Antibacterial bio-based polyurethane dressing and preparation method thereof

Abstract

The antibacterial bio-based cyclic polyurethane dressing is prepared from the following components in parts by weight: 140 to 160 parts of polyether polyol, 25 to 30 parts of poly delta-caprolactone polyol, 0.2 to 0.8 part of a catalyst, 1.5 to 2.5 parts of an organic silicon foam stabilizer, 1 to 3 parts of deionized water, 6 to 12 parts of a foaming agent, 1 to 10 parts of sodium alginate, 1 to 10 parts of hyaluronic acid, 15 to 22 parts of diisocyanate and 30 to 40 parts of cyclic oligomeric disulfide isocyanate. The antibacterial bio-based annular polyurethane dressing disclosed by the invention integrates broad-spectrum efficient antibacterial, rapid hemostasis, repair promotion and excellent water absorption and retention properties, and is superior to commercially available polyurethane dressings.

Description

[0001] The present invention belongs to the technical field of biomedical materials, and in particular relates to an antibacterial bio-based polyurethane dressing and a preparation method thereof. Background Art

[0002] Medical wound dressings form a protective barrier by covering the skin wound, which can not only prevent secondary damage to the wound, but also create a favorable microenvironment for tissue repair. They are mainly used to cover sores, wounds and other skin injuries. They are an important type of biomedical material, and their research and development have always been a hot topic in the field.

[0003] Polyurethane materials are widely used in the field of wound dressings due to their excellent biosafety: no teratogenic effects, no allergic reactions, excellent anticoagulant properties, and toxicity tests that meet medical requirements. They also have good toughness, elasticity and diverse processing properties. Common forms include films, hydrogels, foams, etc. Due to the risk of medical dressings coming into contact with blood and body fluids, their water absorption rate must also meet specific requirements. However, most polyurethane dressings on the market currently use modified polyethers, and the application of natural polymer hydrophilic additives is relatively scarce, leaving a certain market gap. In addition, current bio-based polyurethane dressings have defects such as single functions and components, making them difficult to adapt to wounds with high exudate; at the same time, wounds are susceptible to bacterial infection during healing, a problem that seriously hinders the repair process.

[0004] Based on the above situation, the development of bio-based antibacterial polyurethane dressings with long-lasting antibacterial effects and adjustable component ratios has become a key issue that needs to be urgently addressed in this field. Summary of the Invention

[0005] In order to overcome the above-mentioned deficiencies of the prior art, the present invention provides an antibacterial bio-based polyurethane dressing, which combines broad-spectrum and high-efficiency antibacterial properties, rapid hemostasis, promoted repair, and excellent water absorption and retention properties, and is superior to commercially available polyurethane dressings.

[0006] The technical solutions for achieving the purpose of the present invention are as follows:

[0007] An antibacterial bio-based polyurethane dressing comprises, by weight, 140-160 parts of polyether polyol, 25-30 parts of poly-δ-caprolactone polyol, 0.2-0.8 parts of a catalyst, 1.5-2.5 parts of an organosilicon foam leveling agent, 1-3 parts of deionized water, 6-12 parts of a foaming agent, 1-10 parts of sodium alginate, 1-10 parts of hyaluronic acid, 15-22 parts of a diisocyanate, and 30-40 parts of a cyclic oligomeric disulfide isocyanate; the general structural formula of the cyclic oligomeric disulfide isocyanate is shown in Formula 1:

[0008] Formula 1; R is One or more of the above; said ran indicates that the cyclic oligomeric disulfide is a random cyclic molecule, wherein x+y is any integer between 3 and 8.

[0009] Specifically, the polyether polyol is one or more of polyethylene glycol, polypropylene glycol, propylene glycol-ethylene glycol copolymer, and polytetramethylene glycol.

[0010] Specifically, the cyclic oligomeric disulfide isocyanate is obtained by reacting cyclic oligomeric disulfide with diisocyanate.

[0011] Specifically, the catalyst is an amine catalyst and a zinc catalyst in a molar ratio of 1: (0.1-0.5); the amine catalyst is one or more of triethylenediamine, ethylenediamine, triethylamine, triethanolamine and hexamethylenediamine; the zinc catalyst is organic zinc ZCAT-H22; the foaming agent is any one of cyclopentane or dichloromethane;

[0012] Preferably, the cyclic oligomeric disulfide isocyanate is prepared by the following preparation method:

[0013] The cyclic oligomeric disulfide is dissolved in anhydrous DMF preheated at 35-45° C. and stirred to dissolve into a homogeneous phase; 1.05-1.15 eq of diisocyanate relative to the molar amount of hydroxyl groups of the cyclic oligomeric disulfide is added dropwise to the DMF solution under nitrogen protection and in an ice bath at 0-5° C., the addition rate is controlled within 1 mL / min, and the reaction is carried out at 35-40° C. for 2-4 hours; after the reaction is completed, the solvent is removed under reduced pressure, and the cyclic oligomeric disulfide isocyanate is purified by silica gel column chromatography.

[0014] Preferably, the method for preparing the cyclic oligomeric disulfide comprises the following steps:

[0015] (1) Synthesis of amino-terminated protected cyclic disulfide: Dissolve lipoic acid and carbonyldiimidazole in acetonitrile at a molar ratio of 1: (1.3-1.4) and stir at room temperature for 25-35 min; add N-Boc ethylenediamine solution in an amount equivalent to 1.5-2 times the molar amount of lipoic acid dropwise, control the reaction temperature to be stirred at 0°C for 25-35 min, then raise the temperature to room temperature and stir for 4-5 h; concentrate under reduced pressure to remove acetonitrile, add dichloromethane to dilute the reaction solution, wash with saturated ammonium chloride aqueous solution and deionized water in sequence, and purify the organic phase by silica gel column chromatography to obtain amino-terminated protected cyclic disulfide, the structure of which is shown below:

[0016]

[0017] (2) Synthesis of ethanolamine cyclic disulfide: Under nitrogen atmosphere, lipoic acid, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide in a molar ratio of 1:(1-1.2):(1-1.2) were dissolved in anhydrous DMF, 4-dimethylaminopyridine equivalent to 0.1-0.2 times the molar amount of lipoic acid was added and stirred in an ice bath at 0°C for 25-35 minutes; diethanolamine equivalent to 1.2-1.3 times the molar amount of lipoic acid was dissolved in anhydrous DMF and added dropwise to the reaction system, and the temperature was raised to 35-45°C for 5-6 hours; after the reaction, the mixture was washed with 5% citric acid aqueous solution, saturated NaHCO3 solution and brine in sequence, dried over anhydrous sodium sulfate solid, and purified by silica gel column chromatography to obtain ethanolamine cyclic disulfide, the structure of which is shown below:

[0018]

[0019] (3) Synthesis of cyclic oligomeric disulfides: Add amino-protected cyclic disulfides and ethanolamine cyclic disulfides at a molar ratio of 3:2 into a thick-walled pressure-resistant bottle, replace the atmosphere with nitrogen three times to ensure that the air is free of water and oxygen, and then add anhydrous tetrahydrofuran; dissolve thiophenol and (tert-butylimino)tri(pyrrolidino)phosphine at a molar ratio of 1:1 in 80 μL anhydrous tetrahydrofuran to prepare an initiator solution; inject the initiator solution into the system and stir in an ice bath at 0°C for 2 to 3 hours to initiate ring-opening polymerization; add trifluoroacetic acid at a molar amount of 0.5 times that of the ethanolamine cyclic disulfide and stir at room temperature for 25 to 30 minutes to terminate the reaction; add 40 mL of pre-cooled ether dropwise into the reaction solution to induce precipitation; dry the precipitate under high vacuum for 3 to 4 hours to obtain a cyclic oligomeric disulfide, the structure of which is shown in the following formula:

[0020]

[0021] The preparation method of the poly-δ-caprolactone polyol comprises the following steps:

[0022] In a glove box, a Schlenk tube was flame-dried to remove water and oxygen, and a base catalyst, 1,3-diphenylurea, benzyl alcohol, and δ-caprolactone in a molar ratio of (0.5-2):(1-3):(0.5-2):100 were added to initiate polymerization. After polymerization at room temperature of 25°C for 1-2 hours, acetic acid was added dropwise to quench the reaction. The crude product was dissolved in 0.5 mL of tetrahydrofuran, and a trace amount was taken for nuclear magnetic resonance hydrogen spectrum analysis. The above solution was added dropwise to an excess of pre-cooled methanol to precipitate a polymer, which was washed twice with cold methanol. The precipitate was vacuum-dried at 30°C to obtain a polyδ-caprolactone polyol.

[0023] Preferably, the base catalyst is a phosphazene ligand P2-tert-butyl solution.

[0024] Preferably, the molecular weight of the poly δ-caprolactone polyol is 4000-6000 Da.

[0025] Preferably, the diisocyanate includes one or more of diphenylmethane diisocyanate, toluene diisocyanate, isophorone diisocyanate, hexamethylene diisocyanate, and dicyclohexylmethane diisocyanate.

[0026] A method for preparing an antibacterial bio-based polyurethane dressing comprises the following steps:

[0027] S1. The polyether polyol, poly δ-caprolactone polyol, catalyst, silicone foaming agent, deionized water, foaming agent, sodium alginate, hyaluronic acid are added according to the ratio of the premixed material aging equipment 1 for premixing, cooling cycle aging after the material is transported through the pipeline to the storage tank 2 for secondary cooling constant temperature homogenous stirring;

[0028] S2 diisocyanate and cyclic oligomeric disulfide isocyanate was injected into the homogenizing stirring tank 3 constant temperature homogenous stirring preservation;

[0029] S3. The storage cylinder 2 and the homogenizing mixing tank 3 are homogenized and matured. The raw materials are injected into the static closed mixing mechanism 4 by a screw pump through different speed ratios; after uniform high-speed mixing, they are uniformly injected through a hose into the bottom release paper coating and maturation mechanism 5 to mature the product;

[0030] S4 matured product is transported to the main device release mechanism 11, the upper and lower layers of release paper peeling and winding and mature product delivery;

[0031] S5. The product enters the drying and sterilization dehydration process through the synchronous traction of the coating and aging mechanism 5 and the microwave sterilization and drying equipment 15. After sterilization and drying, it enters the air shower dust removal mechanism 16 to remove dust from the surface of the product. It is then transported by the powered guide rollers of the air shower dust removal equipment to the winding and slitting equipment 17 for slitting. The slit products are conveyed tensionlessly to the winding guide rollers for tensionless winding. The wound products are then packaged and stored in a light-proof and airtight manner.

[0032] Preferably, the coating and curing mechanism includes an upper release paper feeding mechanism 6 , a lower release paper feeding mechanism 7 , a comma scraper 8 , a width adjustment roller 9 and a curing drying tunnel 10 .

[0033] Preferably, the speed ratio is 1:(1.1-1.5); the temperature of the microwave sterilization is ≤60° C., and the concentration of the diisocyanate DMF solution is 20 wt %.

[0034] The application of the antibacterial bio-based polyurethane dressing obtained as described above has excellent biocompatibility, the functions of self-repair, promotion of wound healing, and regeneration, and can be widely used in the field of medical materials.

[0035] Beneficial effects

[0036] This paper develops an antibacterial bio-based cyclic polyurethane dressing that, through material design and performance optimization, exhibits significant multi-dimensional beneficial effects, as follows:

[0037] 1. Synergistic effect of multiple antibacterial mechanisms: Relying on the triple mechanism of disulfide bonds (SS) to destroy the integrity of microbial cell membranes, electrostatic adsorption of quaternary ammonium groups to cause cell membrane perforation, and cyclic oligomeric structures to enhance the contact efficiency with microbial surfaces, it can achieve strong inhibition of multiple pathogens such as Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans.

[0038] 2. Adjustable and controllable antimicrobial performance: By adjusting the dosage and type of cyclic oligomeric disulfide isocyanates, such as aromatic diphenylmethane diisocyanate or aliphatic isophorone diisocyanate, a balance between antimicrobial efficacy and biocompatibility can be achieved. Aromatic isocyanates enhance bacterial membrane binding through the hydrophobic interaction of the benzene ring, resulting in slightly better antibacterial effects; aliphatic isocyanates offer greater biocompatibility, meeting the needs of different scenarios.

[0039] 3. Promote wound healing: Hyaluronic acid activates fibroblast proliferation, and the dynamic exchange characteristics of disulfide bonds adapt to the contraction stress of the wound to achieve rapid wound healing.

[0040] 4. Excellent water absorption / retention performance, adaptable to various wound needs. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 This is a synthetic route for cyclic oligomeric disulfide polyurethanes.

[0042] Figure 2 This is the H NMR spectrum of the amino-terminated cyclic disulfide 1.

[0043] Figure 3 This is the H NMR spectrum of ethanolamination cyclic disulfide 1.

[0044] Figure 4 This is the H NMR spectrum of cyclic oligomeric disulfide 1.

[0045] Figure 5 This is the H NMR spectrum of cyclic oligomeric disulfide isocyanate 1.

[0046] Figure 6 It is a device for preparing antibacterial bio-based polyurethane dressing.

[0047] Reference numerals include:

[0048] 1—Premixed material curing equipment

[0049] 2—Storage cylinder

[0050] 3—Homogeneous mixing tank

[0051] 4—Static closed mixing mechanism

[0052] 5—Coating and curing mechanism

[0053] 6—Upper release paper feeding mechanism

[0054] 7—Lower release paper feeding mechanism

[0055] 8—Comma Scraper

[0056] 9—Width adjustment roller

[0057] 10—Curing and drying tunnel

[0058] 11—Separation mechanism of the main equipment

[0059] 12—Receiving mechanism for upper release paper

[0060] 13—Receiving mechanism for lower release paper

[0061] 14—Up and down automatic spraying equipment

[0062] 15—Microwave sterilization and drying equipment

[0063] 16—Air shower dust removal mechanism

[0064] 17—Reeling and slitting equipment. DETAILED DESCRIPTION

[0065] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative efforts shall fall within the scope of protection of the present invention.

[0066] In the examples, the experimental methods used are conventional methods unless otherwise specified, and the materials, reagents, etc. used are all commercially available unless otherwise specified.

[0067] The raw materials and equipment used in the embodiments and comparative examples are described below:

[0068] Cyclic oligodisulfide 1: Homemade, prepared as follows:

[0069] (1) Synthesis of amino-terminated protected cyclic disulfide: 1.0 eq of thioctic acid and 1.3 times the molar amount of carbonyldiimidazole relative to thioctic acid were dissolved in anhydrous acetonitrile and stirred at room temperature for 30 min; a solution of N-Boc ethylenediamine dissolved in anhydrous acetonitrile at a molar amount of 1.5 times the molar amount of thioctic acid was added dropwise to the above system, the reaction temperature was controlled to be stirred at 0°C for 30 min, and then raised to room temperature and stirred for 4.5 h; the acetonitrile was removed by concentration under reduced pressure, and dichloromethane was added to dilute the reaction solution, and the reaction solution was washed with saturated aqueous ammonium chloride and deionized water in sequence. The organic phase was purified by silica gel column chromatography to obtain an amino-terminated protected cyclic disulfide, the structure of which is shown below:

[0070]

[0071] (2) Synthesis of ethanolamine cyclic disulfide: Under nitrogen atmosphere, 1 eq of thioctic acid, 1.2 times the molar amount of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride relative to the molar amount of thioctic acid, and 1.2 times the molar amount of N-hydroxysuccinimide relative to the molar amount of thioctic acid were dissolved in anhydrous DMF, and 0.1-0.2 times the molar amount of 4-dimethylaminopyridine relative to the molar amount of thioctic acid was added and stirred in an ice bath at 0°C for 30 minutes; 1.2 times the molar amount of diethanolamine relative to the molar amount of thioctic acid was dissolved in anhydrous DMF and added dropwise to the reaction system, and the temperature was raised to 40°C for reaction for 5 hours; after the reaction, the mixture was washed with 5% citric acid aqueous solution, NaHCO3 saturated solution and brine in sequence, dried over anhydrous sodium sulfate solid, and purified by silica gel column chromatography to obtain ethanolamine cyclic disulfide, the structure of which is shown below:

[0072]

[0073] (3) Synthesis of cyclic oligomeric disulfide 1: 30 eq of amino-protected cyclic disulfide and 20 eq of ethanolamine-modified cyclic disulfide were added to a thick-walled pressure-resistant bottle, and the atmosphere was replaced with nitrogen three times to ensure that the air was free of water and oxygen, and then anhydrous tetrahydrofuran was added; 1 eq of thiophenol and 1 eq of (tert-butylimino)tris(pyrrolidino)phosphine were dissolved in 80 μL of anhydrous tetrahydrofuran to prepare an initiator solution; the initiator solution was injected into the system and stirred in an ice bath at 0°C for 2 h to initiate ring-opening polymerization; 10 eq of trifluoroacetic acid was added and stirred at room temperature for 30 min to terminate the reaction, and 40 mL of pre-cooled ether was added dropwise to the reaction solution to induce precipitation; the precipitate was dried under high vacuum for 4 h to obtain cyclic oligomeric disulfide 1, the structure of which is shown in the following formula:

[0074]

[0075] Cyclic oligomeric disulfide 2: homemade. The preparation method is similar to that of cyclic oligomeric disulfide 1, except that N-Boc ethylenediamine solution is not added in step (1). Other conditions remain unchanged, yielding cyclic oligomeric disulfide 2.

[0076] Linear disulfide 3: Homemade. The preparation method is similar to that of cyclic oligomeric disulfide 1, except that lipoic acid in step (2) is replaced by 3-carboxypropyl disulfide, and steps (1) and (3) are omitted, yielding linear disulfide 3.

[0077] Poly-δ-caprolactone polyol: homemade, preparation method is as follows:

[0078] In a glove box, the Schlenk tube was flame-dried to remove water and oxygen, and a base catalyst, 1,3-diphenylurea, benzyl alcohol, and δ-caprolactone in a molar ratio of (0.5-2):(1-3):(0.5-2):100 were added to initiate polymerization. After polymerization at room temperature of 25°C for 1 hour, acetic acid was added dropwise to quench the reaction; the crude product was dissolved in 0.5 mL of tetrahydrofuran; the above solution was added dropwise to an excess of pre-cooled methanol to precipitate the polymer, which was washed twice with cold methanol; the precipitate was vacuum-dried at 30°C to obtain a polyδ-caprolactone polyol with a molecular weight of 5000 Da and a hydroxyl value of 22.4 mgKOH / g.

[0079] Thiophenol: Homemade, prepared as follows: suspend 1 eq sodium thiophenolate in ice water, slowly add 30 mL of 10% dilute hydrochloric acid dropwise, control the temperature to ≤10°C, and stir at room temperature for 25-35 min. After the reaction is complete, extract with ether, combine the organic phases, wash with 5% NaHCO3 solution, and then with deionized water until neutral. Dry the organic phase over anhydrous sodium sulfate, filter, and distill under reduced pressure to obtain thiophenol.

[0080] Diisocyanate: diphenylmethane diisocyanate, purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.;

[0081] Polyether polyol: polyethylene glycol: molecular weight 2000 Da, hydroxyl value 56.1 mgKOH / g, commercially available;

[0082] Blowing agent: cyclopentane, commercially available;

[0083] Sodium alginate: purity 99%, purchased from Hubei Xinghengkang Chemical Technology Co., Ltd.

[0084] Hyaluronic acid: purity 99%, Jinan Luxin Chemical Technology Co., Ltd.

[0085] Catalyst: triethylenediamine and organic zinc ZCAT-H22 in a molar ratio of 1:0.2, commercially available;

[0086] Silicone foam leveling agent: Synde-217 PU synthetic leather foam leveling agent, purchased from Zhuhai Xiande New Materials Technology Co., Ltd.

[0087] Base catalyst: phosphazene ligand P2-tert-butyl solution, phosphazene ligand P2-tert-butyl tetrahydrofuran solution with a concentration of 2 mol / L;

[0088] δ-Caprolactone: Product No. D155361, purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.

[0089] 1,3-Diphenylurea: product number 1015136, purchased from Shanghai Haohong Biopharmaceutical Technology Co., Ltd.;

[0090] 1,4-Butanediol: Product No. B110391, purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.;

[0091] Diphenyl phosphate: product number 1044516, purchased from Shanghai Haohong Biopharmaceutical Technology Co., Ltd.

[0092] 1-Ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride: purchased from Shanghai Covalent Chemical Technology Co., Ltd.;

[0093] N-Hydroxysuccinimide: purchased from Shanghai Changming Pharmaceutical Technology Co., Ltd.

[0094] Preparation Example

[0095] Preparation Example 1

[0096] Cyclic oligomeric disulfide isocyanate 1: Homemade, prepared as follows:

[0097] 1 eq of cyclic oligomeric disulfide 1, calculated as hydroxyl groups, was dissolved in anhydrous DMF preheated at 40°C and stirred to dissolve into a homogeneous phase. Under nitrogen protection and in an ice bath at 0-5°C, 1.1 eq of diphenylmethane diisocyanate was added to the above DMF solution at a dropwise addition rate of less than 1 mL / min, and the reaction was carried out at 40°C for 4 h. After the reaction, the solvent was removed under reduced pressure, and the cyclic oligomeric disulfide isocyanate 1 was purified by silica gel column chromatography.

[0098] Preparation Example 2

[0099] Cyclic oligomeric disulfide isocyanate 2: Homemade. The preparation method is similar to that of cyclic oligomeric disulfide isocyanate 1, except that cyclic oligomeric disulfide 1 is replaced by cyclic oligomeric disulfide 2. Other conditions remain unchanged, resulting in cyclic oligomeric disulfide isocyanate 2.

[0100] Preparation Example 3

[0101] Cyclic oligomeric disulfide isocyanate 3: Homemade. The preparation method is similar to that of cyclic oligomeric disulfide isocyanate 1, except that diphenylmethane diisocyanate is replaced by isophorone diisocyanate. Other conditions remain unchanged, resulting in cyclic oligomeric disulfide isocyanate 3.

[0102] Preparation Example 4

[0103] Linear disulfide isocyanate 4: Homemade. The preparation method is similar to that of cyclic oligomeric disulfide isocyanate 1, except that cyclic oligomeric disulfide 1 is replaced by linear disulfide 3. Other conditions remain unchanged, resulting in linear disulfide isocyanate 4.

[0104] Example

[0105] Examples 1 to 5

[0106] Antibacterial bio-based polyurethane dressings 1-5: Homemade, preparation method is as follows:

[0107] S1. The polyether polyol, poly δ-caprolactone polyol, catalyst, silicone foaming agent, deionized water, foaming agent, sodium alginate, hyaluronic acid are added to the premixed material aging equipment 1 according to the ratio and premixed. After the cooling cycle is matured, the material is transported through the pipeline to the storage tank 2 for secondary cooling at a constant temperature of 20 to 25 ° C and homogenized at 500 to 800 rpm;

[0108] S2. The diisocyanate and cyclic oligomeric disulfide isocyanate 1 to 3 are injected into a homogenizing stirring tank 3 at 40 ° C and homogenized at 300 to 400 rpm for storage;

[0109] S3. The homogenized and matured raw materials in the storage tank 2 and the homogenizing and mixing tank 3 are injected into the static closed mixing mechanism 4 at a speed ratio of 1: (1.1-1.5) using a screw pump at a temperature of 35-40°C. After uniform high-speed mixing, the raw materials are uniformly injected through a hose onto the bottom release paper of the coating and curing mechanism 5 to cure the product. The hose swings at a frequency of 10-15 times / min. The release paper is a PET release film with a thickness of 100 μm.

[0110] S4 matured product is transported to the main device release mechanism 11, the upper and lower layers of release paper peeling and winding and mature product delivery;

[0111] S5. The product enters the drying and sterilization dehydration process through the synchronous traction of the coating and aging mechanism 5 and the microwave sterilization and drying equipment 15. After sterilization and drying, it enters the air shower dust removal mechanism 16 to remove dust from the surface of the product. It is then transported by the powered guide rollers of the air shower dust removal equipment to the winding and slitting equipment 17 for slitting. The slit products are conveyed tensionlessly to the winding guide rollers for tensionless winding. The wound products are then packaged and stored in a light-proof and airtight manner.

[0112] Comparative Example

[0113] Comparative Example 1

[0114] Commercially available polyurethane dressing: 3M polyester foam dressing 90613, purchased from Henan Zeyuan Medical Equipment Sales Co., Ltd.

[0115] Comparative Example 2

[0116] Antibacterial bio-based polyurethane dressing 6: Homemade. The preparation method is the same as that in the example, except that the cyclic oligomeric disulfide isocyanates 1 to 3 are replaced by linear disulfide isocyanate 4. Other conditions remain unchanged, and antibacterial bio-based polyurethane dressing 6 is obtained.

[0117] Table 1: Formulas of Examples 1 to 5 and Comparative Examples (by weight)

[0118]

[0119] The following are the test methods for the performance parameters involved in the present invention:

[0120] 1. Antibacterial test

[0121] 1.1 Sample Preparation: The polyurethane dressings prepared in Examples 1-5 of the present invention were cut into circles with a diameter of 5 cm, which were the experimental groups 1-5; the polyurethane dressings prepared in the comparative example were cut into circles of the same size, which were the comparative example group; the experimental groups 1-5 and the comparative example group were placed in 6 triangular flasks, sealed, and sterilized at 120°C for 15 min.

[0122] 1.2 Preparation of bacterial suspension: Use an inoculating loop to streak the preserved bacteria onto a nutrient agar plate and incubate in a 37°C incubator for 24 hours. Transfer a typical colony from the plate to a flask containing broth culture medium and incubate at 37°C for 24 hours. Perform serial dilutions with broth to a concentration of 1 × 105 cfu / mL to 5 × 105 cfu / mL.

[0123] 1.3 Test steps: Take 1 mL of bacterial suspension and inoculate on the dressings in 6 Erlenmeyer flasks respectively. Incubate with shaking in a 37°C incubator for 48 hours. Take the sample before and after shaking respectively, dilute with 9 mL of 0.03 mol / L PBS buffer, inoculate the plate by the agar pour method, count the colonies, and then calculate the inhibition rate. The inhibition rate is the ratio of the difference between the average colony counts of the test sample before and after shaking to the average colony count before shaking, expressed as a percentage, as shown in the following formula:

[0124]

[0125] The selected bacterial species were Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans, and the antibacterial tests were carried out in sequence according to the above method.

[0126] 2. Body surface experiment: 60 rabbits of similar weight and age were selected and randomly divided into 6 groups, with 10 rabbits in each group. After removing the hair on the back of the rabbits with a depilatory agent, anesthesia was performed by intravenous injection of 1% sodium pentobarbital at the ear edge. Under sterile conditions, a well-shaped wound was made on the skin surface of the depilated area of ​​the rabbits. The polyurethane dressings of Examples 1 to 5 and the comparative example were placed on the wound site of the rabbits in Groups 1 to 6 in sequence. Filter paper strips were used to gently absorb blood until no more blood oozes out, and the bleeding was observed. After 12 hours, the polyurethane dressing was removed and the wound condition was recorded. The polyurethane dressing was changed daily for 3 consecutive days. After 3 days, the polyurethane dressing was removed and the wound condition was observed.

[0127] 3. Water absorption rate: For a 50mm×50mm×50mm medical dressing foam, the mass is measured as m1, then it is soaked in water and squeezed repeatedly 30 times. After soaking in water for another hour, the mass is measured as m2. The water absorption rate is calculated using the following formula:

[0128]

[0129] 4. Water retention rate: Take a 50mm×50mm×50mm medical dressing foam, and measure its mass as m1. Then soak it in water and squeeze it repeatedly 30 times. After 1 hour, place the foam on a horizontal plate. After another 1 hour, measure the foam mass as m3. Calculate the water absorption rate using the following formula:

[0130]

[0131] Table 2 Test results of Examples 1 to 5 and Comparative Examples

[0132]

[0133] As shown in Table 2, the antibacterial activity of the antimicrobial bio-based polyurethane dressing of the present invention stems from a synergistic combination of multiple mechanisms: disulfide bonds disrupt the integrity of microbial cell membranes, quaternary ammonium groups perforate cell membranes through electrostatic adsorption, and the cyclic oligomeric disulfide structure enhances contact efficiency with microbial surfaces. A comparison of different examples reveals that Example 3 performs best, achieving an inhibition rate of 99.3% against Staphylococcus aureus, presumably due to the higher dosage of cyclic oligomeric disulfide isocyanate 1. In contrast, Example 2 exhibits relatively weaker antibacterial performance due to the lowest dosage of cyclic oligomeric disulfide isocyanate. Furthermore, Examples 1 and 4, which utilize diphenylmethane diisocyanate, enhance their binding efficiency to bacterial membranes through the enhanced hydrophobic interaction of the benzene ring, resulting in superior antibacterial efficacy compared to Example 5, which utilizes isophorone diisocyanate. However, the aliphatic isocyanate structure of Example 5 imparts improved biocompatibility, resulting in a slightly lower inhibition rate.

[0134] In vivo testing revealed that the hemostatic performance of the dressings primarily relied on the ionic crosslinking effect of sodium alginate, with the hemostasis speed ranking as follows: Example 3 > Example 1 > Example 5 > Example 4 > Example 2. Example 3, due to its greater presence of negatively charged sites, accelerated blood cell aggregation. The control sample, lacking functionalized disulfide bonds and relying solely on physical compression, experienced a significantly slower hemostasis time of 45 seconds.

[0135] The comparison of water absorption / water retention performance reflects the relationship between material structure and performance. The water absorption rate is ranked as follows: Example 2 > Example 4 > Example 1 > Example 5 > Example 3. The high water absorption rate of Example 2 is due to the low cross-linking density, and hyaluronic acid and sodium alginate further enhance the water absorption capacity; while Example 3 has the lowest water absorption rate because the high dose of cyclic oligomeric disulfide isocyanate increases the cross-linking points and limits the swelling space. The water retention rate is ranked in the opposite direction: Example 3 > Example 5 > Example 1 > Example 4 > Example 2; at the same time, the isophorone diisocyanate structure of Example 5 enhances the flexibility of the chain segments and strengthens the ability to wrap water molecules, while the water retention rate of commercially available polyurethane dressings is 81.2%, which is significantly lower than that of the dressing of the present invention.

[0136] The preferred embodiments of the present invention disclosed above are intended only to help illustrate the present invention. These preferred embodiments do not exhaustively describe all details, nor do they limit the present invention to the specific embodiments described. Obviously, many modifications and variations are possible based on the content of this specification. These embodiments are selected and described in detail in this specification to better explain the principles and practical applications of the present invention, thereby enabling those skilled in the art to better understand and utilize the present invention. The present invention is limited only by the claims and their full scope and equivalents.

Claims

1. An antibacterial bio-based polyurethane dressing, characterized in that: The composition comprises, by weight, 140 to 160 parts of polyether polyol, 25 to 30 parts of poly-δ-caprolactone polyol, 0.2 to 0.8 parts of catalyst, 1.5 to 2.5 parts of organosilicon foam leveling agent, 1 to 3 parts of deionized water, 6 to 12 parts of foaming agent, 1 to 10 parts of sodium alginate, 1 to 10 parts of hyaluronic acid, 15 to 22 parts of diisocyanate, and 30 to 40 parts of cyclic oligomeric disulfide isocyanate; the general structural formula of the cyclic oligomeric disulfide isocyanate is shown in Formula 1: The R is One or more of the above; said ran indicates that the molecule is an irregular cyclic molecule, wherein x+y is any integer between 3 and 8.

2. The antibacterial bio-based polyurethane dressing according to claim 1, characterized in that: The preparation method of the poly-δ-caprolactone polyol comprises the following steps: Under anhydrous and oxygen-free conditions, a base catalyst, 1,3-diphenylurea, benzyl alcohol and δ-caprolactone in a molar ratio of (0.5-2):(1-3):(0.5-2):100 are polymerized at room temperature for 1-3 hours, and acetic acid is added dropwise to quench the reaction. After purification, polyδ-caprolactone polyol is obtained.

3. The antibacterial bio-based polyurethane dressing according to claim 1, characterized in that: The polyether polyol is one or more of polyethylene glycol, polypropylene glycol, propylene glycol-ethylene glycol copolymer, and polytetramethylene glycol.

4. The antibacterial bio-based polyurethane dressing according to claim 1, characterized in that: The catalyst is an amine catalyst and a zinc catalyst in a molar ratio of 1: (0.1-0.5); the amine catalyst is one or more of triethylenediamine, ethylenediamine, triethylamine, triethanolamine and hexamethylenediamine; the zinc catalyst is organic zinc ZCAT-H22; and the foaming agent is any one of cyclopentane or dichloromethane.

5. The antibacterial bio-based polyurethane dressing according to claim 1, characterized in that: The cyclic oligomeric disulfide isocyanate is obtained by reacting cyclic oligomeric disulfide with diisocyanate; the molecular weight of the cyclic oligomeric disulfide ranges from 1000 to 4000 Da; the molecular weight of the cyclic oligomeric disulfide isocyanate ranges from 1200 to 4200 Da, and the average molecular weight is from 2800 to 3200 Da.

6. The antibacterial bio-based polyurethane dressing according to claim 1, characterized in that: The diisocyanate includes one or more of diphenylmethane diisocyanate, toluene diisocyanate, isophorone diisocyanate, hexamethylene diisocyanate, and dicyclohexylmethane diisocyanate.

7. The antibacterial bio-based polyurethane dressing according to claim 1, characterized in that: The cyclic oligomeric disulfide isocyanate is prepared by the following preparation method: The cyclic oligomeric disulfide is dissolved in anhydrous DMF preheated at 35-45° C. and stirred to dissolve into a homogeneous phase; under nitrogen protection and in an ice bath at 0-5° C., a diisocyanate having a molar amount of 1.05-1.15 eq relative to the hydroxyl group of the cyclic oligomeric disulfide is added dropwise to the above DMF solution, and the reaction is carried out at 35-40° C. for 2-4 hours; after the reaction is completed, the solvent is removed under reduced pressure, and the cyclic oligomeric disulfide isocyanate is purified by silica gel column chromatography.

8. The antibacterial bio-based polyurethane dressing according to claim 1, characterized in that: The cyclic oligomeric disulfide is prepared by the following preparation method: (1) Synthesis of amino-terminated protected cyclic disulfide: Dissolve lipoic acid and carbonyldiimidazole in a molar ratio of 1: (1.3-1.4) in acetonitrile, add N-Boc ethylenediamine solution equivalent to 1.5-2 times the molar amount of lipoic acid dropwise, stir at 0-5°C for 25-35 minutes, then heat to room temperature and stir for 4-5 hours to obtain amino-terminated protected cyclic disulfide; (2) Synthesis of ethanolamine cyclic disulfide: Under nitrogen atmosphere, dissolve lipoic acid, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide in a molar ratio of 1:(1-1.2):(1-1.2) in DMF in an ice bath. Add 4-dimethylaminopyridine in an amount equivalent to 0.1-0.2 times the molar amount of lipoic acid and stir. Add diethanolamine in an amount equivalent to 1.2-1.3 times the molar amount of lipoic acid and react at 35-45°C for 5-6 hours to obtain ethanolamine cyclic disulfide. (3) Synthesis of cyclic oligomeric disulfides: Under anhydrous and oxygen-free conditions, amino-terminated cyclic disulfides and ethanolamine-modified cyclic disulfides at a molar ratio of 3:2 are added to a thick-walled pressure-resistant bottle, tetrahydrofuran and an initiator are added, and the mixture is stirred in an ice bath at 0°C for 2 to 3 hours to initiate ring-opening polymerization; trifluoroacetic acid is then added to terminate the reaction, and pre-cooled ether is added dropwise to induce precipitation; the precipitate is dried under high vacuum to obtain a cyclic oligomeric disulfide having the structure shown below:

9. The method for preparing the antibacterial bio-based polyurethane dressing according to any one of claims 1 to 8, characterized in that: The following steps are involved: S1. The polyether polyol, poly-δ-caprolactone polyol, catalyst, silicone foaming agent, deionized water, foaming agent, sodium alginate, hyaluronic acid were added to the premixed material aging equipment according to the ratio of premixed stirring, and the cooling cycle was matured and the material was transported through the pipeline to the storage tank for secondary cooling and constant temperature homogenization stirring; S2. The diisocyanate and cyclic oligomeric disulfide isocyanate are injected into a homogenizing stirring tank and stirred at a constant temperature for storage; S3. The storage cylinder and homogenizing mixing tank homogenized and matured raw materials are injected into the static closed mixing mechanism by a screw pump through different speed ratios; after uniform high-speed mixing, the mixture is evenly injected through a hose into the bottom release paper coating and aging mechanism to mature the product; S4. The matured product is transported to the release mechanism of the main device, where the upper and lower release paper layers are peeled and rewound, and the matured product is transported; S5. The product enters the drying and sterilization dehydration process through the synchronous traction of the coating and aging mechanism and the microwave sterilization and drying equipment; after sterilization and drying, it enters the air shower dust removal mechanism to remove dust from the surface of the product, and then is transported to the winding and slitting equipment by the powered guide roller of the air shower dust removal equipment for slitting. The slit products are conveyed tensionlessly to the winding guide roller for tensionless winding; the wound products are packaged and stored in a light-proof and airtight manner.

10. The method for preparing the antibacterial bio-based polyurethane dressing according to claim 9, wherein: The coating and curing mechanism comprises an upper release paper feeding mechanism, a lower release paper feeding mechanism, a comma scraper, a width adjustment roller and a curing drying tunnel.

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