Hemostatic hydrophilic polyurethane foam dressing and preparation method thereof

Abstract

The invention relates to the technical field of medical instruments, and discloses a hemostatic hydrophilic polyurethane foam dressing and a preparation method thereof. The dressing is prepared by mixing and foaming a hemostatic hydrophilic prepolymer and a functional foaming mixture according to the mass ratio of (1: 2)-(2: 1), the hemostatic hydrophilic prepolymer is obtained by reacting polyether polyol, isocyanate, tranexamic acid, a chain extender and an antioxidant; the functional foaming mixture is prepared by mixing polyether glycol, a surfactant, a foam stabilizer and purified water. The tranexamic acid directly reacts with the polyether polyol, the isocyanate and the like to prepare the hemostatic hydrophilic prepolymer, the prepared polyurethane foam dressing has an excellent hemostatic function, meanwhile, the good liquid absorption rate and the anti-adhesion effect of polyurethane foam are not affected, and wound healing can be effectively promoted.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, and in particular to a hemostatic hydrophilic polyurethane foam dressing and its preparation method. Background Technology

[0002] In clinical practice, the choice of dressings is crucial for the treatment of various traumatic wounds (such as surgical incisions, burns, and chronic ulcers). An ideal wound dressing not only needs to protect the wound surface but also actively create and maintain a moist microenvironment conducive to tissue regeneration, thereby accelerating the healing process. Polyurethane foam dressings are an important type of medical device developed based on this concept. Made of polyurethane, they possess inherent properties such as softness, breathability, and high absorbency, effectively absorbing wound exudate and maintaining appropriate wound moisture. Simultaneously, their porous structure allows for gas exchange, providing excellent conditions for wound healing. Furthermore, this dressing can form a physical barrier on the wound surface, preventing the invasion of external bacteria and contaminants, significantly reducing the risk of infection.

[0003] However, when faced with wounds accompanied by active bleeding or oozing, simple absorption and barrier functions are no longer sufficient to meet clinical needs. Rapid and effective hemostasis is the first step in wound management and the foundation for preventing subsequent infection and promoting healing. Therefore, those skilled in the art have attempted to develop polyurethane foam dressings with hemostatic properties. Currently, common commercial solutions typically involve applying a layer of hemostatic active ingredients (such as chitosan, alginate, etc.) to the surface of a pre-made polyurethane foam product produced using conventional methods through physical spraying or impregnation, thereby imparting hemostatic properties.

[0004] However, this post-processing modification method has several inherent technical drawbacks: 1. Unstable material properties: The hemostatic agent and the polyurethane foam matrix are mainly bonded through physical adsorption, resulting in weak interfacial forces. During transportation, storage, or use, the hemostatic agent is prone to detaching from the foam surface, leading to uneven and unreliable hemostatic function.

[0005] 2. Impact on core physical properties: Hemostatic agents adhering to the surface may partially block the open pore structure of the foam, leading to a decrease in its absorbency. This not only affects the dressing's ability to manage exudate but also fails to maintain an ideal moist environment for the wound.

[0006] 3. Clinical side effects: Due to poor adhesion, detached hemostatic agent particles may remain on the wound surface; at the same time, due to decreased absorption rate and changes in surface properties, the dressing is prone to adhesion to newly formed granulation tissue, causing secondary damage when changing the dressing, causing pain to the patient and slowing down the wound healing process.

[0007] In summary, the existing simple composite model of "foam matrix + surface hemostatic coating" suffers from inherent structural and functional contradictions, making it difficult to achieve stable and efficient hemostasis while maintaining the original excellent properties of polyurethane foam dressings. Therefore, there is an urgent need in this field for a novel technical solution that can fundamentally solve the integration problem between hemostatic agents and the foam matrix, developing a hydrophilic polyurethane foam dressing that combines excellent hemostatic properties, high absorbency, and good anti-adhesion properties to meet the clinical needs of complex wound care. Summary of the Invention

[0008] The main objective of this invention is to provide a hemostatic hydrophilic polyurethane foam dressing that has excellent hemostatic properties and promotes faster wound healing.

[0009] To achieve the above objectives, the present invention proposes a hemostatic hydrophilic polyurethane foam dressing, wherein the dressing is prepared by mixing and foaming a hemostatic hydrophilic prepolymer and a functional foam mixture in a mass ratio of 1:2 to 2:1. The hemostatic hydrophilic prepolymer is obtained by reacting polyether polyol, isocyanate, tranexamic acid, chain extender and antioxidant. The functional foaming mixture is prepared by mixing polyether glycol, surfactant, foam stabilizer and purified water.

[0010] This invention directly reacts tranexamic acid with polyether polyols, isocyanates, etc. to prepare a hemostatic hydrophilic prepolymer. The resulting polyurethane foam dressing not only has excellent hemostatic function, but also does not affect the good liquid absorption rate and anti-adhesion effect of the polyurethane foam itself, and can effectively promote wound healing.

[0011] Preferably, the amount of each raw material added to the hemostatic hydrophilic prepolymer by mass parts is: 60-100 parts of polyether polyol, 30-70 parts of isocyanate, 0.5-4 parts of tranexamic acid, 1-5 parts of chain extender, and 0.5-2 parts of antioxidant.

[0012] Preferably, the amount of each raw material added in the functional foaming mixture by mass is: 1-10 parts of polyether glycol, 0.5-2 parts of surfactant, 0.5-2 parts of foam stabilizer, and 10-100 parts of purified water.

[0013] Preferably, the polyether polyol is polyethylene glycol and ethylene oxide. propylene oxide (EO) One or more of the following copolyols (PO), wherein the average functionality of the polyether polyol is 2-3, the average molecular weight is 200-20000, and the molar percentage of EO block is not less than 80%; The polyether diol is one or more of polyethylene oxide diol, polypropylene oxide diol, polytetrahydrofuran diol, and copolymer / modified polyether diol, wherein the average functionality of the polyether diol is 2 and the average molecular weight is 250 to 12000.

[0014] Preferably, the isocyanate is one or more selected from diphenylmethane diisocyanate, toluene diisocyanate, hexamethylene diisocyanate, dicyclohexylmethane diisocyanate, and isophorone diisocyanate.

[0015] Preferably, the chain extender is one or more selected from 1,4-butanediol, ethylene glycol, 1,6-hexanediol, trimethylolpropane, and neopentyl glycol; the antioxidant is antioxidant 1135, antioxidant 245, antioxidant GA-80, aromatic amines, antioxidant V-900, IRGASTAB PUR 68, Irganox B215, and NIAX CS. One or more of 15.

[0016] Preferably, the surfactant is one or more of fatty alcohol polyoxyethylene ether, alkyl polyglucoside, polyoxyethylene fatty acid ester, EO / PO block polyether, polyglycerol fatty acid ester, castor oil polyoxyethylene ether, linear octacarbon isooctyl alcohol polyoxyethylene ether, polyoxyethylene alkyl ether, and sorbitan fatty acid ester; the foam stabilizer is one or more of polysiloxane, non-silicone foam stabilizer, L-580, H-8800, F-5580, H-963, and H-962.

[0017] Preferably, the NCO content in the hemostatic hydrophilic prepolymer is 7%.

[0018] This invention also discloses a method for preparing the above-mentioned hemostatic hydrophilic polyurethane foam dressing, comprising the following steps: S1. In an anhydrous and oxygen-free environment, polyether polyol and isocyanate are mixed and subjected to a prepolymerization reaction to obtain the first prepolymer; S2. Add tranexamic acid to the first prepolymer, and after reaction, obtain the second prepolymer; S3. In an anhydrous and oxygen-free environment, the chain extender is added to the second prepolymer and mixed and stirred. After the reaction, the third prepolymer is obtained. S4. In an anhydrous and oxygen-free environment, the antioxidant is added to the third prepolymer and mixed and stirred. After the reaction, a hemostatic hydrophilic prepolymer is obtained. S5. Mix polyether glycol, surfactant, foam stabilizer and purified water evenly to obtain a functional foaming mixture; S6. The functional foaming mixture is added to the hemostatic hydrophilic prepolymer in proportion, stirred and dispersed, and after foaming and curing, the hemostatic hydrophilic polyurethane foam dressing is obtained.

[0019] Preferably, in step S1, the polyether polyol needs to be vacuum dried at 120°C for 4 hours before the prepolymerization reaction; the prepolymerization reaction temperature is 60~95°C and the time is 2~5 hours. In step S2, the reaction temperature is 90~105 ℃ and the time is 2~4 h; In step S3, the reaction temperature is 90~100 ℃ and the time is 1~2 h; In step S4, the reaction temperature is 60~90 ℃ and the time is 0.5~1h; In step S6, before foaming, the hemostatic hydrophilic prepolymer is heated to 38~45℃; the stirring rate is 3000~6000 rpm, the stirring time is 15~40 s; the curing temperature is 80~115℃, and the curing time is 1~4 h. Preferably, the method further includes a step of laminating the foamed and cured hemostatic hydrophilic polyurethane foam with a backing layer and a protective layer, wherein the backing layer is any one of non-woven tape or adhesive PU film; and the protective layer is release paper.

[0020] Compared with the prior art, the present invention has the following beneficial effects: The present invention breaks the existing simple composite mode of "foam matrix + surface hemostatic coating", and uses tranexamic acid as a hemostatic agent to prepare a hemostatic hydrophilic prepolymer, which is then mixed with a functional foaming mixture to produce a hemostatic hydrophilic polyurethane foam. It has high hemostatic efficiency, good water absorption, promotes wound healing, and can significantly improve the speed of wound hemostasis, shortening the wound healing time to 5-8 days. Detailed Implementation

[0021] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. It should be noted that, in the absence of conflict, the embodiments and features in the embodiments of this application can be combined with each other. At the same time, the raw materials mentioned below, unless otherwise specified, are all commercially available products; the process steps or preparation methods not mentioned in detail are all process steps or preparation methods known to those skilled in the art.

[0022] This invention proposes a hemostatic hydrophilic polyurethane foam dressing, which is prepared by mixing and foaming a hemostatic hydrophilic prepolymer and a functional foam mixture in a mass ratio of 1:2 to 2:1. The hemostatic hydrophilic prepolymer is obtained by reacting polyether polyol, isocyanate, tranexamic acid, chain extender and antioxidant. The amount of each raw material added to the hemostatic hydrophilic prepolymer by mass parts is: 60-100 parts of polyether polyol, 30-70 parts of isocyanate, 0.5-4 parts of tranexamic acid, 1-5 parts of chain extender and 0.5-2 parts of antioxidant.

[0023] The functional foaming mixture is prepared by mixing polyether glycol, surfactant, foam stabilizer and purified water. By mass, the amount of each raw material added to the functional foaming mixture is: 1-10 parts of polyether glycol, 0.5-2 parts of surfactant, 0.5-2 parts of foam stabilizer and 10-100 parts of purified water.

[0024] Furthermore, in this invention, the polyether polyol is polyethylene glycol and ethylene oxide. propylene oxide (EO) The polyether diol is one or more of the following: PO (poly(ethylene oxide) diol), wherein the average functionality of the polyether diol is 2-3, the average molecular weight is 200-20000, and the molar percentage content of the EO block is not less than 80%. The polyether diol is one or more of the following: polyethylene glycol, polypropylene glycol, polytetrahydrofuran diol, and copolymer / modified polyether diol, wherein the average functionality of the polyether diol is 2, and the average molecular weight is 250-12000. The isocyanate may be selected from one or more of diphenylmethane diisocyanate, toluene diisocyanate, hexamethylene diisocyanate, dicyclohexylmethane diisocyanate, and isophorone diisocyanate. The chain extender may be selected from one or more of 1,4-butanediol, ethylene glycol, 1,6-hexanediol, trimethylolpropane, and neopentyl glycol; the antioxidant may be selected from antioxidant 1135, antioxidant 245, antioxidant GA-80, aromatic amines, antioxidant V-900, IRGASTABPUR 68, Irganox B215, and NIAX CS. One or more of the following 15. The surfactant may be selected from one or more of fatty alcohol polyoxyethylene ethers, alkyl polyglucosides, polyoxyethylene fatty acid esters, EO / PO block polyethers, polyglycerol fatty acid esters, castor oil polyoxyethylene ethers, linear octacarbon isooctyl alcohol polyoxyethylene ethers, polyoxyethylene alkyl ethers, and sorbitan fatty acid esters. The foam leveler may be selected from one or more of polysiloxanes, non-silicone foam levelers, L-580, H-8800, F-5580, H-963, and H-962.

[0025] The preparation method of the above-mentioned hemostatic hydrophilic polyurethane foam dressing includes the following steps: S1. The polyether polyol was vacuum dried at 120°C for 4 hours to remove water, cooled to 60-70°C, and added to isocyanate in an anhydrous and oxygen-free environment. The prepolymerization reaction was carried out at 60-95°C for 2-5 hours to obtain the first prepolymer. S2. Add tranexamic acid to the first prepolymer and react at 90~105℃ for 2~4 h to obtain the second prepolymer; S3. In an anhydrous and oxygen-free environment, add the chain extender to the second prepolymer and mix and stir. React at 90~100℃ for 1~2 h to obtain the third prepolymer. S4. In an anhydrous and oxygen-free environment, add the antioxidant to the third prepolymer and mix and stir. React at 60~90 ℃ for 0.5~1h until the NCO content is 7% to obtain the hemostatic hydrophilic prepolymer. S5. Mix polyether glycol, surfactant, foam stabilizer and purified water evenly to obtain a functional foaming mixture; S6. Heat the hemostatic hydrophilic prepolymer to 38~45 ℃, stir at a rate of 3000~6000 rpm, add the functional foaming mixture, continue stirring and dispersing for 15~40 s, pour into a mold for foaming, and cure the foamed material at 80~115 ℃ for 1~4 h to obtain hemostatic hydrophilic polyurethane foam; after composite molding and die cutting, the hemostatic hydrophilic polyurethane foam dressing is obtained.

[0026] It should be noted that the hemostatic hydrophilic prepolymer of this invention is synthesized through a stepwise addition process, which ensures that the resulting prepolymer molecular chains are more ordered and regular, avoiding the presence of various chemical additives. The addition of polyether glycol to the functional foaming mixture further enhances the resilience of the dressing.

[0027] The composite molding process specifically includes the step of laminating the foamed and cured hemostatic hydrophilic polyurethane foam with a backing layer and a protective layer. The backing layer can be a well-known base material applicable to dressings, including but not limited to non-woven tape, adhesive PU film, etc.; the protective layer can be a known protective film material with release properties, including but not limited to release paper, etc.

[0028] In existing technologies, hemostatic agents are typically sprayed onto the surface of polyurethane foam dressings or impregnated with the hemostatic agent to achieve hemostasis. However, this process is problematic because the hemostatic agent is prone to detachment, leading to unstable hemostatic effects. Furthermore, the polyurethane foam coated or impregnated with the hemostatic agent exhibits reduced absorbency and anti-adhesion properties, thus affecting wound healing. This invention directly uses tranexamic acid as a synthetic raw material, reacting it with polyether polyols, isocyanates, etc., to first synthesize a hemostatic hydrophilic prepolymer. This prepolymer is then mixed and foamed with a functional foaming mixture. The resulting hemostatic hydrophilic polyurethane foam retains good hemostatic effects while maintaining the excellent absorbency and anti-adhesion properties of polyurethane foam itself. It is suitable for rapid hemostasis of bleeding wounds and can effectively promote wound healing and increase the healing rate.

[0029] The following examples further illustrate the present invention in detail. It should also be understood that the following examples are only for further explanation of the present invention and should not be construed as limiting the scope of protection of the present invention. Any non-essential improvements and adjustments made by those skilled in the art based on the above description of the present invention are within the scope of protection of the present invention. The specific process parameters in the following examples are merely one example within a suitable range; that is, those skilled in the art can make appropriate selections within the range based on the description herein, and are not intended to be limited to the specific values ​​in the examples below. Where specific conditions are not specified in the examples, conventional conditions or conditions recommended by the manufacturer shall apply.

[0030] In the following examples, the surfactants used are all alkyl polyglucosides, specifically BASF's Plantacare® 1200UP.

[0031] Example 1 A method for preparing a hemostatic hydrophilic polyurethane foam dressing includes the following steps: S1. 100 g of polyethylene glycol 4000 was vacuum dried at 120°C for 4 h to remove water, cooled to 70°C, and 47 g of diphenylmethane diisocyanate was added in an anhydrous and oxygen-free environment. The prepolymerization reaction was carried out at 70°C for 3 h to obtain the first prepolymer. S2. Add 1.5 g of tranexamic acid to the first prepolymer and react at 95 °C for 3 h to obtain the second prepolymer; S3. In an anhydrous and oxygen-free environment, 1.8 g of 1,4-butanediol was added to the second prepolymer and mixed and stirred. The mixture was reacted at 95 °C for 1 h to obtain the third prepolymer. S4. In an anhydrous and oxygen-free environment, 1.3 g of antioxidant 1135 was added to the third prepolymer and mixed and stirred. The mixture was reacted at 85 °C for 1 h until the NCO content was 7% to obtain the hemostatic hydrophilic prepolymer. S5. Mix 5 g of polytetrahydrofurandiol 6000, 1.5 g of Plantacare® 1200UP, 2 g of L-580 and 100 g of purified water until homogeneous to obtain a functional foaming mixture. S6. Heat 100 g of hemostatic hydrophilic prepolymer to 42 ℃ and stir at 4000 rpm. Add 100 g of functional foaming mixture and continue stirring and dispersing for 20 s. Pour into a mold for foaming. Cure the foamed material at 90 ℃ for 3 hours to obtain hemostatic hydrophilic polyurethane foam. Composite the hemostatic hydrophilic polyurethane foam with adhesive PU film and release paper using a laminating machine, and then die-cut to obtain the hemostatic hydrophilic polyurethane foam dressing.

[0032] Example 2 A method for preparing a hemostatic hydrophilic polyurethane foam dressing includes the following steps: S1. 100 g of polypropylene glycol 2000 was vacuum dried at 120°C for 4 h to remove water, cooled to 70°C, and added to 47 g of toluene diisocyanate in an anhydrous and oxygen-free environment. The prepolymerization reaction was carried out at 70°C for 3 h to obtain the first prepolymer. S2. Add 1.5 g of tranexamic acid to the first prepolymer and react at 95 °C for 3 h to obtain the second prepolymer; S3. In an anhydrous and oxygen-free environment, 1.8 g of 1,4-butanediol was added to the second prepolymer and stirred. The mixture was reacted at 95 °C for 1 h to obtain the third prepolymer. S4. In an anhydrous and oxygen-free environment, 1.3g of antioxidant 1135 was added to the third prepolymer and mixed and stirred. The mixture was reacted at 85 °C for 1 h until the NCO content was 7% to obtain the hemostatic hydrophilic prepolymer. S5. Mix 5 g of polytetrahydrofurandiol 6000, 1.5 g of Plantacare® 1200UP, 2 g of L-580 and 100 g of purified water until homogeneous to obtain a functional foaming mixture. S6. Heat 100 g of hemostatic hydrophilic prepolymer to 42 ℃ and stir at 4000 rpm. Add 100 g of functional foaming mixture and continue stirring and dispersing for 20 s. Pour into a mold for foaming. Cure the foamed material at 90 ℃ for 3 hours to obtain hemostatic hydrophilic polyurethane foam. Composite the hemostatic hydrophilic polyurethane foam with adhesive PU film and release paper using a laminating machine, and then die-cut to obtain the hemostatic hydrophilic polyurethane foam dressing.

[0033] Example 3 A method for preparing a hemostatic hydrophilic polyurethane foam dressing includes the following steps: S1. 100 g of polyethylene glycol 4000 was vacuum dried at 120°C for 4 h to remove water, cooled to 70°C, and 47 g of diphenylmethane diisocyanate was added in an anhydrous and oxygen-free environment. The prepolymerization reaction was carried out at 70°C for 3 h to obtain the first prepolymer. S2. Add 0.5 g of tranexamic acid to the first prepolymer and react at 95°C for 3 h to obtain the second prepolymer; S3. In an anhydrous and oxygen-free environment, 1.8 g of ethylene glycol was added to the second prepolymer and mixed and stirred. The mixture was reacted at 95 °C for 1 h to obtain the third prepolymer. S4. In an anhydrous and oxygen-free environment, 1.3g of IRGASTAB PUR 68 was added to the third prepolymer and mixed and stirred. The mixture was reacted at 85 °C for 1 h until the NCO content was 7% to obtain the hemostatic hydrophilic prepolymer. S5. Mix 5 g of polytetrahydrofurandiol 6000, 1.5 g of Plantacare® 1200UP, 2 g of L-580 and 100 g of purified water until homogeneous to obtain a functional foaming mixture. S6. Heat 100 g of hemostatic hydrophilic prepolymer to 42 ℃ and stir at 4000 rpm. Add 100 g of functional foaming mixture and continue stirring and dispersing for 20 s. Pour into a mold for foaming. Cure the foamed material at 90 ℃ for 3 hours to obtain hemostatic hydrophilic polyurethane foam. Composite the hemostatic hydrophilic polyurethane foam with adhesive PU film and release paper using a laminating machine, and then die-cut to obtain the hemostatic hydrophilic polyurethane foam dressing.

[0034] Comparative Example 1 This comparative example is a common polyurethane foam dressing, and its preparation method includes the following steps: S1. 100 g of polyethylene glycol 4000 was vacuum dried at 120°C for 4 h to remove water, cooled to 70°C, and 47 g of diphenylmethane diisocyanate was added in an anhydrous and oxygen-free environment. The prepolymerization reaction was carried out at 70°C for 3 h to obtain the first prepolymer. S2. In an anhydrous and oxygen-free environment, 1.8 g of 1,4-butanediol was added to the first prepolymer and mixed and stirred. The mixture was reacted at 95 °C for 3 h to obtain the second prepolymer. S3. In an anhydrous and oxygen-free environment, 1.3g of antioxidant 1135 was added to the second prepolymer and mixed and stirred. The mixture was reacted at 85 °C for 1 h until the NCO content was 7% to obtain the hydrophilic prepolymer. S4. Mix 5 g of polytetrahydrofurandiol 6000, 1.5 g of Plantacare® 1200UP, 2 g of L-580 and 100 g of purified water until homogeneous to obtain a functional foaming mixture. S5. Heat 100 g of hydrophilic prepolymer to 42 ℃ and stir at 4000 rpm. Add 100 g of functional foaming mixture and continue stirring and dispersing for 20 s. Pour into a mold to foam. Cure the foamed material at 90 ℃ for 3 h to obtain polyurethane foam. Composite the polyurethane foam with adhesive PU film and release paper using a laminating machine, and then punch-cut to obtain polyurethane foam dressing.

[0035] Comparative Example 2 This comparative example is a polyurethane foam dressing with a hemostatic coating, and the preparation method includes the following steps: S1. 100 g of polyethylene glycol 4000 was vacuum dried at 120°C for 4 h to remove water, cooled to 70°C, and 47 g of diphenylmethane diisocyanate was added in an anhydrous and oxygen-free environment. The prepolymerization reaction was carried out at 70°C for 3 h to obtain the first prepolymer. S2. In an anhydrous and oxygen-free environment, 1.8 g of 1,4-butanediol was added to the first prepolymer and mixed and stirred. The mixture was reacted at 95 °C for 3 h to obtain the second prepolymer. S3. In an anhydrous and oxygen-free environment, 1.3g of antioxidant 1135 was added to the second prepolymer and mixed and stirred. The mixture was reacted at 85 °C for 1 hour until the NCO content was 7% to obtain the hydrophilic prepolymer. S4. Mix 5 g of polytetrahydrofurandiol 6000, 1.5 g of Plantacare® 1200UP, 2 g of L-580 and 100 g of purified water until homogeneous to obtain a functional foaming mixture. S5. Heat 100 g of hydrophilic prepolymer to 42 ℃ and stir at 4000 rpm. Add 100 g of functional foaming mixture and continue stirring and dispersing for 20 s. Pour into a mold for foaming. Cure the foamed material at 90 ℃ for 3 h to obtain polyurethane foam. Coat the surface of the polyurethane foam with 1.5 g of tranexamic acid. Combine the tranexamic acid-coated polyurethane foam with an adhesive PU film and release paper using a laminating machine and die-cut to obtain a polyurethane foam dressing with a hemostatic coating.

[0036] Performance testing Verify the physical properties and efficacy of the polyurethane foam dressings prepared in Examples 1-3 and Comparative Examples 1-2.

[0037] The coagulation test was conducted according to YY / T 1477.5-2020 "Standard Test Models for Evaluating the Performance of Contact Wound Dressings - Part 5: In Vitro Models for Evaluating Hemostatic Performance". Under constant temperature conditions of (37±1)℃, anticoagulated fresh animal blood was placed in a simulated blood vessel device, and a constant pressure was applied through a pressure control system, causing the blood to flow out from a standardized "wound" (an orifice of a specific diameter). After the dressing to be tested was applied to the wound, the time required from the dressing contacting the blood to the complete cessation of bleeding (i.e., hemostasis time) was recorded, and the outflowing blood throughout the process was collected and weighed to calculate the blood loss.

[0038] The test results are shown in Table 1.

[0039] Table 1 As shown in Table 1, the hemostasis time of Examples 1-3 was shorter than that of Comparative Examples 1 and 2. The blood absorption volume of Examples 1-3 was similar to that of Comparative Example 1, but slightly higher than that of Comparative Example 2. Examples 1-3 showed less blood loss, better blood clot strength, and better integrity of the material after hemostasis. Therefore, the hemostatic hydrophilic polyurethane foam dressing described in this invention has a significant hemostatic promoting effect.

[0040] Example 1 is used as an example to illustrate the hemostatic performance parameters, such as hemostasis time, bleeding volume, and biocompatibility, of the polyurethane foam dressings prepared in Example 1 and Comparative Examples 1-2 in rabbit liver and spleen parenchymal organ wound models.

[0041] Sixty New Zealand rabbits were randomly divided into six groups of 10 each, corresponding to: Experimental group (Example 1): Hemostatic hydrophilic polyurethane foam; Negative control group 1 (comparative example 1): ordinary polyurethane foam; Negative control group 2: Medical degreased gauze; Positive control group 1 (comparative example 2): polyurethane foam with hemostatic coating; Positive control group 2: medical degreased gauze soaked in thrombin; Blank control group: treated with physiological saline only.

[0042] Model establishment: Rabbits were anesthetized by intravenous injection of 2% sodium pentobarbital (30 mg / kg) via the ear vein. The abdomen was prepared and disinfected, and the liver and spleen were exposed by laparotomy. A standardized wound with a depth of 1.0 cm × 0.5 cm × 0.3 cm was made on the surface of the liver with a sterile scalpel, and a wound with a depth of 0.8 cm × 0.5 cm × 0.2 cm was made on the surface of the spleen, ensuring uniform bleeding from the wounds.

[0043] Hemostasis treatment: In the experimental group, the hemostatic hydrophilic polyurethane foam prepared in Example 1 was used to cover the wound and gently pressed for 30 seconds; in the negative control group 1, the ordinary polyurethane foam prepared in Comparative Example 1 was treated in the same way; in the negative control group 2, medical degreased gauze was treated in the same way; in the positive control group 1, the polyurethane foam with hemostatic coating prepared in Comparative Example 2 was treated in the same way; in the positive control group 2, medical degreased gauze soaked in thrombin was treated in the same way; in the blank control group, only gauze soaked in physiological saline was gently pressed.

[0044] Indicator detection: Hemostasis time: Record the time from material contact with the wound to complete cessation of bleeding, with no visible bleeding from the wound as the standard; Bleeding volume: Use the wound bleeding collection and weighing method, collect bleeding with pre-weighed sterile filter paper, and calculate the bleeding volume by weight difference (blood density converted to 1.05 g / mL); Coagulation function: Collect blood from the marginal ear vein after the experiment, and use a coagulation analyzer to detect prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen (FIB) levels; Histopathological examination: Sacrifice the animals 72 hours after the operation, and prepare pathological sections from the wound and surrounding tissues to observe the inflammatory response and tissue compatibility.

[0045] The test results are shown in Table 2.

[0046] Table 2 Note: There was no statistically significant difference in the amount of bleeding in the liver and spleen wounds of the rabbits in each group during modeling (P > 0.05), indicating that the model was established stably and there was no group bias.

[0047] As shown in Table 2, the hemostasis time of liver and spleen wounds in Example 1 was shortened by 31.84% and 23.66% respectively compared with ordinary polyurethane foam (Comparative Example 1), and by 70.21% and 54.90% respectively compared with degreased gauze, with a significant reduction in bleeding (P < 0.05); the fibrinogen level was higher than that of each control group (P < 0.05), which is consistent with the pharmacological mechanism of tranexamic acid inhibiting fibrinolysis, and has good biocompatibility.

[0048] In the experimental group (Example 1), only mild inflammatory cell infiltration was observed around the wound, with no obvious tissue necrosis, and the material adhered well to the wound. In the positive control group 1 (Comparative Example 1), the inflammatory reaction was slightly more severe, and in the positive control group 2, obvious bleeding marks and moderate inflammatory infiltration were observed. The wound healing of the blank control group was delayed.

[0049] Therefore, the hemostatic hydrophilic polyurethane foam of the present invention exhibits significant hemostatic properties in rabbit liver and spleen parenchymal organ wound models. It can shorten the hemostasis time and reduce the amount of bleeding through the dual effects of rapid absorption of oozing blood and inhibition of fibrinolysis. It also has good tissue compatibility and its hemostatic effect is superior to that of ordinary polyurethane foam dressings and traditional medical degreased gauze.

[0050] Clinical efficacy observation The trial involved 150 participants divided into five experimental groups of 30 each. Each group used the hemostatic hydrophilic polyurethane foam dressings of Examples 1-3, the ordinary polyurethane foam dressing prepared in Comparative Example 1, and the polyurethane foam dressing with a hemostatic coating prepared in Comparative Example 2, respectively. No adverse effects were observed during the trial period. Wound healing improved in all participants, with 90 participants experiencing rapid wound healing within 5-8 days without scarring. Performance test results are shown in Table 3.

[0051] Table 3 Here are some typical cases: Ms. Li, 34 years old, cut her left index finger while chopping vegetables. The wound was 3.1 cm long. After rinsing the wound with tap water, it continued to bleed. She immediately applied this product externally, and the bleeding stopped. The wound healed after 5 days without infection or scarring.

[0052] Mr. Tan, male, 59 years old, suffered abrasions on his palm when he fell. The wound was approximately 5x8cm² in size. After the epidermis was peeled off and the wound was cleaned, this product was applied externally. The wound healed after 5 days without infection or scarring.

[0053] Ms. Wang, 26 years old, suffered a knee abrasion from a fall. The wound covered an area of ​​approximately 8x12cm², with peeling of the epidermis and a relatively deep wound. After cleaning, this product was applied externally. The wound healed after 7 days without infection or scarring.

[0054] Clinical efficacy observations show that the hemostatic hydrophilic polyurethane foam dressing prepared in this invention has good hemostatic effect and can significantly improve the wound healing speed.

[0055] The above description is merely a preferred embodiment of the present invention and does not limit the patent scope of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the protection scope of the present invention; or direct / indirect applications in other related technical fields are all included within the patent protection scope of the present invention.

Claims

1. A hemostatic hydrophilic polyurethane foam dressing, characterized in that, The dressing is prepared by mixing and foaming a hemostatic hydrophilic prepolymer and a functional foaming mixture in a mass ratio of 1:2 to 2:

1. The hemostatic hydrophilic prepolymer is obtained by reacting polyether polyol, isocyanate, tranexamic acid, chain extender and antioxidant. The functional foaming mixture is prepared by mixing polyether glycol, surfactant, foam stabilizer and purified water.

2. The hemostatic hydrophilic polyurethane foam dressing as described in claim 1, characterized in that, The amount of each raw material added to the hemostatic hydrophilic prepolymer by mass parts is as follows: 60-100 parts of polyether polyol, 30-70 parts of isocyanate, 0.5-4 parts of tranexamic acid, 1-5 parts of chain extender, and 0.5-2 parts of antioxidant.

3. The hemostatic hydrophilic polyurethane foam dressing as described in claim 1, characterized in that, The amount of each raw material added in the functional foaming mixture by mass is as follows: 1-10 parts of polyether glycol, 0.5-2 parts of surfactant, 0.5-2 parts of foam stabilizer, and 10-100 parts of purified water.

4. The hemostatic hydrophilic polyurethane foam dressing as described in claim 1, characterized in that, The polyether polyol is polyethylene glycol and ethylene oxide. propylene oxide (EO) One or more of the following copolyols (PO), wherein the average functionality of the polyether polyol is 2-3, the average molecular weight is 200-20000, and the molar percentage of EO block is not less than 80%; The polyether diol is one or more of polyethylene oxide diol, polypropylene oxide diol, polytetrahydrofuran diol, and copolymer / modified polyether diol, wherein the average functionality of the polyether diol is 2 and the average molecular weight is 250 to 12000.

5. The hemostatic hydrophilic polyurethane foam dressing as described in claim 1, characterized in that, The isocyanate is one or more selected from diphenylmethane diisocyanate, toluene diisocyanate, hexamethylene diisocyanate, dicyclohexylmethane diisocyanate, and isophorone diisocyanate.

6. The hemostatic hydrophilic polyurethane foam dressing as described in claim 1, characterized in that, The chain extender is one or more selected from 1,4-butanediol, ethylene glycol, 1,6-hexanediol, trimethylolpropane, and neopentyl glycol; The antioxidants are antioxidant 1135, antioxidant 245, antioxidant GA-80, aromatic amines, antioxidant V-900, IRGASTAB PUR 68, Irganox B215, and NIAX CS. One or more of 15.

7. The hemostatic hydrophilic polyurethane foam dressing as described in claim 1, characterized in that, The surfactant is one or more of the following: fatty alcohol polyoxyethylene ether, alkyl polyglucoside, polyoxyethylene fatty acid ester, EO / PO block polyether, polyglycerol fatty acid ester, castor oil polyoxyethylene ether, linear octane isooctyl alcohol polyoxyethylene ether, polyoxyethylene alkyl ether, and sorbitol fatty acid ester. The foam leveling agent is one or more of polysiloxane, non-silicone foam leveling agents, L-580, H-8800, F-5580, H-963 and H-962.

8. The hemostatic hydrophilic polyurethane foam dressing as described in claim 1, characterized in that, The NCO content in the hemostatic hydrophilic prepolymer is 7%.

9. A method for preparing a hemostatic hydrophilic polyurethane foam dressing as described in any one of claims 1 to 8, characterized in that, Includes the following steps: S1. In an anhydrous and oxygen-free environment, polyether polyol and isocyanate are mixed and subjected to a prepolymerization reaction to obtain the first prepolymer; S2. Add tranexamic acid to the first prepolymer, and after reaction, obtain the second prepolymer; S3. In an anhydrous and oxygen-free environment, the chain extender is added to the second prepolymer and mixed and stirred to obtain the third prepolymer; S4. In an anhydrous and oxygen-free environment, add the antioxidant to the third prepolymer and mix and stir to obtain a hemostatic hydrophilic prepolymer. S5. Mix polyether glycol, surfactant, foam stabilizer and purified water evenly to obtain a functional foaming mixture; S6. The functional foaming mixture is added to the hemostatic hydrophilic prepolymer in proportion, stirred and dispersed, and after foaming and curing, the hemostatic hydrophilic polyurethane foam dressing is obtained.

10. The preparation method according to claim 9, characterized in that, In step S1, the polyether polyol needs to be vacuum dried at 120°C for 4 hours before the prepolymerization reaction; the prepolymerization reaction temperature is 60~95°C and the time is 2~5 hours. In step S2, the reaction temperature is 90~105 ℃ and the time is 2~4 h; In step S3, the reaction temperature is 90~100 ℃ and the time is 1~2 h; In step S4, the reaction temperature is 60~90 ℃ and the time is 0.5~1h; In step S6, before foaming, the hemostatic hydrophilic prepolymer is heated to 38~45℃; the stirring rate is 3000~6000 rpm, the stirring time is 15~40 s; the curing temperature is 80~115℃, and the curing time is 1~4 h.

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