpene-modified rosin beeswax includes: preparing materials in the following mass ratio: rosin: white beeswax: α-pinene: di-tert-butylperoxyisopropylbenzene: maleic anhydride: trimethylolpropane = 23:15:1.5:0.25:0.25:0.2; adding rosin to a high-pressure reactor equipped with a reflux condenser and a pressure relief valve, purging the reactor with nitrogen to replace the air in the reactor four times, and heating to a temperature range of 175-185℃ to completely melt the rosin; adding α-pinene and di-tert-butylperoxyisopropylbenzene, sealing the reactor, maintaining positive nitrogen pressure, controlling the temperature range of 190-198℃, and operating at 300 rpm. The mixture was stirred for 2.5 hours, with reflux condensation running throughout to recover volatile terpenes. The temperature was lowered to 170°C, and the mixture was fed under nitrogen pressure in a sealed environment. White beeswax and maleic anhydride were added, and the mixture was stirred for 2.5 hours at 160–170°C. The temperature was then raised to 185–195°C, and trimethylolpropane was added and stirred for crosslinking reaction for 2 hours. Low-boiling-point substances were pre-removed for 40 minutes under vacuum of -0.06–-0.07 MPa, followed by vacuum distillation for 2 hours at -0.085–-0.095 MPa to remove unreacted monomers and low-molecular-weight byproducts. The mixture was then naturally cooled to room temperature to obtain terpene-modified rosin beeswax.

[0038] The preparation method of stearic acid hydrophobically modified microcrystalline cellulose includes: microcrystalline cellulose and stearic acid are uniformly mixed at a mass ratio of 100:5 in a temperature range of 80-85℃ to ensure uniform coating of stearic acid, and after cooling, the mixture is passed through a 150-mesh sieve to obtain stearic acid hydrophobically modified microcrystalline cellulose.

[0039] The preparation method of coated citric acid includes: pulverizing citric acid through a 250-mesh sieve, and mixing it at a mass ratio of citric acid: hydrogenated castor oil = 100:10; heating the hydrogenated castor oil to a temperature range of 90-95℃ to melt it, adding citric acid, stirring and dispersing it evenly in a sealed environment to ensure that the coating material is completely melted and evenly coats the citric acid particles, cooling and solidifying it, and pulverizing it through a 250-mesh sieve to obtain coated citric acid.

[0040] The preparation method of the above-mentioned breathable plaster matrix for application includes the following steps: S1 Oil Refining: Camellia oil and castor oil are mixed, and nitrogen gas (0.8L / min) is introduced into a sealed refining pot. The temperature is raised to 115-125℃ and dehydrated for 35 minutes. Then the temperature is raised to 185-195℃ and refined for 35 minutes (acid value <8mg KOH / g, peroxide value <5meq / kg, water droplets form beads and do not stick to the hand, no oil residue and no odor), to obtain refined oil. S2 resin melt homogenization: The refined oil is cooled to a temperature range of 155-165℃, and terpene-modified rosin beeswax and hydrogenated rosin glycerol ester are added. The mixture is stirred at 250 r / min for 15 min to obtain a melt. S3 Low-Temperature Stepwise Feeding: The melt is cooled to 70–75°C, and polyethylene glycol (PEG-400), glycerol, 2,6-di-tert-butyl-4-methylphenol, stearic acid hydrophobically modified microcrystalline cellulose, and coated citric acid are added sequentially. The mixture is stirred at 200 rpm for 5 min and then at 90 rpm for 5 min to ensure uniform dispersion. The temperature is then lowered to 55–60°C, and zinc oxide, sodium bicarbonate, camphor, and menthol are added under nitrogen positive pressure in a closed system. The mixture is stirred at 150 rpm for 5 min, and the entire process is kept closed to reduce sublimation loss, thus obtaining the matrix. S4 constant temperature coating molding: The substrate is roller-coated onto a medical pure cotton backing at a temperature range of 58–65℃ to a thickness of 1.2 mm. Immediately afterward, a release film is applied to prevent cooling and skin formation and loss of volatile components, thus obtaining the coated blank. S5 Three-Segment Gradient Hole Shaping: The coated preform is placed in a tunnel oven with condensation recovery, with the medical-grade pure cotton backing side facing upwards (to facilitate gas dissipation through the cotton backing). Zone 1 (foaming zone): temperature 96℃, hold for 3 minutes, the hydrogenated castor oil coating melts and unseales, citric acid comes into contact with sodium bicarbonate, releasing carbon dioxide and forming closed-cell cavities; Zone 2 (through zone): temperature 102℃, hold for 2 minutes; Zone 3 (shaping zone): temperature 38℃, hold for 3 minutes, rapid cooling locks in the pore structure, resulting in a sheet material; S6 Sealed Moisture-proof Curing and Shaping: Remove the release film and place the sheet in a closed clean environment with a temperature range of 20-28℃ and a relative humidity range of 40-55% for 26 hours. The final setting point is when the substrate surface is no longer sticky to the touch, the shape is unchanged, and there is no residue after peeling. This yields a breathable hard plaster substrate.

[0041] In the above embodiments, one of the three methods of adding the therapeutic drug is selected based on the characteristics of the drug: Option 1: High-temperature blending with drug delivery: Suitable for: Carbonized Chinese medicinal herbs, calcined mineral drugs, and chemically stabilized drugs (decomposition temperature > 120℃). Contraindicated for: Heat-sensitive extracts, volatile oils, and protein / peptide components.

[0042] The operating steps include: passing the drug through a 200-250 mesh sieve to form a fine powder, pre-dispersing it with the glycerin already included in the prescription, without adding any additional glycerin; and stirring and dispersing it evenly in S3.

[0043] Option 2, double-layer composite drug delivery: The drug is made into an ointment and applied to the skin contact surface of a breathable plaster base with a thickness of 0.10-0.20 mm. The area of ​​the ointment is smaller than the area of ​​the plaster base and is located in the center of the plaster base to avoid hindering the adhesion and breathability of the plaster base. It is then covered with release paper.

[0044] Option 3: Solvent impregnation of drug-loaded drugs: Solvent: Anhydrous ethanol; if it is a water-soluble drug, use a mixture of ethanol and water as the solvent, with a water content of <8% to avoid swelling and loss of viscosity of the matrix, and a drug concentration of 5% to 18% (w / v).

[0045] The operating steps include: immersing the breathable plaster base in the drug solution for a strictly controlled immersion time of 20–30 seconds; removing it and allowing it to air dry vertically for 1–2 minutes, avoiding wiping or squeezing to prevent collapse of the microporous structure; drying at a low temperature of 32–38℃ for 2–5 hours, ensuring solvent residue meets ICH Q3C limits; covering with release paper and testing the uniformity of drug content (RSD < 5%).

[0046] In the above embodiments, the terpene-modified rosin beeswax is a complex mixture system and cannot be represented by a unified chemical structural formula. The surface coating of stearic acid hydrophobically modified microcrystalline cellulose polydisperse polymer is not a single compound and cannot be represented by a unified chemical structural formula. The lipid coating of coated citrate organic acid salts is a mixture and cannot be represented by a unified structural formula.

[0047] The raw materials and their sources involved in the above embodiments are as follows: Hydrogenated rosin glycerol ester is from Hubei Guangao Biotechnology Co., Ltd., with a purity of 99%. Camellia oil is from Shanxi Jinyang Pharmaceutical Excipients Co., Ltd., injection grade, with a purity of 99%. Castor oil is from Shanxi Jinyang Pharmaceutical Excipients Co., Ltd., with a purity of 99%. Zinc oxide passes through a 200-250 mesh sieve and is from Shanxi Jinyang Pharmaceutical Excipients Co., Ltd., with a purity of 99%. Glycerin is from Xi'an Xinfengda Pharmaceutical Excipients Co., Ltd., 1,2,3-propanetriol, containing no less than 98% C3H8O3. Sodium bicarbonate passes through a 200-250 mesh sieve, with a purity of over 99%. Polyethylene glycol: PEG-400 and PEG-600 are both from Guangzhou Zhuocen Chemical Co., Ltd., pharmaceutical grade. Camphor passes through a 100-150 mesh sieve, with a purity of over 99%. Menthol passes through a 100-150 mesh sieve, with a purity of over 99%. 2,6-Di-tert-butyl-4-methylphenol, purity ≥ 99%. Rosin, sourced from Xi'an Jinxiang Pharmaceutical Excipients Co., Ltd., acid value 160–170 mg KOH / g, melting point 110–135℃. White beeswax, sourced from Shaanxi Mingcheng Pharmaceutical Co., Ltd., melting point 62–67℃. α-Pinene, bis-tert-butylperoxyisopropylbenzene (BIPB), maleic anhydride, trimethylolpropane, stearic acid, and citric acid all have purity ≥ 99%. Microcrystalline cellulose, sourced from Shanxi Jinyang Pharmaceutical Excipients Co., Ltd. Hydrogenated castor oil, sourced from Shanxi Jinyang Pharmaceutical Excipients Co., Ltd., melting point 85–88℃.

[0048] Comparative Example 1 The difference from Example 1 is that the terpene-modified rosin beeswax is replaced by rosin and white beeswax in a mass ratio of 21:13.

[0049] Comparative Example 2 The difference from Example 1 is that maleic anhydride is not added in the preparation of terpene-modified rosin beeswax.

[0050] Comparative Example 3 The difference from Example 1 is that the step of "heating to 185-195°C and adding trimethylolpropane for stirring and crosslinking reaction for 1.5 h" is omitted in the preparation of terpene-modified rosin beeswax.

[0051] Comparative Example 4 The difference from Example 1 is that the mass ratio of rosin to white beeswax is changed to 13:21.

[0052] Comparative Example 5 The difference from Example 1 is that stearic acid hydrophobically modified microcrystalline cellulose is directly replaced by microcrystalline cellulose.

[0053] Comparative Example 6 The difference from Example 1 is that the coated citric acid is directly replaced by citric acid.

[0054] Comparative Example 7 The difference from Example 1 is that the terpene-modified rosin beeswax is replaced with 20 parts and hydrogenated rosin glycerol ester with 30 parts.

[0055] Comparative Example 8 The difference from Example 1 is that the hydrogenated rosin glyceride is replaced with 10 parts and camellia oil with 20 parts.

[0056] Comparative Example 9 The difference from Example 1 is that no coated citric acid and sodium bicarbonate are added.

[0057] I. Cytotoxicity test: Sample preparation: Take the plaster base, remove the backing and release film, and cut it into 10mm × 10mm pieces; cut into 6cm... 2 Add MEM medium containing 10% fetal bovine serum at a ratio of / mL, statically extract at 37℃ and 5% CO2 for 24h, and then filter through a 0.22μm filter membrane to obtain the extract sample.

[0058] Detection method: Mouse fibroblast L-929 cells were cultured in MEM medium containing 10% FBS and 1% penicillin antibiotics in a 37℃, 5% CO2 incubator; 1×10 5 Seeds were inoculated at a density of 100 μL / mL in 96-well plates and cultured for 24 h until 80% confluence was achieved. The original culture medium was discarded, and extract was added to the experimental groups. Blank control (cell-free medium), negative control (medical-grade high-density polyethylene extract), and positive control (MEM medium containing 5% DMSO) were included. Cultures were continued for 24 h, 48 h, and 72 h. 20 μL of 5 mg / mL MTT solution was added to each well and incubated for 4 h. After discarding the supernatant, 150 μL of DMSO was added and the plate was shaken for 10 min. OD values ​​were measured at 570 nm using a microplate reader, with a reference wavelength of 650 nm. Five replicates were prepared for each sample. Cell viability (%) = (OD sample − OD blank control) / (OD negative control − OD blank control) × 100%.

[0059] II. Skin irritation test: Sample preparation: Take an intact sheet of matrix and cut it into Φ8mm diameter discs using a sterile punch, then remove the release film. The negative control was sterile physiological saline, the positive control was 5% SDS solution, and the blank control was an untreated RHE model.

[0060] Detection Procedure: After receiving the RHE model, pre-cultured it at 37℃ and 5% CO2 for 16 h. Add 30 μL of sterile saline to the surface of the RHE model, and then attach the matrix disc to the model surface, ensuring complete adhesion without air bubbles. Incubate at 37℃ and 5% CO2 for 60 min. Gently rinse the model surface with sterile PBS to remove surface residues. Transfer the model to fresh RHE-specific medium and continue incubation for 42 h. After incubation, completely immerse the model in 0.5 mg / mL MTT solution and incubate at 37℃ in the dark for 3 h. Discard the MTT solution, add isopropanol to extract formazan, and measure the absorbance at 570 nm using a microplate reader. Five replicates were set for each sample. Cell viability (%) = (OD sample - OD blank control) / (OD negative control - OD blank control) × 100%.

[0061] III. Water vapor transmission rate (air permeability) test: Sample preparation: Take a matrix sheet and cut it into circular samples with a diameter of Φ70mm, with 5 parallel samples per group.

[0062] Test method: Distilled water is added to the permeation cup, maintaining a 15mm distance between the liquid level and the sample. The sample matrix side is facing down, and the cup opening is sealed. The cup is placed in a constant temperature and humidity chamber at 38℃ and 90% relative humidity, with an air velocity of 0.5m / s. Weighing is performed every 24 hours. The first 24 hours are considered an equilibrium period and are not included in the calculation. After reaching steady state, three consecutive 24-hour weighings with constant mass differences are used to calculate the water vapor transmission rate (WVTR). 2 ·24h))=Δm / A;Where: Δm is the steady-state moisture permeability mass loss in 24 hours, g; A is the effective moisture permeability area, m 2 .

[0063] IV. Adhesion performance testing: Sample preparation: The matrix sheet was equilibrated for 24 hours at 23℃±2℃ and 50%±5% relative humidity, and the release film was removed; the initial tack sample was cut into 15mm×100mm, the peel strength sample was cut into 25mm×200mm, and the holding tack sample was cut into 25mm×150mm; 5 parallel samples were prepared for each group.

[0064] Detection method: 1. Initial adhesion (rolling ball method): Incline the plate at an angle of 40° and record the number of the largest steel ball that can be stuck.

[0065] 2. 180° peel strength: Universal testing machine, peel speed 300mm / min, measure average peel force.

[0066] 3. Adhesion: The sample is pasted onto a mirror-finished stainless steel plate, and a 1kg standard weight is suspended vertically. The time it takes for the sample to completely detach is recorded.

[0067] Table 1. Test Results (Average Values)

[0068] Of the above results, Examples 1 to 3 exhibited excellent overall performance, achieving a good balance between adhesion and breathability. Terpene-modified rosin beeswax uses rosin and white beeswax as a matrix, undergoing α-pinene grafting, maleic anhydride functionalization, and trimethylolpropane crosslinking to form a dual network of chemical and physical crosslinking. This balances hardness and extensibility, improves component compatibility and structural stability, and reduces cytotoxicity and skin irritation. The hydrophobic modification of stearic acid-modified microcrystalline cellulose solves the problem of hydrophilic cellulose aggregation in a hydrophobic matrix, uniformly dispersing it to form a microscopic rigid framework, improving cohesive strength and creep resistance; simultaneously, it regulates interfacial wettability, preventing skin maceration and optimizing application comfort. The system utilizes a coated citric acid and a three-stage gradient pore-forming design. Hydrogenated castor oil coating enables temperature-triggered, controlled foaming at specific points, with low-temperature unsealing and gas generation forming closed pores. Polyethylene glycol plasticizes and improves flexibility, while hydrophilic channels aid moisture permeability. Camphor and menthol exhibit trace sublimation to expand pores, and rapid cooling locks in the interconnected microporous structure, achieving high air permeability without sacrificing adhesion. Hydrogenated rosin glycerol stabilizes cohesion and initial adhesion; camellia oil and castor oil soften and toughen; and antioxidants inhibit oil oxidation and deterioration. The entire system achieves a four-in-one integration of air permeability, adhesion, drug delivery, and biocompatibility.

[0069] Comparative Example 1 (physical blend of ordinary rosin and white beeswax) did not undergo terpene grafting, functionalization, or cross-linking, resulting in weak molecular forces and a loose adhesive network, leading to a comprehensive decline in adhesion performance. The unmodified rosin lacked passivation of irritating components, resulting in poor biocompatibility; the microstructure of the process was poorly adapted, and the air permeability channels were insufficient.

[0070] Comparative Example 2 (without maleic anhydride) lacks a carboxyl functional group donor, making it unable to form effective crosslinks with zinc oxide and trimethylolpropane. This results in decreased interfacial compatibility and easy phase separation of components. Cohesive strength decreases, adhesive properties deteriorate, and the arrangement becomes denser, limiting the construction of breathable channels.

[0071] Comparative Example 3 (omitting trimethylolpropane crosslinking) showed a linear resin structure with significantly reduced heat resistance and structural stability. It was prone to deformation under stress, and its holding and peel strengths declined markedly. The molecules were more densely packed, resulting in fewer pores, increased resistance to water vapor penetration, and decreased air permeability.

[0072] Comparative Example 4 (Rosin: White Beeswax ratio reversed): Excessive white beeswax made the matrix too soft, with insufficient cohesion, resulting in a comprehensive reduction in adhesion. Beeswax accumulation caused the hydrophobic film to block the pores, reducing air permeability; excessive softness made it sticky to the skin, and reduced biocompatibility.

[0073] Comparative Example 5 (ordinary microcrystalline cellulose): Hydrophilic cellulose has poor compatibility with the hydrophobic matrix, easily agglomerates to form defects, disrupts the continuity of adhesion, and reduces adhesive performance. Agglomeration affects air permeability gaps, resulting in uneven air permeability, and increased moisture absorption further obstructs air permeability.

[0074] In Comparative Example 6 (ordinary citric acid), the lack of coating led to premature gas generation during the low-temperature reaction. The bubbles escaped and collapsed before coating, failing to form stable, interconnected pores, resulting in a significant decrease in permeability. Premature gas generation and escape, pore structure collapse, and localized cohesive defects reduced adhesion stability and resulted in a non-uniform structure.

[0075] Comparative Example 7 (reduced amount of modified rosin beeswax, increased amount of hydrogenated rosin glycerol ester): Excessive tackifying resin increased initial surface tack, but the proportion of cross-linked backbone decreased, weakening cohesion and structural stability. The high-viscosity component filled and closed some pores, reducing air permeability; the matrix was too sticky, reducing biocompatibility.

[0076] In Comparative Example 8 (with reduced hydrogenated rosin glycerol ester and significantly increased camellia oil), insufficient binder resin led to a lack of cohesive and adhesive substrates, resulting in a significant decline in adhesive performance. Excessive oil made the matrix too soft, with excessive extensibility but poor moldability; excessive oil was also prone to oxidation.

[0077] Comparative Example 9 (non-foamed system) lacks chemical foaming and pore creation; the matrix is ​​a dense, continuous membrane, resulting in extremely high resistance to water vapor diffusion and the lowest air permeability among all groups. Although initial adhesion properties are retained, the dense matrix hinders water vapor exchange, making it prone to stuffiness and impregnation.

Claims

1. A hard plaster base for a compress, characterized by, The matrix is ​​prepared from the following raw materials in parts by weight: 26-34 parts of terpene-modified rosin beeswax, 18-23 parts of hydrogenated rosin glycerol ester, 8-12 parts of camellia oil, 8-12 parts of castor oil, 4-6 parts of stearic acid hydrophobically modified microcrystalline cellulose, 3-5 parts of zinc oxide, 1-3 parts of glycerol, 1.5-2.5 parts of coated citric acid, 3-4 parts of sodium bicarbonate, 2-3 parts of polyethylene glycol, 7-11 parts of camphor, 2-5 parts of menthol, and 0.2-0.5 parts of 2,6-di-tert-butyl-4-methylphenol; The terpene-modified rosin beeswax is prepared by reacting rosin and α-pinene in the presence of bis(tert-butylperoxyisopropylbenzene), followed by the addition of white beeswax and maleic anhydride, and then the addition of trimethylolpropane. The stearic acid hydrophobically modified microcrystalline cellulose is prepared by coating microcrystalline cellulose with stearic acid. The coated citric acid is prepared by coating citric acid with hydrogenated castor oil.

2. The flexible, breathable, occlusive plaster base of claim 1, wherein, The mass ratio of rosin, white beeswax, α-pinene, bis(tert-butylperoxyisopropylbenzene), maleic anhydride, and trimethylolpropane is (20-23):(12-15):(1.0-1.5):(0.16-0.25):(0.15-0.25):(0.1-0.2).

3. The breathable plaster base for application according to claim 1, characterized in that, The rosin, α-pinene, and bis-tert-butylperoxyisopropylbenzene are reacted at 190–198°C, white beeswax and maleic anhydride are added and reacted at 160–170°C, and trimethylolpropane is added and reacted at 185–195°C.

4. A breathable plaster base for application according to claim 1 or 2, characterized in that, The preparation method of the terpene-modified rosin beeswax includes: heating rosin to 175-185℃ to melt it, adding α-pinene and di-tert-butylperoxyisopropylbenzene, stirring and reacting at 190-198℃, cooling to 160-170℃, adding white beeswax and maleic anhydride, stirring and reacting at 160-170℃; heating to 185-195℃, adding trimethylolpropane and stirring for crosslinking reaction, removing low-boiling substances, unreacted monomers and low-molecular-weight byproducts under reduced pressure; cooling to obtain terpene-modified rosin beeswax.

5. The breathable plaster base for application according to claim 1, characterized in that, The preparation method of the stearic acid hydrophobically modified microcrystalline cellulose includes: microcrystalline cellulose and stearic acid are uniformly mixed at a mass ratio of 100:(3-5) in a temperature range of 80-85℃, cooled and sieved to obtain stearic acid hydrophobically modified microcrystalline cellulose.

6. The breathable plaster base for application according to claim 1, characterized in that, The preparation method of the coated citric acid includes: pulverizing citric acid through a 200-250 mesh sieve, and heating the hydrogenated castor oil to 90-95℃ to melt it, adding citric acid, stirring and dispersing it evenly in a sealed environment, cooling and solidifying it, and pulverizing it through a 200-250 mesh sieve to obtain coated citric acid.

7. The breathable plaster base for application according to claim 1, characterized in that, The polyethylene glycol is PEG-400 or PEG-600.

8. The method for preparing a breathable plaster matrix for application according to claim 1, characterized in that, Includes the following steps: S1: Mix camellia oil and castor oil, and refine them until the acid value is <8mg KOH / g, the peroxide value is <5meq / kg, water droplets form beads without stickiness, and there is no oil residue or odor, to obtain refined oil; S2: At 155-165℃, terpene-modified rosin beeswax and hydrogenated rosin glycerol esters are added to refined oil and stirred to obtain a melt; S3: Cool the melt to 70-75℃, add polyethylene glycol, glycerin, 2,6-di-tert-butyl-4-methylphenol, stearic acid hydrophobically modified microcrystalline cellulose, and coated citric acid in sequence, and stir until uniform; cool to 55-60℃, add zinc oxide, sodium bicarbonate, camphor, and menthol, and stir until uniform to obtain the matrix; S4: The matrix is ​​roller-coated onto a medical pure cotton backing at 58-65℃, and immediately covered with a release film to obtain the coated blank; S5: The coated blank is pore-forming, held at 91-96℃ for 3-5 minutes, at 98-102℃ for 2-3 minutes, and at 30-38℃ for 3-5 minutes to obtain a sheet; S6: Remove the release film, let the sheet stand, and obtain the breathable plaster matrix.

9. The method for preparing a breathable plaster matrix for application according to claim 8, characterized in that, In S4, the thickness of the substrate coated by roller is 0.9 to 1.2 mm.

10. The method for preparing a breathable plaster matrix for application according to claim 8, characterized in that, In S6, the settling is to place the substrate in a closed clean environment at 20-28°C and 40-55% relative humidity for 22-26 hours, with the final setting point being when the substrate surface is no longer sticky to the touch, the shape is unchanged, and there is no residue after peeling.

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